Suchergebnisse

IMPORTANCE: Interpreting randomized clinical trials (RCTs) and their clinical relevance is challenging when P values are either marginally above or below the P = .05 threshold. OBJECTIVE: To use the concept of reverse fragility index (RFI) to provide a measure of confidence in the neutrality of RCT results when assessed from the clinical perspective. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, a MEDLINE search was conducted for RCTs published from January 1, 2013, to December 31, 2018, in JAMA, the New England Journal of Medicine (NEJM), and The Lancet. Eligible studies were phase 3 and 4 trials with 1:1 randomization and statistically nonsignificant binary primary end points. Data analysis was performed from August 1, 2019, to August 31, 2019. EXPOSURES: Single vs multicenter enrollment, total number of events, private vs government funding, placebo vs active control, and time to event vs frequency data. MAIN OUTCOMES AND MEASURES: The primary outcome was the median RFI with interquartile range (IQR) at the P = .05 threshold. Secondary outcomes were the number of RCTs in which the number of participants lost to follow-up was greater than the RFI; the median RFI with IQR at different P value thresholds; the median reverse fragility quotient with IQR; and the correlation between sample sizes, number of events, and P values of the RCT and RFI. RESULTS: Of the 167 RCTs included, 76 (46%) were published in the NEJM, 50 (30%) in JAMA, and 41 (24%) in The Lancet. The median (IQR) sample size was 970 (470-3427) participants, and the median (IQR) number of events was 251 (105-570). The median (IQR) RFI at the P = .05 threshold was 8 (5-13). Fifty-seven RCTs (34%) had an RFI of 5 or lower, and in 68 RCTs (41%) the number of participants lost to follow-up was greater than the RFI. Trials with P values ranging from P = .06 to P = .10 had a median (IQR) RFI of 3 (2-4). When compared, median (IQR) RFIs were not statistically significant for single-center vs multicenter enrollment (5 [4-13] vs 8 [5-13]; ...

Insurance status affects access to care, which may affect health outcomes. The objective was to determine whether patients without insurance or with government-sponsored insurance had worse quality of care or in-hospital outcomes in acute ischemic stroke. Multivariable logistic regressions with generalized estimating equations stratified by age under or at least 65years were adjusted for patient demographics and comorbidities, presenting factors, and hospital characteristics to determine differences in in-hospital mortality and postdischarge destination. We included 589320 ischemic stroke patients treated at 1604 US hospitals participating in the Get With The Guidelines-Stroke program between 2012 and 2015. Uninsured patients with hypertension, high cholesterol, or diabetes mellitus were less likely to be taking appropriate control medications prior to stroke, to use an ambulance to arrive to the ED, or to arrive early after symptom onset. Even after adjustment, the uninsured were more likely than the privately insured to die in the hospital (<65years, OR 1.33 [95% CI 1.22-1.45]; ≥65years OR 1.54 [95% CI 1.34-1.75]), and among survivors, were less likely to go to inpatient rehab (<65 OR 0.63 [95% CI 0.6-0.67]; ≥65 OR 0.56 [95% CI 0.5-0.63]). In contrast, patients with Medicare and Medicaid were more likely to be discharged to a Skilled Nursing Facility (<65years OR 2.08 [CI 1.96-2.2]; OR 2.01 [95% CI 1.91-2.13]; ≥65years OR 1.1 [95% CI 1.07-1.13]; OR 1.41 [95% CI 1.35-1.46]). Preventative care prior to ischemic stroke, time to presentation for acute treatment, access to rehabilitation, and in-hospital mortality differ by patient insurance status.

BackgroundInsurance status affects access to care, which may affect health outcomes. The objective was to determine whether patients without insurance or with government-sponsored insurance had worse quality of care or in-hospital outcomes in acute ischemic stroke.Methods and resultsMultivariable logistic regressions with generalized estimating equations stratified by age under or at least 65years were adjusted for patient demographics and comorbidities, presenting factors, and hospital characteristics to determine differences in in-hospital mortality and postdischarge destination. We included 589320 ischemic stroke patients treated at 1604 US hospitals participating in the Get With The Guidelines-Stroke program between 2012 and 2015. Uninsured patients with hypertension, high cholesterol, or diabetes mellitus were less likely to be taking appropriate control medications prior to stroke, to use an ambulance to arrive to the ED, or to arrive early after symptom onset. Even after adjustment, the uninsured were more likely than the privately insured to die in the hospital (<65years, OR 1.33 [95% CI 1.22-1.45]; ≥65years OR 1.54 [95% CI 1.34-1.75]), and among survivors, were less likely to go to inpatient rehab (<65 OR 0.63 [95% CI 0.6-0.67]; ≥65 OR 0.56 [95% CI 0.5-0.63]). In contrast, patients with Medicare and Medicaid were more likely to be discharged to a Skilled Nursing Facility (<65years OR 2.08 [CI 1.96-2.2]; OR 2.01 [95% CI 1.91-2.13]; ≥65years OR 1.1 [95% CI 1.07-1.13]; OR 1.41 [95% CI 1.35-1.46]).ConclusionsPreventative care prior to ischemic stroke, time to presentation for acute treatment, access to rehabilitation, and in-hospital mortality differ by patient insurance status.

With the current landscape of approved therapies for heart failure (HF), there is a need to determine the role of a standard background therapy against which novel therapies are studied. The Heart Failure Collaboratory convened a multistakeholder group of clinical investigators, clinicians, patients, government representatives including U.S. Food and Drug Administration and National Institutes of Health participants, payers, and industry in March 2021 to discuss whether standardization of background drug therapy is necessary in clinical trials in patients with HF. The current paper summarizes the discussion and provides potential conceptual approaches, with a focus on therapies indicated for HF with reduced ejection fraction.