High-cited favorable studies for COVID-19 treatments ineffective in large trials

Importance. COVID-19 has resulted in massive production, publication and wide dissemination of clinical studies trying to identify effective treatments. However, several widely touted treatments failed to show effectiveness in large well-done randomized controlled trials (RCTs). Objective. To evaluate for COVID-19 treatments that showed no benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results for these interventions. Methods. Scopus (last update December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine/azithromycin, remdesivir, convalescent plasma, colchicine or interferon (index interventions) that represented clinical trials and that had received >150 citations. Their conclusions were assessed and correlated with study design features. The ten most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly-cited study. Altmetric scores were also obtained. Findings. 40 articles of clinical studies on these index interventions had received >150 citations (7 exceeded 1,000 citations). 20/40 (50%) had favorable conclusions and 4 were equivocal. Highly-cited articles with favorable conclusions were rarely RCTs while those without favorable conclusions were mostly RCTs (3/20 vs 15/20, p=0.0003). Only 1 RCT with favorable conclusions had sample size >160. Citation counts correlated strongly with Altmetric scores, in particular news items. Only 9 (15%) of 60 recent citations to the most highly-cited studies with favorable or equivocal conclusions were critical to the highly-cited study. Conclusion. Many clinical studies with favorable conclusions for largely ineffective COVID-19 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.

Bioactive effects of citrus flavonoids and role in the prevention of atherosclerosis and cancer

Citrus fruits are the main fruits of the Mediterranean diet and have been long recognized for their beneficial effects on human health. Observational studies have shown a significant association between dietary flavo-noid intake and reduced risk of cardiovascular and malignant diseases. The beneficial effects of citrus fruits on human health appear to be due to their high content in vitamins, minerals and fibers. In particular, the an-tioxidant and anti-inflammatory activities have been indicated as some of the mechanisms through which citrus fruits may thwarts the development of chronic degenerative diseases such as atherosclerosis and can-cer. This review would critically examine the results from numerous studies carried out in order assess the contribute of citrus flavonoids to the prevention of chronic pathological conditions including athero-sclerosis and cancer.

Are there non-linear relationships between alcohol consumption and long-term health?: a systematic review of observational studies employing approaches to improve causal inference

Background Research has long found ‘J-shaped’ relationships between alcohol consumption and certain health outcomes, indicating a protective effect of moderate consumption. However, methodological limitations in most studies hinder causal inference. This review aimed to identify all observational studies employing improved approaches to mitigate confounding in characterizing alcohol–long-term health relationships, and to qualitatively synthesize their findings. Methods Eligible studies met the above description, were longitudinal (with pre-defined exceptions), discretized alcohol consumption, and were conducted with human populations. MEDLINE, PsycINFO, Embase and SCOPUS were searched in May 2020, yielding 16 published manuscripts reporting on cancer, diabetes, dementia, mental health, cardiovascular health, mortality, HIV seroconversion, and musculoskeletal health. Risk of bias of cohort studies was evaluated using the Newcastle-Ottawa Scale, and a recently developed tool was used for Mendelian Randomization studies. Results A variety of functional forms were found, including reverse J/J-shaped relationships for prostate cancer and related mortality, dementia risk, mental health, and certain lipids. However, most outcomes were only evaluated by a single study, and few studies provided information on the role of alcohol consumption pattern. Conclusions More research employing enhanced causal inference methods is urgently required to accurately characterize alcohol–long-term health relationships. Those studies that have been conducted find a variety of linear and non-linear functional forms, with results tending to be discrepant even within specific health outcomes. Trial registration PROSPERO registration number CRD42020185861.