Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. 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 by 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 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration PROSPERO CRD42014013953.

Background: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. Individual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. Objectives: To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. Data sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. Study selection: Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D₃ or vitamin D₂ of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. Study appraisal: Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. Results: We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96; heterogeneity p < 0.001]. Subgroup analysis revealed that protective effects were seen in individuals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in individuals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of < 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95; p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20; p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Limitations: Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. Conclusions: Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient individuals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. Study registration: This study is registered as PROSPERO CRD42014013953. Funding: The National Institute for Health Research Health Technology Assessment programme.

Vitamin D has a role in regulating immune function, and its deficiency is a suggested risk factor for childhood pneumonia. Our aim was to assess whether oral supplementation of vitamin D(3) (cholecalciferol) will reduce the incidence and severity of pneumonia in a high-risk infant population. We did a randomised placebo-controlled trial to compare oral 100,000 IU (2·5 mg) vitamin D(3) with placebo given to children aged 1-11 months in Kabul, Afghanistan. Randomisation was by use of a computer-generated list. Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months. Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically. Our primary outcome was the first or only episode of radiologically confirmed pneumonia. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00548379. 1524 children were assigned to receive vitamin D(3) and 1522 placebo. There was no significant difference between the incidence of first or only pneumonia between the vitamin D (0·145 per child per year, 95% CI 0·129-0·164) and the placebo group (0.137, 0·121-0·155); the incidence rate ratio was 1·06 (95% CI 0·89-1·27). From 652 children during five separate periods of testing serum calcifediol, only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group--a toxic level. Quarterly bolus doses of oral vitamin D(3) supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting. Wellcome Trust and British Council.

Objectives To determine whether (i) supplementation of oral 100 000 iu of vitamin D₃ (cholecalciferol) along with antibiotics will reduce the duration of illness in children with pneumonia; (ii) supplementation will reduce the risk of repeat episodes. Methods Double‐blind individually randomised placebo‐controlled trial in an inner‐city hospital in Kabul, of 453 children aged 1–36 months, diagnosed with non‐severe or severe pneumonia at the outpatient clinic. Children with rickets, other concurrent severe diseases, very severe pneumonia or wheeze, were excluded. Children were given vitamin D₃ or placebo drops additional to routine pneumonia treatment. Results Two hundred and twenty‐four children received vitamin D_3; and 229 received placebo. There was no significant difference in the mean number of days to recovery between the vitamin D₃ (4.74 days; SD 2.22) and placebo arms (4.98 days; SD 2.89; P = 0.17). The risk of a repeat episode of pneumonia within 90 days of supplementation was lower in the intervention (92/204; 45%) than the placebo group [122/211; (58%; relative risk 0.78; 95% CI 0.64, 0.94; P = 0.01]. Children in the vitamin D₃ group survived longer without experiencing a repeat episode (72 days vs. 59 days; HR 0.71; 95% CI 0.53–0.95; P = 0.02). Conclusion A single high‐dose oral vitamin D₃ supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia.

Forty to 70 % of medical devices and equipment in low- and middle-income countries are broken, unused or unfit for purpose; this impairs service delivery to patients and results in lost resources. Undiscerning procurement processes are at the heart of this issue. We conducted a systematic review of the literature to August 2013 with no time or language restrictions to identify what product selection or prioritization methods are recommended or used for medical device and equipment procurement planning within low- and middle-income countries. We explore the factors/evidence-base proposed for consideration within such methods and identify prioritization criteria. We included 217 documents (corresponding to 250 texts) in the narrative synthesis. Of these 111 featured in the meta-summary. We identify experience and needs-based methods used to reach procurement decisions. Equipment costs (including maintenance) and health needs are the dominant issues considered. Extracted data suggest that procurement officials should prioritize devices with low- and middle-income country appropriate technical specifications – i.e. devices and equipment that can be used given available human resources, infrastructure and maintenance capacity. Suboptimal device use is directly linked to incomplete costing and inadequate consideration of maintenance services and user training during procurement planning. Accurate estimation of life-cycle costing and careful consideration of device servicing are of crucial importance.