结合珠蛋白基因型与颅内动脉瘤性蛛网膜下腔出血：个体患者数据分析。
Haptoglobin genotype and aneurysmal subarachnoid hemorrhage: Individual patient data analysis.
机构信息
From 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.
出版信息
Neurology. 2019 Apr 30;92(18):e2150-e2164. doi: 10.1212/WNL.0000000000007397. Epub 2019 Apr 5.
OBJECTIVE
To perform an individual patient-level data (IPLD) analysis and to determine the relationship between haptoglobin () 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a 2-stage IPLD analysis was conducted, followed by these sensitivity analyses: (1) unadjusted; (2) exclusion of unpublished studies; (3) all permutations of genotypes; (4) sliding dichotomy; (5) ordinal regression; (6) 1-stage analysis; (7) exclusion of studies not in Hardy-Weinberg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. 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.
目的
进行个体患者水平数据（IPLD）分析，并确定血红蛋白（）基因型与蛛网膜下腔出血（aSAH）后结局之间的关系。
方法
主要结局是发病后 12 个月改良 Rankin 量表或格拉斯哥结局量表上的良好结局。次要结局是迟发性缺血性神经功能缺损、影像学梗死、血管造影性血管痉挛和经颅多普勒血管痉挛的证据。世界神经外科学联合会（WFNS）量表、Fisher 分级、年龄和动脉瘤治疗方式是主要和次要结局的协变量。按照预先计划，进行了 2 阶段 IPLD 分析，随后进行了这些敏感性分析：（1）未调整；（2）排除未发表的研究；（3）所有 基因型的排列组合；（4）滑动二分法；（5）有序回归；（6）1 阶段分析；（7）排除不符合 Hardy-Weinberg 平衡（HWE）的研究；（8）纳入没有必要协变量的研究；（9）纳入其他协变量；（10）仅纳入单变量分析中有统计学意义的协变量。
结果
纳入了 11 项研究（5 项已发表，6 项未发表），共计 939 例患者。总体而言，研究人群符合 HWE。355、516 和 438 例患者的随访时间分别为 1、3 和 6 个月。基因型与任何主要或次要结局均无关。未观察到趋势。按照相同的分析方法，年龄较高和 WFNS 量表较高与不良结局相关，这是预期的结果。
结论
这项全面的 IPLD 分析，仔细控制协变量，反驳了先前表明 HP1-1 与 aSAH 后更好结局相关的研究。
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