Search

A patient with a history of bipolar II disorder and end-stage renal disease who required hemodialysis for five years abruptly wished to withdraw from dialysis on day seven of her hospital admission for a urinary tract infection. She had never discussed wishing to withdraw from dialysis prior to this hospital admission. She had experienced several symptoms of depression during her stay. Her desire to withdraw from dialysis treatment was discordant with her previously expressed desires, and the psychiatry team determined that her judgment was likely altered by her depressive episode. Given her previous positive response to electroconvulsive therapy (ECT), the psychiatry team recommended that she receive ECT before she choose to withdraw from dialysis.

Objectives To better understand patterns of potentially inappropriate medications (PIMs) from the Beers criteria among older adults hospitalized with heart failure (HF). Design/Setting Observational study of hospitalizations derived from the geographically-diverse REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Participants We examined participants aged ≥65 years with an expert-adjudicated hospitalization for HF. Measurements Beers criteria medications were abstracted from medical records. Results The prevalence of PIMs was 61.1% at admission and 64.0% at discharge. Participants were taking a median of 1 (IQR: 0-1) PIM at hospital admission and a median of 1 (IQR: 0-2) PIM at hospital discharge. Between admission and discharge, 19.1% of patients experienced an increase in the number of PIMs, 15.1% experienced a decrease, and 37% remained on the same number between hospital admission and discharge. The medications with the greatest increase from admission to discharge were proton pump inhibitors (32.6% to 38.6%) and amiodarone (6.2% to 12.2%). The strongest determinant of potentially harmful prescribing patterns was polypharmacy (RR: 1.34, 95% CI: [1.16-1.55], p Conclusions PIMs are common among older adults hospitalized for HF and may be an important target to improve outcomes in this vulnerable population.

BACKGROUND/OBJECTIVES Attitudes toward deprescribing could vary among subpopulations. We sought to understand patient attitudes toward deprescribing among patients with heart failure with preserved ejection fraction (HFpEF). DESIGN Retrospective cohort study. SETTING Academic medical center in New York City. PARTICIPANTS Consecutive patients with HFpEF seen in July 2018-December 2019 at a program dedicated to providing care to older adults with HFpEF. MEASUREMENTS We assessed the prevalence of vulnerabilities outlined in the domain management approach for caring for patients with heart failure and examined data on patient attitudes toward having their medicines deprescribed via the revised Patient Attitudes Toward Deprescribing (rPATD). RESULTS Among 134 patients with HFpEF, median age was 75 (interquartile range 69-82), 60.4% were women, and 35.8% were nonwhite. Almost all patients had polypharmacy (94.0%) and 56.0% had hyperpolypharmacy; multimorbidity (80.6%) and frailty (78.7%) were also common. Overall, 90.3% reported that they would be willing to have one or more of their medicines deprescribed if told it was possible by their doctors; and 26.9% reported that they would like to try stopping one of their medicines to see how they feel without it. Notably, 91.8% of patients reported that they would like to be involved in decisions about their medicines. In bivariate logistic regression, nonwhite participants were less likely to want to try stopping one of their medicines to see how they feel without it (odds ratio 0.25, 95% confidence interval [0.09-0.62], p = 0.005). CONCLUSIONS Patients with HFpEF contend with many vulnerabilities that could prompt consideration for deprescribing. Most patients with HFpEF were amenable to deprescribing. Race may be an important factor that impacts patient attitudes toward deprescribing.

Interferon-alpha (rIFNα) is the only disease-modifying treatment for polycythemia vera (PV), but whether or not it prolongs survival is unknown. This large single center retrospective study of 470 PV patients compares the myelofibrosis-free survival (MFS) and overall survival (OS) with rIFNα to two other primary treatments, hydroxyurea (HU) and phlebotomy-only (PHL-O). The median age at diagnosis was 54 years (range 20-94) and the median follow-up was 10 years (range 0-45). Two hundred and twenty-nine patients were women (49%) and 208 were high-risk (44%). The primary treatment was rIFNα in 93 (20%), HU in 189 (40%), PHL-O in 133 (28%) and other cytoreductive drugs in 55 (12%). The treatment groups differed by ELN risk score (p < 0.001). In low-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 84%, 65% and 55% respectively (p < 0.001) and 20-year OS was 100%, 85% and 80% respectively (p = 0.44). In high-risk patients, 20-year MFS for rIFNα, HU, and PHL-O was 89%, 41% and 36% respectively (p = 0.19) and 20-year OS was 66%, 40%, 14% respectively (p = 0.016). In multivariable analysis, longer time on rIFNα was associated with a lower risk of myelofibrosis (HR: 0.91, p < 0.001) and lower mortality (HR: 0.94, p = 0.012). In conclusion, this study supports treatment of PV with rIFNα to prevent myelofibrosis and potentially prolong survival.

Introduction: The progression of polycythemia vera (PV) to myelofibrosis (MF) is associated with significant morbidity and mortality. Interferon alfa (rIFNa), a disease-modifying agent, has potential to delay or prevent post-PV MF and improve overall survival but supporting data are required. We present results of the largest study demonstrating improved myelofibrosis-free and overall survival (MFS and OS) of rIFNa treated PV patients (pts) compared to other PV pts. Objectives: To estimate the MFS and OS of treated PV pts and determine the relative risk for post-PV MF and mortality of those treated with rIFNa compared to those treated with other standard therapy. Methods and Study Design: To ensure sufficient follow-up for analysis of long-term outcomes, this IRB approved study identified all adult pts treated at our center from 1974-2019 according to PVSG criteria (1974-2007), our published criteria (2008-2016) and WHO criteria (2016-2019) using a standardized query of electronic medical records. Demographic data, clinical characteristics, treatment history and outcomes were collected. The extended follow-up of this large PV cohort permitted us to evaluate the effectiveness of PV therapy using both intention-to-treat (ITT) and treatment duration (on-treatment) analyses. In the ITT analysis, pts were assigned to rIFNa or hydroxyurea (HU) arms according to the first cytoreductive treatment they received for at least one year or to phlebotomy only (PHL-O) if no cytoreductive treatment was given. On-treatment analysis was performed to account for cross-over and assess how duration of a given therapy influenced outcomes. The onset of post-PV MF was defined by IWG-MRT criteria. MFS and OS were estimated using Kaplan-Meier methods and the log-rank test compared survival between treatment arms in ITT analysis. Multivariate analysis of post-PV MF risk and mortality was performed using a Cox proportional hazards model. The model accounts for age at diagnosis and is stratified by treatment arms (ITT) or by treatment as a time-dependent covariate (on-treatment). Results: We identified 306 PV pts whose median age at diagnosis was 54 years (yr) (range 20-91) and of whom 151 (49%) were women. The median follow-up was 11 yr (range 1-45). The first line treatment was rIFNa in 75 (25%), HU in 134 (44%) or other cytoreductive regimens in 37 (12%). PHL-O was instituted in 60 pts (20%). Treatment cross-over occurred in 82 pts (27%), with the least from rIFNa arm (22%) (Table2). Treatment arms differed by age at diagnosis with a median of 50, 59 and 52 years for rIFNa, HU and PHL-O (p The median MFS and OS was 19.5 and 26.3 yr for the entire group; 27 and 28 yr for rIFNa arm; 18 and 26 yr for HU arm; and 14 and 25 yr for PHL-O (log-rank p Accounting for cross-over, 138 pts received rIFNa at any time for a cumulative of 980 patient-years (median: 5.3, range 1-25 yr). On-treatment analysis associated rIFNa with an 8% and 7% relative risk reduction of post-PV MF and all-cause mortality respectively (age-adjusted HR of 0.92, p Discussion: This is the largest study with the longest follow-up of rIFNa treated PV pts and the first to demonstrate that rIFNa yields superior MFS and OS compared to HU or PHL-O. This study addresses the critical issue that randomized controlled trials to date failed to answer owing to limited follow-up duration and lack of surrogate endpoints for survival. Although the median age of the entire group is younger than the reported median age at PV diagnosis, multivariate analysis showed that both the survival benefit of rIFNa and the reduced risk of fibrosis are independent of age. This study supports early use of rIFNa for PV, especially in younger patients who should not be deprived of a disease-modifying therapy for being "low risk" by consensus criteria. Conclusions: rIFNa yields improved MFS and OS of PV patients, independent of age, in this large study with extended follow up. Early use of rIFNa should be considered routinely in the management of PV. Disclosures Ritchie: agios: Other: Advisory board; Tolero: Other: Advisory board; Genentech: Other: Advisory board; Celgene, Incyte, Novartis, Pfizer: Consultancy; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Jazz Pharmaceuticals: Research Funding; Celgene, Novartis: Other: travel support; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Celgene: Other: Advisory board; Pfizer: Other: Advisory board, travel support. Silver:PharmEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction: Polycythemia vera (PV) is characterized by an increased red cell mass resulting in whole blood hyperviscosity, a strong predictor for thrombosis which remains a significant cause of morbidity and mortality1. Leukocytosis, thrombocytosis, and phlebotomy (PHL) rates are reported additive risk factors for thrombosis but their relative significance has been debated. PHL and cytoreductive therapy mitigates the risk of thrombotic complications. However, the relevance of these parameters remain insufficiently studied2,3. Our primary objectives were to assess the significance of these risks and their associations with thrombosis. We also evaluated whether first-line interferon-α (rIFNα), hydroxyurea (HU), and phlebotomy-only (PHL-O) therapy is associated with reduced thrombotic risk. Methods: After IRB approval, 328 patients (pts) were evaluated after diagnosis according to PVSG criteria (1974-2007), published Weill Cornell criteria (2008-2016)4, or WHO 2016 criteria. Demographics, clinical history, laboratory values, bone marrow findings, and genetic mutations were collected by querying our platform containing aggregated clinical data, the Observational Medical Outcomes Partnership Common Data Model5. Using intention-to-treat analysis, pts were assigned to a first-line therapy defined as continuous cytoreductive therapy for ≥1 consecutive year or PHL-O. Covariate differences between the first-line therapy groups at diagnosis were determined using χ2 tests for categorical variables. Overall survival (OS) was derived by the Kaplan-Meier estimator and comparisons of thrombosis risk were performed using a Cox proportional hazards model adjusted for clinically significant covariates such as age. Results: The characteristics of 165 men (50.3%) and 163 women (49.7%) with PV are shown in Table 1. Followup extended up to 45.0 years (yrs) with a median of 10.3 yrs. Median OS was 32.5 yrs. Splanchnic vein thrombosis, stroke, and deep vein thrombosis were the most common events. Median age at first event was 59.1 yrs. Predisposing factors associated with thrombosis included uncontrolled HCT, increasing leukocytosis, and ≥5 PHL during the first year after diagnosis. Elevated HCT was the greatest contributor to thrombosis: males with HCT of 53.0% had thrombotic complications at 10 times the rate of those with HCT of 43.5% and females with HCT of 51.9% had a thrombosis at 6 times the rate of those with HCT 40.0% (Fig 1). Pts with leukocytosis (30.8x109/L) had a thrombosis at 2.5 times the rate of those with a white blood cell (WBC) value of 9.4x109/L. There was a weak association between platelet (PLT) count and thrombosis (data not shown). The mean number of first-year PHL was 5.3±4.3; those pts requiring ≥5 had a thrombosis at 2 times the rate of those that required less (p=0.011). The difference in cumulative incidence of thrombotic events within 10 yrs was statistically significant for pts requiring ≥5 first-year PHL (p=0.031, Fig 2). There was a significant difference in the cumulative incidence of thrombosis during the first 10 yrs of diagnosis dependent on first-line therapy (PHL-O: n=117, HU: n=84, rIFNα: n=40) (p=0.021, Fig 3). The apparent superiority of IFN over HU and PHL in this retrospective study is suggested by 10 year cumulative incidences of thrombotic events of 3.2, 18.0, and 30.6%, respectively. Discussion: There was a significant correlation between HCT, WBC count, and PHL requirements, but not PLT count, with thrombotic events. Elevated HCT was the most important risk factor. However, leukocytosis and first-year PHL rates also contribute as indicated by the higher hazard ratios. This suggests a need for cytoreductive therapy from disease onset. Our analysis shows that rIFNα reduces thrombotic risk when compared to HU and PHL. Conclusion: Multivariate analysis indicates that elevated HCT level is the most important parameter for correlation with thrombosis within the first 10 yrs of illness. However, WBC and PHL rates are also significant. Since thrombosis occurs from the time of diagnosis, our data suggest the need for cytoreductive intervention from onset. Analysis of the three most common first-year therapies shows that HU and PHL are inferior to rIFNα in reducing thrombotic risk. Disclosures Ritchie: Celgene: Other: Advisory board; Pfizer: Other: Advisory board, travel support; Celgene, Novartis: Other: travel support; Jazz Pharmaceuticals: Research Funding; Genentech: Other: Advisory board; agios: Other: Advisory board; Tolero: Other: Advisory board; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Celgene, Incyte, Novartis, Pfizer: Consultancy. Silver:PharmEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.