Phase II Study of Acalabrutinib, Venetoclax, and Obinutuzumab in a Treatment-Naïve Chronic Lymphocytic Leukemia Population Enriched for High-Risk Disease.

Purpose: The AMPLIFY trial recently established fixed-duration acalabrutinib, venetoclax, and obinutuzumab (AVO) as a new standard-of-care option for patients with previously untreated chronic lymphocytic leukemia (CLL) with wild-type ; however, due to the chemoimmunotherapy control arm, AMPLIFY excluded patients with high-risk aberration, for whom current standards of care are continuous Bruton tyrosine kinase inhibitor therapy or alternatively fixed-duration venetoclax-based doublets. AVO has not previously been evaluated in patients with CLL with aberration.

Methods: This investigator-sponsored, multicenter, phase II study enrolled patients with treatment-naïve CLL enriched for high-risk CLL, defined by aberration (ClinicalTrials.

Placental extracellular vesicles promote cardiomyocyte maturation and fetal heart development.

Congenital heart defects are leading causes of neonatal mortality and are often associated with placental abnormalities, but mechanisms linking placenta and heart development are poorly understood. Herein, we investigated a potential signaling network connecting the placenta and nascent heart in mice. We found that fetal hearts exposed to media conditioned by placental tissue or differentiated wild-type trophoblast stem (TS) cells, but not undifferentiated TS cells, showed increased heart rate and epicardial cell outgrowth.

Construction and validation of an algorithm to separate focal and generalised epilepsy using clinical variables: A comparison of machine learning approaches.

Purpose: Epilepsy type, whether focal or generalised, is important in deciding anti-seizure medication (ASM). In resource-limited settings, investigations are usually not available, so a clinical separation is required. We used a naïve Bayes approach to devise an algorithm to do this, and compared its accuracy with algorithms devised by five other machine learning methods.

Impact of sociodemographic factors, stress, and communication on health-related quality of life in survivors of pediatric cancer.

Background: While most research has largely focused on medical risks associated with reduced health-related quality of life (HRQOL) in survivors, sociodemographic and family factors may also play a role. Thus, we longitudinally examined sociodemographic factors and family factors associated with survivor HRQOL, including adolescent's cancer-specific stress, mother's general stress, and mother-adolescent communication.

Methods: Mothers (N = 80) and survivors (ages 10-23, N = 50) were assessed 5 years following initial diagnosis.

Evaluating the Effect of COVID-19 on Outpatient Opioid Utilization Among Health First Colorado Members and a National Non-Medicaid Cohort: An Interrupted Time Series Analysis.

Objective: COVID-19, coinciding with the opioid epidemic in the United States, has had significant impacts on health-care utilization. While mixed, early analyses signaled a potential resurgence in opioid use following the pandemic. The primary study objective was to assess the association of the COVID-19 pandemic with opioid utilization among Health First Colorado (Colorado's Medicaid Program) members and a non-Medicaid managed care cohort who did not have a diagnosis of cancer or sickle cell disease.

An epilepsy type algorithm developed in India is accurate in Sudan: A prospective validation study.

Purpose: The effects of epilepsy are worse in lower- and middle-income countries (LMICs) where most people with epilepsy live, and where most are untreated. Correct treatment depends on determining whether focal or generalised epilepsy is present. EEG and MRI are usually not available to help so an entirely clinical method is required.

Associations between parental depression, communication, and self-worth of siblings bereaved by cancer.

A child's death from cancer may increase the risk for poor self-worth in bereaved siblings. Furthermore, bereaved parents may experience depressive symptoms and communicate differently with their surviving children. However, limited research has examined family factors associated with self-worth in bereaved siblings.

Intestinal permeability and peripheral immune cell composition are altered by pregnancy and adiposity at mid- and late-gestation in the mouse.

It is clear that the gastrointestinal tract influences metabolism and immune function. Most studies to date have used male test subjects, with a focus on effects of obesity and dietary challenges. Despite significant physiological maternal adaptations that occur across gestation, relatively few studies have examined pregnancy-related gut function.

Interleukin-15 deficient rats have reduced osteopontin at the maternal-fetal interface.

Uterine Natural Killer (NK) cells are the predominant immune cells within the decidua during early pregnancy. These cells are thought to regulate aspects of decidualization and placental development, but their functions remain poorly characterized, especially in species with deeply invading trophoblasts such as humans and rats. Interleukin-15 (IL-15) is a cytokine required for NK cell development and survival.

Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.

We report 21 families displaying neurodevelopmental differences and multiple congenital anomalies while bearing a series of rare variants in (). MAP4K4 has been implicated in many signaling pathways including c-Jun N-terminal and RAS kinases and is currently under investigation as a druggable target for multiple disorders. Using several zebrafish models, we demonstrate that these human variants are either loss-of-function or dominant-negative alleles and show that decreasing Map4k4 activity causes developmental defects.

A Neurology Advanced Referral Management System (NARMS) Reduces Face-to-Face Consultations By Over Sixty Percent.

Background: The COVID-19 pandemic has made neurology clinic waiting times longer. To prevent a build-up of patients waiting, we introduced a neurology advanced referral management system (NARMS) to deal with new referrals from GPs, using advice, investigations, or the telephone, as alternatives to face-to-face (FF) assessment.

Methods: For six months, electronic referrals from GPs were triaged to the above categories.

Differences in cardiac testing resource utilization using two different risk stratification schemes.

Objective: Assess whether changing an emergency department (ED) chest pain pathway from utilizing the Thrombolysis in Myocardial Infarction (TIMI) score for risk stratification to an approach utilizing the History, EKG, Age, Risk, Troponin (HEART) score was associated with reductions in healthcare resource utilization.

Methods: A retrospective, quasi-experimental study using difference-in-differences and interrupted time series specifications evaluated all ED patients with a chest pain encounter from 8/2015 to 7/2019 at a large academic medical center. We included patients age ≥ 18 with negative troponin testing discharged from the ED.

A multiple baseline trial of adapted prolonged exposure psychotherapy for individuals with early phase psychosis, comorbid substance misuse, and a history of adversity: A study protocol.

Background: Adversity is prevalent among people with psychotic disorders, especially those within the first 5 years of a psychotic disorder, called early phase psychosis. Although adversity can lead to many negative outcomes (e.g.

Evaluation of an opioid pain teleconsultation service to address the opioid overdose epidemic in Colorado: A Health First Colorado demonstration project.

Background: Since the mid-1990s, more than 500,000 deaths have been attributed to the opioid overdose epidemic, which has created a serious national crisis affecting public health and social and economic welfare. To mitigate these opioid-related overdoses and deaths, interventions targeted at both the patient and community level are needed.

Objective: This demonstration project sought to determine whether implementation of a provider-to-provider opioid pain teleconsultation service with a pain specialist was correlated with a reduction in inappropriate opioid use and improve health outcomes.

Expression of subunits of an insecticide target receptor varies across tissues, life stages, castes, and species of social bees.

Global losses of insects jeopardize ecosystem stability and crop pollination. Robust evidence indicates that insecticides have contributed to these losses. Notably, insecticides targeting nicotinic acetylcholine receptors (nAChRs) have neurotoxic effects on beneficial insects.

Brentuximab vedotin plus doxorubicin and dacarbazine in nonbulky limited-stage classical Hodgkin lymphoma.

ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) with or without radiation has been the standard treatment for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim positron emission tomography response.

Interprofessional education faculty development survey: Perspectives on IPE and collaborative practice and COVID-19.

The cancellation of in-person classes in March 2020 due to COVID-19 caused a sudden shift in the educational experiences of health profession students enrolled at the University of Michigan (U-M). With the move to remote learning, educators engaging in interprofessional education (IPE) were faced with the challenge of preparing students for interprofessional collaboration from a distance. A survey was designed to investigate the impact of the pandemic on IPE practices and discover educator development needs.

Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism†.

Paternal obesity predisposes offspring to metabolic dysfunction, but the underlying mechanisms remain unclear. We investigated whether this metabolic dysfunction is associated with changes in placental vascular development and is fueled by endoplasmic reticulum (ER) stress-mediated changes in fetal hepatic development. We also determined whether paternal obesity indirectly affects the in utero environment by disrupting maternal metabolic adaptations to pregnancy.

An Internet-Based Cognitive Behavioral Therapy Program for Anxiety and Depression (Tranquility): Adaptation Co-design and Fidelity Evaluation Study.

Background: Internet-based cognitive behavioral therapy (iCBT) is a necessary step toward increasing the accessibility of mental health services. Yet, few iCBT programs have been evaluated for their fidelity to the therapeutic principles of cognitive behavioral therapy (CBT) or usability standards. In addition, many existing iCBT programs do not include treatments targeting both anxiety and depression, which are commonly co-occurring conditions.

Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study.

Background: Both continuous therapy with acalabrutinib and fixed-duration therapy with venetoclax-obinutuzumab are effective for previously untreated chronic lymphocytic leukaemia. We hypothesised that frontline time-limited, minimal residual disease (MRD)-guided triplet therapy with acalabrutinib, venetoclax, and obinutuzumab would induce deep (ie, more patients with undetectable MRD) and durable remissions.

Methods: In this open-label, single-arm, investigator-sponsored, phase 2 study, patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma were recruited from two academic hospitals in Boston, MA, USA.

The influence of a Sprint optimization and training intervention on time spent in the electronic health record (EHR).

Objective: We report the influence of Sprint electronic health record (EHR) training and optimization on clinician time spent in the EHR.

Materials And Methods: We studied the Sprint process in one academic internal medicine practice with 26 providers. Program offerings included individualized training sessions, and the ability to clean up, fix, or build new EHR tools during the 2-week intervention.

A children's epilepsy diagnosis aid: Development and early validation using a Bayesian approach.

Introduction: The diagnosis of epilepsy in children is difficult and misdiagnosis rates can be as much as 36%. Diagnosis in all countries is essentially clinical, based on asking a series of questions and interpreting the answers. Doctors experienced enough to do this are either scarce or absent in very many parts of the world so there is a need to develop a diagnostic aid to help less-experienced doctors or non-physician health workers (NPHWs) do this.

A Framework and Recommendations to Recruit and Engage Faculty Facilitators for Large-Scale IPE Events.

Aims: As integration of interprofessional education (IPE) events gains traction in health sciences, there is an increased need to recruit and train faculty to facilitate student groups from multiple health care disciplines. This report describes a framework used to effectively recruit and prepare faculty as facilitators for a large-scale, one-time IPE event. We detail recruitment strategies, training tools, facilitators' perceptions about the training, and recommendations for future training.