Compared with routine care, pharmacist-managed outpatient-based anticoagulation services attained better quality of anticoagulation control, lower bleeding and thromboembolic events, and resulted in lower health care utilization.

OBJECTIVES Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the U.S. Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. This study estimates the long-term health and economic value of PCSK9 inhibitors for older Americans (aged 51 and older). METHODS We conducted simulations using the Future Elderly Model (FEM), an established dynamic microsimulation model, to project the lifetime outcomes for the U.S. population aged 51 or older. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, and lifetime medical spending resulting from use of PCSK9 inhibitors. We considered two treatment scenarios: 1) current FDA eligibility; and 2) an extended eligibility scenario which includes patients with no pre-existing cardiovascular disease (CVD) but at high-risk. We assumed the price of PCSK9 inhibitors was discounted by 35% in the first 12 years and by 57% thereafter, with gradual uptake of the drug in eligible populations. RESULTS Utilization of PCSK9 inhibitors by individuals covered by current FDA approval would extend life-expectancy at age 51 by an estimated 1.1 years and would yield a lifetime net value of $5,800 per person. If utilization were extended to those at high-risk for CVD, PCSK9 inhibitors would generate a lifetime net benefit of $14,100 per person. CONCLUSION Expanded access to PCSK9 inhibitors would offer positive long-term net value for patients and the U.S. healthcare system at the current discounted prices.

[1] We develop a flow path model for the optimization of a regional water distribution system. The model simultaneously describes a water distribution system in two parts: (1) the water delivery relationship between suppliers and receivers and (2) the physical water delivery network. In the first part, the model considers waters from different suppliers as multiple commodities. This helps the model clearly describe water deliveries by identifying the relationship between suppliers and receivers. The physical part characterizes a physical water distribution network by all possible flow paths. The flow path model can be used to optimize not only the suppliers to each receiver but also their associated flow paths for supplying water. This characteristic leads to the optimum solution that contains the optimal scheduling results and detailed information concerning water distribution in the physical system. That is, the water rights owner, water quantity, water location, and associated flow path of each delivery action are represented explicitly in the results rather than merely as an optimized total flow quantity in each arc of a distribution network. We first verify the proposed methodology on a hypothetical water distribution system. Then we apply the methodology to the water distribution system associated with the Tou-Qian River basin in northern Taiwan. The results show that the flow path model can be used to optimize the quantity of each water delivery, the associated flow path, and the water trade and transfer strategy.

Patients with relapsed/refractory (R/R) higher‐risk myelodysplastic syndromes (MDS) have a dismal median overall survival (OS) after failing hypomethylating agent (HMA) treatment. There is no standard of care for patients after HMA therapy failure; hence, there is a critical need for effective therapeutic strategies. Herein, we present the safety and efficacy of venetoclax + azacitidine in patients with R/R MDS. This phase 1b, open‐label, multicenter study enrolled patients ≥18 years. Patients were treated with escalating doses of oral venetoclax: 100, 200, or 400 mg daily for 14 days every 28‐day cycle. Azacitidine was administered on Days 1–7 every cycle at 75 mg/m2/day intravenously/subcutaneously. Responses were assessed per modified 2006 International Working Group (IWG) criteria. Forty‐four patients (male 86%, median age 74 years) received venetoclax + azacitidine treatment. Median follow‐up was 21.2 months. Hematological adverse events of Grade ≥ 3 included febrile neutropenia (34%), thrombocytopenia (32%), neutropenia (27%), and anemia (18%). Pneumonia (23%) was the most common Grade ≥ 3 infection. Marrow responses were seen including complete remission (CR, n = 3, 7%) and marrow CR (mCR, n = 14, 32%); 36% (16/44) achieved transfusion independence (TI) for RBCs and/or platelets, and 43% (6/14) with mCR achieved hematological improvement (HI). The median time to CR/mCR was 1.2 months, and the median duration of response for CR + mCR was 8.6 months. Median OS was 12.6 months. Venetoclax + azacitidine shows activity in patients with R/R MDS following prior HMA therapy failure and provides clinically meaningful benefits, including HI and TI, and encouraging OS.

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