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ABSTRACT

Background: To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza.

Background:

Objective: We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren.

Objective:

Design: From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D 3 supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen.

Design:

Results: Influenza A occurred in 18 of 167 (10.8%) children in the vitamin D 3 group compared with 31 of 167 (18.6%) children in the placebo group [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who started nursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P = 0.005). In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D 3 compared with 12 children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006).

Results:

Conclusion: This study suggests that vitamin D 3 supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren. This trial was registered at https://center.umin.ac.jp as UMIN000001373.

Conclusion:
Issue Section:

Seasonal oscillation of influenza is prominent, its epidemic is explosive, and it ends abruptly. To explain this peculiar pattern, Cannell et al ( 1 ) hypothesized that the seasonal oscillation of serum vitamin D concentrations, which was recently discovered to up-regulate innate immunity, may affect the epidemic pattern of influenza. Vitamin D is mostly obtained from sun exposure; thus, serum vitamin D concentrations can be affected by season. In fact, serum concentrations of vitamin D have been shown to decrease in winter, the season when influenza occurs, to concentrations half those during the summer ( 1 ). In a post hoc analysis of side effect questions asked during a randomized controlled trial performed to determine whether vitamin D could prevent osteoporosis ( 2 ), cold and flu symptoms were reported 3 times less often in the vitamin D group than in the placebo group ( 3 ). However, although the authors conducted an additional randomized trial in 162 healthy adults, they could not reconfirm the benefit of vitamin D supplementation for the prevention of symptomatic upper respiratory tract infections ( 4 ). On the other hand, a significant inverse association between serum vitamin D intake and recent upper respiratory tract infections was seen in the third National Health and Nutrition Examination Survey ( 5 ). However, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician-diagnosed influenza or delineated the necessary changes to prepare for an influenza pandemic ( 6 ). We conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D 3 supplements with placebo in schoolchildren to elucidate whether preventive intake of vitamin D supplements during winter and early spring seasons can reduce the incidence of seasonal influenza A.

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By the spring of 1945, he had seen further. He saw that the bombs would be used on cities. And he realized that to murder vast numbers of innocent civilians in the hope that it might make repetition of the crime less likely was immoral. The deaths would be certain. The future benefit was only hypothetical.

I think you give the wartime decision-makers too much credit in suggesting that their statements about the bomb were trying to preserve ambiguity. I think that any ambiguity reflects only their muddled thinking. As they marveled at the power of the bomb, the vast ocean of its implications lay undiscovered all around them.

As for the common perception that Hiroshima and Nagasaki created a moral barrier to future use of the bomb, I think that there is more truth to the opposite view. All the war-planning of the nuclear arms race was based on the assumption that using nuclear weapons on cities was legitimate. In other words, the nuclear arms race was predicated on the precedents of Hiroshima and Nagasaki. To this day, the USA hasn’t renounced or condemned such use.

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Thanks for the feedback, Gene. I am not trying to say they were trying to preserve ambiguity actively —I am saying what you are saying that their own thinking was ambiguous and not yet “settled.”

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Another fine post, Alex. I am a fan of John Dower’s work. I recommend Embracing Defeat: Japan in the Wake of World War II. The argument that doesn’t show up very much in these debates, but that I find persuasive, is this: Truman, Stimson and the rest were intent to do their utmost to end the war as quickly as possible. They, more than anyone, were acutely aware of the casualty counts. And what was in store the longer the war in the Pacific dragged on. Any argument that would have delayed a surrender would have been — and was — a very tough sell. MK

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Hi Michael: I hope you are well! While there is no doubt that they wanted a swift end to the war, there is the question of how much they thought the atomic bomb would help with this, and how to optimally achieve this, and how to weigh that need against all of their other desires (e.g. re: the demands for unconditional surrender, which is an area where Stimson and Truman disagreed deeply). It is a complex issue, and they were trying to come up with the right solution for both the near and far time horizons.

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I wonder: Did the US consider nuking an already devastated city like Tokyo or Osaka as a demo?

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The Target Committee ruled out nuking already-bombed cities because they didn’t think it would provide much “demonstration.” And I would note that Tokyo was still probably the most populous city in Japan in 1945 (3 million or so), even after all of that bombing and death.

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1. Preamble

Guidelines and Expert Consensus Documents summarize and evaluate all available evidence with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on outcome and the risk-benefit ratio of diagnostic or therapeutic means. Guidelines are no substitutes for textbooks and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s).

The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC website ( http://www.escardio.org/knowledge/guidelines/rules ).

Members of this Task Force were selected by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) to represent all physicians involved with the medical and surgical care of patients with coronary artery disease (CAD). A critical evaluation of diagnostic and therapeutic procedures is performed including assessment of the risk-benefit ratio. Estimates of expected health outcomes for society are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in Tables 1 and 2 .

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Table 2
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Levels of evidence

The members of the Task Force have provided disclosure statements of all relationships that might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at European Heart House, headquarters of the ESC. Any changes in conflict of interest that arose during the writing period were notified to the ESC. The Task Force report received its entire financial support from the ESC and EACTS, without any involvement of the pharmaceutical, device, or surgical industry.

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