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The primary outcome of the meta-analysis was incidence of acute respiratory tract infection, incorporating events classified as upper respiratory tract infection, lower respiratory tract infection, and acute 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 IPD meta-analysis approach la roche posay sunscreen published guidelines.

We did not adjust for other covariates because missing values 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 the 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, sex, and study 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 in 14 countries on four continents and enrolled participants of both sexes from birth to 95 years of age. Baseline characteristics la roche posay sunscreen 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 month 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 primary or co-primary outcome for 14 studies and a secondary outcome for 11 studies. IPD integrity was confirmed by replication of primary analyses in published ecology articles where applicable. The process of checking IPD identified three typographical errors la roche posay sunscreen 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 la roche posay sunscreen the risk of bias assessment. All but two trials were assessed as being at low risk of bias for all aspects assessed. Two trials were assessed as being at unclear risk of bias owing to high rates of loss to follow-up. Vitamin D supplementation resulted in a statistically significant reduction in the proportion of participants experiencing at least one acute respiratory tract infection (adjusted odds ratio 0.

This evidence was assessed as being of high quality (see supplementary table S3). An exploratory analysis testing the effects of vitamin D supplementation in those with baseline 25-hydroxyvitamin D concentrations in the ranges 25-49. Meta-analysis of data from trials in which vitamin D was administered using a daily or weekly regimen without additional bolus doses revealed a protective effect against acute respiratory tract infection (adjusted odds ratio 0.

Dot plots revealed a trend towards lower median baseline serum 25-hydroxyvitamin D concentration and higher median age for studies employing bolus compared with daily or weekly dosing (see supplementary figures S2 and S3). To establish which of these potential effect modifiers was acting independently, we repeated the analysis to include treatment-covariate interaction terms for baseline vitamin D status, dosing frequency, and age.

When all studies were analysed together, no statistically significant effect of vitamin D was seen on the proportion of participants with at least one upper respiratory tract infection, lower respiratory tract infection, hospital admission or emergency department attendance for acute respiratory tract infection, course of antimicrobials for acute respiratory tract infection, or absence from work or school due to acute respiratory tract infection.

However, when this analysis was stratified by dosing frequency, a borderline statistically significant protective effect of daily or weekly vitamin D supplementation against upper respiratory tract infection was seen (adjusted odds ratio 0.

One step individual participant data meta-analysis of secondary la roche posay sunscreen step individual participant data meta-analysis of secondary outcomes, stratified by dosing frequencyUse of vitamin D did not influence risk of serious adverse events of any cause (adjusted odds ratio 0. Instances of potential adverse reactions to vitamin D were rare. A funnel plot for the proportion of participants experiencing at least one acute respiratory tract infection showed a degree of asymmetry, raising the possibility that small trials showing adverse effects of vitamin D might not have been included in the meta-analysis (see supplementary figure S5).

Supplementary table S7 presents the results of responder analyses. IPD la roche posay sunscreen of the proportion of participants experiencing at least one acute respiratory tract infection, excluding two trials assessed as being at unclear risk Ulipristal Acetate Tablet (Ella)- Multum bias,3637 revealed protective effects of vitamin D supplementation consistent with the main analysis (adjusted odds ratio 0.

Sensitivity analysis for the same outcome, restricted to the 14 trials that investigated acute respiratory tract infection as the primary or coprimary outcome, also revealed protective effects of vitamin D supplementation consistent with the main analysis (0. In this individual participant la roche posay sunscreen (IPD) meta-analysis of randomised controlled trials, vitamin La roche posay sunscreen supplementation reduced the risk of experiencing at least one acute Thiethylperazine (Torecan)- FDA tract infection.

Subgroup analysis revealed that daily or weekly vitamin D supplementation without additional bolus doses protected against acute respiratory la roche posay sunscreen infection, whereas regimens containing large bolus doses did not.

Among those receiving daily or weekly vitamin D, protective effects were strongest in la roche posay sunscreen formulary profound vitamin D la roche posay sunscreen at baseline, although those with higher baseline 25-hydroxyvitamin D concentrations also experienced benefit. This evidence was assessed as being of high quality, using the GRADE criteria. Use la roche posay sunscreen vitamin D was safe: potential adverse reactions were rare, and the risk of such events was la roche posay sunscreen same la roche posay sunscreen participants randomised to intervention and control arms.

Why might use of bolus dose vitamin D be ineffective for prevention of acute respiratory tract infection. One explanation relates to the potentially adverse effects of wide fluctuations in circulating 25-hydroxyvitamin D concentrations, which are seen after use of mg dl doses but not with daily or weekly supplementation.

Vieth has proposed that high la roche posay sunscreen concentrations after bolus dosing may chronically dysregulate activity of enzymes responsible for synthesis and degradation of the active vitamin D metabolite 1,25-dihydroxyvitamin D, resulting in decreased concentrations of this metabolite in extra-renal tissues. Increased efficacy of vitamin D supplementation in those with lower baseline vitamin D status is more readily explicable, based on the principle that people who are the most deficient in a micronutrient will be the most likely to respond to its replacement.

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