Exact boundary conditions in numerical relativity using multiple grids: scalar field tests

Cauchy-Characteristic Matching (CCM), the combination of a central 3+1 Cauchy code with an exterior characteristic code connected across a time-like interface, is a promising technique for the generation and extraction of gravitational waves. While it provides a tool for the exact specification of boundary conditions for the Cauchy evolution, it also allows to follow gravitational radiation all the way to infinity, where it is unambiguously defined. We present a new fourth order accurate finite difference CCM scheme for a first order reduction of the wave equation around a Schwarzschild black hole in axisymmetry. The matching at the interface between the Cauchy and the characteristic regions is done by transfering appropriate characteristic/null variables. Numerical experiments indicate that the algorithm is fourth order convergent. As an application we reproduce the expected late-time tail decay for the scalar field.Comment: 14 pages, 5 figures. Included changes suggested by referee

Impact of a community-based naloxone distribution program on opioid overdose death rates

Background: In August 2013, a naloxone distribution program was implemented in North Carolina (NC). This study evaluated that program by quantifying the association between the program and county-level opioid overdose death (OOD) rates and conducting a cost-benefit analysis. Methods: One-group pre-post design. Data included annual county-level counts of naloxone kits distributed from 2013 to 2016 and mortality data from 2000-2016. We used generalized estimating equations to estimate the association between cumulative rates of naloxone kits distributed and annual OOD rates. Costs included naloxone kit purchases and distribution costs; benefits were quantified as OODs avoided and monetized using a conservative value of a life. Results: The rate of OOD in counties with 1–100 cumulative naloxone kits distributed per 100,000 population was 0.90 times (95% CI: 0.78, 1.04) that of counties that had not received kits. In counties that received >100 cumulative kits per 100,000 population, the OOD rate was 0.88 times (95% CI: 0.76, 1.02) that of counties that had not received kits. By December 2016, an estimated 352 NC deaths were avoided by naloxone distribution (95% CI: 189, 580). On average, for every dollar spent on the program, there was $2742 of benefit due to OODs avoided (95$1,237, $4882). Conclusions: Our estimates suggest that community-based naloxone distribution is associated with lower OOD rates. The program generated substantial societal benefits due to averted OODs. States and communities should continue to support efforts to increase naloxone access, which may include reducing legal, financial, and normative barriers

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P 5.01; HR, 1.71; P,.001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P 5.002, and HR, 1.47; P,.001), as was overall survival (HR, 1.32; P,.001, and HR, 1.45; P,.001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease

Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes for acute myeloid leukemia (AML) patients. We evaluated 8709 AML patients from the CIBMTR database and, after selection and manual curation of cytogenetics data, 3779 patients in CR1 were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis compared to intermediate-risk patients detected an increased risk of relapse for KMT2A-rearranged and adverse-risk patients (HR 1.27, p = 0.01 and HR 1.71, p < 0.001, respectively). Leukemia-free survival (LFS) was similar for KMT2A and adverse-risk patients (HR 1.26, p = 0.002 and HR 1.47, p < 0.001), as was overall survival (OS) (HR 1.32, p < 0.001 and HR 1.45, p < 0.001). No differences in outcome could be detected when patients were stratified by KMT2A fusion partner. This is the largest study conducted to date on post-HCT outcomes in AML using manually curated cytogenetics for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A rearrangements and adverse-risk disease

Cost effectiveness analysis of Year 2 of an elementary school-located influenza vaccination program–Results from a randomized controlled trial

BACKGROUND: School-located vaccination against influenza (SLV-I) has the potential to improve current suboptimal influenza immunization coverage for U.S. school-aged children. However, little is known about SLV-I’s cost-effectiveness. The objective of this study is to establish the cost-effectiveness of SLV-I based on a two-year community-based randomized controlled trial (Year 1: 2009–2010 vaccination season, an unusual H1N1 pandemic influenza season, and Year 2: 2010–2011, a more typical influenza season). METHODS: We performed a cost-effectiveness analysis on a two-year randomized controlled trial of a Western New York SLV-I program. SLV-I clinics were offered in 21 intervention elementary schools (Year 1 n = 9,027; Year 2 n = 9,145 children) with standard-of-care (no SLV-I) in control schools (Year 1 n = 4,534 (10 schools); Year 2 n = 4,796 children (11 schools)). We estimated the cost-per-vaccinated child, by dividing the incremental cost of the intervention by the incremental effectiveness (i.e., the number of additionally vaccinated students in intervention schools compared to control schools). RESULTS: In Years 1 and 2, respectively, the effectiveness measure (proportion of children vaccinated) was 11.2 and 12.0 percentage points higher in intervention (40.7 % and 40.4 %) than control schools. In year 2, the cost-per-vaccinated child excluding vaccine purchase ($59.88 in 2010 US$) consisted of three component costs: (A) the school costs ($8.25); (B) the project coordination costs ($32.33); and (C) the vendor costs excluding vaccine purchase ($16.68), summed through Monte Carlo simulation. Compared to Year 1, the two component costs (A) and (C) decreased, while the component cost (B) increased in Year 2. The cost-per-vaccinated child, excluding vaccine purchase, was$59.73 (Year 1) and $59.88 (Year 2, statistically indistinguishable from Year 1), higher than the published cost of providing influenza vaccination in medical practices ($39.54). However, taking indirect costs (e.g., averted parental costs to visit medical practices) into account, vaccination was less costly in SLV-I ($23.96 in Year 1,$24.07 in Year 2) than in medical practices. CONCLUSIONS: Our two-year trial’s findings reinforced the evidence to support SLV-I as a potentially favorable system to increase childhood influenza vaccination rates in a cost-efficient way. Increased efficiencies in SLV-I are needed for a sustainable and scalable SLV-I program

Allogeneic Hematopoietic Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A CIBMTR Analysis

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes