Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction

Aims: In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex. Methods and results: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62–0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09–1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76–1.03 for females, SMR 1.43; 95% CI 1.33–1.53 for males). Conclusion: Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries

Reproducibility of onset and recovery oxygen uptake kinetics in moderately impaired patients with chronic heart failure

Oxygen (O2) kinetics reflect the ability to adapt to or recover from exercise that is indicative of daily life. In patients with chronic heart failure (CHF), parameters of O2 kinetics have shown to be useful for clinical purposes like grading of functional impairment and assessment of prognosis. This study compared the goodness of fit and reproducibility of previously described methods to assess O2 kinetics in these patients. Nineteen CHF patients, New York Heart Association class II–III, performed two constant-load tests on a cycle ergometer at 50% of the maximum workload. Time constants of O2 onset- and recovery kinetics (τ) were calculated by mono-exponential modeling with four different sampling intervals (5 and 10 s, 5 and 8 breaths). The goodness of fit was expressed as the coefficient of determination (R2). Onset kinetics were also evaluated by the mean response time (MRT). Considering O2 onset kinetics, τ showed a significant inverse correlation with peak- \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} \ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{2} \end{document} (R = −0.88, using 10 s sampling intervals). The limits of agreement of both τ and MRT, however, were not clinically acceptable. O2 recovery kinetics yielded better reproducibility and goodness of fit. Using the most optimal sampling interval (5 breaths), a change of at least 13 s in τ is needed to exceed normal test-to-test variations. In conclusion, O2 recovery kinetics are more reproducible for clinical purposes than O2 onset kinetics in moderately impaired patients with CHF. It should be recognized that this observation cannot be assumed to be generalizable to more severely impaired CHF patients

Performance measures of the specialty referral process: a systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>Performance of specialty referrals is coming under scrutiny, but a lack of identifiable measures impedes measurement efforts. The objective of this study was to systematically review the literature to identify published measures that assess specialty referrals.</p> <p>Methods</p> <p>We performed a systematic review of the literature for measures of specialty referral. Searches were made of MEDLINE and HealthSTAR databases, references of eligible papers, and citations provided by content experts. Measures were eligible if they were published from January 1973 to June 2009, reported on validity and/or reliability of the measure, and were applicable to Organization for Economic Cooperation and Development healthcare systems. We classified measures according to a conceptual framework, which underwent content validation with an expert panel.</p> <p>Results</p> <p>We identified 2,964 potentially eligible papers. After abstract and full-text review, we selected 214 papers containing 244 measures. Most measures were applied in adults (57%), assessed structural elements of the referral process (60%), and collected data via survey (62%). Measures were classified into non-mutually exclusive domains: need for specialty care (N = 14), referral initiation (N = 73), entry into specialty care (N = 53), coordination (N = 60), referral type (N = 3), clinical tasks (N = 19), resource use (N = 13), quality (N = 57), and outcomes (N = 9).</p> <p>Conclusions</p> <p>Published measures are available to assess the specialty referral process, although some domains are limited. Because many of these measures have been not been extensively validated in general populations, assess limited aspects of the referral process, and require new data collection, their applicability and preference in assessment of the specialty referral process is needed.</p