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Haptoglobin after subarachnoid haemorrhade: individual patient level data (ipld)meta-analysis

He, Tian (2018) Haptoglobin after subarachnoid haemorrhade: individual patient level data (ipld)meta-analysis. Master's Thesis, University of Pittsburgh. (Unpublished)

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Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating subtype of stroke with high mortality and morbidity. aSAH has approximate incidence of 9 cases per 100,000 person-years, and approximately 1 in 6 patients die during the initial hemorrhage. Further, secondary injuries, including cerebral vasospasm and delayed cerebral infarct, are quite common after aSAH contributing to the overall mortality rate of nearly 50%. The goal of this study is to gain a better understanding of association between aSAH and Haptoglobin genotype (Hp) by conducting IPLD meta-analysis.
Data including 960 subjects from 11 studies were recruited from all published studies identified by Pubmed and Web of Science searches, including reference lists within publication, and unpublished studies identified via HATCH (Haemoglobin After in TraCranial Haemorrhage) consortium and the networks of individual consortium members by the 31st March 2016.
Given the individual patient level data available, both two-stage and one-stage meta-analysis were conducted. For two-stage meta-analysis, the primary outcomes were dichotomized as unfavorable and favorable outcome, and all secondary outcomes were binary outcomes. Logistic regression models were used in the first stage of two-stage meta-analysis to assess the association between Hp and aSAH recovery in each study. Generalized estimating equations (GEE) with exchangeable correlation were used to fit logistic regression model to estimate the association between Hp and primary outcomes accounting for the correlations between repeated measurements over 1, 3, and 6 months for each study in the first stage. Logistic regression models were fit via maximum likelihood to assess the association in each study. In second stage, meta-analysis via random-effect models was conducted to obtain pooled odds ratio. Q tests and I2 were used to test heterogeneity, and to measure possible inconsistency. Publication bias was assessed by funnel plots and using the Egger method. In one-stage analyses, mixed effects logistic regression was used to generate overall odds ratios using all individual level data from different studies simultaneously within one model.
Both two-stage and one-stage meta-analyses indicated there was no significant association between Hp and aSAH. Although Q tests showed there was no heterogeneity, I2 in some studies were large, which indicated that the majority of the variability across studies were due to heterogeneity instead of chance. In the test of publication bias, both funnel plot and Egger test indicated there was no publication bias issue.
Public Health Significance: There were inconsistent findings from the literature regarding the association between Hp and outcome of aSAH. The work here investigates the relationship between haptoglobin genotype and outcomes after aSAH using meta-analysis based on current literature reports. While our findings were negative, there are a small number of studies with fairly small simple sizes, so results may still inform efforts at effective personalized preventive care and disease treatments with better specificity, targeted to the genetic makeup of each patient.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
He, Tiantih28@pitt.edutih28
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairRen,
Committee MemberYouk,
Committee MemberKrafty, Robert
Committee MemberAlexander, Sheila
Date: 28 June 2018
Date Type: Publication
Defense Date: 23 April 2018
Approval Date: 28 June 2018
Submission Date: 5 April 2018
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 138
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Biostatistics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Haptoglobin; subarachnoid haemorrhage; meta-analysis; GEE
Date Deposited: 28 Jun 2018 20:08
Last Modified: 01 May 2020 05:15


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