BackgroundTemporal structuring is determined by practices and social norms and affects the quality and timing of care. In this case study of hyperacute stroke wards which provide initial stroke investigation, treatment and care, we explored temporal structuring patterns to explain how these may affect quality of care.MethodsThis paper presents a thematic analysis of qualitative interviews with hyperacute stroke staff (n=76), non-participant observations (n=41, ~102 hours) and documentary analysis of the relevant service standards guidance. We used an inductive coding process to generate thematic findings around the concept of temporal structuring, with graphically illustrated examples.ResultsFive temporal structures influence what-happens-when: (1) clinical priorities and quality assurance metrics motivate rapid activity for the initial life-prolonging assessments and interventions; (2) static features of ward organisation such as rotas and ward rounds impact consistency of care, determining timing and quality of care for patients; (3) some services experimented with staff rotas to try to meet peaks in demand, sometimes unsuccessfully; (4) implicit social norms or heuristics about perceived necessity affected staff motivation to make changes or improvements to consistency of care, particularly around weekend work; and (5) after-effects such as bottlenecks or backlogs affect quality of care, which are hard to measure effectively to drive service improvement.ConclusionsPatients need temporally consistent high quality of care. Temporal consistency stems from the design of services, including staffing, targets and patient pathway design as well as cultural attitudes to working patterns. Improvements to consistency of care will be limited without changes to structures such as rotas and ward rounds, but also social norms around weekend work for certain professional groups.

The tumor microenvironment and wound healing after injury both contain extremely high concentrations of the extracellular signaling molecule, adenosine triphosphate (ATP) compared to normal tissue. P2Y2 receptor, an ATP-activated purinergic receptor, is typically associated with pulmonary, endothelial, and neurological cell signaling. Here we report its role and importance in breast epithelial cell signaling and how it is altered in metastatic breast cancer. In response to ATP activation, P2Y2 receptor signaling causes an increase of intracellular Ca 2+ in non-tumorigenic breast epithelial cells, while their tumorigenic and metastatic counterparts have significantly reduced Ca 2+ responses. The non-tumorigenic cells respond to increased Ca 2+ with actin polymerization and localization to cell edges, while the metastatic cells remained unaffected. The increase in intracellular Ca 2+ after ATP stimulation was blunted using a P2Y2 antagonist, which also prevented actin mobilization and caused cell dissemination from spheroids in non-tumorigenic breast epithelial cells. Furthermore, the lack of Ca 2+ concentration changes and actin mobilization in the metastatic breast cancer cells could be due to reduced P2Y2 expression, which correlates with poorer overall survival in breast cancer patients. This study elucidates rapid changes that occur after elevated intracellular Ca 2+ in breast epithelial cells and how metastatic cancer cells have adapted to evade this cellular response.

Abstract Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 (SGLT2) inhibitors have dramatic clinical benefits, but uptake has been slow. We developed a quality improvement (QI) intervention to increase the adoption of these drugs in patients with Type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and/or heart failure (HF). Methods: The intervention included: 1) education, academic detailing (1:1 pharmacist to clinician coaching), and audit and feedback directed at providers and allied health professionals at the Veterans Affairs Ann Arbor Healthcare System (VAAAHS); 2) outreach and inreach to patients with T2D and ASCVD, CKD, and/or HF who were not on GLP-1 RA or SGLT2 inhibitors at baseline. Patients were identified and outcomes evaluated using existing VA national reports. We performed a difference-in-difference analysis of the change in GLP-1 RA and SGLT2 prescribing rates before, during, and after the intervention, comparing rates in VAAAHS to rates in the same VA region (called a Veterans Integrated Service Network (VISN)) and the VA nationally to determine whether the rates of prescribing increased faster in VAAAHS than the VISN or VA nationally. Results: Home telehealth nurses and clinical pharmacy practitioners (CPPs) provided outreach to 445 patients; 48% (n = 215) of whom initiated SGLT2 inhibitor or GLP-1 RAs. Four CPPs provided 101 academic detailing sessions to 72 providers. Prior to the intervention, the prescribing rate was 22.7% in VAAAHS, 20.3% in the VISN 10 region, and 18.7% in VA nationally. At the end of the 12-month intervention, the prescribing rate had increased to 37.9% in VAAAHS, 28.4% in the VISN 10 region, and 26.5% in VA nationally. Six-months post-intervention, the prescribing rate continued to increase to 42.4% in VAAAHS, 32.2% in the VISN 10 region, and 30.2% in VA nationally. The rate of prescribing growth in VAAAHS was significantly faster than in the VISN or VA nationally (p < 0.001). Conclusion: We developed a multidisciplinary QI intervention using existing VA data that increased SGLT2 inhibitor and GLP-1 RA prescribing substantially.

The construct of psychological resilience has received increasing attention in the mental health field. This article describes the development and initial validation of a novel self-report resilience scale, which addresses gaps in the resilience measurement literature by assessing thoughts and behaviors that help promote resilience rather than traits, and simultaneously evaluating multiple factors previously associated with resilience. Following consensus meetings focused on scale development, we conducted an online study (n = 1,864) of U.S. adults to develop and validate an initial version of the Mount Sinai Resilience Scale (MSRS). An exploratory factor analysis in a random 50% of the sample suggested a seven-factor solution; this solution was then generally supported by a follow-up confirmatory factor analysis in the remaining 50% of the sample. After removing poor-fitting items, a revised 24-item scale correlated in the expected directions with established measures of perceived resilience and resilience-related constructs (e.g., social support and optimism). Collectively, the results of this study provide initial support for the convergent and discriminant validity of the MSRS and describe its factor structure. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Standardized operational definitions are an important tool to improve reproducibility of research using secondary real-world healthcare data. This approach was leveraged for studies evaluating the effectiveness of AZD7442 as COVID-19 pre-exposure prophylaxis across multiple healthcare systems. Value sets were defined, grouped, and mapped. Results of this exercise were reviewed and recorded. Value sets were updated to reflect findings.

Genome-wide association studies (GWAS) have identified a large number of candidate genes believed to affect longitudinal bone growth and bone mass. One of these candidate genes, TMEM263, encodes a poorly characterized plasma membrane protein. Single nucleotide polymorphisms in TMEM263 are associated with bone mineral density in humans and mutations are associated with dwarfism in chicken and severe skeletal dysplasia in at least one human fetus. Whether this genotype-phenotype relationship is causal, however, remains unclear. Here, we determine whether and how TMEM263 is required for postnatal growth. Deletion of the Tmem263 gene in mice causes severe postnatal growth failure, proportional dwarfism, and impaired skeletal acquisition. Mice lacking Tmem263 show no differences in body weight within the first 2 weeks of postnatal life. However, by P21 there is a dramatic growth deficit due to a disrupted growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, which is critical for longitudinal bone growth. Tmem263-null mice have low circulating IGF-1 levels and pronounced reductions in bone mass and growth plate length. The low serum IGF-1 in Tmem263-null mice is associated with reduced hepatic GH receptor (GHR) expression and GH-induced JAK2/STAT5 signaling. A deficit in GH signaling dramatically alters GH-regulated genes and feminizes the liver transcriptome of Tmem263-null male mice, with their expression profile resembling wild-type female, hypophysectomized male, and Stat5b-null male mice. Collectively, our data validates the causal role for Tmem263 in regulating postnatal growth and raises the possibility that rare mutations or variants of TMEM263 may potentially cause GH insensitivity and impair linear growth.

Abstract The sustainability of evidence-based practices (EBPs) is a pressing issue for implementation science and healthcare systems. The COVID-19 pandemic and related policies severely strained healthcare systems, thus representing a key test of the sustainability of EBPs. The current study examined the sustainability of one EBP- cognitive-behavioral therapy for chronic pain (CBT-CP) - in the Veterans Health Administration. Changes in provision of CBT-CP after the onset of COVID-19 were examined both qualitatively, using administrative datasets, and qualitatively, through interviews with CBT-CP providers. Changes in total psychotherapy services were also examined for reference. Results indicated CBT-CP provision was substantially disrupted by COVID-19. Interviewees reported difficulties regarding engagement in virtual sessions, disruptions from the home environment, and logistical challenges. Results indicate specific pathways by which the pandemic may have negatively affected the sustainability of this EBP.

Veterans who do not know about their posttraumatic stress disorder (PTSD) diagnosis experience a fundamental barrier to accessing effective treatment. Little is known about the characteristics that influence veterans’ PTSD diagnosis knowledge (i.e., report of being told they have a PTSD diagnosis by a healthcare provider). Veterans who met probable and provisional criteria for PTSD on the self-report PTSD checklist for DSM-5 were identified from the Comparative Health Assessment Interview Research Study (n = 2335). Weighted logistic regression was performed to identify demographic variables, clinical characteristics, and social determinants of health (e.g., economic instability, homelessness, healthcare coverage) associated with PTSD diagnosis knowledge among post-9/11 veterans. Approximately 62% of veterans with probable and provisional PTSD had PTSD diagnosis knowledge. Predictors with the strongest associations included another mental health diagnosis (OR = 6.10, CI95:4.58,8.12) and having Veterans Affairs (VA) healthcare coverage (OR = 2.63, CI95:1.97,3.51). Veterans with combat or sexual trauma were more likely to have PTSD diagnosis knowledge than those with different trauma types. Results suggest veterans with VA healthcare coverage and military-related trauma are more likely to be informed by a healthcare professional about a PTSD diagnosis. Further research is needed to improve PTSD diagnosis knowledge for those with non-military-related trauma and those without VA healthcare coverage.

This paper brings together researchers, clinicians, technology developers and digital innovators to outline current applications of remote symptom monitoring being developed for palliative cancer care delivery in Africa. We outline three remote symptom monitoring approaches from three countries, highlighting their models of delivery and intended outcomes, and draw on their experiences of implementation to guide further developments and evaluations of this approach for palliative cancer care in the region. Through highlighting these experiences and priority areas for future research, we hope to steer efforts to develop and optimise remote symptom monitoring for palliative cancer care in Africa.