Optimal treatment allocations in space and time for on-line control of an emerging infectious disease

A key component in controlling the spread of an epidemic is deciding where, whenand to whom to apply an intervention.We develop a framework for using data to informthese decisionsin realtime.We formalize a treatment allocation strategy as a sequence of functions, oneper treatment period, that map up-to-date information on the spread of an infectious diseaseto a subset of locations where treatment should be allocated. An optimal allocation strategyoptimizes some cumulative outcome, e.g. the number of uninfected locations, the geographicfootprint of the disease or the cost of the epidemic. Estimation of an optimal allocation strategyfor an emerging infectious disease is challenging because spatial proximity induces interferencebetween locations, the number of possible allocations is exponential in the number oflocations, and because disease dynamics and intervention effectiveness are unknown at outbreak.We derive a Bayesian on-line estimator of the optimal allocation strategy that combinessimulation–optimization with Thompson sampling.The estimator proposed performs favourablyin simulation experiments. This work is motivated by and illustrated using data on the spread ofwhite nose syndrome, which is a highly fatal infectious disease devastating bat populations inNorth America

FLT3-ITD compared with DNMT3A R882 mutation is a more powerful independent inferior prognostic factor in adult acute myeloid leukemia patients after allogeneic hematopoietic stem cell transplantation: A retrospective cohort study Allojenik hematopoetik kök hücre nakli sonrası yeti�kin akut myeloid lösemi hastalarında, FLT3-ITD, DNMT3A R882 mutasyonu ile kar�ıla�tırıldı�ında daha güçlü bir ba�ımsız kötü prognostik faktördür: Retrospektif kohort çalı�ması

Objective: This study aimed to evaluate DNMT3A exon 23 mutations and their prognostic impacts in the presence of NPM1 and FLT3 mutations in acute myeloid leukemia (AML) patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). Materials and Methods: This study comprised 128 adult AML patients referred to the Hematology-Oncology and Stem Cell Research Center of Shariati Hospital. NPM1 and FLT3-ITD mutations were detected by fragment analysis. For DNMT3A exon 23 mutation analysis, we used Sanger sequencing. Overall survival (OS) and relapse-free survival (RFS) curves were estimated by the Kaplan-Meier method and the log-rank test was used to calculate differences between groups. Results: The prevalence of DNMT3A exon 23 mutations was 15.6 and hotspot region R882 mutations were prominent. RFS and OS were compared in patients with and without DNMT3A exon 23 mutations using univariate analysis and there was no significant difference between these groups of patients. On the contrary, the FLT3-ITD mutation significantly reduced the OS (p=0.009) and RFS (p=0.006) in AML patients after allogeneic HSCT. In the next step, patients with AML were divided into four groups regarding FLT3-ITD and DNMT3A mutations. Patients with DNMT3A R882mut/FLT3-ITDpos had the worst OS and RFS. These results indicate that DNMT3A mutations alone do not affect the clinical outcomes of AML patients undergoing allogeneic HSCT, but when accompanied by FLT3-ITD mutations, the OS was significantly reduced (5-year OS 0 for DNMT3A R882mut/ FLT3-ITDpos patients vs. 62 DNMT3A R882wt/FLT3-ITDneg, p=0.025) and the relapse rate increased. Conclusion: It can be deduced that DNMT3A R882mut/FLT3-ITDpos is an unfavorable prognostic factor in AML patients even after allogeneic HSCT. © 2018 by Turkish Society of Hematology

Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source

Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials

We aimed to elucidate the role of vitamin D supplementation on adipokines through a systematic review and a meta-analysis of randomized placebo-controlled trials (RCTs). The search included PUBMED, Scopus, Web of Science and Google Scholar through July 1st, 2015. Finally we identified 9 RCTs and 484 participants. Meta-analysis of data from 7 studies did not find a significant change in plasma adiponectin concentrations following vitamin D supplementation (mean difference [MD]: 4.45%, 95%CI: −3.04, 11.93, p = 0.244; Q = 2.18, I2 = 0%). In meta-regression, changes in plasma adiponectin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: 0.25; 95%CI: −0.69, 1.19; p = 0.603) and changes in serum 25-hydroxy vitamin D [25(OH)D] levels (slope: −0.02; 95%CI: −0.15, 0.12; p = 0.780). Meta-analysis of data from 6 studies did not find a significant change in plasma leptin concentrations following vitamin D supplementation (MD: −4.51%, 95%CI: −25.13, 16.11, p = 0.668; Q = 6.41, I2 = 21.97%). Sensitivity analysis showed that this effect size is sensitive to one of the studies; removing it resulted in a significant reduction in plasma leptin levels (MD: −12.81%, 95%CI: −24.33, −1.30, p = 0.029). In meta-regression, changes in plasma leptin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: −1.93; 95%CI: −4.08, 0.23; p = 0.080). However, changes in serum 25(OH)D were found to be significantly associated with changes in plasma leptin levels following vitamin D supplementation (slope: 1.05; 95%CI: 0.08, 2.02; p = 0.033). In conclusion, current data did not indicate a significant effect of vitamin D supplementation on adiponectin and leptin levels

Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?—A multicenter EBMT-PDWP study

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.Transplantation and immunomodulatio