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Comorbidity and outcomes in traumatic brain injury: protocol for a systematic review on functional status and risk of death.

ABSTRACT: INTRODUCTION:Reports on the association between comorbidity and functional status and risk of death in patients with traumatic brain injury (TBI) have been inconsistent; it is currently unknown which additional clinical entities (comorbidities) have an adverse influence on the evolution of outcomes across the lifespan of men and women with TBI. The current protocol outlines a strategy for a systematic review of the current evidence examining the impact of comorbidity on functional status and early-term and late-term mortality, taking into account known risk factors of these adverse outcomes (ie, demographic (age and sex) and injury-related characteristics). METHODS AND ANALYSIS:A comprehensive search strategy for TBI prognosis, functional (cognitive and physical) status and mortality studies has been developed in collaboration with a medical information specialist of the large rehabilitation teaching hospital. All peer-reviewed English language studies with longitudinal design in adults with TBI of any severity, published from May 1997 to April 2017, found through Medline, Central, Embase, Scopus, PsycINFO and bibliographies of identified articles, will be considered eligible. Study quality will be assessed using published guidelines. ETHICS AND DISSEMINATION:The authors will publish findings from this review in a peer-reviewed scientific journal(s) and present the results at national and international conferences. This work aims to understand how comorbidity may contribute to adverse outcomes in TBI, to inform risk stratification of patients and guide the management of brain injury acutely and at the chronic stages postinjury on a population level. PROSPERO REGISTRATION NUMBER:CRD42017070033.

SUBMITTER: Mollayeva T

PROVIDER: S-EPMC5652528 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Comorbidity and outcomes in traumatic brain injury: protocol for a systematic review on functional status and risk of death.

Mollayeva Tatyana T Xiong Chen C Hanafy Sara S Chan Vincy V Hu Zheng Jing ZJ Sutton Mitchell M Escobar Michael M Colantonio Angela A

BMJ open 20171013 10

<h4>Introduction</h4>Reports on the association between comorbidity and functional status and risk of death in patients with traumatic brain injury (TBI) have been inconsistent; it is currently unknown which additional clinical entities (comorbidities) have an adverse influence on the evolution of outcomes across the lifespan of men and women with TBI. The current protocol outlines a strategy for a systematic review of the current evidence examining the impact of comorbidity on functional status ...[more]

PMID: 29030415

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Project description:BackgroundComorbidity can affect health-care utilization and outcomes, and the results and interpretation of risk adjustment studies that attempt to predict rehabilitation utilization and outcomes are influenced by the choice of comorbidity measurement. Although the identification of an appropriate measurement has been conducted in some populations and outcomes, this information is currently lacking for the non-traumatic brain injury (nTBI) population in inpatient rehabilitation settings. As such, this is a systematic review protocol to survey the methods used to measure comorbidities in the rehabilitation setting for patients with nTBI.Methods/designMEDLINE, MEDLINE In-Process, Embase, The Cochrane Database of Systematic Reviews, PsycINFO, and Health and Psychosocial Instruments will be systematically searched using the concepts 'nTBI,' 'comorbidity,' and 'rehabilitation.' Grey matters and the reference list of eligible articles will also be searched. Study selection will be performed independently by two reviewers based on predetermined eligibility criteria through two rounds of screening using, first, the title and abstract, followed by full-text. Extracted information will include study purpose, design, and setting; data source and type; outcomes variables; statistical methods; comorbidity measurement method, rationale, justification, or validation; and results involving comorbidity. The data will be tabulated and narratively synthesized. Meta-analyses will be performed if appropriate.Systematic review registrationThis protocol has not been registered with PROSPERO.DiscussionThis protocol provides a systematic method for surveying current practice as well as monitoring the progress on comorbidity measurement methodology and effects of comorbidity on rehabilitation outcomes for patients with nTBI. The selection of an appropriate comorbidity measurement method has implications for the interpretation of both descriptive and risk adjustment studies, and thus, the validity of evidence used to inform planning and delivery of services.

Project description:OBJECTIVES:Comorbidity in traumatic brain injury (TBI) has been recognised to alter the clinical course of patients and influence short-term and long-term outcomes. We synthesised the evidence on the effects of different comorbid conditions on early and late mortality post-TBI in order to (1) examine the relationship between comorbid condition(s) and all-cause mortality in TBI and (2) determine the influence of sociodemographic and clinical characteristics of patients with a TBI at baseline on all-cause mortality. DESIGN:Systematic review. DATA SOURCES:Medline, Central, Embase, PsycINFO and bibliographies of identified articles were searched from May 1997 to January 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:Included studies met the following criteria: (1) focused on comorbidity as it related to our outcome of interest in adults (ie, ≥18 years of age) diagnosed with a TBI; (2) comorbidity was detected by any means excluding self-report; (3) reported the proportion of participants without comorbidity and (4) followed participants for any period of time. DATA EXTRACTION AND SYNTHESIS:Two independent reviewers extracted the data and assessed risk of bias using the Quality in Prognosis Studies tool. Data were synthesised through tabulation and qualitative description. RESULTS:A total of 27 cohort studies were included. Among the wide range of individual comorbid conditions studied, only low blood pressure was a consistent predictors of post-TBI mortality. Other consistent predictors were traditional sociodemographic risk factors. Higher comorbidity scale, scores and the number of comorbid conditions were not consistently associated with post-TBI mortality. CONCLUSIONS:Given the high number of comorbid conditions that were examined by the single studies, research is required to further substantiate the evidence and address conflicting findings. Finally, an enhanced set of comorbidity measures that are suited for the TBI population will allow for better risk stratification to guide TBI management and treatment. PROSPERO REGISTRATION NUMBER:CRD42017070033.

Project description:OBJECTIVES:Traumatic brain injury triggers multiple cell death pathways, possibly including ferroptosis-a recently described cell death pathway that results from accumulation of 15-lipoxygenase-mediated lipid oxidation products, specifically oxidized phosphatidylethanolamine containing arachidonic or adrenic acid. This study aimed to investigate whether ferroptosis contributed to the pathogenesis of in vitro and in vivo traumatic brain injury, and whether inhibition of 15-lipoxygenase provided neuroprotection. DESIGN:Cell culture study and randomized controlled animal study. SETTING:University research laboratory. SUBJECTS:HT22 neuronal cell line and adult male C57BL/6 mice. INTERVENTIONS:HT22 cells were subjected to pharmacologic induction of ferroptosis or mechanical stretch injury with and without administration of inhibitors of ferroptosis. Mice were subjected to sham or controlled cortical impact injury. Injured mice were randomized to receive vehicle or baicalein (12/15-lipoxygenase inhibitor) at 10-15 minutes postinjury. MEASUREMENTS AND MAIN RESULTS:Pharmacologic inducers of ferroptosis and mechanical stretch injury resulted in cell death that was rescued by prototypical antiferroptotic agents including baicalein. Liquid chromatography tandem-mass spectrometry revealed the abundance of arachidonic/adrenic-phosphatidylethanolamine compared with other arachidonic/adrenic acid-containing phospholipids in the brain. Controlled cortical impact resulted in accumulation of oxidized phosphatidylethanolamine, increased expression of 15-lipoxygenase and acyl-CoA synthetase long-chain family member 4 (enzyme that generates substrate for the esterification of arachidonic/adrenic acid into phosphatidylethanolamine), and depletion of glutathione in the ipsilateral cortex. Postinjury administration of baicalein attenuated oxidation of arachidonic/adrenic acid-containing-phosphatidylethanolamine, decreased the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells in the hippocampus, and improved spatial memory acquisition versus vehicle. CONCLUSIONS:Biomarkers of ferroptotic death were increased after traumatic brain injury. Baicalein decreased ferroptotic phosphatidylethanolamine oxidation and improved outcome after controlled cortical impact, suggesting that 15-lipoxygenase pathway might be a valuable therapeutic target after traumatic brain injury.

Project description:INTRODUCTION:Children who suffer from traumatic brain injury (TBI) are at risk of permanent brain damage and developmental deficits. Reports on neurodevelopmental outcomes in paediatric TBI suffer from small sample size and varying outcome definitions in the neurocognitive domains tested. This protocol describes a systematic review and meta-analysis of paediatric TBI in the following key neurocognitive domains: executive function, perceptual-motor function, language, learning and memory, social cognition and complex attention. METHODS:A comprehensive search comprising studies from Medline, Cochrane, Embase and PsycINFO published from 1988 to 2019 will be conducted. We will include studies on children ?18 years old who suffer from mild, moderate and severe TBI as determined by the Glasgow Coma Scale that report neurocognitive outcomes in domains predetermined by the Diagnostic and Statistical Manual of Mental Disorders fifth edition criteria. Systematic reviews, meta-analyses, randomised controlled trials, case-control, cohort and cross-sectional studies will be included. References from systematic reviews and meta-analyses will be hand-searched for relevant articles. A meta-analysis will be performed and effect sizes will be calculated to summarise the magnitude of change in each neurocognitive domain compared at different timepoints and stratified by severity of TBI. Included studies will be pooled using pooled standardised mean differences with a random effects model to determine an overall effect. In the scenario that we are unable to pool the studies, we will perform a narrative analysis. ETHICS AND DISSEMINATION:Ethics approval is not required for this study.The authors of this study will publish and present the findings in a peer-reviewed journal as well as national and international conferences. The results of this study will provide understanding into the association between different severities of paediatric TBI and long-term neurocognitive outcomes. PROSPERO REGISTRATION NUMBER:CRD42020152680.

Project description:IntroductionPost-traumatic epilepsy (PTE) is a recognised complication of traumatic brain injury (TBI), and is associated with higher rates of mortality and morbidity when compared with patients with TBI who do not develop PTE. The majority of the literature on PTE has focused on adult populations, and consequently there is a paucity of information regarding paediatric cohorts. Additionally, there is considerable heterogeneity surrounding the reported incidence of PTE following childhood TBI in the current literature. The primary aim of our study is to summarise reported PTE incidences in paediatric populations to derive an accurate estimate of the global incidence of PTE following childhood TBI. Our secondary aim is to explore risk factors that increase the likelihood of developing PTE.Methods and analysisA systematic literature search of Embase (1947-2021), PubMed (1996-2021) and Web of Science (1900-2021) will be conducted. Publications in English that report the incidence of PTE in populations under 18 years of age will be included. Publications that evaluate fewer than 10 patients, report an alternative cause of epilepsy, or in which a paediatric cohort is not discernable, will be excluded. Independent investigators will identify the relevant publications, and discrepancies will be adjudicated by a third independent investigator. Data extracted will include incidence of PTE, time intervals between TBI and PTE, seizure characteristics, injury characteristics, patient demographics and clinical data. Data extraction will be performed by two independent investigators and cross-checked by a third investigator. A descriptive analysis of PTE incidence will be conducted and a weighted mean will be calculated. If sufficient data are available, stratified meta-analysis of subgroups will also be conducted.Ethics and disseminationEthics approval was not required for this study. We intend to publish our findings in a high-quality peer-reviewed journal on completion.Prospero registration numberCRD42021245802.

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Comorbidity and outcomes in traumatic brain injury: protocol for a systematic review on functional status and risk of death.

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Comorbidity and outcomes in traumatic brain injury: protocol for a systematic review on functional status and risk of death.

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