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A Murine Model of Subarachnoid Hemorrhage
Published on: November 21, 2013
Haptoglobin genotype and aneurysmal subarachnoid hemorrhage: Individual patient data analysis
Ben Gaastra1, Dianxu Ren1, Sheila Alexander1
1From the Wessex Neurological Centre (B.G., D.O.B., I.G.), University Hospital Southampton NHS Foundation Trust, UK; School of Nursing (D.R., S.A.) and Department of Biostatistics (D.R., T.E.), University of Pittsburgh, PA; Department of Neurology (E.R.B.), Duke University School of Medicine, Durham, NC; NeuroSpring (D.M.B., M.K.B.), Dover, DE; Department of Neurosurgery (S.L.B.), University of Texas Health Science Center at Houston; Department of Anesthesiology, Neurology, Psychiatry, Psychology, Pharmaceutics, and Neuroscience (S.D., J.L.L.), College of Medicine, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, Gainesville; Brain Injury Research Group (J.G.), Division of Cardiovascular Sciences (University of Manchester), Salford Royal NHS Foundation Trust, UK; Clinical Neurosciences, Clinical & Experimental Sciences (P.G., I.G.), Faculty of Medicine, University of Southampton, UK; Department of Neurosurgery (K.I., Y.K.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Neurology (J.F.M., M.A.P.), Mayo Clinic, Jacksonville, FL; and Division of Cerebrovascular Neurosurgery (R.J.T.) and Departments of Neurology, Anesthesia/Critical Care Medicine, and Neurosurgery (W.Y., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
Objective:
To perform an individual patient-level data (IPLD) analysis and to determine the relationship between haptoglobin (HP) genotype and outcomes after aneurysmal subarachnoid hemorrhage (aSAH).
Methods:
The primary outcome was favorable outcome on the modified Rankin Scale or Glasgow Outcome Scale up to 12 months after ictus. The secondary outcomes were occurrence of delayed ischemic neurologic deficit, radiologic infarction, angiographic vasospasm, and transcranial Doppler evidence of vasospasm. World Federation of Neurological Surgeons (WFNS) scale, Fisher grade, age, and aneurysmal treatment modality were covariates for both primary and secondary outcomes. As preplanned, a 2-stage IPLD analysis was conducted, followed by these sensitivity analyses: (1) unadjusted; (2) exclusion of unpublished studies; (3) all permutations of HP genotypes; (4) sliding dichotomy; (5) ordinal regression; (6) 1-stage analysis; (7) exclusion of studies not in Hardy-Weinberg equilibrium (HWE); (8) inclusion of studies without the essential covariates; (9) inclusion of additional covariates; and (10) including only covariates significant in univariate analysis.
Results:
Eleven studies (5 published, 6 unpublished) totaling 939 patients were included. Overall, the study population was in HWE. Follow-up times were 1, 3, and 6 months for 355, 516, and 438 patients. HP genotype was not associated with any primary or secondary outcome. No trends were observed. When taken through the same analysis, higher age and WFNS scale were associated with an unfavorable outcome as expected.
Conclusion:
This comprehensive IPLD analysis, carefully controlling for covariates, refutes previous studies showing that HP1-1 associates with better outcome after aSAH.
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