Objectives: This systematic review (SR) highlights principles for nutrient clinical trials and explore the diverse physiological functions of vitamin D beyond its traditional role in the musculoskeletal system related to clinical study designs. Background: Thousands of published research articles have investigated the benefits of vitamin D (a nutrient example taken in this SR) beyond the musculoskeletal system, including the immune, pulmonary, and cardiovascular systems; pregnancy; autoimmune disorders; and cancer. They illustrated vitamin D's molecular mechanisms, interactions, and genomic and nongenomic actions. Methods: This SR was designed to identify shortcomings in clinical study designs, statistical methods, and data interpretation that led to inconsistent findings in vitamin D-related publications. SR also highlights examples and insights into avoiding study design errors in future clinical studies, including randomized controlled clinical trials (RCTs). The SR adheres to the latest PRISMA statement, guidelines, and the PICOS process. Results: Inappropriate or flawed study designs were frequent in clinical trials. Major failures discussed here include too short clinical study duration, inadequate or infrequent doses, insufficient statistical power, failure to measure baseline and achieved levels, and recruiting vitamin D-sufficient participants. These design errors have led to misleading interpretations. Thus, conclusions from such studies should not be generalized or used in guidelines, recommendations, or policymaking. Conclusion: Adequately powered epidemiological studies and RCTs with sufficient vitamin D and duration in individuals with vitamin D deficiency reported favorable clinical outcomes, enriching the literature, enabling to understand its physiology and mechanisms. Proper study designs with rigorous methodologies and cautious interpretation of outcomes are crucial in advancing the nutrient field. The principles discussed apply not only to vitamin D, but also other micro-nutrients and nutraceutical research. Adhering to them enhances the credibility and reliability of clinical trials, SRs, and meta-analysis outcomes. The study emphasizes the importance of focused, hypothesis-driven, well-designed, statistically powered RCTs to explore the diverse benefits of nutrients, conducted in index nutrient deficient participants, and avoidance of study design errors. Findings from such studies should be incorporated into clinical practice, policymaking, and public health guidelines, improving the health of the nation and reducing healthcare costs.

Purpose of review: Glomerulonephritis refers to a rare group of diseases characterized by glomerular inflammation, which collectively are a common cause of kidney failure. Until recently, there was a lack of high-quality clinical trials to inform the care of patients with glomerulonephritides. We identified examples of successful translational research spanning from basic science to clinical applications, and highlight gaps in implementation science. Sources of information: The focus of our review was derived from discussions between health care professionals, researchers, and patient partners. We also performed literature searches pertaining to the treatment of glomerulonephritis in PubMed and Google Scholar. Methods: Examples of successful knowledge translation were generated through review of new evidence in the past 5 years and by iterative discussions by the authors. We then conducted a narrative review of several themes related to knowledge translation in glomerulonephritis. This was complemented by an interview with a patient partner to provide an example of a patient's perspective living with glomerulonephritis. Key findings: We summarized selected recent advances in glomerulonephritis and its knowledge translation in the following domains: (1) identification of auto-antibodies in membranous nephropathy and minimal change disease; (2) clinical trials of novel targeted therapies for IgA nephropathy and lupus nephritis, which have led to approval of new treatments; (3) developments in research networks and clinical trials in glomerulonephritis; (4) recognition of the importance in developing standardized patient reported outcome measures in clinical trials; and (5) barriers in knowledge translation including access to medication. Limitations: A systematic search of the literature and formal assessment of quality of evidence were beyond the scope of this review.

To explore the current state of research on off-label drug use in children and identify the existing research gaps in this topic. Six literature databases were searched to identify studies focusing exclusively on off-label drug use in children (aged < 18 years) published in Chinese or English between 2016 and 2021. We also searched clinicaltrials.gov for pediatric clinical trials conducted in the same period and compared the numbers of studies on off-label use and clinical trials for the most commonly reported drugs and drug types. Our search revealed 568 studies on off-label drug use. Almost half of the studies (n = 240) were cross-sectional. A total of 212 specific drugs or drug types were addressed in 361 studies, the most frequent being antipsychotic agents (n = 12), dexmedetomidine (n = 10), and rituximab (n = 8). Antipsychotic agents were also the most common type of drug examined in clinical trials in children. We identified a total of 435 different types of off-label use, the top three being unapproved indication (n = 157), population (n = 96), or age (n = 36). Only about one-third of the studies reported collecting informed consent (n = 195) or having ethics committee approval (n = 166). Conclusions: Off-label use of antipsychotics in children is widely reported in the literature. We suggest pediatric researchers to consider the number of studies on off-label use and existing clinical trials on different drugs when selecting target drugs for new studies and systematic reviews. What is Known: center dot There exist a large number of studies on off-label drug use in children. What is New: center dot This is the first scoping review of studies on off-label drug use in children. center dot Off-label use of antipsychotic agents is widely reported.

Objective: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect. Study design: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect. Results: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled < 50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect. Conclusions: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs. (C) 2021 Elsevier Inc. All rights reserved.

Objective: To determine the difference in level of dental caries in adults and children who chew sugar-free gum (SFG), compared with those who do not chew SFG or use alternatives such as lozenges, candies, rinses, tablets, and other nonchewing controls. Methods: Systematic review of published literature. Results: Twelve studies of interventions of SFG for dental caries outcomes were included. SFGs were found to significantly reduce caries increment, giving a preventative fraction (PF) of 28% (95% CI, 7% to 48%). Including the 8 trials that used xylitol gum only as the basis of the intervention, the PF was 33% (95% CI, 4% to 61%). No adverse effects were recorded. There was a high level of heterogeneity among the trials included. Conclusion: The findings of this review provide tentative evidence that chewing SFG reduces caries increment in comparison to nonchewing controls. However, there is a considerable degree of variability in the effect and the trials included were generally of moderate quality. There is a need for future research to explore the acceptability and feasibility of the use of SFG as a public health intervention (PROSPERO 2018 CRD42018094676). Knowledge Transfer Statement: The results of this study can be used by clinicians when deciding how best to implement dental caries prevention regimes for their patients. With consideration of cost and patient preference, this information could help to develop national policy directives on caries prevention and dictate the direction of future clinical research.

Objective: A systematic literature review of randomized clinical trials (RCTs) assessing depression treatments in primary care for Latinos is conducted. The authors rate the methodological quality of studies, examine cultural and linguistic adaptations, summarize clinical outcomes and cost-effectiveness findings, and draw conclusions for improving depression care among this diverse population. Method: Electronic bibliographic databases, Web sites, and manual searches are used to identify nine peer-reviewed articles covering four RCTs. Results: Across trials, collaborative care models were more effective than usual care in reducing depression and improving functioning and accessibility to guideline-congruent care. Conclusion: The use of evidence-based treatments in primary care seems to be an effective and cost-effective strategy to reduce mental health care disparities among Latinos served in primary care.