Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Since regulatory elements are conserved between humans and mice, a thorough annotation of cis regulatory variants in mice could aid in this process. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. These effects influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect. We also observe two types of parent-of-origin effects, including classical imprinting and a novel, global allelic imbalance in favor of the paternal allele. We conclude that, as with humans, pervasive regulatory variation influences complex genetic traits in mice and provide a new resource toward understanding the genetic control of transcription in mammals.

Background The objectives of this study were to develop and test in real-world clinical practice the effectiveness of a comprehensive postacute stroke transitional care (TC) management program. Methods and Results The COMPASS study (Comprehensive Post-Acute Stroke Services) was a pragmatic cluster-randomized trial where the hospital was the unit of randomization. The intervention (COMPASS-TC) was initiated at 20 hospitals, and 20 hospitals provided their usual care. Hospital staff enrolled 6024 adult stroke and transient ischemic attack patients discharged home between 2016 and 2018. COMPASS-TC was patient-centered and assessed social and functional determinates of health to inform individualized care plans. Ninety-day outcomes were evaluated by blinded telephone interviewers. The primary outcome was functional status (Stroke Impact Scale-16); secondary outcomes were mortality, disability, medication adherence, depression, cognition, self-rated health, fatigue, care satisfaction, home blood pressure monitoring, and falls. The primary analysis was intention to treat. Of intervention hospitals, 58% had uninterrupted intervention delivery. Thirty-five percent of patients at intervention hospitals attended a COMPASS clinic visit. The primary outcome was measured for 59% of patients and was not significantly influenced by the intervention. Mean Stroke Impact Scale-16 (±SD) was 80.6±21.1 in TC versus 79.9±21.4 in usual care. Home blood pressure monitoring was self-reported by 72% of intervention patients versus 64% of usual care patients (adjusted odds ratio, 1.43 [95% CI, 1.21–1.70]). No other secondary outcomes differed. Conclusions Although designed according to the best available evidence with input from various stakeholders and consistent with Centers for Medicare and Medicaid Services TC policies, the COMPASS model of TC was not consistently incorporated into real-world health care. We found no significant effect of the intervention on functional status at 90 days post-discharge. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02588664.

By allowing for multiple quit attempts over the course of individuals' lives, the simulation can provide more reliable estimates on the health and economic impact of interventions designed to increase abstinence from smoking. Furthermore, the individual nature of the simulation allows for evaluation of outcomes in populations with different baseline profiles. DES provides a framework for comprehensive and appropriate predictions when applied to smoking cessation over smoker lifetimes.

BackgroundThe COMprehensive Post-Acute Stroke Services (COMPASS) pragmatic trial compared the effectiveness of comprehensive transitional care (COMPASS-TC) versus usual care among stroke and transient ischemic attack (TIA) patients discharged home from North Carolina hospitals. We evaluated implementation of COMPASS-TC in 20 hospitals randomized to the intervention using the RE-AIM framework.MethodsWe evaluated hospital-level Adoption of COMPASS-TC; patient Reach (meeting transitional care management requirements of timely telephone and face-to-face follow-up); Implementation using hospital quality measures (concurrent enrollment, two-day telephone follow-up, 14-day clinic visit scheduling); and hospital-level sustainability (Maintenance). Effectiveness compared 90-day physical function (Stroke Impact Scale-16), between patients receiving COMPASS-TC versus not. Associations between hospital and patient characteristics with Implementation and Reach measures were estimated with mixed logistic regression models.ResultsAdoption: Of 95 eligible hospitals, 41 (43%) participated in the trial. Of the 20 hospitals randomized to the intervention, 19 (95%) initiated COMPASS-TC.Reach: A total of 24% (656/2751) of patients enrolled received a billable TC intervention, ranging from 6 to 66% across hospitals.Implementation: Of eligible patients enrolled, 75.9% received two-day calls (or two attempts) and 77.5% were scheduled/offered clinic visits. Most completed visits (78% of 975) occurred within 14 days.Effectiveness: Physical function was better among patients who attended a 14-day visit versus those who did not (adjusted mean difference: 3.84, 95% CI 1.42–6.27, p = 0.002).Maintenance: Of the 19 adopting hospitals, 14 (74%) sustained COMPASS-TC.ConclusionsCOMPASS-TC implementation varied widely. The greatest challenge was reaching patients because of system difficulties maintaining consistent delivery of follow-up visits and patient preferences to pursue alternate post-acute care. Receiving COMPASS-TC was associated with better functional status.Trial registrationClinicalTrials.gov number: NCT02588664. Registered 28 October 2015.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

PEG-ASP doses higher than 3,750 IU are associated with higher rates of VTE, pancreatitis, and hyperglycemia in pediatric patients with pre-B-cell ALL. Patients receiving more than 3,750 IU should have increased monitoring, and larger, multicenter trials are needed to determine if monitoring, VTE prophylaxis, and potential dose capping recommendations should be added to clinical trial protocols.

The model accurately replicated abstinence patterns observed in the clinical trial data using individualized predictions and indicated that varenicline was more effective and may be less costly than bupropion. This simulation incorporated individual predictions of abstinence and relapse, and provides a framework for lifetime modelling that considers multiple quit attempts over time in diverse patient populations using a variety of quit attempt strategies.

Results suggest that increased use of quetiapine for bipolar mania in the US is economically justified and improves health outcomes. In addition, this model illustrates that discrete event simulation is a useful and versatile tool for budget impact analyses.