Treatment decisions in primary myelofibrosis (PMF) are guided by numerous prognostic systems. Patient specific comorbidities have influence on treatment related survival, and are considered in clinical contexts, but have not been routinely incorporated into current prognostic models. We hypothesized that patient specific comorbidities would inform prognosis and could be incorporated into a quantitative score. All patients with PMF or secondary MF (sMF) with available DNA and comprehensive electronic health record (EHR) data treated at Vanderbilt University Medical Center between 1995-2016 were identified within Vanderbilt's Synthetic Derivative and BioVU Biobank. We recapitulated established PMF risk scores (e.g., DIPSS, DIPSS plus, GPSS, MIPSS 70+) and comorbidities through EHR chart extraction and next generation sequencing (NGS) on biobanked peripheral blood DNA. The impact of comorbidities was assessed via DIPSS-adjusted overall survival using Bonferroni correction. Comorbidities associated with inferior survival include renal failure/dysfunction (hazard ratio [HR] 4.3; 95% CI 2.1-8.9; p = 0.0001), intracranial hemorrhage (HR 28.7; 95% CI 7.0-116.8; p=2.83e-06), invasive fungal infection (HR 41.2; 95% CI 7.2-235.2; p=2.90e-05), chronic encephalopathy (HR 15.1; 95% CI 3.8-59.4; p=0.0001). The extended DIPSS model including all four significant comorbidities showed a significantly higher discriminating power (C-index 0.81; 95% CI 0.78-0.84) than the original DIPSS model (C-index 0.73; 95% CI 0.70-0.77). In summary, we repurposed an institutional biobank to identify and risk-classify an uncommon hematologic malignancy by established (e.g., DIPSS) and other clinical and pathologic factors (e.g., comorbidities) in an unbiased fashion. The inclusion of comorbidities into risk evaluation may augment prognostic capability of future genetics-based scoring systems.
Background Women with HIV (WWH) have low rates of hormonal or long-acting contraceptive use. Few studies have described contraception use among WWH over time. Methods We examined contraception (including all forms of hormonal contraception, intrauterine devices, and bilateral tubal ligations) use among cis-gender women aged 18-45 years in care at Vanderbilt's HIV clinic (Nashville, TN) from 1998-2018. Weighted annual prevalence estimates of contraception use were described. Cox proportional hazards models examined factors associated with incident contraception use and pregnancy. Results Of the 737 women included, median age at clinic entry was 31 years, average follow-up was 4.1 years. At clinic entry, 47 (6%) women were on contraception and 164 (22%) were pregnant. The median annual percent of time on any contraception use among non-pregnant women was 31.7% and remained stable throughout the study period. Younger age was associated with increased risk of pregnancy and contraceptive use. Psychiatric comorbidity decreased likelihood of contraception (adjusted HR [aHR] 0.52 [95%CI: 0.29-0.93]) and increased likelihood of pregnancy (aHR 1.77 [95%CI: 0.97-3.25]). While not associated with contraceptive use, more recent year of clinic entry was associated with higher pregnancy risk. Race, substance use, CD4 cell count, HIV RNA, smoking, and antiretroviral therapy were not associated with contraception use nor pregnancy. Conclusions Most WWH did not use contraception at baseline nor during follow-up. Likelihood of pregnancy increased with recent clinic entry while contraception use remained stable over time. Continued efforts to ensure access to effective contraception options are needed in HIV clinics.
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