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84; 95% CI, 0.67-1.07) was associated with a similar risk of stroke/SE. Apixaban (HR, 0.60; 95% CI, 0.56-0.65) and dabigatran (HR, 0.78; 95% CI, 0.69-0.88) were associated with a lower risk of MB; rivaroxaban (HR, 1.02; 95% CI, 0.94-1.10) was associated with a similar risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of MB. Compared with rivaroxaban, dabigatran was associated with a lower risk of MB. CONCLUSION This study-the largest observational study to date of patients with NVAF and diabetes taking anticoagulants-found that NOACs were associated with variable rates of stroke/SE and MB compared with warfarin. TRIAL REGISTRATION clinicaltrials.gov Identifier NCT03087487. OBJECTIVE To identify differences between participants and nonparticipants in a survey of physical and psychosocial aspects of health among a population-based sample of patients with heart failure (HF). PATIENTS AND METHODS Residents from 11 Minnesota counties with a first-ever code for HF (International Classification of Diseases, Ninth Revision 428 and Tenth Revision I50) between January 1, 2013, and December 31, 2016, were identified. Participants completed a questionnaire by mail or telephone. Characteristics and outcomes were extracted from medical records and compared between participants and nonparticipants. Response rate was calculated using guidelines of the American Association for Public Opinion Research. The association between nonparticipation and outcomes was examined using Cox proportional hazards regression for death and Andersen-Gill modeling for hospitalizations. RESULTS Among 7911 patients, 3438 responded to the survey (American Association for Public Opinion Research response rate calculated using formula 2 = 43%). Lysipressin molecular weight Clinical and demographic differences between participants and nonparticipants were noted, particularly for education, marital status, and neuropsychiatric conditions. After a mean ± SD of 1.5±1.0 years after survey administration, 1575 deaths and 5857 hospitalizations occurred. Nonparticipation was associated with a 2-fold increased risk for death (hazard ratio, 2.29; 95% CI, 2.05-2.56) and 11% increased risk for hospitalization (hazard ratio, 1.11; 95% CI, 1.02-1.22) after adjusting for age, sex, time from HF diagnosis to index date, marital status, coronary disease, arrhythmia, hyperlipidemia, diabetes, cancer, chronic kidney disease, arthritis, osteoporosis, depression, and anxiety. CONCLUSION In a large survey of patients with HF, participation was associated with notable differences in clinical and demographic characteristics and outcomes. Examining the impact of participation is critical to draw inference from studies of patient-reported measures. OBJECTIVE To characterize what proportion of all randomized controlled trials (RCTs) among patients experiencing cardiac arrest find that an established practice is ineffective or harmful, that is, a medical reversal. METHODS We reviewed a database of all published RCTs of cardiac arrest patient populations between 1995 and 2014. Articles were classified on the basis of whether they tested a new or existing therapy and whether results were positive or negative. A reversal was defined as a negative RCT of an established practice. Further review and categorization were performed to confirm that reversals were supported by subsequent systematic review, as well as to identify the type of medical practice studied in each reversal. This study was conducted from October 2017 to June 17, 2019. RESULTS We reviewed 92 original articles, 76 of which could be conclusively categorized. Of these, 18 (24%) articles examined a new medical practice, whereas 58 (76%) tested an established practice. A total of 18 (24%) studies had positive findings, whereas 58 (76%) reached a negative conclusion. Of the 58 articles testing existing standard of care, 44 (76%) reversed that practice, whereas 14 (24%) reaffirmed it. CONCLUSION Reversal of cardiopulmonary resuscitation practices is widespread. This investigation sheds new light on low-value practices and patterns of medical research and suggests that novel resuscitation practices have low pretest probability and should be empirically tested with rigorous trials before implementation. OBJECTIVE To investigate whether the inverse associations of cardiorespiratory fitness (CRF) with all-cause and cardiovascular mortality in the general population vary among individuals who are at different levels of pretest risk. PATIENTS AND METHODS Cardiorespiratory fitness was assessed through submaximal bicycle tests in 58,892 participants aged 40 to 69 years who completed baseline questionnaires between January 1, 2006, and December 31, 2010, in the UK Biobank Prospective Study. Participants were categorized into risk categories, which determined allocation to an individualized bicycle protocol. The groups at minimal risk (category 1), small risk (category 2), and medium risk (category 3) were tested at 50%, 35% of the predicted maximal workload, and constant level, respectively. We investigated associations of CRF with mortality across different levels of pretest risk and determined whether CRF improves risk prediction. RESULTS During a median follow-up of 5.8 years, 936 deaths occurred. Cardiorespiratory fitness was linearly associated with mortality risk. Comparing extreme fifths of CRF, the multivariable-adjusted hazard ratios (95% CIs) for mortality were 0.63 (0.52-0.77), 0.54 (0.36-0.82), 0.81 (0.46-1.43), and 0.58 (0.48-0.69) in categories 1, 2, and 3 and overall population, respectively. The addition of CRF to a 5-year mortality risk score containing established risk factors was associated with a C-index change (0.0012; P=.49), integrated discrimination improvement (0.0005; P less then .001), net reclassification improvement (+0.0361; P=.005), and improved goodness of fit (likelihood ratio test, P less then .001). Differences in 5-year survival were more pronounced across levels of age, smoking status, and sex. CONCLUSION Cardiorespiratory fitness, assessed by submaximal exercise testing, improves mortality risk prediction beyond conventional risk factors and its prognostic relevance varies across cardiovascular risk levels.
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