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      Vitamin D deficiency in critically ill children: a systematic review and meta-analysis

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          Abstract

          Background

          Vitamin D deficiency (VDD) has been hypothesized not only to be common but also to represent a potentially modifiable risk factor for greater illness severity and clinical outcome during critical illness. The objective of this systematic review was to determine the frequency of VDD in pediatric critical illness and its association with clinical outcomes.

          Methods

          MEDLINE, Embase, and CENTRAL were searched through December 12, 2016, with no date or language restrictions. The primary objective was to estimate the prevalence of VDD in the pediatric intensive care unit (PICU) and compare vitamin D status with healthy control populations. Secondary objectives were to evaluate whether VDD is associated with mortality, increased illness severity, PICU interventions, and patient clinical course. Random effects meta-analysis was used to calculate pooled VDD event rate, compare levels with those of control subjects, and evaluate for associations between VDD and clinical outcome.

          Results

          Among 2700 citations, 17 studies meeting study eligibility were identified. The studies reported a total of 2783 critically ill children and had a median sample size of 120 (range 12–511). The majority of studies used a 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/L to define VDD, and the pooled VDD prevalence was 54.8 (95% CI 45.4–63.9). Average 25(OH)D levels were significantly lower in PICU patients than in healthy control subjects (pooled difference −17.3 nmol/L, 95% CI −14.0 to −20.6). In a meta-analysis calculation, we found that VDD was associated with increased mortality (OR 1.62, 95% CI 1.11–2.36), illness severity, and need for PICU interventions.

          Conclusions

          Approximately 50% of critically ill children have VDD at the time of PICU admission, defined as a blood total 25(OH)D concentration under 50 nmol/L. VDD was further determined to be associated with greater illness severity, multiple organ dysfunction, and mortality in the PICU setting. Clinical trials are required to determine if optimization of vitamin D status improves patient outcome.

          Trial registration

          PROSPERO, CRD42016026617. Registered on 11 January 2016.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13054-017-1875-y) contains supplementary material, which is available to authorized users.

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          Most cited references62

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          Prevention of rickets and vitamin D deficiency in infants, children, and adolescents.

          Rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continues to be reported in the United States. There are also concerns for vitamin D deficiency in older children and adolescents. Because there are limited natural dietary sources of vitamin D and adequate sunshine exposure for the cutaneous synthesis of vitamin D is not easily determined for a given individual and may increase the risk of skin cancer, the recommendations to ensure adequate vitamin D status have been revised to include all infants, including those who are exclusively breastfed and older children and adolescents. It is now recommended that all infants and children, including adolescents, have a minimum daily intake of 400 IU of vitamin D beginning soon after birth. The current recommendation replaces the previous recommendation of a minimum daily intake of 200 IU/day of vitamin D supplementation beginning in the first 2 months after birth and continuing through adolescence. These revised guidelines for vitamin D intake for healthy infants, children, and adolescents are based on evidence from new clinical trials and the historical precedence of safely giving 400 IU of vitamin D per day in the pediatric and adolescent population. New evidence supports a potential role for vitamin D in maintaining innate immunity and preventing diseases such as diabetes and cancer. The new data may eventually refine what constitutes vitamin D sufficiency or deficiency.
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            An evidence-based practice guideline for the peer review of electronic search strategies.

            Complex and highly sensitive electronic literature search strategies are required for systematic reviews; however, no guidelines exist for their peer review. Poor searches may fail to identify existing evidence because of inadequate recall (sensitivity) or increase the resource requirements of reviews as a result of inadequate precision. Our objective was to create an annotated checklist for electronic search strategy peer review. A systematic review of the library and information retrieval literature for important elements in electronic search strategies was conducted, along with a survey of individuals experienced in systematic review searching. Six elements with a strong consensus as to their importance in peer review were accurate translation of the research question into search concepts, correct choice of Boolean operators and of line numbers, adequate translation of the search strategy for each database, inclusion of relevant subject headings, and absence of spelling errors. Seven additional elements had partial support and are included in this guideline. This evidence-based guideline facilitates the improvement of search quality through peer review, and thus the improvement in quality of systematic reviews. It is relevant for librarians/information specialists, journal editors, developers of knowledge translation tools, research organizations, and funding bodies.
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              The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty.

              Studies indicate that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with a range of disease processes, many of which are inflammatory. However, other lipid-soluble vitamins decrease during the systemic inflammatory response, and this response may confound the interpretation of plasma 25(OH)D. The objective was to examine whether plasma 25(OH)D concentrations change during evolution of the systemic inflammatory response. Patients (n = 33) who underwent primary knee arthroplasty had venous blood samples collected preoperatively and postoperatively (beginning 6-12 h after surgery and on each morning for 5 d) for the measurement of 25(OH) D, vitamin D-binding protein, parathyroid hormone (PTH), calcium, C-reactive protein, and albumin. A final sample was collected at 3 mo. Preoperatively, most patients were 25(OH)D deficient ( 5 pmol/L). Age, sex, body mass index, season, medical history, and medication use were not associated with significant differences in preoperative plasma 25(OH)D concentrations. By day 2 there was a large increase in C-reactive protein concentrations (P < 0.001) and a significant decrease in 25(OH)D of ≈40% (P < 0.001). C-reactive protein, 25(OH)D, and calculated free 25(OH)D had not returned to preoperative concentrations by 5 d postoperatively (all P < 0.001). At 3 mo, 25(OH)D and free 25(OH)D remained significantly lower (20% and 30%, respectively; P < 0.01). Plasma concentrations of 25(OH)D decrease after an inflammatory insult and therefore are unlikely to be a reliable measure of 25(OH)D status in subjects with evidence of a significant systemic inflammatory response.
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                Author and article information

                Contributors
                613-737-7600 , dmcnally@cheo.on.ca
                nassr.nama@gmail.com
                kohearn@cheo.on.ca
                msampson@cheo.on.ca
                karin.amrein@medunigraz.at
                klevis.iliriani@gmail.com
                lmcintyre@ohri.ca
                dafergusson@ohri.ca
                menon@cheo.on.ca
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                23 November 2017
                23 November 2017
                2017
                : 21
                : 287
                Affiliations
                [1 ]ISNI 0000 0000 9402 6172, GRID grid.414148.c, Children’s Hospital of Eastern Ontario, ; 401 Smyth Road, Ottawa, ON K1H 8L1 Canada
                [2 ]Division of Critical Care, Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON K1H 8L1 Canada
                [3 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, Faculty of Medicine, , University of Ottawa, ; Ottawa, ON Canada
                [4 ]ISNI 0000 0000 9402 6172, GRID grid.414148.c, Children’s Hospital of Eastern Ontario Research Institute, ; 501 Smyth Road, Ottawa, ON K1H 8L6 Canada
                [5 ]ISNI 0000 0000 8988 2476, GRID grid.11598.34, Division of Endocrinology and Metabolism, Department of Internal Medicine, , Medical University of Graz, ; Graz, Austria
                [6 ]ISNI 0000 0004 1936 9705, GRID grid.8217.c, School of Medicine, Trinity College Dublin, ; Dublin, Ireland
                [7 ]Division of Critical Care, Department of Medicine, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, ON Canada
                [8 ]Department of Epidemiology and Community Medicine, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, Ontario Canada
                Article
                1875
                10.1186/s13054-017-1875-y
                5701429
                29169388
                d740a4ac-5478-4b7b-9651-113b89f5180f
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 May 2017
                : 26 October 2017
                Funding
                Funded by: Children's Hospital of Eastern Ontario Research Institute
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Emergency medicine & Trauma
                vitamin d,systematic review,meta-analyses,pediatrics,mortality,nutrition
                Emergency medicine & Trauma
                vitamin d, systematic review, meta-analyses, pediatrics, mortality, nutrition

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