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Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol.

ABSTRACT: Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding genetic determinants of outcome will help to improve prognostic modelling, stratify patients in clinical trials and target novel strategies to treat this devastating disease. This protocol details a two-stage genome-wide association study to identify susceptibility loci for clinical outcome after aSAH using individual patient-level data from multiple international cohorts. Clinical outcome will be assessed using the modified Rankin Scale or Glasgow Outcome Scale at 1-24 months. The stage 1 discovery will involve meta-analysis of individual-level genotypes from different cohorts, controlling for key covariates. Based on statistical significance, supplemented by biological relevance, top single nucleotide polymorphisms will be selected for replication at stage 2. The study has national and local ethical approval. The results of this study will be rapidly communicated to clinicians, researchers and patients through open-access publication(s), presentation(s) at international conferences and via our patient and public network.

SUBMITTER: Gaastra B

PROVIDER: S-EPMC9232474 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol.

Gaastra Ben B Alexander Sheila S Bakker Mark K MK Bhagat Hemant H Bijlenga Philippe P Blackburn Spiros S Collins Malie K MK Doré Sylvain S Griessenauer Christoph C Hendrix Philipp P Hong Eun Pyo EP Hostettler Isabel C IC Houlden Henry H IIhara Koji K Jeon Jin Pyeong JP Kim Bong Jun BJ Kumar Munish M Morel Sandrine S Nyquist Paul P Ren Dianxu D Ruigrok Ynte M YM Werring David D Galea Ian I Bulters Diederik D Tapper Will W

Translational stroke research 20220106 4

Aneurysmal subarachnoid haemorrhage (aSAH) results in persistent clinical deficits which prevent survivors from returning to normal daily functioning. Only a small fraction of the variation in clinical outcome following aSAH is explained by known clinical, demographic and imaging variables; meaning additional unknown factors must play a key role in clinical outcome. There is a growing body of evidence that genetic variation is important in determining outcome following aSAH. Understanding geneti ...[more]

PMID: 34988871

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Project description:ObjectiveThe objective of the study was to assess the long-term self-reported health status and quality of life (QoL) of patients following an aneurysmal subarachnoid haemorrhage (ASAH) using a self-completed questionnaire booklet.DesignA two-cohort study.SettingA regional tertiary neurosurgical centre.Participants2 cohorts of patients with ASAH treated between 1998 and 2008 and followed up at approximately 1 year.InterventionsRoutine care.Primary and secondary outcomesA range of standardised scales included: AKC Short Sentences Test, the Barthel Index, the Self-Report Dysexecutive Questionnaire, the Everyday Memory Questionnaire, Stroke Symptom Checklist, Wimbledon Self-Report Scale, Modified Rankin Score (MRS) and a new Stroke-QoL. The data from summated scales were fit to the Rasch measurement model to validate the summed score.Results214 patients (48%) returned the questionnaires; the majority (76%) had a World Federation of Neurosurgeons grade of 1 or 2. The most frequent aneurysm type was that of the anterior communicating artery (28%) with approximately 90% of aneurysms of the anterior circulation. Of those previously in full or part-time employment, 48.9% were unemployed at follow-up. All summated scales satisfied the Rasch measurement model requirements, such that their summed scores were a sufficient statistic. Given this, one-third of patients were noted to have a significant mood disorder and 25% had significant dysexecutive function. Patients with an MRS of 3, 4 or 5 had significantly worse scores on most outcome measures, but a significant minority of those with a score of zero had failed to return to work and displayed significant mood disorder.ConclusionsA range of self-reported cognitive and physical deficits have been highlighted in a cohort of patients with ASAH. While the MRS has been shown to provide a reasonable indication of outcome, in routine clinical follow-up it requires supplementation by instruments assessing dysexecutive function, memory and mood.

Project description:IntroductionAneurysmal subarachnoid haemorrhage (aSAH) is a devastating disease associated with high mortality and morbidity. The main threat to patients is delayed cerebral ischaemia (DCI). Near-infrared spectroscopy (NIRS) is a recent technology allowing continuous, non-invasive cerebral oximetry that could permit timely detection of impending DCI and appropriate intervention to improve outcomes. However, the ability of regional oxygen saturation to detect DCI, its association to the outcome, or benefits of any interventions based on NIRS data, are lacking. Our aims are to evaluate NIRS technology both as a therapeutic tool to improve outcomes in aSAH patients and as a diagnostic tool for DCI.Methods and analysisMEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews will be searched from their inception and without language restriction. Our search strategy will cover the themes of subarachnoid haemorrhage and cerebral oximetry, without limitations regarding studied outcomes. We will identify all observational and interventional human studies of adult patients hospitalised after aSAH that were monitored using NIRS. Functional outcome measures, including the modified Rankin Scale, the Glasgow Outcome Scale and the Barthel Index, will constitute the primary outcome. The Cochrane Risk of Bias tool will be used for randomised controlled trials, the ROBINS-I tool to assess non-randomised studies of interventions and the Newcastle-Ottawa Scale for cohort or case-control studies. The Quality Assessment of Diagnostic Accuracy Studies-2 will be applied to studies evaluating NIRS diagnostic accuracy for DCI. We will evaluate the quality of the evidence of the effect based on the Grading of Recommendations Assessment, Development and Evaluation methodology.Ethics and disseminationDissemination will proceed through submission for journal publication, trial registry completion and abstract presentation. Ethics approval is not required.Prospero registration numberCRD42020077522.

Dataset Information

Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol.

Publications

Genome-Wide Association Study of Clinical Outcome After Aneurysmal Subarachnoid Haemorrhage: Protocol.

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