Study Protocol for a Cluster-Randomized Trial of a Bundle of Implementation Support Strategies to Improve the Fidelity of Implementation of Schoolwide Positive Behavioral Interventions and Supports in Rural Schools

Background: Improving the implementation of evidence-based interventions is important for population-level impacts. Positive Behavioral Interventions and Supports (PBIS) is effective for improving school climate and students’ behavioral outcomes, but rural schools often lag behind urban and suburban schools in implementing such initiatives. Methods/Design: This paper describes a Type 3 hybrid implementation-effectiveness trial of Rural School Support Strategies (RS3), a bundle of implementation support strategies selected to improve implementation outcomes in rural schools. In this two-arm parallel group trial, 40 rural public schools are randomized to receive: 1) a series of trainings about PBIS; or 2) an enhanced condition with training plus RS3. The trial was planned for two years, but due to the pandemic has been extended another year. RS3 draws from the Interactive Systems Framework, with a university-based team (support system) that works with a team at each school (school-based delivery system), increasing engagement through strategies such as: providing technical assistance, facilitating school team functioning, and educating implementers. The primary organizational-level outcome is fidelity of implementation, with additional implementation outcomes of feasibility, acceptability, appropriateness, and cost. Staff-level outcomes include perceived climate and self-reported adoption of PBIS core components. Student-level outcomes include disciplinary referrals, academic achievement, and perceived climate. Mediators being evaluated include organizational readiness, school team functioning, and psychological safety. Discussion: The study tests implementation strategies, with strengths including a theory-based design, mixed methods data collection, and consideration of mediational mechanisms. Results will yield knowledge about how to improve implementation of universal prevention initiatives in rural schools

Changing practice in dementia care in the community: developing and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM)

Background Dementia has an enormous impact on the lives of individuals and families, and on health and social services, and this will increase as the population ages. The needs of people with dementia and their carers for information and support are inadequately addressed at all key points in the illness trajectory. Methods The Unit is working specifically on an evaluation of the impact of the Mental Capacity Act 2005, and will develop practice guidance to enhance concordance with the Act. Phase One of the study has involved baseline interviews with practitioners across a wide range of services to establish knowledge and expectations of the Act, and to consider change processes when new policy and legislation are implemented. Findings Phase 1, involving baseline interviews with 115 practitioners, identified variable knowledge and understanding about the principles of the Act. Phase 2 is exploring everyday decision-making by people with memory problems and their carers

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Acceptability, appropriateness, and feasibility of Rural School Support Strategies for behavioral interventions: a mixed methods evaluation over two years of a hybrid type 3 implementation-effectiveness trial

Abstract Background Positive Behavioral Interventions and Supports (PBIS) is a framework for implementing evidence-based interventions for preventing behavioral issues and improving climate in schools. The implementation of school-wide PBIS with fidelity is complex, requiring leadership commitment, teaming, and coordination of systems for tracking behaviors and consequences. Putting these components in place while ensuring alignment with the values and needs of the school community can be difficult for schools with fewer resources, such as rural schools. Implementation supports are needed, including strategies such as technical assistance, but it is unclear whether lower-cost modalities such as virtual support are acceptable, appropriate, and feasible and whether perceptions vary throughout the implementation process. Methods A type 3 hybrid implementation-effectiveness trial is taking place in 40 Idaho schools, testing a bundle of implementation supports selected to meet the needs of schools in rural areas. Supports include technical assistance from an implementation support practitioner (ISP), didactic trainings, virtual learning sessions, and an online resource portal. Surveys and interviews in the first 2 years of implementation (fall 2019 to spring 2021) explored outcomes of acceptability, appropriateness, and feasibility regarding the implementation supports among more than 150 school stakeholders. Results Evaluations showed high acceptability and appropriateness of the PBIS concepts and training. The 20 schools receiving additional implementation support rated the technical assistance and support from the project’s ISPs as the most acceptable and appropriate resource. Reasons for acceptability were the relationship built with the ISP, the ISP’s expertise, and being a “neutral party.” Although in-person support from the ISP was preferred, remote support was acceptable and increased feasibility of attendance. Virtual learning sessions were acceptable for learning and collaboration, particularly in the second year of implementation, once ISPs had developed closer relationships with school teams. Conclusions School staff found training, technical assistance, and virtual learning sessions to be acceptable and appropriate. Virtual formats of training and technical assistance decreased in acceptability but increased feasibility of attendance. In-person support was preferred during initial implementation, and virtual support was more acceptable thereafter. Trial registration This trial was prospectively registered on ClinicalTrials.gov ( NCT03736395 ), on November 9, 2018