Browsing by Author "Brock, Guy"

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    A multistate transition model for statin‐induced myopathy and statin discontinuation
    (Wiley, 2021) Zhu, Yuxi; Chiang, Chien-Wei; Wang, Lei; Brock, Guy; Milks, M. Wesley; Cao, Weidan; Zhang, Pengyue; Zeng, Donglin; Donneyong, Macarius; Li, Lang; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    The overarching goal of this study was to simultaneously model the dynamic relationships among statin exposure, statin discontinuation, and potentially statin-related myopathic outcomes. We extracted data from the Indiana Network of Patient Care for 134,815 patients who received statin therapy between January 4, 2004, and December 31, 2008. All individuals began statin treatment, some discontinued statin use, and some experienced myopathy and/or rhabdomyolysis while taking the drug or after discontinuation. We developed a militate model to characterize 12 transition probabilities among six different states defined by use or discontinuation of statin and its associated myopathy or rhabdomyolysis. We found that discontinuation of statin therapy was common and frequently early, with 44.4% of patients discontinuing therapy after 1 month, and discontinuation is a strong indicator for statin-induced myopathy (risk ratio, 10.8; p < 0.05). Women more likely than men (p < 0.05) and patients aged 65 years and older had a higher risk than those aged younger than 65 years to discontinue statin use or experience myopathy. In conclusion, we introduce an innovative multistate model that allows clear depiction of the relationship between statin discontinuation and statin-induced myopathy. For the first time, we have successfully demonstrated and quantified the relative risk of myopathy between patients who continued and discontinued statin therapy. Age and sex were two strong risk factors for both statin discontinuation and incident myopathy.
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    Multiple functional variants in the IL1RL1 region are pretransplant markers for risk of GVHD and infection deaths
    (American Society of Hematology, 2019-08-27) Karaesmen, Ezgi; Hahn, Theresa; Dile, Alexander James; Rizvi, Abbas A.; Wang, Junke; Wang, Tao; Haagenson, Michael D.; Preus, Leah; Zhu, Qianqian; Liu, Qian; Yan, Li; Liu, Song; Haiman, Christopher A.; Stram, Daniel; Pooler, Loreall; Sheng, Xin; Van Den Berg, David; Brock, Guy; Webb, Amy; McCarthy, Philip L.; Pasquini, Marcelo C.; Spellman, Stephen R.; Lee, Stephanie J.; Paczesny, Sophie; Sucheston-Campbell, Lara E.; Pediatrics, School of Medicine
    Graft-versus-host disease (GVHD) and infections are the 2 main causes of death without relapse after allogeneic hematopoietic cell transplantation (HCT). Elevated soluble serum simulation-2 (sST2), the product of IL1RL1 in plasma/serum post-HCT, is a validated GVHD biomarker. Hundreds of SNPs at 2q12.1 have been shown to be strongly associated with sST2 concentrations in healthy populations. We therefore hypothesized that the donor genetic variants in IL1RL1 correlate with sST2 protein levels associated with patient survival outcomes after HCT. We used DISCOVeRY-BMT (Determining the Influence of Susceptibility Conveying Variants Related to 1-Year Mortality after Blood and Marrow Transplantation), a genomic study of >3000 donor-recipient pairs, to inform our hypothesis. We first measured pre-HCT plasma/serum sST2 levels in a subset of DISCOVeRY-BMT donors (n = 757) and tested the association of donor sST2 levels with donor single nucleotide polymorphisms (SNPs) in the 2q12.1 region. Donor SNPs associated with sST2 levels were then tested for association with recipient death caused by acute GVHD (aGVHD)-, infection-, and transplant-related mortality in cohorts 1 and 2. Meta-analyses of cohorts 1 and 2 were performed using fixed-effects inverse variance weighting, and P values were corrected for multiple comparisons. Donor risk alleles in rs22441131 (P meta = .00026) and rs2310241 (P meta = .00033) increased the cumulative incidence of aGVHD death up to fourfold and were associated with high sST2 levels. Donor risk alleles at rs4851601 (P meta = 9.7 × 10-7), rs13019803 (P meta = 8.9 × 10-6), and rs13015714 (P meta = 5.3 × 10-4) increased cumulative incidence of infection death to almost sevenfold and were associated with low sST2 levels. These functional variants are biomarkers of infection or aGVHD death and could facilitate donor selection, prophylaxis, and a conditioning regimen to reduce post-HCT mortality.
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    Validation of genetic associations with acute GVHD and nonrelapse mortality in DISCOVeRY-BMT
    (American Society of Hematology, 2019-08-13) Tang, Hancong; Hahn, Theresa; Karaesmen, Ezgi; Rizvi, Abbas A.; Wang, Junke; Paczesny, Sophie; Wang, Tao; Preus, Leah; Zhu, Qianqian; Wang, Yiwen; Haiman, Christopher A.; Stram, Daniel; Pooler, Loreall; Sheng, Xin; Van Den Berg, David; Brock, Guy; Webb, Amy; Pasquini, Marcelo C.; McCarthy, Philip L.; Spellman, Stephen R.; Sucheston-Campbell, Lara E.; Pediatrics, School of Medicine