{"text_format":"1","workbook":"xlsx","n_sheets":16,"sheets":["Cover","Original","Abbreviations","Mapper","CitationIndex","Citations","Dashboard","custom","Setup","studymethodCategories","subpopulationCategories","studytypeCategories","diseaseCategories","protoolCategories","locationCategories","interventionCategories"],"not_rendered":{"charts":0,"images":5,"macros":1,"external_links":2,"defined_names":148,"comments":0,"pivot_tables":0},"unopened":[],"bounds":{"document_bytes":16777216,"sheet_cells":100000,"rows_first":2000,"rows_last":500,"rows_between":2000,"halvings":0,"cell_chars":16384,"cell_head_chars":4096},"cells_cut":0,"cells_raw":0,"read":"whole","date_system":"1900"}

{"sheet":"Cover","index":0,"n_rows":27,"n_cols":4,"rows_kept":27,"cut":false,"hidden":false,"merged":[[32,2,32,8],[4,2,5,36],[25,2,25,8],[20,2,20,16]]}
[]
[]
[]
[]
[null,null,"This Excel workbook contains the Evidence Map generated from heoro.com on\nPRO instruments used in pulmonary hypertension since 2000."]
[]
[]
[]
[]
[]
[null,null,"How this Evidence Map was generated"]
[null,null,"We searched heoro.com on 16 May 2017 for PRO studies on pulmonary arterial hypertension."]
[null,null,"The searches identified 70 abstracts published since 2000, which were indexed to the following fields: "]
[null,null,null,"Diseases - the diseases assessed in the study."]
[null,null,null,"Locations - the geographical location of the study. "]
[null,null,null,"Interventions - the interventions assessed in each study, where relevant."]
[null,null,null,"PRO tools - the PRO instruments cited in the abstract, where relevant"]
[null,null,"In addition the following publication date segmentations are used:"]
[null,null,null,"1960 to 1999, 2000 to 2004, 2005 to 2009, 2010 to 2014, 2015 to 2017"]
[]
[null,null,"All data in this Evidence Map is taken from the heoro.com database"]
[]
[null,null,"Details of the PubMed search strategy used to populate the heoro.com database can be found here."]
[null,null,"Contact us:"]
[null,null,"Address: Crystallise Ltd. Unit 21, Thames Enterpise Centre, Thames Industrial Park, East Tilbury, Essex, UK RM18 8RH"]
[null,null,"Tel: +44 (0)1375 488020"]
[null,null,"Email: alison.martin@crystallise.com"]

{"sheet":"Original","index":1,"n_rows":71,"n_cols":33,"rows_kept":71,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNT(A2:A966)","v":70},"Full citation","DOI","Authors","Title","Abstract","Citation","Locations","Year","Diseases","Interventions","PROtools","Subpopulations","Study types","Study methodologies","LocationsTags","SubpopulationsTags","DiseaseTags","InterventionsTags","StudytypesTags","StudyMethodologyTags","PROtoolTags","DateBand","C1","C2","C3","C4","C5","C6","C7","C8","C9","C10"]
[1,"Petrucci L,Carlisi E,Ricotti S,Zanellato S,Klersy C,D'Armini AM,Nicolardi S,Morsolini M,Viganò M,Dalla Toffola E. Functional assessment and quality of life before and after pulmonary endoarterectomy. G Ital Med Lav Ergon. 2015 Jul-Sep;37(3):170-5.",null,"Petrucci L,Carlisi E,Ricotti S,Zanellato S,Klersy C,D'Armini AM,Nicolardi S,Morsolini M,Viganò M,Dalla Toffola E.","Functional assessment and quality of life before and after pulmonary endoarterectomy.","The study investigates Quality of Life (QOL) and correlation with functional status of patients affected by Chronic Thromboembolic Pulmonary Hypertension who undergo Pulmonary Endoarterectomy. We investigated with an observational design (before surgery,three and twelve months afterwards) the hemodynamic data (NYHA class,mean pulmonary arterial pressure,cardiac output and pulmonary vascular resistance),the functional status (using the 6-Minute Walk Test) and the QOL,using three questionnaires: Medical Outcome Study Short Form-36 (SF-36),Minnesota Living with Heart Failure Questionnaire (MLHFQ),Saint George Respiratory Questionnaire (SGRQ). We report the results of forty-nine patients. After surgery there was an improvement on functional and hemodynamic parameters and on QOL. The physical domain (PCS) of SF-36 was weakly but significantly associated with all functional parameters. There was no association between functional parameters and mental domain (MCS) of SF-36 or SGRQ. The improvement in 6-Minute Walk Distance was associated with an increase in MLHFQ. Both QOL and submaximal exercise tolerance improve after surgery. However only the physical domains of SF-36 appear to be significantly associated to the functional data.","G Ital Med Lav Ergon. 2015 Jul-Sep;37(3):170-5.","Unknown",2015,"CTEPH","Surgery","MLHFQ,SF-36,SGRQ"]
[2,"Pandey A,Garg S,Khunger M,Garg S,Kumbhani DJ,Chin KM,Berry JD. Efficacy and Safety of Exercise Training in Chronic Pulmonary Hypertension: Systematic Review and Meta-Analysis. Circ Heart Fail. 2015 Nov;8(6):1032-43. doi: 10.1161/CIRCHEARTFAILURE.115.002130. Epub 2015 Jul 16.","doi: 10.1161/CIRCHEARTFAILURE.115.002130. Epub 2015 Jul 16.","Pandey A,Garg S,Khunger M,Garg S,Kumbhani DJ,Chin KM,Berry JD.","Efficacy and Safety of Exercise Training in Chronic Pulmonary Hypertension: Systematic Review and Meta-Analysis.","Exercise training has been shown to improve cardiorespiratory fitness,physical capacity,and quality of life in patients with cardiopulmonary conditions,such as heart failure and chronic obstructive pulmonary disease. However,its role in management of pulmonary hypertension is not well defined. In this study,we aim to evaluate the efficacy and safety of exercise training in patients with pulmonary hypertension. We included all prospective intervention studies that evaluated the efficacy and safety of exercise training in patients with pulmonary hypertension. Primary outcome of this meta-analysis was a change in 6-minute walk distance. We also assessed the effect of exercise on peak oxygen uptake,resting pulmonary arterial systolic pressure,peak exercise heart rate,and quality of life. A total of 469 exercise-training participants enrolled in 16 separate training studies were included. In the pooled analysis,exercise training was associated with significant improvement in 6-minute walk distance (weighted mean difference,53.3 m; 95% confidence interval,39.5-67.2),peak oxygen uptake (weighted mean difference,1.8 mL/kg per minute; 95% confidence interval,1.4-2.3),pulmonary arterial systolic pressure (weighted mean difference,-3.7 mm Hg; 95% confidence interval,-5.4 to -1.9),peak exercise heart rate (weighted mean difference,10 beats per min; 95% confidence interval,6-15),and quality of life as measured on SF-36 questionnaire subscale scores. Furthermore,exercise training was well tolerated with a low dropout rate,and no major adverse events were related to exercise training. Exercise training in patients with pulmonary hypertension appears safe and is associated with a significant improvement in exercise capacity,pulmonary arterial pressure,and quality of life.","Circ Heart Fail. 2015 Nov;8(6):1032-43.","International",2015,"Any PAH","Exercise","SF-36"]
[3,"Singer LG,Chowdhury NA,Faughnan ME,Granton J,Keshavjee S,Marras TK,Tullis DE,Waddell TK,Tomlinson G. Effects of Recipient Age and Diagnosis on Health-related Quality-of-Life Benefit of Lung Transplantation. Am J Respir Crit Care Med. 2015 Oct 15;192(8):965-73. doi: 10.1164/rccm.201501-0126OC.","doi: 10.1164/rccm.201501-0126OC.","Singer LG,Chowdhury NA,Faughnan ME,Granton J,Keshavjee S,Marras TK,Tullis DE,Waddell TK,Tomlinson G.","Effects of Recipient Age and Diagnosis on Health-related Quality-of-Life Benefit of Lung Transplantation.","The average age of lung transplant recipients is increasing,and the mix of recipient indications for transplantation is changing. To determine whether the health-related quality-of-life (HRQL) benefit of lung transplantation differs by recipient age and diagnosis. In this prospective cohort study,we obtained serial HRQL measurements in adults with advanced lung disease who subsequently underwent lung transplantation (2004-2012). HRQL assessments included the St. George's Respiratory Questionnaire,36-Item Short-Form Health Survey (SF-36),EQ-5D,Standard Gamble,and Visual Analog Scale for current health. We used linear mixed effects models for associations between age or diagnosis and changes in HRQL with transplantation. To address potential survivorship bias,we fitted Markov models to the distribution of discrete post-transplant health states (HRQL better than pretransplant,not better,or dead) and estimated quality-adjusted life-years post-transplant. A total of 430 subjects were listed,387 were transplanted,and 326 provided both pretransplant and post-transplant data. Transplantation conferred large improvements in all HRQL measures: St. George's change of -47 units (95% confidence interval,-48 to -44),36-Item Short-Form Health Survey physical component summary score of 17.7 (16.5-18.9),EQ-5D of 0.27 (0.24-0.30),Standard Gamble of 0.48 (0.44-0.51),and Visual Analog of 44 (42-47). Age was not associated with meaningful differences in the HRQL benefits of transplantation. There was less HRQL benefit in interstitial lung disease than in cystic fibrosis. Lung transplantation confers large HRQL benefits,which vary by recipient diagnosis,but do not differ substantially in older recipients.","Am J Respir Crit Care Med. 2015 Oct 15;192(8):965-73.","Canada",2015,"Interstitial lung disease","Lung transplant","SF-36,StGm,SGRQ,VAS"]
[4,"Matura LA,Ventetuolo CE,Palevsky HI,Lederer DJ,Horn EM,Mathai SC,Pinder D,Archer-Chicko C,Bagiella E,Roberts KE,Tracy RP,Hassoun PM,Girgis RE,Kawut SM. Interleukin-6 and tumor necrosis factor-α are associated with quality of life-related symptoms in pulmonary arterial hypertension. Ann Am Thorac Soc. 2015 Mar;12(3):370-5. doi: 10.1513/AnnalsATS.201410-463OC.","doi: 10.1513/AnnalsATS.201410-463OC.","Matura LA,Ventetuolo CE,Palevsky HI,Lederer DJ,Horn EM,Mathai SC,Pinder D,Archer-Chicko C,Bagiella E,Roberts KE,Tracy RP,Hassoun PM,Girgis RE,Kawut SM.","Interleukin-6 and tumor necrosis factor-α are associated with quality of life-related symptoms in pulmonary arterial hypertension.","Inflammation is associated with symptoms in many chronic illnesses; however,this link has not been established in pulmonary arterial hypertension. The objective of this study was to investigate the association between inflammatory markers and quality of life-related symptoms in patients with pulmonary arterial hypertension. We hypothesized that higher circulating IL-6 and tumor necrosis factor-α levels would be associated with worse quality of life-related symptoms. We performed a secondary analysis using baseline and 3-month assessments of 62 subjects in a clinical trial of aspirin and simvastatin to determine the association between plasma IL-6 and tumor necrosis factor-α levels and the Medical Outcomes Study Short Form-36 subscales (pain,vitality,mental health). The mean age was 49.7±13.4 years; 87% were female. Higher IL-6 levels were significantly associated with lower Medical Outcomes Study Short Form-36 subscale scores,indicating worse bodily pain,vitality,and mental health (all P<0.01). Higher tumor necrosis factor-α levels were significantly associated with increased bodily pain,but better mental health scores. IL-6 and tumor necrosis factor-α levels are associated with certain quality of life domains in patients with pulmonary arterial hypertension. Clinical trial registered with www.clinicaltrials.gov (NCT00384865).\n","Ann Am Thorac Soc. 2015 Mar;12(3):370-5.","USA",2015,"Any PAH","Aspirin,Simvastatin","SF-36"]
[5,"Fernandes CJ,Martins BC,Jardim CV,Ciconelli RM,Morinaga LK,Breda AP,Hoette S,Souza R. Quality of life as a prognostic marker in pulmonary arterial hypertension. Health Qual Life Outcomes. 2014 Aug 30;12():130. doi: 10.1186/s12955-014-0130-3. Epub 2014 Aug 30.","doi: 10.1186/s12955-014-0130-3. Epub 2014 Aug 30.","Fernandes CJ,Martins BC,Jardim CV,Ciconelli RM,Morinaga LK,Breda AP,Hoette S,Souza R.","Quality of life as a prognostic marker in pulmonary arterial hypertension.","Improvement in quality of life together with better survival are the ultimate goals in the treatment of pulmonary arterial hypertension (PAH) patients. The objective of this study was to evaluate the health-related quality of life (HRQL) of pulmonary arterial hypertension (PAH) patients with the SF-36 generic questionnaire and to identify the prognostic implication of this assessment. Fifty-four consecutive newly diagnosed PAH patients (WHO classification group I) in a single PAH reference center were included. Patients were evaluated at baseline for clinical and hemodynamic parameters,and they subsequently received first-line therapy with either an endothelin receptor antagonist or a phosphodiesterase-5 inhibitor. After 16 weeks of specific PAH therapy,all patients were re-evaluated using a 6MWT and a SF 36 questionnaire,and then they were followed up for at least 36 months. After treatment,the patients demonstrated an improved 6MWT (414 ± 124 m vs. 440 ± 113 m,p = 0.001). Specific PAH therapy also improved the HRQL scores.Patients with a baseline Physical Component Score (PCS) higher than 32 had a better survival rate than those who had a score under 32 (p = 0.04). Similarly,patients with a PCS of at least a 38 after the 16 week therapy period had a better survival rate when compared with those who did not achieve this value (p = 0.016). Unlike the absolute PCS values,the post-treatment PCS variability was unable to predict better survival rates (p = 0.58). Our findings suggest that HRQL is associated with prognosis in PAH. Furthermore,achieving pre-determined PCS scores might represent a specific goal to be reached in treatment-to-target strategies.","Health Qual Life Outcomes. 2014 Aug 30;12():130.","Brazil",2014,"Any PAH","Any ERA,Any PDE-5I","SF-36"]
[6,"Rival G,Lacasse Y,Martin S,Bonnet S,Provencher S. Effect of pulmonary arterial hypertension-specific therapies on health-related quality of life: a systematic review. Chest. 2014 Sep;146(3):686-708. doi: 10.1378/chest.13-2634.","doi: 10.1378/chest.13-2634.","Rival G,Lacasse Y,Martin S,Bonnet S,Provencher S.","Effect of pulmonary arterial hypertension-specific therapies on health-related quality of life: a systematic review.","Health-related quality of life (HRQoL) is severely impaired in pulmonary arterial hypertension (PAH). We aimed to assess the effect of PAH-specific therapies on HRQoL. A literature search was performed in MEDLINE and Embase databases (January 1990 to September 2013) to retrieve prospective placebo-controlled randomized trials of at least 6 weeks duration reporting the effect of PAH-specific therapies on HRQoL in adult patients with PAH. The articles were independently reviewed,and the validity of the trials was assessed using the Cochrane's Risk of Bias Tool. The literature search identified 1,172 titles. Seventeen articles reporting on 14 trials were retrieved,all of which were associated with a low risk of bias. The median study duration of the different trials was 12 weeks. Most patients had idiopathic PAH or PAH associated with connective tissue disease. A variety of HRQoL questionnaires were used in these trials,and most were generic. HRQoL results were most commonly minimally detailed,and some pivotal trials did not even assess HRQoL. Nevertheless,these trials consistently demonstrated statistically significant improvements in HRQoL with PAH-specific therapies,especially for the physical domains. In most cases,however,these improvements were smaller than the minimal important difference in HRQoL previously reported in PAH. This review shows that PAH-specific therapies improve HRQoL in PAH. However,it remains difficult to draw any firm conclusion about the clinical significance of these improvements. Further work is mandatory to validate PAH-specific questionnaires that are responsive to clinical changes as well as to establish their interpretability.","Chest. 2014 Sep;146(3):686-708.","International",2014,"Any PAH,Interstitial lung disease","None or unknown","Unknown"]
[7,"Yorke J,Armstrong I. The assessment of breathlessness in pulmonary arterial hypertension: reliability and validity of the Dyspnoea-12. Eur J Cardiovasc Nurs. 2014 Dec;13(6):506-14. doi: 10.1177/1474515113514891. Epub 2013 Dec 3.","doi: 10.1177/1474515113514891. Epub 2013 Dec 3.","Yorke J,Armstrong I.","The assessment of breathlessness in pulmonary arterial hypertension: reliability and validity of the Dyspnoea-12.","Breathlessness is a cardinal symptom of pulmonary arterial hypertension (PAH); yet no breathlessness instrument has been previously tested for reliability and validity for this population. Using a cross-sectional design,we tested the psychometric properties of the Dyspnoea-12 (D-12),for the assessment of breathlessness in PAH. Pearson's correlations with World Health Organization functional class (WHO FC),Minnesota Living with Heart failure - pulmonary hypertension modified version (MLHF-PH),Hospital Anxiety and Depression scale (HADS) and 6-minute walk distance test (6MWD) were conducted. Participants (n = 176) were mostly female (70.5%),mean age 54.3±14 years; diagnosed with idiopathic PAH (48.9%),congenital heart disease (27.8%) and connective tissue disease (23.3%); and most were WHO FC II (32.4%) and III (52.3%). The D-12 showed excellent internal consistency for the total and two-component scores for physical and emotional (Cronbach's α 0.95,0.93 and 0.94,respectively). D-12 total score was significantly associated with MLHF-PH (r = 0.70),HADS (anxiety r = 0.54 and depression r = 0.68),WHO FC (r = 0.49),and 6MWD (r = -0.26). In patients with PAH,the D-12 - a short patient reported measure of breathlessness severity that taps the physical and emotional components,is a reliable and valid instrument.","Eur J Cardiovasc Nurs. 2014 Dec;13(6):506-14.","UK",2014,"Any PAH","None or unknown","D-12,HADS,MLHFQ"]
[8,"Yorke J,Corris P,Gaine S,Gibbs JS,Kiely DG,Harries C,Pollock V,Armstrong I. emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension. Eur Respir J. 2014 Apr;43(4):1106-13. doi: 10.1183/09031936.00127113. Epub 2013 Nov 14.","doi: 10.1183/09031936.00127113. Epub 2013 Nov 14.","Yorke J,Corris P,Gaine S,Gibbs JS,Kiely DG,Harries C,Pollock V,Armstrong I.","emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension.","The aim of this study was to develop a measure of the impact of pulmonary hypertension (PH) on health-related quality of life (HRQoL) as there is a need for a short,validated instrument that can be used in routine clinical practice. Interviews were conducted with 30 PH patients to derive 32 statements,which were presented as a semantic differential six-point scale (0-5),with contrasting adjectives at each end. This item list was completed by patients attending PH clinics across the UK and Ireland. Rasch analysis was applied to identify items fitting a uni-dimensional model. 226 patients (mean age 55.6±14 years; 70% female) with PH (82% had pulmonary arterial hypertension) completed the study questionnaires. 10 of the 32 items demonstrated fit to the Rasch model (Chi-squared 16; p>0.05) and generated the emPHasis-10 questionnaire. Test-retest (intraclass correlation coefficient 0.95,n=33) and internal consistency (Chronbach's α=0.9) were strong. emPHasis-10 scores correlated consistently with other relevant measures and discriminated subgroups of patients stratified by World Health Organization functional class (ANOVA F=1.73; p<0.001). The emPHasis-10 is a short questionnaire for assessing HRQoL in pulmonary arterial hypertension. It has excellent measurement properties and is sensitive to differences in relevant clinical parameters. It is freely available for clinical and academic use.","Eur Respir J. 2014 Apr;43(4):1106-13.","UK",2014,"Any PAH","None or unknown","EmPHasis-10"]
[9,"Harzheim D,Klose H,Pinado FP,Ehlken N,Nagel C,Fischer C,Ghofrani A,Rosenkranz S,Seyfarth HJ,Halank M,Mayer E,Grünig E,Guth S. Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Respir Res. 2013 Oct 9;14():104. doi: 10.1186/1465-9921-14-104. Epub 2013 Oct 9.","doi: 10.1186/1465-9921-14-104. Epub 2013 Oct 9.","Harzheim D,Klose H,Pinado FP,Ehlken N,Nagel C,Fischer C,Ghofrani A,Rosenkranz S,Seyfarth HJ,Halank M,Mayer E,Grünig E,Guth S.","Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.","The objective of this prospective study was to assess the prevalence of anxiety and depression disorders and their association with quality of life (QoL),clinical parameters and survival in patients with pulmonary hypertension (PH). We prospectively assessed 158 patients invasively diagnosed with pulmonary arterial hypertension (n = 138) and inoperable chronic thromboembolic PH (n = 20) by clinical measures including quality of life (QoL,SF-36 questionnaire),cardiopulmonary exercise testing and six minute walking distance and by questionnaires for depression (PHQ-9) and anxiety (GAD-7). According to the results of the clinical examination and the questionnaires for mental disorders (MD) patients were classified into two groups,1) with moderate to severe MD (n = 36,22,8%),and 2) with mild or no MD (n = 122). Patients were followed for a median of 2.7 years. Investigators of QoL,SF-36 were blinded to the clinical data. At baseline the 2 groups did not differ in their severity of PH or exercise capacity. Patients with moderate to severe MD (group 1) had a significantly lower QoL shown in all subscales of SF-36 (p < 0.002). QoL impairment significantly correlated with the severity of depression (p < 0.001) and anxiety (p < 0.05). During follow-up period 32 patients died and 3 were lost to follow-up. There was no significant difference between groups regarding survival. Only 8% of the patients with MD received psychopharmacological treatment. Anxiety and depression were frequently diagnosed in our patients and significantly correlated with quality of life,but not with long term survival. Further prospective studies are needed to confirm the results.","Respir Res. 2013 Oct 9;14():104.","Germany",2013,"Any PAH,CTEPH","None or unknown","GAD-7,PHQ-9,SF-36"]
[10,"Cha KS,Cho KI,Seo JS,Choi JH,Park YH,Yang DH,Hong GR,Kim DS. Effects of inhaled iloprost on exercise capacity,quality of life,and cardiac function in patients with pulmonary arterial hypertension secondary to congenital heart disease (the Eisenmenger syndrome) (from the EIGER Study). Am J Cardiol. 2013 Dec 1;112(11):1834-9. doi: 10.1016/j.amjcard.2013.08.003. Epub 2013 Sep 5.","doi: 10.1016/j.amjcard.2013.08.003. Epub 2013 Sep 5.","Cha KS,Cho KI,Seo JS,Choi JH,Park YH,Yang DH,Hong GR,Kim DS.","Effects of inhaled iloprost on exercise capacity,quality of life,and cardiac function in patients with pulmonary arterial hypertension secondary to congenital heart disease (the Eisenmenger syndrome) (from the EIGER Study).","There are limited data on the effect of iloprost therapy in patients with Eisenmenger syndrome (ES). The aim of our study was to evaluate the effect of inhaled iloprost therapy on exercise capacity,quality of life (QoL),cardiac function,and hemodynamics in patients with ES. Eighteen consecutive patients with ES and exertional dyspnea according to the World Health Organization functional class III or IV were prospectively recruited. Exercise capacity was assessed by a 6-minute walk test,and QoL was measured on a 12-Item Short-Form Health Survey. Echocardiographic measurements included peak systolic and mean pulmonary arterial pressures,pulmonary vascular resistance,and myocardial performance index of the right ventricle (RV). All patients underwent comprehensive evaluation at baseline and after 24 weeks of treatment. Of the 18 patients with ES,13 were included for analysis. After 24 weeks of iloprost therapy,6-minute walk test distance significantly increased (289.1 ± 76.9 to 369.5 ± 93.4 m,p = 0.032) in addition to concomitant improvements in the 12-Item Short-Form Health Survey physical and mental component summaries (20.6 ± 19.3 to 52.6 ± 28.0,p <0.05; 33.9 ± 19.7 to 54.9 ± 21.3,p <0.05,respectively). RV myocardial performance index improved significantly after treatment (0.80 ± 0.31 to 0.59 ± 0.12,p = 0.042). Pulmonary arterial pressure and pulmonary vascular resistance did not improve with iloprost therapy. This study showed that 24 weeks of inhaled iloprost therapy in patients with ES led to significant improvements in exercise capacity,QoL,and RV function. These results likely explain the symptomatic relief reported by patients with ES receiving iloprost therapy.","Am J Cardiol. 2013 Dec 1;112(11):1834-9.","Korea",2013,"Congenital HD","None or unknown","SF-12"]
[11,"Roman A,Barbera JA,Castillo MJ,Muñoz R,Escribano P. Health-related quality of life in a national cohort of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Arch Bronconeumol. 2013 May;49(5):181-8. doi: 10.1016/j.arbres.2012.12.007. Epub 2013 Feb 27.","doi: 10.1016/j.arbres.2012.12.007. Epub 2013 Feb 27.","Roman A,Barbera JA,Castillo MJ,Muñoz R,Escribano P.","Health-related quality of life in a national cohort of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.","Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) experience impaired health-related quality of life (HRQL). The objective of this study was to evaluate HRQL in a nation-wide sample. This is a prospective,multicenter,non-interventional study of HRQL including 139 (89%) PAH and 17 (11%) CTEPH patients (women 70.5%; mean age,52.2) recruited from 21 Spanish hospitals. 55% had idiopathic PAH,34% other PAH and 11% CTEPH. HRQL was measured using the Short Form 36 Health Survey (SF-36) and EuroQoL-5D (baseline and after 6 months). HRQL in the patients with PAH or CTEPH was impaired. The physical component of SF-36 and the EuroQol-5D correlated with the functional class (FC). Mean EuroQol-5D visual analogical scale (EQ-5D VAS) scores were 73.5±18.4,62.9±20.7 and 51.3±16.0 (P<.0001) in patients with FC I,II and III,respectively. Every increase of one FC represented a loss of 4.0 on the PCS SF-36 and a loss of 9.5 on the EQ-5D VAS. Eight patients who died or received a transplant during the study period presented poorer initial HRQL compared with the rest of the population. No significant changes in HRQL were observed in survivors after 6 months of follow-up. HRQL is impaired in this population,especially in PAH/CTEPH patients near death. HRQL measurements could help predict the prognosis in PAH and CTPH and provide additional information in these patients.","Arch Bronconeumol. 2013 May;49(5):181-8.","Spain",2013,"Any PAH,CTEPH","None or unknown","EQ-5D,SF-36"]
[12,"Judson MA,Highland KB,Kwon S,Donohue JF,Aris R,Craft N,Burt S,Ford HJ. Ambrisentan for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2011 Oct;28(2):139-45.",null,"Judson MA,Highland KB,Kwon S,Donohue JF,Aris R,Craft N,Burt S,Ford HJ.","Ambrisentan for sarcoidosis associated pulmonary hypertension.","Sarcoidosis associated pulmonary hypertension (SAPH) is associated with significant morbidity and mortality. There is a paucity of information concerning therapy for this condition. We performed a prospective,open-label,proof of concept trial of ambrisentan for SAPH. 21 subjects with SAPH received 5 mg/day of ambrisentan for 4 weeks and then 10/mg day for 20 subsequent weeks. No significant change was noted in the 6-minute walk distance over the course of the study (mean change between week 0 and 24: 9.8 +/- 54.6 meters,p: NS). There were also no significant differences between weeks 0 and 24 in terms of dyspnea as measured by the modified Borg scale,serum brain naturetic peptide,diffusing capacity,and quality of life as measured by the Short Form-36. There was a high dropout rate: overall: 11/21,52%; social reasons: 3/21,14%; medical reasons: 8/21,38% because of dyspnea: 6/21,29% and/or edema: 4/21,19%. Of those who completed the 24 week study (10/21,48%),there was an improvement in their WHO functional class and a marked improvement in their health related quality of life as measured by the St. George Respiratory questionnaire (-15.3 +/- 25.0). However both these improvments did not reach statistical significance possibly because of the small sample size. Although ambrisentan was not well tolerated by many of these subjects with SAPH,in those who remained in this 24-week trial,improvements in WHO functional class and in health related quality of life suggested a possible benefit of this drug in selected patients.","Sarcoidosis Vasc Diffuse Lung Dis. 2011 Oct;28(2):139-45.","USA",2011,"Sarcoidosis","Ambrisentan","BDI,SF-36,SGRQ"]
[13,"Kowal-Bielecka O,Avouac J,Pittrow D,Huscher D,Behrens F,Denton CP,Foeldvari I,Humbert M,Matucci-Cerinic M,Nash P,Opitz CF,Rubin LJ,Seibold JR,Strand V,Furst DE,Distler O,Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension Related to Systemic Sclerosis. Analysis of the validation status of quality of life and functional disability measures in pulmonary arterial hypertension related to systemic sclerosis: results of a systematic literature analysis by the Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis (EPOSS). J Rheumatol. 2011 Nov;38(11):2419-27. doi: 10.3899/jrheum.110344. Epub 2011 Oct 1.","doi: 10.3899/jrheum.110344. Epub 2011 Oct 1.","Kowal-Bielecka O,Avouac J,Pittrow D,Huscher D,Behrens F,Denton CP,Foeldvari I,Humbert M,Matucci-Cerinic M,Nash P,Opitz CF,Rubin LJ,Seibold JR,Strand V,Furst DE,Distler O,Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension Related to Systemic Sclerosis.","Analysis of the validation status of quality of life and functional disability measures in pulmonary arterial hypertension related to systemic sclerosis: results of a systematic literature analysis by the Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis (EPOSS).","We aimed to assess the current validity status of the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the 36-item Medical Outcomes Study Short Form Health Survey (SF-36). Studies using HAQ-DI and/or SF-36 in patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (PAH-SSc) were identified through a systematic literature review and assessed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus group criteria. Both HAQ-DI and SF-36 were considered credible (having face validity) and feasible. Based on expert opinion,neither HAQ-DI nor SF-36 was specific for PAH-SSc since their results may be influenced by other aspects of SSc (judged \"unclear\" with respect to the content validity criterion). In the overall SSc population,there was significant albeit weak correlation between physical component SF-36 scores and pulmonary artery systolic pressure (PASP) by echocardiography (Kendall tau b = -0.2,p < 0.01). Although HAQ-DI also correlated with PASP by echocardiography,there were no significant correlations in SSc patients with PAH proven by right heart catheterization between changes in HAQ-DI over time and changes in other PAH measures including 6-min walk distance (r = -0.04,p = 0.86),expert global assessment (r = 0.06,p = 0.97),and New York Heart Association functional class (r = 0.38,p = 0.39),indicating lack of construct validity for HAQ-DI in PAH-SSc. No studies enabling assessment of criterion validity or discrimination of HAQ-DI or SF-36 in PAH-SSc could be identified. Further validation of HAQ and SF-36 in PAH-SSc is needed. Alternatively,more specific assessments for functional disability or quality of life in PAH-SSc might be required.","J Rheumatol. 2011 Nov;38(11):2419-27.","International",2011,"Systemic sclerosis","None or unknown","HAQ-DI,SF-36"]
[14,"Chen H,De Marco T,Kobashigawa EA,Katz PP,Chang VW,Blanc PD. Comparison of cardiac and pulmonary-specific quality-of-life measures in pulmonary arterial hypertension. Eur Respir J. 2011 Sep;38(3):608-16. doi: 10.1183/09031936.00161410. Epub 2011 Jan 27.","doi: 10.1183/09031936.00161410. Epub 2011 Jan 27.","Chen H,De Marco T,Kobashigawa EA,Katz PP,Chang VW,Blanc PD.","Comparison of cardiac and pulmonary-specific quality-of-life measures in pulmonary arterial hypertension.","Studies systematically comparing the performance of health-related quality-of-life (HRQoL) instruments in pulmonary arterial hypertension (PAH) are lacking. We sought to address this by comparing cardiac and respiratory-specific measures of HRQoL in PAH. We prospectively assessed HRQoL in 128 patients with catheterisation-confirmed PAH at baseline and at 6,12 and post-24 month follow-up visits. Cardiac-specific HRQoL was assessed using the Minnesota Living with Heart Failure Questionnaire (LHFQ); respiratory-specific HRQoL was assessed using the Airways Questionnaire 20 (AQ20); and general health status was assessed using the 36-item Short Form physical component summary (SF-36 PCS). The LHFQ and AQ20 were highly intercorrelated. Both demonstrated strong internal consistency and converged with the SF-36 PCS. Both discriminated patients based on World Health Organization (WHO) functional class,6-min walking distance (6MWD) and Borg dyspnoea index (BDI),with the exception of a potential floor effect associated with low 6MWD. The LHFQ was more responsive than the AQ20 to changes over time in WHO functional class,6MWD and BDI. In multivariate analyses,the LHFQ and AQ20 were each longitudinal predictors of general health status,independent of functional class,6MWD and BDI. In conclusion,both cardiac-specific and respiratory-specific measures appropriately assess HRQoL in most patients with PAH. Overall,the LHFQ demonstrates stronger performance characteristics than the AQ20.","Eur Respir J. 2011 Sep;38(3):608-16.","USA",2011,"Any PAH","None or unknown","AQ20,MLHFQ,SF-36"]
[15,"Tyndall AJ,Bannert B,Vonk M,Airò P,Cozzi F,Carreira PE,Bancel DF,Allanore Y,Müller-Ladner U,Distler O,Iannone F,Pellerito R,Pileckyte M,Miniati I,Ananieva L,Gurman AB,Damjanov N,Mueller A,Valentini G,Riemekasten G,Tikly M,Hummers L,Henriques MJ,Caramaschi P,Scheja A,Rozman B,Ton E,Kumánovics G,Coleiro B,Feierl E,Szucs G,Von Mühlen CA,Riccieri V,Novak S,Chizzolini C,Kotulska A,Denton C,Coelho PC,Kötter I,Simsek I,de la Pena Lefebvre PG,Hachulla E,Seibold JR,Rednic S,Stork J,Morovic-Vergles J,Walker UA. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010 Oct;69(10):1809-15. doi: 10.1136/ard.2009.114264. Epub 2010 Jun 15.","doi: 10.1136/ard.2009.114264. Epub 2010 Jun 15.","Tyndall AJ,Bannert B,Vonk M,Airò P,Cozzi F,Carreira PE,Bancel DF,Allanore Y,Müller-Ladner U,Distler O,Iannone F,Pellerito R,Pileckyte M,Miniati I,Ananieva L,Gurman AB,Damjanov N,Mueller A,Valentini G,Riemekasten G,Tikly M,Hummers L,Henriques MJ,Caramaschi P,Scheja A,Rozman B,Ton E,Kumánovics G,Coleiro B,Feierl E,Szucs G,Von Mühlen CA,Riccieri V,Novak S,Chizzolini C,Kotulska A,Denton C,Coelho PC,Kötter I,Simsek I,de la Pena Lefebvre PG,Hachulla E,Seibold JR,Rednic S,Stork J,Morovic-Vergles J,Walker UA.","Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database.","To determine the causes and predictors of mortality in systemic sclerosis (SSc). Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths,35% were attributed to pulmonary fibrosis,26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes,infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities,25% died of causes in which SSc-related complications may have participated (pneumonia,sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34),the presence of PAH based on echocardiography (HR 2.02),pulmonary restriction (forced vital capacity below 80% of normal,HR 1.64),dyspnoea above New York Heart Association class II (HR 1.61),diffusing capacity of the lung (HR 1.20 per 10% decrease),patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). Disease-related causes,in particular pulmonary fibrosis,PAH and cardiac causes,accounted for the majority of deaths in Ssc.","Ann Rheum Dis. 2010 Oct;69(10):1809-15.","International",2010,"Systemic sclerosis","None or unknown","RSS"]
[16,"Ovaert C,Thijs D,Dewolf D,Ottenkamp J,Dessy H,Moons P,Gewillig M,Mertens L. The effect of bosentan in patients with a failing Fontan circulation. Cardiol Young. 2009 Aug;19(4):331-9. doi: 10.1017/S1047951109990023. Epub 2009 Jun 11.","doi: 10.1017/S1047951109990023. Epub 2009 Jun 11.","Ovaert C,Thijs D,Dewolf D,Ottenkamp J,Dessy H,Moons P,Gewillig M,Mertens L.","The effect of bosentan in patients with a failing Fontan circulation.","To investigate the effect of bosentan in patients with a failing Fontan circulation. A multicentric open label,non-controlled study. 5 tertiary care centres for congenital cardiology. We included 10 patients with a failing Fontan circulation. Their median age at inclusion was 12.12 years,with a range from 4.41 to 33,41 years. The median interval between the Fontan operation and inclusion was 7.84 years,with a range from 1.96 to 12,18 years. Participants received half the usual dose of bosentan for 4 weeks,and then the full dose for a further 12 weeks. MAIN MEASURES OF OUTCOMES: We assessed saturations of oxygen at rest and during exercise,using a 6 minutes walk test,at baseline,and during and after 16 weeks of treatment. At each visit,we assessed blood chemistry and hepatic function,and asked the patients to complete a questionnaire concerning quality of life. All medical events and possible side effects were recorded. Of the cohort,1 patient withdrew. The changes in saturations of oxygen,exercise performance,and scores for the questionnaire did not reach statistical significance for the whole group. We noted,nonetheless,that saturations of oxygen and/or exercise capacity improved in 5 of the patients. This was further confirmed when those patients deteriorated again when the drug was discontinued. Our study failed to show significant improvement after 3 months of treatment with bosentan in a small group of patients with failing Fontan circulations. Some individuals,nonetheless,did improve. When planning larger trials,it would be better to identify those patients who might potentially benefit from the treatment prior to commencing the trial.","Cardiol Young. 2009 Aug;19(4):331-9.","Belgium",2009,"Congenital HD","Bosentan","Unknown"]
[17,"Sitbon O,Gressin V,Speich R,Macdonald PS,Opravil M,Cooper DA,Fourme T,Humbert M,Delfraissy JF,Simonneau G. Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2004 Dec 1;170(11):1212-7. doi: 10.1164/rccm.200404-445OC. Epub 2004 Aug 18.","doi: 10.1164/rccm.200404-445OC. Epub 2004 Aug 18.","Sitbon O,Gressin V,Speich R,Macdonald PS,Opravil M,Cooper DA,Fourme T,Humbert M,Delfraissy JF,Simonneau G.","Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension.","Clinical studies have shown the importance of endothelin as a pathogenic mediator in pulmonary arterial hypertension (PAH). We describe the effects of bosentan,an oral dual endothelin receptor antagonist,in patients with PAH associated with human immunodeficiency virus (HIV) infection. In this prospective study,16 patients with PAH associated with HIV infection in stable condition received bosentan for 16 weeks. Efficacy endpoints included exercise capacity,cardiopulmonary hemodynamics,Doppler echocardiography,New York Heart Association functional class,and quality of life (SF-36 and EQ-5D). Safety was assessed by laboratory tests,vital signs,and adverse events. Improvements were observed from baseline to Week 16 in all efficacy parameters: 6-minute walk distance (+91 +/- 60 m,p < 0.001),New York Heart Association class (14 patients improved),hemodynamics (cardiac index: +0.9 +/- 0.7 L/minute/m(2),p < 0.001),Doppler echocardiographic variables,and quality of life. During the study,no patient died and none required epoprostenol treatment. Hepatic tolerability was similar to that reported in patients with PAH. Bosentan had no negative impact on control of HIV infection. Although limited by uncontrolled design,small sample size and short duration,this study suggests that bosentan may benefit patients with PAH associated with HIV infection,and that endothelin is an important pathogenic mediator in this disease.","Am J Respir Crit Care Med. 2004 Dec 1;170(11):1212-7.","France",2004,"HIV","Bosentan","EQ-5D,SF-36"]
[18,"Morris NR,Kermeen FD,Holland AE. Exercise-based rehabilitation programmes for pulmonary hypertension. Cochrane Database Syst Rev. 2017 Jan 19;1():CD011285. doi: 10.1002/14651858.CD011285.pub2. Epub 2017 Jan 19.","doi: 10.1002/14651858.CD011285.pub2. Epub 2017 Jan 19.","Morris NR,Kermeen FD,Holland AE.","Exercise-based rehabilitation programmes for pulmonary hypertension.","Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group,several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation in PH. To assess the efficacy and safety of exercise-based rehabilitation for people with PH. Primary outcomes were exercise capacity,adverse events during the intervention period and health-related quality of life (HRQoL). Secondary outcomes included cardiopulmonary haemodynamics,functional class,clinical worsening during follow-up,mortality and changes in B-type natriuretic peptide. We searched the Cochrane Airways Specialised Register of Trials up to August 2016,which is based on regular searches of CINAHL,AMED,Embase,PubMed,MEDLINE,PsycINFO and registries of clinical trials. In addition we searched CENTRAL and the PEDro database up to August 2016 and handsearched relevant journals. All randomised controlled trials (RCTs) focusing on exercise-based rehabilitation programmes for PH. Two reviewers extracted data independently. For binary outcomes,we calculated odds ratios and their 95% confidence interval (CI),on an intention-to-treat basis. For continuous data,we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. We included six RCTs and were able to extract data from five studies. The majority of participants were Group I pulmonary artery hypertension (PAH). Study duration ranged from three to 15 weeks. Exercise programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise training was 60.12 metres higher than control (30.17 to 90.07 metres,n = 165,5 RCTs,low-quality evidence; minimal important difference was 30 metres),the mean peak oxygen uptake was 2.4 ml/kg/minute higher (1.4 to 3.4 ml/kg/min,n = 145,4 RCTs,low-quality evidence) and the mean peak power in the intervention groups was 16.4 W higher (10.9 to 22.0 higher,n = 145,4 RCTs,low-quality evidence). The mean change in HRQoL for the SF-36 physical component score was 4.63 points higher (0.80 to 8.47 points,n = 33,2 RCTs,low-quality evidence) and for the SF-36 mental component score was 4.17 points higher (0.01 to 8.34 points; n = 33; 2 RCTs,low-quality evidence). One study reported a single adverse event,where a participant stopped exercise training due to lightheadedness. In people with PH,exercise-based rehabilitation results in clinically relevant improvements in exercise capacity. Exercise training was not associated with any serious adverse events. Whilst most studies reported improvements in HRQoL,these may not be clinically important. Overall,we assessed the quality of the evidence to be low. The small number of studies and lack of information on participant selection makes it difficult to generalise these results across the spectrum of people with PH.","Cochrane Database Syst Rev. 2017 Jan 19;1():CD011285.","International",2017,"Any PAH","Exercise","SF-36"]
[19,"Mehta S,Sastry BK,Souza R,Torbicki A,Ghofrani HA,Channick RN,Delcroix M,Pulido T,Simonneau G,Wlodarczyk J,Rubin LJ,Jansa P,Hunsche E,Galiè N,Perchenet L,Sitbon O. Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial. Chest. 2017 Jan;151(1):106-118. doi: 10.1016/j.chest.2016.08.1473. Epub 2016 Sep 23.","doi: 10.1016/j.chest.2016.08.1473. Epub 2016 Sep 23.","Mehta S,Sastry BK,Souza R,Torbicki A,Ghofrani HA,Channick RN,Delcroix M,Pulido T,Simonneau G,Wlodarczyk J,Rubin LJ,Jansa P,Hunsche E,Galiè N,Perchenet L,Sitbon O.","Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial.","Pulmonary arterial hypertension (PAH) leads to reduced health-related quality of life (HRQoL). The objectives of this analysis were to evaluate the effect of macitentan on HRQoL in patients with PAH in the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) study. The association between baseline HRQoL and long-term outcomes was also investigated. Patients were randomized to placebo,macitentan 3 mg,or macitentan 10 mg once daily. Patients aged 14 years or older completed the 36-Item Short Form Survey (SF-36) at baseline,at month 6 and month 12,and at the end of treatment (EOT). The absolute change from baseline to month 6 in SF-36 scores was calculated. The time to a clinically meaningful deterioration in the SF-36 physical component summary and mental component summary (PCS and MCS) scores and associations between baseline PCS/MCS scores and time to morbidity/mortality events were also assessed. At month 6,macitentan 10 mg significantly improved seven of eight SF-36 domains and the PCS and MCS scores vs placebo. Macitentan 10 mg significantly reduced the risk of a three-point or greater deterioration in PCS (hazard ratio [HR],0.60; 95% CI,0.47-0.76; P < .0001) and MCS scores (HR,0.76; 95% CI,0.61-0.95; P = .0173) until EOT vs placebo. Patients with a baseline PCS score greater than the median baseline value had a significantly reduced risk of morbidity/mortality compared with patients with a PCS score less than the median; a similar result was observed for the MCS score. Macitentan significantly improved HRQoL in patients with PAH compared with placebo and significantly reduced the risk of a clinically meaningful HRQoL deterioration. An association between better baseline HRQoL and improved long-term outcomes was shown. ClinicalTrials.gov; No.: NCT00660179; URL: clinicaltrials.gov.","Chest. 2017 Jan;151(1):106-118.","International",2017,"Any PAH","Macitentan","SF-36"]
[20,"Reis A,Twiss J,Vicente M,Gonçalves F,Carvalho L,Meireles J,Melo A,McKenna SP,Almeida L. Portuguese validation of the Cambridge pulmonary hypertension outcome review (CAMPHOR) questionnaire. Health Qual Life Outcomes. 2016 Jul 26;14(1):110. doi: 10.1186/s12955-016-0513-8. Epub 2016 Jul 26.","doi: 10.1186/s12955-016-0513-8. Epub 2016 Jul 26.","Reis A,Twiss J,Vicente M,Gonçalves F,Carvalho L,Meireles J,Melo A,McKenna SP,Almeida L.","Portuguese validation of the Cambridge pulmonary hypertension outcome review (CAMPHOR) questionnaire.","Patients with pulmonary arterial hypertension (PAH) and other forms of precapillary pulmonary hypertension (PH) have impaired quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a PH-specific patient-reported outcome measure that assesses symptoms,activity limitations and QoL. It was originally developed in UK-English. The main objective of this study was to create an adaptation of the CAMPHOR suitable for a Portuguese-speaking population. A multi-step approach was followed: bilingual and lay panel translation; cognitive debriefing interviews; and psychometric testing in repeated postal surveys (2 weeks apart) including assessment of internal consistency,reproducibility and validity. The Nottingham Health Profile (NHP) questionnaire was used as a comparator instrument to test convergent validity. The CAMPHOR was translated without difficulty by the two panels. Cognitive debriefing interviews showed the questionnaire was easily understood and considered relevant to patients' experience with their illness. Psychometric evaluation was performed with 50 PAH patients (47 ± 14 years,37 women). Cronbach's alpha coefficients showed good internal consistency for the three CAMPHOR scales [Symptoms = 0.95; Activities = 0.93 and QoL = 0.94]. Test-retest coefficients showed that all scales had excellent reliability (Symptoms = 0.94; Activities = 0.89 and QoL = 0.93),indicating low levels of random measurement error. The CAMPHOR correlated as expected with the NHP. The magnitude of correlations followed a similar pattern to those in the original development study. The CAMPHOR also exhibited evidence of known group validity in its ability to distinguish between self-reported severity and general health groups. A valid and reliable version of the CAMPHOR questionnaire for the European Portuguese-speaking population was developed and is recommended for use.","Health Qual Life Outcomes. 2016 Jul 26;14(1):110.","Portugal",2016,"Any PAH","None or unknown","CAMPHOR"]
[21,"Matura LA,McDonough A,Hanlon AL,Carroll DL. Developmental and Initial Validation of the Pulmonary Arterial Hypertension Symptom Inference Scale. J Nurs Meas. 2016;24(1):40-53. doi: 10.1891/1061-3749.24.1.40.","doi: 10.1891/1061-3749.24.1.40.","Matura LA,McDonough A,Hanlon AL,Carroll DL.","Developmental and Initial Validation of the Pulmonary Arterial Hypertension Symptom Inference Scale.","Pulmonary arterial hypertension is a chronic illness that produces multiple symptoms and impairs quality of life. The purpose of this study was to describe the initial psychometric properties of the Pulmonary Arterial Hypertension Symptom Interference Scale (PAHSIS). Participants completed a sociodemographic and clinical data form: the PAHSIS and the Medical Outcomes Study Short Form-36 (SF-36). Data analysis included descriptive statistics,principal component analysis (PCA),and Pearson r correlations. PCA revealed a 3-factor solution: Cardiopulmonary,Weary,and Gastric. Correlations between the 3 factors and the SF-36 subscales and composite summary scores ranged from acceptable to high. These findings support the initial validity and reliability of the PAHSIS. Nursing can use the PAHSIS to assess the impact of patient symptoms to deploy effective,targeted interventions.","J Nurs Meas. 2016;24(1):40-53.","USA",2016,"Any PAH","None or unknown","PAHSIS,SF-36"]
[22,"Amedro P,Basquin A,Gressin V,Clerson P,Jais X,Thambo JB,Guerin P,Cohen S,Bonnet D. Health-related quality of life of patients with pulmonary arterial hypertension associated with CHD: the multicentre cross-sectional ACHILLE study. Cardiol Young. 2016 Oct;26(7):1250-9. doi: 10.1017/S1047951116000056. Epub 2016 Mar 16.","doi: 10.1017/S1047951116000056. Epub 2016 Mar 16.","Amedro P,Basquin A,Gressin V,Clerson P,Jais X,Thambo JB,Guerin P,Cohen S,Bonnet D.","Health-related quality of life of patients with pulmonary arterial hypertension associated with CHD: the multicentre cross-sectional ACHILLE study.","The aim of this study was to assess health-related quality of life in patients with pulmonary arterial hypertension associated with CHD and correlations with clinical status. This prospective cross-sectional observational study included CHD patients with pulmonary arterial hypertension in 14 tertiary-care centres in France. We used two health-related quality of life questionnaires - SF-36 and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) - and one anxiety/depression Hospital Anxiety and Depression Scale (HADS) questionnaire. Clinical data were collected for the 208 included patients (mean age: 42.6 years,range from 15.1 to 85.8 years,69.7% female). Most patients were in NYHA functional class II (48.1%) and III (37.5%). Patients' phenotype was classified as Eisenmenger syndrome (70.7%),pulmonary arterial hypertension associated with systemic-to-pulmonary shunts (12.0%),with small defects (3.4%),or after corrective cardiac surgery (13.9%). In total,76.4% of the patients were receiving pulmonary arterial hypertension-specific treatments. SF-36 scores showed impairment compared with normalised data. Health-related quality of life scores were significantly lower in females than in males for most dimensions of both questionnaires and were independent of the patients' phenotype,even after gender adjustment - except for CAMPHOR functioning - but significantly depended on NYHA functional class. The Hospital Anxiety and Depression Scale (HADS) scores suggested anxiety and depression associated with increasing NYHA functional class but independent of patients' phenotype. NYHA functional class,6-minute walk distance,HADS,gender,and recent stressful event significantly affected quality of life in the multivariate analysis. This study showed impairment of quality of life in a large cohort of patients with pulmonary arterial hypertension associated with CHD with both generic and specific questionnaires. NYHA functional class and HADS scores were predictive of most quality of life scores.","Cardiol Young. 2016 Oct;26(7):1250-9.","France",2016,"Congenital HD","None or unknown","CAMPHOR,HADS,SF-36"]
[23,"Karsenty C,Maury P,Blot-Souletie N,Ladouceur M,Leobon B,Senac V,Mondoly P,Elbaz M,Galinier M,Dulac Y,Carrié D,Acar P,Hascoet S. The medical history of adults with complex congenital heart disease affects their social development and professional activity. Arch Cardiovasc Dis. 2015 Nov;108(11):589-97. doi: 10.1016/j.acvd.2015.06.004. Epub 2015 Sep 11.","doi: 10.1016/j.acvd.2015.06.004. Epub 2015 Sep 11.","Karsenty C,Maury P,Blot-Souletie N,Ladouceur M,Leobon B,Senac V,Mondoly P,Elbaz M,Galinier M,Dulac Y,Carrié D,Acar P,Hascoet S.","The medical history of adults with complex congenital heart disease affects their social development and professional activity.","In recent decades,advances in surgery and therapeutic catheterization have steadily increased the life expectancy and prevalence of adults with congenital heart disease (CHD). We assessed medical and psychosocial variables of adults with CHD,according to the disease complexity. We included,from a single-centre observational cohort study,135 consecutive adults with CHD (median age of 40 years,interquartile range: 28.0-51.0) followed in our cardiology unit,who answered a questionnaire assessing daily activity and psychosocial functioning. Disease complexity was classified according to the Bethesda conference. Cardiac malformation complexity was simple in 61 (45.2%),moderate in 50 (37.0%) and complex in 24 (17.8%) patients. Cardiac surgery had been performed in 86.5% of moderate and complex patients. Complications (such as heart failure,arrhythmia and pulmonary hypertension) were mainly observed in the complex group (P=0.003). Physical activity was lower in the complex group (no activity in 58.8%,but sport previously contraindicated in 50% of these; P=0.03). Education level tended to be lower in the complex and moderate groups than in the simple group (respectively,31.2% and 33.3% vs. 45.7% had passed the Baccalaureate; P=0.47). The pass rate was lower in patients with complications (P=0.037) or more than one cardiac surgery (P=0.03). In the complex group,56.3% of patients were unemployed (P=0.048). Complexity of heart disease and medical history affect education level and employment of adults with CHD. Academic education of children with a complex defect and career counselling are important to prevent unemployment among adults with CHD.","Arch Cardiovasc Dis. 2015 Nov;108(11):589-97.","France",2015,"Congenital HD","Surgery","Unknown"]
[24,"Provencher S,Paruchuru P,Spezzi A,Waterhouse B,Gomberg-Maitland M,pH12 Flolan reformulation study group. Quality of life,safety and efficacy profile of thermostable flolan in pulmonary arterial hypertension. PLoS One. 2015;10(3):e0120657. doi: 10.1371/journal.pone.0120657. Epub 2015 Mar 20.","doi: 10.1371/journal.pone.0120657. Epub 2015 Mar 20.","Provencher S,Paruchuru P,Spezzi A,Waterhouse B,Gomberg-Maitland M,pH12 Flolan reformulation study group.","Quality of life,safety and efficacy profile of thermostable flolan in pulmonary arterial hypertension.","Flolan (epoprostenol sodium) is most commonly prescribed to patients with severe pulmonary arterial hypertension (PAH) owing to the requirement that the drug be delivered by continuous intravenous infusion and the reconstituted solution may only be administered up to 24 hours when it is maintained between a temperature of 2°C and 8°C. The aim of this single-arm,open label study was to describe the effects of the new thermostable formulation of Flolan on health-related quality of life (HRQoL) and ease of administration in subjects switching from the currently marketed Flolan to the reformulated product. Following a 4-week run-in period and after 4 weeks of treatment with the reformulated product,patients completed the SF-36 HRQoL questionnaire and a study-specific questionnaire evaluating ease of administration,along with World Health Organization (WHO) functional class,six-minute walked distance (6MWD) and N-terminal-pro B-type natriuretic peptide (NT-proBNP) assessment. 16 participants completed the study. The SF-36 scores remained unchanged from baseline to Week 4. Conversely,there were small improvements for the majority of the study-specific questionnaire items and 14 (88%) subjects preferred the reformulated product to the currently marketed Flolan. There was no significant change in the dose of reformulated product,6MWD,Borg dyspnoea index,WHO functional class and mean NT-proBNP levels. No significant changes in haemodynamic parameters were seen from baseline to 2 hours post transition in a subset of patients undergoing catheterization. The reformulated product was not associated with significant improvement in HRQoL compared with the currently marketed Flolan as measured by the SF-36. However,most subjects preferred the reformulated product to the currently marketed Flolan. Moreover,the 2 formulations of Flolan had similar safety and efficacy profiles. ClinicalTrials.gov NCT01462565.","PLoS One. 2015;10(3):e0120657.","Canada,USA",2015,"Any PAH","Epoprostanol","SF-36"]
[25,"Mathai SC,Hassoun PM,Puhan MA,Zhou Y,Wise RA. Sex differences in response to tadalafil in pulmonary arterial hypertension. Chest. 2015 Jan;147(1):188-97. doi: 10.1378/chest.14-0263.","doi: 10.1378/chest.14-0263.","Mathai SC,Hassoun PM,Puhan MA,Zhou Y,Wise RA.","Sex differences in response to tadalafil in pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) is a progressive disease with high rates of morbidity and mortality. Current therapies improve symptoms,functional capacity,and,in select cases,survival. Little is known about patient factors that may predict the likelihood of patient-important,clinically relevant responses to therapy such as the 6-min walk distance (6MWD) and health-related quality of life (HRQoL). Data from the randomized clinical trial of tadalafil in PAH were used. Adjusted logistic regression models were created to examine the relationship between baseline characteristics and odds of achieving the minimal important difference (MID) in three parameters,defined as either a > 33-m increase in 6MWD,a > 5-unit increase in physical component summary score of the Medical Outcomes Study Short Form-36 (SF-36),or a > 5-unit increase in mental component summary score of the SF-36. The study included 405 subjects. Younger age,male sex,lower baseline 6MWD,and disease etiology were associated with greater odds of achieving the MID for the 6-min walk test. Active treatment,younger age,and male sex were associated with greater odds of achieving the MID for the physical component summary score. Male sex was associated with greater odds of achieving the MID for the mental component summary score. Age,sex,baseline functional capacity,and disease etiology are variably associated with the likelihood of achieving clinically relevant responses in patient-important outcomes to PAH-specific therapy such as 6MWD and HRQoL. The increased likelihood of response in men compared with women is a novel finding and may reflect pathophysiologic differences between sexes.","Chest. 2015 Jan;147(1):188-97.",null,2015,"Any PAH","Tadalafil","SF-36"]
[26,"Matura LA,McDonough A,Hanlon AL,Carroll DL,Riegel B. Sleep disturbance,symptoms,psychological distress,and health-related quality of life in pulmonary arterial hypertension. Eur J Cardiovasc Nurs. 2015 Oct;14(5):423-30. doi: 10.1177/1474515114537951. Epub 2014 May 27.","doi: 10.1177/1474515114537951. Epub 2014 May 27.","Matura LA,McDonough A,Hanlon AL,Carroll DL,Riegel B.","Sleep disturbance,symptoms,psychological distress,and health-related quality of life in pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) is a devastating disease characterized by elevated pulmonary pressures that lead to right heart failure and premature mortality. Patients experience multiple symptoms including dyspnea,fatigue and chest pain,but little is known about sleep disturbance,PAH symptoms,psychological distress and health-related quality of life (HRQOL) in PAH. The purpose of this study was to describe the occurrence of sleep disturbance and compare PAH symptoms,psychological distress,and HRQOL across severity of sleep disturbance. One hundred and ninety-one participants completed a socio-demographic and clinical data form,PAH Symptom Severity Scale,Profile of Mood States (POMS) short form and the Medical Outcomes Short Form-36 (SF-36). Descriptive statistics were used to describe sleep disturbances; analysis of variance models were used to quantify differences in PAH symptoms,psychological distress and HRQOL by sleep disturbance groups. The majority of participants (n=162,85%) were women with a mean age of 53 years. Sixty-five (34%) reported no sleep disturbance; 54 (28%) mild sleep disturbance; 41 (22%) moderate sleep disturbance; and 31 (16%) severe sleep disturbance. Those reporting higher sleep disturbance severity reported worse PAH symptoms,psychological distress,and HRQOL. Sleep disturbance is a significant finding in PAH. Increasing levels of sleep disturbance are associated with worse PAH symptoms,psychological states,and health-related quality of life. Interventions that decrease sleep disturbances may improve symptoms and HRQOL.","Eur J Cardiovasc Nurs. 2015 Oct;14(5):423-30.","USA",2015,"Any PAH","None or unknown","PAH-SSS,POMS,SF-36"]
[27,"Ozdemirel TS,Ulaşli SS,Yetiş B,Karaçağlar E,Bayraktar N,Ulubay G. Effects of right ventricular dysfunction on exercise capacity and quality of life and associations with serum NT-proBNP levels in COPD: an observational study. Anadolu Kardiyol Derg. 2014 Jun;14(4):370-7. doi: 10.5152/akd.2014.4687. Epub 2014 Apr 16.","doi: 10.5152/akd.2014.4687. Epub 2014 Apr 16.","Ozdemirel TS,Ulaşli SS,Yetiş B,Karaçağlar E,Bayraktar N,Ulubay G.","Effects of right ventricular dysfunction on exercise capacity and quality of life and associations with serum NT-proBNP levels in COPD: an observational study.","During the course of chronic obstructive pulmonary disease (COPD),pulmonary hypertension (PH) and right ventricular (RV) failure may develop due to elevated afterload of the RV. In those patients,exercise capacity is reduced due to pulmonary and cardiac limitations. We investigated relationships between serum N-terminal of proB-type natriuretic peptide (NT-proBNP) and RV functions with exercise capacity and quality of life in patients COPD. An observational case-control study was conducted. We enrolled 31 moderate and severe COPD patients,and 20 subjects without chronic diseases as control group. Parameters reflecting the right ventricular diastolic and systolic functions by echocardiography along with serum NT-proBNP levels were assessed. Cardiopulmonary exercise testing and Short Form-36 (SF-36) were applied. Serum NT-proBNP levels were higher in COPD patients than control group (p=0.003). Serum NT-proBNP level was found to be related with pulmonary arterial pressure. Serum NT-proBNP levels were negatively correlated with anaerobic threshold oxygen uptake (AT VO2) and peak oxygen uptake (PVO2) values. Early ventricular filling velocity (Em) was lower in COPD patients. Em wave was significantly correlated with O2 pulse. There was a positive relationship between tricuspid E/A ratio and VO2 value at AT. SF-36 domains of physical functioning,general health and role limitation due to physical disorder were significantly correlated with AT VO2,PVO2 and O2 pulse. Exercise limitation may be predicted by assessment of right ventricule functions and NT-proBNP levels and exercise limitation impairs quality of life in COPD patients.","Anadolu Kardiyol Derg. 2014 Jun;14(4):370-7.","Turkey",2014,"COPD","None or unknown","SF-36"]
[28,"Goudie AR,Lipworth BJ,Hopkinson PJ,Wei L,Struthers AD. Tadalafil in patients with chronic obstructive pulmonary disease: a randomised,double-blind,parallel-group,placebo-controlled trial. Lancet Respir Med. 2014 Apr;2(4):293-300. doi: 10.1016/S2213-2600(14)70013-X. Epub 2014 Mar 5.","doi: 10.1016/S2213-2600(14)70013-X. Epub 2014 Mar 5.","Goudie AR,Lipworth BJ,Hopkinson PJ,Wei L,Struthers AD.","Tadalafil in patients with chronic obstructive pulmonary disease: a randomised,double-blind,parallel-group,placebo-controlled trial.","Phosphodiesterase-5 (PDE5) inhibitors improve exercise capacity and quality of life in patients with idiopathic pulmonary arterial hypertension. However,whether such beneficial effects take place in selected populations with chronic obstructive pulmonary disease (COPD) remains uncertain. We aimed to assess the effects of tadalafil--a PDE5 inhibitor--on exercise capacity and quality of life in patients with COPD and mild pulmonary hypertension. We did a randomised,double-blind,parallel-group,placebo-controlled trial at three centres in Scotland,UK,between Sept 1,2010,and Sept 1,2012. Patients with moderate to severe COPD were randomly assigned (1:1),via centralised randomisation with a computer-generated sequence and block sizes of four,to receive daily tadalafil 10 mg or placebo for 12 weeks. Patients,study investigators,outcome assessors,and those administering drugs were masked to group allocation. The primary endpoint was the mean placebo-corrected difference between the baseline and final 6 min walk distance after 12 weeks. We measured change in quality of life at baseline,8 weeks,and 12 weeks,with standardised questionnaires. Analysis was per protocol and by intention to treat. This trial is registered with ClinicalTrials.gov,number NCT01197469. 120 patients were randomly assigned to receive tadalafil (n=60) or placebo (n=60),of whom 56 (93%) versus 57 (95%) completed the study. At 12 weeks the difference in 6 min walking distance between the tadalafil and placebo groups was 0·5 m (95% CI -11·6 to 12·5; p=0·937). We recorded no statistically significant changes in quality of life (between-group difference on the St George's Respiratory Questionnaire -2·64 [95% CI -6·43 to 1·15]; Research and Development version 1 short-form-36 4·08 [-1·35 to 9·52]; Minnesota Living with Heart Failure questionnaire -2·31 [-7·06 to 2·45]). 19 (32%) of 60 patients in the treatment group had dyspepsia; the severity of dyspepsia ranged from mild to severe,with four (21%) of 19 patients needing a proton-pump inhibitor. Five (8%) of 60 participants had dyspepsia in the placebo group. Headache was noted in 17 (28%) patients in the treatment group versus 5 (8%) in the placebo group,but was mild in all patients. Two (3%) patients in the treatment group had facial flushing,which resulted in one withdrawal. Other withdrawals within the tadalafil group happened after a transient ischaemic attack and two deaths (ruptured abdominal aortic aneurysm and pneumonia). Tadalafil does not improve exercise capacity or quality of life despite exerting pulmonary vasodilation. Chief Scientist Office for Scotland.","Lancet Respir Med. 2014 Apr;2(4):293-300.","UK",2014,"COPD","Tadalafil","MLHFQ,SF-36,SGRQ"]
[29,"Sitbon O,Delcroix M,Bergot E,Boonstra AB,Granton J,Langleben D,Subías PE,Galiè N,Pfister T,Lemarié JC,Simonneau G. EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension. Am Heart J. 2014 Feb;167(2):210-7. doi: 10.1016/j.ahj.2013.08.007. Epub 2013 Oct 3.","doi: 10.1016/j.ahj.2013.08.007. Epub 2013 Oct 3.","Sitbon O,Delcroix M,Bergot E,Boonstra AB,Granton J,Langleben D,Subías PE,Galiè N,Pfister T,Lemarié JC,Simonneau G.","EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension.","Continuous infusion of epoprostenol is the treatment of choice in patients with pulmonary arterial hypertension in functional classes III to IV. However,this treatment's limitations include instability at room temperature. A new epoprostenol formulation offers improved storage conditions and patient convenience. The EPITOME-2 trial was an open-label,prospective,multicenter,single-arm,phase IIIb study. Patients with pulmonary arterial hypertension on long-term,stable epoprostenol therapy were transitioned from epoprostenol with glycine and mannitol excipients (Flolan; GlaxoSmithKline,Durham,NC) to epoprostenol with arginine and sucrose excipients (Veletri; Actelion Pharmaceuticals Ltd,Allschwil,Switzerland). Patients were followed up for 3 months,and dose adjustments were recorded. Efficacy measures included the 6-minute walk distance,hemodynamics assessed by right heart catheterization,and New York Heart Association functional class. Safety and tolerability of the transition were also evaluated. Quality of life was assessed using the Treatment Satisfaction Questionnaire for Medication. Forty-two patients enrolled in the study,and 1 patient withdrew consent before treatment; thus,41 patients received treatment and completed the study. Six patients required dose adjustments. There were no clinically relevant changes from baseline to month 3 in any of the efficacy end points. Adverse events were those previously described with intravenous prostacyclin therapy. Treatment Satisfaction Questionnaire for Medication scores showed an improvement from baseline to month 3 in the domain of treatment convenience. Transition from epoprostenol with glycine and mannitol excipients to epoprostenol with arginine and sucrose excipients did not affect treatment efficacy,raised no new safety or tolerability concerns,and provided patients with an increased sense of treatment convenience.","Am Heart J. 2014 Feb;167(2):210-7.","International",2014,"Any PAH","Epoprostanol","TSQM"]
[30,"Saggar R,Khanna D,Vaidya A,Derhovanessian A,Maranian P,Duffy E,Belperio JA,Weigt SS,Dua S,Shapiro SS,Goldin JG,Abtin F,Lynch JP 3rd,Ross DJ,Forfia PR,Saggar R. Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis. Thorax. 2014 Feb;69(2):123-9. doi: 10.1136/thoraxjnl-2013-204150.","doi: 10.1136/thoraxjnl-2013-204150.","Saggar R,Khanna D,Vaidya A,Derhovanessian A,Maranian P,Duffy E,Belperio JA,Weigt SS,Dua S,Shapiro SS,Goldin JG,Abtin F,Lynch JP 3rd,Ross DJ,Forfia PR,Saggar R.","Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis.","Pulmonary hypertension (PH)-targeted therapy in the setting of pulmonary fibrosis (PF) is controversial; the main clinical concern is worsening of systemic hypoxaemia. We sought to determine the effects of gentle initiation and chronic administration of parenteral treprostinil on right heart function in patients with PF associated with an advanced PH phenotype. Open-label,prospective analysis of patients with PF-PH referred for lung transplantation (LT). Advanced PH was defined as mean pulmonary artery pressure (mPAP) ≥35 mm Hg. We compared haemodynamics,Doppler echocardiography (DE),oxygenation,dyspnoea and quality of life indices,and 6 min walk distance (6MWD) before and 12 weeks after parenteral treprostinil. 15 patients were recruited in the study. After therapy,there were significant improvements in right heart haemodynamics (right atrial pressure (9.5 ± 3.4 vs 6.0 ± 3.7); mPAP (47 ± 8 vs 38.9 ± 13.4); CI (2.3 ± 0.5 vs 2.7 ± 0.6); pulmonary vascular resistance (698 ± 278 vs 496 ± 229); transpulmonary gradient (34.7 ± 8.7 vs 28.5 ± 10.3); mvO2 (65 ± 7.2 vs 70.9 ± 7.4); and stroke volume index (29.2 ± 6.7 vs 33 ± 7.3)) and DE parameters reflecting right heart function (right ventricular (RV) end diastolic area (36.4 ± 5.2 vs 30.9 ± 8.2 cm(2)),left ventricular eccentricity index (1.7 ± 0.6 vs 1.3 ± 0.5),tricuspid annular planar systolic excursion (1.6 ± 0.5 vs 1.9 ± 0.2 cm)). These changes occurred without significant alteration in systemic oxygenation,heart rate,or mean systemic arterial pressure. In addition,improvements were seen in 6MWD (171 ± 93 vs 230 ± 114),36-Item Short Form Health Survey Mental Component Summary aggregate (38 ± 11 vs 44.2 ± 10.7),University of California,San Diego Shortness of Breath Questionnaire (87 ± 17.1 vs 73.1 ± 21),and brain natriuretic peptide (558 ± 859 vs 228 ± 340). PH-targeted therapy may improve right heart haemodynamics and echocardiographic function without affecting systemic oxygen saturation in an advanced PH phenotype associated with RV dysfunction in the setting of PF.","Thorax. 2014 Feb;69(2):123-9.","USA",2014,"Interstitial lung disease","None or unknown","SF-36,UCSD-SBQ"]
[31,"Ulrich S,Keusch S,Hildenbrand FF,Lo Cascio C,Huber LC,Tanner FC,Speich R,Bloch KE. Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized,double-blind,cross-over trial. Eur Heart J. 2015 Mar 7;36(10):615-23. doi: 10.1093/eurheartj/eht540. Epub 2013 Dec 23.","doi: 10.1093/eurheartj/eht540. Epub 2013 Dec 23.","Ulrich S,Keusch S,Hildenbrand FF,Lo Cascio C,Huber LC,Tanner FC,Speich R,Bloch KE.","Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized,double-blind,cross-over trial.","Sleep-disturbed breathing (SDB) is common in pre-capillary pulmonary hypertension (PH) and impairs daytime performance. In lack of proven effective treatments,we tested whether nocturnal oxygen therapy (NOT) or acetazolamide improve exercise performance and quality of life in patients with pre-capillary PH and SDB. This was a randomized,placebo-controlled,double-blind,three period cross-over trial. Participants received NOT (3 L/min),acetazolamide tablets (2 × 250 mg),and sham-NOT/placebo tablets each during 1 week with 1-week washout between treatment periods. Twenty-three patients,16 with pulmonary arterial PH,7 with chronic thromboembolic PH,and with SDB defined as mean nocturnal oxygen saturation <90% or oxygen saturation dips >10 h(-1) with daytime PaO2 ≥7.3 kPa participated. Assessments at the end of the treatment periods included a 6 min walk distance (MWD),SF-36 quality of life,polysomnography,and echocardiography. Medians (quartiles) of the 6 MWD after NOT,acetazolamide,and placebo were 480 m (390;528),440 m (368;468),and 454 m (367;510),respectively,mean differences: NOT vs. placebo +25 m (95% CI 3-46,P= 0.027),acetazolamide vs. placebo -9 m (-34-17,P = 0.223),and NOT vs. acetazolamide +33 (12-45,P < 0.001). SF-36 quality of life was similar with all treatments. Nocturnal oxygen saturation significantly improved with both NOT and acetazolamide. Right ventricular fractional area change was greater on NOT compared with placebo (P = 0.042) and acetazolamide (P = 0.027). In patients with pre-capillary PH and SDB on optimized pharmacological therapy,NOT improved the 6 MWD compared with placebo already after 1 week along with improvements in SDB and haemodynamics. NTC01427192.","Eur Heart J. 2015 Mar 7;36(10):615-23.","Switzerland",2015,"CTEPH","Acetazolamide,Oxygen","SF-36"]
[32,"Twiss J,McKenna S,Ganderton L,Jenkins S,Ben-L'amri M,Gain K,Fowler R,Gabbay E. Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension. BMC Pulm Med. 2013 Jul 12;13():45. doi: 10.1186/1471-2466-13-45. Epub 2013 Jul 12.","doi: 10.1186/1471-2466-13-45. Epub 2013 Jul 12.","Twiss J,McKenna S,Ganderton L,Jenkins S,Ben-L'amri M,Gain K,Fowler R,Gabbay E.","Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension.","The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and the Medical Outcomes Study Short Form 36 (SF-36) are widely used to assess patient-reported outcome in individuals with pulmonary hypertension (PH). The aim of the study was to compare the psychometric properties of the two measures. Participants were recruited from specialist PH centres in Australia and New Zealand. Participants completed the CAMPHOR and SF-36 at two time points two weeks apart. The SF-36 is a generic health status questionnaire consisting of 36 items split into 8 sections. The CAMPHOR is a PH-specific measure consisting of 3 scales; symptoms,activity limitations and needs-based QoL. The questionnaires were assessed for distributional properties (floor and ceiling effects),internal consistency (Cronbach's alpha),test-retest reliability and construct validity (scores by World Health Organisation functional classification). The sample comprised 65 participants (mean (SD) age = 57.2 (14.5) years; n(%) male = 14 (21.5%)). Most of the patients were in WHO class 2 (27.7%) and 3 (61.5%). High ceiling effects were observed for the SF-36 bodily pain,social functioning and role emotional domains. Test-retest reliability was poor for six of the eight SF-36 domains,indicating high levels of random measurement error. Three of the SF-36 domains did not distinguish between WHO classes. In contrast,all CAMPHOR scales exhibited good distributional properties,test retest reliability and distinguished between WHO functional classes. The CAMPHOR exhibited superior psychometric properties,compared with the SF-36,in the assessment of PH patient-reported outcome.","BMC Pulm Med. 2013 Jul 12;13():45.","Australia,New Zealand",2013,"Any PAH","None or unknown","CAMPHOR,SF-36"]
[33,"Halank M,Einsle F,Lehman S,Bremer H,Ewert R,Wilkens H,Meyer FJ,Grünig E,Seyfarth HJ,Kolditz M,Wieder G,Höffken G,Köllner V. Exercise capacity affects quality of life in patients with pulmonary hypertension. Lung. 2013 Aug;191(4):337-43. doi: 10.1007/s00408-013-9472-6. Epub 2013 May 17.","doi: 10.1007/s00408-013-9472-6. Epub 2013 May 17.","Halank M,Einsle F,Lehman S,Bremer H,Ewert R,Wilkens H,Meyer FJ,Grünig E,Seyfarth HJ,Kolditz M,Wieder G,Höffken G,Köllner V.","Exercise capacity affects quality of life in patients with pulmonary hypertension.","The objective of this prospective study was to evaluate the impact of exercise capacity,mental disorders,and hemodynamics on quality-of-life (QoL) parameters in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Sixty-three patients with invasively diagnosed PAH (n = 48) or CTEPH (n = 15) underwent a broad panel of assessments,including cardiopulmonary exercise testing (CPET),6-minute walking distance (6-MWD),World Health Organization functional class (WHO-FC),and assessment of hemodynamics. QoL was evaluated by the 36-item Medical Outcome Study Short Form Health Survey Questionnaire (SF-36). Exercise capacity,hemodynamics,age,gender,and mental disorders (anxiety and depression) were assessed for association with QoL subscores by uni- and multivariate regression analyses. Exercise capacity,WHO-FC,oxygen therapy,symptoms of right heart failure,right atrial pressure,and mental disorders were significantly associated with QoL (p < 0.05). In the stepwise backward selection multivariate analysis,depression remained an independent parameter in seven of eight subscales of the SF-36. Furthermore,peak oxygen uptake (peakVO2) during CPET,6-MWD,anxiety,long-term oxygen therapy,right heart failure,and age remained independent factors for QoL. Hemodynamic parameters at rest did not independently correlate with any domain of the SF-36 QoL subscores. Mental disorders,exercise capacity,long-term oxygen therapy,right heart failure,and age play important role in the quality of life in patients with PAH and CTEPH.","Lung. 2013 Aug;191(4):337-43.","Germany",2013,"Any PAH,CTEPH","None or unknown","SF-36"]
[34,"Chen H,Rosenzweig EB,Gotzkowsky SK,Arneson C,Nelsen AC,Bourge RC. Treatment satisfaction is associated with improved quality of life in patients treated with inhaled treprostinil for pulmonary arterial hypertension. Health Qual Life Outcomes. 2013 Mar 6;11():31. doi: 10.1186/1477-7525-11-31. Epub 2013 Mar 6.","doi: 10.1186/1477-7525-11-31. Epub 2013 Mar 6.","Chen H,Rosenzweig EB,Gotzkowsky SK,Arneson C,Nelsen AC,Bourge RC.","Treatment satisfaction is associated with improved quality of life in patients treated with inhaled treprostinil for pulmonary arterial hypertension.","Patient treatment satisfaction is likely to be a highly relevant outcome measure in pulmonary arterial hypertension (PAH),a condition for which the benefits of treatment must be weighed against frequent,undesirable side effects,inconvenience,and complications associated with therapy. In this study,we sought to evaluate the psychometric properties of a patient-reported treatment satisfaction measure and its relationship to quality of life (QoL) among patients transitioning from inhaled iloprost (iILO) to inhaled treprostinil (iTRE). We studied treatment satisfaction among 66 subjects with PAH in a single-arm,open-label,multi-center trial of iTRE following transition from iILO. Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM,version 1.4) administered to subjects immediately before and 12 weeks after transition of inhaled therapy. The TSQM is comprised of 4 domains: effectiveness,side effects,convenience,and global satisfaction. Scores range from 0 to 100 with higher scores indicating greater satisfaction. Six-minute walk distance (6MWD),functional class,adverse events,drug administration time,and PAH-specific QoL (CAMPHOR) were concurrently assessed. Domains of the TSQM demonstrated evidence of strong internal consistency at baseline and at 12 weeks (Cronbach α = 0.88-0.93). Transition from iILO to iTRE was associated with an improvement in 3 of 4 TSQM domains: effectiveness (+20 ± 21,p < 0.0001),side effects (0 ± 22,p = 0.97),convenience (+39 ± 26,p < 0.0001),and global satisfaction (+20 ± 24,p = 0.0005). Change in effectiveness scores correlated with change in 6MWD (r = 0.43,p = 0.0004) and side effects scores at 12 weeks correlated inversely with number of severity-weighted treatment-emergent adverse events (r = -0.44,p = 0.0002). In multiple regression models adjusted for baseline characteristics,changes in effectiveness and convenience satisfaction scores were significantly associated with improvement in PAH-specific QoL (p = 0.002 and p = 0.01). The TSQM demonstrated acceptable performance characteristics in patients with PAH. Changes in treatment satisfaction resulting from transitioning from iILO to iTRE were associated with improvements in PAH-specific QoL.\nTags","Health Qual Life Outcomes. 2013 Mar 6;11():31.","USA",2013,"Any PAH","Treprostanil","CAMPHOR,TSQM"]
[35,"Schuuring MJ,Vis JC,van Dijk AP,van Melle JP,Vliegen HW,Pieper PG,Sieswerda GT,de Bruin-Bon RH,Mulder BJ,Bouma BJ. Impact of bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial. Eur J Heart Fail. 2013 Jun;15(6):690-8. doi: 10.1093/eurjhf/hft017. Epub 2013 Jan 29.","doi: 10.1093/eurjhf/hft017. Epub 2013 Jan 29.","Schuuring MJ,Vis JC,van Dijk AP,van Melle JP,Vliegen HW,Pieper PG,Sieswerda GT,de Bruin-Bon RH,Mulder BJ,Bouma BJ.","Impact of bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial.","An endothelin-1 receptor blocker,shown to be effective in patients with pulmonary arterial hypertension,might decrease pulmonary vascular resistance to increase cardiac filling and consequently improve exercise capacity in Fontan patients. This was a prospective,multicentre randomized open label trial in Fontan patients. One group received bosentan for 6 months. The other group did not receive study medication for the first 3 months,followed by bosentan for 6 months. The primary endpoint was exercise capacity,and secondary endpoints were NT-proBNP level,cardiac output,SF-36 (Short Form-36) quality of life (QoL),and NYHA class. Forty-two adults (median age 29 (range 18-56) years,52% male,88% NYHA class I-II) from five tertiary referral centres participated in the study. Ten patients were on diuretics. Ten patients were not motivated to finish the study. Analysis of all 32 patients who finished the study at 6 months of treatment showed that mean peak V'O2 (24 vs. 25 mL/kg/min),median SQUASH score (6614 vs. 6390),median NT-proBNP (314 vs. 274 ng/L),and mental QoL (50 vs. 51) remained unchanged as compared with baseline (P = NS,for all). After treatment,NYHA class had improved in 6 (19%),was unchanged in 24 (75%),and declined in 2 (6%) patients. Subgroup analysis on age,ventricular morphology,type of Fontan circulation,or baseline NT-proBNP level did not reveal efficacy of bosentan. Six transient adverse effects were reported. An increased NT-proBNP level was present in the majority of Fontan patients. Six months of bosentan treatment was not beneficial. Trial registration NTR1557.","Eur J Heart Fail. 2013 Jun;15(6):690-8.","Netherlands",2013,"Congenital HD","Bosentan","SF-36"]
[36,"Cooper TJ,Guazzi M,Al-Mohammad A,Amir O,Bengal T,Cleland JG,Dickstein K. Sildenafil in Heart failure (SilHF).  An investigator-initiated multinational randomized controlled clinical trial: rationale and design. Eur J Heart Fail. 2013 Jan;15(1):119-22. doi: 10.1093/eurjhf/hfs152. Epub 2012 Oct 24.","doi: 10.1093/eurjhf/hfs152. Epub 2012 Oct 24.","Cooper TJ,Guazzi M,Al-Mohammad A,Amir O,Bengal T,Cleland JG,Dickstein K.","Sildenafil in Heart failure (SilHF).  An investigator-initiated multinational randomized controlled clinical trial: rationale and design.","Heart failure (HF) is a major clinical problem and,despite advances in both pharmacological and device therapy,the mortality remains high and quality of life poor. Over the last decade there has been growing interest in using phosphodiesterase-5 (PDE-5) inhibitors in HF associated with group 2 pulmonary hypertension (PH),with benefits reported on pulmonary haemodynamic and functional status in single-centre trials Methods The Sildenafil in Heart Failure (SilHF) trial is a randomized,placebo-controlled multinational trial designed to assess efficacy and tolerability of PDE-5 inhibition with sildenafil (target dose 40 mg three times per day) in 210 patients with HF,New York Heart Association (NYHA) functional class II or III,and evidence of group 2 PH. The co-primary endpoints are patient global assessment and the 6 min walk test. Secondary endpoints include NYHA functional class and the quality of life tools Euro QoL 5D and the Kansas City questionnaire. Patients will be followed up for 6 months. The authors hypothesize that PDE-5 inhibition can improve exercise capacity and symptoms with acceptable tolerability in patients with HF and group 2 PH.","Eur J Heart Fail. 2013 Jan;15(1):119-22.","International",2013,"Any PAH","Sildenafil","EQ-5D,KCQ"]
[37,"Chan L,Chin LM,Kennedy M,Woolstenhulme JG,Nathan SD,Weinstein AA,Connors G,Weir NA,Drinkard B,Lamberti J,Keyser RE. Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension. Chest. 2013 Feb 1;143(2):333-43. doi: 10.1378/chest.12-0993.","doi: 10.1378/chest.12-0993.","Chan L,Chin LM,Kennedy M,Woolstenhulme JG,Nathan SD,Weinstein AA,Connors G,Weir NA,Drinkard B,Lamberti J,Keyser RE.","Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension.","Pulmonary hypertension (PH) restricts the ability to engage in physical activity and decreases longevity. We examined the impact of aerobic exercise training on function and quality of life in patients with World Health Organization group 1 PH. Patients were randomized to a 10-week education only (EDU) or education/exercise combined (EXE) group. The exercise program consisted of 24-30 sessions of treadmill walking for 30-45 min per session at 70% to 80% of heart rate reserve. Outcome variables included changes in 6-min walk test (6MWT) distance,time to exercise intolerance,peak work rate (WR) from a cardiopulmonary treadmill test,and quality-of-life measures,including the Short Form Health Survey,version 2 (SF-36v2) and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). Data are presented as mean SD. Twenty-three women (age,54 11 years; BMI,31 7 kg/m 2 ) were randomized to the EDU (n 5 13) or EXE (n 5 10) groups. Following 10 weeks of intervention,patients in the EXE group demonstrated an improvement in 6MWT distance (56 45 m; P 5 .002),increased time to exercise intolerance (1.9 1.3 min; P 5 .001),and peak WR (26 23 W; P 5 .004). Additionally,the EXE group scored significantly ( P,.050) better on six of the eight scales on SF-36v2,and fi ve of the six scales on CAMPHOR. In contrast,no significant improvement was observed for any of the outcome measures following EDU. No adverse events were noted in either group. Ten weeks of brisk treadmill walking improved 6MWT distance,cardiorespiratory function,and patient-reported quality of life in female patients with group 1 PH.","Chest. 2013 Feb 1;143(2):333-43.","USA",2013,"Any PAH","Exercise","CAMPHOR,SF-36"]
[38,"Nagel C,Prange F,Guth S,Herb J,Ehlken N,Fischer C,Reichenberger F,Rosenkranz S,Seyfarth HJ,Mayer E,Halank M,Grünig E. Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension. PLoS One. 2012;7(7):e41603. doi: 10.1371/journal.pone.0041603. Epub 2012 Jul 25.","doi: 10.1371/journal.pone.0041603. Epub 2012 Jul 25.","Nagel C,Prange F,Guth S,Herb J,Ehlken N,Fischer C,Reichenberger F,Rosenkranz S,Seyfarth HJ,Mayer E,Halank M,Grünig E.","Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension.","Aim of this prospective study was to evaluate the effects of exercise training in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH). Thirty-five consecutive patients with invasively confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61±15 years,mean pulmonary artery pressure,63±20 mmHg; primary inoperable n = 33,persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable disease-targeted medication received exercise training in-hospital for 3 weeks and continued at home for 15 weeks. Medication remained unchanged during the study period. Efficacy parameters have been evaluated at baseline,after 3 and 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of median 36.4 months (interquartile range 26.6-46.6 months). All patients tolerated exercise training without severe adverse events. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 61±54 meters after 3 weeks (p<0.001) and by 71±70 meters after 15 weeks (p = 0.001),as well as scores of quality-of-life questionnaire,peak oxygen consumption and maximal workload. NT-proBNP improved significantly after 3 weeks of exercise training (p = 0.046). The 1-year survival rate was 97%,2-year survival rate was 94% and the 3-year-survival 86% respectively. Training as add-on to medical therapy may be effective in patients with CTEPH to improve work capacity,quality of life and further prognostic relevant parameters and possibly improves the 1-,2- and 3-year survival rate. Further multicentric randomized controlled studies are needed to confirm these promising results. ClinicalTrials.gov NCT01398345.","PLoS One. 2012;7(7):e41603.","Germany",2012,"CTEPH","Exercise","Unknown"]
[39,"Baughman RP,Judson MA,Lower EE,Highland K,Kwon S,Craft N,Engel PJ. Inhaled iloprost for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2009 Jul;26(2):110-20.",null,"Baughman RP,Judson MA,Lower EE,Highland K,Kwon S,Craft N,Engel PJ.","Inhaled iloprost for sarcoidosis associated pulmonary hypertension.","Patients with sarcoidosis associated pulmonary hypertension (SAPH) have responded to systemic prostacyclin therapy. To determine the rate of response to inhaled prostacyclin,iloprost,in SAPH. Sarcoidosis patients with pulmonary hypertension and no evidence for left ventricular dysfunction were enrolled in an open label,prospective study. Patients underwent right heart catheterization and six minute walk (6MW) test. Quality of life was evaluated using several instruments,including the Saint George Respiratory Questionnaire (SGRQ). Patients received 5 mcg of inhaled iloprost every 2-3 hours while awake. After four months of therapy,patients underwent repeat cardiac catheterization,6 MW test,and completed quality of life questionnaires. Of the 22 patients enrolled,15 completed all 16 weeks of therapy. The most common reasons for study discontinuation included drug associated cough (3 patients) and compliance with the prescribed number of treatments per day (2 patients). Six patients experienced a 20% or greater decrease in pulmonary vascular resistance (PVR) from baseline with five of these six patients also showing > or = 5 mm Hg reduction in PA mean. Although three patients improved the 6MW distance by at least 30 meters,only one had a decrease in PVR. At 16 weeks a significant decrease was reported in the SGRQ activity score (p = 0.0273),with seven patients having a 4 point or greater decrease. Inhaled iloprost as monotherapy was associated with an improvement in pulmonary hemodynamics and quality of life as assessed by the SGRQ activity score in some sarcoidosis patients with SAPH.","Sarcoidosis Vasc Diffuse Lung Dis. 2009 Jul;26(2):110-20.","USA",2009,"Sarcoidosis","Iloprost","SGRQ"]
[40,"Minier T,Nagy Z,Bálint Z,Farkas H,Radics J,Kumánovics G,Czömpöly T,Simon D,Varjú C,Németh P,Czirják L. Construct validity evaluation of the European Scleroderma Study Group activity index,and investigation of possible new disease activity markers in systemic sclerosis. Rheumatology (Oxford). 2010 Jun;49(6):1133-45. doi: 10.1093/rheumatology/keq022. Epub 2010 Mar 17.","doi: 10.1093/rheumatology/keq022. Epub 2010 Mar 17.","Minier T,Nagy Z,Bálint Z,Farkas H,Radics J,Kumánovics G,Czömpöly T,Simon D,Varjú C,Németh P,Czirják L.","Construct validity evaluation of the European Scleroderma Study Group activity index,and investigation of possible new disease activity markers in systemic sclerosis.","To evaluate the construct validity of the European Scleroderma Study Group (EScSG) activity index and to propose modifications if necessary. One hundred and thirty-one consecutive patients were investigated and re-evaluated 1 year later. Modified Rodnan skin score (MRSS),skin ulcers and joint contracture numbers,hand anatomic index (HAI),BMI,spirometry,carbon monoxide diffusing capacity (DL(CO)),left ventricular ejection fraction,pulmonary arterial hypertension,HAQ Disability Index (HAQ-DI),patient skin self-assessment questionnaire and several biomarkers were recorded,in addition to the data required for the EScSG activity index. Statistical analysis was performed by categorical principal component analysis (CATPCA). The EScSG activity index appeared in the same dimension as the HAQ-DI,ulcer score and joint contractures,MRSS,patient-reported skin score and HAI by CATPCA. Parameters of lung involvement appeared in another dimension. We constructed a 12-point activity index that was equally associated with both dimensions,by adding the forced vital capacity/DL(CO),change in DL(CO),change in the ulcer scores,HAQ-DI and patient-reported skin score. Biomarkers including vascular endothelial growth factor,soluble P-selectin glycoprotein ligand-1,CRP and albumin were related to both the EScSG and the 12-point index,though they did not improve the total variance of the model. The construct validity of the EScSG activity index is good,though the lung-related disease activity may not be sufficiently represented. Further validation steps may be required for both the EScSG and our 12-point activity index.","Rheumatology (Oxford). 2010 Jun;49(6):1133-45.","Hungary",2010,"Systemic sclerosis","None or unknown","EscSG,HAQ-DI,RSS"]
[41,"Fraisse A,Jais X,Schleich JM,di Filippo S,Maragnès P,Beghetti M,Gressin V,Voisin M,Dauphin C,Clerson P,Godart F,Bonnet D. Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France. Arch Cardiovasc Dis. 2010 Feb;103(2):66-74. doi: 10.1016/j.acvd.2009.12.001. Epub 2010 Feb 11.","doi: 10.1016/j.acvd.2009.12.001. Epub 2010 Feb 11.","Fraisse A,Jais X,Schleich JM,di Filippo S,Maragnès P,Beghetti M,Gressin V,Voisin M,Dauphin C,Clerson P,Godart F,Bonnet D.","Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France.","Limited data are available describing paediatric pulmonary arterial hypertension. To characterize the epidemiology,management and impact on quality of life and outcome of paediatric pulmonary arterial hypertension,excluding persistent pulmonary hypertension of the newborn and pulmonary arterial hypertension caused by congenital heart disease. In this multicentre study,children with pulmonary arterial hypertension were included and followed prospectively for two years at 21 referral centres in France. WHO functional class,6-minute walk distance and quality of life (CHQ-PF50 questionnaire) were evaluated. Fifty children were included with a mean age of 8.9 +/- 5.4 years from May 2005 until June 2006. The estimated prevalence for pulmonary arterial hypertension was 3.7 cases/million. Patients had idiopathic pulmonary arterial hypertension (60%),familial pulmonary arterial hypertension (10%),pulmonary arterial hypertension associated with,but not caused by,congenital heart disease (24%),pulmonary arterial hypertension associated with connective tissue disease (4%) or portal hypertension (2%). During follow-up,the combination of pulmonary arterial hypertension-specific therapies was increasingly prescribed (44% patients versus 22% at inclusion). Patients remained stable regarding clinical status,6-minute walk distance and quality of life. Survival estimates after one and two years were 86% (95% CI 76,96) and 82% (95% CI 71,93),respectively. In children,idiopathic/familial pulmonary arterial hypertension accounts for the majority of cases. A specific pulmonary arterial hypertension group in conjunction with congenital heart disease can be identified that resembles patients with idiopathic pulmonary arterial hypertension. Combined pulmonary arterial hypertension-specific therapies may have contributed to disease stability and favourable survival.","Arch Cardiovasc Dis. 2010 Feb;103(2):66-74.","France",2010,"Any PAH","None or unknown","CHQ-PF50"]
[42,"Viganò G,Guidotti A,Taramasso M,Giacomini A,Alfieri O. Clinical mid-term results after tricuspid valve replacement. Interact Cardiovasc Thorac Surg. 2010 May;10(5):709-13. doi: 10.1510/icvts.2009.224212. Epub 2010 Feb 10.","doi: 10.1510/icvts.2009.224212. Epub 2010 Feb 10.","Viganò G,Guidotti A,Taramasso M,Giacomini A,Alfieri O.","Clinical mid-term results after tricuspid valve replacement.","Tricuspid valve replacement (TVR) is associated with high mortality and morbidity. Frequently,TVR is performed in critically ill patients with high frequency of re-intervention. We analyzed our experience in TVR focusing on predicting risk factors,mid-term survival and quality of life assessed with a Short-Form 36 Health Survey (SF-36) questionnaire. Between January 1992 and May 2007,81 consecutive patients underwent TVR (54 re-interventions,66.7%; 46 procedures,associated with a left-sided operation,56.8%). There were 59 females (73%) with a mean age of 59.3+/-11.6 years. The most prevalent etiology was rheumatic fever (61.7%). Pulmonary hypertension was present in 64%. Mean left ventricle ejection fraction (LVEF) was 56.6% and mean right ventricle ejection fraction (RVEF) was 48.1%. All but four patients (4.9%) received a bio-prosthesis. Hospital mortality was 9.88%. The mean follow-up was 61+/-42 months. Survival was 68% at five years. Univariate predictors of hospital mortality were atrial fibrillation (AFib) (P<0.01),associated procedures on the left heart (P=0.025) and preoperative chronic right heart failure symptoms (P<0.01). At follow-up: 10.8% of patients had a pace-maker (PM) induced rhythm; the mean SF-36 score was 51.1+/-4.8 (range 59-38). Age (P=0.015),associated procedures (P=0.024) and previous cardiovascular surgery (P=0.015) were univariate predictors of the SF-36 score. At a multivariate analysis LVEF,venous congestion and pulmonary artery pressures (PAPs) were related with a SF-36 score.","Interact Cardiovasc Thorac Surg. 2010 May;10(5):709-13.","Italy",2010,"Any PAH","Surgery","SF-36"]
[43,"Pepke-Zaba J,Beardsworth A,Chan M,Angalakuditi M. Tadalafil therapy and health-related quality of life in pulmonary arterial hypertension. Curr Med Res Opin. 2009 Oct;25(10):2479-85. doi: 10.1185/03007990903210066.","doi: 10.1185/03007990903210066.","Pepke-Zaba J,Beardsworth A,Chan M,Angalakuditi M.","Tadalafil therapy and health-related quality of life in pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) is a rare,progressive lung disorder that impairs performance of daily activities and quality of life (QoL),leading to right heart failure and death. Treatment options include prostanoids,endothelin antagonists,and phosphodiesterase type 5 inhibitors (e.g.,tadalafil). Currently there is no cure for PAH,but tadalafil has improved exercise capacity in these patients. To explore the effect of tadalafil on health-related quality of life (HRQoL) measures. The Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) clinical trial examined the efficacy and tolerability of tadalafil for the treatment of PAH. The impact of tadalafil on HRQoL and exercise capacity,as measured by 6-minute walk test (6MW test),was also examined. Change from baseline to last non-missing post-baseline was examined for the SF-36,EQ-5D,and 6MW test,along with the relationship between HRQoL and 6MW test performance. Tadalafil 40 mg showed significant improvement over placebo for six of eight SF-36 domains,and EQ-5D index scores. Also,the tadalafil 40-mg group showed significant improvement over placebo on the 6MW test (p < 0.001),but no clear relationship was found between 6MW test performance and HRQoL. Results suggest that tadalafil 40 mg may significantly improve HRQoL and exercise capacity for PAH patients. Limitations of this study include its relatively short nature limited to 16 weeks and the relative heterogeneity of the study population.","Curr Med Res Opin. 2009 Oct;25(10):2479-85.","UK",2009,"Any PAH","Tadalafil","EQ-5D,SF-36"]
[44,"Duffels MG,Vis JC,van Loon RL,Nieuwkerk PT,van Dijk AP,Hoendermis ES,de Bruin-Bon RH,Bouma BJ,Bresser P,Berger RM,Mulder BJ. Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome. Am J Cardiol. 2009 May 1;103(9):1309-15. doi: 10.1016/j.amjcard.2009.01.021. Epub 2009 Mar 13.","doi: 10.1016/j.amjcard.2009.01.021. Epub 2009 Mar 13.","Duffels MG,Vis JC,van Loon RL,Nieuwkerk PT,van Dijk AP,Hoendermis ES,de Bruin-Bon RH,Bouma BJ,Bresser P,Berger RM,Mulder BJ.","Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome.","Pulmonary arterial hypertension associated with congenital heart disease caused by systemic-to-pulmonary shunting was associated with a high risk of morbidity and mortality. In this retrospective study,the longer term treatment effect of bosentan on exercise capacity and quality of life (QoL) were evaluated in 58 adult patients (>18 years) with pulmonary arterial hypertension associated with congenital heart disease,including patients with Down's syndrome. All patients were evaluated at baseline and during follow-up using laboratory tests,6-minute walk test,QoL questionnaires,and Doppler echocardiography. Treatment efficacy was analyzed separately for patients without (n = 30) and with Down's syndrome (n = 28). Median follow-up of all patients treated with bosentan was 22 months (range 3 to 36). In patients without Down's syndrome,mean 6-minute walk distance increased from 427 +/- 97 to 461 +/- 104 m (p <0.01) after 6 months of treatment,followed by a gradual return to baseline and disease stabilization. QoL improved significantly during treatment and was maintained during 18 months of follow-up (p <0.05). In patients with Down's syndrome,6-minute walk distance and QoL were stable during treatment. In conclusion,findings suggested that in patients without Down's syndrome,longer term bosentan treatment resulted in a persistent improvement in QoL and stabilization of exercise capacity.","Am J Cardiol. 2009 May 1;103(9):1309-15.","Netherlands",2009,"Congenital HD","Bosentan","Unknown"]
[45,"Chow S,Pope JE,Mehta S. Lack of correlation of the health assessment questionnaire disability index with lung parameters in systemic sclerosis associated pulmonary arterial hypertension. Clin Exp Rheumatol. 2008 Nov-Dec;26(6):1012-7.",null,"Chow S,Pope JE,Mehta S.","Lack of correlation of the health assessment questionnaire disability index with lung parameters in systemic sclerosis associated pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) affects the quality of life (QoL) and the ability to perform the activities of daily living (ADLs) in patients with systemic sclerosis (SSc). We determined whether the Health Assessment Questionnaire-Disability Index (HAQ-DI),a self-assessment measure of function,correlates with a patient's PAH status in a population of SSc patients with PAH. Forty-one patients from one centre with systemic scleroderma,dyspnea and PAH were included. All patients filled in a HAQ-DI,and underwent evaluation with pulmonary function tests (PFTs),6-minute walk distance (6MWD),degree of dyspnea (Borg dyspnea index),NYHA functional class,and expert PAH physician global assessment every 6 months. Change in HAQ DI was studied to determine relationship to changes in PAH. The HAQ-DI scores had no significant correlation with PAH,including NYHA functional class (r=0.38,p=0.39),Borg dyspnea index (r=0.60,p=0.37),6MWD (r=-0.04,p=0.86),% predicted DLCO (r=0.31,p=0.25),% predicted FVC (r=0.02,p=0.93),and expert PAH physician global assessment (r=0.06,p=0.97). HAQ-DI is not an adequate measure of PAH status in SSc patients with PAH. Although PAH causes severe morbidity and death,changes in PAH severity were not reflected in an overall functional status change as assessed by the HAQ-DI. Thus,HAQ-DI changes do not reflect PAH status in Ssc.","Clin Exp Rheumatol. 2008 Nov-Dec;26(6):1012-7.","Canada",2008,"Systemic sclerosis","None or unknown","BDI,HAQ-DI"]
[46,"Gilbert C,Brown MC,Cappelleri JC,Carlsson M,McKenna SP. Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil. Chest. 2009 Jan;135(1):137-42. doi: 10.1378/chest.07-0275. Epub 2008 Sep 23.","doi: 10.1378/chest.07-0275. Epub 2008 Sep 23.","Gilbert C,Brown MC,Cappelleri JC,Carlsson M,McKenna SP.","Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil.","No guidelines exist to help physicians determine whether functional and health-related quality of life (HRQoL) changes observed following treatment of patients with pulmonary arterial hypertension (PAH) represent important benefits. These analyses were undertaken to help define a minimally important difference (MID) in exercise capacity,measured by the 6-min walk distance (6MWD),and HRQoL,measured by the Short Form-36 (SF-36) questionnaire in patients with PAH. Data from a 12-week sildenafil study in patients with PAH were used to calculate MIDs for 6MWD and the SF-36 physical functioning,role-physical,social functioning,and vitality scales using effect size,SEM,and SE of the difference approaches. Data from all patients enrolled into the treatment groups in the study were included. A range of plausible MID estimates,including a score change for SF-36 scales and a change in distance walked in meters for 6MWD,were generated for each end point. Mean values were calculated for each outcome and recommended as MIDs for each parameter. Based on these computations,the mean MIDs for the SF-36 physical functioning,role-physical,social functioning,and vitality scales and for 6MWD were 13,25,21,and 15 points,and 41 m,respectively. This is the first clinical investigation to estimate MIDs for key SF-36 domains and 6MWD in patients with PAH and provides a much needed metric for interpreting the level of change in patients with PAH against which other treatments and trials can be measured.","Chest. 2009 Jan;135(1):137-42.","UK",2009,"Any PAH","Sildenafil","SF-36"]
[47,"McKenna SP,Ratcliffe J,Meads DM,Brazier JE. Development and validation of a preference based measure derived from the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for use in cost utility analyses. Health Qual Life Outcomes. 2008 Aug 21;6():65. doi: 10.1186/1477-7525-6-65. Epub 2008 Aug 21.","doi: 10.1186/1477-7525-6-65. Epub 2008 Aug 21.","McKenna SP,Ratcliffe J,Meads DM,Brazier JE.","Development and validation of a preference based measure derived from the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for use in cost utility analyses.","Pulmonary Hypertension is a severe and incurable disease with poor prognosis. A suite of new disease-specific measures--the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) - was recently developed for use in this condition. The purpose of this study was to develop and validate a preference based measure from the CAMPHOR that could be used in cost-utility analyses. Items were selected that covered major issues covered by the CAMPHOR QoL scale (activities,travelling,dependence and communication). These were used to create 36 health states that were valued by 249 people representative of the UK adult population,using the time trade-off (TTO) technique. Data from the TTO interviews were analysed using both aggregate and individual level modelling. Finally,the original CAMPHOR validation data were used to validate the new preference based model. The predicted health state values ranged from 0.962 to 0.136. The mean level model selected for analyzing the data had good explanatory power (0.936),did not systematically over- or underestimate the observed mean health state values and showed no evidence of auto correlation in the prediction errors. The value of less than 1 reflects a background level of ill health in state 1111,as judged by the respondents. Scores derived from the new measure had excellent test-retest reliability (0.85) and construct validity. The CAMPHOR utility score appears better able to distinguish between WHO functional classes (II and III) than the EQ-5D and SF-6D. The tariff derived in this study can be used to classify an individual into a health state based on their responses to the CAMPHOR. The results of this study widen the evidence base for conducting economic evaluations of interventions designed to improve QoL for patients with PH.","Health Qual Life Outcomes. 2008 Aug 21;6():65.","UK",2008,"Any PAH","None or unknown","CAMPHOR,EQ-5D,SF-6D,TTO"]
[48,"Strange G,Keogh AM,Williams TJ,Wlodarczyk J,McNeil KD,Gabbay E. Bosentan therapy in patients with pulmonary arterial hypertension: the relationship between improvements in 6 minute walk distance and quality of life. Respirology. 2008 Sep;13(5):674-82. doi: 10.1111/j.1440-1843.2008.01326.x.","doi: 10.1111/j.1440-1843.2008.01326.x.","Strange G,Keogh AM,Williams TJ,Wlodarczyk J,McNeil KD,Gabbay E.","Bosentan therapy in patients with pulmonary arterial hypertension: the relationship between improvements in 6 minute walk distance and quality of life.","Bosentan,an oral,dual endothelin receptor antagonist,significantly improves functional status,haemodynamic measures and survival in patients with pulmonary arterial hypertension (PAH). However,there are limited data on the effect of bosentan on quality of life (QOL) and its relationship to changes in functional status,as measured by the 6 minute walk distance (6MWD). A retrospective analysis was performed of a large,open-label,multicentre trial (VITAL) of bosentan in patients with PAH. Data for 6MWD were collected at baseline,3 or 6 months and these results were correlated with QOL measurements collected as part of the assessment of patients enrolled in the trial. Sixty-nine patients with PAH (mean age 52 years) who were enrolled in the trial had valid QOL (SF-36) measurements and 6MWD data that could be retrieved from clinical notes. At 3 and 6 months,bosentan therapy improved 6MWD compared with baseline (49.5 m and 47.2 m,respectively,P < 0.001) as well as QOL domains,with a significant correlation between these two markers on cross-sectional analysis. However,there was a poor relationship when comparing changes in 6MWD with changes in QOL,in response to therapy. Bosentan therapy was associated with improvements in QOL and 6MWD for at least 6 months. At all measured time points,there was a close correlation between 6MWD and most QOL domains. QOL is an important parameter and should be considered as part of the standard assessment for any trial investigating therapy in PAH.","Respirology. 2008 Sep;13(5):674-82.","Australia",2008,"Any PAH","Bosentan","SF-36"]
[49,"Zlupko M,Harhay MO,Gallop R,Shin J,Archer-Chicko C,Patel R,Palevsky HI,Taichman DB. Evaluation of disease-specific health-related quality of life in patients with pulmonary arterial hypertension. Respir Med. 2008 Oct;102(10):1431-8. doi: 10.1016/j.rmed.2008.04.016. Epub 2008 Jul 9.","doi: 10.1016/j.rmed.2008.04.016. Epub 2008 Jul 9.","Zlupko M,Harhay MO,Gallop R,Shin J,Archer-Chicko C,Patel R,Palevsky HI,Taichman DB.","Evaluation of disease-specific health-related quality of life in patients with pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) remains a debilitating and life-threatening disease despite improvements in hemodynamics,exercise capacity and survival with recent therapeutic advances. Health-related quality of life (HRQOL) has,therefore,been proposed as an important outcome for evaluating care. Relatively little,however,is known regarding HRQOL or its determinants in PAH. The Minnesota Living with Heart Failure questionnaire was recently adapted and validated for HRQOL measurement in PAH. We applied this pulmonary hypertension-specific version (MLHF-PH) to a larger population of PAH patients. Ninety-three consecutive outpatients with PAH completed the MLHF-PH. Scores were assessed for correlations with demographics,symptoms,hemodynamics and treatments. Patients with PAH had significantly impaired HRQOL as assessed by the disease-specific MLHF-PH. Each physical and emotional component,as well as total scores on the MLHF-PH indicated severely depressed HRQOL. As compared to other diagnoses,PAH associated with scleroderma had the worst HRQOL. Patients with WHO functional Class II symptoms reported better HRQOL than Class III patients. Fatigue,weakness and abdominal discomfort were each associated with more severely depressed HRQOL,as was current epoprostenol use. With the sole exception of the right atrial pressure,hemodynamic measurements did not correlate with HRQOL scores. Simultaneous evaluation of HRQOL with a non-disease-specific questionnaire (SF-36) revealed a similarly impaired status,although identified fewer associations with patient-specific factors. Severely impaired HRQOL is present in this population of patients with PAH evaluated with a disease-specific questionnaire. The availability of a pulmonary hypertension-specific HRQOL questionnaire may enable further targeted investigations of factors that might improve outcomes.","Respir Med. 2008 Oct;102(10):1431-8.","USA",2008,"Any PAH","None or unknown","MLHFQ,SF-36"]
[50,"Frantz RP,Benza RL,Kjellström B,Bourge RC,Barst RJ,Bennett TD,McGoon MD. Continuous hemodynamic monitoring in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2008 Jul;27(7):780-8. doi: 10.1016/j.healun.2008.04.009. Epub 2008 Jun 2.","doi: 10.1016/j.healun.2008.04.009. Epub 2008 Jun 2.","Frantz RP,Benza RL,Kjellström B,Bourge RC,Barst RJ,Bennett TD,McGoon MD.","Continuous hemodynamic monitoring in patients with pulmonary arterial hypertension.","The purpose of this study was to determine whether an implantable hemodynamic monitor (IHM) could be used to judge the response of pulmonary arterial hypertension (PAH) patients to changes in therapy. A prospective,non-randomized,multi-center study evaluated physical examination,functional class,echocardiography,brain natriuretic peptide (BNP) levels,exercise capacity assessed by 6-minute walk and cardiopulmonary exercise tests,and quality of life at baseline and at 12 weeks. IHM measurements were continuously available to clinicians between clinic visits. Based on a priori,pre-specified analyses,the relationships between hemodynamic values,PAH treatments and clinical parameters were tracked in an observational fashion. Twenty-four PAH patients underwent IHM implantation prior to a change in PAH therapy. IHM data identified 13 of the 15 patients who improved their 6-minute walk distance by >30 m at 12 weeks (+48 +/- 65 m,p < 0.05),whereas the others walked less (-78 +/- 115 m,not statistically significant). In addition,peak Vo(2),BNP levels and Minnesota Living with Heart Failure Questionnaire scores only improved in the former group. The change in mean pulmonary artery pressure correlated with the change in 6-minute walk distance at 12 weeks (r = -0.71,p < 0.001). Device-related adverse events were comparable to those known to occur with a pacemaker-like device. Changes in ambulatory continuous hemodynamic measurements predicted changes in 6-minute walk distance after the start or addition of PAH therapy. The IHM also identified patients who had improved exercise tolerance,BNP levels and quality of life. The IHM appeared to be well tolerated and allowed rapid hemodynamic feedback between clinic visits.","J Heart Lung Transplant. 2008 Jul;27(7):780-8.","USA",2008,"Any PAH","None or unknown","MLHFQ"]
[51,"Umehara M,Yamaguchi A,Itakura S,Suenaga M,Sakaki Y,Nakashiki K,Miyata M,Tei C. Repeated waon therapy improves pulmonary hypertension during exercise in patients with severe chronic obstructive pulmonary disease. J Cardiol. 2008 Apr;51(2):106-13. doi: 10.1016/j.jjcc.2008.01.004.","doi: 10.1016/j.jjcc.2008.01.004.","Umehara M,Yamaguchi A,Itakura S,Suenaga M,Sakaki Y,Nakashiki K,Miyata M,Tei C.","Repeated waon therapy improves pulmonary hypertension during exercise in patients with severe chronic obstructive pulmonary disease.","Repeated Waon therapy,which uses a far infrared-ray dry sauna system,improved the vascular endothelial function and the cardiac function in patients with chronic heart failure. In patients with chronic obstructive pulmonary disease (COPD),pulmonary hypertension (PH) is associated with a poor prognosis. We investigated whether repeated Waon therapy improves PH,cardiac function,exercise tolerance,and the quality of life (QOL) in patients with COPD. Consecutive 13 patients with COPD,who met the Global Initiative for Chronic Obstructive Lung Disease criteria and had breathlessness despite receiving conventional treatments,were recruited for this study. They underwent Waon therapy at 60 degrees C in sauna for 15 min following 30 min warmth with blankets outside of the sauna room. This therapy was performed once a day,for 4 weeks. Cardiac function,exercise tolerance,and St. George's Respiratory Questionnaire (SGRQ) were assessed before and 4 weeks after Waon therapy. Right ventricular positive dP/dt at rest elevated significantly from 397 +/- 266 to 512 +/- 320 mmHg/s (p = 0.024) after the therapy. While the PH at rest did not significantly decrease,the PH during exercise decreased significantly from 64 +/- 18 to 51 +/- 13 mmHg (p = 0.028) after Waon therapy. Furthermore,the therapy prolonged the mean exercise time of the constant load of cycle ergometer exercise test from 360 +/- 107 to 392 +/- 97 s (p = 0.032). The total scores of SGRQ improved from 59.7 +/- 16.9 to 55.3 +/- 17.2 (p = 0.002). In addition,no adverse effects were observed related to Waon therapy. Repeated Waon therapy improved right ventricular positive dP/dt,PH during exercise,exercise tolerance and the QOL in patients with severe COPD.","J Cardiol. 2008 Apr;51(2):106-13.","Japan",2008,"COPD","Waon therapy","SGRQ"]
[52,"Yoshimi S,Tanabe N,Masuda M,Sakao S,Uruma T,Shimizu H,Kasahara Y,Takiguchi Y,Tatsumi K,Nakajima N,Kuriyama T. Survival and quality of life for patients with peripheral type chronic thromboembolic pulmonary hypertension. Circ J. 2008 Jun;72(6):958-65.",null,"Yoshimi S,Tanabe N,Masuda M,Sakao S,Uruma T,Shimizu H,Kasahara Y,Takiguchi Y,Tatsumi K,Nakajima N,Kuriyama T.","Survival and quality of life for patients with peripheral type chronic thromboembolic pulmonary hypertension.","The validity of pulmonary thromboendarterectomy for treatment of relatively peripheral type of chronic thromboembolic pulmonary hypertension (CTEPH) remains uncertain. The survival and quality of life (QOL) of patients with relatively peripheral type of CTEPH was investigated at follow up. Between April 1999 and March 2006,83 consecutive patients with CTEPH were evaluated for surgical indication and underwent computed tomography angiography. The extent of central disease was scored (ie,CD score),and a CD score of <or=1 was judged as relatively peripheral disease. Forty-three patients were excluded from surgery,and 40 patients,including 14 cases of relatively peripheral disease,underwent surgery. Long-term survival and QOL scores at follow up (1-3 years) were compared between the surgically and medically treated groups of relatively peripheral disease. Survival curves between the 2 treatment groups were not significantly different (p=0.78) because of high operative mortality (21.4%). However,improvement in physical functioning,role function (physically related),general health perception (as assessed by the Medical Outcome Study Short Form 36),and baseline dyspnea index were significantly higher in the group treated surgically compared with the medically treated group. CONCLUSIONS: Pulmonary thromboendarterectomy offers better QOL even in those patients with relatively peripheral type of CTEPH,although operative mortality must be reduced.","Circ J. 2008 Jun;72(6):958-65.","Japan",2008,"CTEPH","Surgery","SF-36"]
[53,"Pepke-Zaba J,Gilbert C,Collings L,Brown MC. Sildenafil improves health-related quality of life in patients with pulmonary arterial hypertension. Chest. 2008 Jan;133(1):183-9. doi: 10.1378/chest.07-0592.","doi: 10.1378/chest.07-0592.","Pepke-Zaba J,Gilbert C,Collings L,Brown MC.","Sildenafil improves health-related quality of life in patients with pulmonary arterial hypertension.","Sildenafil inhibits phosphodiesterase-5,enhancing cyclic guanosine monophosphate- mediated relaxation of pulmonary vasculature and is effective in treating patients with pulmonary arterial hypertension (PAH). Patients with PAH (n = 278) received oral sildenafil (20,40,or 80 mg three times daily) in a 12-week,double-blind,placebo-controlled study and an open-label extension. Health-related quality of life (HRQoL) was recorded by patients using the Medical Outcomes Study 36-item short form (SF-36) and EuroQol 5D (EQ-5D) questionnaires at baseline and after 12 and 24 weeks of therapy. Data are presented for patients who received sildenafil for up to 24 weeks. Sildenafil-treated patients,compared with placebo-treated patients,exhibited significant improvement in exercise capacity at week 12 (p < 0.001). Increases from baseline to week 12 were observed in all SF-36 domains for sildenafil-treated patients,with statistically significant improvements,compared with placebo-treated control subjects,in physical functioning (p < 0.001),general health (p < 0.001),and vitality (p < 0.05). Statistically significant improvements were also observed for the EQ-5D current health status (p < 0.01) and utility index (p < 0.01). These benefits were maintained for 24 weeks. Treatment groups were pooled for analyses as the results for the 6-min walk distance,SF-36,and EQ-5D were not dose dependent. Sildenafil improves HRQoL of PAH patients. These improvements appear to be maintained for at least 24 weeks. The effects are strongest in domains addressing the physical impact of health on daily activities and patients' overall perception of health.","Chest. 2008 Jan;133(1):183-9.","UK",2008,"Any PAH","Sildenafil","EQ-5D,SF-36"]
[54,"Gomberg-Maitland M,Thenappan T,Rizvi K,Chandra S,Meads DM,McKenna SP. United States validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). J Heart Lung Transplant. 2008 Jan;27(1):124-30. doi: 10.1016/j.healun.2007.10.004.","doi: 10.1016/j.healun.2007.10.004.","Gomberg-Maitland M,Thenappan T,Rizvi K,Chandra S,Meads DM,McKenna SP.","United States validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).","The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first pulmonary hypertension-specific instrument for assessing patient-reported symptoms,functioning,and quality of life. To enable use in the United States,this study adapted,field-tested,and evaluated its reliability and validity at a single center in Chicago. A lay panel confirmed appropriate wording of CAMPHOR for United States patients,and 15 patients with pulmonary hypertension field-tested the CAMPHOR for face and content validity. A postal validation study,with the Medical Outcomes Study Short Form 36 (SF-36) Health Survey as a comparator,was sent to patients on 2 occasions,2 weeks apart. World Health Organization (WHO) functional class and 6-minute walk test data were obtained. Field-test interviews found the CAMPHOR relevant and comprehensible. A total of 147 patients (84.0% women) with a mean of 50 +/- 14.6 years participated in the validation study. The new scales had good test-retest reliability (range,0.80-0.95) and internal consistency (range,0.78-0.95). The CAMPHOR scales correlated with the SF-36 and 6-minute walk test. Patients in WHO functional class III had worse scores than those in class II (p = 0.02),as did patients who rated their health worse (p < 0.001). The US CAMPHOR is a reliable and valid measure of quality of life and health status in pulmonary hypertension and can be recommended for use in clinical practice and trials in the United States.","J Heart Lung Transplant. 2008 Jan;27(1):124-30.","USA",2008,"Any PAH","None or unknown","CAMPHOR,SF-36"]
[55,"Denton CP,Pope JE,Peter HH,Gabrielli A,Boonstra A,van den Hoogen FH,Riemekasten G,De Vita S,Morganti A,Dölberg M,Berkani O,Guillevin L,TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators. Long-term effects of bosentan on quality of life,survival,safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis. 2008 Sep;67(9):1222-8. doi: 10.1136/ard.2007.079921. Epub 2007 Nov 30.","doi: 10.1136/ard.2007.079921. Epub 2007 Nov 30.","Denton CP,Pope JE,Peter HH,Gabrielli A,Boonstra A,van den Hoogen FH,Riemekasten G,De Vita S,Morganti A,Dölberg M,Berkani O,Guillevin L,TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators.","Long-term effects of bosentan on quality of life,survival,safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases.","This study investigated the long-term effects of bosentan,an oral endothelin ET(A)/ET(B) receptor antagonist,in patients with pulmonary arterial hypertension (PAH) exclusively related to connective tissue diseases (CTD). A total of 53 patients with PAH related to connective tissue diseases (PAH-CTD) in World Health Organization (WHO) functional class III received bosentan 62.5 mg twice a day for 4 weeks and then 125 mg twice a day for 44 weeks in this open non-comparative study. Assessments at weeks 16 and 48 included WHO class,clinical worsening,quality of life (Short-Form Health Survey (SF-36) and health assessment questionnaire (HAQ) modified for scleroderma),and survival (week 48 only). Safety and tolerability were monitored throughout the study. At week 48,WHO class improved in 27% of patients (95% CI 16-42%) and worsened in 16% (95% CI 7-29%). Kaplan-Meier estimates were 68% (95% CI 55-82%) for absence of clinical worsening and 92% (95% CI 85-100%) for survival. Overall changes in quality of life were minimal. There were no unexpected side effects observed during the study. In most patients,bosentan was associated with improvement or stability of clinical status. The 92% estimate for survival at 48 weeks is a significant achievement in this patient population.","Ann Rheum Dis. 2008 Sep;67(9):1222-8.","UK",2008,"Interstitial lung disease","Bosentan","HAQ-DI,SF-36"]
[56,"Ulrich S,Speich R,Domenighetti G,Geiser T,Aubert JD,Rochat T,Huber L,Treder U,Fischler M. Bosentan therapy for chronic thromboembolic pulmonary hypertension.  A national open label study assessing the effect of Bosentan on haemodynamics,exercise capacity,quality of life,safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study). Swiss Med Wkly. 2007 Oct 20;137(41-42):573-80. doi: 2007/41/smw-11819.","doi: 2007/41/smw-11819.","Ulrich S,Speich R,Domenighetti G,Geiser T,Aubert JD,Rochat T,Huber L,Treder U,Fischler M.","Bosentan therapy for chronic thromboembolic pulmonary hypertension.  A national open label study assessing the effect of Bosentan on haemodynamics,exercise capacity,quality of life,safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study).","we performed an open-label national study to evaluate the effects of Bosentan on haemodynamics,exercise capacity,quality of life,safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (CTEPH). fifteen patients with CTEPH not eligible or waiting for surgery were enrolled. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included quality of life (measured by the Minnesota living with heart failure questionnaire,MLHF),6 minute walk distance (6MWD),World Health Organization (WHO) functional class,Borg dyspnoea scale,plasma endothelin,serum values of disease severity such as uric acid,N-terminal-pro brain natriuretic peptide (NTproBNP),C-reactive protein measured by a highly sensitive method (CRPs) and other serum and haemodynamic parameters. after six months of treatment with bosentan,the PVR decreased from 852 (319) to 657(249) dyn*s*m-5 (p = 0.02). Quality of life considerably improved from a mean total score of 48(14) to 35(17) (p = 0.003) with improvements in the physical (from 25(5) to 17(7)) and emotional (from 11(6) to 6(5)) subscores (p = 0.005 and 0.011),respectively. The 6MWD improved from 389(78) to 443(79) meters (p = 0.005). 4 patients (27%) improved and 11 patients (73%) maintained their WHO class with no deterioration during the six months of bosentan treatment (p = 0.02). Uric acid serum levels declined from 525(145) to 453(151) micromol/l (p = 0.006),NTproBNP and CRPs declined insignificantly. Endothelin serum levels increased from 4.3(1.5) to 5.9(2.2) pg/ml (p = 0.025). Patients tolerated the treatment well,and there were no severe adverse events or deaths. this open-label study suggests a beneficial effect of bosentan therapy not only on pulmonary haemodynamics,but also on quality of life and exercise capacity for patients with severe CTEPH.","Swiss Med Wkly. 2007 Oct 20;137(41-42):573-80.","Switzerland",2007,"CTEPH","Bosentan","BDI,MLHFQ"]
[57,"Furst D,Khanna D,Matucci-Cerinic M,Clements P,Steen V,Pope J,Merkel P,Foeldvari I,Seibold J,Pittrow D,Polisson R,Strand V. Systemic sclerosis - continuing progress in developing clinical measures of response. J Rheumatol. 2007 May;34(5):1194-200.",null,"Furst D,Khanna D,Matucci-Cerinic M,Clements P,Steen V,Pope J,Merkel P,Foeldvari I,Seibold J,Pittrow D,Polisson R,Strand V.","Systemic sclerosis - continuing progress in developing clinical measures of response.","Few randomized controlled trials (RCT) have shown a demonstrable treatment effect in systemic sclerosis (SSc),making it difficult to evaluate outcome measures in this disease indication. Results from recent RCT,including those evaluating cyclophosphamide for SSc interstitial lung disease and endothelin receptor antagonists for pulmonary hypertension,have allowed analysis of certain organ-specific endpoints using the OMERACT filter. An earlier metaanalysis established that skin score,measures of Raynaud's,pulmonary function tests,blood pressure,pain,Health Assessment Questionnaire,and Medical Outcomes Survey Short-Form 36 are validated outcome measures in SSc. At OMERACT 8,data regarding validation of high-resolution computed tomography of the lungs,6-minute walk test,and patient reported outcomes in SSc were presented. A Delphi exercise to develop consensus regarding a combined set of noninvasive measures for pulmonary arterial hypertension (PAH) is under way. Given the protean nature of this illness and its multiorgan system involvement,a composite responder index may be preferable. Another Delphi exercise is designed to develop consensus regarding a combined SSc response index to be validated in future RCT.","J Rheumatol. 2007 May;34(5):1194-200.","International",2007,"Systemic sclerosis","Any ERA","HAQ-DI,SF-36"]
[58,"Mok MY,Tsang PL,Lam YM,Lo Y,Wong WS,Lau CS. Bosentan use in systemic lupus erythematosus patients with pulmonary arterial hypertension. Lupus. 2007;16(4):279-85. doi: 10.1177/0961203307076509.","doi: 10.1177/0961203307076509.","Mok MY,Tsang PL,Lam YM,Lo Y,Wong WS,Lau CS.","Bosentan use in systemic lupus erythematosus patients with pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE) is uncommon but is associated with poor survival. This study aimed to examine the long-term effects of bosentan,a dual endothelin-1 receptor antagonist,on symptomatology,haemodynamics and quality of life measures in SLE patients with symptomatic PAH. Four local patients had been followed up prospectively with pre-defined protocol during 12-months of bosentan treatment. Six minute walk distance (6MWD),NYHA functional class,Borg Dyspnoea Index (BDI) and SF-36 were measured at 0,3,6,9 and 12 months. Systolic pulmonary arterial pressure (PAP) was measured by transthoracic echocardiography at zero,six and 12 months. Clinical parameters were analysed,pooling data from other SLE patients reported in the literature (n = 4). Bosentan was found to result in significant improvement in 6MWD compared to baseline [+24.8 m,+26.2 m,+54 m and +62.7 m at three (P = 0.001),six (P = 0.001),nine (P = 0.24) and 12 (P = 0.01) months respectively]. A differential effect was found with greater response in patients with lower exercise capacity. This was accompanied by decrease in NYHA functional class,BDI,transient or sustained drop in systolic PAP and mild improvement in SF-36 domains including mental health,vitality,social function and general health. Significantly deranged liver function was found in one patient.","Lupus. 2007;16(4):279-85.","China",2007,"SLE","Bosentan","BDI,SF-36"]
[59,"Keogh AM,McNeil KD,Wlodarczyk J,Gabbay E,Williams TJ. Quality of life in pulmonary arterial hypertension: improvement and maintenance with bosentan. J Heart Lung Transplant. 2007 Feb;26(2):181-7. doi: 10.1016/j.healun.2006.11.009.","doi: 10.1016/j.healun.2006.11.009.","Keogh AM,McNeil KD,Wlodarczyk J,Gabbay E,Williams TJ.","Quality of life in pulmonary arterial hypertension: improvement and maintenance with bosentan.","Bosentan (an oral dual endothelin receptor antagonist) improves symptoms and cardiac hemodynamics and reduces clinical worsening in patients with pulmonary arterial hypertension (PAH). The VITAL study assessed the effect of bosentan on quality of life in patients with WHO Functional Class III or IV PAH (idiopathic or associated with connective tissue diseases). Quality of life was assessed prospectively using the MOS SF-36 and AQOL questionnaires. Baseline readings and scores at 3 and 6 months were collected,in addition to other efficacy and safety data. Among the 177 study patients,SF-36 scores were significantly improved at 3 months in the domains of physical functioning (27.3 to 34.8; p < 0.0001),role-physical (16.6 to 30.9; p < 0.0001),vitality (35.2 to 41.1; p = 0.0003),social functioning (48.0 to 58.6; p < 0.0001),mental health (64.2 to 72.0; p = 0.005) and role-emotional (44.8 to 58.1; p = 0.001). Improvements were seen in all etiologic sub-groups and were maintained in patients who remained on bosentan. An improvement in AQOL measures at 3 months was also noted for patients with baseline WHO Functional Class III. Bosentan significantly improves quality of life in patients with idiopathic PAH or PAH associated with connective tissue diseases.","J Heart Lung Transplant. 2007 Feb;26(2):181-7.","Australia",2007,"Any PAH","Bosentan","AQOL,SF-36"]
[60,"Ibrahim R,Granton JT,Mehta S. An open-label,multicentre pilot study of bosentan in pulmonary arterial hypertension related to congenital heart disease. Can Respir J. 2006 Nov-Dec;13(8):415-20.",null,"Ibrahim R,Granton JT,Mehta S.","An open-label,multicentre pilot study of bosentan in pulmonary arterial hypertension related to congenital heart disease.","Bosentan has been shown to be a safe and efficacious treatment for idiopathic pulmonary arterial hypertension (PAH) and PAH associated with connective tissue disease. However,there are limited studies examining the benefits of bosentan in PAH associated with congenital heart disease (CHD). The aim of the present pilot study was to explore the safety and efficacy of bosentan in patients with PAH associated with CHD. In the present study,11 patients with PAH associated with CHD were enrolled to receive bosentan for a minimum of 16 weeks (62.5 mg twice a day for four weeks; thereafter 125 mg twice a day). Safety was assessed by monitoring adverse events,oxygen saturation,systemic blood pressure,pulse,complete blood count and liver function tests. Efficacy was assessed by the World Health Organization functional class,6 min walk test (6-MWT),modified Borg dyspnea index,echocardiography and the 36-item short form health survey. Ten patients completed the 16-week treatment period (one patient withdrew). Bosentan was not associated with a deterioration in resting oxygen saturation (83.0+/-4.6% at week 16 versus 81.9+/-6.1% at baseline; P = 0.402),or a deterioration in post-6-MWT oxygen saturation (70.1+/-10.9% at week 16 versus 68.7+/-15.1% at baseline; P = 0.747). Two patients experienced three serious adverse events. The distance walked in 6 min improved significantly by 28 m (P = 0.005) at week 16 compared with baseline,and the modified Borg dyspnea index also improved at week 16 compared with baseline (P = 0.050). The World Health Organization functional class improved from class III to class II for five of 10 patients (50%). Patients' self-rated quality of life (36-item short form health survey) demonstrated a nonsignificant improvement in each of the eight domains. Obtaining reliable echocardiographic measurements was difficult. Most echocardiographic parameters were only measurable on few patients,and none were measured on all patients,questioning the usefulness of echocardiography as a measuring tool for patients with complex CHD. Bosentan was not associated with worsening of resting oxygen saturation or exercise systemic oxygen saturation,suggesting its potential as a safe treatment option for patients with PAH associated with CHD. Improved 6-MWT and the modified Borg dyspnea index also suggested the possibility of bosentan as an efficacious treatment option for these patients. The results of the present study provide evidence for the need and feasibility of a large randomized,placebo-controlled clinical trial.","Can Respir J. 2006 Nov-Dec;13(8):415-20.","Canada",2006,"Congenital HD","Bosentan","BDI,SF-36"]
[61,"Chua R,Keogh AM,Byth K,O'Loughlin A. Comparison and validation of three measures of quality of life in patients with pulmonary hypertension. Intern Med J. 2006 Nov;36(11):705-10. doi: 10.1111/j.1445-5994.2006.01169.x.","doi: 10.1111/j.1445-5994.2006.01169.x.","Chua R,Keogh AM,Byth K,O'Loughlin A.","Comparison and validation of three measures of quality of life in patients with pulmonary hypertension.","Pulmonary hypertension,when advanced,markedly limits exercise capacity,activities of daily living and quality of life (QoL). No measure of QoL has yet been validated for the assessment of pulmonary hypertension. The aim of the study was to compare the validity of the Minnesota Living with Heart Failure (MLwHF) questionnaire,the Short Form-36 (SF-36) questionnaire and the Australian Quality of Life (AQoL) measure for assessing pulmonary hypertension treatment. Eighty-three patients were enrolled in three studies of pulmonary hypertension treatment (treprostinil,bosentan and sildenafil). They were assessed at baseline and 3 months with the MLwHF questionnaire. Treprostinil and bosentan groups also had 6 and 12 months' data. Twenty-one patients in the sildenafil trial completed concurrently,the SF-36 and AQoL measures at baseline and 3 months. QoL scores were correlated with the 6-min walk test distance,New York Heart Association functional class and right heart catheter-derived haemodynamic parameters of the disease for all matching time points and for changes in scores and clinical measurements over time. The MLwHF and SF-36 scores correlated well with the 6-min walk test distance and New York Heart Association functional class,but did not correlate with haemodynamic measurements. MLwHF and SF-36 scores also correlated with the rate of change of the 6-min walk test distance and New York Heart Association functional class over time. The MLwHF questionnaire and SF-36 are useful tools for the assessment of QoL in pulmonary hypertension and may be useful in the ongoing evaluation of QoL in the treatment and study of pulmonary hypertension.","Intern Med J. 2006 Nov;36(11):705-10.","Australia",2006,"Any PAH","Bosentan,Sildenafil,Treprostanil","AQOL,MLHFQ,SF-36"]
[62,"Mereles D,Ehlken N,Kreuscher S,Ghofrani S,Hoeper MM,Halank M,Meyer FJ,Karger G,Buss J,Juenger J,Holzapfel N,Opitz C,Winkler J,Herth FF,Wilkens H,Katus HA,Olschewski H,Grünig E. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation. 2006 Oct 3;114(14):1482-9. doi: 10.1161/CIRCULATIONAHA.106.618397. Epub 2006 Sep 18.","doi: 10.1161/CIRCULATIONAHA.106.618397. Epub 2006 Sep 18.","Mereles D,Ehlken N,Kreuscher S,Ghofrani S,Hoeper MM,Halank M,Meyer FJ,Karger G,Buss J,Juenger J,Holzapfel N,Opitz C,Winkler J,Herth FF,Wilkens H,Katus HA,Olschewski H,Grünig E.","Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension.","Pulmonary hypertension (PH) is associated with restricted physical capacity,limited quality of life,and a poor prognosis because of right heart failure. The present study is the first prospective randomized study to evaluate the effects of exercise and respiratory training in patients with severe symptomatic PH. Thirty patients with PH (21 women; mean age,50+/-13 years; mean pulmonary artery pressure,50+/-15 mm Hg; mean World Health Organization [WHO] class,2.9+/-0.5; pulmonary arterial hypertension,n=23; chronic thromboembolic PH,n=7) on stable disease-targeted medication were randomly assigned to a control (n=15) and a primary training (n=15) group. Medication remained unchanged during the study period. Primary end points were the changes from baseline to week 15 in the distance walked in 6 minutes and in scores of the Short Form Health Survey quality-of-life questionnaire. Changes in WHO functional class,Borg scale,and parameters of echocardiography and gas exchange also were assessed. At week 15,patients in the primary and secondary training groups had an improved 6-minute walking distance; the mean difference between the control and the primary training group was 111 m (95% confidence interval,65 to 139 m; P<0.001). Exercise training was well tolerated and improved scores of quality of life,WHO functional class,peak oxygen consumption,oxygen consumption at the anaerobic threshold,and achieved workload. Systolic pulmonary artery pressure values at rest did not change significantly after 15 weeks of exercise and respiratory training (from 61+/-18 to 54+/-18 mm Hg) within the training group. This study indicates that respiratory and physical training could be a promising adjunct to medical treatment in severe PH. The effects add to the beneficial results of modern medical treatment.","Circulation. 2006 Oct 3;114(14):1482-9.","Germany",2006,"Any PAH","Exercise","BDI"]
[63,"Cenedese E,Speich R,Dorschner L,Ulrich S,Maggiorini M,Jenni R,Fischler M. Measurement of quality of life in pulmonary hypertension and its significance. Eur Respir J. 2006 Oct;28(4):808-15. doi: 10.1183/09031936.06.00130405. Epub 2006 May 17.","doi: 10.1183/09031936.06.00130405. Epub 2006 May 17.","Cenedese E,Speich R,Dorschner L,Ulrich S,Maggiorini M,Jenni R,Fischler M.","Measurement of quality of life in pulmonary hypertension and its significance.","Until recently,assessment of patients with pulmonary hypertension has mainly relied on functional and haemodynamic parameters. Health-related quality of life (HRQOL),however,has become increasingly important in defining overall health status. The present study investigated the performance and clinical relevance of the Minnesota Living with Heart Failure (MLHF) questionnaire by prospectively studying 48 patients with either pulmonary arterial hypertension (n = 26) or chronic thromboembolic pulmonary hypertension (n = 22). The MLHF scores were correlated to various clinical and haemodynamic parameters. Prognostic outcome was evaluated by calculating the time taken to reach an adverse clinical event defined as death,lung transplantation or pulmonary endarterectomy. The reliability of test-re-test and internal consistency of this HRQOL tool was high. The MLHF score and its physical subscore correlated moderately to well with functional and haemodynamic parameters,except in the case of pulmonary artery pressures. Both scores significantly improved during vasodilator therapy. This figure was surpassed only by the New York Heart Association/World Health Organization functional class. A multivariate analysis of all variables revealed that the MLHF score was the sole factor predicting subsequent outcome. The Minnesota Living with Heart Failure questionnaire is highly reproducible,consistent,and a moderately valid and responsive tool in assessing health-related quality of life in pulmonary hypertension. Moreover,it is a significant predictor of outcome in these patients.","Eur Respir J. 2006 Oct;28(4):808-15.","Switzerland",2006,"Any PAH,CTEPH","None or unknown","MLHFQ"]
[64,"McKenna SP,Doughty N,Meads DM,Doward LC,Pepke-Zaba J. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension. Qual Life Res. 2006 Feb;15(1):103-15. doi: 10.1007/s11136-005-3513-4.","doi: 10.1007/s11136-005-3513-4.","McKenna SP,Doughty N,Meads DM,Doward LC,Pepke-Zaba J.","The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension.","No outcome measures specific to pulmonary hypertension (PH) currently exist. The aim of the study was to develop health-related quality of life (symptoms and functioning) scales and a quality of life scale that would allow comprehensive,accurate and valid patient-reported outcome assessment in clinical studies. The content of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was derived from qualitative interviews conducted with 35 patients. Item reduction was based on the analysis of responses to a postal survey (n=75) and patient interviews (n=15) designed to determine face and content validity. A final postal validation study (n=91) was performed to determine reproducibility and construct validity. The questionnaire was well received by participants who found it to be relevant,comprehensible and quick and easy to complete. Rasch and factor analyses were conducted to ensure unidimensionality of the final CAMPHOR scales; Overall symptoms (made up of Energy,Breathlessness and Mood subscales),Functioning and Quality of life. The CAMPHOR scales had good internal consistency (alpha=0.90-0.92) and reproducibility (test-retest correlations=0.86-0.92). They also exhibited convergent,divergent and known groups validity. The CAMPHOR is a valuable new instrument for assessing patient-reported outcome in PH clinical trials and routine practice.","Qual Life Res. 2006 Feb;15(1):103-15.","UK",2006,"Any PAH","None or unknown","CAMPHOR"]
[65,"Souza R,Jardim C,Martins B,Cortopassi F,Yaksic M,Rabelo R,Bogossian H. Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension. Curr Med Res Opin. 2005 Jun;21(6):907-11. doi: 10.1185/030079905X46232.","doi: 10.1185/030079905X46232.","Souza R,Jardim C,Martins B,Cortopassi F,Yaksic M,Rabelo R,Bogossian H.","Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension.","The aim of this study was to evaluate the effect of the oral dual ET(A)/ET(B) receptor antagonist bosentan on different surrogate markers in patients with pulmonary arterial hypertension (PAH). Prospective,open label,uncontrolled study in a University Hospital in Brazil. Fifteen PAH patients (11 females) with mean age of 40 +/- 11 years (5 in WHO functional class II,10 in class III). All patients were investigated at baseline and after 16 weeks of bosentan treatment. We used the following surrogate markers for patients' evaluation: 6-min walk test,quality of life questionnaire (Short Form SF-36) and N-terminal proBNP (B type natriuretic peptide) fraction levels in blood. Between the evaluation at baseline and week 16,the 6-min walk test distance changed from 396 +/- 135 to 434 +/- 137 m (p < 0.05). Each of the eight domains of the SF-36 was significantly improved. Mean NT-proBNP levels were decreased from a mean of 1670 pg/mL to 1010 pg/mL (p = 0.01). The study suggests that bosentan treatment results in the improvement of different kinds of surrogate markers independently of their specificity to reflect functional capacity,quality of life and myocardial stress. It is concluded that the combined use of these different markers may be an alternative endpoint for future short duration clinical trials.","Curr Med Res Opin. 2005 Jun;21(6):907-11.","Brazil",2005,"Any PAH","Bosentan","SF-36"]
[66,"Shafazand S,Goldstein MK,Doyle RL,Hlatky MA,Gould MK. Health-related quality of life in patients with pulmonary arterial hypertension. Chest. 2004 Nov;126(5):1452-9. doi: 10.1378/chest.126.5.1452.","doi: 10.1378/chest.126.5.1452.","Shafazand S,Goldstein MK,Doyle RL,Hlatky MA,Gould MK.","Health-related quality of life in patients with pulmonary arterial hypertension.","Patients with pulmonary arterial hypertension (PAH) often present with dyspnea and severe functional limitations,but their health-related quality of life (HRQOL) has not been studied extensively. This study describes HRQOL in a cohort of patients with PAH. Cross-sectional study. A tertiary care,university hospital-based,pulmonary hypertension (PH) clinic. We studied HRQOL in 53 patients with PAH (mean age,47 years; median duration of disease,559 days). Eighty-three percent were women,53% received epoprostenol,and 72% reported moderate-to-severe functional limitations with a New York Heart Association class 3 or 4 at enrollment. We examined HRQOL by administering the Nottingham Health Profile,Congestive Heart Failure Questionnaire,and Hospital Anxiety and Depression Scale. We used the Visual Analog Scale and standard gamble (SG) techniques to measure preferences for current health (utilities). Compared with population norms,participants reported moderate-to-severe impairment in multiple domains of HRQOL,including physical mobility,emotional reaction,pain,energy,sleep,and social isolation. Mean SG utilities were 0.71,suggesting that,on average,participants were willing to accept a 29% risk of death in order to be cured of PH. PAH is a devastating condition that affects predominately young women in the prime of their life. Understanding HRQOL and preferences are important in the care and management of these patients. Compared with population norms,patients with PAH have substantial functional and emotional limitations that adversely affect their HRQOL.","Chest. 2004 Nov;126(5):1452-9.","USA",2004,"Any PAH","None or unknown","CHFQ,HADS,NHP,StGm,VAS"]
[67,"Hoeper MM,Oudiz RJ,Peacock A,Tapson VF,Haworth SG,Frost AE,Torbicki A. End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives. J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):48S-55S. doi: 10.1016/j.jacc.2004.02.010.","doi: 10.1016/j.jacc.2004.02.010.","Hoeper MM,Oudiz RJ,Peacock A,Tapson VF,Haworth SG,Frost AE,Torbicki A.","End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives.","To date,randomized controlled clinical trials performed in pulmonary arterial hypertension (PAH) have been relatively short-term studies involving mainly patients with advanced disease. The primary end points in these trials have addressed exercise capacity,usually by using the 6-min walk test. Although this approach is still warranted in future trials assessing new treatments,it is likely that the focus will shift toward trials of longer duration,involving patients with less advanced disease,and that different drugs and drug-combination regimens will be compared. In such trials,it is possible that a composite of markers indicating clinical deterioration (e.g.,hospitalization for right heart failure,the requirement for the introduction of an alternative treatment,and predefined indicators of worsening exercise tolerance) may be more useful as primary end points. Quality of life will become a very important issue; however,appropriate quality-of-life questionnaires for PAH have yet to be developed. In addition,hemodynamics will likely remain valuable as secondary end points,but future clinical trials should include hemodynamics obtained both during exercise and at rest. Finally,cardiopulmonary exercise testing,echocardiographic studies,and biochemical parameters,such as brain natriuretic peptide or troponin T,may also prove useful as secondary end points in the future.","J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):48S-55S.","International",2004,"Any PAH","None or unknown","Unknown"]
[68,"Sastry BK,Narasimhan C,Reddy NK,Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized,placebo-controlled,double-blind,crossover study. J Am Coll Cardiol. 2004 Apr 7;43(7):1149-53. doi: 10.1016/j.jacc.2003.10.056.","doi: 10.1016/j.jacc.2003.10.056.","Sastry BK,Narasimhan C,Reddy NK,Raju BS.","Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized,placebo-controlled,double-blind,crossover study.","In a randomized,double-blind,crossover design,we compared the efficacy of sildenafil with placebo in patients with primary pulmonary hypertension (PPH). The primary end point was the change in exercise time on treadmill using the Naughton protocol. Secondary end points were change in cardiac index and pulmonary artery systolic pressure as assessed by Doppler echocardiography and quality of life (QOL) as assessed by a questionnaire. Primary pulmonary hypertension is a disorder with limited treatment options. Uncontrolled studies had shown sildenafil to be beneficial in the treatment of PPH. After initial clinical evaluation,including Doppler echocardiography and treadmill exercise test,patients were randomized to placebo or sildenafil with dosages ranging from 25 to 100 mg thrice daily on the basis of body weight. The evaluation was repeated after six weeks. Then patients were crossed over to alternate therapy. Final evaluation was performed after another six weeks of treatment. Twenty-two patients completed the study. Exercise time increased by 44% from 475 +/- 168 s at the end of placebo phase to 686 +/- 224 s at the end of sildenafil phase (p < 0.0001). With sildenafil,cardiac index improved from 2.80 +/- 0.9 l/m2 to 3.45 +/- 1.1 l/m(2) (p < 0.0001),whereas pulmonary artery systolic pressure decreased insignificantly from 105.23 +/- 17.82 mm Hg to 98.50 +/- 24.38 mm Hg. There was significant improvement in the dyspnea and fatigue components of the QOL questionnaire. During the placebo phase,one patient died and another had syncope. There were no serious side effects with sildenafil. Sildenafil significantly improves exercise tolerance,cardiac index,and QOL in patients with PPH.","J Am Coll Cardiol. 2004 Apr 7;43(7):1149-53.","India",2004,"Any PAH","Sildenafil","Unknown"]
[69,"Mikhail GW,Prasad SK,Li W,Rogers P,Chester AH,Bayne S,Stephens D,Khan M,Gibbs JS,Evans TW,Mitchell A,Yacoub MH,Gatzoulis MA. Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects. Eur Heart J. 2004 Mar;25(5):431-6. doi: 10.1016/j.ehj.2004.01.013.","doi: 10.1016/j.ehj.2004.01.013.","Mikhail GW,Prasad SK,Li W,Rogers P,Chester AH,Bayne S,Stephens D,Khan M,Gibbs JS,Evans TW,Mitchell A,Yacoub MH,Gatzoulis MA.","Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects.","The treatment of patients with pulmonary arterial hypertension remains a challenge. We set out to investigate the use of sildenafil,a selective inhibitor of phosphodiesterase type 5,in patients with this disease. Ten patients (8 females,mean age 34.5+/-3.3 years) with pulmonary hypertension underwent right heart catheterisation with vasodilator testing using incremental doses of intravenous sildenafil without adverse events. All patients were subsequently commenced on oral sildenafil 50 mg t.d.s. Nine patients had repeat right heart catheterisation 3 months after the commencement of oral therapy. There was a significant reduction in mean pulmonary artery pressure (from 55.8+/-5.9 to 50.4+/-6.1 mmHg,p=0.038 ) and pulmonary vascular resistance (from 10.1+/-1.7 to 8.6+/-1.5 Wood units,p=0.009 ),and an increase in cardiac output (from 4.7+/-0.3 to 5.0+/-0.4 l/min,p=0.15 ). Furthermore,there was a significant increase in the 6-minute walk test,a mean of 112 m. In response to a quality-of-life questionnaire,patients indicated marked clinical improvement on sildenafil. Sildenafil was discontinued in 1 patient due to a transient visual disturbance. The only patient previously awaiting transplantation was removed from the active transplantation list. Sildenafil is well tolerated in its intravenous and oral forms and appears to improve both pulmonary haemodynamics and the clinical status of patients with pulmonary hypertension after 3 months of oral therapy.","Eur Heart J. 2004 Mar;25(5):431-6.","UK",2004,"Any PAH","Sildenafil","Unknown"]
[70,"Archibald CJ,Auger WR,Fedullo PF,Channick RN,Kerr KM,Jamieson SW,Kapelanski DP,Watt CN,Moser KM. Long-term outcome after pulmonary thromboendarterectomy. Am J Respir Crit Care Med. 1999 Aug;160(2):523-8. doi: 10.1164/ajrccm.160.2.9808109.","doi: 10.1164/ajrccm.160.2.9808109.","Archibald CJ,Auger WR,Fedullo PF,Channick RN,Kerr KM,Jamieson SW,Kapelanski DP,Watt CN,Moser KM.","Long-term outcome after pulmonary thromboendarterectomy.","This study evaluated long-term outcome of pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Survival,functional status,quality of life,health care utilization,and relationships between these parameters and postoperative pulmonary hemodynamics were assessed. Questionnaires were mailed to 420 patients who were more than 1 yr post-PTE; 308 responded (mean age,56 yr [range,19-89 yr]; mean years since PTE,3.3 [range,1- 16]). Survival after PTE was 75% at > 6 yr. After surgery,symptoms were markedly reduced. Median distance walked was 5,280 ft; 56 patients could walk \"indefinitely.\" Of the working population,62% of patients unemployed before PTE returned to work. Post-PTE patients scored several quality of life components of the Rand SF-36 slightly lower than reported normals but significantly higher than did pre-PTE patients. Ten percent of patients used oxygen. Ninety-three percent were in NYHA Class I or II. Disease-related hospitalizations/ER visits were minimal. A relationship was shown between 48 h postoperative pulmonary vascular resistance (PVR) and walking and stair-climbing ability,NYHA class,dyspnea scores,and the physical function and general health quality of life components. These data indicate that PTE offers most CTEPH patients substantial improvement in survival,function,and quality of life,with minimal disease-related health care utilization.","Am J Respir Crit Care Med. 1999 Aug;160(2):523-8.","USA",1999,"CTEPH","Surgery","Unknown"]

{"sheet":"Abbreviations","index":2,"n_rows":38,"n_cols":1,"rows_kept":38,"cut":false,"hidden":false,"merged":[]}
[]
[]
["AQ20 –  Airways Questionnaire 20"]
["AQOL – Australian Quality of Life"]
["BDI – Borg Dyspnoea Index"]
["CAMPHOR – Cambridge Pulmonary Hypertension Outcome Review"]
["CHD – Congenital heart disease (including Eisenmenger syndrome)"]
["CHFQ – Congestive Heart Failure Questionnaire"]
["CHQ-PF50 – Child Health Questionnaire – Parent Form"]
["COPD – Chronic obstructive pulmonary disease"]
["CTEPH – chronic thromboembolic pulmonary hypertension"]
["D-12 – Dyspnoea-12"]
["EQ-5D – EuroQol Questionnaire"]
["EscSG – European Scleroderma Study Group activity index"]
["ERA – Endothelin receptor antagonist"]
["GAD-7 – General Anxiety Disorder Scale"]
["HADS – Hospital Anxiety and Depression Scale"]
["HAQ-DI – Health Assessment Questionnaire – Disability Index"]
["ILD- Interstitial lung disease"]
["KCQ – Kansas City Questionnaire"]
["MLHFQ – Minnesota Living with Heart Failure Questionnaire"]
["NHP – Nottingham Health Profile"]
["PAH – Pulmonary arterial hypertension"]
["PAHSIS – PAH Symptom Interference Scale"]
["PAH-SSS – PAH Symptom Severity Scale"]
["PDE-5 – Phosphodiesterase-5 inhibitor"]
["POMS – Profile Of Mood States"]
["RSS – Rodnan Skin Score"]
["SF-6D – Short Form 6 items"]
["SF-12 – Short Form 12 items"]
["SF-36 – Short Form 36 items"]
["SG – Standard Gamble"]
["SGRQ – St. George’s Respiratory Questionnaire"]
["SLE – Systemic lupus erythematosus"]
["TSQM – Treatment Satisfaction Questionnaire for Medication"]
["TTO – Time Trade-Off"]
["UCSD-SBQ – University of California San Diego Shortness of Breath Questionnaire"]
["VAS – Visual Analogue Scale"]

{"sheet":"Mapper","index":3,"n_rows":613,"n_cols":11,"rows_kept":613,"cut":false,"hidden":false,"merged":[[22,1,22,6]]}
[]
[]
[null,"1. Select the first category to be included in the",null,null,null,null,null,null,null,null,"Count"]
[null," Evidence Map. This will show as a series of rows",null,null,null,null,null,null,null,"1960:1999",1]
[null,"in the Map",null,null,null,null,null,null,null,"2000:2004",5]
[null,"First dimension",null,null,null,null,null,null,null,"2005:2009",25]
[null,5,{"$f":"OFFSET(C531,B7,0)","v":"Dates"},null,{"$f":"COUNTA(J4:J503)","v":5},null,null,null,null,"2010:2014",25]
[null,null,null,null,null,null,null,null,null,"2015:2018",14]
[]
[null,"2. Then select the second category to be shown "]
[null,"as the columns of the Map, or leave blank"]
[null,"Second dimension"]
[null,8,{"$f":"OFFSET(C531,B13,0)","v":0},null,{"$f":"COUNTA(K3:PZ3)","v":1}]
[]
[null,"3. Click on a cell in the Map, then click the Show"]
[null,"Citation button below to see the relevant"]
[null,"citations for that cell "]
[]
[]
[null,"Row",{"$f":"IF(AND(selectedRow>3,selectedRow<(4+E7)),OFFSET(tableLoc,(selectedRow-3),0),\"\")","v":""},null,null,null,null," "]
[null,"Column",{"$f":"IF(AND(selectedColumn>10,selectedColumn<(11+columnCount)),OFFSET(tableLoc,0,(selectedColumn-10)),\"\")","v":""},null,null,null,null," "]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[null,null,"Dates"]
[null,null,"None"]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[null,"Locations",{"$f":"COUNTA(C532:C550)","v":6}]
[1,"Locations","Locations"]
[2,"Interventions","Interventions"]
[3,"Diseases","Diseases"]
[4,{"$f":"INDEX(domainList,A535)","v":"PRO tools"},"PRO tools"]
[5,{"$f":"INDEX(domainList,A536)","v":"subPopulations"},"Dates"]
[6,{"$f":"INDEX(domainList,A537)","v":"Study types"},"None"]
[7,{"$f":"INDEX(domainList,A538)","v":"Study methodologies"}]
[1,{"$f":"INDEX(customList,A539)","v":"C1"}]
[2,"C2"]
[3,"C3"]
[4,"C4"]
[5,"C5"]
[6,"C6"]
[7,"C7"]
[8,"C8"]
[9,"C9"]
[10,"C10"]
[null,"Dates"]
[null,"None"]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[null,"Row",1]
[null,"Column",1]
[null,"columnCount",{"$f":"COUNTA(K3:ZZ3)","v":1}]

{"sheet":"CitationIndex","index":4,"n_rows":34,"n_cols":3,"rows_kept":34,"cut":false,"hidden":true,"merged":[]}
[null,"Column","Column number"]
[null,"Full citation",{"$f":"MATCH(B2,Citations!A$1:BB$1,0)","v":2}]
[null,"Authors",{"$f":"MATCH(B3,Citations!A$1:BB$1,0)","v":4}]
[null,"Title",{"$f":"MATCH(B4,Citations!A$1:BB$1,0)","v":5}]
[null,"Citation",{"$f":"MATCH(B5,Citations!A$1:BB$1,0)","v":7}]
[null,"DOI",{"$f":"MATCH(B6,Citations!A$1:BB$1,0)","v":3}]
[null,"Abstract",{"$f":"MATCH(B7,Citations!A$1:BB$1,0)","v":6}]
[null,"Locations",{"$f":"MATCH(B8,Citations!A$1:BB$1,0)","v":8}]
[null,"Year",{"$f":"MATCH(B9,Citations!A$1:BB$1,0)","v":9}]
[null,"Diseases",{"$f":"MATCH(B10,Citations!A$1:BB$1,0)","v":10}]
[null,"Interventions",{"$f":"MATCH(B11,Citations!A$1:BB$1,0)","v":11}]
[null,"Subpopulations",{"$f":"MATCH(B12,Citations!A$1:BB$1,0)","v":13}]
[null,"Study types",{"$f":"MATCH(B13,Citations!A$1:BB$1,0)","v":14}]
[null,"Study methodologies",{"$f":"MATCH(B14,Citations!A$1:BB$1,0)","v":15}]
[null,"PROtools",{"$f":"MATCH(B15,Citations!A$1:BB$1,0)","v":12}]
[null,"LocationsTags",{"$f":"MATCH(B16,Citations!A$1:BB$1,0)","v":16}]
[null,"SubpopulationsTags",{"$f":"MATCH(B17,Citations!A$1:BB$1,0)","v":17}]
[null,"DiseaseTags",{"$f":"MATCH(B18,Citations!A$1:BB$1,0)","v":18}]
[null,"InterventionsTags",{"$f":"MATCH(B19,Citations!A$1:BB$1,0)","v":19}]
[null,"StudytypesTags",{"$f":"MATCH(B20,Citations!A$1:BB$1,0)","v":20}]
[null,"StudyMethodologyTags",{"$f":"MATCH(B21,Citations!A$1:BB$1,0)","v":21}]
[null,"PROtoolTags",{"$f":"MATCH(B22,Citations!A$1:BB$1,0)","v":22}]
[null,"DateBand",{"$f":"MATCH(B23,Citations!A$1:BB$1,0)","v":23}]
[null,{"$f":"Custom1","v":"C1"},{"$f":"MATCH(B24,Citations!A$1:BB$1,0)","v":24}]
[null,{"$f":"Custom2","v":"C2"},{"$f":"MATCH(B25,Citations!A$1:BB$1,0)","v":25}]
[null,{"$f":"Custom3","v":"C3"},{"$f":"MATCH(B26,Citations!A$1:BB$1,0)","v":26}]
[null,{"$f":"Custom4","v":"C4"},{"$f":"MATCH(B27,Citations!A$1:BB$1,0)","v":27}]
[null,{"$f":"Custom5","v":"C5"},{"$f":"MATCH(B28,Citations!A$1:BB$1,0)","v":28}]
[null,{"$f":"Custom4","v":"C4"},{"$f":"MATCH(B29,Citations!A$1:BB$1,0)","v":27}]
[null,{"$f":"Custom5","v":"C5"},{"$f":"MATCH(B30,Citations!A$1:BB$1,0)","v":28}]
[null,{"$f":"Custom4","v":"C4"},{"$f":"MATCH(B31,Citations!A$1:BB$1,0)","v":27}]
[null,{"$f":"Custom5","v":"C5"},{"$f":"MATCH(B32,Citations!A$1:BB$1,0)","v":28}]
[null,{"$f":"Custom4","v":"C4"},{"$f":"MATCH(B33,Citations!A$1:BB$1,0)","v":27}]
[null,{"$f":"Custom5","v":"C5"},{"$f":"MATCH(B34,Citations!A$1:BB$1,0)","v":28}]

{"sheet":"Citations","index":5,"n_rows":71,"n_cols":33,"rows_kept":71,"cut":false,"hidden":true,"merged":[]}
[70,"Full citation","DOI","Authors","Title","Abstract","Citation","Locations","Year","Diseases","Interventions","PROtools","Subpopulations","Study types","Study methodologies","LocationsTags","SubpopulationsTags","DiseaseTags","InterventionsTags","StudytypesTags","StudyMethodologyTags","PROtoolTags","DateBand","C1","C2","C3","C4","C5","C6","C7","C8","C9","C10"]
[1,"Petrucci L,Carlisi E,Ricotti S,Zanellato S,Klersy C,D'Armini AM,Nicolardi S,Morsolini M,Viganò M,Dalla Toffola E. Functional assessment and quality of life before and after pulmonary endoarterectomy. G Ital Med Lav Ergon. 2015 Jul-Sep;37(3):170-5.",null,"Petrucci L,Carlisi E,Ricotti S,Zanellato S,Klersy C,D'Armini AM,Nicolardi S,Morsolini M,Viganò M,Dalla Toffola E.","Functional assessment and quality of life before and after pulmonary endoarterectomy.","The study investigates Quality of Life (QOL) and correlation with functional status of patients affected by Chronic Thromboembolic Pulmonary Hypertension who undergo Pulmonary Endoarterectomy. We investigated with an observational design (before surgery,three and twelve months afterwards) the hemodynamic data (NYHA class,mean pulmonary arterial pressure,cardiac output and pulmonary vascular resistance),the functional status (using the 6-Minute Walk Test) and the QOL,using three questionnaires: Medical Outcome Study Short Form-36 (SF-36),Minnesota Living with Heart Failure Questionnaire (MLHFQ),Saint George Respiratory Questionnaire (SGRQ). We report the results of forty-nine patients. After surgery there was an improvement on functional and hemodynamic parameters and on QOL. The physical domain (PCS) of SF-36 was weakly but significantly associated with all functional parameters. There was no association between functional parameters and mental domain (MCS) of SF-36 or SGRQ. The improvement in 6-Minute Walk Distance was associated with an increase in MLHFQ. Both QOL and submaximal exercise tolerance improve after surgery. However only the physical domains of SF-36 appear to be significantly associated to the functional data.","G Ital Med Lav Ergon. 2015 Jul-Sep;37(3):170-5.","Unknown",2015,"CTEPH","Surgery","MLHFQ,SF-36,SGRQ",null,null,null,"Unknown",null,"CTEPH","Surgery",null,null,"MLHFQ,SF-36,SGRQ","2015:2018"]
[2,"Pandey A,Garg S,Khunger M,Garg S,Kumbhani DJ,Chin KM,Berry JD. Efficacy and Safety of Exercise Training in Chronic Pulmonary Hypertension: Systematic Review and Meta-Analysis. Circ Heart Fail. 2015 Nov;8(6):1032-43. doi: 10.1161/CIRCHEARTFAILURE.115.002130. Epub 2015 Jul 16.","doi: 10.1161/CIRCHEARTFAILURE.115.002130. Epub 2015 Jul 16.","Pandey A,Garg S,Khunger M,Garg S,Kumbhani DJ,Chin KM,Berry JD.","Efficacy and Safety of Exercise Training in Chronic Pulmonary Hypertension: Systematic Review and Meta-Analysis.","Exercise training has been shown to improve cardiorespiratory fitness,physical capacity,and quality of life in patients with cardiopulmonary conditions,such as heart failure and chronic obstructive pulmonary disease. However,its role in management of pulmonary hypertension is not well defined. In this study,we aim to evaluate the efficacy and safety of exercise training in patients with pulmonary hypertension. We included all prospective intervention studies that evaluated the efficacy and safety of exercise training in patients with pulmonary hypertension. Primary outcome of this meta-analysis was a change in 6-minute walk distance. We also assessed the effect of exercise on peak oxygen uptake,resting pulmonary arterial systolic pressure,peak exercise heart rate,and quality of life. A total of 469 exercise-training participants enrolled in 16 separate training studies were included. In the pooled analysis,exercise training was associated with significant improvement in 6-minute walk distance (weighted mean difference,53.3 m; 95% confidence interval,39.5-67.2),peak oxygen uptake (weighted mean difference,1.8 mL/kg per minute; 95% confidence interval,1.4-2.3),pulmonary arterial systolic pressure (weighted mean difference,-3.7 mm Hg; 95% confidence interval,-5.4 to -1.9),peak exercise heart rate (weighted mean difference,10 beats per min; 95% confidence interval,6-15),and quality of life as measured on SF-36 questionnaire subscale scores. Furthermore,exercise training was well tolerated with a low dropout rate,and no major adverse events were related to exercise training. Exercise training in patients with pulmonary hypertension appears safe and is associated with a significant improvement in exercise capacity,pulmonary arterial pressure,and quality of life.","Circ Heart Fail. 2015 Nov;8(6):1032-43.","International",2015,"Any PAH","Exercise","SF-36",null,null,null,"International",null,"Any PAH","Exercise",null,null,"SF-36","2015:2018"]
[3,"Singer LG,Chowdhury NA,Faughnan ME,Granton J,Keshavjee S,Marras TK,Tullis DE,Waddell TK,Tomlinson G. Effects of Recipient Age and Diagnosis on Health-related Quality-of-Life Benefit of Lung Transplantation. Am J Respir Crit Care Med. 2015 Oct 15;192(8):965-73. doi: 10.1164/rccm.201501-0126OC.","doi: 10.1164/rccm.201501-0126OC.","Singer LG,Chowdhury NA,Faughnan ME,Granton J,Keshavjee S,Marras TK,Tullis DE,Waddell TK,Tomlinson G.","Effects of Recipient Age and Diagnosis on Health-related Quality-of-Life Benefit of Lung Transplantation.","The average age of lung transplant recipients is increasing,and the mix of recipient indications for transplantation is changing. To determine whether the health-related quality-of-life (HRQL) benefit of lung transplantation differs by recipient age and diagnosis. In this prospective cohort study,we obtained serial HRQL measurements in adults with advanced lung disease who subsequently underwent lung transplantation (2004-2012). HRQL assessments included the St. George's Respiratory Questionnaire,36-Item Short-Form Health Survey (SF-36),EQ-5D,Standard Gamble,and Visual Analog Scale for current health. We used linear mixed effects models for associations between age or diagnosis and changes in HRQL with transplantation. To address potential survivorship bias,we fitted Markov models to the distribution of discrete post-transplant health states (HRQL better than pretransplant,not better,or dead) and estimated quality-adjusted life-years post-transplant. A total of 430 subjects were listed,387 were transplanted,and 326 provided both pretransplant and post-transplant data. Transplantation conferred large improvements in all HRQL measures: St. George's change of -47 units (95% confidence interval,-48 to -44),36-Item Short-Form Health Survey physical component summary score of 17.7 (16.5-18.9),EQ-5D of 0.27 (0.24-0.30),Standard Gamble of 0.48 (0.44-0.51),and Visual Analog of 44 (42-47). Age was not associated with meaningful differences in the HRQL benefits of transplantation. There was less HRQL benefit in interstitial lung disease than in cystic fibrosis. Lung transplantation confers large HRQL benefits,which vary by recipient diagnosis,but do not differ substantially in older recipients.","Am J Respir Crit Care Med. 2015 Oct 15;192(8):965-73.","Canada",2015,"Interstitial lung disease","Lung transplant","SF-36,StGm,SGRQ,VAS",null,null,null,"Canada",null,"Interstitial lung disease","Lung transplant",null,null,"SF-36,StGm,SGRQ,VAS","2015:2018"]
[4,"Matura LA,Ventetuolo CE,Palevsky HI,Lederer DJ,Horn EM,Mathai SC,Pinder D,Archer-Chicko C,Bagiella E,Roberts KE,Tracy RP,Hassoun PM,Girgis RE,Kawut SM. Interleukin-6 and tumor necrosis factor-α are associated with quality of life-related symptoms in pulmonary arterial hypertension. Ann Am Thorac Soc. 2015 Mar;12(3):370-5. doi: 10.1513/AnnalsATS.201410-463OC.","doi: 10.1513/AnnalsATS.201410-463OC.","Matura LA,Ventetuolo CE,Palevsky HI,Lederer DJ,Horn EM,Mathai SC,Pinder D,Archer-Chicko C,Bagiella E,Roberts KE,Tracy RP,Hassoun PM,Girgis RE,Kawut SM.","Interleukin-6 and tumor necrosis factor-α are associated with quality of life-related symptoms in pulmonary arterial hypertension.","Inflammation is associated with symptoms in many chronic illnesses; however,this link has not been established in pulmonary arterial hypertension. The objective of this study was to investigate the association between inflammatory markers and quality of life-related symptoms in patients with pulmonary arterial hypertension. We hypothesized that higher circulating IL-6 and tumor necrosis factor-α levels would be associated with worse quality of life-related symptoms. We performed a secondary analysis using baseline and 3-month assessments of 62 subjects in a clinical trial of aspirin and simvastatin to determine the association between plasma IL-6 and tumor necrosis factor-α levels and the Medical Outcomes Study Short Form-36 subscales (pain,vitality,mental health). The mean age was 49.7±13.4 years; 87% were female. Higher IL-6 levels were significantly associated with lower Medical Outcomes Study Short Form-36 subscale scores,indicating worse bodily pain,vitality,and mental health (all P<0.01). Higher tumor necrosis factor-α levels were significantly associated with increased bodily pain,but better mental health scores. IL-6 and tumor necrosis factor-α levels are associated with certain quality of life domains in patients with pulmonary arterial hypertension. Clinical trial registered with www.clinicaltrials.gov (NCT00384865).\n","Ann Am Thorac Soc. 2015 Mar;12(3):370-5.","USA",2015,"Any PAH","Aspirin,Simvastatin","SF-36",null,null,null,"USA",null,"Any PAH","Aspirin,Simvastatin",null,null,"SF-36","2015:2018"]
[5,"Fernandes CJ,Martins BC,Jardim CV,Ciconelli RM,Morinaga LK,Breda AP,Hoette S,Souza R. Quality of life as a prognostic marker in pulmonary arterial hypertension. Health Qual Life Outcomes. 2014 Aug 30;12():130. doi: 10.1186/s12955-014-0130-3. Epub 2014 Aug 30.","doi: 10.1186/s12955-014-0130-3. Epub 2014 Aug 30.","Fernandes CJ,Martins BC,Jardim CV,Ciconelli RM,Morinaga LK,Breda AP,Hoette S,Souza R.","Quality of life as a prognostic marker in pulmonary arterial hypertension.","Improvement in quality of life together with better survival are the ultimate goals in the treatment of pulmonary arterial hypertension (PAH) patients. The objective of this study was to evaluate the health-related quality of life (HRQL) of pulmonary arterial hypertension (PAH) patients with the SF-36 generic questionnaire and to identify the prognostic implication of this assessment. Fifty-four consecutive newly diagnosed PAH patients (WHO classification group I) in a single PAH reference center were included. Patients were evaluated at baseline for clinical and hemodynamic parameters,and they subsequently received first-line therapy with either an endothelin receptor antagonist or a phosphodiesterase-5 inhibitor. After 16 weeks of specific PAH therapy,all patients were re-evaluated using a 6MWT and a SF 36 questionnaire,and then they were followed up for at least 36 months. After treatment,the patients demonstrated an improved 6MWT (414 ± 124 m vs. 440 ± 113 m,p = 0.001). Specific PAH therapy also improved the HRQL scores.Patients with a baseline Physical Component Score (PCS) higher than 32 had a better survival rate than those who had a score under 32 (p = 0.04). Similarly,patients with a PCS of at least a 38 after the 16 week therapy period had a better survival rate when compared with those who did not achieve this value (p = 0.016). Unlike the absolute PCS values,the post-treatment PCS variability was unable to predict better survival rates (p = 0.58). Our findings suggest that HRQL is associated with prognosis in PAH. Furthermore,achieving pre-determined PCS scores might represent a specific goal to be reached in treatment-to-target strategies.","Health Qual Life Outcomes. 2014 Aug 30;12():130.","Brazil",2014,"Any PAH","Any ERA,Any PDE-5I","SF-36",null,null,null,"Brazil",null,"Any PAH","Any ERA,Any PDE-5I",null,null,"SF-36","2010:2014"]
[6,"Rival G,Lacasse Y,Martin S,Bonnet S,Provencher S. Effect of pulmonary arterial hypertension-specific therapies on health-related quality of life: a systematic review. Chest. 2014 Sep;146(3):686-708. doi: 10.1378/chest.13-2634.","doi: 10.1378/chest.13-2634.","Rival G,Lacasse Y,Martin S,Bonnet S,Provencher S.","Effect of pulmonary arterial hypertension-specific therapies on health-related quality of life: a systematic review.","Health-related quality of life (HRQoL) is severely impaired in pulmonary arterial hypertension (PAH). We aimed to assess the effect of PAH-specific therapies on HRQoL. A literature search was performed in MEDLINE and Embase databases (January 1990 to September 2013) to retrieve prospective placebo-controlled randomized trials of at least 6 weeks duration reporting the effect of PAH-specific therapies on HRQoL in adult patients with PAH. The articles were independently reviewed,and the validity of the trials was assessed using the Cochrane's Risk of Bias Tool. The literature search identified 1,172 titles. Seventeen articles reporting on 14 trials were retrieved,all of which were associated with a low risk of bias. The median study duration of the different trials was 12 weeks. Most patients had idiopathic PAH or PAH associated with connective tissue disease. A variety of HRQoL questionnaires were used in these trials,and most were generic. HRQoL results were most commonly minimally detailed,and some pivotal trials did not even assess HRQoL. Nevertheless,these trials consistently demonstrated statistically significant improvements in HRQoL with PAH-specific therapies,especially for the physical domains. In most cases,however,these improvements were smaller than the minimal important difference in HRQoL previously reported in PAH. This review shows that PAH-specific therapies improve HRQoL in PAH. However,it remains difficult to draw any firm conclusion about the clinical significance of these improvements. Further work is mandatory to validate PAH-specific questionnaires that are responsive to clinical changes as well as to establish their interpretability.","Chest. 2014 Sep;146(3):686-708.","International",2014,"Any PAH,Interstitial lung disease","None or unknown","Unknown",null,null,null,"International",null,"Any PAH,Interstitial lung disease","None or unknown",null,null,"Unknown","2010:2014"]
[7,"Yorke J,Armstrong I. The assessment of breathlessness in pulmonary arterial hypertension: reliability and validity of the Dyspnoea-12. Eur J Cardiovasc Nurs. 2014 Dec;13(6):506-14. doi: 10.1177/1474515113514891. Epub 2013 Dec 3.","doi: 10.1177/1474515113514891. Epub 2013 Dec 3.","Yorke J,Armstrong I.","The assessment of breathlessness in pulmonary arterial hypertension: reliability and validity of the Dyspnoea-12.","Breathlessness is a cardinal symptom of pulmonary arterial hypertension (PAH); yet no breathlessness instrument has been previously tested for reliability and validity for this population. Using a cross-sectional design,we tested the psychometric properties of the Dyspnoea-12 (D-12),for the assessment of breathlessness in PAH. Pearson's correlations with World Health Organization functional class (WHO FC),Minnesota Living with Heart failure - pulmonary hypertension modified version (MLHF-PH),Hospital Anxiety and Depression scale (HADS) and 6-minute walk distance test (6MWD) were conducted. Participants (n = 176) were mostly female (70.5%),mean age 54.3±14 years; diagnosed with idiopathic PAH (48.9%),congenital heart disease (27.8%) and connective tissue disease (23.3%); and most were WHO FC II (32.4%) and III (52.3%). The D-12 showed excellent internal consistency for the total and two-component scores for physical and emotional (Cronbach's α 0.95,0.93 and 0.94,respectively). D-12 total score was significantly associated with MLHF-PH (r = 0.70),HADS (anxiety r = 0.54 and depression r = 0.68),WHO FC (r = 0.49),and 6MWD (r = -0.26). In patients with PAH,the D-12 - a short patient reported measure of breathlessness severity that taps the physical and emotional components,is a reliable and valid instrument.","Eur J Cardiovasc Nurs. 2014 Dec;13(6):506-14.","UK",2014,"Any PAH","None or unknown","D-12,HADS,MLHFQ",null,null,null,"UK",null,"Any PAH","None or unknown",null,null,"D-12,HADS,MLHFQ","2010:2014"]
[8,"Yorke J,Corris P,Gaine S,Gibbs JS,Kiely DG,Harries C,Pollock V,Armstrong I. emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension. Eur Respir J. 2014 Apr;43(4):1106-13. doi: 10.1183/09031936.00127113. Epub 2013 Nov 14.","doi: 10.1183/09031936.00127113. Epub 2013 Nov 14.","Yorke J,Corris P,Gaine S,Gibbs JS,Kiely DG,Harries C,Pollock V,Armstrong I.","emPHasis-10: development of a health-related quality of life measure in pulmonary hypertension.","The aim of this study was to develop a measure of the impact of pulmonary hypertension (PH) on health-related quality of life (HRQoL) as there is a need for a short,validated instrument that can be used in routine clinical practice. Interviews were conducted with 30 PH patients to derive 32 statements,which were presented as a semantic differential six-point scale (0-5),with contrasting adjectives at each end. This item list was completed by patients attending PH clinics across the UK and Ireland. Rasch analysis was applied to identify items fitting a uni-dimensional model. 226 patients (mean age 55.6±14 years; 70% female) with PH (82% had pulmonary arterial hypertension) completed the study questionnaires. 10 of the 32 items demonstrated fit to the Rasch model (Chi-squared 16; p>0.05) and generated the emPHasis-10 questionnaire. Test-retest (intraclass correlation coefficient 0.95,n=33) and internal consistency (Chronbach's α=0.9) were strong. emPHasis-10 scores correlated consistently with other relevant measures and discriminated subgroups of patients stratified by World Health Organization functional class (ANOVA F=1.73; p<0.001). The emPHasis-10 is a short questionnaire for assessing HRQoL in pulmonary arterial hypertension. It has excellent measurement properties and is sensitive to differences in relevant clinical parameters. It is freely available for clinical and academic use.","Eur Respir J. 2014 Apr;43(4):1106-13.","UK",2014,"Any PAH","None or unknown","EmPHasis-10",null,null,null,"UK",null,"Any PAH","None or unknown",null,null,"EmPHasis-10","2010:2014"]
[9,"Harzheim D,Klose H,Pinado FP,Ehlken N,Nagel C,Fischer C,Ghofrani A,Rosenkranz S,Seyfarth HJ,Halank M,Mayer E,Grünig E,Guth S. Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Respir Res. 2013 Oct 9;14():104. doi: 10.1186/1465-9921-14-104. Epub 2013 Oct 9.","doi: 10.1186/1465-9921-14-104. Epub 2013 Oct 9.","Harzheim D,Klose H,Pinado FP,Ehlken N,Nagel C,Fischer C,Ghofrani A,Rosenkranz S,Seyfarth HJ,Halank M,Mayer E,Grünig E,Guth S.","Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.","The objective of this prospective study was to assess the prevalence of anxiety and depression disorders and their association with quality of life (QoL),clinical parameters and survival in patients with pulmonary hypertension (PH). We prospectively assessed 158 patients invasively diagnosed with pulmonary arterial hypertension (n = 138) and inoperable chronic thromboembolic PH (n = 20) by clinical measures including quality of life (QoL,SF-36 questionnaire),cardiopulmonary exercise testing and six minute walking distance and by questionnaires for depression (PHQ-9) and anxiety (GAD-7). According to the results of the clinical examination and the questionnaires for mental disorders (MD) patients were classified into two groups,1) with moderate to severe MD (n = 36,22,8%),and 2) with mild or no MD (n = 122). Patients were followed for a median of 2.7 years. Investigators of QoL,SF-36 were blinded to the clinical data. At baseline the 2 groups did not differ in their severity of PH or exercise capacity. Patients with moderate to severe MD (group 1) had a significantly lower QoL shown in all subscales of SF-36 (p < 0.002). QoL impairment significantly correlated with the severity of depression (p < 0.001) and anxiety (p < 0.05). During follow-up period 32 patients died and 3 were lost to follow-up. There was no significant difference between groups regarding survival. Only 8% of the patients with MD received psychopharmacological treatment. Anxiety and depression were frequently diagnosed in our patients and significantly correlated with quality of life,but not with long term survival. Further prospective studies are needed to confirm the results.","Respir Res. 2013 Oct 9;14():104.","Germany",2013,"Any PAH,CTEPH","None or unknown","GAD-7,PHQ-9,SF-36",null,null,null,"Germany",null,"Any PAH,CTEPH","None or unknown",null,null,"GAD-7,PHQ-9,SF-36","2010:2014"]
[10,"Cha KS,Cho KI,Seo JS,Choi JH,Park YH,Yang DH,Hong GR,Kim DS. Effects of inhaled iloprost on exercise capacity,quality of life,and cardiac function in patients with pulmonary arterial hypertension secondary to congenital heart disease (the Eisenmenger syndrome) (from the EIGER Study). Am J Cardiol. 2013 Dec 1;112(11):1834-9. doi: 10.1016/j.amjcard.2013.08.003. Epub 2013 Sep 5.","doi: 10.1016/j.amjcard.2013.08.003. Epub 2013 Sep 5.","Cha KS,Cho KI,Seo JS,Choi JH,Park YH,Yang DH,Hong GR,Kim DS.","Effects of inhaled iloprost on exercise capacity,quality of life,and cardiac function in patients with pulmonary arterial hypertension secondary to congenital heart disease (the Eisenmenger syndrome) (from the EIGER Study).","There are limited data on the effect of iloprost therapy in patients with Eisenmenger syndrome (ES). The aim of our study was to evaluate the effect of inhaled iloprost therapy on exercise capacity,quality of life (QoL),cardiac function,and hemodynamics in patients with ES. Eighteen consecutive patients with ES and exertional dyspnea according to the World Health Organization functional class III or IV were prospectively recruited. Exercise capacity was assessed by a 6-minute walk test,and QoL was measured on a 12-Item Short-Form Health Survey. Echocardiographic measurements included peak systolic and mean pulmonary arterial pressures,pulmonary vascular resistance,and myocardial performance index of the right ventricle (RV). All patients underwent comprehensive evaluation at baseline and after 24 weeks of treatment. Of the 18 patients with ES,13 were included for analysis. After 24 weeks of iloprost therapy,6-minute walk test distance significantly increased (289.1 ± 76.9 to 369.5 ± 93.4 m,p = 0.032) in addition to concomitant improvements in the 12-Item Short-Form Health Survey physical and mental component summaries (20.6 ± 19.3 to 52.6 ± 28.0,p <0.05; 33.9 ± 19.7 to 54.9 ± 21.3,p <0.05,respectively). RV myocardial performance index improved significantly after treatment (0.80 ± 0.31 to 0.59 ± 0.12,p = 0.042). Pulmonary arterial pressure and pulmonary vascular resistance did not improve with iloprost therapy. This study showed that 24 weeks of inhaled iloprost therapy in patients with ES led to significant improvements in exercise capacity,QoL,and RV function. These results likely explain the symptomatic relief reported by patients with ES receiving iloprost therapy.","Am J Cardiol. 2013 Dec 1;112(11):1834-9.","Korea",2013,"Congenital HD","None or unknown","SF-12",null,null,null,"Korea",null,"Congenital HD","None or unknown",null,null,"SF-12","2010:2014"]
[11,"Roman A,Barbera JA,Castillo MJ,Muñoz R,Escribano P. Health-related quality of life in a national cohort of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Arch Bronconeumol. 2013 May;49(5):181-8. doi: 10.1016/j.arbres.2012.12.007. Epub 2013 Feb 27.","doi: 10.1016/j.arbres.2012.12.007. Epub 2013 Feb 27.","Roman A,Barbera JA,Castillo MJ,Muñoz R,Escribano P.","Health-related quality of life in a national cohort of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.","Patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) experience impaired health-related quality of life (HRQL). The objective of this study was to evaluate HRQL in a nation-wide sample. This is a prospective,multicenter,non-interventional study of HRQL including 139 (89%) PAH and 17 (11%) CTEPH patients (women 70.5%; mean age,52.2) recruited from 21 Spanish hospitals. 55% had idiopathic PAH,34% other PAH and 11% CTEPH. HRQL was measured using the Short Form 36 Health Survey (SF-36) and EuroQoL-5D (baseline and after 6 months). HRQL in the patients with PAH or CTEPH was impaired. The physical component of SF-36 and the EuroQol-5D correlated with the functional class (FC). Mean EuroQol-5D visual analogical scale (EQ-5D VAS) scores were 73.5±18.4,62.9±20.7 and 51.3±16.0 (P<.0001) in patients with FC I,II and III,respectively. Every increase of one FC represented a loss of 4.0 on the PCS SF-36 and a loss of 9.5 on the EQ-5D VAS. Eight patients who died or received a transplant during the study period presented poorer initial HRQL compared with the rest of the population. No significant changes in HRQL were observed in survivors after 6 months of follow-up. HRQL is impaired in this population,especially in PAH/CTEPH patients near death. HRQL measurements could help predict the prognosis in PAH and CTPH and provide additional information in these patients.","Arch Bronconeumol. 2013 May;49(5):181-8.","Spain",2013,"Any PAH,CTEPH","None or unknown","EQ-5D,SF-36",null,null,null,"Spain",null,"Any PAH,CTEPH","None or unknown",null,null,"EQ-5D,SF-36","2010:2014"]
[12,"Judson MA,Highland KB,Kwon S,Donohue JF,Aris R,Craft N,Burt S,Ford HJ. Ambrisentan for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2011 Oct;28(2):139-45.",null,"Judson MA,Highland KB,Kwon S,Donohue JF,Aris R,Craft N,Burt S,Ford HJ.","Ambrisentan for sarcoidosis associated pulmonary hypertension.","Sarcoidosis associated pulmonary hypertension (SAPH) is associated with significant morbidity and mortality. There is a paucity of information concerning therapy for this condition. We performed a prospective,open-label,proof of concept trial of ambrisentan for SAPH. 21 subjects with SAPH received 5 mg/day of ambrisentan for 4 weeks and then 10/mg day for 20 subsequent weeks. No significant change was noted in the 6-minute walk distance over the course of the study (mean change between week 0 and 24: 9.8 +/- 54.6 meters,p: NS). There were also no significant differences between weeks 0 and 24 in terms of dyspnea as measured by the modified Borg scale,serum brain naturetic peptide,diffusing capacity,and quality of life as measured by the Short Form-36. There was a high dropout rate: overall: 11/21,52%; social reasons: 3/21,14%; medical reasons: 8/21,38% because of dyspnea: 6/21,29% and/or edema: 4/21,19%. Of those who completed the 24 week study (10/21,48%),there was an improvement in their WHO functional class and a marked improvement in their health related quality of life as measured by the St. George Respiratory questionnaire (-15.3 +/- 25.0). However both these improvments did not reach statistical significance possibly because of the small sample size. Although ambrisentan was not well tolerated by many of these subjects with SAPH,in those who remained in this 24-week trial,improvements in WHO functional class and in health related quality of life suggested a possible benefit of this drug in selected patients.","Sarcoidosis Vasc Diffuse Lung Dis. 2011 Oct;28(2):139-45.","USA",2011,"Sarcoidosis","Ambrisentan","BDI,SF-36,SGRQ",null,null,null,"USA",null,"Sarcoidosis","Ambrisentan",null,null,"BDI,SF-36,SGRQ","2010:2014"]
[13,"Kowal-Bielecka O,Avouac J,Pittrow D,Huscher D,Behrens F,Denton CP,Foeldvari I,Humbert M,Matucci-Cerinic M,Nash P,Opitz CF,Rubin LJ,Seibold JR,Strand V,Furst DE,Distler O,Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension Related to Systemic Sclerosis. Analysis of the validation status of quality of life and functional disability measures in pulmonary arterial hypertension related to systemic sclerosis: results of a systematic literature analysis by the Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis (EPOSS). J Rheumatol. 2011 Nov;38(11):2419-27. doi: 10.3899/jrheum.110344. Epub 2011 Oct 1.","doi: 10.3899/jrheum.110344. Epub 2011 Oct 1.","Kowal-Bielecka O,Avouac J,Pittrow D,Huscher D,Behrens F,Denton CP,Foeldvari I,Humbert M,Matucci-Cerinic M,Nash P,Opitz CF,Rubin LJ,Seibold JR,Strand V,Furst DE,Distler O,Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension Related to Systemic Sclerosis.","Analysis of the validation status of quality of life and functional disability measures in pulmonary arterial hypertension related to systemic sclerosis: results of a systematic literature analysis by the Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension related to Systemic Sclerosis (EPOSS).","We aimed to assess the current validity status of the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the 36-item Medical Outcomes Study Short Form Health Survey (SF-36). Studies using HAQ-DI and/or SF-36 in patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (PAH-SSc) were identified through a systematic literature review and assessed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus group criteria. Both HAQ-DI and SF-36 were considered credible (having face validity) and feasible. Based on expert opinion,neither HAQ-DI nor SF-36 was specific for PAH-SSc since their results may be influenced by other aspects of SSc (judged \"unclear\" with respect to the content validity criterion). In the overall SSc population,there was significant albeit weak correlation between physical component SF-36 scores and pulmonary artery systolic pressure (PASP) by echocardiography (Kendall tau b = -0.2,p < 0.01). Although HAQ-DI also correlated with PASP by echocardiography,there were no significant correlations in SSc patients with PAH proven by right heart catheterization between changes in HAQ-DI over time and changes in other PAH measures including 6-min walk distance (r = -0.04,p = 0.86),expert global assessment (r = 0.06,p = 0.97),and New York Heart Association functional class (r = 0.38,p = 0.39),indicating lack of construct validity for HAQ-DI in PAH-SSc. No studies enabling assessment of criterion validity or discrimination of HAQ-DI or SF-36 in PAH-SSc could be identified. Further validation of HAQ and SF-36 in PAH-SSc is needed. Alternatively,more specific assessments for functional disability or quality of life in PAH-SSc might be required.","J Rheumatol. 2011 Nov;38(11):2419-27.","International",2011,"Systemic sclerosis","None or unknown","HAQ-DI,SF-36",null,null,null,"International",null,"Systemic sclerosis","None or unknown",null,null,"HAQ-DI,SF-36","2010:2014"]
[14,"Chen H,De Marco T,Kobashigawa EA,Katz PP,Chang VW,Blanc PD. Comparison of cardiac and pulmonary-specific quality-of-life measures in pulmonary arterial hypertension. Eur Respir J. 2011 Sep;38(3):608-16. doi: 10.1183/09031936.00161410. Epub 2011 Jan 27.","doi: 10.1183/09031936.00161410. Epub 2011 Jan 27.","Chen H,De Marco T,Kobashigawa EA,Katz PP,Chang VW,Blanc PD.","Comparison of cardiac and pulmonary-specific quality-of-life measures in pulmonary arterial hypertension.","Studies systematically comparing the performance of health-related quality-of-life (HRQoL) instruments in pulmonary arterial hypertension (PAH) are lacking. We sought to address this by comparing cardiac and respiratory-specific measures of HRQoL in PAH. We prospectively assessed HRQoL in 128 patients with catheterisation-confirmed PAH at baseline and at 6,12 and post-24 month follow-up visits. Cardiac-specific HRQoL was assessed using the Minnesota Living with Heart Failure Questionnaire (LHFQ); respiratory-specific HRQoL was assessed using the Airways Questionnaire 20 (AQ20); and general health status was assessed using the 36-item Short Form physical component summary (SF-36 PCS). The LHFQ and AQ20 were highly intercorrelated. Both demonstrated strong internal consistency and converged with the SF-36 PCS. Both discriminated patients based on World Health Organization (WHO) functional class,6-min walking distance (6MWD) and Borg dyspnoea index (BDI),with the exception of a potential floor effect associated with low 6MWD. The LHFQ was more responsive than the AQ20 to changes over time in WHO functional class,6MWD and BDI. In multivariate analyses,the LHFQ and AQ20 were each longitudinal predictors of general health status,independent of functional class,6MWD and BDI. In conclusion,both cardiac-specific and respiratory-specific measures appropriately assess HRQoL in most patients with PAH. Overall,the LHFQ demonstrates stronger performance characteristics than the AQ20.","Eur Respir J. 2011 Sep;38(3):608-16.","USA",2011,"Any PAH","None or unknown","AQ20,MLHFQ,SF-36",null,null,null,"USA",null,"Any PAH","None or unknown",null,null,"AQ20,MLHFQ,SF-36","2010:2014"]
[15,"Tyndall AJ,Bannert B,Vonk M,Airò P,Cozzi F,Carreira PE,Bancel DF,Allanore Y,Müller-Ladner U,Distler O,Iannone F,Pellerito R,Pileckyte M,Miniati I,Ananieva L,Gurman AB,Damjanov N,Mueller A,Valentini G,Riemekasten G,Tikly M,Hummers L,Henriques MJ,Caramaschi P,Scheja A,Rozman B,Ton E,Kumánovics G,Coleiro B,Feierl E,Szucs G,Von Mühlen CA,Riccieri V,Novak S,Chizzolini C,Kotulska A,Denton C,Coelho PC,Kötter I,Simsek I,de la Pena Lefebvre PG,Hachulla E,Seibold JR,Rednic S,Stork J,Morovic-Vergles J,Walker UA. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis. 2010 Oct;69(10):1809-15. doi: 10.1136/ard.2009.114264. Epub 2010 Jun 15.","doi: 10.1136/ard.2009.114264. Epub 2010 Jun 15.","Tyndall AJ,Bannert B,Vonk M,Airò P,Cozzi F,Carreira PE,Bancel DF,Allanore Y,Müller-Ladner U,Distler O,Iannone F,Pellerito R,Pileckyte M,Miniati I,Ananieva L,Gurman AB,Damjanov N,Mueller A,Valentini G,Riemekasten G,Tikly M,Hummers L,Henriques MJ,Caramaschi P,Scheja A,Rozman B,Ton E,Kumánovics G,Coleiro B,Feierl E,Szucs G,Von Mühlen CA,Riccieri V,Novak S,Chizzolini C,Kotulska A,Denton C,Coelho PC,Kötter I,Simsek I,de la Pena Lefebvre PG,Hachulla E,Seibold JR,Rednic S,Stork J,Morovic-Vergles J,Walker UA.","Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database.","To determine the causes and predictors of mortality in systemic sclerosis (SSc). Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths,35% were attributed to pulmonary fibrosis,26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes,infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities,25% died of causes in which SSc-related complications may have participated (pneumonia,sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34),the presence of PAH based on echocardiography (HR 2.02),pulmonary restriction (forced vital capacity below 80% of normal,HR 1.64),dyspnoea above New York Heart Association class II (HR 1.61),diffusing capacity of the lung (HR 1.20 per 10% decrease),patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). Disease-related causes,in particular pulmonary fibrosis,PAH and cardiac causes,accounted for the majority of deaths in Ssc.","Ann Rheum Dis. 2010 Oct;69(10):1809-15.","International",2010,"Systemic sclerosis","None or unknown","RSS",null,null,null,"International",null,"Systemic sclerosis","None or unknown",null,null,"RSS","2010:2014"]
[16,"Ovaert C,Thijs D,Dewolf D,Ottenkamp J,Dessy H,Moons P,Gewillig M,Mertens L. The effect of bosentan in patients with a failing Fontan circulation. Cardiol Young. 2009 Aug;19(4):331-9. doi: 10.1017/S1047951109990023. Epub 2009 Jun 11.","doi: 10.1017/S1047951109990023. Epub 2009 Jun 11.","Ovaert C,Thijs D,Dewolf D,Ottenkamp J,Dessy H,Moons P,Gewillig M,Mertens L.","The effect of bosentan in patients with a failing Fontan circulation.","To investigate the effect of bosentan in patients with a failing Fontan circulation. A multicentric open label,non-controlled study. 5 tertiary care centres for congenital cardiology. We included 10 patients with a failing Fontan circulation. Their median age at inclusion was 12.12 years,with a range from 4.41 to 33,41 years. The median interval between the Fontan operation and inclusion was 7.84 years,with a range from 1.96 to 12,18 years. Participants received half the usual dose of bosentan for 4 weeks,and then the full dose for a further 12 weeks. MAIN MEASURES OF OUTCOMES: We assessed saturations of oxygen at rest and during exercise,using a 6 minutes walk test,at baseline,and during and after 16 weeks of treatment. At each visit,we assessed blood chemistry and hepatic function,and asked the patients to complete a questionnaire concerning quality of life. All medical events and possible side effects were recorded. Of the cohort,1 patient withdrew. The changes in saturations of oxygen,exercise performance,and scores for the questionnaire did not reach statistical significance for the whole group. We noted,nonetheless,that saturations of oxygen and/or exercise capacity improved in 5 of the patients. This was further confirmed when those patients deteriorated again when the drug was discontinued. Our study failed to show significant improvement after 3 months of treatment with bosentan in a small group of patients with failing Fontan circulations. Some individuals,nonetheless,did improve. When planning larger trials,it would be better to identify those patients who might potentially benefit from the treatment prior to commencing the trial.","Cardiol Young. 2009 Aug;19(4):331-9.","Belgium",2009,"Congenital HD","Bosentan","Unknown",null,null,null,"Belgium",null,"Congenital HD","Bosentan",null,null,"Unknown","2005:2009"]
[17,"Sitbon O,Gressin V,Speich R,Macdonald PS,Opravil M,Cooper DA,Fourme T,Humbert M,Delfraissy JF,Simonneau G. Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension. Am J Respir Crit Care Med. 2004 Dec 1;170(11):1212-7. doi: 10.1164/rccm.200404-445OC. Epub 2004 Aug 18.","doi: 10.1164/rccm.200404-445OC. Epub 2004 Aug 18.","Sitbon O,Gressin V,Speich R,Macdonald PS,Opravil M,Cooper DA,Fourme T,Humbert M,Delfraissy JF,Simonneau G.","Bosentan for the treatment of human immunodeficiency virus-associated pulmonary arterial hypertension.","Clinical studies have shown the importance of endothelin as a pathogenic mediator in pulmonary arterial hypertension (PAH). We describe the effects of bosentan,an oral dual endothelin receptor antagonist,in patients with PAH associated with human immunodeficiency virus (HIV) infection. In this prospective study,16 patients with PAH associated with HIV infection in stable condition received bosentan for 16 weeks. Efficacy endpoints included exercise capacity,cardiopulmonary hemodynamics,Doppler echocardiography,New York Heart Association functional class,and quality of life (SF-36 and EQ-5D). Safety was assessed by laboratory tests,vital signs,and adverse events. Improvements were observed from baseline to Week 16 in all efficacy parameters: 6-minute walk distance (+91 +/- 60 m,p < 0.001),New York Heart Association class (14 patients improved),hemodynamics (cardiac index: +0.9 +/- 0.7 L/minute/m(2),p < 0.001),Doppler echocardiographic variables,and quality of life. During the study,no patient died and none required epoprostenol treatment. Hepatic tolerability was similar to that reported in patients with PAH. Bosentan had no negative impact on control of HIV infection. Although limited by uncontrolled design,small sample size and short duration,this study suggests that bosentan may benefit patients with PAH associated with HIV infection,and that endothelin is an important pathogenic mediator in this disease.","Am J Respir Crit Care Med. 2004 Dec 1;170(11):1212-7.","France",2004,"HIV","Bosentan","EQ-5D,SF-36",null,null,null,"France",null,"HIV","Bosentan",null,null,"EQ-5D,SF-36","2000:2004"]
[18,"Morris NR,Kermeen FD,Holland AE. Exercise-based rehabilitation programmes for pulmonary hypertension. Cochrane Database Syst Rev. 2017 Jan 19;1():CD011285. doi: 10.1002/14651858.CD011285.pub2. Epub 2017 Jan 19.","doi: 10.1002/14651858.CD011285.pub2. Epub 2017 Jan 19.","Morris NR,Kermeen FD,Holland AE.","Exercise-based rehabilitation programmes for pulmonary hypertension.","Individuals with pulmonary hypertension (PH) have reduced exercise capacity and quality of life. Despite initial concerns that exercise training may worsen symptoms in this group,several studies have reported improvements in functional capacity and well-being following exercise-based rehabilitation in PH. To assess the efficacy and safety of exercise-based rehabilitation for people with PH. Primary outcomes were exercise capacity,adverse events during the intervention period and health-related quality of life (HRQoL). Secondary outcomes included cardiopulmonary haemodynamics,functional class,clinical worsening during follow-up,mortality and changes in B-type natriuretic peptide. We searched the Cochrane Airways Specialised Register of Trials up to August 2016,which is based on regular searches of CINAHL,AMED,Embase,PubMed,MEDLINE,PsycINFO and registries of clinical trials. In addition we searched CENTRAL and the PEDro database up to August 2016 and handsearched relevant journals. All randomised controlled trials (RCTs) focusing on exercise-based rehabilitation programmes for PH. Two reviewers extracted data independently. For binary outcomes,we calculated odds ratios and their 95% confidence interval (CI),on an intention-to-treat basis. For continuous data,we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. We included six RCTs and were able to extract data from five studies. The majority of participants were Group I pulmonary artery hypertension (PAH). Study duration ranged from three to 15 weeks. Exercise programmes included both inpatient- and outpatient-based rehabilitation that incorporated both upper and lower limb exercise. The mean six-minute walk distance following exercise training was 60.12 metres higher than control (30.17 to 90.07 metres,n = 165,5 RCTs,low-quality evidence; minimal important difference was 30 metres),the mean peak oxygen uptake was 2.4 ml/kg/minute higher (1.4 to 3.4 ml/kg/min,n = 145,4 RCTs,low-quality evidence) and the mean peak power in the intervention groups was 16.4 W higher (10.9 to 22.0 higher,n = 145,4 RCTs,low-quality evidence). The mean change in HRQoL for the SF-36 physical component score was 4.63 points higher (0.80 to 8.47 points,n = 33,2 RCTs,low-quality evidence) and for the SF-36 mental component score was 4.17 points higher (0.01 to 8.34 points; n = 33; 2 RCTs,low-quality evidence). One study reported a single adverse event,where a participant stopped exercise training due to lightheadedness. In people with PH,exercise-based rehabilitation results in clinically relevant improvements in exercise capacity. Exercise training was not associated with any serious adverse events. Whilst most studies reported improvements in HRQoL,these may not be clinically important. Overall,we assessed the quality of the evidence to be low. The small number of studies and lack of information on participant selection makes it difficult to generalise these results across the spectrum of people with PH.","Cochrane Database Syst Rev. 2017 Jan 19;1():CD011285.","International",2017,"Any PAH","Exercise","SF-36",null,null,null,"International",null,"Any PAH","Exercise",null,null,"SF-36","2015:2018"]
[19,"Mehta S,Sastry BK,Souza R,Torbicki A,Ghofrani HA,Channick RN,Delcroix M,Pulido T,Simonneau G,Wlodarczyk J,Rubin LJ,Jansa P,Hunsche E,Galiè N,Perchenet L,Sitbon O. Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial. Chest. 2017 Jan;151(1):106-118. doi: 10.1016/j.chest.2016.08.1473. Epub 2016 Sep 23.","doi: 10.1016/j.chest.2016.08.1473. Epub 2016 Sep 23.","Mehta S,Sastry BK,Souza R,Torbicki A,Ghofrani HA,Channick RN,Delcroix M,Pulido T,Simonneau G,Wlodarczyk J,Rubin LJ,Jansa P,Hunsche E,Galiè N,Perchenet L,Sitbon O.","Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial.","Pulmonary arterial hypertension (PAH) leads to reduced health-related quality of life (HRQoL). The objectives of this analysis were to evaluate the effect of macitentan on HRQoL in patients with PAH in the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) study. The association between baseline HRQoL and long-term outcomes was also investigated. Patients were randomized to placebo,macitentan 3 mg,or macitentan 10 mg once daily. Patients aged 14 years or older completed the 36-Item Short Form Survey (SF-36) at baseline,at month 6 and month 12,and at the end of treatment (EOT). The absolute change from baseline to month 6 in SF-36 scores was calculated. The time to a clinically meaningful deterioration in the SF-36 physical component summary and mental component summary (PCS and MCS) scores and associations between baseline PCS/MCS scores and time to morbidity/mortality events were also assessed. At month 6,macitentan 10 mg significantly improved seven of eight SF-36 domains and the PCS and MCS scores vs placebo. Macitentan 10 mg significantly reduced the risk of a three-point or greater deterioration in PCS (hazard ratio [HR],0.60; 95% CI,0.47-0.76; P < .0001) and MCS scores (HR,0.76; 95% CI,0.61-0.95; P = .0173) until EOT vs placebo. Patients with a baseline PCS score greater than the median baseline value had a significantly reduced risk of morbidity/mortality compared with patients with a PCS score less than the median; a similar result was observed for the MCS score. Macitentan significantly improved HRQoL in patients with PAH compared with placebo and significantly reduced the risk of a clinically meaningful HRQoL deterioration. An association between better baseline HRQoL and improved long-term outcomes was shown. ClinicalTrials.gov; No.: NCT00660179; URL: clinicaltrials.gov.","Chest. 2017 Jan;151(1):106-118.","International",2017,"Any PAH","Macitentan","SF-36",null,null,null,"International",null,"Any PAH","Macitentan",null,null,"SF-36","2015:2018"]
[20,"Reis A,Twiss J,Vicente M,Gonçalves F,Carvalho L,Meireles J,Melo A,McKenna SP,Almeida L. Portuguese validation of the Cambridge pulmonary hypertension outcome review (CAMPHOR) questionnaire. Health Qual Life Outcomes. 2016 Jul 26;14(1):110. doi: 10.1186/s12955-016-0513-8. Epub 2016 Jul 26.","doi: 10.1186/s12955-016-0513-8. Epub 2016 Jul 26.","Reis A,Twiss J,Vicente M,Gonçalves F,Carvalho L,Meireles J,Melo A,McKenna SP,Almeida L.","Portuguese validation of the Cambridge pulmonary hypertension outcome review (CAMPHOR) questionnaire.","Patients with pulmonary arterial hypertension (PAH) and other forms of precapillary pulmonary hypertension (PH) have impaired quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a PH-specific patient-reported outcome measure that assesses symptoms,activity limitations and QoL. It was originally developed in UK-English. The main objective of this study was to create an adaptation of the CAMPHOR suitable for a Portuguese-speaking population. A multi-step approach was followed: bilingual and lay panel translation; cognitive debriefing interviews; and psychometric testing in repeated postal surveys (2 weeks apart) including assessment of internal consistency,reproducibility and validity. The Nottingham Health Profile (NHP) questionnaire was used as a comparator instrument to test convergent validity. The CAMPHOR was translated without difficulty by the two panels. Cognitive debriefing interviews showed the questionnaire was easily understood and considered relevant to patients' experience with their illness. Psychometric evaluation was performed with 50 PAH patients (47 ± 14 years,37 women). Cronbach's alpha coefficients showed good internal consistency for the three CAMPHOR scales [Symptoms = 0.95; Activities = 0.93 and QoL = 0.94]. Test-retest coefficients showed that all scales had excellent reliability (Symptoms = 0.94; Activities = 0.89 and QoL = 0.93),indicating low levels of random measurement error. The CAMPHOR correlated as expected with the NHP. The magnitude of correlations followed a similar pattern to those in the original development study. The CAMPHOR also exhibited evidence of known group validity in its ability to distinguish between self-reported severity and general health groups. A valid and reliable version of the CAMPHOR questionnaire for the European Portuguese-speaking population was developed and is recommended for use.","Health Qual Life Outcomes. 2016 Jul 26;14(1):110.","Portugal",2016,"Any PAH","None or unknown","CAMPHOR",null,null,null,"Portugal",null,"Any PAH","None or unknown",null,null,"CAMPHOR","2015:2018"]
[21,"Matura LA,McDonough A,Hanlon AL,Carroll DL. Developmental and Initial Validation of the Pulmonary Arterial Hypertension Symptom Inference Scale. J Nurs Meas. 2016;24(1):40-53. doi: 10.1891/1061-3749.24.1.40.","doi: 10.1891/1061-3749.24.1.40.","Matura LA,McDonough A,Hanlon AL,Carroll DL.","Developmental and Initial Validation of the Pulmonary Arterial Hypertension Symptom Inference Scale.","Pulmonary arterial hypertension is a chronic illness that produces multiple symptoms and impairs quality of life. The purpose of this study was to describe the initial psychometric properties of the Pulmonary Arterial Hypertension Symptom Interference Scale (PAHSIS). Participants completed a sociodemographic and clinical data form: the PAHSIS and the Medical Outcomes Study Short Form-36 (SF-36). Data analysis included descriptive statistics,principal component analysis (PCA),and Pearson r correlations. PCA revealed a 3-factor solution: Cardiopulmonary,Weary,and Gastric. Correlations between the 3 factors and the SF-36 subscales and composite summary scores ranged from acceptable to high. These findings support the initial validity and reliability of the PAHSIS. Nursing can use the PAHSIS to assess the impact of patient symptoms to deploy effective,targeted interventions.","J Nurs Meas. 2016;24(1):40-53.","USA",2016,"Any PAH","None or unknown","PAHSIS,SF-36",null,null,null,"USA",null,"Any PAH","None or unknown",null,null,"PAHSIS,SF-36","2015:2018"]
[22,"Amedro P,Basquin A,Gressin V,Clerson P,Jais X,Thambo JB,Guerin P,Cohen S,Bonnet D. Health-related quality of life of patients with pulmonary arterial hypertension associated with CHD: the multicentre cross-sectional ACHILLE study. Cardiol Young. 2016 Oct;26(7):1250-9. doi: 10.1017/S1047951116000056. Epub 2016 Mar 16.","doi: 10.1017/S1047951116000056. Epub 2016 Mar 16.","Amedro P,Basquin A,Gressin V,Clerson P,Jais X,Thambo JB,Guerin P,Cohen S,Bonnet D.","Health-related quality of life of patients with pulmonary arterial hypertension associated with CHD: the multicentre cross-sectional ACHILLE study.","The aim of this study was to assess health-related quality of life in patients with pulmonary arterial hypertension associated with CHD and correlations with clinical status. This prospective cross-sectional observational study included CHD patients with pulmonary arterial hypertension in 14 tertiary-care centres in France. We used two health-related quality of life questionnaires - SF-36 and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) - and one anxiety/depression Hospital Anxiety and Depression Scale (HADS) questionnaire. Clinical data were collected for the 208 included patients (mean age: 42.6 years,range from 15.1 to 85.8 years,69.7% female). Most patients were in NYHA functional class II (48.1%) and III (37.5%). Patients' phenotype was classified as Eisenmenger syndrome (70.7%),pulmonary arterial hypertension associated with systemic-to-pulmonary shunts (12.0%),with small defects (3.4%),or after corrective cardiac surgery (13.9%). In total,76.4% of the patients were receiving pulmonary arterial hypertension-specific treatments. SF-36 scores showed impairment compared with normalised data. Health-related quality of life scores were significantly lower in females than in males for most dimensions of both questionnaires and were independent of the patients' phenotype,even after gender adjustment - except for CAMPHOR functioning - but significantly depended on NYHA functional class. The Hospital Anxiety and Depression Scale (HADS) scores suggested anxiety and depression associated with increasing NYHA functional class but independent of patients' phenotype. NYHA functional class,6-minute walk distance,HADS,gender,and recent stressful event significantly affected quality of life in the multivariate analysis. This study showed impairment of quality of life in a large cohort of patients with pulmonary arterial hypertension associated with CHD with both generic and specific questionnaires. NYHA functional class and HADS scores were predictive of most quality of life scores.","Cardiol Young. 2016 Oct;26(7):1250-9.","France",2016,"Congenital HD","None or unknown","CAMPHOR,HADS,SF-36",null,null,null,"France",null,"Congenital HD","None or unknown",null,null,"CAMPHOR,HADS,SF-36","2015:2018"]
[23,"Karsenty C,Maury P,Blot-Souletie N,Ladouceur M,Leobon B,Senac V,Mondoly P,Elbaz M,Galinier M,Dulac Y,Carrié D,Acar P,Hascoet S. The medical history of adults with complex congenital heart disease affects their social development and professional activity. Arch Cardiovasc Dis. 2015 Nov;108(11):589-97. doi: 10.1016/j.acvd.2015.06.004. Epub 2015 Sep 11.","doi: 10.1016/j.acvd.2015.06.004. Epub 2015 Sep 11.","Karsenty C,Maury P,Blot-Souletie N,Ladouceur M,Leobon B,Senac V,Mondoly P,Elbaz M,Galinier M,Dulac Y,Carrié D,Acar P,Hascoet S.","The medical history of adults with complex congenital heart disease affects their social development and professional activity.","In recent decades,advances in surgery and therapeutic catheterization have steadily increased the life expectancy and prevalence of adults with congenital heart disease (CHD). We assessed medical and psychosocial variables of adults with CHD,according to the disease complexity. We included,from a single-centre observational cohort study,135 consecutive adults with CHD (median age of 40 years,interquartile range: 28.0-51.0) followed in our cardiology unit,who answered a questionnaire assessing daily activity and psychosocial functioning. Disease complexity was classified according to the Bethesda conference. Cardiac malformation complexity was simple in 61 (45.2%),moderate in 50 (37.0%) and complex in 24 (17.8%) patients. Cardiac surgery had been performed in 86.5% of moderate and complex patients. Complications (such as heart failure,arrhythmia and pulmonary hypertension) were mainly observed in the complex group (P=0.003). Physical activity was lower in the complex group (no activity in 58.8%,but sport previously contraindicated in 50% of these; P=0.03). Education level tended to be lower in the complex and moderate groups than in the simple group (respectively,31.2% and 33.3% vs. 45.7% had passed the Baccalaureate; P=0.47). The pass rate was lower in patients with complications (P=0.037) or more than one cardiac surgery (P=0.03). In the complex group,56.3% of patients were unemployed (P=0.048). Complexity of heart disease and medical history affect education level and employment of adults with CHD. Academic education of children with a complex defect and career counselling are important to prevent unemployment among adults with CHD.","Arch Cardiovasc Dis. 2015 Nov;108(11):589-97.","France",2015,"Congenital HD","Surgery","Unknown",null,null,null,"France",null,"Congenital HD","Surgery",null,null,"Unknown","2015:2018"]
[24,"Provencher S,Paruchuru P,Spezzi A,Waterhouse B,Gomberg-Maitland M,pH12 Flolan reformulation study group. Quality of life,safety and efficacy profile of thermostable flolan in pulmonary arterial hypertension. PLoS One. 2015;10(3):e0120657. doi: 10.1371/journal.pone.0120657. Epub 2015 Mar 20.","doi: 10.1371/journal.pone.0120657. Epub 2015 Mar 20.","Provencher S,Paruchuru P,Spezzi A,Waterhouse B,Gomberg-Maitland M,pH12 Flolan reformulation study group.","Quality of life,safety and efficacy profile of thermostable flolan in pulmonary arterial hypertension.","Flolan (epoprostenol sodium) is most commonly prescribed to patients with severe pulmonary arterial hypertension (PAH) owing to the requirement that the drug be delivered by continuous intravenous infusion and the reconstituted solution may only be administered up to 24 hours when it is maintained between a temperature of 2°C and 8°C. The aim of this single-arm,open label study was to describe the effects of the new thermostable formulation of Flolan on health-related quality of life (HRQoL) and ease of administration in subjects switching from the currently marketed Flolan to the reformulated product. Following a 4-week run-in period and after 4 weeks of treatment with the reformulated product,patients completed the SF-36 HRQoL questionnaire and a study-specific questionnaire evaluating ease of administration,along with World Health Organization (WHO) functional class,six-minute walked distance (6MWD) and N-terminal-pro B-type natriuretic peptide (NT-proBNP) assessment. 16 participants completed the study. The SF-36 scores remained unchanged from baseline to Week 4. Conversely,there were small improvements for the majority of the study-specific questionnaire items and 14 (88%) subjects preferred the reformulated product to the currently marketed Flolan. There was no significant change in the dose of reformulated product,6MWD,Borg dyspnoea index,WHO functional class and mean NT-proBNP levels. No significant changes in haemodynamic parameters were seen from baseline to 2 hours post transition in a subset of patients undergoing catheterization. The reformulated product was not associated with significant improvement in HRQoL compared with the currently marketed Flolan as measured by the SF-36. However,most subjects preferred the reformulated product to the currently marketed Flolan. Moreover,the 2 formulations of Flolan had similar safety and efficacy profiles. ClinicalTrials.gov NCT01462565.","PLoS One. 2015;10(3):e0120657.","Canada,USA",2015,"Any PAH","Epoprostanol","SF-36",null,null,null,"Canada,USA",null,"Any PAH","Epoprostanol",null,null,"SF-36","2015:2018"]
[25,"Mathai SC,Hassoun PM,Puhan MA,Zhou Y,Wise RA. Sex differences in response to tadalafil in pulmonary arterial hypertension. Chest. 2015 Jan;147(1):188-97. doi: 10.1378/chest.14-0263.","doi: 10.1378/chest.14-0263.","Mathai SC,Hassoun PM,Puhan MA,Zhou Y,Wise RA.","Sex differences in response to tadalafil in pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) is a progressive disease with high rates of morbidity and mortality. Current therapies improve symptoms,functional capacity,and,in select cases,survival. Little is known about patient factors that may predict the likelihood of patient-important,clinically relevant responses to therapy such as the 6-min walk distance (6MWD) and health-related quality of life (HRQoL). Data from the randomized clinical trial of tadalafil in PAH were used. Adjusted logistic regression models were created to examine the relationship between baseline characteristics and odds of achieving the minimal important difference (MID) in three parameters,defined as either a > 33-m increase in 6MWD,a > 5-unit increase in physical component summary score of the Medical Outcomes Study Short Form-36 (SF-36),or a > 5-unit increase in mental component summary score of the SF-36. The study included 405 subjects. Younger age,male sex,lower baseline 6MWD,and disease etiology were associated with greater odds of achieving the MID for the 6-min walk test. Active treatment,younger age,and male sex were associated with greater odds of achieving the MID for the physical component summary score. Male sex was associated with greater odds of achieving the MID for the mental component summary score. Age,sex,baseline functional capacity,and disease etiology are variably associated with the likelihood of achieving clinically relevant responses in patient-important outcomes to PAH-specific therapy such as 6MWD and HRQoL. The increased likelihood of response in men compared with women is a novel finding and may reflect pathophysiologic differences between sexes.","Chest. 2015 Jan;147(1):188-97.",null,2015,"Any PAH","Tadalafil","SF-36",null,null,null,null,null,"Any PAH","Tadalafil",null,null,"SF-36","2015:2018"]
[26,"Matura LA,McDonough A,Hanlon AL,Carroll DL,Riegel B. Sleep disturbance,symptoms,psychological distress,and health-related quality of life in pulmonary arterial hypertension. Eur J Cardiovasc Nurs. 2015 Oct;14(5):423-30. doi: 10.1177/1474515114537951. Epub 2014 May 27.","doi: 10.1177/1474515114537951. Epub 2014 May 27.","Matura LA,McDonough A,Hanlon AL,Carroll DL,Riegel B.","Sleep disturbance,symptoms,psychological distress,and health-related quality of life in pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) is a devastating disease characterized by elevated pulmonary pressures that lead to right heart failure and premature mortality. Patients experience multiple symptoms including dyspnea,fatigue and chest pain,but little is known about sleep disturbance,PAH symptoms,psychological distress and health-related quality of life (HRQOL) in PAH. The purpose of this study was to describe the occurrence of sleep disturbance and compare PAH symptoms,psychological distress,and HRQOL across severity of sleep disturbance. One hundred and ninety-one participants completed a socio-demographic and clinical data form,PAH Symptom Severity Scale,Profile of Mood States (POMS) short form and the Medical Outcomes Short Form-36 (SF-36). Descriptive statistics were used to describe sleep disturbances; analysis of variance models were used to quantify differences in PAH symptoms,psychological distress and HRQOL by sleep disturbance groups. The majority of participants (n=162,85%) were women with a mean age of 53 years. Sixty-five (34%) reported no sleep disturbance; 54 (28%) mild sleep disturbance; 41 (22%) moderate sleep disturbance; and 31 (16%) severe sleep disturbance. Those reporting higher sleep disturbance severity reported worse PAH symptoms,psychological distress,and HRQOL. Sleep disturbance is a significant finding in PAH. Increasing levels of sleep disturbance are associated with worse PAH symptoms,psychological states,and health-related quality of life. Interventions that decrease sleep disturbances may improve symptoms and HRQOL.","Eur J Cardiovasc Nurs. 2015 Oct;14(5):423-30.","USA",2015,"Any PAH","None or unknown","PAH-SSS,POMS,SF-36",null,null,null,"USA",null,"Any PAH","None or unknown",null,null,"PAH-SSS,POMS,SF-36","2015:2018"]
[27,"Ozdemirel TS,Ulaşli SS,Yetiş B,Karaçağlar E,Bayraktar N,Ulubay G. Effects of right ventricular dysfunction on exercise capacity and quality of life and associations with serum NT-proBNP levels in COPD: an observational study. Anadolu Kardiyol Derg. 2014 Jun;14(4):370-7. doi: 10.5152/akd.2014.4687. Epub 2014 Apr 16.","doi: 10.5152/akd.2014.4687. Epub 2014 Apr 16.","Ozdemirel TS,Ulaşli SS,Yetiş B,Karaçağlar E,Bayraktar N,Ulubay G.","Effects of right ventricular dysfunction on exercise capacity and quality of life and associations with serum NT-proBNP levels in COPD: an observational study.","During the course of chronic obstructive pulmonary disease (COPD),pulmonary hypertension (PH) and right ventricular (RV) failure may develop due to elevated afterload of the RV. In those patients,exercise capacity is reduced due to pulmonary and cardiac limitations. We investigated relationships between serum N-terminal of proB-type natriuretic peptide (NT-proBNP) and RV functions with exercise capacity and quality of life in patients COPD. An observational case-control study was conducted. We enrolled 31 moderate and severe COPD patients,and 20 subjects without chronic diseases as control group. Parameters reflecting the right ventricular diastolic and systolic functions by echocardiography along with serum NT-proBNP levels were assessed. Cardiopulmonary exercise testing and Short Form-36 (SF-36) were applied. Serum NT-proBNP levels were higher in COPD patients than control group (p=0.003). Serum NT-proBNP level was found to be related with pulmonary arterial pressure. Serum NT-proBNP levels were negatively correlated with anaerobic threshold oxygen uptake (AT VO2) and peak oxygen uptake (PVO2) values. Early ventricular filling velocity (Em) was lower in COPD patients. Em wave was significantly correlated with O2 pulse. There was a positive relationship between tricuspid E/A ratio and VO2 value at AT. SF-36 domains of physical functioning,general health and role limitation due to physical disorder were significantly correlated with AT VO2,PVO2 and O2 pulse. Exercise limitation may be predicted by assessment of right ventricule functions and NT-proBNP levels and exercise limitation impairs quality of life in COPD patients.","Anadolu Kardiyol Derg. 2014 Jun;14(4):370-7.","Turkey",2014,"COPD","None or unknown","SF-36",null,null,null,"Turkey",null,"COPD","None or unknown",null,null,"SF-36","2010:2014"]
[28,"Goudie AR,Lipworth BJ,Hopkinson PJ,Wei L,Struthers AD. Tadalafil in patients with chronic obstructive pulmonary disease: a randomised,double-blind,parallel-group,placebo-controlled trial. Lancet Respir Med. 2014 Apr;2(4):293-300. doi: 10.1016/S2213-2600(14)70013-X. Epub 2014 Mar 5.","doi: 10.1016/S2213-2600(14)70013-X. Epub 2014 Mar 5.","Goudie AR,Lipworth BJ,Hopkinson PJ,Wei L,Struthers AD.","Tadalafil in patients with chronic obstructive pulmonary disease: a randomised,double-blind,parallel-group,placebo-controlled trial.","Phosphodiesterase-5 (PDE5) inhibitors improve exercise capacity and quality of life in patients with idiopathic pulmonary arterial hypertension. However,whether such beneficial effects take place in selected populations with chronic obstructive pulmonary disease (COPD) remains uncertain. We aimed to assess the effects of tadalafil--a PDE5 inhibitor--on exercise capacity and quality of life in patients with COPD and mild pulmonary hypertension. We did a randomised,double-blind,parallel-group,placebo-controlled trial at three centres in Scotland,UK,between Sept 1,2010,and Sept 1,2012. Patients with moderate to severe COPD were randomly assigned (1:1),via centralised randomisation with a computer-generated sequence and block sizes of four,to receive daily tadalafil 10 mg or placebo for 12 weeks. Patients,study investigators,outcome assessors,and those administering drugs were masked to group allocation. The primary endpoint was the mean placebo-corrected difference between the baseline and final 6 min walk distance after 12 weeks. We measured change in quality of life at baseline,8 weeks,and 12 weeks,with standardised questionnaires. Analysis was per protocol and by intention to treat. This trial is registered with ClinicalTrials.gov,number NCT01197469. 120 patients were randomly assigned to receive tadalafil (n=60) or placebo (n=60),of whom 56 (93%) versus 57 (95%) completed the study. At 12 weeks the difference in 6 min walking distance between the tadalafil and placebo groups was 0·5 m (95% CI -11·6 to 12·5; p=0·937). We recorded no statistically significant changes in quality of life (between-group difference on the St George's Respiratory Questionnaire -2·64 [95% CI -6·43 to 1·15]; Research and Development version 1 short-form-36 4·08 [-1·35 to 9·52]; Minnesota Living with Heart Failure questionnaire -2·31 [-7·06 to 2·45]). 19 (32%) of 60 patients in the treatment group had dyspepsia; the severity of dyspepsia ranged from mild to severe,with four (21%) of 19 patients needing a proton-pump inhibitor. Five (8%) of 60 participants had dyspepsia in the placebo group. Headache was noted in 17 (28%) patients in the treatment group versus 5 (8%) in the placebo group,but was mild in all patients. Two (3%) patients in the treatment group had facial flushing,which resulted in one withdrawal. Other withdrawals within the tadalafil group happened after a transient ischaemic attack and two deaths (ruptured abdominal aortic aneurysm and pneumonia). Tadalafil does not improve exercise capacity or quality of life despite exerting pulmonary vasodilation. Chief Scientist Office for Scotland.","Lancet Respir Med. 2014 Apr;2(4):293-300.","UK",2014,"COPD","Tadalafil","MLHFQ,SF-36,SGRQ",null,null,null,"UK",null,"COPD","Tadalafil",null,null,"MLHFQ,SF-36,SGRQ","2010:2014"]
[29,"Sitbon O,Delcroix M,Bergot E,Boonstra AB,Granton J,Langleben D,Subías PE,Galiè N,Pfister T,Lemarié JC,Simonneau G. EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension. Am Heart J. 2014 Feb;167(2):210-7. doi: 10.1016/j.ahj.2013.08.007. Epub 2013 Oct 3.","doi: 10.1016/j.ahj.2013.08.007. Epub 2013 Oct 3.","Sitbon O,Delcroix M,Bergot E,Boonstra AB,Granton J,Langleben D,Subías PE,Galiè N,Pfister T,Lemarié JC,Simonneau G.","EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension.","Continuous infusion of epoprostenol is the treatment of choice in patients with pulmonary arterial hypertension in functional classes III to IV. However,this treatment's limitations include instability at room temperature. A new epoprostenol formulation offers improved storage conditions and patient convenience. The EPITOME-2 trial was an open-label,prospective,multicenter,single-arm,phase IIIb study. Patients with pulmonary arterial hypertension on long-term,stable epoprostenol therapy were transitioned from epoprostenol with glycine and mannitol excipients (Flolan; GlaxoSmithKline,Durham,NC) to epoprostenol with arginine and sucrose excipients (Veletri; Actelion Pharmaceuticals Ltd,Allschwil,Switzerland). Patients were followed up for 3 months,and dose adjustments were recorded. Efficacy measures included the 6-minute walk distance,hemodynamics assessed by right heart catheterization,and New York Heart Association functional class. Safety and tolerability of the transition were also evaluated. Quality of life was assessed using the Treatment Satisfaction Questionnaire for Medication. Forty-two patients enrolled in the study,and 1 patient withdrew consent before treatment; thus,41 patients received treatment and completed the study. Six patients required dose adjustments. There were no clinically relevant changes from baseline to month 3 in any of the efficacy end points. Adverse events were those previously described with intravenous prostacyclin therapy. Treatment Satisfaction Questionnaire for Medication scores showed an improvement from baseline to month 3 in the domain of treatment convenience. Transition from epoprostenol with glycine and mannitol excipients to epoprostenol with arginine and sucrose excipients did not affect treatment efficacy,raised no new safety or tolerability concerns,and provided patients with an increased sense of treatment convenience.","Am Heart J. 2014 Feb;167(2):210-7.","International",2014,"Any PAH","Epoprostanol","TSQM",null,null,null,"International",null,"Any PAH","Epoprostanol",null,null,"TSQM","2010:2014"]
[30,"Saggar R,Khanna D,Vaidya A,Derhovanessian A,Maranian P,Duffy E,Belperio JA,Weigt SS,Dua S,Shapiro SS,Goldin JG,Abtin F,Lynch JP 3rd,Ross DJ,Forfia PR,Saggar R. Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis. Thorax. 2014 Feb;69(2):123-9. doi: 10.1136/thoraxjnl-2013-204150.","doi: 10.1136/thoraxjnl-2013-204150.","Saggar R,Khanna D,Vaidya A,Derhovanessian A,Maranian P,Duffy E,Belperio JA,Weigt SS,Dua S,Shapiro SS,Goldin JG,Abtin F,Lynch JP 3rd,Ross DJ,Forfia PR,Saggar R.","Changes in right heart haemodynamics and echocardiographic function in an advanced phenotype of pulmonary hypertension and right heart dysfunction associated with pulmonary fibrosis.","Pulmonary hypertension (PH)-targeted therapy in the setting of pulmonary fibrosis (PF) is controversial; the main clinical concern is worsening of systemic hypoxaemia. We sought to determine the effects of gentle initiation and chronic administration of parenteral treprostinil on right heart function in patients with PF associated with an advanced PH phenotype. Open-label,prospective analysis of patients with PF-PH referred for lung transplantation (LT). Advanced PH was defined as mean pulmonary artery pressure (mPAP) ≥35 mm Hg. We compared haemodynamics,Doppler echocardiography (DE),oxygenation,dyspnoea and quality of life indices,and 6 min walk distance (6MWD) before and 12 weeks after parenteral treprostinil. 15 patients were recruited in the study. After therapy,there were significant improvements in right heart haemodynamics (right atrial pressure (9.5 ± 3.4 vs 6.0 ± 3.7); mPAP (47 ± 8 vs 38.9 ± 13.4); CI (2.3 ± 0.5 vs 2.7 ± 0.6); pulmonary vascular resistance (698 ± 278 vs 496 ± 229); transpulmonary gradient (34.7 ± 8.7 vs 28.5 ± 10.3); mvO2 (65 ± 7.2 vs 70.9 ± 7.4); and stroke volume index (29.2 ± 6.7 vs 33 ± 7.3)) and DE parameters reflecting right heart function (right ventricular (RV) end diastolic area (36.4 ± 5.2 vs 30.9 ± 8.2 cm(2)),left ventricular eccentricity index (1.7 ± 0.6 vs 1.3 ± 0.5),tricuspid annular planar systolic excursion (1.6 ± 0.5 vs 1.9 ± 0.2 cm)). These changes occurred without significant alteration in systemic oxygenation,heart rate,or mean systemic arterial pressure. In addition,improvements were seen in 6MWD (171 ± 93 vs 230 ± 114),36-Item Short Form Health Survey Mental Component Summary aggregate (38 ± 11 vs 44.2 ± 10.7),University of California,San Diego Shortness of Breath Questionnaire (87 ± 17.1 vs 73.1 ± 21),and brain natriuretic peptide (558 ± 859 vs 228 ± 340). PH-targeted therapy may improve right heart haemodynamics and echocardiographic function without affecting systemic oxygen saturation in an advanced PH phenotype associated with RV dysfunction in the setting of PF.","Thorax. 2014 Feb;69(2):123-9.","USA",2014,"Interstitial lung disease","None or unknown","SF-36,UCSD-SBQ",null,null,null,"USA",null,"Interstitial lung disease","None or unknown",null,null,"SF-36,UCSD-SBQ","2010:2014"]
[31,"Ulrich S,Keusch S,Hildenbrand FF,Lo Cascio C,Huber LC,Tanner FC,Speich R,Bloch KE. Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized,double-blind,cross-over trial. Eur Heart J. 2015 Mar 7;36(10):615-23. doi: 10.1093/eurheartj/eht540. Epub 2013 Dec 23.","doi: 10.1093/eurheartj/eht540. Epub 2013 Dec 23.","Ulrich S,Keusch S,Hildenbrand FF,Lo Cascio C,Huber LC,Tanner FC,Speich R,Bloch KE.","Effect of nocturnal oxygen and acetazolamide on exercise performance in patients with pre-capillary pulmonary hypertension and sleep-disturbed breathing: randomized,double-blind,cross-over trial.","Sleep-disturbed breathing (SDB) is common in pre-capillary pulmonary hypertension (PH) and impairs daytime performance. In lack of proven effective treatments,we tested whether nocturnal oxygen therapy (NOT) or acetazolamide improve exercise performance and quality of life in patients with pre-capillary PH and SDB. This was a randomized,placebo-controlled,double-blind,three period cross-over trial. Participants received NOT (3 L/min),acetazolamide tablets (2 × 250 mg),and sham-NOT/placebo tablets each during 1 week with 1-week washout between treatment periods. Twenty-three patients,16 with pulmonary arterial PH,7 with chronic thromboembolic PH,and with SDB defined as mean nocturnal oxygen saturation <90% or oxygen saturation dips >10 h(-1) with daytime PaO2 ≥7.3 kPa participated. Assessments at the end of the treatment periods included a 6 min walk distance (MWD),SF-36 quality of life,polysomnography,and echocardiography. Medians (quartiles) of the 6 MWD after NOT,acetazolamide,and placebo were 480 m (390;528),440 m (368;468),and 454 m (367;510),respectively,mean differences: NOT vs. placebo +25 m (95% CI 3-46,P= 0.027),acetazolamide vs. placebo -9 m (-34-17,P = 0.223),and NOT vs. acetazolamide +33 (12-45,P < 0.001). SF-36 quality of life was similar with all treatments. Nocturnal oxygen saturation significantly improved with both NOT and acetazolamide. Right ventricular fractional area change was greater on NOT compared with placebo (P = 0.042) and acetazolamide (P = 0.027). In patients with pre-capillary PH and SDB on optimized pharmacological therapy,NOT improved the 6 MWD compared with placebo already after 1 week along with improvements in SDB and haemodynamics. NTC01427192.","Eur Heart J. 2015 Mar 7;36(10):615-23.","Switzerland",2015,"CTEPH","Acetazolamide,Oxygen","SF-36",null,null,null,"Switzerland",null,"CTEPH","Acetazolamide,Oxygen",null,null,"SF-36","2015:2018"]
[32,"Twiss J,McKenna S,Ganderton L,Jenkins S,Ben-L'amri M,Gain K,Fowler R,Gabbay E. Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension. BMC Pulm Med. 2013 Jul 12;13():45. doi: 10.1186/1471-2466-13-45. Epub 2013 Jul 12.","doi: 10.1186/1471-2466-13-45. Epub 2013 Jul 12.","Twiss J,McKenna S,Ganderton L,Jenkins S,Ben-L'amri M,Gain K,Fowler R,Gabbay E.","Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension.","The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and the Medical Outcomes Study Short Form 36 (SF-36) are widely used to assess patient-reported outcome in individuals with pulmonary hypertension (PH). The aim of the study was to compare the psychometric properties of the two measures. Participants were recruited from specialist PH centres in Australia and New Zealand. Participants completed the CAMPHOR and SF-36 at two time points two weeks apart. The SF-36 is a generic health status questionnaire consisting of 36 items split into 8 sections. The CAMPHOR is a PH-specific measure consisting of 3 scales; symptoms,activity limitations and needs-based QoL. The questionnaires were assessed for distributional properties (floor and ceiling effects),internal consistency (Cronbach's alpha),test-retest reliability and construct validity (scores by World Health Organisation functional classification). The sample comprised 65 participants (mean (SD) age = 57.2 (14.5) years; n(%) male = 14 (21.5%)). Most of the patients were in WHO class 2 (27.7%) and 3 (61.5%). High ceiling effects were observed for the SF-36 bodily pain,social functioning and role emotional domains. Test-retest reliability was poor for six of the eight SF-36 domains,indicating high levels of random measurement error. Three of the SF-36 domains did not distinguish between WHO classes. In contrast,all CAMPHOR scales exhibited good distributional properties,test retest reliability and distinguished between WHO functional classes. The CAMPHOR exhibited superior psychometric properties,compared with the SF-36,in the assessment of PH patient-reported outcome.","BMC Pulm Med. 2013 Jul 12;13():45.","Australia,New Zealand",2013,"Any PAH","None or unknown","CAMPHOR,SF-36",null,null,null,"Australia,New Zealand",null,"Any PAH","None or unknown",null,null,"CAMPHOR,SF-36","2010:2014"]
[33,"Halank M,Einsle F,Lehman S,Bremer H,Ewert R,Wilkens H,Meyer FJ,Grünig E,Seyfarth HJ,Kolditz M,Wieder G,Höffken G,Köllner V. Exercise capacity affects quality of life in patients with pulmonary hypertension. Lung. 2013 Aug;191(4):337-43. doi: 10.1007/s00408-013-9472-6. Epub 2013 May 17.","doi: 10.1007/s00408-013-9472-6. Epub 2013 May 17.","Halank M,Einsle F,Lehman S,Bremer H,Ewert R,Wilkens H,Meyer FJ,Grünig E,Seyfarth HJ,Kolditz M,Wieder G,Höffken G,Köllner V.","Exercise capacity affects quality of life in patients with pulmonary hypertension.","The objective of this prospective study was to evaluate the impact of exercise capacity,mental disorders,and hemodynamics on quality-of-life (QoL) parameters in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Sixty-three patients with invasively diagnosed PAH (n = 48) or CTEPH (n = 15) underwent a broad panel of assessments,including cardiopulmonary exercise testing (CPET),6-minute walking distance (6-MWD),World Health Organization functional class (WHO-FC),and assessment of hemodynamics. QoL was evaluated by the 36-item Medical Outcome Study Short Form Health Survey Questionnaire (SF-36). Exercise capacity,hemodynamics,age,gender,and mental disorders (anxiety and depression) were assessed for association with QoL subscores by uni- and multivariate regression analyses. Exercise capacity,WHO-FC,oxygen therapy,symptoms of right heart failure,right atrial pressure,and mental disorders were significantly associated with QoL (p < 0.05). In the stepwise backward selection multivariate analysis,depression remained an independent parameter in seven of eight subscales of the SF-36. Furthermore,peak oxygen uptake (peakVO2) during CPET,6-MWD,anxiety,long-term oxygen therapy,right heart failure,and age remained independent factors for QoL. Hemodynamic parameters at rest did not independently correlate with any domain of the SF-36 QoL subscores. Mental disorders,exercise capacity,long-term oxygen therapy,right heart failure,and age play important role in the quality of life in patients with PAH and CTEPH.","Lung. 2013 Aug;191(4):337-43.","Germany",2013,"Any PAH,CTEPH","None or unknown","SF-36",null,null,null,"Germany",null,"Any PAH,CTEPH","None or unknown",null,null,"SF-36","2010:2014"]
[34,"Chen H,Rosenzweig EB,Gotzkowsky SK,Arneson C,Nelsen AC,Bourge RC. Treatment satisfaction is associated with improved quality of life in patients treated with inhaled treprostinil for pulmonary arterial hypertension. Health Qual Life Outcomes. 2013 Mar 6;11():31. doi: 10.1186/1477-7525-11-31. Epub 2013 Mar 6.","doi: 10.1186/1477-7525-11-31. Epub 2013 Mar 6.","Chen H,Rosenzweig EB,Gotzkowsky SK,Arneson C,Nelsen AC,Bourge RC.","Treatment satisfaction is associated with improved quality of life in patients treated with inhaled treprostinil for pulmonary arterial hypertension.","Patient treatment satisfaction is likely to be a highly relevant outcome measure in pulmonary arterial hypertension (PAH),a condition for which the benefits of treatment must be weighed against frequent,undesirable side effects,inconvenience,and complications associated with therapy. In this study,we sought to evaluate the psychometric properties of a patient-reported treatment satisfaction measure and its relationship to quality of life (QoL) among patients transitioning from inhaled iloprost (iILO) to inhaled treprostinil (iTRE). We studied treatment satisfaction among 66 subjects with PAH in a single-arm,open-label,multi-center trial of iTRE following transition from iILO. Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM,version 1.4) administered to subjects immediately before and 12 weeks after transition of inhaled therapy. The TSQM is comprised of 4 domains: effectiveness,side effects,convenience,and global satisfaction. Scores range from 0 to 100 with higher scores indicating greater satisfaction. Six-minute walk distance (6MWD),functional class,adverse events,drug administration time,and PAH-specific QoL (CAMPHOR) were concurrently assessed. Domains of the TSQM demonstrated evidence of strong internal consistency at baseline and at 12 weeks (Cronbach α = 0.88-0.93). Transition from iILO to iTRE was associated with an improvement in 3 of 4 TSQM domains: effectiveness (+20 ± 21,p < 0.0001),side effects (0 ± 22,p = 0.97),convenience (+39 ± 26,p < 0.0001),and global satisfaction (+20 ± 24,p = 0.0005). Change in effectiveness scores correlated with change in 6MWD (r = 0.43,p = 0.0004) and side effects scores at 12 weeks correlated inversely with number of severity-weighted treatment-emergent adverse events (r = -0.44,p = 0.0002). In multiple regression models adjusted for baseline characteristics,changes in effectiveness and convenience satisfaction scores were significantly associated with improvement in PAH-specific QoL (p = 0.002 and p = 0.01). The TSQM demonstrated acceptable performance characteristics in patients with PAH. Changes in treatment satisfaction resulting from transitioning from iILO to iTRE were associated with improvements in PAH-specific QoL.\nTags","Health Qual Life Outcomes. 2013 Mar 6;11():31.","USA",2013,"Any PAH","Treprostanil","CAMPHOR,TSQM",null,null,null,"USA",null,"Any PAH","Treprostanil",null,null,"CAMPHOR,TSQM","2010:2014"]
[35,"Schuuring MJ,Vis JC,van Dijk AP,van Melle JP,Vliegen HW,Pieper PG,Sieswerda GT,de Bruin-Bon RH,Mulder BJ,Bouma BJ. Impact of bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial. Eur J Heart Fail. 2013 Jun;15(6):690-8. doi: 10.1093/eurjhf/hft017. Epub 2013 Jan 29.","doi: 10.1093/eurjhf/hft017. Epub 2013 Jan 29.","Schuuring MJ,Vis JC,van Dijk AP,van Melle JP,Vliegen HW,Pieper PG,Sieswerda GT,de Bruin-Bon RH,Mulder BJ,Bouma BJ.","Impact of bosentan on exercise capacity in adults after the Fontan procedure: a randomized controlled trial.","An endothelin-1 receptor blocker,shown to be effective in patients with pulmonary arterial hypertension,might decrease pulmonary vascular resistance to increase cardiac filling and consequently improve exercise capacity in Fontan patients. This was a prospective,multicentre randomized open label trial in Fontan patients. One group received bosentan for 6 months. The other group did not receive study medication for the first 3 months,followed by bosentan for 6 months. The primary endpoint was exercise capacity,and secondary endpoints were NT-proBNP level,cardiac output,SF-36 (Short Form-36) quality of life (QoL),and NYHA class. Forty-two adults (median age 29 (range 18-56) years,52% male,88% NYHA class I-II) from five tertiary referral centres participated in the study. Ten patients were on diuretics. Ten patients were not motivated to finish the study. Analysis of all 32 patients who finished the study at 6 months of treatment showed that mean peak V'O2 (24 vs. 25 mL/kg/min),median SQUASH score (6614 vs. 6390),median NT-proBNP (314 vs. 274 ng/L),and mental QoL (50 vs. 51) remained unchanged as compared with baseline (P = NS,for all). After treatment,NYHA class had improved in 6 (19%),was unchanged in 24 (75%),and declined in 2 (6%) patients. Subgroup analysis on age,ventricular morphology,type of Fontan circulation,or baseline NT-proBNP level did not reveal efficacy of bosentan. Six transient adverse effects were reported. An increased NT-proBNP level was present in the majority of Fontan patients. Six months of bosentan treatment was not beneficial. Trial registration NTR1557.","Eur J Heart Fail. 2013 Jun;15(6):690-8.","Netherlands",2013,"Congenital HD","Bosentan","SF-36",null,null,null,"Netherlands",null,"Congenital HD","Bosentan",null,null,"SF-36","2010:2014"]
[36,"Cooper TJ,Guazzi M,Al-Mohammad A,Amir O,Bengal T,Cleland JG,Dickstein K. Sildenafil in Heart failure (SilHF).  An investigator-initiated multinational randomized controlled clinical trial: rationale and design. Eur J Heart Fail. 2013 Jan;15(1):119-22. doi: 10.1093/eurjhf/hfs152. Epub 2012 Oct 24.","doi: 10.1093/eurjhf/hfs152. Epub 2012 Oct 24.","Cooper TJ,Guazzi M,Al-Mohammad A,Amir O,Bengal T,Cleland JG,Dickstein K.","Sildenafil in Heart failure (SilHF).  An investigator-initiated multinational randomized controlled clinical trial: rationale and design.","Heart failure (HF) is a major clinical problem and,despite advances in both pharmacological and device therapy,the mortality remains high and quality of life poor. Over the last decade there has been growing interest in using phosphodiesterase-5 (PDE-5) inhibitors in HF associated with group 2 pulmonary hypertension (PH),with benefits reported on pulmonary haemodynamic and functional status in single-centre trials Methods The Sildenafil in Heart Failure (SilHF) trial is a randomized,placebo-controlled multinational trial designed to assess efficacy and tolerability of PDE-5 inhibition with sildenafil (target dose 40 mg three times per day) in 210 patients with HF,New York Heart Association (NYHA) functional class II or III,and evidence of group 2 PH. The co-primary endpoints are patient global assessment and the 6 min walk test. Secondary endpoints include NYHA functional class and the quality of life tools Euro QoL 5D and the Kansas City questionnaire. Patients will be followed up for 6 months. The authors hypothesize that PDE-5 inhibition can improve exercise capacity and symptoms with acceptable tolerability in patients with HF and group 2 PH.","Eur J Heart Fail. 2013 Jan;15(1):119-22.","International",2013,"Any PAH","Sildenafil","EQ-5D,KCQ",null,null,null,"International",null,"Any PAH","Sildenafil",null,null,"EQ-5D,KCQ","2010:2014"]
[37,"Chan L,Chin LM,Kennedy M,Woolstenhulme JG,Nathan SD,Weinstein AA,Connors G,Weir NA,Drinkard B,Lamberti J,Keyser RE. Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension. Chest. 2013 Feb 1;143(2):333-43. doi: 10.1378/chest.12-0993.","doi: 10.1378/chest.12-0993.","Chan L,Chin LM,Kennedy M,Woolstenhulme JG,Nathan SD,Weinstein AA,Connors G,Weir NA,Drinkard B,Lamberti J,Keyser RE.","Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension.","Pulmonary hypertension (PH) restricts the ability to engage in physical activity and decreases longevity. We examined the impact of aerobic exercise training on function and quality of life in patients with World Health Organization group 1 PH. Patients were randomized to a 10-week education only (EDU) or education/exercise combined (EXE) group. The exercise program consisted of 24-30 sessions of treadmill walking for 30-45 min per session at 70% to 80% of heart rate reserve. Outcome variables included changes in 6-min walk test (6MWT) distance,time to exercise intolerance,peak work rate (WR) from a cardiopulmonary treadmill test,and quality-of-life measures,including the Short Form Health Survey,version 2 (SF-36v2) and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). Data are presented as mean SD. Twenty-three women (age,54 11 years; BMI,31 7 kg/m 2 ) were randomized to the EDU (n 5 13) or EXE (n 5 10) groups. Following 10 weeks of intervention,patients in the EXE group demonstrated an improvement in 6MWT distance (56 45 m; P 5 .002),increased time to exercise intolerance (1.9 1.3 min; P 5 .001),and peak WR (26 23 W; P 5 .004). Additionally,the EXE group scored significantly ( P,.050) better on six of the eight scales on SF-36v2,and fi ve of the six scales on CAMPHOR. In contrast,no significant improvement was observed for any of the outcome measures following EDU. No adverse events were noted in either group. Ten weeks of brisk treadmill walking improved 6MWT distance,cardiorespiratory function,and patient-reported quality of life in female patients with group 1 PH.","Chest. 2013 Feb 1;143(2):333-43.","USA",2013,"Any PAH","Exercise","CAMPHOR,SF-36",null,null,null,"USA",null,"Any PAH","Exercise",null,null,"CAMPHOR,SF-36","2010:2014"]
[38,"Nagel C,Prange F,Guth S,Herb J,Ehlken N,Fischer C,Reichenberger F,Rosenkranz S,Seyfarth HJ,Mayer E,Halank M,Grünig E. Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension. PLoS One. 2012;7(7):e41603. doi: 10.1371/journal.pone.0041603. Epub 2012 Jul 25.","doi: 10.1371/journal.pone.0041603. Epub 2012 Jul 25.","Nagel C,Prange F,Guth S,Herb J,Ehlken N,Fischer C,Reichenberger F,Rosenkranz S,Seyfarth HJ,Mayer E,Halank M,Grünig E.","Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension.","Aim of this prospective study was to evaluate the effects of exercise training in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH). Thirty-five consecutive patients with invasively confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61±15 years,mean pulmonary artery pressure,63±20 mmHg; primary inoperable n = 33,persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable disease-targeted medication received exercise training in-hospital for 3 weeks and continued at home for 15 weeks. Medication remained unchanged during the study period. Efficacy parameters have been evaluated at baseline,after 3 and 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of median 36.4 months (interquartile range 26.6-46.6 months). All patients tolerated exercise training without severe adverse events. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 61±54 meters after 3 weeks (p<0.001) and by 71±70 meters after 15 weeks (p = 0.001),as well as scores of quality-of-life questionnaire,peak oxygen consumption and maximal workload. NT-proBNP improved significantly after 3 weeks of exercise training (p = 0.046). The 1-year survival rate was 97%,2-year survival rate was 94% and the 3-year-survival 86% respectively. Training as add-on to medical therapy may be effective in patients with CTEPH to improve work capacity,quality of life and further prognostic relevant parameters and possibly improves the 1-,2- and 3-year survival rate. Further multicentric randomized controlled studies are needed to confirm these promising results. ClinicalTrials.gov NCT01398345.","PLoS One. 2012;7(7):e41603.","Germany",2012,"CTEPH","Exercise","Unknown",null,null,null,"Germany",null,"CTEPH","Exercise",null,null,"Unknown","2010:2014"]
[39,"Baughman RP,Judson MA,Lower EE,Highland K,Kwon S,Craft N,Engel PJ. Inhaled iloprost for sarcoidosis associated pulmonary hypertension. Sarcoidosis Vasc Diffuse Lung Dis. 2009 Jul;26(2):110-20.",null,"Baughman RP,Judson MA,Lower EE,Highland K,Kwon S,Craft N,Engel PJ.","Inhaled iloprost for sarcoidosis associated pulmonary hypertension.","Patients with sarcoidosis associated pulmonary hypertension (SAPH) have responded to systemic prostacyclin therapy. To determine the rate of response to inhaled prostacyclin,iloprost,in SAPH. Sarcoidosis patients with pulmonary hypertension and no evidence for left ventricular dysfunction were enrolled in an open label,prospective study. Patients underwent right heart catheterization and six minute walk (6MW) test. Quality of life was evaluated using several instruments,including the Saint George Respiratory Questionnaire (SGRQ). Patients received 5 mcg of inhaled iloprost every 2-3 hours while awake. After four months of therapy,patients underwent repeat cardiac catheterization,6 MW test,and completed quality of life questionnaires. Of the 22 patients enrolled,15 completed all 16 weeks of therapy. The most common reasons for study discontinuation included drug associated cough (3 patients) and compliance with the prescribed number of treatments per day (2 patients). Six patients experienced a 20% or greater decrease in pulmonary vascular resistance (PVR) from baseline with five of these six patients also showing > or = 5 mm Hg reduction in PA mean. Although three patients improved the 6MW distance by at least 30 meters,only one had a decrease in PVR. At 16 weeks a significant decrease was reported in the SGRQ activity score (p = 0.0273),with seven patients having a 4 point or greater decrease. Inhaled iloprost as monotherapy was associated with an improvement in pulmonary hemodynamics and quality of life as assessed by the SGRQ activity score in some sarcoidosis patients with SAPH.","Sarcoidosis Vasc Diffuse Lung Dis. 2009 Jul;26(2):110-20.","USA",2009,"Sarcoidosis","Iloprost","SGRQ",null,null,null,"USA",null,"Sarcoidosis","Iloprost",null,null,"SGRQ","2005:2009"]
[40,"Minier T,Nagy Z,Bálint Z,Farkas H,Radics J,Kumánovics G,Czömpöly T,Simon D,Varjú C,Németh P,Czirják L. Construct validity evaluation of the European Scleroderma Study Group activity index,and investigation of possible new disease activity markers in systemic sclerosis. Rheumatology (Oxford). 2010 Jun;49(6):1133-45. doi: 10.1093/rheumatology/keq022. Epub 2010 Mar 17.","doi: 10.1093/rheumatology/keq022. Epub 2010 Mar 17.","Minier T,Nagy Z,Bálint Z,Farkas H,Radics J,Kumánovics G,Czömpöly T,Simon D,Varjú C,Németh P,Czirják L.","Construct validity evaluation of the European Scleroderma Study Group activity index,and investigation of possible new disease activity markers in systemic sclerosis.","To evaluate the construct validity of the European Scleroderma Study Group (EScSG) activity index and to propose modifications if necessary. One hundred and thirty-one consecutive patients were investigated and re-evaluated 1 year later. Modified Rodnan skin score (MRSS),skin ulcers and joint contracture numbers,hand anatomic index (HAI),BMI,spirometry,carbon monoxide diffusing capacity (DL(CO)),left ventricular ejection fraction,pulmonary arterial hypertension,HAQ Disability Index (HAQ-DI),patient skin self-assessment questionnaire and several biomarkers were recorded,in addition to the data required for the EScSG activity index. Statistical analysis was performed by categorical principal component analysis (CATPCA). The EScSG activity index appeared in the same dimension as the HAQ-DI,ulcer score and joint contractures,MRSS,patient-reported skin score and HAI by CATPCA. Parameters of lung involvement appeared in another dimension. We constructed a 12-point activity index that was equally associated with both dimensions,by adding the forced vital capacity/DL(CO),change in DL(CO),change in the ulcer scores,HAQ-DI and patient-reported skin score. Biomarkers including vascular endothelial growth factor,soluble P-selectin glycoprotein ligand-1,CRP and albumin were related to both the EScSG and the 12-point index,though they did not improve the total variance of the model. The construct validity of the EScSG activity index is good,though the lung-related disease activity may not be sufficiently represented. Further validation steps may be required for both the EScSG and our 12-point activity index.","Rheumatology (Oxford). 2010 Jun;49(6):1133-45.","Hungary",2010,"Systemic sclerosis","None or unknown","EscSG,HAQ-DI,RSS",null,null,null,"Hungary",null,"Systemic sclerosis","None or unknown",null,null,"EscSG,HAQ-DI,RSS","2010:2014"]
[41,"Fraisse A,Jais X,Schleich JM,di Filippo S,Maragnès P,Beghetti M,Gressin V,Voisin M,Dauphin C,Clerson P,Godart F,Bonnet D. Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France. Arch Cardiovasc Dis. 2010 Feb;103(2):66-74. doi: 10.1016/j.acvd.2009.12.001. Epub 2010 Feb 11.","doi: 10.1016/j.acvd.2009.12.001. Epub 2010 Feb 11.","Fraisse A,Jais X,Schleich JM,di Filippo S,Maragnès P,Beghetti M,Gressin V,Voisin M,Dauphin C,Clerson P,Godart F,Bonnet D.","Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France.","Limited data are available describing paediatric pulmonary arterial hypertension. To characterize the epidemiology,management and impact on quality of life and outcome of paediatric pulmonary arterial hypertension,excluding persistent pulmonary hypertension of the newborn and pulmonary arterial hypertension caused by congenital heart disease. In this multicentre study,children with pulmonary arterial hypertension were included and followed prospectively for two years at 21 referral centres in France. WHO functional class,6-minute walk distance and quality of life (CHQ-PF50 questionnaire) were evaluated. Fifty children were included with a mean age of 8.9 +/- 5.4 years from May 2005 until June 2006. The estimated prevalence for pulmonary arterial hypertension was 3.7 cases/million. Patients had idiopathic pulmonary arterial hypertension (60%),familial pulmonary arterial hypertension (10%),pulmonary arterial hypertension associated with,but not caused by,congenital heart disease (24%),pulmonary arterial hypertension associated with connective tissue disease (4%) or portal hypertension (2%). During follow-up,the combination of pulmonary arterial hypertension-specific therapies was increasingly prescribed (44% patients versus 22% at inclusion). Patients remained stable regarding clinical status,6-minute walk distance and quality of life. Survival estimates after one and two years were 86% (95% CI 76,96) and 82% (95% CI 71,93),respectively. In children,idiopathic/familial pulmonary arterial hypertension accounts for the majority of cases. A specific pulmonary arterial hypertension group in conjunction with congenital heart disease can be identified that resembles patients with idiopathic pulmonary arterial hypertension. Combined pulmonary arterial hypertension-specific therapies may have contributed to disease stability and favourable survival.","Arch Cardiovasc Dis. 2010 Feb;103(2):66-74.","France",2010,"Any PAH","None or unknown","CHQ-PF50",null,null,null,"France",null,"Any PAH","None or unknown",null,null,"CHQ-PF50","2010:2014"]
[42,"Viganò G,Guidotti A,Taramasso M,Giacomini A,Alfieri O. Clinical mid-term results after tricuspid valve replacement. Interact Cardiovasc Thorac Surg. 2010 May;10(5):709-13. doi: 10.1510/icvts.2009.224212. Epub 2010 Feb 10.","doi: 10.1510/icvts.2009.224212. Epub 2010 Feb 10.","Viganò G,Guidotti A,Taramasso M,Giacomini A,Alfieri O.","Clinical mid-term results after tricuspid valve replacement.","Tricuspid valve replacement (TVR) is associated with high mortality and morbidity. Frequently,TVR is performed in critically ill patients with high frequency of re-intervention. We analyzed our experience in TVR focusing on predicting risk factors,mid-term survival and quality of life assessed with a Short-Form 36 Health Survey (SF-36) questionnaire. Between January 1992 and May 2007,81 consecutive patients underwent TVR (54 re-interventions,66.7%; 46 procedures,associated with a left-sided operation,56.8%). There were 59 females (73%) with a mean age of 59.3+/-11.6 years. The most prevalent etiology was rheumatic fever (61.7%). Pulmonary hypertension was present in 64%. Mean left ventricle ejection fraction (LVEF) was 56.6% and mean right ventricle ejection fraction (RVEF) was 48.1%. All but four patients (4.9%) received a bio-prosthesis. Hospital mortality was 9.88%. The mean follow-up was 61+/-42 months. Survival was 68% at five years. Univariate predictors of hospital mortality were atrial fibrillation (AFib) (P<0.01),associated procedures on the left heart (P=0.025) and preoperative chronic right heart failure symptoms (P<0.01). At follow-up: 10.8% of patients had a pace-maker (PM) induced rhythm; the mean SF-36 score was 51.1+/-4.8 (range 59-38). Age (P=0.015),associated procedures (P=0.024) and previous cardiovascular surgery (P=0.015) were univariate predictors of the SF-36 score. At a multivariate analysis LVEF,venous congestion and pulmonary artery pressures (PAPs) were related with a SF-36 score.","Interact Cardiovasc Thorac Surg. 2010 May;10(5):709-13.","Italy",2010,"Any PAH","Surgery","SF-36",null,null,null,"Italy",null,"Any PAH","Surgery",null,null,"SF-36","2010:2014"]
[43,"Pepke-Zaba J,Beardsworth A,Chan M,Angalakuditi M. Tadalafil therapy and health-related quality of life in pulmonary arterial hypertension. Curr Med Res Opin. 2009 Oct;25(10):2479-85. doi: 10.1185/03007990903210066.","doi: 10.1185/03007990903210066.","Pepke-Zaba J,Beardsworth A,Chan M,Angalakuditi M.","Tadalafil therapy and health-related quality of life in pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) is a rare,progressive lung disorder that impairs performance of daily activities and quality of life (QoL),leading to right heart failure and death. Treatment options include prostanoids,endothelin antagonists,and phosphodiesterase type 5 inhibitors (e.g.,tadalafil). Currently there is no cure for PAH,but tadalafil has improved exercise capacity in these patients. To explore the effect of tadalafil on health-related quality of life (HRQoL) measures. The Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) clinical trial examined the efficacy and tolerability of tadalafil for the treatment of PAH. The impact of tadalafil on HRQoL and exercise capacity,as measured by 6-minute walk test (6MW test),was also examined. Change from baseline to last non-missing post-baseline was examined for the SF-36,EQ-5D,and 6MW test,along with the relationship between HRQoL and 6MW test performance. Tadalafil 40 mg showed significant improvement over placebo for six of eight SF-36 domains,and EQ-5D index scores. Also,the tadalafil 40-mg group showed significant improvement over placebo on the 6MW test (p < 0.001),but no clear relationship was found between 6MW test performance and HRQoL. Results suggest that tadalafil 40 mg may significantly improve HRQoL and exercise capacity for PAH patients. Limitations of this study include its relatively short nature limited to 16 weeks and the relative heterogeneity of the study population.","Curr Med Res Opin. 2009 Oct;25(10):2479-85.","UK",2009,"Any PAH","Tadalafil","EQ-5D,SF-36",null,null,null,"UK",null,"Any PAH","Tadalafil",null,null,"EQ-5D,SF-36","2005:2009"]
[44,"Duffels MG,Vis JC,van Loon RL,Nieuwkerk PT,van Dijk AP,Hoendermis ES,de Bruin-Bon RH,Bouma BJ,Bresser P,Berger RM,Mulder BJ. Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome. Am J Cardiol. 2009 May 1;103(9):1309-15. doi: 10.1016/j.amjcard.2009.01.021. Epub 2009 Mar 13.","doi: 10.1016/j.amjcard.2009.01.021. Epub 2009 Mar 13.","Duffels MG,Vis JC,van Loon RL,Nieuwkerk PT,van Dijk AP,Hoendermis ES,de Bruin-Bon RH,Bouma BJ,Bresser P,Berger RM,Mulder BJ.","Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome.","Pulmonary arterial hypertension associated with congenital heart disease caused by systemic-to-pulmonary shunting was associated with a high risk of morbidity and mortality. In this retrospective study,the longer term treatment effect of bosentan on exercise capacity and quality of life (QoL) were evaluated in 58 adult patients (>18 years) with pulmonary arterial hypertension associated with congenital heart disease,including patients with Down's syndrome. All patients were evaluated at baseline and during follow-up using laboratory tests,6-minute walk test,QoL questionnaires,and Doppler echocardiography. Treatment efficacy was analyzed separately for patients without (n = 30) and with Down's syndrome (n = 28). Median follow-up of all patients treated with bosentan was 22 months (range 3 to 36). In patients without Down's syndrome,mean 6-minute walk distance increased from 427 +/- 97 to 461 +/- 104 m (p <0.01) after 6 months of treatment,followed by a gradual return to baseline and disease stabilization. QoL improved significantly during treatment and was maintained during 18 months of follow-up (p <0.05). In patients with Down's syndrome,6-minute walk distance and QoL were stable during treatment. In conclusion,findings suggested that in patients without Down's syndrome,longer term bosentan treatment resulted in a persistent improvement in QoL and stabilization of exercise capacity.","Am J Cardiol. 2009 May 1;103(9):1309-15.","Netherlands",2009,"Congenital HD","Bosentan","Unknown",null,null,null,"Netherlands",null,"Congenital HD","Bosentan",null,null,"Unknown","2005:2009"]
[45,"Chow S,Pope JE,Mehta S. Lack of correlation of the health assessment questionnaire disability index with lung parameters in systemic sclerosis associated pulmonary arterial hypertension. Clin Exp Rheumatol. 2008 Nov-Dec;26(6):1012-7.",null,"Chow S,Pope JE,Mehta S.","Lack of correlation of the health assessment questionnaire disability index with lung parameters in systemic sclerosis associated pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) affects the quality of life (QoL) and the ability to perform the activities of daily living (ADLs) in patients with systemic sclerosis (SSc). We determined whether the Health Assessment Questionnaire-Disability Index (HAQ-DI),a self-assessment measure of function,correlates with a patient's PAH status in a population of SSc patients with PAH. Forty-one patients from one centre with systemic scleroderma,dyspnea and PAH were included. All patients filled in a HAQ-DI,and underwent evaluation with pulmonary function tests (PFTs),6-minute walk distance (6MWD),degree of dyspnea (Borg dyspnea index),NYHA functional class,and expert PAH physician global assessment every 6 months. Change in HAQ DI was studied to determine relationship to changes in PAH. The HAQ-DI scores had no significant correlation with PAH,including NYHA functional class (r=0.38,p=0.39),Borg dyspnea index (r=0.60,p=0.37),6MWD (r=-0.04,p=0.86),% predicted DLCO (r=0.31,p=0.25),% predicted FVC (r=0.02,p=0.93),and expert PAH physician global assessment (r=0.06,p=0.97). HAQ-DI is not an adequate measure of PAH status in SSc patients with PAH. Although PAH causes severe morbidity and death,changes in PAH severity were not reflected in an overall functional status change as assessed by the HAQ-DI. Thus,HAQ-DI changes do not reflect PAH status in Ssc.","Clin Exp Rheumatol. 2008 Nov-Dec;26(6):1012-7.","Canada",2008,"Systemic sclerosis","None or unknown","BDI,HAQ-DI",null,null,null,"Canada",null,"Systemic sclerosis","None or unknown",null,null,"BDI,HAQ-DI","2005:2009"]
[46,"Gilbert C,Brown MC,Cappelleri JC,Carlsson M,McKenna SP. Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil. Chest. 2009 Jan;135(1):137-42. doi: 10.1378/chest.07-0275. Epub 2008 Sep 23.","doi: 10.1378/chest.07-0275. Epub 2008 Sep 23.","Gilbert C,Brown MC,Cappelleri JC,Carlsson M,McKenna SP.","Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil.","No guidelines exist to help physicians determine whether functional and health-related quality of life (HRQoL) changes observed following treatment of patients with pulmonary arterial hypertension (PAH) represent important benefits. These analyses were undertaken to help define a minimally important difference (MID) in exercise capacity,measured by the 6-min walk distance (6MWD),and HRQoL,measured by the Short Form-36 (SF-36) questionnaire in patients with PAH. Data from a 12-week sildenafil study in patients with PAH were used to calculate MIDs for 6MWD and the SF-36 physical functioning,role-physical,social functioning,and vitality scales using effect size,SEM,and SE of the difference approaches. Data from all patients enrolled into the treatment groups in the study were included. A range of plausible MID estimates,including a score change for SF-36 scales and a change in distance walked in meters for 6MWD,were generated for each end point. Mean values were calculated for each outcome and recommended as MIDs for each parameter. Based on these computations,the mean MIDs for the SF-36 physical functioning,role-physical,social functioning,and vitality scales and for 6MWD were 13,25,21,and 15 points,and 41 m,respectively. This is the first clinical investigation to estimate MIDs for key SF-36 domains and 6MWD in patients with PAH and provides a much needed metric for interpreting the level of change in patients with PAH against which other treatments and trials can be measured.","Chest. 2009 Jan;135(1):137-42.","UK",2009,"Any PAH","Sildenafil","SF-36",null,null,null,"UK",null,"Any PAH","Sildenafil",null,null,"SF-36","2005:2009"]
[47,"McKenna SP,Ratcliffe J,Meads DM,Brazier JE. Development and validation of a preference based measure derived from the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for use in cost utility analyses. Health Qual Life Outcomes. 2008 Aug 21;6():65. doi: 10.1186/1477-7525-6-65. Epub 2008 Aug 21.","doi: 10.1186/1477-7525-6-65. Epub 2008 Aug 21.","McKenna SP,Ratcliffe J,Meads DM,Brazier JE.","Development and validation of a preference based measure derived from the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for use in cost utility analyses.","Pulmonary Hypertension is a severe and incurable disease with poor prognosis. A suite of new disease-specific measures--the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) - was recently developed for use in this condition. The purpose of this study was to develop and validate a preference based measure from the CAMPHOR that could be used in cost-utility analyses. Items were selected that covered major issues covered by the CAMPHOR QoL scale (activities,travelling,dependence and communication). These were used to create 36 health states that were valued by 249 people representative of the UK adult population,using the time trade-off (TTO) technique. Data from the TTO interviews were analysed using both aggregate and individual level modelling. Finally,the original CAMPHOR validation data were used to validate the new preference based model. The predicted health state values ranged from 0.962 to 0.136. The mean level model selected for analyzing the data had good explanatory power (0.936),did not systematically over- or underestimate the observed mean health state values and showed no evidence of auto correlation in the prediction errors. The value of less than 1 reflects a background level of ill health in state 1111,as judged by the respondents. Scores derived from the new measure had excellent test-retest reliability (0.85) and construct validity. The CAMPHOR utility score appears better able to distinguish between WHO functional classes (II and III) than the EQ-5D and SF-6D. The tariff derived in this study can be used to classify an individual into a health state based on their responses to the CAMPHOR. The results of this study widen the evidence base for conducting economic evaluations of interventions designed to improve QoL for patients with PH.","Health Qual Life Outcomes. 2008 Aug 21;6():65.","UK",2008,"Any PAH","None or unknown","CAMPHOR,EQ-5D,SF-6D,TTO",null,null,null,"UK",null,"Any PAH","None or unknown",null,null,"CAMPHOR,EQ-5D,SF-6D,TTO","2005:2009"]
[48,"Strange G,Keogh AM,Williams TJ,Wlodarczyk J,McNeil KD,Gabbay E. Bosentan therapy in patients with pulmonary arterial hypertension: the relationship between improvements in 6 minute walk distance and quality of life. Respirology. 2008 Sep;13(5):674-82. doi: 10.1111/j.1440-1843.2008.01326.x.","doi: 10.1111/j.1440-1843.2008.01326.x.","Strange G,Keogh AM,Williams TJ,Wlodarczyk J,McNeil KD,Gabbay E.","Bosentan therapy in patients with pulmonary arterial hypertension: the relationship between improvements in 6 minute walk distance and quality of life.","Bosentan,an oral,dual endothelin receptor antagonist,significantly improves functional status,haemodynamic measures and survival in patients with pulmonary arterial hypertension (PAH). However,there are limited data on the effect of bosentan on quality of life (QOL) and its relationship to changes in functional status,as measured by the 6 minute walk distance (6MWD). A retrospective analysis was performed of a large,open-label,multicentre trial (VITAL) of bosentan in patients with PAH. Data for 6MWD were collected at baseline,3 or 6 months and these results were correlated with QOL measurements collected as part of the assessment of patients enrolled in the trial. Sixty-nine patients with PAH (mean age 52 years) who were enrolled in the trial had valid QOL (SF-36) measurements and 6MWD data that could be retrieved from clinical notes. At 3 and 6 months,bosentan therapy improved 6MWD compared with baseline (49.5 m and 47.2 m,respectively,P < 0.001) as well as QOL domains,with a significant correlation between these two markers on cross-sectional analysis. However,there was a poor relationship when comparing changes in 6MWD with changes in QOL,in response to therapy. Bosentan therapy was associated with improvements in QOL and 6MWD for at least 6 months. At all measured time points,there was a close correlation between 6MWD and most QOL domains. QOL is an important parameter and should be considered as part of the standard assessment for any trial investigating therapy in PAH.","Respirology. 2008 Sep;13(5):674-82.","Australia",2008,"Any PAH","Bosentan","SF-36",null,null,null,"Australia",null,"Any PAH","Bosentan",null,null,"SF-36","2005:2009"]
[49,"Zlupko M,Harhay MO,Gallop R,Shin J,Archer-Chicko C,Patel R,Palevsky HI,Taichman DB. Evaluation of disease-specific health-related quality of life in patients with pulmonary arterial hypertension. Respir Med. 2008 Oct;102(10):1431-8. doi: 10.1016/j.rmed.2008.04.016. Epub 2008 Jul 9.","doi: 10.1016/j.rmed.2008.04.016. Epub 2008 Jul 9.","Zlupko M,Harhay MO,Gallop R,Shin J,Archer-Chicko C,Patel R,Palevsky HI,Taichman DB.","Evaluation of disease-specific health-related quality of life in patients with pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) remains a debilitating and life-threatening disease despite improvements in hemodynamics,exercise capacity and survival with recent therapeutic advances. Health-related quality of life (HRQOL) has,therefore,been proposed as an important outcome for evaluating care. Relatively little,however,is known regarding HRQOL or its determinants in PAH. The Minnesota Living with Heart Failure questionnaire was recently adapted and validated for HRQOL measurement in PAH. We applied this pulmonary hypertension-specific version (MLHF-PH) to a larger population of PAH patients. Ninety-three consecutive outpatients with PAH completed the MLHF-PH. Scores were assessed for correlations with demographics,symptoms,hemodynamics and treatments. Patients with PAH had significantly impaired HRQOL as assessed by the disease-specific MLHF-PH. Each physical and emotional component,as well as total scores on the MLHF-PH indicated severely depressed HRQOL. As compared to other diagnoses,PAH associated with scleroderma had the worst HRQOL. Patients with WHO functional Class II symptoms reported better HRQOL than Class III patients. Fatigue,weakness and abdominal discomfort were each associated with more severely depressed HRQOL,as was current epoprostenol use. With the sole exception of the right atrial pressure,hemodynamic measurements did not correlate with HRQOL scores. Simultaneous evaluation of HRQOL with a non-disease-specific questionnaire (SF-36) revealed a similarly impaired status,although identified fewer associations with patient-specific factors. Severely impaired HRQOL is present in this population of patients with PAH evaluated with a disease-specific questionnaire. The availability of a pulmonary hypertension-specific HRQOL questionnaire may enable further targeted investigations of factors that might improve outcomes.","Respir Med. 2008 Oct;102(10):1431-8.","USA",2008,"Any PAH","None or unknown","MLHFQ,SF-36",null,null,null,"USA",null,"Any PAH","None or unknown",null,null,"MLHFQ,SF-36","2005:2009"]
[50,"Frantz RP,Benza RL,Kjellström B,Bourge RC,Barst RJ,Bennett TD,McGoon MD. Continuous hemodynamic monitoring in patients with pulmonary arterial hypertension. J Heart Lung Transplant. 2008 Jul;27(7):780-8. doi: 10.1016/j.healun.2008.04.009. Epub 2008 Jun 2.","doi: 10.1016/j.healun.2008.04.009. Epub 2008 Jun 2.","Frantz RP,Benza RL,Kjellström B,Bourge RC,Barst RJ,Bennett TD,McGoon MD.","Continuous hemodynamic monitoring in patients with pulmonary arterial hypertension.","The purpose of this study was to determine whether an implantable hemodynamic monitor (IHM) could be used to judge the response of pulmonary arterial hypertension (PAH) patients to changes in therapy. A prospective,non-randomized,multi-center study evaluated physical examination,functional class,echocardiography,brain natriuretic peptide (BNP) levels,exercise capacity assessed by 6-minute walk and cardiopulmonary exercise tests,and quality of life at baseline and at 12 weeks. IHM measurements were continuously available to clinicians between clinic visits. Based on a priori,pre-specified analyses,the relationships between hemodynamic values,PAH treatments and clinical parameters were tracked in an observational fashion. Twenty-four PAH patients underwent IHM implantation prior to a change in PAH therapy. IHM data identified 13 of the 15 patients who improved their 6-minute walk distance by >30 m at 12 weeks (+48 +/- 65 m,p < 0.05),whereas the others walked less (-78 +/- 115 m,not statistically significant). In addition,peak Vo(2),BNP levels and Minnesota Living with Heart Failure Questionnaire scores only improved in the former group. The change in mean pulmonary artery pressure correlated with the change in 6-minute walk distance at 12 weeks (r = -0.71,p < 0.001). Device-related adverse events were comparable to those known to occur with a pacemaker-like device. Changes in ambulatory continuous hemodynamic measurements predicted changes in 6-minute walk distance after the start or addition of PAH therapy. The IHM also identified patients who had improved exercise tolerance,BNP levels and quality of life. The IHM appeared to be well tolerated and allowed rapid hemodynamic feedback between clinic visits.","J Heart Lung Transplant. 2008 Jul;27(7):780-8.","USA",2008,"Any PAH","None or unknown","MLHFQ",null,null,null,"USA",null,"Any PAH","None or unknown",null,null,"MLHFQ","2005:2009"]
[51,"Umehara M,Yamaguchi A,Itakura S,Suenaga M,Sakaki Y,Nakashiki K,Miyata M,Tei C. Repeated waon therapy improves pulmonary hypertension during exercise in patients with severe chronic obstructive pulmonary disease. J Cardiol. 2008 Apr;51(2):106-13. doi: 10.1016/j.jjcc.2008.01.004.","doi: 10.1016/j.jjcc.2008.01.004.","Umehara M,Yamaguchi A,Itakura S,Suenaga M,Sakaki Y,Nakashiki K,Miyata M,Tei C.","Repeated waon therapy improves pulmonary hypertension during exercise in patients with severe chronic obstructive pulmonary disease.","Repeated Waon therapy,which uses a far infrared-ray dry sauna system,improved the vascular endothelial function and the cardiac function in patients with chronic heart failure. In patients with chronic obstructive pulmonary disease (COPD),pulmonary hypertension (PH) is associated with a poor prognosis. We investigated whether repeated Waon therapy improves PH,cardiac function,exercise tolerance,and the quality of life (QOL) in patients with COPD. Consecutive 13 patients with COPD,who met the Global Initiative for Chronic Obstructive Lung Disease criteria and had breathlessness despite receiving conventional treatments,were recruited for this study. They underwent Waon therapy at 60 degrees C in sauna for 15 min following 30 min warmth with blankets outside of the sauna room. This therapy was performed once a day,for 4 weeks. Cardiac function,exercise tolerance,and St. George's Respiratory Questionnaire (SGRQ) were assessed before and 4 weeks after Waon therapy. Right ventricular positive dP/dt at rest elevated significantly from 397 +/- 266 to 512 +/- 320 mmHg/s (p = 0.024) after the therapy. While the PH at rest did not significantly decrease,the PH during exercise decreased significantly from 64 +/- 18 to 51 +/- 13 mmHg (p = 0.028) after Waon therapy. Furthermore,the therapy prolonged the mean exercise time of the constant load of cycle ergometer exercise test from 360 +/- 107 to 392 +/- 97 s (p = 0.032). The total scores of SGRQ improved from 59.7 +/- 16.9 to 55.3 +/- 17.2 (p = 0.002). In addition,no adverse effects were observed related to Waon therapy. Repeated Waon therapy improved right ventricular positive dP/dt,PH during exercise,exercise tolerance and the QOL in patients with severe COPD.","J Cardiol. 2008 Apr;51(2):106-13.","Japan",2008,"COPD","Waon therapy","SGRQ",null,null,null,"Japan",null,"COPD","Waon therapy",null,null,"SGRQ","2005:2009"]
[52,"Yoshimi S,Tanabe N,Masuda M,Sakao S,Uruma T,Shimizu H,Kasahara Y,Takiguchi Y,Tatsumi K,Nakajima N,Kuriyama T. Survival and quality of life for patients with peripheral type chronic thromboembolic pulmonary hypertension. Circ J. 2008 Jun;72(6):958-65.",null,"Yoshimi S,Tanabe N,Masuda M,Sakao S,Uruma T,Shimizu H,Kasahara Y,Takiguchi Y,Tatsumi K,Nakajima N,Kuriyama T.","Survival and quality of life for patients with peripheral type chronic thromboembolic pulmonary hypertension.","The validity of pulmonary thromboendarterectomy for treatment of relatively peripheral type of chronic thromboembolic pulmonary hypertension (CTEPH) remains uncertain. The survival and quality of life (QOL) of patients with relatively peripheral type of CTEPH was investigated at follow up. Between April 1999 and March 2006,83 consecutive patients with CTEPH were evaluated for surgical indication and underwent computed tomography angiography. The extent of central disease was scored (ie,CD score),and a CD score of <or=1 was judged as relatively peripheral disease. Forty-three patients were excluded from surgery,and 40 patients,including 14 cases of relatively peripheral disease,underwent surgery. Long-term survival and QOL scores at follow up (1-3 years) were compared between the surgically and medically treated groups of relatively peripheral disease. Survival curves between the 2 treatment groups were not significantly different (p=0.78) because of high operative mortality (21.4%). However,improvement in physical functioning,role function (physically related),general health perception (as assessed by the Medical Outcome Study Short Form 36),and baseline dyspnea index were significantly higher in the group treated surgically compared with the medically treated group. CONCLUSIONS: Pulmonary thromboendarterectomy offers better QOL even in those patients with relatively peripheral type of CTEPH,although operative mortality must be reduced.","Circ J. 2008 Jun;72(6):958-65.","Japan",2008,"CTEPH","Surgery","SF-36",null,null,null,"Japan",null,"CTEPH","Surgery",null,null,"SF-36","2005:2009"]
[53,"Pepke-Zaba J,Gilbert C,Collings L,Brown MC. Sildenafil improves health-related quality of life in patients with pulmonary arterial hypertension. Chest. 2008 Jan;133(1):183-9. doi: 10.1378/chest.07-0592.","doi: 10.1378/chest.07-0592.","Pepke-Zaba J,Gilbert C,Collings L,Brown MC.","Sildenafil improves health-related quality of life in patients with pulmonary arterial hypertension.","Sildenafil inhibits phosphodiesterase-5,enhancing cyclic guanosine monophosphate- mediated relaxation of pulmonary vasculature and is effective in treating patients with pulmonary arterial hypertension (PAH). Patients with PAH (n = 278) received oral sildenafil (20,40,or 80 mg three times daily) in a 12-week,double-blind,placebo-controlled study and an open-label extension. Health-related quality of life (HRQoL) was recorded by patients using the Medical Outcomes Study 36-item short form (SF-36) and EuroQol 5D (EQ-5D) questionnaires at baseline and after 12 and 24 weeks of therapy. Data are presented for patients who received sildenafil for up to 24 weeks. Sildenafil-treated patients,compared with placebo-treated patients,exhibited significant improvement in exercise capacity at week 12 (p < 0.001). Increases from baseline to week 12 were observed in all SF-36 domains for sildenafil-treated patients,with statistically significant improvements,compared with placebo-treated control subjects,in physical functioning (p < 0.001),general health (p < 0.001),and vitality (p < 0.05). Statistically significant improvements were also observed for the EQ-5D current health status (p < 0.01) and utility index (p < 0.01). These benefits were maintained for 24 weeks. Treatment groups were pooled for analyses as the results for the 6-min walk distance,SF-36,and EQ-5D were not dose dependent. Sildenafil improves HRQoL of PAH patients. These improvements appear to be maintained for at least 24 weeks. The effects are strongest in domains addressing the physical impact of health on daily activities and patients' overall perception of health.","Chest. 2008 Jan;133(1):183-9.","UK",2008,"Any PAH","Sildenafil","EQ-5D,SF-36",null,null,null,"UK",null,"Any PAH","Sildenafil",null,null,"EQ-5D,SF-36","2005:2009"]
[54,"Gomberg-Maitland M,Thenappan T,Rizvi K,Chandra S,Meads DM,McKenna SP. United States validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). J Heart Lung Transplant. 2008 Jan;27(1):124-30. doi: 10.1016/j.healun.2007.10.004.","doi: 10.1016/j.healun.2007.10.004.","Gomberg-Maitland M,Thenappan T,Rizvi K,Chandra S,Meads DM,McKenna SP.","United States validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).","The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first pulmonary hypertension-specific instrument for assessing patient-reported symptoms,functioning,and quality of life. To enable use in the United States,this study adapted,field-tested,and evaluated its reliability and validity at a single center in Chicago. A lay panel confirmed appropriate wording of CAMPHOR for United States patients,and 15 patients with pulmonary hypertension field-tested the CAMPHOR for face and content validity. A postal validation study,with the Medical Outcomes Study Short Form 36 (SF-36) Health Survey as a comparator,was sent to patients on 2 occasions,2 weeks apart. World Health Organization (WHO) functional class and 6-minute walk test data were obtained. Field-test interviews found the CAMPHOR relevant and comprehensible. A total of 147 patients (84.0% women) with a mean of 50 +/- 14.6 years participated in the validation study. The new scales had good test-retest reliability (range,0.80-0.95) and internal consistency (range,0.78-0.95). The CAMPHOR scales correlated with the SF-36 and 6-minute walk test. Patients in WHO functional class III had worse scores than those in class II (p = 0.02),as did patients who rated their health worse (p < 0.001). The US CAMPHOR is a reliable and valid measure of quality of life and health status in pulmonary hypertension and can be recommended for use in clinical practice and trials in the United States.","J Heart Lung Transplant. 2008 Jan;27(1):124-30.","USA",2008,"Any PAH","None or unknown","CAMPHOR,SF-36",null,null,null,"USA",null,"Any PAH","None or unknown",null,null,"CAMPHOR,SF-36","2005:2009"]
[55,"Denton CP,Pope JE,Peter HH,Gabrielli A,Boonstra A,van den Hoogen FH,Riemekasten G,De Vita S,Morganti A,Dölberg M,Berkani O,Guillevin L,TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators. Long-term effects of bosentan on quality of life,survival,safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis. 2008 Sep;67(9):1222-8. doi: 10.1136/ard.2007.079921. Epub 2007 Nov 30.","doi: 10.1136/ard.2007.079921. Epub 2007 Nov 30.","Denton CP,Pope JE,Peter HH,Gabrielli A,Boonstra A,van den Hoogen FH,Riemekasten G,De Vita S,Morganti A,Dölberg M,Berkani O,Guillevin L,TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators.","Long-term effects of bosentan on quality of life,survival,safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases.","This study investigated the long-term effects of bosentan,an oral endothelin ET(A)/ET(B) receptor antagonist,in patients with pulmonary arterial hypertension (PAH) exclusively related to connective tissue diseases (CTD). A total of 53 patients with PAH related to connective tissue diseases (PAH-CTD) in World Health Organization (WHO) functional class III received bosentan 62.5 mg twice a day for 4 weeks and then 125 mg twice a day for 44 weeks in this open non-comparative study. Assessments at weeks 16 and 48 included WHO class,clinical worsening,quality of life (Short-Form Health Survey (SF-36) and health assessment questionnaire (HAQ) modified for scleroderma),and survival (week 48 only). Safety and tolerability were monitored throughout the study. At week 48,WHO class improved in 27% of patients (95% CI 16-42%) and worsened in 16% (95% CI 7-29%). Kaplan-Meier estimates were 68% (95% CI 55-82%) for absence of clinical worsening and 92% (95% CI 85-100%) for survival. Overall changes in quality of life were minimal. There were no unexpected side effects observed during the study. In most patients,bosentan was associated with improvement or stability of clinical status. The 92% estimate for survival at 48 weeks is a significant achievement in this patient population.","Ann Rheum Dis. 2008 Sep;67(9):1222-8.","UK",2008,"Interstitial lung disease","Bosentan","HAQ-DI,SF-36",null,null,null,"UK",null,"Interstitial lung disease","Bosentan",null,null,"HAQ-DI,SF-36","2005:2009"]
[56,"Ulrich S,Speich R,Domenighetti G,Geiser T,Aubert JD,Rochat T,Huber L,Treder U,Fischler M. Bosentan therapy for chronic thromboembolic pulmonary hypertension.  A national open label study assessing the effect of Bosentan on haemodynamics,exercise capacity,quality of life,safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study). Swiss Med Wkly. 2007 Oct 20;137(41-42):573-80. doi: 2007/41/smw-11819.","doi: 2007/41/smw-11819.","Ulrich S,Speich R,Domenighetti G,Geiser T,Aubert JD,Rochat T,Huber L,Treder U,Fischler M.","Bosentan therapy for chronic thromboembolic pulmonary hypertension.  A national open label study assessing the effect of Bosentan on haemodynamics,exercise capacity,quality of life,safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study).","we performed an open-label national study to evaluate the effects of Bosentan on haemodynamics,exercise capacity,quality of life,safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (CTEPH). fifteen patients with CTEPH not eligible or waiting for surgery were enrolled. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included quality of life (measured by the Minnesota living with heart failure questionnaire,MLHF),6 minute walk distance (6MWD),World Health Organization (WHO) functional class,Borg dyspnoea scale,plasma endothelin,serum values of disease severity such as uric acid,N-terminal-pro brain natriuretic peptide (NTproBNP),C-reactive protein measured by a highly sensitive method (CRPs) and other serum and haemodynamic parameters. after six months of treatment with bosentan,the PVR decreased from 852 (319) to 657(249) dyn*s*m-5 (p = 0.02). Quality of life considerably improved from a mean total score of 48(14) to 35(17) (p = 0.003) with improvements in the physical (from 25(5) to 17(7)) and emotional (from 11(6) to 6(5)) subscores (p = 0.005 and 0.011),respectively. The 6MWD improved from 389(78) to 443(79) meters (p = 0.005). 4 patients (27%) improved and 11 patients (73%) maintained their WHO class with no deterioration during the six months of bosentan treatment (p = 0.02). Uric acid serum levels declined from 525(145) to 453(151) micromol/l (p = 0.006),NTproBNP and CRPs declined insignificantly. Endothelin serum levels increased from 4.3(1.5) to 5.9(2.2) pg/ml (p = 0.025). Patients tolerated the treatment well,and there were no severe adverse events or deaths. this open-label study suggests a beneficial effect of bosentan therapy not only on pulmonary haemodynamics,but also on quality of life and exercise capacity for patients with severe CTEPH.","Swiss Med Wkly. 2007 Oct 20;137(41-42):573-80.","Switzerland",2007,"CTEPH","Bosentan","BDI,MLHFQ",null,null,null,"Switzerland",null,"CTEPH","Bosentan",null,null,"BDI,MLHFQ","2005:2009"]
[57,"Furst D,Khanna D,Matucci-Cerinic M,Clements P,Steen V,Pope J,Merkel P,Foeldvari I,Seibold J,Pittrow D,Polisson R,Strand V. Systemic sclerosis - continuing progress in developing clinical measures of response. J Rheumatol. 2007 May;34(5):1194-200.",null,"Furst D,Khanna D,Matucci-Cerinic M,Clements P,Steen V,Pope J,Merkel P,Foeldvari I,Seibold J,Pittrow D,Polisson R,Strand V.","Systemic sclerosis - continuing progress in developing clinical measures of response.","Few randomized controlled trials (RCT) have shown a demonstrable treatment effect in systemic sclerosis (SSc),making it difficult to evaluate outcome measures in this disease indication. Results from recent RCT,including those evaluating cyclophosphamide for SSc interstitial lung disease and endothelin receptor antagonists for pulmonary hypertension,have allowed analysis of certain organ-specific endpoints using the OMERACT filter. An earlier metaanalysis established that skin score,measures of Raynaud's,pulmonary function tests,blood pressure,pain,Health Assessment Questionnaire,and Medical Outcomes Survey Short-Form 36 are validated outcome measures in SSc. At OMERACT 8,data regarding validation of high-resolution computed tomography of the lungs,6-minute walk test,and patient reported outcomes in SSc were presented. A Delphi exercise to develop consensus regarding a combined set of noninvasive measures for pulmonary arterial hypertension (PAH) is under way. Given the protean nature of this illness and its multiorgan system involvement,a composite responder index may be preferable. Another Delphi exercise is designed to develop consensus regarding a combined SSc response index to be validated in future RCT.","J Rheumatol. 2007 May;34(5):1194-200.","International",2007,"Systemic sclerosis","Any ERA","HAQ-DI,SF-36",null,null,null,"International",null,"Systemic sclerosis","Any ERA",null,null,"HAQ-DI,SF-36","2005:2009"]
[58,"Mok MY,Tsang PL,Lam YM,Lo Y,Wong WS,Lau CS. Bosentan use in systemic lupus erythematosus patients with pulmonary arterial hypertension. Lupus. 2007;16(4):279-85. doi: 10.1177/0961203307076509.","doi: 10.1177/0961203307076509.","Mok MY,Tsang PL,Lam YM,Lo Y,Wong WS,Lau CS.","Bosentan use in systemic lupus erythematosus patients with pulmonary arterial hypertension.","Pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE) is uncommon but is associated with poor survival. This study aimed to examine the long-term effects of bosentan,a dual endothelin-1 receptor antagonist,on symptomatology,haemodynamics and quality of life measures in SLE patients with symptomatic PAH. Four local patients had been followed up prospectively with pre-defined protocol during 12-months of bosentan treatment. Six minute walk distance (6MWD),NYHA functional class,Borg Dyspnoea Index (BDI) and SF-36 were measured at 0,3,6,9 and 12 months. Systolic pulmonary arterial pressure (PAP) was measured by transthoracic echocardiography at zero,six and 12 months. Clinical parameters were analysed,pooling data from other SLE patients reported in the literature (n = 4). Bosentan was found to result in significant improvement in 6MWD compared to baseline [+24.8 m,+26.2 m,+54 m and +62.7 m at three (P = 0.001),six (P = 0.001),nine (P = 0.24) and 12 (P = 0.01) months respectively]. A differential effect was found with greater response in patients with lower exercise capacity. This was accompanied by decrease in NYHA functional class,BDI,transient or sustained drop in systolic PAP and mild improvement in SF-36 domains including mental health,vitality,social function and general health. Significantly deranged liver function was found in one patient.","Lupus. 2007;16(4):279-85.","China",2007,"SLE","Bosentan","BDI,SF-36",null,null,null,"China",null,"SLE","Bosentan",null,null,"BDI,SF-36","2005:2009"]
[59,"Keogh AM,McNeil KD,Wlodarczyk J,Gabbay E,Williams TJ. Quality of life in pulmonary arterial hypertension: improvement and maintenance with bosentan. J Heart Lung Transplant. 2007 Feb;26(2):181-7. doi: 10.1016/j.healun.2006.11.009.","doi: 10.1016/j.healun.2006.11.009.","Keogh AM,McNeil KD,Wlodarczyk J,Gabbay E,Williams TJ.","Quality of life in pulmonary arterial hypertension: improvement and maintenance with bosentan.","Bosentan (an oral dual endothelin receptor antagonist) improves symptoms and cardiac hemodynamics and reduces clinical worsening in patients with pulmonary arterial hypertension (PAH). The VITAL study assessed the effect of bosentan on quality of life in patients with WHO Functional Class III or IV PAH (idiopathic or associated with connective tissue diseases). Quality of life was assessed prospectively using the MOS SF-36 and AQOL questionnaires. Baseline readings and scores at 3 and 6 months were collected,in addition to other efficacy and safety data. Among the 177 study patients,SF-36 scores were significantly improved at 3 months in the domains of physical functioning (27.3 to 34.8; p < 0.0001),role-physical (16.6 to 30.9; p < 0.0001),vitality (35.2 to 41.1; p = 0.0003),social functioning (48.0 to 58.6; p < 0.0001),mental health (64.2 to 72.0; p = 0.005) and role-emotional (44.8 to 58.1; p = 0.001). Improvements were seen in all etiologic sub-groups and were maintained in patients who remained on bosentan. An improvement in AQOL measures at 3 months was also noted for patients with baseline WHO Functional Class III. Bosentan significantly improves quality of life in patients with idiopathic PAH or PAH associated with connective tissue diseases.","J Heart Lung Transplant. 2007 Feb;26(2):181-7.","Australia",2007,"Any PAH","Bosentan","AQOL,SF-36",null,null,null,"Australia",null,"Any PAH","Bosentan",null,null,"AQOL,SF-36","2005:2009"]
[60,"Ibrahim R,Granton JT,Mehta S. An open-label,multicentre pilot study of bosentan in pulmonary arterial hypertension related to congenital heart disease. Can Respir J. 2006 Nov-Dec;13(8):415-20.",null,"Ibrahim R,Granton JT,Mehta S.","An open-label,multicentre pilot study of bosentan in pulmonary arterial hypertension related to congenital heart disease.","Bosentan has been shown to be a safe and efficacious treatment for idiopathic pulmonary arterial hypertension (PAH) and PAH associated with connective tissue disease. However,there are limited studies examining the benefits of bosentan in PAH associated with congenital heart disease (CHD). The aim of the present pilot study was to explore the safety and efficacy of bosentan in patients with PAH associated with CHD. In the present study,11 patients with PAH associated with CHD were enrolled to receive bosentan for a minimum of 16 weeks (62.5 mg twice a day for four weeks; thereafter 125 mg twice a day). Safety was assessed by monitoring adverse events,oxygen saturation,systemic blood pressure,pulse,complete blood count and liver function tests. Efficacy was assessed by the World Health Organization functional class,6 min walk test (6-MWT),modified Borg dyspnea index,echocardiography and the 36-item short form health survey. Ten patients completed the 16-week treatment period (one patient withdrew). Bosentan was not associated with a deterioration in resting oxygen saturation (83.0+/-4.6% at week 16 versus 81.9+/-6.1% at baseline; P = 0.402),or a deterioration in post-6-MWT oxygen saturation (70.1+/-10.9% at week 16 versus 68.7+/-15.1% at baseline; P = 0.747). Two patients experienced three serious adverse events. The distance walked in 6 min improved significantly by 28 m (P = 0.005) at week 16 compared with baseline,and the modified Borg dyspnea index also improved at week 16 compared with baseline (P = 0.050). The World Health Organization functional class improved from class III to class II for five of 10 patients (50%). Patients' self-rated quality of life (36-item short form health survey) demonstrated a nonsignificant improvement in each of the eight domains. Obtaining reliable echocardiographic measurements was difficult. Most echocardiographic parameters were only measurable on few patients,and none were measured on all patients,questioning the usefulness of echocardiography as a measuring tool for patients with complex CHD. Bosentan was not associated with worsening of resting oxygen saturation or exercise systemic oxygen saturation,suggesting its potential as a safe treatment option for patients with PAH associated with CHD. Improved 6-MWT and the modified Borg dyspnea index also suggested the possibility of bosentan as an efficacious treatment option for these patients. The results of the present study provide evidence for the need and feasibility of a large randomized,placebo-controlled clinical trial.","Can Respir J. 2006 Nov-Dec;13(8):415-20.","Canada",2006,"Congenital HD","Bosentan","BDI,SF-36",null,null,null,"Canada",null,"Congenital HD","Bosentan",null,null,"BDI,SF-36","2005:2009"]
[61,"Chua R,Keogh AM,Byth K,O'Loughlin A. Comparison and validation of three measures of quality of life in patients with pulmonary hypertension. Intern Med J. 2006 Nov;36(11):705-10. doi: 10.1111/j.1445-5994.2006.01169.x.","doi: 10.1111/j.1445-5994.2006.01169.x.","Chua R,Keogh AM,Byth K,O'Loughlin A.","Comparison and validation of three measures of quality of life in patients with pulmonary hypertension.","Pulmonary hypertension,when advanced,markedly limits exercise capacity,activities of daily living and quality of life (QoL). No measure of QoL has yet been validated for the assessment of pulmonary hypertension. The aim of the study was to compare the validity of the Minnesota Living with Heart Failure (MLwHF) questionnaire,the Short Form-36 (SF-36) questionnaire and the Australian Quality of Life (AQoL) measure for assessing pulmonary hypertension treatment. Eighty-three patients were enrolled in three studies of pulmonary hypertension treatment (treprostinil,bosentan and sildenafil). They were assessed at baseline and 3 months with the MLwHF questionnaire. Treprostinil and bosentan groups also had 6 and 12 months' data. Twenty-one patients in the sildenafil trial completed concurrently,the SF-36 and AQoL measures at baseline and 3 months. QoL scores were correlated with the 6-min walk test distance,New York Heart Association functional class and right heart catheter-derived haemodynamic parameters of the disease for all matching time points and for changes in scores and clinical measurements over time. The MLwHF and SF-36 scores correlated well with the 6-min walk test distance and New York Heart Association functional class,but did not correlate with haemodynamic measurements. MLwHF and SF-36 scores also correlated with the rate of change of the 6-min walk test distance and New York Heart Association functional class over time. The MLwHF questionnaire and SF-36 are useful tools for the assessment of QoL in pulmonary hypertension and may be useful in the ongoing evaluation of QoL in the treatment and study of pulmonary hypertension.","Intern Med J. 2006 Nov;36(11):705-10.","Australia",2006,"Any PAH","Bosentan,Sildenafil,Treprostanil","AQOL,MLHFQ,SF-36",null,null,null,"Australia",null,"Any PAH","Bosentan,Sildenafil,Treprostanil",null,null,"AQOL,MLHFQ,SF-36","2005:2009"]
[62,"Mereles D,Ehlken N,Kreuscher S,Ghofrani S,Hoeper MM,Halank M,Meyer FJ,Karger G,Buss J,Juenger J,Holzapfel N,Opitz C,Winkler J,Herth FF,Wilkens H,Katus HA,Olschewski H,Grünig E. Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation. 2006 Oct 3;114(14):1482-9. doi: 10.1161/CIRCULATIONAHA.106.618397. Epub 2006 Sep 18.","doi: 10.1161/CIRCULATIONAHA.106.618397. Epub 2006 Sep 18.","Mereles D,Ehlken N,Kreuscher S,Ghofrani S,Hoeper MM,Halank M,Meyer FJ,Karger G,Buss J,Juenger J,Holzapfel N,Opitz C,Winkler J,Herth FF,Wilkens H,Katus HA,Olschewski H,Grünig E.","Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension.","Pulmonary hypertension (PH) is associated with restricted physical capacity,limited quality of life,and a poor prognosis because of right heart failure. The present study is the first prospective randomized study to evaluate the effects of exercise and respiratory training in patients with severe symptomatic PH. Thirty patients with PH (21 women; mean age,50+/-13 years; mean pulmonary artery pressure,50+/-15 mm Hg; mean World Health Organization [WHO] class,2.9+/-0.5; pulmonary arterial hypertension,n=23; chronic thromboembolic PH,n=7) on stable disease-targeted medication were randomly assigned to a control (n=15) and a primary training (n=15) group. Medication remained unchanged during the study period. Primary end points were the changes from baseline to week 15 in the distance walked in 6 minutes and in scores of the Short Form Health Survey quality-of-life questionnaire. Changes in WHO functional class,Borg scale,and parameters of echocardiography and gas exchange also were assessed. At week 15,patients in the primary and secondary training groups had an improved 6-minute walking distance; the mean difference between the control and the primary training group was 111 m (95% confidence interval,65 to 139 m; P<0.001). Exercise training was well tolerated and improved scores of quality of life,WHO functional class,peak oxygen consumption,oxygen consumption at the anaerobic threshold,and achieved workload. Systolic pulmonary artery pressure values at rest did not change significantly after 15 weeks of exercise and respiratory training (from 61+/-18 to 54+/-18 mm Hg) within the training group. This study indicates that respiratory and physical training could be a promising adjunct to medical treatment in severe PH. The effects add to the beneficial results of modern medical treatment.","Circulation. 2006 Oct 3;114(14):1482-9.","Germany",2006,"Any PAH","Exercise","BDI",null,null,null,"Germany",null,"Any PAH","Exercise",null,null,"BDI","2005:2009"]
[63,"Cenedese E,Speich R,Dorschner L,Ulrich S,Maggiorini M,Jenni R,Fischler M. Measurement of quality of life in pulmonary hypertension and its significance. Eur Respir J. 2006 Oct;28(4):808-15. doi: 10.1183/09031936.06.00130405. Epub 2006 May 17.","doi: 10.1183/09031936.06.00130405. Epub 2006 May 17.","Cenedese E,Speich R,Dorschner L,Ulrich S,Maggiorini M,Jenni R,Fischler M.","Measurement of quality of life in pulmonary hypertension and its significance.","Until recently,assessment of patients with pulmonary hypertension has mainly relied on functional and haemodynamic parameters. Health-related quality of life (HRQOL),however,has become increasingly important in defining overall health status. The present study investigated the performance and clinical relevance of the Minnesota Living with Heart Failure (MLHF) questionnaire by prospectively studying 48 patients with either pulmonary arterial hypertension (n = 26) or chronic thromboembolic pulmonary hypertension (n = 22). The MLHF scores were correlated to various clinical and haemodynamic parameters. Prognostic outcome was evaluated by calculating the time taken to reach an adverse clinical event defined as death,lung transplantation or pulmonary endarterectomy. The reliability of test-re-test and internal consistency of this HRQOL tool was high. The MLHF score and its physical subscore correlated moderately to well with functional and haemodynamic parameters,except in the case of pulmonary artery pressures. Both scores significantly improved during vasodilator therapy. This figure was surpassed only by the New York Heart Association/World Health Organization functional class. A multivariate analysis of all variables revealed that the MLHF score was the sole factor predicting subsequent outcome. The Minnesota Living with Heart Failure questionnaire is highly reproducible,consistent,and a moderately valid and responsive tool in assessing health-related quality of life in pulmonary hypertension. Moreover,it is a significant predictor of outcome in these patients.","Eur Respir J. 2006 Oct;28(4):808-15.","Switzerland",2006,"Any PAH,CTEPH","None or unknown","MLHFQ",null,null,null,"Switzerland",null,"Any PAH,CTEPH","None or unknown",null,null,"MLHFQ","2005:2009"]
[64,"McKenna SP,Doughty N,Meads DM,Doward LC,Pepke-Zaba J. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension. Qual Life Res. 2006 Feb;15(1):103-15. doi: 10.1007/s11136-005-3513-4.","doi: 10.1007/s11136-005-3513-4.","McKenna SP,Doughty N,Meads DM,Doward LC,Pepke-Zaba J.","The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension.","No outcome measures specific to pulmonary hypertension (PH) currently exist. The aim of the study was to develop health-related quality of life (symptoms and functioning) scales and a quality of life scale that would allow comprehensive,accurate and valid patient-reported outcome assessment in clinical studies. The content of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was derived from qualitative interviews conducted with 35 patients. Item reduction was based on the analysis of responses to a postal survey (n=75) and patient interviews (n=15) designed to determine face and content validity. A final postal validation study (n=91) was performed to determine reproducibility and construct validity. The questionnaire was well received by participants who found it to be relevant,comprehensible and quick and easy to complete. Rasch and factor analyses were conducted to ensure unidimensionality of the final CAMPHOR scales; Overall symptoms (made up of Energy,Breathlessness and Mood subscales),Functioning and Quality of life. The CAMPHOR scales had good internal consistency (alpha=0.90-0.92) and reproducibility (test-retest correlations=0.86-0.92). They also exhibited convergent,divergent and known groups validity. The CAMPHOR is a valuable new instrument for assessing patient-reported outcome in PH clinical trials and routine practice.","Qual Life Res. 2006 Feb;15(1):103-15.","UK",2006,"Any PAH","None or unknown","CAMPHOR",null,null,null,"UK",null,"Any PAH","None or unknown",null,null,"CAMPHOR","2005:2009"]
[65,"Souza R,Jardim C,Martins B,Cortopassi F,Yaksic M,Rabelo R,Bogossian H. Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension. Curr Med Res Opin. 2005 Jun;21(6):907-11. doi: 10.1185/030079905X46232.","doi: 10.1185/030079905X46232.","Souza R,Jardim C,Martins B,Cortopassi F,Yaksic M,Rabelo R,Bogossian H.","Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension.","The aim of this study was to evaluate the effect of the oral dual ET(A)/ET(B) receptor antagonist bosentan on different surrogate markers in patients with pulmonary arterial hypertension (PAH). Prospective,open label,uncontrolled study in a University Hospital in Brazil. Fifteen PAH patients (11 females) with mean age of 40 +/- 11 years (5 in WHO functional class II,10 in class III). All patients were investigated at baseline and after 16 weeks of bosentan treatment. We used the following surrogate markers for patients' evaluation: 6-min walk test,quality of life questionnaire (Short Form SF-36) and N-terminal proBNP (B type natriuretic peptide) fraction levels in blood. Between the evaluation at baseline and week 16,the 6-min walk test distance changed from 396 +/- 135 to 434 +/- 137 m (p < 0.05). Each of the eight domains of the SF-36 was significantly improved. Mean NT-proBNP levels were decreased from a mean of 1670 pg/mL to 1010 pg/mL (p = 0.01). The study suggests that bosentan treatment results in the improvement of different kinds of surrogate markers independently of their specificity to reflect functional capacity,quality of life and myocardial stress. It is concluded that the combined use of these different markers may be an alternative endpoint for future short duration clinical trials.","Curr Med Res Opin. 2005 Jun;21(6):907-11.","Brazil",2005,"Any PAH","Bosentan","SF-36",null,null,null,"Brazil",null,"Any PAH","Bosentan",null,null,"SF-36","2005:2009"]
[66,"Shafazand S,Goldstein MK,Doyle RL,Hlatky MA,Gould MK. Health-related quality of life in patients with pulmonary arterial hypertension. Chest. 2004 Nov;126(5):1452-9. doi: 10.1378/chest.126.5.1452.","doi: 10.1378/chest.126.5.1452.","Shafazand S,Goldstein MK,Doyle RL,Hlatky MA,Gould MK.","Health-related quality of life in patients with pulmonary arterial hypertension.","Patients with pulmonary arterial hypertension (PAH) often present with dyspnea and severe functional limitations,but their health-related quality of life (HRQOL) has not been studied extensively. This study describes HRQOL in a cohort of patients with PAH. Cross-sectional study. A tertiary care,university hospital-based,pulmonary hypertension (PH) clinic. We studied HRQOL in 53 patients with PAH (mean age,47 years; median duration of disease,559 days). Eighty-three percent were women,53% received epoprostenol,and 72% reported moderate-to-severe functional limitations with a New York Heart Association class 3 or 4 at enrollment. We examined HRQOL by administering the Nottingham Health Profile,Congestive Heart Failure Questionnaire,and Hospital Anxiety and Depression Scale. We used the Visual Analog Scale and standard gamble (SG) techniques to measure preferences for current health (utilities). Compared with population norms,participants reported moderate-to-severe impairment in multiple domains of HRQOL,including physical mobility,emotional reaction,pain,energy,sleep,and social isolation. Mean SG utilities were 0.71,suggesting that,on average,participants were willing to accept a 29% risk of death in order to be cured of PH. PAH is a devastating condition that affects predominately young women in the prime of their life. Understanding HRQOL and preferences are important in the care and management of these patients. Compared with population norms,patients with PAH have substantial functional and emotional limitations that adversely affect their HRQOL.","Chest. 2004 Nov;126(5):1452-9.","USA",2004,"Any PAH","None or unknown","CHFQ,HADS,NHP,StGm,VAS",null,null,null,"USA",null,"Any PAH","None or unknown",null,null,"CHFQ,HADS,NHP,StGm,VAS","2000:2004"]
[67,"Hoeper MM,Oudiz RJ,Peacock A,Tapson VF,Haworth SG,Frost AE,Torbicki A. End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives. J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):48S-55S. doi: 10.1016/j.jacc.2004.02.010.","doi: 10.1016/j.jacc.2004.02.010.","Hoeper MM,Oudiz RJ,Peacock A,Tapson VF,Haworth SG,Frost AE,Torbicki A.","End points and clinical trial designs in pulmonary arterial hypertension: clinical and regulatory perspectives.","To date,randomized controlled clinical trials performed in pulmonary arterial hypertension (PAH) have been relatively short-term studies involving mainly patients with advanced disease. The primary end points in these trials have addressed exercise capacity,usually by using the 6-min walk test. Although this approach is still warranted in future trials assessing new treatments,it is likely that the focus will shift toward trials of longer duration,involving patients with less advanced disease,and that different drugs and drug-combination regimens will be compared. In such trials,it is possible that a composite of markers indicating clinical deterioration (e.g.,hospitalization for right heart failure,the requirement for the introduction of an alternative treatment,and predefined indicators of worsening exercise tolerance) may be more useful as primary end points. Quality of life will become a very important issue; however,appropriate quality-of-life questionnaires for PAH have yet to be developed. In addition,hemodynamics will likely remain valuable as secondary end points,but future clinical trials should include hemodynamics obtained both during exercise and at rest. Finally,cardiopulmonary exercise testing,echocardiographic studies,and biochemical parameters,such as brain natriuretic peptide or troponin T,may also prove useful as secondary end points in the future.","J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):48S-55S.","International",2004,"Any PAH","None or unknown","Unknown",null,null,null,"International",null,"Any PAH","None or unknown",null,null,"Unknown","2000:2004"]
[68,"Sastry BK,Narasimhan C,Reddy NK,Raju BS. Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized,placebo-controlled,double-blind,crossover study. J Am Coll Cardiol. 2004 Apr 7;43(7):1149-53. doi: 10.1016/j.jacc.2003.10.056.","doi: 10.1016/j.jacc.2003.10.056.","Sastry BK,Narasimhan C,Reddy NK,Raju BS.","Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized,placebo-controlled,double-blind,crossover study.","In a randomized,double-blind,crossover design,we compared the efficacy of sildenafil with placebo in patients with primary pulmonary hypertension (PPH). The primary end point was the change in exercise time on treadmill using the Naughton protocol. Secondary end points were change in cardiac index and pulmonary artery systolic pressure as assessed by Doppler echocardiography and quality of life (QOL) as assessed by a questionnaire. Primary pulmonary hypertension is a disorder with limited treatment options. Uncontrolled studies had shown sildenafil to be beneficial in the treatment of PPH. After initial clinical evaluation,including Doppler echocardiography and treadmill exercise test,patients were randomized to placebo or sildenafil with dosages ranging from 25 to 100 mg thrice daily on the basis of body weight. The evaluation was repeated after six weeks. Then patients were crossed over to alternate therapy. Final evaluation was performed after another six weeks of treatment. Twenty-two patients completed the study. Exercise time increased by 44% from 475 +/- 168 s at the end of placebo phase to 686 +/- 224 s at the end of sildenafil phase (p < 0.0001). With sildenafil,cardiac index improved from 2.80 +/- 0.9 l/m2 to 3.45 +/- 1.1 l/m(2) (p < 0.0001),whereas pulmonary artery systolic pressure decreased insignificantly from 105.23 +/- 17.82 mm Hg to 98.50 +/- 24.38 mm Hg. There was significant improvement in the dyspnea and fatigue components of the QOL questionnaire. During the placebo phase,one patient died and another had syncope. There were no serious side effects with sildenafil. Sildenafil significantly improves exercise tolerance,cardiac index,and QOL in patients with PPH.","J Am Coll Cardiol. 2004 Apr 7;43(7):1149-53.","India",2004,"Any PAH","Sildenafil","Unknown",null,null,null,"India",null,"Any PAH","Sildenafil",null,null,"Unknown","2000:2004"]
[69,"Mikhail GW,Prasad SK,Li W,Rogers P,Chester AH,Bayne S,Stephens D,Khan M,Gibbs JS,Evans TW,Mitchell A,Yacoub MH,Gatzoulis MA. Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects. Eur Heart J. 2004 Mar;25(5):431-6. doi: 10.1016/j.ehj.2004.01.013.","doi: 10.1016/j.ehj.2004.01.013.","Mikhail GW,Prasad SK,Li W,Rogers P,Chester AH,Bayne S,Stephens D,Khan M,Gibbs JS,Evans TW,Mitchell A,Yacoub MH,Gatzoulis MA.","Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects.","The treatment of patients with pulmonary arterial hypertension remains a challenge. We set out to investigate the use of sildenafil,a selective inhibitor of phosphodiesterase type 5,in patients with this disease. Ten patients (8 females,mean age 34.5+/-3.3 years) with pulmonary hypertension underwent right heart catheterisation with vasodilator testing using incremental doses of intravenous sildenafil without adverse events. All patients were subsequently commenced on oral sildenafil 50 mg t.d.s. Nine patients had repeat right heart catheterisation 3 months after the commencement of oral therapy. There was a significant reduction in mean pulmonary artery pressure (from 55.8+/-5.9 to 50.4+/-6.1 mmHg,p=0.038 ) and pulmonary vascular resistance (from 10.1+/-1.7 to 8.6+/-1.5 Wood units,p=0.009 ),and an increase in cardiac output (from 4.7+/-0.3 to 5.0+/-0.4 l/min,p=0.15 ). Furthermore,there was a significant increase in the 6-minute walk test,a mean of 112 m. In response to a quality-of-life questionnaire,patients indicated marked clinical improvement on sildenafil. Sildenafil was discontinued in 1 patient due to a transient visual disturbance. The only patient previously awaiting transplantation was removed from the active transplantation list. Sildenafil is well tolerated in its intravenous and oral forms and appears to improve both pulmonary haemodynamics and the clinical status of patients with pulmonary hypertension after 3 months of oral therapy.","Eur Heart J. 2004 Mar;25(5):431-6.","UK",2004,"Any PAH","Sildenafil","Unknown",null,null,null,"UK",null,"Any PAH","Sildenafil",null,null,"Unknown","2000:2004"]
[70,"Archibald CJ,Auger WR,Fedullo PF,Channick RN,Kerr KM,Jamieson SW,Kapelanski DP,Watt CN,Moser KM. Long-term outcome after pulmonary thromboendarterectomy. Am J Respir Crit Care Med. 1999 Aug;160(2):523-8. doi: 10.1164/ajrccm.160.2.9808109.","doi: 10.1164/ajrccm.160.2.9808109.","Archibald CJ,Auger WR,Fedullo PF,Channick RN,Kerr KM,Jamieson SW,Kapelanski DP,Watt CN,Moser KM.","Long-term outcome after pulmonary thromboendarterectomy.","This study evaluated long-term outcome of pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Survival,functional status,quality of life,health care utilization,and relationships between these parameters and postoperative pulmonary hemodynamics were assessed. Questionnaires were mailed to 420 patients who were more than 1 yr post-PTE; 308 responded (mean age,56 yr [range,19-89 yr]; mean years since PTE,3.3 [range,1- 16]). Survival after PTE was 75% at > 6 yr. After surgery,symptoms were markedly reduced. Median distance walked was 5,280 ft; 56 patients could walk \"indefinitely.\" Of the working population,62% of patients unemployed before PTE returned to work. Post-PTE patients scored several quality of life components of the Rand SF-36 slightly lower than reported normals but significantly higher than did pre-PTE patients. Ten percent of patients used oxygen. Ninety-three percent were in NYHA Class I or II. Disease-related hospitalizations/ER visits were minimal. A relationship was shown between 48 h postoperative pulmonary vascular resistance (PVR) and walking and stair-climbing ability,NYHA class,dyspnea scores,and the physical function and general health quality of life components. These data indicate that PTE offers most CTEPH patients substantial improvement in survival,function,and quality of life,with minimal disease-related health care utilization.","Am J Respir Crit Care Med. 1999 Aug;160(2):523-8.","USA",1999,"CTEPH","Surgery","Unknown",null,null,null,"USA",null,"CTEPH","Surgery",null,null,"Unknown","1960:1999"]

{"sheet":"Dashboard","index":6,"n_rows":36,"n_cols":51,"rows_kept":36,"cut":false,"hidden":true,"merged":[[65,2,65,4],[65,5,65,7],[60,2,60,4],[60,5,60,7],[61,2,61,4],[61,5,61,7],[62,2,62,4],[62,5,62,7],[63,2,63,4],[63,5,63,7],[64,2,64,4],[64,5,64,7],[55,2,55,4],[55,5,55,7],[56,2,56,4],[56,5,56,7],[57,2,57,4],[57,5,57,7],[58,2,58,4],[58,5,58,7],[59,2,59,4],[59,5,59,7],[50,2,50,4],[50,5,50,7],[51,2,51,4],[51,5,51,7],[52,2,52,4],[52,5,52,7],[53,2,53,4],[53,5,53,7],[54,2,54,4],[54,5,54,7],[45,2,45,4],[45,5,45,7],[46,2,46,4],[46,5,46,7],[47,2,47,4],[47,5,47,7],[48,2,48,4],[48,5,48,7],[49,2,49,4],[49,5,49,7],[40,2,40,4],[40,5,40,7],[41,2,41,4],[41,5,41,7],[42,2,42,4],[42,5,42,7],[43,2,43,4],[43,5,43,7],[44,2,44,4],[44,5,44,7],[1,1,1,4],[3,2,4,38],[16,40,16,46],[17,40,17,46],[18,40,18,46],[19,40,19,46],[20,40,20,46],[39,2,39,4],[39,5,39,7],[22,2,22,7],[24,2,24,4],[24,5,24,7],[25,2,25,4],[25,5,25,7],[26,2,26,4],[27,2,27,4],[27,5,27,7],[38,2,38,4],[38,5,38,7],[35,2,35,4],[35,5,35,7],[36,2,36,4],[36,5,36,7],[37,2,37,4],[37,5,37,7],[28,2,28,8],[29,2,29,8],[30,2,30,8],[31,2,31,8],[33,2,33,8],[34,2,34,8],[11,40,11,46],[12,40,12,46],[13,40,13,46],[14,40,14,46],[15,40,15,46],[21,40,21,46],[22,40,22,46],[23,40,23,46],[24,40,24,46],[28,9,28,28],[29,9,29,28],[30,9,30,28],[31,9,31,28],[32,9,32,28],[33,9,33,28],[34,9,34,28],[32,2,32,8],[26,11,26,12],[26,13,26,28],[26,5,26,8],[1,40,1,41],[1,44,1,46],[2,44,2,46],[5,40,5,46],[6,40,6,46],[7,40,7,46],[8,40,8,46],[9,40,9,46],[10,40,10,46]]}
[]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,4,null,null,null,"Year"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"SelectedYear","v":2015}]
[null,null,{"$f":"SelectedTitle","v":"Matura LA,Ventetuolo CE,Palevsky HI,Lederer DJ,Horn EM,Mathai SC,Pinder D,Archer-Chicko C,Bagiella E,Roberts KE,Tracy RP,Hassoun PM,Girgis RE,Kawut SM."}]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,6,0,null,null,null,null,null,null,1]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[]
[null,null,"PMID",null,null,{"$f":"SelectedPMID","v":"Any PAH"},null,null,null,null,null,"DOI",null,{"$f":"SelectedDOI","v":"Aspirin,Simvastatin"}]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null," "]
[null,null,"Locations",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null," "]
[null,null,"Interventions",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null," "]
[null,null,"Diseases",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null," ",null," ",null,null," "]
[null,null,"PRO tools"]
[null,null,"Sub-populations"]
[null,null,"Study types",null,null,null,null,null,null,"Case control",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null," "]
[null,null,"Study methodologies"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null," "]

{"sheet":"custom","index":7,"n_rows":27,"n_cols":15,"rows_kept":27,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNTA(B1:AB1)","v":14},{"$f":"Setup!V4","v":"C1"},{"$f":"Setup!V5","v":"C2"},{"$f":"Setup!V6","v":"C3"},{"$f":"Setup!V7","v":"C4"},{"$f":"Setup!V8","v":"C5"},{"$f":"Setup!V9","v":"C6"},{"$f":"Setup!V10","v":"C7"},{"$f":"Setup!V11","v":"C8"},{"$f":"Setup!V12","v":"C9"},{"$f":"Setup!V13","v":"C10"},"newCustom","newCustom","newCustom","newCustom"]
[{"$f":"IF(OFFSET($B$1,0,ROW()-2)=\"\",\"\",OFFSET($B$1,0,ROW()-2))","v":"C1"}]
[{"$f":"IF(OFFSET($B$1,0,ROW()-2)=\"\",\"\",OFFSET($B$1,0,ROW()-2))","v":"C2"}]
["C3"]
["C4"]
["C5"]
["C6"]
["C7"]
["C8"]
["C9"]
["C10"]
[{"$f":"COUNTA(B:B)-1","v":0}]
[{"$f":"COUNTA(C:C)-1","v":0}]
[{"$f":"COUNTA(D:D)-1","v":0}]
[{"$f":"COUNTA(E:E)-1","v":0}]
[{"$f":"COUNTA(F:F)-1","v":0}]
[{"$f":"COUNTA(G:G)-1","v":0}]
[{"$f":"COUNTA(H:H)-1","v":0}]
[{"$f":"COUNTA(I:I)-1","v":0}]
[{"$f":"COUNTA(J:J)-1","v":0}]
[{"$f":"COUNTA(K:K)-1","v":0}]
[""]
[""]
[""]
[""]
[""]
[""]

{"sheet":"Setup","index":8,"n_rows":304,"n_cols":100,"rows_kept":304,"cut":false,"hidden":true,"merged":[[5,1,5,3],[5,4,5,6],[1,1,1,6],[3,1,3,3],[3,4,3,6],[4,1,4,3],[4,4,4,6],[6,1,6,3],[6,4,6,6],[7,1,7,3],[7,4,7,6],[8,1,8,3],[8,4,8,6],[10,1,10,3],[10,4,10,6],[11,1,11,3],[11,4,11,6],[9,1,9,3],[9,4,9,6],[12,1,12,3],[12,4,12,6],[13,1,13,3],[13,4,13,6],[14,1,14,3],[14,4,14,6],[15,1,15,3],[15,4,15,6],[16,1,16,3],[16,4,16,6],[17,1,17,3],[17,4,17,6],[18,1,18,3],[18,4,18,6],[19,1,19,3],[19,4,19,6],[20,1,20,3],[20,4,20,6],[21,1,21,3],[21,4,21,6],[22,1,22,3],[22,4,22,6],[23,1,23,3],[23,4,23,6],[24,1,24,3],[24,4,24,6],[25,1,25,3],[25,4,25,6],[26,1,26,3],[26,4,26,6],[36,1,36,3],[36,4,36,6],[37,1,37,3],[37,4,37,6],[38,1,38,3],[38,4,38,6],[44,1,44,3],[44,4,44,6],[39,1,39,3],[39,4,39,6],[40,1,40,3],[40,4,40,6],[41,1,41,3],[41,4,41,6],[32,4,32,6],[27,1,27,3],[27,4,27,6],[28,1,28,3],[28,4,28,6],[29,1,29,3],[29,4,29,6],[1,51,1,52],[42,1,42,3],[42,4,42,6],[43,1,43,3],[43,4,43,6],[33,1,33,3],[33,4,33,6],[34,1,34,3],[34,4,34,6],[35,1,35,3],[35,4,35,6],[30,1,30,3],[30,4,30,6],[31,1,31,3],[31,4,31,6],[32,1,32,3],[22,11,25,17],[2,11,5,17],[1,20,8,20],[15,21,17,22],[8,11,10,17],[17,11,18,17]]}
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"COUNTA(T4:T474)","v":1},null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"COUNTA(BU3:BU21)","v":0},null,null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"OFFSET($CI$1,0,domainChoice)","v":31},{"$f":"COUNTA(CJ3:CJ513)","v":22},{"$f":"COUNTA(CK3:CK513)","v":19},9,31,0,0,0,null,null,null,null,{"$f":"ADDRESS(2,1,1,1,domainSheet)","v":"protoolCategories!$A$2"},{"$f":"INDIRECT(CU1)","v":"Unallocated"}]
[null,"Toggle age cut-offs",null,null,null,null,null,null,4,1,null,null,"Start here",null,null,null,null,null,null,2,"5. Select each custom domain in turn using cell T2. Then click 'Update tags' which imports the existing tagging into the custom domain definitions.",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Known headings",null,null,"Unrecognised headings",null,null,null,null,"This year =",{"$f":"YEAR(NOW())","v":2018},null,"Years","Cut","Selected cut state","Start","End",{"$f":"COUNTA(CF3:CF58)","v":5},{"$f":"OFFSET($CI$2,0,domainChoice)","v":"PRO tools"},"Locations","Interventions","Diseases","PRO tools","subPopulations","Study types","Study methodologies",null,null,null,null,"selected categories"]
[null,null,56,null,null,null,null,null,"Unallocated","AQ20",null,"1. To create a new map, enter the tagged citation table, with any custom domains into sheet \"Original\". Then click 'Initialise'.",null,null,null,null,null,null,null,null,null,"New names","Existing names",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Full citation",null,null,null,null,null,null,null,"Low year =",{"$f":"MIN($CF$3:$CF$60)","v":1960},false,1960,false,true,1960,1999,{"$f":"CF3&\":\"&CG3","v":"1960:1999"},"Locations","Australia","Acetazolamide","Any PAH","AQ20",null,null,null,null,null,null,null,{"$f":"OFFSET(INDIRECT($CU$1),ROW()-3,0)","v":"Unallocated"}]
[null,"From",null,null,"To",null,null,null,null,"AQ20",null,null,null,null,null,null,null,null,null,null,null,"C1","C1","Locations",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"DOI",null,null,null,null,null,null,{"$f":"OFFSET($BY$5,domainChoice,0)","v":"protoolCategories"},"High year =",{"$f":"MAX(CG3:$CG$60)","v":2018},false,1961,false,null,2000,2004,{"$f":"CF4&\":\"&CG4","v":"2000:2004"},"Interventions","Belgium","Ambrisentan","COPD","AQOL",null,null,null,null,null,null,null,{"$f":"OFFSET(INDIRECT($CU$1),ROW()-3,0)","v":"AQ20"}]
[null,{"$f":"IF(CF3=\"\",\"\",CF3)","v":1960},null,null,{"$f":"IF(CG3=\"\",\"\",CG3)","v":1999},null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C2","C2","Interventions",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Authors",null,null,null,null,null,null,null,null,null,false,1962,false,null,2005,2009,"2005:2009","Diseases","Brazil","Any ERA","CTEPH","BDI",null,null,null,null,null,null,null,"AQOL"]
[null,{"$f":"IF(CF4=\"\",\"\",CF4)","v":2000},null,null,{"$f":"IF(CG4=\"\",\"\",CG4)","v":2004},null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C3","C3","Diseases",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Title",null,null,null,null,null,null,"locationCategories",null,null,false,1963,false,null,2010,2014,"2010:2014","PRO tools","Canada","Any PDE-5I","Congenital HD","CAMPHOR",null,null,null,null,null,null,null,"BDI"]
[null,{"$f":"IF(CF5=\"\",\"\",CF5)","v":2005},null,null,{"$f":"IF(CG5=\"\",\"\",CG5)","v":2009},null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C4","C4","Sub-populations",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Abstract",null,null,null,null,null,null,"interventionCategories",null,null,false,1964,false,null,2015,2018,"2015:2018","subPopulations","China","Aspirin","HIV","CHFQ",null,null,null,null,null,null,null,"CAMPHOR"]
[null,{"$f":"IF(CF6=\"\",\"\",CF6)","v":2010},null,null,{"$f":"IF(CG6=\"\",\"\",CG6)","v":2014},null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C5","C5","PRO tools",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Citation",null,null,null,null,null,null,"diseaseCategories",null,null,false,1965,false,null,null,null,":","Study types","France","Bosentan","Interstitial lung disease","CHQ-PF50",null,null,null,null,null,null,null,"CHFQ"]
[null,{"$f":"IF(CF7=\"\",\"\",CF7)","v":2015},null,null,{"$f":"IF(CG7=\"\",\"\",CG7)","v":2018},null,null,null,null,null,null,"2. Select each domain in turn using cell I2 and use the buttons below to copy them over or redefine them.",null,null,null,null,null,null,null,null,null,"C6","C6","Study types",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Locations",null,null,null,null,null,null,"protoolCategories",null,null,false,1966,false,null,null,null,":","Study methodologies","Germany","Epoprostanol","SLE","D-12",null,null,null,null,null,null,null,"CHQ-PF50"]
[null,{"$f":"IF(CF8=\"\",\"\",CF8)","v":""},null,null,{"$f":"IF(CG8=\"\",\"\",CG8)","v":""},null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C7","C7","Study methodologies",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Year",null,null,null,null,null,null,"subpopulationCategories",null,null,false,1967,false,null,null,null,":",null,"Hungary","Exercise","Sarcoidosis","EQ-5D",null,null,null,null,null,null,null,"D-12"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C8","C8","Location categorised",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Diseases",null,null,null,null,null,null,"studytypeCategories",null,null,false,1968,false,null,null,null,":",null,"India","Iloprost","Systemic sclerosis","EmPHasis-10",null,null,null,null,null,null,null,"EQ-5D"]
[null,{"$f":"IF(CF10=\"\",\"\",CF10)","v":""},null,null,{"$f":"IF(CG10=\"\",\"\",CG10)","v":""},null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C9","C9","Intervention categorised",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Interventions",null,null,null,null,null,null,"studymethodCategories",null,null,false,1969,false,null,null,null,":",null,"International","Lung transplant",null,"EscSG",null,null,null,null,null,null,null,"EmPHasis-10"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C10","C10","Disease categorised",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"PROtools",null,null,null,null,null,null,null,null,null,false,1970,false,null,null,null,":",null,"Italy","Macitentan",null,"GAD-7",null,null,null,null,null,null,null,"EscSG"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Sub-populations categorised",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Subpopulations",null,null,null,null,null,null,null,null,null,false,1971,false,null,null,null,":",null,"Japan","None or unknown",null,"HADS",null,null,null,null,null,null,null,"GAD-7"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"PRO tool categorised",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Study types",null,null,null,null,null,null,null,null,null,false,1972,false,null,null,null,":",null,"Korea","Oxygen",null,"HAQ-DI",null,null,null,null,null,null,null,"HADS"]
[null,"",null,null,{"$f":"IF(CG14=\"\",\"\",CG14)","v":""},null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"6. When you are finished lock the workbook using the buttons below.",null,"Study type categorised",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Study methodologies",null,null,null,null,null,null,null,null,null,false,1973,false,null,null,null,":",null,"Netherlands","Sildenafil",null,"KCQ",null,null,null,null,null,null,null,"HAQ-DI"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Study methodology categorised",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"LocationsTags",null,null,null,null,null,null,null,null,null,false,1974,false,null,null,null,":",null,"New Zealand","Simvastatin",null,"MLHFQ",null,null,null,null,null,null,null,"KCQ"]
[null,"",null,null,"",null,null,null,null,null,null,"3. Use 'Classify domain shown\" to generate the mark-up of tags in the tables.",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"SubpopulationsTags",null,null,null,null,null,null,null,null,null,false,1975,false,null,null,null,":",null,"Portugal","Surgery",null,"NHP",null,null,null,null,null,null,null,"MLHFQ"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"DiseaseTags",null,null,null,null,null,null,null,null,null,false,1976,false,null,null,null,":",null,"Spain","Tadalafil",null,"PAH-SSS",null,null,null,null,null,null,null,"NHP"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"InterventionsTags",null,null,null,null,null,null,null,null,null,false,1977,false,null,null,null,":",null,"Switzerland","Treprostanil",null,"PAHSIS",null,null,null,null,null,null,null,"PAH-SSS"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"StudytypesTags",null,null,null,null,null,null,null,null,null,false,1978,false,null,null,null,":",null,"Turkey","Waon therapy",null,"PHQ-9",null,null,null,null,null,null,null,"PAHSIS"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"StudyMethodologyTags",null,null,null,null,null,null,null,null,null,false,1979,false,null,null,null,":",null,"UK",null,null,"POMS",null,null,null,null,null,null,null,"PHQ-9"]
[null,"",null,null,"",null,null,null,null,null,null,"4. Use the date drp-down in B3 to select cut-off dates and check the cut-point check-box in E3. When all date cut-offs have been declared, then click 'Classify dates\".",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"PROtoolTags",null,null,null,null,null,null,null,null,null,false,1980,false,null,null,null,":",null,"USA",null,null,"RSS",null,null,null,null,null,null,null,"POMS"]
[null,"",22,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"DateBand",null,null,null,null,null,null,null,null,null,false,1981,false,null,null,null,":",null,"Unknown",null,null,"SF-12",null,null,null,null,null,null,null,"RSS"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C1",null,null,null,null,null,null,null,null,null,false,1982,false,null,null,null,":",null,null,null,null,"SF-36",null,null,null,null,null,null,null,"SF-12"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C2",null,null,null,null,null,null,null,null,null,false,1983,false,null,null,null,":",null,null,null,null,"SF-6D",null,null,null,null,null,null,null,"SF-36"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C3",null,null,null,null,null,null,null,null,null,false,1984,false,null,null,null,":",null,null,null,null,"SGRQ",null,null,null,null,null,null,null,"SF-6D"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C4",null,null,null,null,null,null,null,null,null,false,1985,false,null,null,null,":",null,null,null,null,"StGm",null,null,null,null,null,null,null,"SGRQ"]
[null,null,null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C5",null,null,null,null,null,null,null,null,null,false,1986,false,null,null,null,":",null,null,null,null,"TSQM",null,null,null,null,null,null,null,"StGm"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C6",null,null,null,null,null,null,null,null,null,false,1987,false,null,null,null,":",null,null,null,null,"TTO",null,null,null,null,null,null,null,"TSQM"]
[null,null,null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C7",null,null,null,null,null,null,null,null,null,false,1988,false,null,null,null,":",null,null,null,null,"UCSD-SBQ",null,null,null,null,null,null,null,"TTO"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C8",null,null,null,null,null,null,null,null,null,false,1989,false,null,null,null,":",null,null,null,null,"Unknown",null,null,null,null,null,null,null,"UCSD-SBQ"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C9",null,null,null,null,null,null,null,null,null,false,1990,false,null,null,null,":",null,null,null,null,"VAS",null,null,null,null,null,null,null,"Unknown"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"C10",null,null,null,null,null,null,null,null,null,false,1991,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,"VAS"]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,1992,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,1993,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,1994,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,1995,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,1996,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,1997,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,1998,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,1999,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2000,true,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2001,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,"",null,null,"",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2002,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2003,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2004,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2005,true,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2006,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2007,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2008,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2009,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2010,true,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2011,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2012,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2013,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2014,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2015,true,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2016,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2017,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2018,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2019,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2020,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2021,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2022,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2023,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Well tolerated",null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2024,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2025,false,null,null,null,{"$f":"CF68&\":\"&CG68","v":":"},null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"OFFSET(INDIRECT($CU$1),ROW()-3,0)","v":""}]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2026,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,false,2027,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2028,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2029,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2030,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2031,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2032,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2033,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2034,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2035,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2036,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,2037,false,null,null,null,":",null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"OFFSET(INDIRECT($CU$1),ROW()-3,0)","v":""}]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"OFFSET(INDIRECT($CU$1),ROW()-3,0)","v":""}]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"OFFSET(INDIRECT($CU$1),ROW()-3,0)","v":""}]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
[null,null,null,null,null,null,null,null,null,""]

{"sheet":"studymethodCategories","index":9,"n_rows":503,"n_cols":2,"rows_kept":503,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNTA(B1:LT1)","v":1},"Unallocated"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Unallocated"}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]

{"sheet":"subpopulationCategories","index":10,"n_rows":503,"n_cols":2,"rows_kept":503,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNTA(B1:LT1)","v":1},"Unallocated"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Unallocated"}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]

{"sheet":"studytypeCategories","index":11,"n_rows":503,"n_cols":2,"rows_kept":503,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNTA(B1:LT1)","v":1},"Unallocated"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Unallocated"}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]

{"sheet":"diseaseCategories","index":12,"n_rows":503,"n_cols":11,"rows_kept":503,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNTA(B1:LT1)","v":10},"Unallocated","Any PAH","COPD","CTEPH","Congenital HD","HIV","Interstitial lung disease","SLE","Sarcoidosis","Systemic sclerosis"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Unallocated"},null,"Any PAH","COPD","CTEPH","Congenital HD","HIV","Interstitial lung disease","SLE","Sarcoidosis","Systemic sclerosis"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Any PAH"}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"COPD"}]
["CTEPH"]
["Congenital HD"]
["HIV"]
["Interstitial lung disease"]
["SLE"]
["Sarcoidosis"]
["Systemic sclerosis"]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]

{"sheet":"protoolCategories","index":13,"n_rows":503,"n_cols":33,"rows_kept":503,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNTA(B1:LT1)","v":32},"Unallocated","AQ20","AQOL","BDI","CAMPHOR","CHFQ","CHQ-PF50","D-12","EQ-5D","EmPHasis-10","EscSG","GAD-7","HADS","HAQ-DI","KCQ","MLHFQ","NHP","PAH-SSS","PAHSIS","PHQ-9","POMS","RSS","SF-12","SF-36","SF-6D","SGRQ","StGm","TSQM","TTO","UCSD-SBQ","Unknown","VAS"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Unallocated"},null,"AQ20","AQOL","BDI","CAMPHOR","CHFQ","CHQ-PF50","D-12","EQ-5D","EmPHasis-10","EscSG","GAD-7","HADS","HAQ-DI","KCQ","MLHFQ","NHP","PAH-SSS","PAHSIS","PHQ-9","POMS","RSS","SF-12","SF-36","SF-6D","SGRQ","StGm","TSQM","TTO","UCSD-SBQ","Unknown","VAS"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"AQ20"}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"AQOL"}]
["BDI"]
["CAMPHOR"]
["CHFQ"]
["CHQ-PF50"]
["D-12"]
["EQ-5D"]
["EmPHasis-10"]
["EscSG"]
["GAD-7"]
["HADS"]
["HAQ-DI"]
["KCQ"]
["MLHFQ"]
["NHP"]
["PAH-SSS"]
["PAHSIS"]
["PHQ-9"]
["POMS"]
["RSS"]
["SF-12"]
["SF-36"]
["SF-6D"]
["SGRQ"]
["StGm"]
["TSQM"]
["TTO"]
["UCSD-SBQ"]
["Unknown"]
["VAS"]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]

{"sheet":"locationCategories","index":14,"n_rows":503,"n_cols":24,"rows_kept":503,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNTA(B1:LT1)","v":23},"Unallocated","Australia","Belgium","Brazil","Canada","China","France","Germany","Hungary","India","International","Italy","Japan","Korea","Netherlands","New Zealand","Portugal","Spain","Switzerland","Turkey","UK","USA","Unknown"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Unallocated"},null,"Australia","Belgium","Brazil","Canada","China","France","Germany","Hungary","India","International","Italy","Japan","Korea","Netherlands","New Zealand","Portugal","Spain","Switzerland","Turkey","UK","USA","Unknown"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Australia"}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Belgium"}]
["Brazil"]
["Canada"]
["China"]
["France"]
["Germany"]
["Hungary"]
["India"]
["International"]
["Italy"]
["Japan"]
["Korea"]
["Netherlands"]
["New Zealand"]
["Portugal"]
["Spain"]
["Switzerland"]
["Turkey"]
["UK"]
["USA"]
["Unknown"]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]

{"sheet":"interventionCategories","index":15,"n_rows":503,"n_cols":21,"rows_kept":503,"cut":false,"hidden":true,"merged":[]}
[{"$f":"COUNTA(B1:LT1)","v":20},"Unallocated","Acetazolamide","Ambrisentan","Any ERA","Any PDE-5I","Aspirin","Bosentan","Epoprostanol","Exercise","Iloprost","Lung transplant","Macitentan","None or unknown","Oxygen","Sildenafil","Simvastatin","Surgery","Tadalafil","Treprostanil","Waon therapy"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Unallocated"},null,"Acetazolamide","Ambrisentan","Any ERA","Any PDE-5I","Aspirin","Bosentan","Epoprostanol","Exercise","Iloprost","Lung transplant","Macitentan","None or unknown","Oxygen","Sildenafil","Simvastatin","Surgery","Tadalafil","Treprostanil","Waon therapy"]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Acetazolamide"}]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":"Ambrisentan"}]
["Any ERA"]
["Any PDE-5I"]
["Aspirin"]
["Bosentan"]
["Epoprostanol"]
["Exercise"]
["Iloprost"]
["Lung transplant"]
["Macitentan"]
["None or unknown"]
["Oxygen"]
["Sildenafil"]
["Simvastatin"]
["Surgery"]
["Tadalafil"]
["Treprostanil"]
["Waon therapy"]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[{"$f":"IF(OFFSET($A$1,0,ROW()-1)=\"\",\"\",OFFSET($A$1,0,ROW()-1))","v":""}]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]
[""]