IMPORTANCE Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited.OBJECTIVE To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis. DATA SOURCES MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo.DATA EXTRACTION AND SYNTHESIS Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND MEASURESProportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.RESULTS Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI,; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, −10.20 to −7.42 kg); liraglutide, 5.3 kg (95% CrI, −6.06 to −4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, −5.94 to −3.96 kg); lorcaserin, 3.2 kg (95% CrI, −3.97 to −2.46 kg); and orlistat, 2.6 kg (95% CrI, −3.04 to −2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI,) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.CONCLUSIONS AND RELEVANCE Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.

Importance Publicly available datasets hold much potential, but their unique design may require specific analytic approaches. Objective To determine adherence to appropriate research practices for a frequently used large public database, the National Inpatient Sample (NIS) of the Agency for Healthcare Research and Quality (AHRQ). Design, Setting and Participants In this observational study, of the 1082 studies published using the NIS from January 2015 – December 2016, a representative sample of 120 studies was systematically evaluated for adherence to practices required by AHRQ for design and conduct of research using the NIS. Exposure None Main Outcomes All studies were evaluated on 7 required research practices based on AHRQ’s recommendations, compiled under 3 domains: (A) data interpretation (interpreting data as hospitalization records rather than unique patients); (B) research design (avoiding use in performing state-, hospital-, and physician-level assessments where inappropriate; not using non-specific administrative secondary diagnosis codes to study in-hospital events), and (C) data analysis (accounting for complex survey design of the NIS and changes in data structure over time). Results Of 120 published studies, 85% (n=102) did not adhere to ≥1 required practices and 62% (n=74) did not adhere to ≥2 required practices. An estimated 925 (95% CI 852–998) and 696 (95% CI 596–796) NIS publications had violations of ≥1 and ≥2 required practices, respectively. A total of 79 sampled studies, representing 68.3% (95% CI 59.3–77.3) of the 1082 NIS studies, did not account for the effects of sampling error, clustering, and stratification; 62 (54.4%, 95% CI 44.7–64.0) extrapolated non-specific secondary diagnoses to infer in-hospital events; 45 (40.4%, 95% CI 30.9–50.0) miscategorized hospitalizations as individual patients; 10 (7.1%, 95% CI 2.1–12.1) performed state-level analyses; and 3 (2.9%, 95% CI 0.0–6.2) reported physician-level volume estimates. Of 27 studies (weighted: 218 studies, 95% CI 134–303) spanning periods of major changes in the data structure of the NIS, 21 (79.7%, 95% CI 62.5–97.0) did not account for the changes. Among the 24 studies published in journals with an impact factor ≥10, 16 (67%) and 9 (38%) did not adhere to ≥1 and ≥2 practices, respectively. Conclusions and Relevance In this study of 120 recent publications that used data from the NIS, the majority did not adhere to required practices. Further research is needed to identify strategies to improve the quality of research using the NIS and assess whether there are similar problems with use of other publicly available data sets.

Background: Obesity may contribute to adverse outcomes in coronavirus disease 2019 (COVID-19). However, studies of large, broadly generalizable patient populations are lacking, and the effect of body mass index (BMI) on COVID-19 outcomes— particularly in younger adults—remains uncertain. Methods: We analyzed data from patients hospitalized with COVID-19 at 88 US hospitals enrolled in the American Heart Association’s COVID-19 Cardiovascular Disease Registry with data collection through July 22, 2020. BMI was stratified by World Health Organization obesity class, with normal weight prespecified as the reference group. Results: Obesity, and, in particular, class III obesity, was overrepresented in the registry in comparison with the US population, with the largest differences among adults ≤50 years. Among 7606 patients, in-hospital death or mechanical ventilation occurred in 2109 (27.7%), in-hospital death in 1302 (17.1%), and mechanical ventilation in 1602 (21.1%). After multivariable adjustment, classes I to III obesity were associated with higher risks of in-hospital death or mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09–1.51], 1.57 [1.29–1.91], 1.80 [1.47–2.20], respectively), and class III obesity was associated with a higher risk of in-hospital death (hazard ratio, 1.26 [95% CI, 1.00–1.58]). Overweight and class I to III obese individuals were at higher risk for mechanical ventilation (odds ratio, 1.28 [95% CI, 1.09–1.51], 1.54 [1.29–1.84], 1.88 [1.52–2.32], and 2.08 [1.68–2.58], respectively). Significant BMI by age interactions were seen for all primary end points ( P -interaction<0.05 for each), such that the association of BMI with death or mechanical ventilation was strongest in adults ≤50 years, intermediate in adults 51 to 70 years, and weakest in adults >70 years. Severe obesity (BMI ≥40 kg/m 2 ) was associated with an increased risk of in-hospital death only in those ≤50 years (hazard ratio, 1.36 [1.01–1.84]). In adjusted analyses, higher BMI was associated with dialysis initiation and with venous thromboembolism but not with major adverse cardiac events. Conclusions: Obese patients are more likely to be hospitalized with COVID-19, and are at higher risk of in-hospital death or mechanical ventilation, in particular, if young (age ≤50 years). Obese patients are also at higher risk for venous thromboembolism and dialysis. These observations support clear public health messaging and rigorous adherence to COVID-19 prevention strategies in all obese individuals regardless of age.

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ObjectiveTo examine the effect of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guidelines on the prevalence of hypertension and eligibility for initiation and intensification of treatment in nationally representative populations from the United States and China.DesignObservational assessment of nationally representative data.SettingUS National Health and Nutrition Examination Survey (NHANES) for the most recent two cycles (2013-14, 2015-16) and China Health and Retirement Longitudinal Study (CHARLS) (2011-12).ParticipantsAll 45-75 year old adults who would have a diagnosis of hypertension and be candidates for treatment on the basis of the ACC/AHA guidelines, compared with current guidelines.Main outcome measuresDiagnosis of hypertension and candidacy for initiation and intensification of antihypertensive treatment.ResultsAdoption of the 2017 ACC/AHA hypertension guidelines in the US would label 70.1 (95% confidence interval 64.9 to 75.3) million people in the 45-75 year age group as having hypertension, representing 63% (60.6% to 65.4%) of the population in this age group. Their adoption in China would lead to labeling of 266.9 (252.9 to 280.8) million people or 55% (53.4% to 56.7%) of the same age group as having hypertension. This would represent an increase in prevalence of 26.8% (23.2% to 30.9%) in the US and 45.1% (41.3% to 48.9%) in China. Furthermore, on the basis of treatment patterns and current guidelines, 8.1 (6.5 to 9.7) million Americans with hypertension are untreated, which would be expected to increase to 15.6 (13.6 to 17.7) million after the implementation of the ACC/AHA guidelines. In China, on the basis of current treatment patterns, 74.5 (64.1 to 84.8) million patients with hypertension are untreated, estimated to increase to 129.8 (118.7 to 140.9 million. In addition, the ACC/AHA guidelines would label 8.7 (6.0 to 11.5) million adults in the US and 51 (40.3 to 61.6) million in China as having hypertension that would not require antihypertensive treatment, compared with 1.5 (1.2 to 2.1) million and 23.4 (12.1 to 35.1) million with the current guidelines. Finally, even among people receiving treatment, the proportion that are candidates for intensification of treatment is estimated to increase by 13.9 (12.2 to 15.6) million (from 24.0% to 54.4% of treated patients) in the US, and 30 (24.3 to 35.7) million (41.4% to 76.2% of treated patients) in China, if the ACC/AHA treatment targets are adopted.ConclusionsIf adopted, the 2017 ACC/AHA hypertension guidelines will markedly increase the number of people labeled as having hypertension and treated with drugs in both the US and China, leading to more than half of those aged 45-75 years in both countries being considered hypertensive.

Exaggerated complement activation is a key event in the pathogenesis of a range of autoimmune and inflammatory diseases. Complement Receptor 1 (CR1) has emerged as a molecule of immense interest in gaining insight to the susceptibility, pathophysiology, diagnosis, prognosis and therapy of such diseases. This review brings forth a composite view of the current understanding on the structure, functions, genetics, disease associations and therapeutic implications of CR1.

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We performed a Bayesian network meta-analysis combining direct and indirect treatment comparisons to assess the comparative effectiveness of pharmacological agents for the treatment of nonalcoholic steatohepatitis (NASH). Through systematic literature review, we identified nine randomized, controlled trials (RCTs) including 964 patients with biopsy-proven NASH, comparing vitamin E, thiazolidinediones (TZDs), pentoxifylline, or obeticholic acid to one another or placebo. The primary outcome was improvement in fibrosis stage; secondary outcomes were improvement in ballooning degeneration, lobular inflammation, and steatosis. We reported relative risks (RRs) and 95% confidence intervals (CIs) from direct meta-analysis and 95% credible intervals (CrIs) from Bayesian network meta-analysis, and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to appraise quality of evidence. Moderate-quality evidence supports the use of pentoxifylline (RR, 0.26; 95% CrI: 0.05-1.00) and obeticholic acid (RR, 0.81; 95% CI: 0.70-0.95) over placebo in improving fibrosis. High-quality evidence supports the effect of vitamin E, TZDs, and obeticholic acid over placebo in improving ballooning degeneration. All four interventions seemed to have at least moderate-quality evidence over placebo to improve steatosis. Moderate-quality evidence supports that TZDs, pentoxifylline, and obeticholic acid decrease lobular inflammation. All the head-to-head comparisons were supported by verylow-quality evidence except for superiority of TZDs over vitamin E on improving steatosis and lobular inflammation, which had moderate-quality evidence. Conclusions: Based on direct and network meta-analysis, pentoxifylline and obeticholic acid improve fibrosis, and vitamin E, TZDs, and obeticholic acid improve ballooning degeneration in patients with NASH. Future comparative trials of combination therapies targeting distinct histological features are warranted. (HEPATOLOGY 2015;62:1417-1432 N onalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease worldwide and is associated with increased liverrelated mortality and hepatocellular carcinoma.1 It is currently the second-most common indication for liver transplantation in the United States.2 The rate of progression of fibrosis in patients with NAFLD is widely variable and depends on several clinical and histological factors, such as age, diabetes, obesity, hypertension, and presence of steatohepatitis; patients with non-alcoholic steatohepatitis (NASH) progress at a faster rate than patients with isolated fatty liver.3-5