Hematocrit levels and thrombotic events in patients with polycythemia vera: an analysis of Veterans Health Administration data

Patients with polycythemia vera (PV) have a high incidence of thrombotic events (TEs), contributing to a greater mortality risk than the general population. The relationship between hematocrit (HCT) levels and TE occurrence among patients with PV from the Veterans Health Administration (VHA) was evaluated to replicate findings of the CYTO-PV trial with a real-world patient population. This retrospective study used VHA medical record and claims data from the first claim with a PV diagnosis (index) until death, disenrollment, or end of study, collected between October 1, 2005, and September 30, 2012. Patients were aged ? 18 years at index, had ? 2 claims for PV (ICD-9-CM code, 238.4) ? 30 days apart during the identification period, continuous health plan enrollment from 12 months pre-index until end of study, and ? 3 HCT measurements per year during follow-up. This analysis focused on patients with no pre-index TE, and with all HCT values either < 45% or ? 45% during the follow-up period. The difference in TE risk between HCT groups was assessed using unadjusted Cox regression models based on time to first TE. Patients (N = 213) were mean (SD) age 68.9 (11.5) years, 98.6% male, and 61.5% white. TE rates for patients with HCT values < 45% versus ? 45% were 40.3% and 54.2%, respectively. Among patients with ? 1 HCT before TE, TE risk hazard ratio was 1.61 (95% CI, 1.03–2.51; P = 0.036). This analysis of the VHA population further supports effective monitoring and control of HCT levels < 45% to reduce TE risk in patients with PV.WOS:000495797000006Scopus - Affiliation ID: 60105072PMID: 31552445Science Citation Index ExpandedQ2ArticleUluslararası işbirliği ile yapılan - EVETKasım2019YÖK - 2019-2

Elevated white blood cell levels and thrombotic events in patients with polycythemia vera: a real-world analysis of veterans health administration data

Background: Patients with polycythemia vera (PV) have a substantial risk of thrombotic events (TEs). The objective of the present analysis was to describe the association between white blood cell (WBC) levels and occurrence of TEs among patients with PV from a large real-world population. Patients and Methods: The present retrospective analysis using Veterans Health Administration claims data (October 1, 2005, to September 30, 2012) evaluated adult patients assigned to 4 WBC count categories (WBC count < 7.0, 7.0-8.4, 8.5 to < 11.0, and ≥ 11.0 × 109/L) to compare the risk of TEs (reference, WBC count, < 7.0 × 109/L group). Analysis was performed using a Cox proportional hazards model, considering WBC status as a time-dependent covariate. Results: Of the 1565 patients with PV included in the present analysis, the WBC count was < 7.0 × 109/L for 428 (27.3%), 7.0 to 8.4 × 109/L for 375 (24.0%), 8.5 to < 11.0 × 109/L for 284 (18.1%), and ≥ 11.0 × 109/L for 478 (30.5%). Of the 1565 patients, 390 (24.9%) had experienced a TE during the study period. The mean follow-up ranged from 3.6 to 4.5 years. Compared with the reference group (WBC count < 7.0 ×109/L), the hazard ratio for TEs was 1.10 (95% confidence interval [CI], 0.82-1.48; P = .5395), 1.47 (95% CI, 1.10-1.96; P = .0097), and 1.87 (95% CI, 1.44-2.43; P < .0001) for patients with a WBC count of 7.0 to 8.4, 8.5 to < 11.0, and ≥ 11.0 ×109/L, respectively. Conclusion: A positive, significant association between an increased WBC count of ≥ 8.5 ×109/L and the occurrence of TEs was observed in patients with PV. The potential thrombogenic role of WBCs in patients with PV supports the continued inclusion of WBC count control in disease management and evaluation of the response to therapy. © 2019 The AuthorsPatients with polycythemia vera (PV) have a substantial risk of thrombotic events (TEs). In the present retrospective analysis using Veterans Health Administration claims data, 25% of 1565 patients experienced a TE during follow-up. We observed a positive, significant association between white blood cell (WBC) counts ≥ 8.5 × 109/L and TE occurrence (reference, WBC count < 7.0 × 109/L), supporting continued inclusion of WBC count control in disease management. © 2019 The AuthorsIncyte Corporation (Wilmington, DE)WOS:000513918800013Scopus - Affiliation ID: 60105072PMID: 31865003Science Citation Index ExpandedQ3ArticleUluslararası işbirliği ile yapılan - EVETŞubat2020YÖK - 2019-2

Treatment patterns and blood counts in patients with polycythemia vera treated with hydroxyurea in the United States: An analysis from the REVEAL study

BACKGROUND: Polycythemia vera (PV) is associated with increased blood cell counts, risk of thrombosis, and symptoms including fatigue and pruritus. National guidelines support the use of hydroxyurea (HU) in high-risk patients or those with some other clinical indication for cytoreduction. PATIENTS AND METHODS: REVEAL is a prospective, observational study designed to collect data pertaining to demographics, disease burden, clinical management, patient-reported outcomes, and health care resource utilization of patients with PV in the United States. In this analysis, HU treatment patterns and outcomes were assessed from 6 months prior to enrollment to the time of discontinuation, death, or data cutoff. RESULTS: Of the 1381 patients who received HU for ≥ 3 months, the median HU exposure was 23.6 months (range, 3.1-38.5 months). The most common maximum daily HU doses were 1000 mg (30.6%) and 500 mg (30.1%); only 6.4% received ≥ 2 g/d HU. Approximately one-third (32.3%) of patients had dose adjustments, 23.8% had dose interruptions, and 257 (18.6%) discontinued HU. The most common reasons for HU discontinuations and interruptions were adverse events/intolerance (37.1% and 54.5%, respectively) and lack of efficacy (35.5% and 22.1%, respectively). Of those who received HU for ≥ 3 months, 57.1% had hematocrit values \u3e 45% on ≥ 1 occasion, 33.1% continued to receive phlebotomies, and 27.4% had uncontrolled myeloproliferation. CONCLUSION: The results of this analysis emphasize the need for active management of patients with PV with appropriate HU dose titration to maintain blood count control while monitoring for signs and symptoms of HU intolerance

Correlation and variance stabilization in the two group comparison case in high dimensional data under dependencies

Doctor of PhilosophyDepartment of StatisticsGary L. GadburyMultiple testing research has undergone renewed focus in recent years as advances in high throughput technologies have produced data on unprecedented scales. Much of the focus has been on false discovery rates (FDR) and related quantities that are estimated (or controlled for) in large scale multiple testing situations. Recent papers by Efron have directly addressed this issue and incorporated measures to account for high-dimensional correlation structure when estimating false discovery rates and when estimating a density. Other authors also have proposed methods to control or estimate FDR under dependencies with certain assumptions. However, not much focus is given to the stability of the results obtained under dependencies in the literature. This work begins by demonstrating the effect of dependence structure on the variance of the number of discoveries and the false discovery proportion (FDP). A variance of the number of discoveries is shown and the density of a test statistic, conditioned on the status (reject or failure to reject) of a different correlated test, is derived. A closed form solution to the correlation between test statistics is also derived. This correlation is a combination of correlations and variances of the data within groups being compared. It is shown that these correlations among the test statistics affect the conditional density and alters the threshold for significance of a correlated test, causing instability in the results. The concept of performing tests within networks, Conditional Network Testing (CNT) is introduced. This method is based on the conditional density mentioned above and uses the correlation between test statistics to construct networks. A method to simulate realistic data with preserved dependence structures is also presented. CNT is evaluated using simple simulations and the proposed simulation method. In addition, existing methods that controls false discovery rates are used on t-tests and CNT for comparing performance. It was shown that the false discovery proportion and type I error proportions are smaller when using CNT versus using t-tests and, in general, results are more stable when applied to CNT. Finally, applications and steps to further improve CNT are discussed

Recruitment strategies and geographic representativeness for patient survey studies in rare diseases: Experience from the living with myeloproliferative neoplasms patient survey.

BackgroundRecruitment of individuals with rare diseases for studies of real-world patient-reported outcomes is limited by small base populations. Myeloproliferative neoplasms (MPNs) are a group of rare, chronic, hematologic malignancies. In this study, recruitment strategies and geographic representativeness from the Living with MPNs survey are reported.MethodsThe Living with MPNs online cross-sectional survey was conducted between April and November 2016. Individuals 18 to 70 years of age living in the United States and diagnosed with an MPN were eligible to participate. Recruitment approaches included direct contact via emails and postcards; posts on MPN-focused social media and patient advocacy websites; postcard mailings to doctors' offices; and advertisements on medical websites, Google, and Facebook. Geographic representativeness was assessed based on the number of survey respondents living in each state or the District of Columbia and by the number of survey respondents per 10 million residents.ResultsA total of 904 respondents with MPNs completed the survey. The recruitment method yielding the greatest number of respondents was advertisements on MPN-focused social media (47.6% of respondents), followed by emails (35.1%) and postcards (13.9%) sent through MPN advocacy groups. Home state information was provided by 775 respondents from 46 states (range of respondents per state, 1-89). The number of respondents per 10 million residents in the 46 states with respondents ranged from 12.1 to 52.7.ConclusionsRecruitment using social media and communications through patient groups and advocacy organizations are effective in obtaining geographically representative samples of individuals with MPNs in the United States. These approaches may also be effective in other rare diseases

Are patients with high-risk polycythemia vera receiving cytoreductive medications? A retrospective analysis of real-world data

Abstract Background Patients with polycythemia vera (PV) have a higher mortality risk compared with the general population, primarily driven by cardiovascular disease, thrombotic events (TEs), and hematologic transformations. The goal of risk-adapted therapy in PV is prevention of TEs. Current treatment recommendations indicate that high-risk patients (aged ≥ 60 years and/or with history of TEs) should be managed with cytoreductive medications, phlebotomy, and low-dose aspirin. This noninterventional study was conducted to describe real-world cytoreductive medication treatment in adult patients with PV, stratified by risk, in the United States. Methods This retrospective analysis used claims data from the Truven Health MarketScan® database. Inclusion criteria were ≥ 2 nondiagnostic claims for PV ≥ 30 days apart, age ≥ 18 years, continuous enrollment during the preindex period (January 1 to December 31, 2012), and continuous enrollment or death during the postindex period (January 1, 2013, to December 31, 2014). Assessments included patient demographics, clinical characteristics, and treatment with cytoreductive medications. Results A total of 2856 patients were identified for this analysis, including 1823 with high-risk PV and 1033 with low-risk PV. Mean (SD) age was 62.5 (13.5) years, and 65.9% of patients were male. Preindex comorbid conditions of interest were more common in high-risk than low-risk patients, including hypertension (65.0% vs 43.1%), type 2 diabetes (21.7% vs 10.1%), and congestive heart failure (6.6% vs 0.6%). Among patients who received preindex cytoreductive therapy, the most commonly used medications in high-risk (n = 666) and low-risk (n = 160) patients were hydroxyurea (94.7 and 87.5%, respectively), anagrelide (7.4 and 11.9%), and interferon (1.7 and 4.4%). Among patients who initiated cytoreductive therapy postindex, the most commonly used medications in high-risk (n = 100) and low-risk (n = 35) patients were hydroxyurea (97.0 and 91.4%, respectively), anagrelide (4.0 and 2.9%), and interferon (2.0 and 8.6%). Overall, 42.0% of high-risk and 18.9% of low-risk patients received cytoreductive medication during the preindex or postindex periods. Conclusions Despite consistent guideline recommendations for cytoreductive therapy in patients with high-risk PV, this analysis revealed that only a minority of these patients received cytoreductive medication. A notable proportion of high-risk patients with PV would likely benefit from a revised treatment plan that aligns with current guidelines

Cytoreductive treatment patterns among US veterans with polycythemia vera

Abstract Background Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thrombotic and cardiovascular risk, which are key contributors to patient morbidity and mortality. The Veterans Health Administration (VHA) is the largest integrative health network in the United States. Available data concerning patients with PV in this population are limited. Methods This retrospective observational study evaluated the characteristics, management, and outcomes of patients with PV in the VHA Medical SAS® Dataset (October 1, 2005, to September 30, 2012). Inclusion criteria were ≥ 2 claims for PV (ie, PV diagnostic code was recorded) ≥30 days apart during the identification period, age ≥ 18 years, and continuous health plan enrollment from ≥12 months before the index date until the end of follow-up. All data were analyzed using descriptive statistics. Results The analysis included 7718 patients (median age, 64 years; male, 98%; white, 64%). The most common comorbidities before the index date were hypertension (72%), dyslipidemia (54%), and diabetes (24%); 33% had a history of smoking. During the follow-up period (median, 4.8 years), most patients did not receive treatment with cytoreductive therapy, including phlebotomy (53%), or antiplatelet agents, such as aspirin (57%). The thrombotic and cardiovascular event rates per 1000 patient-years were 60.5 and 83.8, respectively. Among patients who received cytoreductive treatment, the thrombotic event rate was 48.9 per 1000 patient-years. The overall mortality rate was 51.2 per 1000 patient-years. Conclusion The notable rates of thrombotic and cardiovascular events observed in this analysis, even among patients receiving cytoreductive treatment, highlight the important unmet clinical needs of patients with PV in the VHA