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Vitamin D Supplementation Cuts Respiratory Infections


 
August 20, 2012 — Supplementing vitamin D in the diets of school children may cut the incidence of acute respiratory infections (ARIs) by as much as half, according to results from a randomized controlled trial carried out in Mongolia.
"This double-blinded [randomized controlled trial] of Mongolian children in winter found that vitamin D3supplementation with only 300 IU daily led to a clinically and statistically significant reduction in risk of parent-reported ARIs," Carlos Camargo Jr, MD, DrPH, from the Harvard School of Public Health, Boston, Massachusetts, and colleagues write in their article, published online August 20 in Pediatrics.
The authors note that a growing number of epidemiologic studies link vitamin D deficiency to heightened risk for ARIs. Other studies have suggested that supplementing vitamin D might cut risks for ARIs and also influenza, but results from those trials have not been consistent.
To find out more, Dr. Camargo and colleagues studied a cohort of 247 children in the central Asian country of Mongolia, where temperatures during much of the year keep residents bundled against the cold and their skin lacking in exposure to sunlight. The human body synthesizes vitamin D when the skin is exposed to sunlight.
In this study of third- and fourth-grade students, carried out from January to March 2009, investigators randomly assigned the children to 1 of 2 groups. The first group (143 children) received milk each day that was fortified with 300 IU of vitamin D3<. The other group (104 children) received milk without vitamin D added.
Vitamin D serum levels were checked both at the beginning of the study and again at the end. Parents then were asked how many ARIs their children had experienced during the previous 3 months.
The researchers report that at baseline, the children's median serum 25(OH)D level was 7 ng/mL, but after the 3-month intervention, there was a significant difference in the 2 groups. Although the control group's vitamin D levels remained at 7 ng/mL, levels in the children who received fortified milk nearly tripled, rising to 19 ng/mL.
That difference appeared to have carried over in numbers of ARIs. "Compared with controls, children receiving vitamin D reported significantly fewer ARIs during the study period (mean: 0.80 vs 0.45; P = .047), with a rate ratio of 0.52 (95% confidence interval: 0.31–0.89)," the authors write. "Adjusting for age, gender, and history of wheezing, vitamin D continued to halve the risk of ARI (rate ratio: 0.50 [95% confidence interval: 0.28–0.88])."
The researchers say they saw similarly positive results when they assessed children whose vitamin D levels at baseline had been either below or above the median.
Although the researchers acknowledge that the Mongolian city where the study was carried out, Ulaanbaatar, is situated at a fairly high latitude (48 degrees north), they point out that Montreal and Paris are both at similar latitudes, and many major North American and European are even farther north.
The authors have disclosed no financial conflicts of interest related to this study.

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The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the risk of bleeding and intracranial hemorrhage, but the studies were hindered by early patient withdrawals and missing data. We Don't Know What We're Missing Based on the ATLAS ACS 2 results, FDA reviewer Dr Karen Hicks recommended approval of rivaroxaban for the requested indications except all-cause mortality. However, another FDA reviewer, Dr Thomas Marciniak, was adamant that the trial results are not interpretable because about 12% of the patients had incomplete follow-up, far higher than the 1% to 1.5% differences in the end-point rates between rivaroxaban and placebo. A total of 1294 subjects discontinued the trial prematurely, and the company was only able to contact 183, of which 177 were confirmed to be alive. Because of the patient dropouts, the company adopted a "modified intention-to-treat analysis," whereby patients were observed for 30 days after randomization or the global end date for the trial, instead of observing all the patients until the end of the trial as the FDA originally suggested. Marciniak criticized the sponsor's efforts to follow the patients and said that three patient deaths not counted in the modified intention-to-treat analysis may just be the "tip of the iceberg." Because the percentage of patients whose ultimate vital status remains unknown is much greater than the reported differences in mortality rates, the claimed mortality benefits are not reliable. The majority of the panel sided with Marciniak. For example, Dr Sanjay Kaul (University of California, Los Angeles) voted "no" because "there was enough uncertainty in the quality and robustness of the data that dissuaded me from voting yes. . . . 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Several panelists said they were concerned that the patients who dropped out of the trial were disproportionately likely to have a bleeding event, which led them to quit the trial, or a "protopathic" event, as statistician Dr Scott Emerson (University of Washington, Seattle) put it. "We're worried that an impending event is what is changing their behavior. We see that all the time in clinical trials--that regularly measured end points do not pick up [all of] the events," he said. He said that since the company was only able to contact 183 of the over 1200 patients who dropped out, it is possible that the dropouts skew the outcomes comparison of the trial. "Differential event rates after dropout are the number-one thing we're afraid of, so you have to explore it" in a statistical sensitivity analysis of the potential impact of these unknown outcomes. "It would not surprise me if, at the end of the day, these data did not hold up under a proper sensitivity analysis," he said. 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