BRENDA

BACKGROUND: We conducted a phase 1 trial to determine the maximum tolerated dose (MTD), toxicity profile, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of cabozantinib in children with refractory or relapsed solid tumors. METHODS: Patients received cabozantinib tablets on a continuous dosing schedule in a rolling-six escalating phase 1 trial design. PK and PD studies were performed. RESULTS: Forty-one patients, median (range) age 13 (4-18) years, received cabozantinib to achieve a weekly cumulative dose equivalent to 30 (n = 6), 40 (n = 23)...

Despite continuing interest in interprofessional teamwork to improve nurse outcomes and quality of care, there is little research that focuses on nurse job satisfaction and retention after an interprofessional team intervention. This study explored registered nurse (RN) job satisfaction and retention after a purposeful interprofessional team training and structured interprofessional bedside rounds were implemented. As part of a larger study, in this comparative cross-sectional study, pre- and post-intervention data on RN job satisfaction and turnover rate were collected and analyzed...

It is widely recognized that burnout is prevalent in medical culture and begins early in training. Studies show pediatricians and pediatric trainees experience burnout rates comparable to other specialties. Newly developed Accreditation Council for Graduate Medical Education (ACGME) core competencies in professionalism and personal development recognize the unacceptably high resident burnout rates and present an important opportunity for programs to improve residents experience throughout training. These competencies encourage healthy lifestyle practices and cultivation of self-awareness, self-regulation, empathy, mindfulness, and compassion—a paradigm shift from traditional medical training underpinned by a culture of unrealistic endurance and self-sacrifice...

BACKGROUND: Trait and automatic approach-avoidance (AA) tendencies are central concepts in research on affective disorders. We longitudinally examined the associations of trait and automatic AA tendencies with the risk of onset and chronicity of anxiety and depressive disorders. METHODS: Participants were subdivided into those with (n = 766) versus without (n = 1,636) a current anxiety or depression diagnosis at baseline. Clinical diagnoses were reassessed after 2-year follow-up...

Pathogenesis of intracranial aneurysm is complex and the precise biomechanical processes leading to their rupture are uncertain. The goal of our study was to characterize the aneurysmal wall histologically and to correlate histological characteristics with clinical and radiological factors used to estimate the risk of rupture. A new biobank of aneurysm domes resected at the Geneva University Hospitals (Switzerland) was used. Histological analysis revealed that unruptured aneurysms have a higher smooth muscle cell (SMC) content and a lower macrophage content than ruptured domes...

This retrospective case series study, using data obtained through questionnaires and histopathological diagnoses from 656 patients enrolled in the Department of Defense (DoD) Clinical Breast Care Project (CBCP), evaluated associations between hormonal contraceptive use and breast cancer pathology including benign breast pathologies. Three combination hormonal contraceptive agents (COCs) Lo Ovral (LO), Ortho Novum (ON), and Ortho Tri-Cyclen (OTC) were evaluated as they represented the most commonly used hormonal contraceptives in our cohort...

BACKGROUND: Efavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens. METHODS: HIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included...

To understand the potential role of women in leadership positions, data from the American Board of Anesthesiology (ABA) were analyzed to explore the impact of women in the specialty of anesthesiology. The number of newly certified ABA diplomates, oral examiners, and directors from 1985 to 2015 was obtained from the ABA database. The percentages of women in each group were calculated for each year. Because it took an average of 10 years for a diplomate to become an oral examiner and an average of 7 years for an oral examiner to be elected as a director during the study period, the following percentages were compared: women oral examiners versus newly certified women diplomates 10 years prior and women directors versus women oral examiners 7 years prior...

BACKGROUND: In the general population, variation in the serotonin-transporter-linked polymorphic region ( 5-HTTLPR) has been shown to modify the association between stressful events and depression/anxiety. This has not been examined in people with multiple sclerosis (MS). OBJECTIVE: We examined the interaction between significant life events (SLE), 5-HTTLPR and depression/anxiety. METHODS: A population-based longitudinal cohort of 198 people with MS was followed biannually for 2...

The distinct feminization of labour migration in Southeast Asia - particularly in the migration of breadwinning mothers as domestic and care workers in gender-segmented global labour markets - has altered care arrangements, gender roles and practices, as well as family relationships within the household significantly. Such changes were experienced by both the migrating women and other left-behind members of the family, particularly 'substitute' carers such as left-behind husbands. During the women's absence from the home, householding strategies have to be reformulated when migrant women-as-mothers rewrite their roles (but often not their identities) through labour migration as productive workers who contribute to the well-being of their children via financial remittances and 'long-distance mothering', while left-behind fathers and/or other family members step up to assume some of the tasks vacated by the mother...

The mammalian hippocampus, comprised of serially connected subfields, participates in diverse behavioral and cognitive functions. It has been postulated that parallel circuitry embedded within hippocampal subfields may underlie such functional diversity. We sought to identify, delineate, and manipulate this putatively parallel architecture in the dorsal subiculum, the primary output subfield of the dorsal hippocampus. Population and single-cell RNA-seq revealed that the subiculum can be divided into two spatially adjacent subregions associated with prominent differences in pyramidal cell gene expression...

OBJECTIVE Somatic variants are a recognized cause of epilepsy-associated focal malformations of cortical development (MCD). We hypothesized that somatic variants may underlie a wider range of focal epilepsy, including non-lesional focal epilepsy (NLFE). Through genetic analysis of brain tissue, we evaluated the role of somatic variation in focal epilepsy with and without MCD. METHODS We identified somatic variants through high-depth exome and ultra-high-depth candidate gene sequencing of DNA from epilepsy surgery specimens and leukocytes from 18 individuals with NLFE and 38 with focal MCD...

OBJECTIVES: To describe the perspectives of clinicians and researchers on identifying, establishing and implementing core outcomes in haemodialysis and their expected impact. DESIGN: Face-to-face, semistructured interviews; thematic analysis. STETTING: Twenty-seven centres across nine countries. PARTICIPANTS: Fifty-eight nephrologists (42 (72%) who were also triallists). RESULTS: We identified six themes: reflecting direct patient relevance and impact (survival as the primary goal of dialysis, enabling well-being and functioning, severe consequences of comorbidities and complications, indicators of treatment success, universal relevance, stakeholder consensus); amenable and responsive to interventions (realistic and possible to intervene on, differentiating between treatments); reflective of economic burden on healthcare; feasibility of implementation (clarity and consistency in definition, easily measurable, requiring minimal resources, creating a cultural shift, aversion to intensifying bureaucracy, allowing justifiable exceptions); authoritative inducement and directive (endorsement for legitimacy, necessity of buy-in from dialysis providers, incentivising uptake); instituting patient-centredness (explicitly addressing patient-important outcomes, reciprocating trial participation, improving comparability of interventions for decision-making, driving quality improvement and compelling a focus on quality of life)...

OBJECTIVE: In 2015, the Advisory Committee on Immunization Practices (ACIP) made a category B recommendation for use of serogroup B meningococcal (MenB) vaccines, meaning individual clinical decision-making should guide recommendations. This was the first use of a category B recommendation pertaining to a large population and the first such recommendation for adolescents. As part of a survey regarding MenB vaccine, our objectives were to assess among pediatricians (Peds) and family physicians (FPs) nationally: 1) knowledge of the meaning of category A versus B recommendations and insurance coverage implications; and 2) attitudes about category A and B recommendations...

INTRODUCTION: Drug use and drug overdose have increased at an alarming rate. OBJECTIVE: To identify demographic and neighborhood social and economic factors associated with higher risk of overdose. These findings can be used to inform development of community programs and appropriately devote resources to prevent and treat drug abuse. METHODS: The electronic health records of all patients seen in the emergency department or admitted to the hospital for a drug overdose in 2016 at Gundersen Health System in La Crosse, Wisconsin, were reviewed retrospectively...

Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascular access is limited. Pharmacokinetic (PK) data in children are sparse, and the bioavailability of intramuscular ketamine in children is unknown. We performed 2 prospective PK studies of ketamine in children receiving either intramuscular or intravenous ketamine and combined the data to develop a pediatric population PK model using nonlinear mixed-effects methods...

Purpose: Retinoic acid (RA) is required for embryonic formation of the anterior segment of the eye and craniofacial structures. The present study further investigated the role of RA in maintaining the function of these neural crest-derived structures in adult zebrafish. Methods: Morphology and histology were analyzed by using live imaging, methylacrylate sections, and TUNEL assay. Functional analysis of vision and aqueous humor outflow were assayed with real-time imaging...

This article highlights how academia and industry leaders in health care communication can partner to provide students practice caring for individuals who are limited English proficient and how such practice opportunities can be integrated into academic programs. Highlighted are key elements to consider when partnering with industry leaders to develop a program for students. A course exemplar provides a comprehensive description of a practice exercise integrated in a nursing physical assessment course. Students obtain hands-on experiences caring for limited English proficient standardized patients using state-of-the-art digital video interpreting technology...

SCOPE: We evaluated the effect of the prebiotic fiber xylooligosaccharide (XOS) on kidney function and gut microbiome in mice with adenine-induced chronic kidney disease (CKD). METHOD AND RESULTS: Mice were fed the control diet containing adenine for three weeks to induce CKD and switched to XOS supplemented (2 or 7%) or control diets for another 3 weeks. Mice with CKD exhibited increased BUN, creatinine and kidney histopathology. XOS significantly reversed kidney injuries in CKD mice...

Burkitt lymphoma (BL) occurs as three subtypes: endemic BL, immunosuppression-related BL and sporadic BL. Descriptive studies of BL age-specific incidence patterns have suggested multimodal peaks near 10, 40 and 70 years of age, but the risk factors for BL at different ages are unknown. We investigated risk factors for BL in the United Kingdom among 156 BL cases and 608 matched BL-free controls identified in the Clinical Practice Research Datalink (CPRD) between 1992 and 2016. Associations with pre-diagnostic body mass index, cigarette smoking, alcohol consumption, hepatitis, Epstein-Barr virus (EBV), human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), malaria, allergic and autoimmune conditions, and prednisone use were evaluated...