Agreement Between Mega-Trials and Smaller Trials: A Systematic Review and Meta-Research Analysis.

Importance: Mega-trials can provide large-scale evidence on important questions. Objective: To explore how the results of mega-trials compare with the meta-analysis results of trials with smaller sample sizes. Data Sources: ClinicalTrials.gov was searched for mega-trials until January 2023. PubMed was searched until June 2023 for meta-analyses incorporating the results of the eligible mega-trials. Study Selection: Mega-trials were eligible if they were noncluster nonvaccine randomized clinical trials, had a sample size over 10 000, and had a peer-reviewed meta-analysis publication presenting results for the primary outcome of the mega-trials and/or all-cause mortality. Data Extraction and Synthesis: For each selected meta-analysis, we extracted results of smaller trials and mega-trials included in the summary effect estimate and combined them separately using random effects. These estimates were used to calculate the ratio of odds ratios (ROR) between mega-trials and smaller trials in each meta-analysis. Next, the RORs were combined using random effects. Risk of bias was extracted for each trial included in our analyses (or when not available, assessed only for mega-trials). Data analysis was conducted from January to June 2024. Main Outcomes and Measures: The main outcomes were the summary ROR for the primary outcome and all-cause mortality between mega-trials and smaller trials. Sensitivity analyses were performed with respect to the year of publication, masking, weight, type of intervention, and specialty. Results: Of 120 mega-trials identified, 41 showed a significant result for the primary outcome and 22 showed a significant result for all-cause mortality. In 35 comparisons of primary outcomes (including 85 point estimates from 69 unique mega-trials and 272 point estimates from smaller trials) and 26 comparisons of all-cause mortality (including 70 point estimates from 65 unique mega-trials and 267 point estimates from smaller trials), no difference existed between the outcomes of the mega-trials and smaller trials for primary outcome (ROR, 1.00; 95% CI, 0.97-1.04) nor for all-cause mortality (ROR, 1.00; 95% CI, 0.97-1.04). For the primary outcomes, smaller trials published before the mega-trials had more favorable results than the mega-trials (ROR, 1.05; 95% CI, 1.01-1.10) and subsequent smaller trials published after the mega-trials (ROR, 1.10; 95% CI, 1.04-1.18). Conclusions and Relevance: In this meta-research analysis, meta-analyses of smaller studies showed overall comparable results with mega-trials, but smaller trials published before the mega-trials gave more favorable results than mega-trials. These findings suggest that mega-trials need to be performed more often given the relative low number of mega-trials found, their low significant rates, and the fact that smaller trials published prior to mega-trial report more beneficial results than mega-trials and subsequent smaller trials.

Calcium Hydroxylapatite (CaHA) and Aesthetic Outcomes: A Systematic Review of Controlled Clinical Trials.

Background: This study aimed to systematically review and summarize the available controlled clinical trials on the effectiveness of calcium hydroxylapatite (CaHA) in terms of aesthetic outcomes, skin-aging-related outcomes, and patient/investigator satisfaction. Methods: We included controlled clinical trials involving at least 10 human adults that examined the effects of CaHA on aesthetic and skin-aging-related outcomes and satisfaction. Due to the high heterogeneity among the included studies, only a qualitative analysis is provided. Results: Out of 2935 relevant references, 13 studies were included, of which 8 studies focused on facial areas and 5 on dorsum of hand. CaHA injection was associated with enhancements in global aesthetic improvement scale, whether applied in facial regions or on the dorsum of hands. The findings suggested high patients' satisfaction following CaHA when applied to facial areas. Studies highlighted improvements in hand grading scales and a reduction in facial wrinkles. Conclusions: Current evidence suggests that CaHA injections improve aesthetic results, including facial areas, such as nasolabial folds and jawline, and hands, with high levels of satisfaction. Considering the methodological limitations and heterogeneous comparisons groups, additional controlled clinical trials would contribute to a better understanding of the applications and advantages offered by CaHA.

Skin regeneration-related mechanisms of Calcium Hydroxylapatite (CaHA): a systematic review.

Introduction: Calcium Hydroxylapatite (CaHA) is a common dermal filler used in aesthetic medicine for volumizing and contouring. Understanding mechanisms of actions of CaHA can help improve our understanding of its clinical applications. Methods: We performed a systematic review to summarize the skin-regeneration related mechanisms of CaHA. Five bibliographic databases were searched for English-language publications that evaluated CaHA in skin regeneration outcomes including neocollagenesis, cell proliferation and growth factors, angiogenesis, vascular dynamic and inflammatory markers, among others. Methodological rigor of included studies was assessed. Results: Of 2,935 identified citations, 12 studies were included for final analysis. Collagen production was reported by nine studies, cell proliferation by four, elastic fibers and/or elastin by four, and three studies on angiogenesis, while limited studies were available on the other outcomes. Six were clinical/observational studies. Only seven studies had a control group. Overall, studies showed CaHA resulted in increased cell proliferation, increased collagen production and angiogenesis, as well as in higher elastic fiber and elastin formation. Limited and inconclusive evidence was available on the other mechanisms. The majority of the studies had methodological limitations. Discussion: Current evidence is limited but indicates several mechanisms through which CaHA could lead to skin regeneration, volume enhancement, and contouring. Systematic review registration: https://doi.org/10.17605/OSF.IO/WY49V.

Perioperative Insulin Regimens in Patients With Insulin-Treated Type 2 Diabetes Mellitus Hospitalized for a Short Time for Minor Eye Surgery.

BACKGROUND: Elective surgery in patients with insulin-treated type 2 diabetes mellitus (T2D) and the admission period in the hospital, comprise a distinctive and challenging situation for physicians, nurses, as well as for the patients themselves. There is a lack of widely accepted evidence-based and standardized approach of care in regard to perioperative management of patients with insulin-treated T2D. METHODS: The main purpose of this proof-of-concept study was to investigate whether a standardized insulin and meal regimen on the day of surgery leads to a better management of diabetes in terms of blood glucose (BG) levels. Two different insulin and meal regimens-group A with half of insulin dose given with a standardized postoperative meal and group B with a custom preoperative breakfast and full insulin dose-were compared with Group C with routine care (no meal and no insulin injection on the day of surgery). Each group consisted of 12 to 15 patients. BG measurements were performed pre- and immediately postoperatively, before meals and at bedtime. RESULTS: Both standardized and well-defined insulin and meal regimens resulted in better average BG levels in the perioperative period, especially in the morning after the surgery. CONCLUSIONS: In this study, we observed that a standardized perioperative insulin regimen efficiently lowered postoperative BG levels. Providing a custom breakfast and a full insulin dose resulted in lower postoperative BG levels. These approaches were not associated with an increase in hypoglycemic events. Physicians and nursing staff gave positive feedback to the structured and well-defined approaches.

Prognostic models in COVID-19 infection that predict severity: a systematic review.

Current evidence on COVID-19 prognostic models is inconsistent and clinical applicability remains controversial. We performed a systematic review to summarize and critically appraise the available studies that have developed, assessed and/or validated prognostic models of COVID-19 predicting health outcomes. We searched six bibliographic databases to identify published articles that investigated univariable and multivariable prognostic models predicting adverse outcomes in adult COVID-19 patients, including intensive care unit (ICU) admission, intubation, high-flow nasal therapy (HFNT), extracorporeal membrane oxygenation (ECMO) and mortality. We identified and assessed 314 eligible articles from more than 40 countries, with 152 of these studies presenting mortality, 66 progression to severe or critical illness, 35 mortality and ICU admission combined, 17 ICU admission only, while the remaining 44 studies reported prediction models for mechanical ventilation (MV) or a combination of multiple outcomes. The sample size of included studies varied from 11 to 7,704,171 participants, with a mean age ranging from 18 to 93 years. There were 353 prognostic models investigated, with area under the curve (AUC) ranging from 0.44 to 0.99. A great proportion of studies (61.5%, 193 out of 314) performed internal or external validation or replication. In 312 (99.4%) studies, prognostic models were reported to be at high risk of bias due to uncertainties and challenges surrounding methodological rigor, sampling, handling of missing data, failure to deal with overfitting and heterogeneous definitions of COVID-19 and severity outcomes. While several clinical prognostic models for COVID-19 have been described in the literature, they are limited in generalizability and/or applicability due to deficiencies in addressing fundamental statistical and methodological concerns. Future large, multi-centric and well-designed prognostic prospective studies are needed to clarify remaining uncertainties.

The Buzz Surrounding Precision Medicine: The Imperative of Incorporating It into Evidence-Based Medical Practice.

Precision medicine (PM), through the integration of omics and environmental data, aims to provide a more precise prevention, diagnosis, and treatment of disease. Currently, PM is one of the emerging approaches in modern healthcare and public health, with wide implications for health care delivery, public health policy making formulation, and entrepreneurial endeavors. In spite of its growing popularity and the buzz surrounding it, PM is still in its nascent phase, facing considerable challenges that need to be addressed and resolved for it to attain the acclaim for which it strives. In this article, we discuss some of the current methodological pitfalls of PM, including the use of big data, and provide a perspective on how these challenges can be overcome by bringing PM closer to evidence-based medicine (EBM). Furthermore, to maximize the potential of PM, we present real-world illustrations of how EBM principles can be integrated into a PM approach.