Prophylaxis against covid-19: living systematic review and network meta-analysis.

UPDATES: This is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity. OBJECTIVE: To determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis (NMA). DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022. STUDY SELECTION: Randomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. RESULTS: The second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation­risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence. CONCLUSIONS: Much of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a supplement. FUNDING: This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).

Prescription of Vitamin D to Fracture Patients: A Lack of Consensus and Evidence.

OBJECTIVES: We conducted a survey to explore practice patterns regarding the assessment of hypovitaminosis D and the prescription of vitamin D in acute fracture patients. Our secondary objective was to determine whether practice patterns differed between fragility and nonfragility fracture patients. DESIGN: Cross-sectional survey. SETTING: All surveys were completed using SurveyMonkey. PATIENTS/PARTICIPANTS: We surveyed surgeon members of the Canadian Orthopaedic Association and the Orthopaedic Trauma Association. INTERVENTION: Survey. MAIN OUTCOME MEASUREMENTS: The proportion of surgeons who routinely prescribe vitamin D to fracture patients. RESULTS: A total of 397 surveys were completed. Of total, 65.8% of surgeons indicated that they routinely prescribe vitamin D to fragility fracture patients and 25.7% routinely prescribe vitamin D to nonfragility fracture patients. We identified considerable variability in dosing regimens, as 45 different dosing regimens were prescribed in fragility fracture patients and 29 in nonfragility fracture patients. They ranged from daily doses of 400 IU to loading doses of 600,000 IU. The most frequently prescribed doses were 1000 IU daily (14.6%), 2000 IU daily (13.4%), and 50,000 IU weekly (8.7%). Respondents indicated that they heavily relied on clinical experience to guide their decisions to prescribe vitamin D to fracture patients. CONCLUSIONS: The results of this survey demonstrate multiple areas of uncertainty and a lack of consensus in the prescription of vitamin D to fracture patients. Fragility patients frequently receive vitamin D supplementation, whereas most surgeons do not prescribe vitamin D to young fracture patients. High-quality clinical research is needed to determine whether vitamin D supplementation is beneficial to fracture patients. LEVEL OF EVIDENCE: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.

What Is the Role of Vitamin D Supplementation in Acute Fracture Patients? A Systematic Review and Meta-Analysis of the Prevalence of Hypovitaminosis D and Supplementation Efficacy.

OBJECTIVES: The objectives of this systematic review and meta-analyses are (1) to estimate the prevalence of hypovitaminosis D in fracture patients and (2) to summarize the available evidence on the efficacy of vitamin D supplementation in fracture patients. DATA SOURCES: A comprehensive search of the MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials databases was conducted. Conference abstracts from relevant meetings were also searched. STUDY SELECTION: We included studies that investigate vitamin D insufficiency or examine the effect of vitamin D supplementation on 25-hydroxy-vitamin D (25(OH)D) serum levels in fracture patients. DATA EXTRACTION: Two authors independently extracted data using a predesigned form. DATA SYNTHESIS: We performed a pooled analysis to determine the prevalence of postfracture hypovitaminosis D and mean postfracture 25(OH)D levels. We present detailed summaries of each of the studies evaluating the impact of vitamin D supplementation. RESULTS: The weighted pooled prevalence of hypovitaminosis D was 70.0% (95% confidence interval: 63.7%-76.0%, I = 97.7). The mean postfracture serum 25(OH)D was 19.5 ng/mL. The studies that evaluated the efficacy of vitamin D supplementation suggest that vitamin D supplementation safely increases serum 25(OH)D levels. Only 1 meeting abstract showed a trend toward reduced risk of nonunion after a single large loading dose of vitamin D. CONCLUSIONS: This review found a high prevalence of hypovitaminosis D in fracture patients and that vitamin D supplementation at a range of doses safely increases 25(OH)D serum levels. To date, only 1 pilot study published as a meeting abstract has demonstrated a trend toward improved fracture healing with vitamin D supplementation. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.