The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension.
ABSTRACT: Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension (PAH), the minimal important difference (MID) of the 6-minute walk test (6MWT) has not been well defined for this population of patients.To estimate the MID in the 6MWT in patients with PAH.Study subjects from the clinical trial of tadalafil in PAH, a 16-week, parallel-group, randomized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist, were eligible. 6MWT was performed using a standardized protocol. Distributional and anchor-based methods were used to estimate the MID; the latter method used the Physical Component Summary Score (PCS) of the Medical Outcomes Study 36-item short form (SF-36).Four hundred five subjects were analyzed. Domains of the SF-36 were weakly to modestly associated with 6MWT. Change in the PCS of the SF-36 was most strongly associated with change in 6MWT (r = 0.40, P < 0.001) and thus was selected as the anchor for subsequent anchor-based analyses. Distributional analyses yielded estimates of the MID ranging from 25.1 to 38.5 m, whereas anchor-based analyses yielded an estimate of 38.6 m.Using both distributional and anchor-based methods, the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implications for (1) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy, and (2) sample size calculations for future study design.
Project description:Pulmonary Mycobacterium avium complex (pMAC) disease is a chronic, slowly progressive disease. The aim of the present study was to determine the association of six-minute walk test (6MWT) parameters with pulmonary function and the health-related quality of life (HRQL) in patients with pMAC disease.This cross-sectional study included adult patients with pMAC and was conducted at Keio University Hospital. We investigated the relationship of 6MWT parameters with clinical parameters, including pulmonary function, and HRQL, which was assessed using the 36-Item Short Form Health Survey (SF-36) and St. George's Respiratory Questionnaire (SGRQ).In total, 103 consecutive patients with pMAC participated in 6MWT (median age, 64 years; 80 women) and completed SF-36 and SGRQ. The six-minute walk distance (6MWD) showed significant negative and positive correlations with all SGRQ domain scores [??=?(-?0.54)-(-?0.32)] and the physical component summary (PCS) score (??=?0.39) in SF-36, respectively; the opposite was observed for the final Borg scale (FBS) score (all SGRQ scores, ??=?0.34-0.58; PCS score, ??=?-?0.50). The distance-saturation product showed significant negative and positive correlations with all SGRQ scores [??=?(-?0.29)-(-?0.55)] and the PCS score (??=?0.40), respectively. Multivariate analysis revealed that 6MWD and the FBS score were significant predictors of HRQL.Our findings suggest that 6MWD and the FBS score are useful parameters for evaluating HRQL in patients with pMAC. Further studies should investigate the impact of 6WMT parameters on disease progression, treatment responses, and prognosis.
Project description:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a rare disease with a median survival of 3-5?years after diagnosis with limited treatment options. The aim of this study is to assess the psychometric characteristics of the Short Form 36 Health Status Questionnaire (SF-36) in IPF and to provide disease specific minimally important differences (MID). METHODS:Data source was the European IPF Registry (eurIPFreg). The psychometric properties of the SF-36 version 2 were evaluated based on objective clinical measures as well as subjective perception. We analysed acceptance, feasibility, discrimination ability, construct and criterion validity, responsiveness and test-retest-reliability. MIDs were estimated via distribution and anchor-based approaches. RESULTS:The study population included 258 individuals (73.3% male; mean age 67.3?years, SD 10.7). Of them 75.2% (194 individuals) had no missing item. The distribution of several items was skewed, although floor effect was acceptable. Physical component score (PCS) correlated significantly and moderately with several anchors, whereas the correlations of mental component score (MCS) and anchors were only small. The tests showed mainly significant lower HRQL in individuals with long-term oxygen therapy. Analyses in stable individuals did not show significant changes of HRQL except for one dimension and anchor. Individuals with relevant changes of the health status based on the anchors had significant changes in all SF-36 dimensions and summary scales except for the dimension PAIN. PCS and MCS had mean MIDs of five and six, respectively. Mean MIDs of the dimensions ranged from seven to 21. CONCLUSION:It seems that the SF-36 is a valid instrument to measure HRQL in IPF and so can be used in RCTs or individual monitoring of disease. Nevertheless, the additional evaluation of longitudinal aspects and MIDs can be recommended to further analyse these factors. Our findings have a great potential impact on the evaluation of IPF patients. TRIAL REGISTRATION:The eurIPFreg and eurIPFbank are listed in https://clinicaltrials.gov ( NCT02951416 ).
Project description: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.
Project description:BACKGROUND:Pompe disease is a rare, progressive metabolic myopathy. The aim of this study is to investigate the associations of physical outcomes with patient-reported outcome measures (PROMs) in late-onset Pompe disease. METHODS:We included 121 Dutch adult patients with Pompe disease. Physical outcomes comprised muscle strength (manual muscle testing using Medical Research Council [MRC] grading, hand-held dynamometry [HHD]), walking ability (6-min walk test [6MWT]), and pulmonary function (forced vital capacity [FVC] in upright and supine positions). PROMs comprised quality of life (Short Form 36 health survey [SF-36]), participation (Rotterdam Handicap Scale [RHS]) and daily-life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale). Analyses were cross-sectional: the time-point before, and closest to, start of Enzyme Replacement Therapy was chosen. Associations between PROMs and physical outcomes were investigated using linear regression models. RESULTS:RHS and R-PAct scores were better in patients with higher FVC supine and upright, HHD, MRC and 6MWT scores, accounting for the effect of sex, disease duration, use of wheelchair and ventilator support. While the SF-36 Physical Component Summary (PCS) was correlated positively with FVC upright, HHD, MRC and 6MWT scores, there was no significant relationship between the SF-36 Mental Component Summary (MCS) and any of the physical outcomes. CONCLUSIONS:Participation, daily-life activities, and the physical component of quality of life of adult Pompe patients are positively correlated to physical outcomes. This work serves as a first step towards assessing how changes over time in physical outcomes are related to changes in PROMs, and to define the minimal change in physical outcomes required to make an important difference for the patient.
Project description:<h4>Background</h4>This systematic review and meta-analysis aimed to determine the effectiveness of systematic early mobilization in improving muscle strength and physical function in mechanically ventilated intensive care unit (ICU) patients.<h4>Methods</h4>We conducted a two-stage systematic literature search in MEDLINE, EMBASE and the Cochrane Library until January 2019 for randomized controlled trials (RCTs) examining the effects of early mobilization initiated within 7 days after ICU admission compared with late mobilization, standard early mobilization or no mobilization. Priority outcomes were Medical Research Council Sum Score (MRC-SS), incidence of ICU-acquired weakness (ICUAW), 6-min walk test (6MWT), proportion of patients reaching independence, time needed until walking, SF-36 Physical Function Domain Score (PFS) and SF-36 Physical Health Component Score (PCS). Meta-analysis was conducted where sufficient comparable evidence was available. We evaluated the certainty of evidence according to the GRADE approach.<h4>Results</h4>We identified 12 eligible RCTs contributing data from 1304 participants. Two RCTs were categorized as comparing systematic early with late mobilization, nine with standard early mobilization and one with no mobilization. We found evidence for a benefit of systematic early mobilization compared to late mobilization for SF-36 PFS (MD 12.3; 95% CI 3.9-20.8) and PCS (MD 3.4; 95% CI 0.01-6.8), as well as on the proportion of patients reaching independence and the time needed to walking, but not for incidence of ICUAW (RR 0.62; 95% CI 0.38-1.03) or MRC-SS. For systematic early compared to standard early mobilization, we found no statistically significant benefit on MRC-SS (MD 5.8; 95% CI -?1.4 to 13.0), incidence of ICUAW (RR 0.90; 95% CI 0.63-1.27), SF-36 PFS (MD 8.1; 95% CI -?15.3 to 31.4) or PCS (MD -?2.4; 95% CI -?6.1 to 1.3) or other priority outcomes except for change in 6MWT from baseline. Generally, effects appeared stronger for systematic early compared to late mobilization than to standard early mobilization. We judged the certainty of evidence for all outcomes as very low to low.<h4>Conclusion</h4>The evidence regarding a benefit of systematic early mobilization remained inconclusive. However, our findings indicate that the larger the difference in the timing between the intervention and the comparator, the more likely an RCT is to find a benefit for early mobilization.<h4>Study registration</h4>PROSPERO (CRD42019122555).
Project description:OBJECTIVE: To determine the minimal important difference (MID) in generic and prostate-specific health-related quality of life (HRQoL) using distribution- and anchor-based methods. STUDY DESIGN AND SETTING: Prospective cohort study of 602 newly diagnosed prostate cancer patients recruited from an urban academic hospital and a Veterans Administration hospital. Participants completed generic (SF-36) and prostate-specific HRQoL surveys at baseline and at 3, 6, 12, and 24 months posttreatment. Anchor-based and distribution-based methods were used to develop MID estimates. We compared the proportion of participants returning to baseline based on MID estimates from the two methods. RESULTS: MID estimates derived from combining distribution- and anchor-based methods for the SF-36 subscales are physical function = 7, role physical = 14, role emotional = 12, vitality = 9, mental health = 6, social function = 9, bodily pain = 9, and general health = 8; and for the prostate-specific scales are urinary function = 8, bowel function = 7, sexual function = 8, urinary bother = 9, bowel bother = 8, and sexual bother = 11. Proportions of participants returning to baseline values corresponding to MID estimates from the two methods were comparable. CONCLUSIONS: This is the first study to assess the MID for generic and prostate-specific HRQoL using anchor-based and distribution-based methods. Although variation exists in the MID estimates derived from these two methods, the recovery patterns corresponding to these estimates were comparable.
Project description: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.
Project description:<h4>Rationale</h4>Health-related quality of life (HRQL) is an important outcome in drug trials. Little is known about how the Short Form-36 (SF-36) and Saint George's Respiratory Questionnaire (SGRQ) perform in idiopathic pulmonary fibrosis (IPF).<h4>Objectives</h4>To examine the validity of the SF-36 and SGRQ and to determine scores from each that would constitute a minimum important difference (MID).<h4>Methods</h4>We analyzed data from a recently completed trial that enrolled subjects with well-defined IPF who completed the SF-36, SGRQ, and Baseline/Transition Dyspnea Index at baseline and six months. We compared mean changes in HRQL scores between groups of subjects whose disease severity changed over six months according to clinical anchors (FVC, DLCO, and dyspnea). We estimated the MID for each domain by using both anchor- and distribution-based approaches.<h4>Main results</h4>Results supported the validity of the SF-36 and SGRQ for use in longitudinal studies. Mean changes in domain scores differed significantly between subjects whose clinical status improved and those whose clinical status declined according to the anchors. MID estimates for the SF-36 ranged from 2-4 points and from 5-8 points for the SGRQ.<h4>Conclusion</h4>In IPF, the SF-36 and SGRQ possess reasonable validity for differentiating subjects whose disease severity changes over time. More studies are needed to continue the validation process, to refine estimates of the MIDs for the SF-36 or SGRQ, and to determine if a disease-specific instrument will perform better than either of these.
Project description:To compare the Short Musculoskeletal Function Assessment Dysfunction Index (SMFA DI) and the Short Form-36 Physical Component Summary (SF-36 PCS) scores among patients undergoing operative management of tibial fractures.Between July 2000 and September 2005, we enrolled 1,319 skeletally mature patients with open or closed fractures of the tibial shaft that were managed with intramedullary nailing. Patients were asked to complete the SMFA Questionnaire and SF-36 at discharge and 3, 6, and 12 months post-surgical fixation.The SMFA DI and SF-36 PCS scores were highly correlated at 3, 6, and 12 months post-surgical fixation. The difference in the mean standardized change scores for SMFA DI and SF-36 PCS, from 3 to 12 months post-surgical fixation, was not statistically significant. Both the SMFA DI and SF-36 PCS scores were able to discriminate between healed and nonhealed tibial fractures at 3, 6, and 12 months postsurgery.In patients with tibial-shaft fractures, the SMFA DI offered no significant advantages over the SF-36 PCS score. These results, along with the usefulness of SF-36 for comparing populations, recommend the SF-36 for assessing physical function in studies of patients with tibial fractures.
Project description:We analyzed the relationship between performance on the 6-min walk test (6MWT) and health-related quality of life (HRQoL) in older subjects. Our secondary aim was to determine the distance to be completed on the 6MWT for the subject to achieve a score of 50 on the Short Form (36) Health Survey (SF-36). Associations were tested using linear correlation and multivariate linear regression. Participants were 130 healthy older individuals. The predictive performance of the 6MWT based on an SF-36 score of 50 was assessed using a receiver operating characteristic curve and its area under curve (AUC). Associations were observed between physical functioning, role-emotional, social functioning, vitality, general health score, and 6MWT performance in women, after adjusting for confounding variables (coefficients: 0.57, 0.38, 0.40, and 0.46, respectively; p < 0.05). No association was found for men. The distance for the 6MWT to predict an SF-36 score of 50 was 481 m for men in the physical functioning (AUC: 0.79) and role-physical (AUC: 0.84) domains, and 420 m for women in role-emotional (AUC: 0.75), role-physical (AUC: 0.80), and general health (AUC: 0.80) domains. Our results indicate that superior 6MWT performance may be associated with better HRQoL in several domains in only healthy older women. No association between 6MWT performance and role-emotional, mental health, or vitality domains was found. We suggest that a score of 50 is represented by a 6MWT distance of 481 m for men and 420 m for women, at least in the role-physical domain.