Background: Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI among young patients, or whether clinical management differs by sex. Methods: The Atherosclerosis Risk in Communities (ARIC) Surveillance study conducts hospital surveillance of AMI in 4 US communities (MD, MN, MS, and NC). AMI was classified by physician review, using a validated algorithm. Medications and procedures were abstracted from the medical record. Our study population was limited to young patients aged 35-54 years. Results: From 1995-2014, 28,732 weighted hospitalizations for AMI were sampled among patients aged 35-74. Of these, 8,737 (30%) were young. The annual incidence of AMI hospitalizations increased for young women but decreased for young men. The overall proportion of AMI admissions attributable to young patients steadily increased, from 27% in 1995-1999 to 32% in 2010-2014 (P for trend =0.002), with the largest increase observed in young women. History of hypertension (59% to 73%, P for trend<0.0001) and diabetes mellitus (25% to 35%, P for trend<0.0001) also increased among young AMI patients. Compared to young men, young women presenting with AMI were more often black and had a greater comorbidity burden. In adjusted analyses, young women had a lower probability of receiving lipid-lowering therapies (RR = 0.87; 95% CI: 0.80-0.94), non-aspirin antiplatelets (RR = 0.83; 95% CI: 0.75-0.91), beta blockers (RR = 0.96; 95% CI: 0.91-0.99), coronary angiography (RR = 0.93; 95% CI: 0.86-0.99) and coronary revascularization (RR = 0.79; 95% CI: 0.71-0.87). However, 1-year all-cause mortality was comparable for women vs. men (HR=1.10; 95% CI: 0.83-1.45). Conclusion: The proportion of AMI hospitalizations attributable to young patients increased from 1995-2014 and was especially pronounced among women. History of hypertension and diabetes among young patients admitted with AMI increased over time as well. Compared with young men, young women presenting with AMI had a lower likelihood of receiving guidelinebased AMI therapies. A better understanding of factors underlying these changes is needed to improve care of young patients with AMI.

BackgroundClinical trial registries can improve the validity of trial results by facilitating comparisons between prospectively planned and reported outcomes. Previous reports on the frequency of planned and reported outcome inconsistencies have reported widely discrepant results. It is unknown whether these discrepancies are due to differences between the included trials, or to methodological differences between studies. We aimed to systematically review the prevalence and nature of discrepancies between registered and published outcomes among clinical trials.MethodsWe searched MEDLINE via PubMed, EMBASE, and CINAHL, and checked references of included publications to identify studies that compared trial outcomes as documented in a publicly accessible clinical trials registry with published trial outcomes. Two authors independently selected eligible studies and performed data extraction. We present summary data rather than pooled analyses owing to methodological heterogeneity among the included studies.ResultsTwenty-seven studies were eligible for inclusion. The overall risk of bias among included studies was moderate to high. These studies assessed outcome agreement for a median of 65 individual trials (interquartile range [IQR] 25–110). The median proportion of trials with an identified discrepancy between the registered and published primary outcome was 31 %; substantial variability in the prevalence of these primary outcome discrepancies was observed among the included studies (range 0 % (0/66) to 100 % (1/1), IQR 17–45 %). We found less variability within the subset of studies that assessed the agreement between prospectively registered outcomes and published outcomes, among which the median observed discrepancy rate was 41 % (range 30 % (13/43) to 100 % (1/1), IQR 33–48 %). The nature of observed primary outcome discrepancies also varied substantially between included studies. Among the studies providing detailed descriptions of these outcome discrepancies, a median of 13 % of trials introduced a new, unregistered outcome in the published manuscript (IQR 5–16 %).ConclusionsDiscrepancies between registered and published outcomes of clinical trials are common regardless of funding mechanism or the journals in which they are published. Consistent reporting of prospectively defined outcomes and consistent utilization of registry data during the peer review process may improve the validity of clinical trial publications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0520-3) contains supplementary material, which is available to authorized users.

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Although recent studies show an improved survival of children with sickle cell disease in the US and Europe, for adult patients mortality remains high. This study was conducted to evaluate the factors associated with mortality in adult patients following the approval of hydroxyurea. We first evaluated the association between selected variables and mortality at an academic center (University of North Carolina). Data sources were then searched for publications from 1998 to June 2016, with meta-analysis of eligible studies conducted in North America and Europe to evaluate the associations of selected variables with mortality in adult patients. Nine studies, combined with the UNC cohort (total n=3257 patients) met the eligibility criteria. Mortality was significantly associated with age (per 10-year increase in age) [7 studies, 2306 participants; hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.10–1.50], tricuspid regurgitant jet velocity 2.5 m/s or more (5 studies, 1577 participants; HR: 3.03; 95%CI: 2.0–4.60), reticulocyte count (3 studies, 1050 participants; HR: 1.05; 95%CI: 1.01–1.10), log(N-terminal-pro-brain natriuretic peptide) (3 studies, 800 participants; HR: 1.68; 95%CI: 1.48–1.90), and fetal hemoglobin (7 studies, 2477 participants; HR: 0.97; 95%CI: 0.94–1.0). This study identifies variables associated with mortality in adult patients with sickle cell disease in the hydroxyurea era.

Background: Anthracycline chemotherapeutics, such as doxorubicin, are used widely in the treatment of numerous malignancies. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that often presents as heart failure due to dilated cardiomyopathy years after anthracycline exposure. Recent data from animal studies indicate that anthracyclines cause cardiac atrophy. The timing of onset and underlying mechanisms are not well defined and the relevance of these findings to human disease is unclear.Methods and Results: Wild type mice were sacrificed one week after intraperitoneal administration of doxorubicin (1-25 mg/kg), revealing a dose-dependent decrease in cardiac mass (R 2 = 0.64, p < 0.0001) and a significant decrease in cardiomyocyte cross-sectional area (336 ± 29 vs. 188 ± 14 μm 2 , p < 0.0001). Myocardial tissue analysis identified a dose-dependent #