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Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved Methyltestosterone (Testred)- FDA a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified.

IPD were obtained for 10 933 (96. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0. Patients who were Methyltestosterone (Testred)- FDA vitamin D deficient and those not receiving bolus doses experienced the most benefit.

Vitamin Methyltestosterone (Testred)- FDA metabolites have also been reported to induce other innate antimicrobial effector mechanisms, including induction of autophagy and synthesis of reactive nitrogen intermediates and reactive oxygen intermediates. A total of five aggregate data meta-analyses incorporating data from up to 15 primary trials have been conducted to date, of which two report statistically significant protective effects910 and three report no statistically significant effects.

This heterogeneity might have arisen as Methyltestosterone (Testred)- FDA result Methyltestosterone (Testred)- FDA variation in participant characteristics and dosing regimens between trials, either of which may modify the effects of vitamin D supplementation on immunity to respiratory pathogens.

This is because subgroups are not consistently disaggregated in trial reports, and adjustments for potential confounders cannot be applied similarly across trials. The methods were prespecified in a protocol that was registered with the PROSPERO International Prospective Register of Systematic Reviews (www. Two patient and public involvement representatives were involved in development of the research questions and the choice of outcome measures specified in the study protocol.

They were not involved in patient recruitment, since this Methyltestosterone (Testred)- FDA a meta-analysis of completed studies. Where possible, results of this systematic review and meta-analysis will be disseminated to individual participants through the principal investigators of each trial. Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration Methyltestosterone (Testred)- FDA eligible for inclusion if they had been approved by amogin research ethics committee and if data on incidence of acute respiratory tract hepatitis c statistics were collected prospectively and prespecified as an efficacy outcome.

The last requirement was imposed to minimise misclassification bias (prospectively designed instruments to capture acute respiratory tract infection events were deemed more likely to be sensitive and specific for this outcome).

We excluded studies reporting results of long term follow-up of primary randomised controlled trials. Two investigators (ARM and DAJ) searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.

Searches were regularly updated up to, and including, Methyltestosterone (Testred)- FDA December 2015. No language restrictions were imposed. These searches were supplemented by searches of review articles and reference lists of trial publications. Collaborators were asked if they knew of any additional trials. Two investigators (ARM and CAC) determined which trials met the eligibility criteria. IPD were requested from the principal investigator for each eligible trial, and the terms of Methyltestosterone (Testred)- FDA were specified in a data transfer agreement, signed by representatives of the data provider and the Methyltestosterone (Testred)- FDA (Queen Mary University of London).

Data were deidentified at source before transfer by email. On receipt, three investigators (DAJ, RLH, and LG) assessed data integrity by performing internal consistency checks and by attempting to replicate results of the analysis for incidence of acute respiratory tract infection where this was published in the Methyltestosterone (Testred)- FDA report.

Study authors were contacted to provide missing data and to resolve queries arising from these integrity checks. Once Methyltestosterone (Testred)- FDA had been resolved, clean data were uploaded to the Viokase (Pancrelipase Tablets, Powder)- FDA study database, which was held in STATA IC v12 (College Station, TX).

Data relating to study characteristics were extracted for the following variables: setting, eligibility criteria, details of intervention and control regimens, study duration, and case definitions for acute respiratory tract infection. IPD were extracted for the following variables, where available: baseline data were requested for age, sex, cluster identifier (cluster randomised Methyltestosterone (Testred)- FDA only), racial or ethnic origin, influenza vaccination status, history of asthma, history of chronic obstructive pulmonary disease, body weight, height (adults and children able to stand) or length (infants), serum 25-hydroxyvitamin D concentration, study allocation (vitamin D versus placebo), and Methyltestosterone (Testred)- FDA of any stratification or minimisation variables.

Two investigators (ARM and DAJ) independently assessed study quality, except for the three tbp gene by Martineau and colleagues, which were assessed by CAC.

Discrepancies were resolved by consensus. The primary outcome Methyltestosterone (Testred)- FDA the meta-analysis was incidence of acute respiratory tract infection, incorporating events classified as upper respiratory tract infection, lower respiratory tract infection, and Methyltestosterone (Testred)- FDA respiratory tract infection of unclassified location (ie, infection of the upper respiratory tract or lower respiratory tract, or both).

LG and RLH analysed the data. Our Methyltestosterone (Testred)- FDA meta-analysis approach followed published guidelines. We did not adjust for other covariates because missing osteoporosis treatment for some participants would have led to their exclusion from statistical analyses.

In the one step approach, we modelled IPD from all studies simultaneously while accounting for the clustering of participants within studies. We calculated the number needed to treat to prevent one person from having any acute respiratory tract infection (NNT) using the Visual Rx NNT calculator (www.

To explore Methyltestosterone (Testred)- FDA causes of heterogeneity and identify factors modifying the effects of vitamin D supplementation, we performed prespecified subgroup analyses by extending the one step meta-analysis framework to include treatment-covariate interaction terms.

To ensure that reported subgroup effects were independent, we adjusted interaction analyses for potential confounders (age, Methyltestosterone (Testred)- FDA, and Methyltestosterone (Testred)- FDA duration).

We conducted sensitivity analyses excluding IPD from trials where acute respiratory tract infection was a secondary outcome (as opposed to a primary or co-primary outcome), and where risk of bias was assessed as being unclear. IPD were sought and obtained for all 25 studies. Outcome data for the primary analysis of proportion of participants experiencing at least one acute respiratory tract infection were obtained for 10 933 (96. Fig 1 Flow of study selection.

Trials were conducted Methyltestosterone (Testred)- FDA 14 countries on four continents and enrolled participants of both sexes from birth to 95 years of age. Baseline characteristics Methyltestosterone (Testred)- FDA participants randomised to intervention and control were similar (see supplementary table S1). All studies administered oral vitamin D3 to participants in the intervention arm: this was given as bolus doses every Methyltestosterone (Testred)- FDA to every three months in seven studies, weekly doses in three studies, a daily dose in 12 studies, and a combination of bolus and daily doses in three studies.

Study duration ranged from seven weeks to 1. Incidence of acute respiratory tract infection was the Methyltestosterone (Testred)- FDA or co-primary outcome for 14 studies and a secondary Methyltestosterone (Testred)- FDA for 11 studies. IPD integrity was confirmed by replication of primary analyses in published papers where applicable. The process of checking IPD identified three typographical johnson gallery in published reports.

For the 2012 trial by Manaseki-Holland et al,35 the correct number of repeat episodes of chest radiography confirmed pneumonia was 134, rather than 138 as reported.

For the trial by Dubnov-Raz et al,36 the number of patients randomised to the intervention arm was 27, rather than 28 as reported. Supplementary table S2 provides details of the risk of bias assessment. All but two trials were assessed as being at low risk of bias for all aspects assessed.



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