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Background Oral anticoagulants (OACs) mitigate stroke risk in patients with atrial fibrillation (AF). The study aim was to analyze prevalence and predictors of OAC underutilization. Methods Newly diagnosed AF patients with a CHA2DS2-VASc score ≥ 2 were identified from the US CMS Database (January 1, 2013–December 31, 2017). Patients were stratified based on having an OAC prescription versus not and the OAC prescription group was stratified by direct OAC (DOACs) versus warfarin. Multivariable logistic regression models were used to examine predictors of OAC underutilization. Results Among 1,204,507 identified AF patients, 617,611 patients (51.3%) were not prescribed an OAC during follow-up (mean: 2.4 years), and 586,896 patients (48.7%) were prescribed an OAC during this period (DOAC: 388,629 [66.2%]; warfarin: 198,267 [33.8%]). Age ≥ 85 years (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.55–0.56), female sex (OR 0.96, 95% CI 0.95–0.96), Black race (OR 0.78, 95% CI 0.77–0.79) and comorbidities such as gastrointestinal (GI; OR 0.43, 95% CI 0.41–0.44) and intracranial bleeding (OR 0.29, 95% CI 0.28–0.31) were associated with lower utilization of OACs. Furthermore, age ≥ 85 years (OR 0.92, 95% CI 0.91–0.94), Black race (OR 0.78, 95% CI 0.76–0.80), ischemic stroke (OR 0.77, 95% CI 0.75–0.80), GI bleeding (OR 0.73, 95% CI 0.68–0.77), and intracranial bleeding (OR 0.72, 95% CI 0.65–0.80) predicted lower use of DOACs versus warfarin. Conclusions Although OAC therapy prescription is the standard of care for stroke prevention in AF patients, its overall utilization is still low among Medicare patients ≥ 65 years old, with specific patient characteristics that predict underutilization.

There has been limited evidence reported about the outcomes of oral anticoagulants among patients with venous thromboembolism (VTE) and chronic kidney disease (CKD), especially those with stage V/end-stage renal disease (ESRD). This retrospective cohort analysis of five U.S. claims databases evaluated the risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB) for apixaban versus warfarin among VTE patients diagnosed with CKD, including ESRD. Inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Hazard ratios (HRs) were calculated for recurrent VTE, MB, and CRNMB among patients with CKD who experienced an index VTE. An interaction analysis was conducted to evaluate treatment effects across different stages of CKD. A total of 29,790 VTE patients with CKD were selected for analyses, of whom 10,669 (35.8%) initiated apixaban and 19,121 (64.2%) initiated warfarin. Among IPTW-balanced patient cohorts, the apixaban group had significantly lower risk of recurrent VTE (HR: 0.78; 95% confidence interval [CI]: 0.66–0.92), MB (HR: 0.76; 95% CI: 0.65–0.88), and CRNMB (HR: 0.86; 95% CI: 0.80–0.93) than the warfarin group. When stratified by CKD stage (stage I/II: 8.2%; stage III: 49.4%; stage IV: 12.8%; stage V/ESRD: 12.0%; stage unspecified: 17.6%), no significant interaction was observed for effects of apixaban versus warfarin on recurrent VTE or MB. In summary, apixaban was associated with a significantly lower risk of recurrent VTE and MB than warfarin among VTE patients with CKD. CKD stages did not have significant impact on treatment effects for recurrent VTE and MB.

Background : Mastocytosis is a risk factor for hymenoptera venom anaphylaxis (HVA). Current guidelines recommend measuring tryptase in HVA patients and that those with mastocytosis pursue lifelong venom immunotherapy (VIT). Available data on HVA and mastocytosis largely derives from European single-center studies and the prevalence of HVA with and without mastocytosis in the United States (US) is unknown. Objective : We sought to determine the prevalence of HVA and mastocytosis in the US using an insurance claims database and evaluate the impact of mastocytosis on VIT in HVA patients in a US cohort. Methods :The IBM Watson Database, consisting of insurance claims from approximately 27 million US patients in 2018, was queried to identify patients with HVA and/or mastocytosis. Further, a retrospective study of 161 patients undergoing VIT between 2015 – 2018 at the University of Michigan (U-M) was conducted. Results :In the IBM Watson Database, the prevalence of HVA was 167 per 100,000 (0.167%) and the prevalence of mastocytosis 10 per 100,000 (0.010%) overall and 97 per 100,000 (0.097%) among those with HVA. Mastocytosis showed a 9.7-fold increase among HVA patients versus the general population. In the U-M cohort, 2.6% of VIT patients had mastocytosis. Tryptase level did not correlate with venom reaction severity but was higher in patients with systemic VIT reactions. Conclusions :We observed a lower US HVA prevalence than previously reported. Mastocytosis was more common in US HVA patients, though at lower rates than previously reported. In VIT patients there was no correlation between tryptase level and reaction severity. Key words :Tryptasevenom allergyvenom immunotherapyanaphylaxismastocytosismast cell activation syndromemast cell disease Abbreviations Hymenoptera venom allergyHVAUnited StatesUSVenom immunotherapyVITMast Cell DiseaseMCDAmerican Academy of Allergy, Asthma, and Immunology WOS:000717466600002 2-s2.0-85106369702 PMID: 33895259 Science Citation Index Expanded Q1 Article Uluslararası işbirliği ile yapılan - EVET Kasım 2021 YÖK - 2021-22

In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs).Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models.Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs.Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

Studies have shown that patients with non-valvular atrial fibrillation (NVAF) who discontinue oral anticoagulants (OACs) are at higher risk of complications such as stroke. This analysis compared the risk of non-persistence with OACs among patients with NVAF. Adult patients with NVAF who initiated apixaban, dabigatran, rivaroxaban, or warfarin were identified using 01JAN2013–30JUN2019 data from Centers for Medicare and Medicaid Services and four US commercial claims databases. Non-persistence was defined as discontinuation (no evidence of index OAC use for ≥ 60 days from the last days’ supply) or switch to another OAC. Kaplan–Meier curves were generated to illustrate time to non-persistence along with cumulative incidences of non-persistence. Baseline and time-varying covariates were evaluated, and adjusted Cox proportional hazards models were used to evaluate non-persistence risk. In total, 363,823 patients receiving apixaban, 57,121 receiving dabigatran, 282,831 receiving rivaroxaban, and 317,337 receiving warfarin were included. Of these, 47–72% discontinued/switched OAC therapy within an average 9-month follow-up. Apixaban was associated with a lower risk of non-persistence than were dabigatran (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.61–0.62), rivaroxaban (HR 0.76; 95% CI 0.75–0.76), and warfarin (HR 0.74; 95% CI 0.74–0.75). Dabigatran was associated with a higher risk of non-persistence than were warfarin (HR 1.21; 95% CI 1.19–1.22) and rivaroxaban (HR 1.23; 95% CI 1.22–1.25), and rivaroxaban was associated with a lower risk of non-persistence than was warfarin (HR 0.98; 95% CI 0.97–0.98). Clinical events (stroke/systemic embolism and major bleeding [MB]) during follow-up were predictors of non-persistence (stroke HR 1.57; 95% CI 1.53–1.61; MB HR 2.96; 95% CI 2.92–3.00). In over one million patients with NVAF, our results suggest differences in anticoagulation treatment persistence across OAC agents, even after accounting for clinical events after OAC initiation. It is important for clinicians and patients to take these differences into consideration, especially as non-persistence to OAC therapy is associated with thromboembolic complications.

Introduction Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES. Methods Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014–December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, and SES. For each subgroup, Cox proportional hazard models were used to evaluate if there was a significant interaction (p

Background Patients with cancer are more likely to develop nonvalvular atrial fibrillation (NVAF). Currently there are no definitive clinical trials or treatment guidelines for NVAF patients with concurrent cancer. Objectives This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (stroke/SE) and major bleeding (MB) among NVAF patients with active cancer who were prescribed non–vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods A retrospective observational study was conducted in NVAF patients with active cancer who newly initiated apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with the use of Medicare and 4 U.S. commercial claims databases. Cox models were used to estimate the risk of stroke/SE and MB in the pooled propensity score–matched cohorts. Results A total of 40,271 patients were included, with main cancer types of prostate (29%), female breast (17%), genitourinary (14%), and lung (13%). Compared with warfarin, apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.45-0.78) and MB (HR: 0.58; 95% CI: 0.50-0.68); dabigatran and rivaroxaban had similar risks of stroke/SE (dabigatran: HR: 0.88 [95% CI: 0.54-1.41]; rivaroxaban: HR: 0.82 [95% CI: 0.62-1.08]) and MB (dabigatran: HR: 0.76 [95% CI: 0.57-1.01]; rivaroxaban: HR: 0.95 [95% CI: 0.85-1.06]). Risks of stroke/SE and MB varied among NOAC-NOAC comparisons, while consistent treatment effects were seen for all treatment comparisons across key cancer types. Conclusions Among this cohort of NVAF patients with active cancer, the risk of stroke/SE and MB varied among oral anticoagulants and were consistent across cancer types., Central Illustration

Introduction Non-valvular atrial fibrillation (NVAF) is often accompanied by multiple comorbid conditions, which increase the associated risks and complexity of patient management. This study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) among multimorbid patients with NVAF who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods A retrospective study of patients with NVAF and high multimorbidity who initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013 to 30 September 2015 was conducted using five insurance claims databases. Multimorbidity was defined as six or more comorbid conditions, and 1:1 propensity score matching (PSM) was conducted between the NOAC-warfarin and NOAC-NOAC cohorts. Cox proportional hazard models were used to evaluate the hazard ratios of stroke/SE and MB. Results Of the NVAF population (n = 466,991), 33.4% (n = 155,959) had multimorbidity, including 36,921 apixaban, 10,248 dabigatran, 45,509 rivaroxaban, and 63,281 warfarin patients. Compared to warfarin, apixaban and rivaroxaban were associated with a lower risk of stroke/SE (hazard ratio [HR] 0.63, 95% CI 0.54–0.74; HR 0.70, 95% CI 0.64–0.77, respectively). Apixaban and dabigatran were associated with a lower risk of MB (HR 0.61, 95% CI 0.56–0.67; HR 0.75, 95% CI 0.66–0.86, respectively) and rivaroxaban was associated with a higher risk of MB (HR 1.06, 95% CI 1.01–1.12) compared to warfarin. Conclusions Among patients with NVAF and six or more comorbid conditions, NOACs were associated with varying risk of stroke/SE and MB compared to warfarin and to each other. Rather than a “one drug fits all” approach, our results may be useful for appropriate OAC treatment for multimorbid patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01724-8.

BACKGROUND: Oral anticoagulants (OACs) mitigate stroke and systemic embolism (SE) risk in non-valvular atrial fibrillation (AF) patients but can increase the risk of major bleeding (MB). This study analyzed the gains in event-free time for these outcomes among OAC treatment options represented in the ARISTOPHANES study.METHODS: This sub-analysis consisted of NVAF patients who initiated warfarin, apixaban, dabigatran, or rivaroxaban from 01JAN2013-30SEP2015, with data pooled from Medicare and 4 US commercial claims databases. Propensity score matching was conducted between non-vitamin K antagonist OAC (NOAC) and warfarin cohorts in each database and results were pooled. Laplace regression was used to evaluate the delay in time to stroke/SE and MB events between NOACs and warfarin and between NOACs after the first 12-months of follow-up.RESULTS: The population included 466,991 patients (167,413 warfarin; 108,852 apixaban; 37,724 dabigatran; and 153,002 rivaroxaban). Event-free time gain (95% confidence interval) for apixaban versus warfarin was 101 days (78- 124) for stroke/SE and 116 (103- 130) days for MB. The gain in event-free time for dabigatran versus warfarin was 45 days (3- 87) for stroke/SE and 92 (68- 116) days for MB. The gain in event-free time for rivaroxaban versus warfarin was 63 days (42- 84) for stroke/SE but event-free time decreased by 18 (-31-6) days for MB.CONCLUSIONS: Over 12 months after initiation, apixaban and dabigatran conferred progressive increases in event free time for stroke/SE and MB vs warfarin, whereas rivaroxaban conferred an increase in stroke/SE-free time but a loss in MB-free time vs warfarin.

Background The AMPLIFY trial found significantly lower major bleeding (MB) and similar recurrent venous thromboembolism (VTE) risks associated with apixaban vs warfarin among patients with VTE. Objectives To compare MB, clinically-relevant non-major (CRNM) bleeding, and recurrent VTE risks among clinically-relevant subgroups of newly diagnosed elderly patients with VTE prescribed apixaban vs warfarin. Methods US Medicare patients prescribed apixaban or warfarin within 30 days post-VTE encounter were identified. Propensity score matching (PSM) was used to control for patient characteristics. Cox models were used to assess MB, CRNM bleeding, and recurrent VTE. Subgroup analyses were conducted for index VTE encounter type, index VTE diagnosis type, index VTE etiology, sex, and frailty. Results Post-PSM, 11,363 matched pairs of patients prescribed apixaban or warfarin were identified. Apixaban had lower MB (Hazard Ratio [HR]:0.76; 95% CI:0.64–0.91) and similar recurrent VTE risks (HR:1.04; 95% CI:0.75–1.43) vs warfarin. No significant interactions were observed between treatment and index VTE encounter type, index VTE diagnosis type, or sex for risk of MB, CRNM bleeding, or recurrent VTE. Significant interactions: frail patients prescribed apixaban had a 15% lower, while non-frail patients prescribed apixaban had 32% lower CRNM bleeding risk vs those prescribed warfarin. Patients with provoked VTE prescribed apixaban trended toward a higher, while those with unprovoked VTE trended toward a lower risk of recurrent VTE vs patients prescribed warfarin. Conclusions Apixaban was associated with significantly lower risks of MB and CRNM bleeding, and similar risk of recurrent VTE as compared with warfarin across the overall population and most subgroups.

In this research, a novel Collatz conjecture-based image transformation and a modified logistic map are used for digital image watermarking. The proposed modified logistic map is utilized as a pseu...

Introduction The purpose of this study was to identify predictors of initial hospitalization and describe the outcomes of high-risk patients hospitalized with influenza. Methods Data were taken from the 5% national US Medicare database from 2012 to 2015. Patients (aged at least 13 years) were required to have at least one diagnosis for influenza and have continuous health plan enrollment for 6 months before (baseline) and 3 months (follow-up) after the date of influenza diagnosis. Patients who died during follow-up were included. Patients were categorized as initially hospitalized if hospitalized within 0–1 day of diagnosis. High-risk initially hospitalized patients were defined as patients aged at least 65 years or those that had a diagnostic code for chronic lung disease, cardiovascular or cerebrovascular disease, or weakened immune system during baseline period. Logistic regression models were developed to determine predictors of initial hospitalization. Results The study population included 8127 high-risk patients who were initially hospitalized and 16,784 who were not hospitalized. Among high-risk patients, 89.3% were diagnosed in the emergency room, whereas 7.5% and 3.2% were diagnosed in a physician’s office or other Medicare settings, respectively. Chronic obstructive pulmonary disorder, congestive heart failure, chronic kidney disease, older age, being male, other comorbidities, number of comorbidities, and baseline healthcare resource use were the predictors of hospitalization. Median length of stay for the hospitalization was 5.0 days, and the 30-day readmission rate was 14%. All-cause mortality rate was 5.1% during the inpatient stay and 9.2% within 30 days of diagnosis. Hospitalized patients with influenza incurred an increase of $16,568 per patient in total all-cause healthcare costs from pre-influenza to post-influenza diagnosis. Conclusion The study characterized the burden of hospitalization for influenza and found that hospitalized high-risk patients experience greater comorbidity burden, higher likelihood of multiple inpatient admissions, and costly medical interventions compared to patients who were not hospitalized. Electronic supplementary material The online version of this article (10.1007/s40121-020-00354-x) contains supplementary material, which is available to authorized users.

**Background:** The study investigated the economic burden of vaso-occlusive crisis (VOC) among sickle cell disease (SCD) patients, through assessment of overall utilization and costs and costs per VOC episode (regarding the number of VOC episodes and health care setting, respectively). **Methods:** Using the Medicaid Analytic Extracts database, the first SCD-related diagnosis claim (index claim) between June 1, 2009–December 31, 2012 was identified among eligible adults. Patients were required to have continuous medical and pharmacy benefits for 6 months pre- and 12 months post-index. Discrete VOC claims identified within a 3-day gap were combined as a single VOC episode. Annual all-cause and SCD-related medical resources and costs were identified and stratified by number of VOC episodes during the 1-year follow-up period. Health care costs per VOC episode were also examined, stratified by care setting. **Results:** Enrollees included 8521 eligible patients with a mean age of 32.88 years (SD=12.21). Of these, 66.5% had a Charlson Comorbidity index (CCI) score of 0 (no comorbidities) and 67.3% were female. The average total medical costs were US$34 136 (median=US$12 691) annually, and SCD accounted for 60% of the total costs (mean=US$20 206, median=US$1204). Patients with >3 episodes had the highest annual SCD-related costs (mean=US$58 950) across all settings. Health care resource utilization (HCRU) and costs increased substantially as the number of VOC episodes increased. This study was limited to observation of associations rather than causal inference, and by possible coding and identification discrepancies and the restricted generalizability of the population. **Conclusions:** VOC has a severe impact on medical resource use and costs among the adult SCD population. Further research among broader study populations is needed to facilitate the reduction of VOC episodes and thereby improve clinical and economic outcomes for SCD patients.

To compare the clinical and economic burden of treatment-resistant depression (TRD) among older adult patients with major depressive disorder (MDD) to non-TRD MDD and non-MDD patients.Retrospective cohort study using 5% Medicare data (January 1, 2012-December 31, 2015) for MDD patients aged ≥65 years who were defined as TRD if they received ≥2 antidepressant treatments in the current episode. MDD patients not meeting TRD criteria were deemed non-TRD MDD; those without an MDD diagnosis were categorized as non-MDD. All were required to have continuous health plan enrollment for ≥6 months pre- and ≥12 months postindex date (index: first antidepressant claim/random [non-MDD]). Three cohorts were matched, and generalized linear and Cox proportional hazards models were used to compare medication use, healthcare resource utilization, costs, and risks of initial hospitalization and readmission ≤30 days postdischarge from initial hospitalization.After matching, 178 patients from each cohort were analyzed. During 12 months of follow-up, TRD patients had higher use of different antidepressants and antipsychotics, higher inpatient and emergency room visits, longer inpatient stays, and higher total healthcare costs ($24,543 versus $16,059, $8,058) than non-TRD MDD and non-MDD cohorts, respectively (all p0.05). Risk of initial hospitalization was higher in the TRD (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 2.08-6.23) and non-TRD MDD cohorts (HR = 1.82, 95% CI = 1.02-3.25) than the non-MDD cohort.The burden of MDD among older adult Medicare beneficiaries is substantial, and even greater among those with TRD compared to non-TRD MDD, demonstrating the need for more effective treatments than those currently available.

In this research, a bio-based graft copolymer (LCC-g-PCL) based on the cellulose of Luffa cylindrica (LCC) main chain possessing poly(ɛ-caprolactone) (PCL) pendant groups is synthesized through a grafting from approach via ring-opening polymerization (ROP). For this purpose, LCC, extracted from luffa sponges by combined method, is utilized for ROP of ɛ-caprolactone (ɛ-CL) as a macro-initiator in the presence of stannous octoate as a catalyst. Fourier transform infrared (FT-IR), proton and carbon nuclear magnetic resonance (

OxyContin was reformulated with a polyethylene oxide matrix in August 2010 to reduce the potential for intravenous abuse and for abuse by insufflation. The objective of this study was to evaluate the impact of OxyContin's reformulation on overdose (OD) risk for individuals dispensed OxyContin in comparison to those dispensed other opioids under regular care.Three national insurance databases with National Death Index linkage identified OD in individuals with any dispensing of OxyContin or a primary comparator opioid (extended release morphine, transdermal fentanyl, or methadone) between July 2008 through September 2015. A difference-in-differences design was used to compare the pre-post reformulation changes in OD rates for OxyContin versus comparators.A total of 297,836 individuals were dispensed OxyContin and 659,673 individuals were dispensed a primary comparator across the 3 databases. Overall, there was little or no difference in the temporal change in OD incidence in comparators versus OxyContin (Medicaid: adjusted ratio-of-rate-ratios (aRoRs) ranging from 0.90 to 1.05; MarketScan/HIRD: aRoR ranging from 1.10 to 1.22). However, restriction to person-time without concomitant opioid use revealed a modestly greater reduction in OD incidence over time during OxyContin use, as the aRoRs comparing the primary comparators to OxyContin ranged from 1.06 to 1.30 in Medicaid and from 1.64 to 1.85 in MarketScan/HIRD.This study did not detect an overall effect of the OxyContin reformulation on OD in insured patients under regular medical care. There is a suggestion of a modestly reduced OxyContin-associated OD risk following the reformulation but only in commercially insured individuals receiving single-opioid regimens.

Aims: Non-valvular atrial fibrillation (NVAF) prevalence increases with age. Hence, evaluating the economic burden among older-aged patients is vital. This study aimed to compare healthcare...

Background This study aimed to evaluate sickle-cell disease (SCD) treatment patterns and economic burden among patients prescribed hydroxyurea (HU) in the US, through claims data. Methods SCD patients with pharmacy claims for HU were selected from the Medicaid Analytic Extracts (MAX) from January 1, 2009 - December 31, 2013. The first HU prescription during the identification period was defined as the index date and patients were required to have had continuous medical and pharmacy benefits for ≥6 months baseline and 12 months follow-up periods. Patient demographics, clinical characteristics, treatment patterns, health care utilization, and costs were examined, and variables were analyzed descriptively. Results A total of 3999 SCD patients prescribed HU were included; the mean age was 19.24 years, most patients were African American (73.3%), and the mean Charlson comorbidity index (CCI) score was 0.6. Asthma (20.3%), acute chest syndrome (15.6%), and infectious and parasitic diseases (20%) were the most prevalent comorbidities. During the 12-month follow-up period, 58.9% (N = 2357) of patients discontinued HU medication. The mean medication possession ratio (MPR) was 0.52, and 22.3% of patients had MPR ≥80%. The average length of stay (LOS) for SCD-related hospitalization was 13.35 days; 64% of patients had ≥1 SCD-related hospitalization. The mean annual total SCD-related costs per patient were $27,779, mostly inpatient costs ($20,128). Conclusions Overall, the study showed the patients had significant unmet needs manifest as poor medication adherence, high treatment discontinuation rates, and high economic burden.

OBJECTIVES Older adult patients are underrepresented in clinical trials comparing non–vitamin K antagonist oral anticoagulants (NOACs) and warfarin. This subgroup analysis of the ARISTOPHANES study used multiple data sources to compare the risk of stroke/systemic embolism (SE) and major bleeding (MB) among very old patients with nonvalvular atrial fibrillation (NVAF) prescribed NOACs or warfarin. DESIGN Retrospective observational study. SETTING The Centers for Medicare & Medicaid Services and three US commercial claims databases. PARTICIPANTS A total of 88 582 very old (aged ≥80 y) NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015. MEASUREMENTS In each database, six 1:1 propensity score matched (PSM) cohorts were created for each drug comparison. Patient cohorts were pooled from all four databases after PSM. Cox proportional hazards models were used to estimate hazard ratios (HRs) of stroke/SE and MB. RESULTS The patients in the six matched cohorts had a mean follow‐up time of 7 to 9 months. Compared with warfarin, apixaban (HR = .58; 95% confidence interval [CI] = .49‐.69), dabigatran (HR = .77; 95% CI = .60‐.99), and rivaroxaban (HR = .74; 95% CI = .65‐.85) were associated with lower risks of stroke/SE. For MB, apixaban (HR = .60; 95% CI = .54‐.67) was associated with a lower risk; dabigatran (HR = .92; 95% CI = .78‐1.07) was associated with a similar risk, and rivaroxaban (HR = 1.16; 95% CI = 1.07‐1.24) was associated with a higher risk compared with warfarin. Apixaban was associated with a lower risk of stroke/SE and MB compared with dabigatran (stroke/SE: HR = .65; 95% CI = .47‐.89; MB: HR = .60; 95% CI = .49‐.73) and rivaroxaban (stroke/SE: HR = .72; 95% CI = .59‐.86; MB: HR = .50; 95% CI = .45‐.55). Dabigatran was associated with a lower risk of MB (HR = .77; 95% CI = .67‐.90) compared with rivaroxaban. CONCLUSION Among very old NVAF patients, NOACs were associated with lower rates of stroke/SE and varying rates of MB compared with warfarin. J Am Geriatr Soc 67:1662–1671, 2019

Atrial fibrillation (AF) prevalence increases with age; > 80% of US adults with AF are aged ≥ 65 years. Compare the risk of stroke/systemic embolism (SE), major bleeding (MB), net clinical outcome (NCO), and major adverse cardiac events (MACE) among elderly non-valvular AF (NVAF) Medicare patients prescribed direct oral anticoagulants (DOACs) vs warfarin. NVAF patients aged ≥ 65 years who initiated DOACs (apixaban, dabigatran, and rivaroxaban) or warfarin were selected from 01JAN2013-31DEC2015 in CMS Medicare data. Propensity score matching was used to balance DOAC and warfarin cohorts. Cox proportional hazards models estimated the risk of stroke/SE, MB, NCO, and MACE. 37,525 apixaban–warfarin, 18,131 dabigatran–warfarin, and 55,359 rivaroxaban–warfarin pairs were included. Compared to warfarin, apixaban (HR: 0.69; 95% CI 0.59–0.81) and rivaroxaban (HR: 0.82; 95% CI 0.73–0.91) had lower risk of stroke/SE, and dabigatran (HR: 0.88; 95% CI 0.72–1.07) had similar risk of stroke/SE. Apixaban (MB: HR: 0.61; 95% CI 0.57–0.67; NCO: HR: 0.64; 95% CI 0.60–0.69) and dabigatran (MB: HR: 0.79; 95% CI 0.71–0.89; NCO: HR: 0.84; 95% CI 0.76–0.93) had lower risk of MB and NCO, and rivaroxaban had higher risk of MB (HR: 1.08; 95% CI 1.02–1.14) and similar risk of NCO (HR: 1.04; 95% CI 0.99–1.09). Compared to warfarin, apixaban had a lower risk for stroke/SE, MB, and NCO; dabigatran had a lower risk of MB and NCO; and rivaroxaban had a lower risk of stroke/SE but higher risk of MB. All DOACs had lower risk of MACE compared to warfarin. Electronic supplementary material The online version of this article (10.1007/s11239-019-01838-5) contains supplementary material, which is available to authorized users.

Background: Purine nucleoside analogs (PNAs) are highly effective for first-line treatment of hairy cell leukemia (HCL). In clinical trials of single PNAs, several adverse events (AEs) were reported; however, little is known regarding the costs and healthcare resource utilization (HRU) resulting from AEs in HCL patients (pts) treated with PNAs in non-clinical trial settings. Objective: Determine the costs and HRU of high incident and clinically important AEs associated with PNA therapy in HCL pts in the Truven MarketScan database. Methods: Adults (aged ≥18 years) with ≥2 HCL diagnosis codes ≥30 days apart during January 1, 2006–December 31, 2015 were included. Pts had ≥1 prescription claim for a PNA (cladribine or pentostatin ± rituximab) after HCL diagnosis date. First PNA claim date was defined as the index date. Pts had continuous health plan enrollment for ≥6 months at baseline and ≥12-months follow-up with no PNA in the baseline period. Pts were placed into cohorts based on the occurrence of myelosuppression (MSPN) and opportunistic infections (OI) as these were highest incident and clinically important AEs observed. Generalized linear models were used to compare outcomes during the 12-month follow-up. Results: Of the 219 pts with no history of MSPN, 101 developed MSPN (incidence [I]: 461 per 1000 pt-years) and of 619 pts with no history of OI, 26 developed OI (I: 42 per 1000 pt-years). Demographics were similar between pts with and without MSPN and OI. Pts who developed OI or MSPN had significantly higher inpatient admissions and costs (Table 1). Conclusions: PNA-treated HCL pts who developed MSPN or OI incurred higher HRU than those who did not develop either condition. This indicates the need for new therapeutic strategies to reduce HCL-treatment-associated toxicities.

Supplemental material, sj-docx-1-tag-10.1177_1756284821997352 for Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients by Steven Deitelzweig, Allison Keshishian, Amiee Kang, Amol D. Dhamane, Xuemei Luo, Neeraja Balachander, Lisa Rosenblatt, Jack Mardekian, Jenny Jiang, Huseyin Yuce and Gregory Y. H. Lip in Therapeutic Advances in Gastroenterology

Importance: Many patients with nonvalvular atrial fibrillation (NVAF) are at a high risk of gastrointestinal (GI) bleeding due to conditions including older age; stage III to V chronic kidney disease (CKD); HAS-BLED (hypertension, kidney or liver disease, stroke history, prior bleeding, unstable international normalized ratio, age >65, drug or alcohol use) score of 3 or greater; corticosteroid, antiplatelet or nonsteroidal anti-inflammatory drug (NSAID) use; or GI conditions. Objective: To compare the risk of stroke and/or systemic embolism (SE) and major bleeding (MB) among patients with NVAF and high risk of GI bleeding who received non-vitamin K antagonist oral anticoagulants (NOACs) vs those who received warfarin. Design, Setting, and Participants: This retrospective cohort study included patients with NVAF who were 75 years and older; had stage III to V CKD; had an HAS-BLED score of 3 or greater; used corticosteroids, antiplatelets, or NSAIDs; or had GI conditions. Data were collected from the Centers for Medicare & Medicaid Services and 4 commercial insurance databases between January 1, 2012, and September 30, 2015. Data analysis was conducted from January 2012 to September 2015. Exposures: New prescription for apixaban, dabigatran, rivaroxaban, or warfarin between January 1, 2013, and September 30, 2015 (identification period). Main Outcomes and Measures: Six propensity score-matched cohorts were created to compare between study drugs. For the primary objective, Cox models were used to estimate stroke and/or SE and MB hazard ratios (HRs). Results: A total of 381054 patients (187489 [49.2%] women) with NVAF and at least 1 high-risk GI bleeding factor were identified (HAS-BLED score ≥3: 284527 [74.7%]; aged ≥75 years: 252835 [66.4%]; corticosteroid, antiplatelet, or NSAID therapy: 107675 [28.3%]; prior GI bleeding conditions: 74818 [19.6%]; and stage III-V CKD: 56892 [14.9%]). All NOACs were associated with a lower risk of stroke and/or SE vs warfarin (apixaban: HR, 0.60; 95% CI, 0.52-0.68; dabigatran: HR, 0.75; 95% CI, 0.64-0.88; rivaroxaban: HR, 0.79; 95% CI, 0.73-0.86). Compared with warfarin, apixaban and dabigatran were associated with a lower risk of MB (apixaban: HR, 0.59; 95% CI, 0.56-0.63; dabigatran: HR, 0.78; 95% CI, 0.70-0.86), while rivaroxaban was associated with a higher risk (HR, 1.11; 95% CI, 1.05-1.16). Conclusions and Relevance: In this study of patients with NVAF and high risk of GI bleed, NOACs were associated with lower rates of stroke and/or SE, but NOACs had varying risks of MB compared with warfarin. These results may help inform treatment options in this patient population..

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Limited evidence is available on outcomes associated with currently available medications from the endothelin receptor antagonist drug class (bosentan, ambrisentan, and macitentan) in elderly patients with pulmonary arterial hypertension. We evaluated mortality in predominantly elderly patients with pulmonary arterial hypertension in the US taking endothelin receptor antagonists. A retrospective administrative claims study was conducted using the Centers for Medicare and Medicaid Services national Medicare database. Patients with pulmonary arterial hypertension were identified using diagnostic codes. Cohort inclusion required age ≥18 years; ≥1 claim for macitentan, ambrisentan, or bosentan between 1 January 2014 and 31 December 2015 (index date and index endothelin receptor antagonist defined by first such claim); continuous enrollment for ≥12 months before and after the index date; and ≥80% of days covered for the index endothelin receptor antagonist. Follow-up was from index date until the earliest of Medicare disenrollment, death, or 31 December 2016. Multivariable Cox proportional hazards regression models were used to estimate mortality hazard ratios with 95% confidence intervals for macitentan vs. ambrisentan or bosentan, adjusting for potential confounders. The study cohort included 1628 patients on index macitentan, 2852 on ambrisentan, and 1972 on bosentan. Overall, 69% of patients were aged ≥65 years and most were females (76%). Macitentan was associated with an 18% lower risk for mortality than ambrisentan (hazard ratio: 0.82, 95% confidence interval: 0.72–0.93; P = 0.0026) and a 39% lower risk than bosentan (hazard ratio: 0.61, 95% confidence interval: 0.53–0.71; P

Background: Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population. Objectives: This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods: This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013-30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score-matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB. Results: Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55–0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72–0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57–0.66) and dabigatran (HR: 0.79, 95% CI: 0.70–0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08–1.21) was associated with a higher risk vs warfarin. Conclusion: Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real-world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population.

This ARISTOPHANES analysis examined stroke/systemic embolism (SE) and major bleeding (MB) among a subgroup of nonvalvular atrial fibrillation (NVAF) patients with obesity prescribed warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) in order to inform clinical decision making. A retrospective observational study was conducted among NVAF patients who were obese and initiated apixaban, dabigatran, rivaroxaban, or warfarin from 1 January 2013&ndash, 30 September 2015, with data pooled from CMS Medicare and four US commercial claims databases. Propensity score matching was completed between NOACs and against warfarin in each database, and the results were pooled. Cox models were used to evaluate the risks of stroke/SE and MB. A total of 88,461 patients with obesity were included in the study. Apixaban and rivaroxaban were associated with a lower risk of stroke/SE vs. warfarin (HR: 0.63, 95% CI: 0.49&ndash, 0.82 and HR: 0.84, 95% CI: 0.72&ndash, 0.98). Dabigatran was associated with a similar risk of stroke/SE compared to warfarin. Compared with warfarin, apixaban and dabigatran had a lower risk of MB (HR: 0.54, 95% CI: 0.49&ndash, 0.61 and HR: 0.75, 95% CI: 0.63&ndash, 0.91). Rivaroxaban was associated with a similar risk of MB compared to warfarin. In this high-risk population with obesity, NOACs had a varying risk of stroke/SE and MB vs. warfarin.

Background Purine nucleoside analogs (PNAs) are the recommended first-line treatment for patients with hairy cell leukemia (HCL), but they are associated with adverse events (AEs). Due to a lack of real-world evidence regarding AEs that are associated with PNAs, we used commercial data to assess AE rates, AE-related health care resource utilization (HCRU), and costs among PNA-treated patients with HCL. Adults aged ≥18 years with ≥2 claims for HCL ≥30 days apart from 1 January 2006 through 31 December 2015 were included. Included patients had ≥1 claim for HCL therapy (cladribine ± rituximab or pentostatin ± rituximab [index date: first claim date]) and continuous enrollment for a ≥ 6-month baseline and ≥ 12-month follow-up period. Patient sub-cohorts were based on the occurrence of myelosuppression and opportunistic infections (OIs). Generalized linear models were used to compare HCRU and costs. Results In total, 647 PNA-treated patients were identified (mean age: 57.1 years). Myelosuppression and OI incidence were 461 and 42 per 1000 patient-years, respectively. Adjusted results indicated that those with myelosuppression had higher rates of hospitalization (47.4% vs 12.4%; P P = .011) and total costs ($57,325 vs $34,733; P = .001) as compared with those without myelosuppression. Similarly, patients with OIs had higher rates of hospitalization (53.8% vs 30.8%; P = .025) and incurred higher mean inpatient costs ($21,494 vs $11,229; P Conclusions PNA therapy is highly effective but associated with significant toxicities that increase costs; these findings indicate a need for therapies with improved toxicity profiles and better risk stratification of patients at risk of developing myelosuppression and OIs.

Supplemental material, sj-pdf-1-pul-10.1177_2045894020954158 for Comparative effectiveness of endothelin receptor antagonists on mortality in patients with pulmonary arterial hypertension in a US Medicare population: a retrospective database analysis by Raymond L. Benza, Cassandra A. Lickert, Lin Xie, William Drake Adesuwa Ogbomo, Huseyin Yuce and Michele R. Cole in Pulmonary Circulation