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BackgroundWe evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic- and community-based health systems within a single Midwestern State.MethodsRetrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011–2018. Primary outcome variables were, proportion of patients with genomic analysis and frequency of mutations. Chemotherapy was categorized as “standard induction” or “other chemotherapy”/targeted therapy, and hypomethylating agents.ResultsOverall, 13% of ND AML patients between 2011 and 2018 had evidence of a genomic sequencing report with a demonstrated increase to 37% since 2016. Genomic testing was more likely performed in patients: aged ≤60 years than >60 years (45% vs. 30%; p = 0.03), treated in academic versus community hospitals (44% vs. 26%; p = 0.01), and in chemotherapy recipients than non-therapy recipients (46% vs. 19%; p < 0.001). Most common mutations were ASXL1, NPM1, and FLT3. Patients ≥75 years had highest proportion (46%) of multiple (≥3) mutations. Overall, 31.2% of patients with AML did not receive any therapy for their disease. This subgroup was older than chemotherapy recipients (mean age: 71.4 vs. 55.7 years, p < 0.001), and was highest (66.2%) in patients ≥75 years.ConclusionsOur results highlight the unmet medical need to increase access to genomic testing to afford treatment options, particularly to older AML patients in the real-world setting, in this new era of targeted therapies.

With the vast development of technology and the evolving needs of patients and health care providers, electronic medical records (EMRs) have become a cornerstone for health information. However, different institutions have used different EMR systems. Our study investigates the potential benefits of implementing an integrated and common platform, known as the Next Generation Electronic Medical Record (NGEMR) in Singapore. The NGEMR allows improved data sharing between health care facilities and can promote better coordination between primary care and specialist care doctors to access patients' records from the same database. This study aims to conduct an economic evaluation of the NGEMR to inform future health care system upgrades. A cost-utility analysis comparing NGEMR with the legacy EMR was conducted using a decision tree model with a 1-year time horizon from a health care system perspective. Input parameters of patients visiting primary care at the National University Polyclinics and specialist outpatient clinics from a General Hospital were extracted from the EMR systems. The incremental cost-effectiveness ratio (ICER) was calculated using costs and quality-adjusted life years (QALYs). NGEMR was cost-effective and yielded a marginal health benefit (0.00006 QALYs gained) at a slightly higher cost (S $2.73; US $2.02), with an ICER of S $46,349 (US $34,298) per QALY. At the willingness-to-pay thresholds of 0.5- and 1-time gross domestic product (GDP) per capita (S $48,899; US $36,185 and S $97,798; US $72,371 per QALY), the implementation of NGEMR had a 52.2% and 64.7% probability of being cost-effective, respectively. The reduction in waiting time to see a specialist resulted in 2.3% fewer hospitalizations. The most influential parameter on the ICER was the probability of receiving duplicate tests, followed by the costs of admission and the probability of seeing a specialist. Reducing the probability of receiving duplicate tests for NGEMR from 20.7% to 13.2% resulted in a cost-saving ICER. A threshold analysis on the proportion of patients with a waiting time of less than 20 days for NGEMR was further explored, as it was a sensitive parameter on the cost-effectiveness of NGEMR. Increasing the proportion of patients with a waiting time of less than 20 days from 45.5% to 56% would result in cost savings for NGEMR. The adoption of NGEMR is cost-effective in Singapore. Beyond cost-effectiveness, the reduction of waiting time between primary and specialist care can lower the possibility of patients' health deterioration, thus reducing hospital admissions. We recommend continuous monitoring of waiting times and the likelihood of having duplicate tests as countries transition from basic to advanced-level EMR systems. Future analyses could benefit from more granular data on timing and clinical indications and incorporate real-world local data as they become available through ongoing NGEMR rollout evaluations.

Cell death mechanisms in T lymphocytes vary according to their developmental stage, cell subset and activation status. The cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are largely unknown. Here we report that MAIT cells express key necroptotic machinery; receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) protein, in abundance. Despite this, we discovered that the loss of RIPK3, but not necroptotic effector MLKL or apoptotic caspase-8, specifically increased MAIT cell abundance at steady-state in the thymus, spleen, liver and lungs, in a cell-intrinsic manner. In contrast, over the course of infection with Francisella tularensis , RIPK3 deficiency did not impact the magnitude of the expansion nor contraction of MAIT cell pools. These findings suggest that, distinct from conventional T cells, the accumulation of MAIT cells is restrained by RIPK3 signalling, likely prior to thymic egress, in a manner independent of canonical apoptotic and necroptotic cell death pathways.