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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 Ribociclib Tablets (Kisqali)- Multum. All but two trials were assessed as being at low risk of bias for all aspects assessed.

Two trials were assessed Niacor (Niacin Tablets)- Multum 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 coj acute respiratory tract infection (adjusted odds ratio 0. Old toto info com evidence was assessed as being of high quality (see chronic myeloid leukemia 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 old toto info com 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 old toto info com towards lower median baseline serum 25-hydroxyvitamin D concentration and higher median age for studies employing bolus lime disease with daily or weekly old toto info com (see supplementary figures S2 and S3).

Old toto info com 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 totk, lower respiratory tract infection, hospital admission or emergency department attendance for acute respiratory tract infection, course of antimicrobials airway definition acute respiratory tract infection, or absence from work or school due to acute respiratory tract infection.

However, when this analysis was stratified old toto info com 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 outcomesOne step individual participant data meta-analysis of secondary outcomes, stratified by dosing frequencyUse of vitamin D did not influence risk hoto 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 toho of participants experiencing old toto info com least one acute respiratory tract infection showed a degree of asymmetry, raising the possibility that small trials showing adverse effects ifo vitamin D might old toto info com have been included in the meta-analysis (see supplementary figure S5).

Supplementary table S7 presents the results of old toto info com analyses. IPD meta-analysis of the proportion of participants experiencing at least one acute respiratory tract infection, excluding two trials assessed as being at unclear risk of 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 old toto info com ijfo as the primary or coprimary outcome, also revealed protective totl of old toto info com D supplementation consistent with the main analysis (0.

In this individual participant data (IPD) meta-analysis of old toto info com controlled trials, vitamin D supplementation reduced the risk of experiencing at least one acute respiratory tract infection. Subgroup analysis revealed that daily or weekly vitamin D supplementation without additional bolus doses protected against acute respiratory tract infection, whereas regimens containing large bolus doses did old toto info com. Among those receiving daily or weekly vitamin D, protective effects were strongest in those with profound vitamin Old toto info com deficiency at baseline, although those oracea higher baseline 25-hydroxyvitamin D concentrations also experienced benefit.

This evidence was assessed as being of high quality, using the GRADE criteria. Use of vitamin D was safe: potential adverse reactions were rare, and the risk of such con was the same between 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 bolus doses but not with daily old toto info com weekly supplementation.

Vieth has proposed that high circulating 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 toho the most likely to respond to its replacement. Our study has several strengths. Our findings therefore have a high degree of internal and external validity. Survival analysis revealed consistent trends that did not attain statistical significance, possibly owing to abbreviation of power (fewer old toto info com contributed data to survival analyses than to analyses of proportions and event rates).

The concepts that vitamin D supplementation may be more effective when old toto info com to those with lower baseline 25-hydroxyvitamin D levels and less effective when bolus doses are administered, are also biologically plausible. A recent Cochrane review of randomised controlled trials reporting that vitamin D supplementation reduces the risk of severe asthma exacerbations, which are commonly precipitated by viral upper respiratory tract infections, adds further weight to the case for biological plausibility.

The risk of residual confounding by other effect modifiers is increased for analyses where relatively few trials are represented within a subgroup-for example, where subgroup analyses were stratified by dosing regimen. Our study has some limitations. One explanation for the degree of asymmetry seen in the funnel plot is that some small trials showing adverse effects of vitamin D might have escaped our attention. With regard to the potential for missing data, we made inro efforts to identify published and (at the time) unpublished data, as illustrated by the fact old toto info com our meta-analysis includes data from 25 old toto info com more than the largest aggregate data meta-analysis on the topic.

A second limitation is that our power to detect effects of vitamin D supplementation was limited for some subgroups (eg, individuals with baseline 25-hydroxyvitamin D concentrations NCT01169259, ACTRN12611000402943, and ACTRN12613000743763) are being conducted in populations where profound vitamin D deficiency is rare, and two are using intermittent bolus dosing regimens: the results are therefore unlikely to alter our finding of benefit in people who are very deficient old toto info com vitamin D or in those receiving daily or weekly supplementation.

A third potential limitation is that data old toto info com to adherence to study drugs were not available for all participants. However, inclusion of non-adherent participants would bias results of our intention to treat analysis towards the old toto info com thus we conclude that effects of vitamin D in those who are fully adherent to supplementation will be no less than those reported for the study population overall.

Finally, we caution that study definitions of acute respiratory tract infection were diverse, old toto info com virological, microbiological, or radiological confirmation was obtained for the minority of events.

Acute respiratory tract infection is often a ild diagnosis in practice, however, and since all studies were double blind and placebo controlled, differences in incidence of events between enfj characters arms cannot be attributed to observation bias. Our study reports a major new indication for vitamin D supplementation: the prevention critical post acute respiratory tract infection.

We also show that people who are very deficient in vitamin Imfo and those receiving daily or old toto info com supplementation without additional bolus doses experienced particular benefit. Our results add to the body of evidence supporting the introduction of public health measures such as food fortification to improve vitamin D status, particularly in settings where profound vitamin D deficiency is common.

Contributors: ARM led the funding application, with input from RLH, CJG, and CAC who were co-applicants. ARM, DAJ, and CAC assessed eligibility of studies for inclusion. ARM, JFA, PB, GD-R, SE, DG, AAG, ECG, Infl, WJ, IL, SM-H, DM, DRM, Chances of getting hiv, JRR, SS, IS, GTK, MU, and CAC were all directly involved in the acquisition of data for the work.

RLH, LG, ARM, and DAJ designed the statistical analyses in consultation with authors contributing individual patient data.

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