Citations

AbstractObjectivesParamedics and emergency medical technicians (EMTs) perform triage at disaster sites. There is a need for disaster triage training. Live simulation training is costly and difficult to deliver. Screen‐based simulations may overcome these training barriers. We hypothesized that a screen‐based simulation, 60 Seconds to Survival (60S), would be associated with in‐game improvements in triage accuracy.MethodsThis was a prospective cohort study of a screen‐based simulation intervention, 60S. Participants included emergency medical services (EMS) personnel from 21 EMS agencies across 12 states. Participants performed assessments (e.g., check for pulse) and actions (e.g., reposition the airway) for 12 patients in each scenario and assigned color‐coded triage levels (red, yellow, green, or black) to each patient. Participants received on‐screen feedback about triage performance immediately after each scenario. A scoring system was designed to encourage accurate and timely triage decisions. Participants who played 60S included practicing EMTs, paramedics, and nurses as well as students studying to assume these roles. Participants played the game at least three times over 13 weeks.ResultsIn total, 2,234 participants began game play and 739 completed the study and were included in the analysis. Overall, the median number of plays of the game was just above the threshold inclusion criteria (three or more plays) with a median of four plays during the study period (interquartile range [IQR] = 3–7). There was a significant difference in triage accuracy from the first play of the game to the last play of the game. Median baseline triage accuracy in the game was 89.7% (IQR = 82.1%–94.9%), which then increased to a median of 100% at the last game play (IQR = 87.5%–100.0%; p < 0.001). There was some variability in median triage accuracy on fourth through 11th game plays, ranging from 95% to 100%, and on the 12th to 16th plays, the median accuracy was sustained at 100%. There was a significant decrease in the rate of undertriage: from 10.3% (IQR = 5.1%–18.0%) to 0 (IQR = 0%–12.5%; p < 0.001).Conclusion60 Seconds to Survival is associated with improved in‐game triage accuracy. Further study of the correlation between in‐game triage accuracy and improvements in live simulation or real‐world triage decisions is warranted.

AbstractThe prevalence of liver dysfunction and its association with outcomes in patients with previously untreated chronic lymphocytic leukemia (CLL) is unknown. Newly diagnosed (<12 months) previously untreated CLL patients seen at Mayo Clinic, Rochester, MN between 9/1993 and 4/2016 who had baseline assessment of at least one liver function test (LFT) were included in this analysis. The prevalence of liver dysfunction at baseline, proportion of patients who acquired LFT abnormalities, time to first therapy (TTFT) and overall survival (OS) were assessed. An abnormal LFT was present in 82/2336 (3.5%) patients at diagnosis and was associated with advanced Rai stage (Rai III–IV) (21% vs. 6%; P < .001), lower hemoglobin (13.1 g/dL vs. 13.9 g/dL; P < .001), and lower platelet count (187 × 109/L vs. 200 × 109/L; P = .03). Additionally, 236 patients with normal LFTs at diagnosis developed acquired liver dysfunction during follow‐up. Patients with abnormal LFTs at diagnosis had a shorter OS compared to those with normal LFTs (HR 1.80 95% CI 1.13‐2.87; P = .014, adjusted for age, sex, Rai stage, and treatment), although TTFT was not different. Of 52 patients who underwent a liver biopsy, CLL was present in liver tissue in 39/52 (73%) patients, with the portal tracts the most common region involved. Histopathology findings of liver involvement by CLL had limited correlation with choice of CLL therapy. In conclusion, approximately 1 of 25 newly diagnosed CLL patients has abnormal LFTs at diagnosis. Although the TTFT was not different among patients with abnormal LFTs, these patients have a shorter OS compared to those with normal LFTs.

This study builds on previous research that identified fears and concerns heard by procurement coordinators during the donation discussion and that classified those concerns according to the ease with which they can be addressed. In this study, 53 coordinators working for 4 procurement agencies provided data on 323 donation discussions, including fears and concerns expressed by families. The fears and concerns were analyzed by outcome (consent or refusal), race and ethnicity of the family, frequency of reports, and difficulty in addressing. This research confirms many of the findings of the earlier study. The results also indicate that the types of concerns expressed by donor and non–donor families vary somewhat by the family's race and ethnicity. The results can be used to provide training targeted at raising consent rates and to train minority requestors.

Key Points Pembrolizumab was first shown to be clinically active in CLL patients with RT. PD-1 and PD-L1 expression in tumor microenvironment are promising biomarkers to select RT patients for PD-1 blockade.

Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK‐2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK‐2206 in combination with BR in relapsed CLL. Single‐agent MK‐2206 (weekly dosed) was administered one‐week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2‐6. Phase II employed the MTD of MK‐2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6‐cycle of therapy. The maximum tolerated dose of MK‐2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial.

Abstract Introduction Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome‐wide association study (GWAS) for late‐onset AD in Stage 1 sample including whites of European Ancestry, African‐Americans, Japanese, and Israeli‐Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome‐wide significant (GWS) associations in single‐nucleotide polymorphism (SNP)–based tests ( P < 5 × 10 −8 ) were identified for SNPs in PFDN1/HBEGF , USP6NL/ECHDC3 , and BZRAP1‐AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence ( P < 2.7 × 10 −6 ) for gene‐based association in the total sample with a novel locus, TPBG ( P = 1.8 × 10 −6 ). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

Abstract Elucidating mechanisms of chemoresistance is critical to improve cancer therapy, especially for the treatment of pancreatic ductal adenocarcinoma (PDAC). Genome-wide association studies have suggested the less studied gene HEAT repeat-containing protein 1 (HEATR1) as a possible determinant of cellular sensitivity to different chemotherapeutic drugs. In this study, we assessed this hypothesized link in PDAC, where HEATR1 expression is downregulated significantly. HEATR1 silencing in PDAC cells increased resistance to gemcitabine and other chemotherapeutics, where this effect was associated with increased AKT kinase phosphorylation at the Thr308 regulatory site. Mechanistically, HEATR1 enhanced cell responsiveness to gemcitabine by acting as a scaffold to facilitate interactions between AKT and the protein phosphatase PP2A, thereby promoting Thr308 dephosphorylation. Consistent with these findings, treatment with the AKT inhibitor triciribine sensitized HEATR1-depleted PDAC cells to gemcitabine, suggesting that this therapeutic combination may overcome gemcitabine resistance in patients with low HEATR1 expression. Clinically, we found that HEATR1 downregulation in PDAC patients was associated with increased AKT phosphorylation, poor response to tumor resection plus gemcitabine standard-of-care treatment, and shorter overall survival. Collectively, our findings establish HEATR1 as a novel regulator of AKT and a candidate predictive and prognostic indicator of drug responsiveness and outcome in PDAC patients. Cancer Res; 76(3); 572–81. ©2015 AACR.