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      Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes

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          Abstract

          Background

          Vitamin C is an essential water-soluble nutrient which cannot be synthesised or stored by humans. It is a potent antioxidant with anti-inflammatory and immune-supportive roles. Previous research has indicated that vitamin C levels are depleted in critically ill patients. In this study we have assessed plasma vitamin C concentrations in critically ill patients relative to infection status (septic shock or non-septic) and level of inflammation (C-reactive protein concentrations). Vitamin C status was also assessed relative to daily enteral and parenteral intakes to determine if standard intensive care unit (ICU) nutritional support is adequate to meet the vitamin C needs of critically ill patients.

          Methods

          Forty-four critically ill patients (24 with septic shock, 17 non-septic, 3 uncategorised) were recruited from the Christchurch Hospital Intensive Care Unit. We measured concentrations of plasma vitamin C and a pro-inflammatory biomarker (C-reactive protein) daily over 4 days and calculated patients’ daily vitamin C intake from the enteral or total parenteral nutrition they received. We compared plasma vitamin C and C-reactive protein concentrations between septic shock and non-septic patients over 4 days using a mixed effects statistical model, and we compared the vitamin C status of the critically ill patients with known vitamin C bioavailability data using a four-parameter log-logistic response model.

          Results

          Overall, the critically ill patients exhibited hypovitaminosis C (i.e., < 23 μmol/L), with a mean plasma vitamin C concentration of 17.8 ± 8.7 μmol/L; of these, one-third had vitamin C deficiency (i.e., < 11 μmol/L). Patients with hypovitaminosis C had elevated inflammation (C-reactive protein levels; P < 0.05). The patients with septic shock had lower vitamin C concentrations and higher C-reactive protein concentrations than the non-septic patients ( P < 0.05). Nearly 40% of the septic shock patients were deficient in vitamin C, compared with 25% of the non-septic patients. These low vitamin C levels were apparent despite receiving recommended intakes via enteral and/or parenteral nutritional therapy (mean 125 mg/d).

          Conclusions

          Critically ill patients have low vitamin C concentrations despite receiving standard ICU nutrition. Septic shock patients have significantly depleted vitamin C levels compared with non-septic patients, likely resulting from increased metabolism due to the enhanced inflammatory response observed in septic shock.

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          Most cited references63

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          Simultaneous inference is a common problem in many areas of application. If multiple null hypotheses are tested simultaneously, the probability of rejecting erroneously at least one of them increases beyond the pre-specified significance level. Simultaneous inference procedures have to be used which adjust for multiplicity and thus control the overall type I error rate. In this paper we describe simultaneous inference procedures in general parametric models, where the experimental questions are specified through a linear combination of elemental model parameters. The framework described here is quite general and extends the canonical theory of multiple comparison procedures in ANOVA models to linear regression problems, generalized linear models, linear mixed effects models, the Cox model, robust linear models, etc. Several examples using a variety of different statistical models illustrate the breadth of the results. For the analyses we use the R add-on package multcomp, which provides a convenient interface to the general approach adopted here. Copyright 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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            A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.

            To develop and validate a new Simplified Acute Physiology Score, the SAPS II, from a large sample of surgical and medical patients, and to provide a method to convert the score to a probability of hospital mortality. The SAPS II and the probability of hospital mortality were developed and validated using data from consecutive admissions to 137 adult medical and/or surgical intensive care units in 12 countries. The 13,152 patients were randomly divided into developmental (65%) and validation (35%) samples. Patients younger than 18 years, burn patients, coronary care patients, and cardiac surgery patients were excluded. Vital status at hospital discharge. The SAPS II includes only 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). Goodness-of-fit tests indicated that the model performed well in the developmental sample and validated well in an independent sample of patients (P = .883 and P = .104 in the developmental and validation samples, respectively). The area under the receiver operating characteristic curve was 0.88 in the developmental sample and 0.86 in the validation sample. The SAPS II, based on a large international sample of patients, provides an estimate of the risk of death without having to specify a primary diagnosis. This is a starting point for future evaluation of the efficiency of intensive care units.
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              Dose-Response Analysis Using R

              Dose-response analysis can be carried out using multi-purpose commercial statistical software, but except for a few special cases the analysis easily becomes cumbersome as relevant, non-standard output requires manual programming. The extension package drc for the statistical environment R provides a flexible and versatile infrastructure for dose-response analyses in general. The present version of the package, reflecting extensions and modifications over the last decade, provides a user-friendly interface to specify the model assumptions about the dose-response relationship and comes with a number of extractors for summarizing fitted models and carrying out inference on derived parameters. The aim of the present paper is to provide an overview of state-of-the-art dose-response analysis, both in terms of general concepts that have evolved and matured over the years and by means of concrete examples.
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                Author and article information

                Contributors
                643 364 0649 , anitra.carr@otago.ac.nz
                patrice.rosengrave@otago.ac.nz
                simone.bayer@otago.ac.nz
                steve.chambers@otago.ac.nz
                jan.mehrtens@cdhb.health.nz
                geoff.shaw@cdhb.health.nz
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                11 December 2017
                11 December 2017
                2017
                : 21
                : 300
                Affiliations
                [1 ]ISNI 0000 0004 1936 7830, GRID grid.29980.3a, Department of Pathology, , University of Otago, Christchurch, ; PO Box 4345, Christchurch, 8140 New Zealand
                [2 ]ISNI 0000 0004 0614 1349, GRID grid.414299.3, Department of Intensive Care Medicine, , Christchurch Hospital, ; Private Bag 4710, Christchurch, 8140 New Zealand
                Article
                1891
                10.1186/s13054-017-1891-y
                5725835
                29228951
                0ff0cf8b-4ccc-48f9-9ebe-d9793e640bcd
                © 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 September 2017
                : 13 November 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001505, Health Research Council of New Zealand;
                Award ID: 16/037
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001530, Canterbury Medical Research Foundation;
                Award ID: 15/06
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100009327, Intensive Care Foundation;
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Emergency medicine & Trauma
                intensive care,vitamin c,hypovitaminosis c,sepsis,critical illness,c-reactive protein,enteral nutrition,parenteral nutrition,septic shock

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