Comparison of Clinical Study Results Reported in medRxiv Preprints vs Peer-reviewed Journal Articles.

Importance: Preprints have been widely adopted to enhance the timely dissemination of research across many scientific fields. Concerns remain that early, public access to preliminary medical research has the potential to propagate misleading or faulty research that has been conducted or interpreted in error. Objective: To evaluate the concordance among study characteristics, results, and interpretations described in preprints of clinical studies posted to medRxiv that are subsequently published in peer-reviewed journals (preprint-journal article pairs). Design, Setting, and Participants: This cross-sectional study assessed all preprints describing clinical studies that were initially posted to medRxiv in September 2020 and subsequently published in a peer-reviewed journal as of September 15, 2022. Main Outcomes and Measures: For preprint-journal article pairs describing clinical trials, observational studies, and meta-analyses that measured health-related outcomes, the sample size, primary end points, corresponding results, and overarching conclusions were abstracted and compared. Sample size and results from primary end points were considered concordant if they had exact numerical equivalence. Results: Among 1399 preprints first posted on medRxiv in September 2020, a total of 1077 (77.0%) had been published as of September 15, 2022, a median of 6 months (IQR, 3-8 months) after preprint posting. Of the 547 preprint-journal article pairs describing clinical trials, observational studies, or meta-analyses, 293 (53.6%) were related to COVID-19. Of the 535 pairs reporting sample sizes in both sources, 462 (86.4%) were concordant; 43 (58.9%) of the 73 pairs with discordant sample sizes had larger samples in the journal publication. There were 534 pairs (97.6%) with concordant and 13 pairs (2.4%) with discordant primary end points. Of the 535 pairs with numerical results for the primary end points, 434 (81.1%) had concordant primary end point results; 66 of the 101 discordant pairs (65.3%) had effect estimates that were in the same direction and were statistically consistent. Overall, 526 pairs (96.2%) had concordant study interpretations, including 82 of the 101 pairs (81.2%) with discordant primary end point results. Conclusions and Relevance: Most clinical studies posted as preprints on medRxiv and subsequently published in peer-reviewed journals had concordant study characteristics, results, and final interpretations. With more than three-fourths of preprints published in journals within 24 months, these results may suggest that many preprints report findings that are consistent with the final peer-reviewed publications.

Associations between cumulative social risk, psychosocial risk, and ideal cardiovascular health: Insights from the HeartSCORE study.

Background: Limited studies have assessed the effects of psychosocial risk factors on achievement of ideal cardiovascular health (CVH). Methods: Using the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) cohort, we examined the cross-sectional associations of cumulative social risk (CSR) and three psychosocial factors (depression, stress, perceived discrimination) with ideal CVH. CSR was calculated by assigning one point for each of: low family income, low education level, minority race (Black), and single-living status. Ideal CVH was calculated by assigning one point for ideal levels of each factor in American Heart Association's Life's Simple 7. Ideal CVH was dichotomized into fewer versus higher by combining participants achieving <3 versus ≥3 factors. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of having fewer ideal CVH factors. Psychosocial factors were assessed as mediators of the association between CSR and ideal CVH. Results: We included 2000 participants (mean age 59.1 [7.5] years, 34.6% male, 42.7% Black, and 29.1% with low income), among whom 60.6% had <3 ideal CVH factors. The odds of having fewer ideal CVH factors increased significantly with increasing CSR scores from 1 to 2, to ≥3 compared to individuals with CSR score of zero, after adjusting for age and sex (OR [95% CIs]: 1.77 [1.41 - 2.22]; 2.09 [1.62 - 2.69] 2.67 [1.97 - 3.62], respectively). Taking the components of ideal CVH separately, higher CSR was directly associated with odds of being in 'non-ideal' category for six of the seven factors, but was inversely associated with probability of being in 'non-ideal' category for cholesterol. The association was modestly attenuated after adjusting for depression, stress, and perceived discrimination (corresponding OR [95% CI]: 1.69 [1.34 - 2.12], 1.96 [1.51 - 2.55], 2.34 [1.71 - 3.20]). The psychosocial factors appeared to mediate between 10% and 20% of relationship between CSR and ideal CVH. Conclusions: Increased CSR was associated with lower probability of achieving ideal CVH factors. A modest amount of the effect of CSR on ideal CVH appeared to be mediated by depression, stress and perceived discrimination. Public health strategies aimed at improving ideal cardiovascular health may benefit from including interventions targeting social and psychosocial risk factors.

Long-term Cardiovascular Manifestations and Complications of COVID-19: Spectrum and Approach to Diagnosis and Management.

Survivors of coronavirus disease 2019 (COVID-19) may experience persistent symptoms, abnormal diagnostic test findings, incident disease in specific organ systems, or progression of existing disease. Post-acute COVID-19 syndrome (PACS) is defined by persistent, recurrent, or new symptoms, findings, or diagnoses beyond four weeks after the initial infection. PACS has been characterized as a multi-organ syndrome, often with cardiopulmonary symptoms that include fatigue, dyspnea, chest pain, and palpitations. Cardiovascular pathologies in PACS include new-onset arrhythmia, myocarditis, unmasked coronary artery disease, and diastolic dysfunction as well as abnormal findings on electrocardiogram, troponin testing, and cardiac magnetic resonance imaging. In this review, we discuss the cardiovascular symptoms, pathophysiology, clinical investigation, and management strategies for cardiopulmonary symptoms of PACS. We offer a treatment algorithm for primary care clinicians encountering patients with cardiopulmonary PACS and discuss ongoing research on this topic.

A Federal Indian Health Insurance Plan: Fulfilling a solemn obligation to American Indians and Alaska Natives in the United States.

The Indian Health Service (IHS) is but the latest effort to honor the constitutional and treaty commitment made to deliver health care to American Indians and Alaska Natives in the United States. The agency currently serves over 2.5 million American Indians and Alaska Natives through IHS-operated health facilities, as well provides funding support for contractual delivery of health services by Tribes to their constituents. Not unlike its predecessors, however, the IHS is struggling to fulfill its stated mission. Access to specialty care remains limited through the agency, particularly for Urban Indians, due to limited fiscal support of the Purchase-Referred Care Program. As a result of chronic underfunding stemming from Congressional inaction, the agency faces perennial understaffing and leadership turnover. In addition, the IHS is structurally unprepared to address the progressive urbanization of Alaska Natives and American Indians, more of whom now live in New York City than in North Dakota. Given these challenges, a renewed approach is warranted. In this essay, we review the history of the IHS, examine its current fiscal challenges, outline the ongoing demographic shift of AI/AN toward urban centers, and call for the creation of a Federal Indian Health Insurance Plan. Offered as a benefit to all American Indians and Alaska Natives without cost-sharing, the plan would be applicable both on and off tribal lands. Funded through mandatory appropriations, the plan would significantly increase fiscal support for AI/AN health programs and work to reduce health disparities affecting AI/ANs in the United States.

A 34-Year-Old Woman with Third-Degree Heart Block and Atrial Flutter Associated with Lyme Carditis: A Case Report.

BACKGROUND Lyme disease is a tick-borne illness caused by bacteria of the Borrelia genus, endemic to the northeastern region of the United States. It typically presents with fevers, myalgias, and erythema migrans, but it can result in disseminated symptoms if left untreated. Lyme carditis is a rare, but potentially fatal complication of Lyme disease, occurring in up to 4-10% of untreated cases. Typically, it presents with atrioventricular conduction abnormalities, which resolve with intravenous antibiotics and temporary pacing if indicated. Diverse cardiac pathology, however, has been associated with Lyme carditis, which may be underrecognized in practice. CASE REPORT A 34-year-old woman with no significant medical history presented with fatigue, dizziness, and shortness of breath, 2 weeks after camping in Rhode Island. Her presenting electrocardiogram demonstrated third-degree heart block. She was noted to have targetoid rashes on her left shoulder and breast on physical examination. On laboratory work-up, she was found to have positive Lyme total antibody enzyme immunoassay and positive Lyme western immunoblot. The findings were diagnostic for Lyme carditis. The patient's cardiac rhythm subsequently converted to slow atrial flutter with variable ventricular response unresponsive to antibiotic therapy. Given evidence suggesting that atrioventricular conduction was preserved, synchronized electrical cardioversion was pursued and was ultimately successful in rhythm conversion to normal sinus rhythm. CONCLUSIONS Although Lyme carditis is rare, this diagnosis should be of high clinical consideration in presentations of cardiac conduction abnormalities with acute onset and without other obvious cause, particularly in Lyme-endemic regions such as the northeastern United States.

An ethical appraisal of living-anonymous kidney donation using Adam Smith's Theory of Moral Sentiments.

Ethical debates continue to shape organ transplant policies, particularly for kidneys. Facing organ shortages, governments have created incentives targeting prospective living-anonymous donors - socially and biologically unrelated to the recipient. However, these policies may transform altruistic exchanges of tissues into trades of commodities. We use Adam Smith's concept of sympathy to outline a new approach to transplantation ethics. This is accomplished using a case study analysis of six countries with established living-anonymous kidney donation practices - Iran, Israel, the Netherlands, Saudi Arabia, the United Kingdom, and the United States. An ethical test was also developed from ethnographies of donors and Smith's Theory of Moral Sentiments. The case study analysis considered the role of religious and historic norms, media campaigns, adherence to the 2008 Declaration of Istanbul guidelines for each case, and how each factor related to Smith's sympathy, categorizing the countries into four tiers of altruism. Iran occupied the least altruistic tier, followed by the Netherlands, the UK and the US, and Saudi Arabia and Israel. The ethical test identified a similar ranking. Our findings suggest that a highly-selected cohort of states with established living-anonymous kidney donation programs may already utilize a Smithian approach for recruiting donors, and that socially-valued government incentives can preserve altruism. The ethical test could become a useful instrument to assess the altruism of emerging incentive policies.

Howler monkey foraging ecology suggests convergent evolution of routine trichromacy as an adaptation for folivory.

Primates possess remarkably variable color vision, and the ecological and social factors shaping this variation remain heavily debated. Here, we test whether central tenants of the folivory hypothesis of routine trichromacy hold for the foraging ecology of howler monkeys. Howler monkeys (genus Alouatta) and paleotropical primates (Parvorder: Catarrhini) have independently acquired routine trichromacy through fixation of distinct mid- to long-wavelength-sensitive (M/LWS) opsin genes on the X-chromosome. The presence of routine trichromacy in howlers, while other diurnal neotropical monkeys (Platyrrhini) possess polymorphic trichromacy, is poorly understood. A selective force proposed to explain the evolution of routine trichromacy in catarrhines-reliance on young, red leaves-has received scant attention in howlers, a gap we fill in this study. We recorded diet, sequenced M/LWS opsin genes in four social groups of Alouatta palliata, and conducted colorimetric analysis of leaves consumed in Sector Santa Rosa, Costa Rica. For a majority of food species, including Ficus trees, an important resource year-round, young leaves were more chromatically conspicuous from mature leaves to trichromatic than to hypothetical dichromatic phenotypes. We found that 18% of opsin genes were MWS/LWS hybrids; when combined with previous research, the incidence of hybrid M/LWS opsins in this species is 13%. In visual models of food discrimination ability, the hybrid trichromatic phenotype performed slightly poorer than normal trichromacy, but substantially better than dichromacy. Our results provide support for the folivory hypothesis of routine trichromacy. Similar ecological pressures, that is, the search for young, reddish leaves, may have driven the independent evolution of routine trichromacy in primates on separate continents. We discuss our results in the context of balancing selection acting on New World monkey opsin genes and hypothesize that howlers experience stronger selection against dichromatic phenotypes than other sympatric species, which rely more heavily on cryptic foods.