Citations

OBJECTIVE Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS From the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use.

Purpose According to the lung cancer staging project, T1a (≤ 2 cm) non–small-cell lung cancer (NSCLC) should be additionally classified into ≤ 1 cm and > 1 to 2 cm groups. This study aimed to investigate the surgical procedure for NSCLC ≤ 1 cm and > 1 to 2 cm. Methods We identified 15,760 patients with T1aN0M0 NSCLC after surgery from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer–specific survival (LCSS) were compared among patients after lobectomy, segmentectomy, or wedge resection. The proportional hazards model was applied to evaluate multiple prognostic factors. Results OS and LCSS favored lobectomy compared with segmentectomy or wedge resection in patients with NSCLC ≤ 1 cm and > 1 to 2 cm. Multivariable analysis showed that segmentectomy and wedge resection were independently associated with poorer OS and LCSS than lobectomy for NSCLC ≤ 1 cm and > 1 to 2 cm. With sublobar resection, lower OS and LCSS emerged for NSCLC > 1 to 2 cm after wedge resection, whereas similar survivals were observed for NSCLC ≤ 1 cm. Multivariable analyses showed that wedge resection is an independent risk factor of survival for NSCLC > 1 to 2 cm but not for NSCLC ≤ 1 cm. Conclusion Lobectomy showed better survival than sublobar resection for patients with NSCLC ≤ 1 cm and > 1 to 2 cm. For patients in whom lobectomy is unsuitable, segmentectomy should be recommended for NSCLC > 1 to 2 cm, whereas surgeons could rely on surgical skills and the patient profile to decide between segmentectomy and wedge resection for NSCLC ≤ 1 cm.

Background: Statins have proven cardioprotective effects, but higher doses are accompanied by various concerns and may not lead to superior clinical outcomes in Chinese/Asian populations. Objective: We designed a trial to test the efficacy of high-intensity statin therapy for the reduction of periprocedural myocardial infarction (MI) and 1-year major adverse cardiovascular events (MACEs, including cardiovascular death, spontaneous MI, unplanned revascularization) in an Asian population. Methods: A total of 798 Chinese patients with stable angina or acute coronary syndrome (ACS) were randomized to high-intensity atorvastatin (80 mg/d before percutaneous coronary intervention [PCI] and 40 mg/d thereafter for 1 year, n = 400) or moderate-intensity atorvastatin (20 mg/d for 1 year, n = 398). The primary end point was 1-year incidence of MACEs. Result: In patients with stable angina, 1-year MACE rates were not significantly different between moderate- and high-intensity groups (7.6% vs 5.7%, P = 0.53). In contrast, in patients with ACS, the 1-year MACE rate was significantly higher in the moderate- than in the high-intensity atorvastatin group (16.8% vs 10.1%, P = 0.021; adjusted hazard ratio = 1.71, 95% CI = 1.08 to 2.77, P = 0.021). Conclusions: Whereas stable angina patients derive similar benefit from moderate- and high-intensity atorvastatin therapy over the duration of 1 year after PCI, high-intensity statin therapy is superior in ACS patients.

Introduction Acute respiratory failure (ARF) often presents and progresses outside of the intensive care unit. However, recognition and treatment of acute critical illness is often delayed with inconsistent adherence to evidence-based care known to decrease the duration of mechanical ventilation (MV) and complications of critical illness. The goal of this trial is to determine whether the implementation of an electronic medical record-based early alert for progressive respiratory failure coupled with a checklist to promote early compliance to best practice in respiratory failure can improve the outcomes of patients at risk for prolonged respiratory failure and death. Methods and analysis A pragmatic stepped-wedged cluster clinical trial involving 6 hospitals is planned. The study will include adult hospitalised patients identified as high risk for MV >48 hours or death because they were mechanically ventilated outside of the operating room or they were identified as high risk for ARF on the Accurate Prediction of PROlonged VEntilation (APPROVE) score. Patients with advanced directives limiting intubation will be excluded. The intervention will consist of (1) automated identification and notification of clinician of high-risk patients by APPROVE or by invasive MV and (2) checklist of evidence-based practices in ARF (Prevention of Organ Failure Checklist—PROOFCheck). APPROVE and PROOFCheck will be developed in the pretrial period. Primary outcome is hospital mortality. Secondary outcomes include length of stay, ventilator and organ failure-free days and 6-month and 12-month mortality. Predefined subgroup analysis of patients with limitation of aggressive care after study entry is planned. Generalised estimating equations will be used to compare patients in the intervention phase with the control phase, adjusting for clustering within hospitals and time. Ethics and dissemination The study was approved by the institutional review boards. Results will be published in peer-reviewed journals and presented at international meetings. Trial registration number NCT02488174.

Objective: We describe health care simulation, designed primarily for training, and provide examples of how human factors experts can collaborate with health care professionals and simulationists—experts in the design and implementation of simulation—to use contemporary simulation to improve health care delivery. Background: The need—and the opportunity—to apply human factors expertise in efforts to achieve improved health outcomes has never been greater. Health care is a complex adaptive system, and simulation is an effective and flexible tool that can be used by human factors experts to better understand and improve individual, team, and system performance within health care. Method: Expert opinion is presented, based on a panel delivered during the 2014 Human Factors and Ergonomics Society Health Care Symposium. Results: Diverse simulators, physically or virtually representing humans or human organs, and simulation applications in education, research, and systems analysis that may be of use to human factors experts are presented. Examples of simulation designed to improve individual, team, and system performance are provided, as are applications in computational modeling, research, and lifelong learning. Conclusion: The adoption or adaptation of current and future training and assessment simulation technologies and facilities provides opportunities for human factors research and engineering, with benefits for health care safety, quality, resilience, and efficiency. Application: Human factors experts, health care providers, and simulationists can use contemporary simulation equipment and techniques to study and improve health care delivery.

A cancer-promoting histone protein Mutations in the chromatin protein histone H3 are found in a number of pediatric cancers. The lysine-36–to–methionine (K36M) “oncohistone” mutation is seen in almost all chondroblastomas. Fang et al. show that the K36M mutant histones inhibit the normal methylation of this same residue in wild-type H3 histones. They do so by interfering with the enzymes that normally methylate this residue. The altered chromatin methylation patterns alter the expression of known cancer-related genes and impart cancer-related characteristics to the chondrocyte cells. Science , this issue p. 1344