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canada goose factory sale Eligibility criteria Three types of studies were eligible for the umbrella review: systematic reviews and meta analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer http://www.canadagoosecanadaoutlet.com compounds of vitamin D).Results 107 systematic literature reviews and 74 meta analyses of observational studies of plasma vitamin D concentrations and 87 meta analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 canadian goose jacket outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta analyses of observational studies and meta analyses of randomised controlled trials, but buy canada goose jacket cheap the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, cheap Canada Goose and parathyroid hormone concentrations in patients with chronic kidney canada goose clearance disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people.Conclusions Despite a few hundred systematic canada goose black friday sale reviews and meta analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.IntroductionThe associations between vitamin D concentrations and various conditions and diseases have been assessed in a large and rapidly expanding literature. In addition to observational studies, numerous randomised trials have examined the effect of vitamin D supplementation on a range of outcomes. Historically, vitamin D had been linked to skeletal disease including calcium, phosphorus, and bone metabolism,1 2 osteoporosis,3 fractures,4 5 muscle strength,6 and falls.7 In the 2000s, growing buy canada goose jacket scientific attention turned to non skeletal chronic diseases as vitamin D deficiency was linked to cancer,8 cardiovascular diseases,9 Canada Goose online 10 metabolic disorders,11 infectious diseases,12 and autoimmune diseases,13 14 15 as well as mortality.16 If causal, these associations might be of great importance for public health, as vitamin D deficiency has been found to be highly prevalent in populations residing at high latitudes or leading an indoors oriented lifestyle.17 However, the composite literature is often confusing and has led to heated debates about the optimal concentrations of vitamin D and related guidelines for supplementation.18 19 20To provide an overview of the breadth and validity of the claimed associations of vitamin D with diverse outcomes, we have done an umbrella review of the evidence across existing systematic reviews and meta analyses. We aimed to do a comprehensive evaluation of systematic reviews and meta analyses of observational studies that examined associations of vitamin D concentrations with a range of clinical outcomes, as well as meta analyses of randomised controlled trials of vitamin D supplementation. We also compared the findings of the observational studies with those from meta analyses of randomised controlled trials of vitamin D supplementation, whenever these could be canada goose outlet juxtaposed. We sought to summarise the health outcomes that have been associated with vitamin D concentrations, evaluate whether evidence exists of biases in this literature, identify health outcomes without evidence of biases, and examine the consistency of inferences from the meta analyses of observational studies canada goose and of randomised controlled trials.MethodsStructure of umbrella reviewAn umbrella review systematically collects and evaluates information from multiple systematic reviews and meta analyses on all clinical outcomes for which these have been performed.21 Here, for evidence on observational associations between vitamin D concentrations and any health outcome, we sought to collect information from systematic reviews regardless of whether they also included quantitative syntheses (meta analyses). Given the very large heterogeneity that may be encountered in observational studies, often meta analysis may not be done in systematic reviews of observational studies, whereas this problem occurs much less frequently in systematic reviews of randomised controlled trials, for which meta analysis is the norm, especially when interventions are drugs or vitamins.22 Where available, we also evaluated in more depth the quantitative results of the meta analyses of observational associations and potential hints of bias in these meta analyses.23 24 25 For evidence on randomised controlled trials of vitamin D supplementation, canada goose deals we considered only formal quantitative meta analyses. We compared results from meta analyses of observational studies and randomised controlled trials, whenever data were available for the same outcome.Search strategyTwo reviewers (IT, ET) searched Medline and Embase in duplicate, using the search algorithm in supplementary table A, from inception to 11 October 2013 (last update) and limited the search to humans and English language, as the overwhelming majority of review studies are published in English language, peer reviewed journals. Any discrepancies were resolved with discussion. We firstly perused the title and abstract of each of these citations and then retrieved potentially eligible articles for perusal in full text.Eligibility criteria and appraisal of included studiesThree types of studies were eligible for the umbrella review: observational associations between circulating vitamin D concentrations and any clinical outcome examined in systematic reviews, meta analyses, or both; and meta analyses of randomised controlled trials assessing supplementation of vitamin D or active compounds (both established and newer compounds of vitamin D). We excluded studies that examined genetic polymorphisms related to vitamin D metabolism (for example, vitamin D receptor); systematic reviews and meta analyses of observational studies assessing dietary or supplementary vitamin D intake or ultraviolet B exposure; studies that had vitamin D status as the outcome; studies that investigated the prevalence of vitamin D deficiency in certain disease populations; and meta analyses of randomised Canada Goose Outlet controlled trials in which the treatment arm combined vitamin D with calcium or other vitamins or compounds versus placebo. When the treatment arm and control arm included the same additional compound (for example vitamin D and calcium versus calcium), we included the meta analysis in the review. We included meta analyses regardless of the baseline characteristics (clinical setting or age) of the examined populations. If an article presented separate meta analyses on more Canada Goose Jackets than one eligible outcome or type of clinical setting, we assessed those separately.Appraisal of individual component studies was beyond the scope of this umbrella review. This was the aim of the original systematic reviews and meta analyses, which should include an appraisal of studies’ quality. In respect to the selected systematic reviews and meta analyses, we used methods that captured essential features of the quality of the evidence, and these are described in detail in the data analysis section.Data extractionThree investigators (ET, IT, LZ) extracted data independently. We categorised the conclusions of each systematic review for the association of vitamin D and the outcome of interest in one of the following four categories: definite association, suggestive (possible) association, no association, or inconclusive (insufficient) evidence. Whenever more than one systematic review had been performed on the same outcome, we examined whether the main reported conclusions were concordant. We retained the most recent systematic review for further analyses.When we identified more than one meta analysis of observational studies examining the association between a given vitamin D biomarker and outcome pair in the same clinical setting, we examined the conclusions for concordance regarding the direction, level of statistical significance (at P0.05), and magnitude (overlapping confidence interval) of the association. Then, we again retained only the most recent meta analysis with eligible data for further statistical analysis. We estimated the summary effect size and its confidence interval by using random effects models and calculated the I2 and its confidence interval metric for heterogeneity for each eligible meta analysis that reported the effect sizes, number of cases, and total number of participants of the component studies.26 27 We used the regression asymmetry test to test for small study effects.28 canada goose coats on sale We also applied the excess significance test, which evaluates whether the observed number of studies with statistically significant results (“positive” studies) differs from the expected number of positive studies, by using a 2 test.29 30 31 The expected number of positive studies for each meta analysis is calculated by the sum of the statistical power estimates for each Canada Goose sale component study. We estimated the power of each study for an effect equal to Canada Goose Parka the effect of the largest study (study with the smallest variance), as previously described.32 We used appropriate equations to estimate the power, on the basis of whether the largest study reported a hazard ratio or an odds ratio.33 34 If the type of the metric was a standardised mean difference, we transformed this to an odds canada goose store ratio before using it in the analysis.Eight meta analyses presented in five papers were not included in the excess significance bias analysis either because individual study data was unavailable35 36 or because it reported the logarithm of geometric mean ratio,37 the weighted mean difference,36 or the Fisher’s z score.38 Both the small study and excess significance tests were considered significant at P23We specifically identified outcomes for which meta analyses of observational studies showed nominally significant associations (at P0.05), did not have large between study heterogeneity, were based on evidence from more than 500 cases (or more than 5000 total participants if the type of metric was continuous), and showed no evidence of small study effects or excess significance. We also noted how many would satisfy the same criteria but with P0.001, which has been considered to be a more appropriate threshold of statistical significance to reduce false positives.39 40 41When we identified more than one meta analysis of randomised controlled trials examining the relation between vitamin D supplementation and outcome pair in the same clinical setting, we examined the conclusions for concordance regarding the direction, level of statistical significance (at P0.05), and magnitude (overlapping confidence interval) of the association.When meta analyses for the same outcome existed both for association studies of vitamin D concentrations and for randomised controlled trials of vitamin D supplementation, we compared their results in terms of whether a nominally statistically significant effect had been described (P0.05) and whether the effect estimate was in the same direction. We did not compare the magnitude of the effect sizes between circulating canada goose coats vitamin D concentrations and vitamin D supplementation, as these are difficult to translate to the same vitamin D concentration/treatment contrasts. Whenever no meta analysis of observational studies existed for an outcome examined by a meta analysis of randomised controlled trials, we compared the main results with the results of a systematic review of observational studies, if available. Finally, we applied a set of criteria to conclude whether the evidence for a given outcome was definite, probable, suggestive, not conclusive, or unlikely (see box).We used Stata version 12.1 for statistical analyses.For only six (8%) of the 76 unique outcomes, the systematic reviews concluded that a definite association existed (supplementary tables B and F). These were rheumatoid arthritis activity, colorectal cancer, hypertension in children, bacterial vaginosis in pregnant women, falls in older people, and rickets in children; for all these outcomes, higher concentrations of vitamin D were associated with lower risk. No systematic reviews concluded that a definite or suggestive association existed for increased risk with higher concentrations of vitamin D canada goose factory sale.

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