Citations

Objective: The objective was to assess processes of care for patients with diabetes undergoing elective surgery. Methods: A retrospective review of medical records was conducted to determine frequency of perioperative glucose monitoring, changes in glucose control, and treatment of intraoperative hyperglycemia. Results: A total of 268 patients underwent 287 elective procedures. Mean age was 67 years, 63% were men, 97% had type 2 diabetes, and most (57%) were treated with oral hypoglycemic agents. Average perioperative time was approximately 8 h. Mean preoperative hemoglobin A1c was 7.0%; however, this value was checked in only 52% of cases. A glucose measurement was obtained in 89% of cases in the preoperative area and in 87% in the postanesthesia care unit, but in only 33% of cases did a value get checked intraoperatively. Average glucose was 139 mg/dl preoperatively, increasing to 166 mg/dl postoperatively ( p <.001). Glucose levels increased regardless of type of outpatient medical therapy used to treat hyperglycemia, except for those on combination oral agents plus insulin ( p =.06). Conclusions: These data indicate suboptimal documentation of outpatient hemoglobin A1c. Intraoperative glucose monitoring seldom occurred, despite prolonged periods under anesthesia and perioperative deterioration of glycemic control. Standards need to be developed and interventions are needed to enhance management of diabetes patients undergoing elective procedures.

Objective: Our objective was to assess the application of insulin regimens in surgical postoperative patients with diabetes. Methods: A chart review was conducted of patients with diabetes who were hospitalized postoperatively between January 1 and April 30, 2011. Analysis was restricted to patients hospitalized for ≥3 days and excluded cases with an endocrinology consult. Insulin regimens were categorized as “basal plus short acting,” “short acting only,” or “none,” and the pattern of use was evaluated by hyperglycemia severity according to tertiles of both mean glucose and the number of glucose measurements >180 mg/dl. Results: Among cases selected for analysis ( n = 119), examination of changes in insulin use based on tertiles of mean glucose showed that use of basal plus short-acting insulin increased from 10% in the lowest tertile (mean glucose, 120 mg/dl) to 18% in the highest tertile (mean glucose, 198 mg/dl; p < .01); however, 70% of patients in the highest tertile continued to receive short-acting insulin only, with 12% receiving no insulin. Intensification of insulin to a basal plus short-acting regimen was also seen when changes were evaluated by the number of measurements >180 mg/dl ( p < .01), but 70% and 12% of patients in the highest tertile still remained only on short-acting insulin or received no insulin, respectively. Conclusions: Use of basal plus short-acting insulin therapy increased with worsening hyperglycemia, but many cases did not have therapy intensified to the recommended insulin regimen—evidence of clinical inertia. Strategies should be devised to overcome inpatient clinical inertia in the treatment of postoperative patients with diabetes.

AbstractBackgroundThis study compared prucalopride, a selective, prokinetic, 5‐HT4 receptor agonist, with polyethylene glycol 3350 + electrolytes (PEG3350), an osmotic laxative, on colonic motility parameters, primarily high‐amplitude propagating contractions (HAPCs) in patients with chronic constipation.MethodsThis randomized, cross‐over, reader‐blinded study was conducted at a single site in the USA. The study was open to men and women aged 18–75 years who met study inclusion criteria. Colonic manometry catheters were inserted the day before investigation. On the investigation days, patients received oral 2 mg prucalopride or 2 × 13.8 g PEG3350 in solution. The primary endpoint was HAPC count (threshold: mean amplitude ≥100 mmHg, propagation ≥20 cm [HAPC1]) in the 12 h after treatment administration. Analyses were also conducted at two co‐primary thresholds: mean amplitude ≥75 mmHg, propagation ≥20 cm (HAPC2); and mean amplitude ≥75 mmHg, propagation ≥10 cm (HAPC3). Secondary endpoints included HAPC area under the curve (AUC), contraction force, amplitude, duration, and propagation velocity.Key ResultsThirteen women were enrolled, with 12 completing the study. Significantly more HAPC1 (8.7 ± 2.06 vs 2.9 ± 2.06; p = 0.012) and HAPC2 (9.0 ± 2.11 vs 3.3 ± 2.11; p = 0.017) were observed in the 12‐h periods with prucalopride than with PEG3350. Prucalopride significantly increased mean propagation distance and velocity (HAPC2) and mean AUC, force, and amplitude (HAPC3) compared with PEG3350. Adverse events were mild or moderate.Conclusions & InferencesPrucalopride was superior to PEG3350 in inducing HAPCs in patients with chronic constipation.ClinicalTrials.gov number NCT01707667.

Abstract Motivation: Prediction and prioritization of human non-coding regulatory variants is critical for understanding the regulatory mechanisms of disease pathogenesis and promoting personalized medicine. Existing tools utilize functional genomics data and evolutionary information to evaluate the pathogenicity or regulatory functions of non-coding variants. However, different algorithms lead to inconsistent and even conflicting predictions. Combining multiple methods may increase accuracy in regulatory variant prediction. Results: Here, we compiled an integrative resource for predictions from eight different tools on functional annotation of non-coding variants. We further developed a composite strategy to integrate multiple predictions and computed the composite likelihood of a given variant being regulatory variant. Benchmarked by multiple independent causal variants datasets, we demonstrated that our composite model significantly improves the prediction performance. Availability and Implementation: We implemented our model and scoring procedure as a tool, named PRVCS, which is freely available to academic and non-profit usage at http://jjwanglab.org/PRVCS. Contact: wang.junwen@mayo.edu, jliu@stat.harvard.edu, or limx54@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.

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.

Purpose Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. Methods In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti–PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. Results Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. Conclusion Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B- and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.

Aim The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine. Methods This double-blind, placebo-controlled study randomized 834 participants to treat one migraine attack with ubrogepant 1 mg, 10 mg, 25 mg, 50 mg, 100 mg, or placebo in a 1:1 ratio. The co-primary endpoints were pain freedom and headache response at two hours. The first primary hypothesis tested the dose-response trend for two-hour pain freedom using a logistic regression model. Subsequent hypotheses tested the effects of each dose on the co-primary endpoints, using a closed sequential testing procedure to control for multiplicity. Results A total of 527 participants received ubrogepant and 113 received placebo. A positive response trend in the proportion of participants achieving two-hour pain freedom was demonstrated ( p < 0.001). Ubrogepant 100 mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response. Per the prespecified multiplicity strategy, this nonsignificant result precluded further formal hypothesis testing, although the 50 mg and 25 mg doses demonstrated nominal significance over placebo for two-hour pain freedom (unadjusted p < 0.05). Overall, adverse events were similar between ubrogepant and placebo. Conclusion This trial supports ubrogepant’s efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.

Lack of treatment fidelity can be an important source of variation affecting the credibility and utility of outcomes from behavioral intervention research. Development and implementation of a well-designed treatment fidelity plan, especially with research involving underserved populations, requires careful conceptualization of study needs in conjunction with what is feasible in the population. The purpose of this article is to review a fidelity-monitoring plan consistent with the National Institutes of Health Behavior Change Consortium guidelines (e.g., design, training, delivery, receipt, and enactment) for an intervention trial designed to improve physical activity and nutrition among immigrant and refugee families. Description of the fidelity monitoring plan is provided and challenges related to monitoring treatment fidelity in a community-based participatory intervention for immigrant and refugee families are discussed.