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Vitamin D in Critically Ill Patients

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Vitamin D in Critically Ill Patients Thesis/Dissertation Sheet Surname/Family Name : Nair Given Name/s : Priya Abbreviation for degree as give in the University calendar : PhD Faculty : Medicine School : St. Vincent’s Clinical School Thesis Title : Vitamin D in critically ill patients The pleiotropic functions of vitamin D, the clinical impact of deficiency and effect of supplementation have been a research focus in many specialties of ambulatory medicine. However, its prevalence in critical illness was not known. The parathyroid-vitamin D- calcium axis is the only endocrine axis that had not been previously described in critically ill patients. To study the effects of correction of deficiency, the dose, route and method of vitamin D supplementation needed investigation. Critically ill patients are heterogeneous and response to supplementation may not be consistent in all cohorts. This information is key to inform the design of a randomised controlled trial of supplementation. This thesis was a program of research that included a prospective observational study to describe serial changes in the parathyroid-vitamin D-calcium axis and the association with clinical outcomes in a sample of critically ill patients. This was followed by a randomised trial comparing two doses of intramuscular vitamin D to study the effectiveness and safety of supplementation. Subsequently, a sample of patients requiring life- sustaining extracorporeal support (ECMO) was studied to study pharmacokinetic profiles of vitamin D in patients with extreme disease severity. The observational study found marked changes in the parathyroid-vitamin D-calcium axis, which was associated with adverse outcomes. The supplementation study showed that a single intramuscular injection of cholecalciferol corrected vitamin D deficiency safely in critically ill patients. Vitamin D repletion was accompanied by a reduction in pro-inflammatory responses. The study on ECMO patients found them to be almost universally deficient in vitamin D. Supplementation by the single intramuscular dose corrected deficiency in only half these patients. Vitamin D deficiency is common in critical illness and is associated with adverse outcomes. Supplementation can be achieved effectively and safely in most patients. Groups of critically ill patients, such as those on ECMO are more susceptible to vitamin D deficiency and supplementation in this group is not easily achieved. This novel work and increasingly emerging evidence in the international literature provide a basis to inform the design of a high-quality comparative effectiveness randomised controlled trial of vitamin D supplementation in critically ill patients. Declaration relating to disposition of project thesis/dissertation I hereby grant to the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or in part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act 1968. I retain all property rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation. I also authorise University Microfilms to use the 350 word abstract of my thesis in Dissertation Abstracts International (this is applicable to doctoral theses only). …………………………………………………………… ……………………………………..……………… ……….……………………...…….… Signature Witness Signature Date The University recognises that there may be exceptional circumstances requiring restrictions on copying or conditions on use. Requests for restriction for a period of up to 2 years must be made in writing. Requests for a longer period of restriction may be considered in exceptional circumstances and require the approval of the Dean of Graduate Research. FOR OFFICE USE ONLY Date of completion of requirements for Award: Vitamin D in critically ill patients Fall Priya Nair 08 A thesis in fulfilment of the requirements for the degree of Doctor of Philosophy St. Vincents Clinical School Faculty of Medicine August 2018 INCLUSION OF PUBLICATIONS STATEMENT UNSW is supportive of candidates publishing their research results during their candidature as detailed in the UNSW Thesis Examination Procedure. Publications can be used in their thesis in lieu of a Chapter if: • The student contributed greater than 50% of the content in the publication and is the "primary author", ie. the student was responsible primarily for the planning, execution and preparation of the work for publication • The student has approval to include the publication in their thesis in lieu of a Chapter from their supervisor and Postgraduate Coordinator. • The publication is not subject to any obligations or contractual agreements with a third partythat would constrain its inclusion in the thesis Please indicate whether this thesis contains published material or not. □ Some of the workdescribed in this thesis has been published and it has been □ documented in the relevant Chapters with acknowledgement - This thesis has publications (eitherpublished or submitted forpublication) incorporatedinto it in lieu of a chapter and the details are presented below CANDIDATE'S DECLARATION I declare that: • I have complied with the Thesis Examination Procedure • where I have used a publication in lieu of a Chapter, the listed publication(s) below meet(s) the requirements to be included in the thesis. Name Signature Date (16107/18} Priya Nair dinator's Declaration ( �) I declare that: • the information below is accurate • where listed publication(s) have been used in lieu of Chapter(s), their use complies with the Thesis Examination Procedure • the minimum requirements for the format of the thesis have been met. PGC's Name PGC's Signature Date (dd/mm/yy) For each publication incorporated into the thesis in lieu of a Chapter, provide all of the requested details and signatures required Details of publication #1: Fulltitle: Significant perturbationof vitamin D-parathyroid-calciumaxis and adverse clinical outcomes in critically illpatients Authors: PriyaNair, Paul Lee, Claire Reynolds, Nguyen Dinh Nguyen, John A. Myburgh, John A. Eisman, Jacqueline R. Center Journal or book name: Intensive Care Medicine Volume/page numbers: 39:267-274 Date accepted/published:9 Sep 2012113 Oct 2012 Status I Published x Accepted and In In progress I I press I I (submitted) I The Candidate's Contribution to the Work The candidate led the study -this included study design, ethics application, patient enrolment, data collection, analysis, drafting of the manuscript and responding to reviewers' comments. Co-authors assisted with data collection, analysis and interpretation. Supervisors (JRC and JAM) supervised and guided the candidate through the process from the concept of the study to publication. Location of the work In the thesis and/or how the work is incorporated in the thesis: This was a study conducted in primarily the St Vincents Hospital ICU along with collaboration from the Royal Prince Alfred and St George ICUs. Primary Supervisor's Declaration I declare that: . the information above is accurate . this has been discussed with the PGC and it is agreed that this publication can be included in this thesis in lieu of a Chapter • All of the co-authors of the publication have reviewed the above information and have aQreed to its veracity by siQninQ a 'Co-Author Authorisation' form. Supervisor'sname Supervisor's Date (16107/18) Prof. Jacqueline R Center signature Details of publication #2: a Fulltitle: A Randomized Study of Single Dose of Intramuscular Cholecalciferol in Critically f/1Adults Authors: Priya Nair, Bala Venkatesh, Paul Lee, Stephen Kerr, Dominik J. Hoechter, Goce Dimeski, Jeffrey Grice, John A Myburgh, Jacqueline R. Center, Journal or book name: Critical Care Medicine Volume/page numbers:43:2313-2320 Date published: November 2015 Status x Published Accepted and In In progress press (submitted) The Candidate's Contribution to the Work The candidate led the study -this included study design, ethics application, patient enrolment, data collection, analysis, drafting of the manuscript and responding to reviewers' comments. Co-authors assisted with data collection, laboratory support, analysis and interpretation. Supervisors (JRC and JAM) supervised and guided the candidate throu h the recess from the conce t of the stud to ublication. Location of the work in the thesis and/or how the work is incorporated in the thesis: Work for this trial was erformed at St Vincent's Hos ital, S dne . Primary Supervisor's Declaration I declare that: ii ·---------------------------------------------- . the information above is accurate . this has been discussed with the PGC and it is agreed that this publication can be included in this thesis in lieu of a Chapter . All of the co-authors of the publication have reviewed the above information and have aareed to its veracity by signinQ a 'Co-Author Authorisation' form. Supervisor's name Supervisor's signature Date (16/07118) Prof. Jacqueline R Center Details of publication #3: Fulltitle: Vitamin D status and supplementation in adult patients receiving Extracorporeal Membrane Oxygenation (ECMO) Authors: Priya Nair, Balasubramaniam Venkatesh, Dominik J Hoechter, Hergen Buscher, Stephen Ken; Jacqueline R Center John A Myburgh Journalor book name: Anaesthesia and lntensWe Care Volume/page numbers: not allocated Date accepted: 617/18 Status Published Accepted and In x In progress I I I press (submitted) I The Candidate's Contribution to the Work I I The candidate led the study
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