Comparison of Longitudinal Outcomes in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis.

RATIONALE: Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are both genetic diseases of mucociliary clearance resulting in progressive lung disease with onset in early life. PCD is often considered to be milder in childhood than CF, based on minimal evidence. Similar to CF, genotype-phenotype associations exist in PCD: pathogenic variants in CCDC39 and CCDC40, causing inner dynein arm/microtubular defects (IDA/MTD) are associated with more severe disease. OBJECTIVES: To compare longitudinal outcomes in matched children with PCD and CF. We hypothesized that children with PCD with IDA/MTD defects would have lower lung function but better nutritional indices than matched children with CF with minimal function genotypes (i.e., those associated with pancreatic insufficiency). METHODS: Children with PCD enrolled in a prospective, multicenter, observational study were matched with CF patients from the CF Foundation Patient Registry by birth cohort, age, sex, race/ethnicity and year of study visit. The association of disease group overall and by severity class (PCD-IDA/MTD versus all other defects and CF-minimal versus residual function) with longitudinal outcomes up to age 17 was evaluated with cubic spline mixed effects models. MEASUREMENT AND MAIN RESULTS: Groups included 136 children with PCD (40 IDA/MTD, 96 other) and 476 with CF (446 minimal function, 30 residual function). Below age 14, the PCD group had similar or lower estimated mean FEV1 % predicted compared to CF (e.g., at age 10, -5.4 % predicted lower (95% CI: -7.7, -3.1)). Compared to the CF-minimal function (pancreatic insufficient) group, the PCD-IDA/MTD group had similar BMI; estimated mean FEV1 % predicted was significantly lower by age 10 (mean difference -10.6% (95% CI: -14.7, -6.4), increasing to -15.7% (95% CI: -20.3, -11.2) at age 14. The CF cohort had increased prevalence of Pseudomonas aeruginosa cultured on one or more occasions compared to children with PCD (67% vs 27%, p<0.001); there was no difference in prevalence of P. aeruginosa between children with PCD-IDA/MTD and PCD-other. CONCLUSIONS: In childhood, average lung function abnormalities in PCD are not milder than CF, particularly for those with IDA/MTD ciliary defects. New guidelines and treatments to improve outcomes in PCD are urgently needed.

Mapping the journey of patients and care partners living with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: developing a framework for improvements in care.

Aim: To identify and raise awareness of healthcare service gaps for individuals with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).Materials & methods: An ALSP patient journey map from symptom onset throughout disease course was developed using existing literature, patient and clinician feedback from a structured workshop and community survey data regarding attitudes toward genetic testing.Results: ALSP diagnosis is frequently delayed due to low awareness of this rare condition and symptom overlap with more common neurological conditions. Multiple factors impact patients' decision-making regarding genetic testing for ALSP, symptom management and participation in research studies.Conclusion: These results highlight the challenges faced by individuals with ALSP and should support program development to improve patient care.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare and fatal neurological disease. Symptoms generally appear between the ages of 40 and 50 years and worsen rapidly. Many patients have changes in memory, personality, behavior, and movement.A patient journey map shows important events that patients experience over the course of a disease. The map can be used to identify challenges that patients face and where the quality of medical care can be improved. This patient journey map for ALSP is based on published scientific articles, a workshop where patients and others who have experience with ALSP talked about their challenges, and answers to questions from a survey on genetic testing for ALSP.The map shows that diagnosis of ALSP is often delayed. Because ALSP is a rare disease, few medical providers have experience managing it. Medical providers may not suspect it because many ALSP symptoms overlap with symptoms of other common neurologic diseases. Genetic testing is needed to be sure that a person has ALSP, but it can be hard for patients to get tested since it is expensive and there may not be a testing center nearby. Finally, some people might not want to get tested if they are fearful of getting a diagnosis.This patient journey map should be used to raise awareness of ALSP and the challenges faced by patients and those who care for them. It may also help researchers and medical providers know how to better support patients who have ALSP.

Modernizing behavioral parent training program for ADHD with mHealth strategies, telehealth groups, and health behavior curriculum: a randomized pilot trial.

OBJECTIVE: Parent behavior management training (BMT) is an evidence-based yet underutilized tool to treat children with ADHD and address related health disparities. This pilot study investigated the acceptability and feasibility of a novel, health behavior-, and technology-adapted BMT (LEAP) vs. standard BMT. METHODS: The weekly 9-session LEAP telemedicine group program is based on a standard BMT curriculum enhanced with strategies for supporting optimal child sleep, problematic media use (PMU), and physical activity, including wrist-worn activity trackers. Children ages 6-10 years with ADHD and their caregivers were randomized to LEAP or standard BMT. Acceptability and feasibility were tracked. Caregivers completed standardized measures, and children wore hip-worn accelerometers for 1 week at baseline, postintervention (10 weeks), and follow-up (20 weeks). RESULTS: 84 parent/child dyads were randomized to LEAP or standard BMT, with high and comparable acceptability and feasibility. Both treatment groups demonstrated decreased ADHD symptoms and improved executive functions postintervention (p < .0001), maintained at follow-up. Average accelerometer-measured MVPA decreased and sleep duration remained unchanged, while PMU and bedtime resistance improved for both groups. CONCLUSIONS: LEAP is highly feasible and acceptable, and yielded similar initial clinical and health behavior improvements to standard BMT. Innovative and targeted supports are needed to promote healthy behaviors in children with ADHD.

MASTering systemic mastocytosis: Lessons learned from a large patient cohort.

Background: Systemic mastocytosis (SM), a rare condition affecting about 32,000 individuals in the United States, is often misdiagnosed or underdiagnosed owing to its nonspecific symptoms and the need for invasive biopsies. Objective: Our aim was to identify, classify, and characterize the natural history of patients with SM. Methods: In a retrospective cohort study, administrative data from a large managed care organization was used to identify patients with confirmed SM, based on World Health Organization criteria. Demographic data, delay to diagnosis, disease progression, and health care resource utilization were examined. Results: Of 116 patients with confirmed SM, 77% had indolent SM, 2% had smoldering SM, 12% had SM with associated hematologic neoplasm, 9% had aggressive SM, and none had mast cell leukemia. In all, 5 patients were misclassified as having a less advanced SM subtype initially and 3 were completely undiagnosed (missed diagnosis). The average delay to diagnosis of SM was 58.3 plus or minus 73.1 months. In all, 18% of patients progressed from a nonadvanced form of SM (indolent or smoldering SM) to an advanced form of SM (aggressive SM, SM with associated hematologic neoplasm, or mast cell leukemia) over an average of 88.3 plus or minus 82.7 months. Patients with SM had increased health care utilization, including increases in their numbers of hospital admissions, emergency room visits, urgent care visits, and specialty provider visits, after diagnosis versus before. Conclusions: Rare diseases such as SM would benefit from increased understanding and awareness to improve diagnostic accuracy. Prospective studies are needed to better characterize this patient population and determine the type of follow-up needed to recognize advanced forms of SM so that appropriate treatment can be implemented.

An Exploratory Study of Dynamic Capabilities and Performance Improvement in Hospitals.

GOAL: Recent efforts to push hospitals to provide high-value care have relied on payment incentives. However, evidence indicates that 70% to 90% of performance improvement projects do not achieve their desired goals. Therefore, in addition to managing external industry pressures, hospitals need to develop performance improvement (PI) capabilities that enable them to capitalize on improvement opportunities, effectively develop and adopt solutions, and ensure the sustainability of improvements over time. While operational capabilities enable hospitals to produce and deliver services, more is needed to attain and sustain superior performance. Dynamic capabilities drive changes in operational capabilities to meet environmental demands. Dynamic capabilities also enable hospitals to renew and reconfigure their resources to optimize performance. This paper proposes the dynamic-capabilities framework as an appropriate way to develop and manage PI capabilities in hospitals, and it discusses the implications of shifting to a strategy that is driven by dynamic-capabilities PI. METHODS: The research team designed a semi-structured interview based on a review of the literature to understand whether hospitals were engaging in the activities outlined in the dynamic-capabilities framework. Nine study participants were recruited from a convenience sample of hospital PI staff at hospitals in Massachusetts and New Hampshire. De-identified transcripts were entered into NVivo12 qualitative data analysis software, and data were thematically indexed and coded following the principles of content analysis. PRINCIPAL FINDINGS: PI structures, improvement methodologies, and weaknesses did not vary significantly among hospitals. Most hospitals had a PI department and were more likely to adopt PI projects initiated by top management. While PI staff were trained in improvement methodologies, no programs were in place that required the rest of the hospital staff to become familiar with PI methods. Common areas of weakness were PI project selection, communication, coordination, learning from current and former PI projects, and systematic approaches to sustain improvements. PRACTICAL APPLICATIONS: Dynamic PI capabilities provide an opportunity to systematically identify improvement opportunities, seize on and learn from those opportunities, and renew and reconfigure resources to optimize performance. Ad hoc PI projects are insufficient to enable a hospital to sustain superior performance. Internal and external pressures to deliver high-value patient care and services require hospitals to exceed their current PI efforts. By developing dynamic PI capabilities, hospitals will adopt a more systematic and effective approach to PI, which will likely result in superior performance.

Work Environment, Burnout, and Intent to Leave Current Job Among Cardiologists and Cardiology Health Care Workers: Results From the National Coping With COVID Survey.

BACKGROUND: Little is known about factors contributing to burnout and intent to leave in cardiologists and other cardiology health care workers. METHODS AND RESULTS: The Coping With COVID survey assessed work conditions, burnout, and intent to leave among physicians, nurses, advanced practice providers, and other clinical staff (OCS) from April 2020 to December 2020. Single-item measures assessed work conditions, burnout (emotional exhaustion), and intent to leave. Multilevel logistic regression examined work life variables' relationships to burnout among role types and feeling valued as a mediator. Open-ended comments analyzed via grounded theory contributed to a conceptual model. Coping With COVID was completed by 1199 US cardiology health care workers (354 physician/520 nurses/198 advanced practice providers/127 OCS). Nurses were most likely to report burnout (59% nurses, 57% OCS, 46% advanced practice providers, 40% physicians, P<0.0001). Workload correlated with burnout in all groups (adjusted odds ratios [aORs], 4.1-17.4; Ps<0.005), whereas anxiety/depression related to burnout in all except OCS (aORs, 3.9-8.3; Ps≤0.001). Feeling valued was related to lower burnout in most groups. Intent to leave was common (23%-45%) and was lower in physicians and advanced practice providers who felt valued (aORs, 0.26 and 0.22, respectively; Ps<0.05). Burnout was highest for nurses in practice 16 to 20 years, and intent to leave was highest for OCS in practice 16 to 20 years. Themes contributing to burnout included personal and patient safety, leadership, and financial issues. CONCLUSIONS: Burnout was prevalent among cardiology health care workers and highest in nurses and OCS. Addressing factors associated with burnout in different role types may improve work life sustainability for all cardiology health care workers.

The Effects of Race, Primary Language, Insurance and Other Factors on Time to Pediatric Outpatient MRI Completion: A Retrospective Cohort Study.

RATIONALE AND OBJECTIVES: Disparities in healthcare access in the United States have been associated with race and ethnicity, as well as socioeconomic factors. Because delays in imaging may result in delayed diagnosis or clinical management, we are evaluating practices within our radiology department in hopes of decreasing disparities in access to imaging. The objective of this study is to determine the disparities in time to outpatient MRI scheduling and completion by race, ethnicity, primary language, socioeconomic status, insurance and other factors at a tertiary children's hospital. METHODS: After Institutional Review Board approval, we retrospectively extracted data from all outpatient MRI exams completed at our center between 10/5/2020 and 8/31/2022. Collected data included sex, age, race/ethnicity, primary language, medical complexity, insurance type, address, need for anesthesia, ordering specialty, and order acuity. We determined times to MRI scheduling or completion using mixed effects Cox regression models and determined associations between unadjusted and fully adjusted models. RESULTS: We analyzed 14,002 completed outpatient MRI orders from 9714 unique patients. 56.2% were White, 19.2% Hispanic, 8.4% Asian, 4.5% Black/African-American, 1.4% American Indian/Alaska Native, 0.7% Native Hawaiian/Pacific Islander, 5.7% two or more races/ethnicities, and 3.8% "Other." In fully adjusted models, there was no significant association between race/ethnicity and time to MRI scheduling and completion. In fully adjusted models, time to completion of MRI was slower among those with Medicaid (adjusted hazard ratio [95% confidence interval] of 0.92 [0.87, 0.98]), a primary language other than English (0.90 [0.82, 0.99]), non-complex chronic illness (0.72 [0.67, 0.79]), complex chronic illness (0.72 [0.67, 0.78]) and need for anesthesia (0.75 [0.71, 0.79]). CONCLUSION: At our tertiary children's hospital, time to completion of outpatient MRI was not associated with race, but was greater among those with Medicaid insurance, whose primary language was not English, and needing anesthesia. Advocating for faster prior authorization by Medicaid, utilizing our hospital's live interpreter phone number for scheduling, and incorporating greater child life support to decrease anesthesia use are considerations for decreasing these disparities, although surveying patients and families most impacted by these discrepancies will be important to identify the most promising interventions. DATA AVAILABILITY STATEMENT: Data are not publicly available to preserve individuals' privacy due to IRB restrictions. Data may be available upon reasonable request by contacting the corresponding author.

Human cell surface-AAV interactomes identify LRP6 as blood-brain barrier transcytosis receptor and immune cytokine IL3 as AAV9 binder.

Adeno-associated viruses (AAVs) are foundational gene delivery tools for basic science and clinical therapeutics. However, lack of mechanistic insight, especially for engineered vectors created by directed evolution, can hamper their application. Here, we adapt an unbiased human cell microarray platform to determine the extracellular and cell surface interactomes of natural and engineered AAVs. We identify a naturally-evolved and serotype-specific interaction between the AAV9 capsid and human interleukin 3 (IL3), with possible roles in host immune modulation, as well as lab-evolved low-density lipoprotein receptor-related protein 6 (LRP6) interactions specific to engineered capsids with enhanced blood-brain barrier crossing in non-human primates after intravenous administration. The unbiased cell microarray screening approach also allows us to identify off-target tissue binding interactions of engineered brain-enriched AAV capsids that may inform vectors' peripheral organ tropism and side effects. Our cryo-electron tomography and AlphaFold modeling of capsid-interactor complexes reveal LRP6 and IL3 binding sites. These results allow confident application of engineered AAVs in diverse organisms and unlock future target-informed engineering of improved viral and non-viral vectors for non-invasive therapeutic delivery to the brain.

Team-based care in specialist practice: a path to improved physician experience in British Columbia.

BACKGROUND: Specialist physicians in the province of British Columbia commonly work on teams in acute care settings such as operating rooms or inpatient hospital units. However, while the implementation of team-based care (TBC) has been supported in primary care clinics, no formal mechanisms have supported specialist physicians in adopting TBC in their private outpatient offices. Adopting TBC models is associated with improving physician experience, efficiency, and patient experience. METHODS: The Institute for Healthcare Improvement Breakthrough Series guided a program to support 11 specialist physicians, representing nine different specialties, to develop and implement TBC in outpatient offices. Participants were supported through resources including funding, mentorship, and learning opportunities. To determine whether the program improved physician experience, quantitative data were collected using the validated Mini Z survey and qualitative data were collected through monthly reports, semi-structured interviews, and focus groups. Patient experience data were collected through surveys and follow-up calls. RESULTS: The fifteen-month program was successful, with 10 of the 11 specialists implementing TBC in their offices. The Mini Z results demonstrated that physician experience improved over the course of the program, with scores on job satisfaction, work pace, and time spent on the electronic medical record improving the most. Interviews with specialists and focus groups with specialists' team members support these findings, with participants stating that TBC modulates workloads, begins to affect burnout, improves work-life balance, and increases the efficiency of care. Patients reported positive experiences while receiving TBC. Patients were less likely to visit the emergency department after consultations with specialist teams, and providers agreed that their patients would be less likely to seek acute care because of the new practice models. CONCLUSION: TBC is a viable model for specialist physicians and their health care teams practicing in British Columbia to foster well-being, job satisfaction, and efficiency, and to improve patient experience. These findings may be of interest to specialists, health care providers, policymakers, and administrators looking to better support and retain specialist practices that are integral to patient care.

Workplace factors related to health care leader well-being in rural settings.

PURPOSE: To examine which workplace factors contribute to health care leader well-being in rural settings. METHODS: Working with two rurally focused organizations, we administered a Rural Leader Burnout survey to executive leaders. The survey contained 25 questions; 24 were closed-item multiple choice and 1 open-ended question. The survey was based on the Mini Z 10 item burnout survey with 5 additional items for leaders. Logistic regression and qualitative content analysis determined factors associated with job satisfaction, burnout, and intent to leave (ITL). FINDINGS: There were 288 respondents (response rate 22%). Of 272 with complete data, 61.4% were women and 51.8% had worked > 10 years. About 81% reported job satisfaction, 40.2% were burned out, and 49.8% intended to leave their administrative roles within 2 years. Factors statistically associated with satisfaction were work control (OR = 3.0), values alignment with leadership (OR = 2.1), and trust in organization (OR = 2.0). Work control (OR = 0.3), trust in organization (OR = 0.4), and stress (OR = 4.1) were associated with burnout. Trust in organization (OR = 0.5), feeling valued (OR = 0.6), and stress (OR = 1.8) associated with ITL. Qualitative data revealed three themes relevant to rural leaders: (1) industry challenges, (2) daily operational issues, and (3) difficult relationships. CONCLUSIONS: These exploratory analyses demonstrate practical ways to improve work conditions to mitigate burnout and turnover in rural leaders. Promoting thriving in leaders would be an important step in maintaining the rural health care workforce.

Viability and Diversity of the Microbial Cultures Available in Retail Kombucha Beverages in the USA.

Kombucha is a two-stage fermented sweetened tea beverage that uses yeast and lactic acid bacteria (LAB) to convert sugars into ethanol and lactate and acetic acid bacteria (AAB) to oxidize ethanol to acetate. Its popularity as a beverage grew from claims of health benefits derived from this vibrant microbial bioconversion. While recent studies have shed light on the diversity of cultures in Kombucha fermentation, there is limited information on the diversity, and especially viability, of cultures in retail beverages that advertise the presence of Kombucha and probiotic cultures. In this study, 12 Kombucha beverages produced by different manufacturers throughout the US were purchased and microbially characterized. Eight of the beverages contained viable Kombucha cultures, while 3 of the remaining 4 had viable Bacillus cultures as added probiotics. Amplicon profiling revealed that all contained Kombucha yeast and bacteria cells. The dominant yeasts detected were Lachancea cidri (10/12), Brettanomyces (9/12), Malassezia (6/12), and Saccharomyces (5/12). Dominant LAB included Liquorilactobacillus and Oenococcus oeni, and AAB were Komagataeibacter, Gluconobacter, and Acetobacter. One beverage had a significant amount of Zymomonas mobilis, an ethanol-producing bacterium from Agave cactus. While Kombucha beverages differ in the types and viability of cultures, all except one beverage contained detectable viable cells.

Lessons for tomorrow: The role of relationships and mindfulness in sustaining services during a crisis.

BACKGROUND: The COVID-19 pandemic placed unprecedented demands on hospitals around the globe, making timely crisis response critical for organizational success. One mechanism that has played an effective role in health care service management during large-scale crises is the Hospital Incident Command System. PURPOSE: The aim of this article was to understand the role of HICS in the management of a large academic medical center and its impact on relationships and communication among providers in the delivery of services during a crisis. METHODOLOGY: This mixed methods study was based on meeting observations, document reviews, semistructured interviews, and two measures of team performance within an academic medical center in the Northeast during the COVID-19 pandemic. Descriptive and bivariate analyses were applied, and qualitative data were coded and analyzed for themes. RESULTS: HICS provided a systematic information-sharing and decision-making process that increased communication and coordination among team members. Analyses indicate a correlation between dimensions of relational coordination and organizational mindfulness. Qualitative data revealed the importance of shared meetings and huddles and the evolution of HICS across multiple waves of the crisis. CONCLUSION: HICS facilitated organizational improvements during the crisis response and generated opportunities to maintain specific coordination practices beyond the crisis. The prolonged implementation of HICS during the COVID-19 pandemic created challenges, including the disruption of the routine leadership structure. PRACTICAL IMPLICATIONS: Applying relational coordination and organizational mindfulness frameworks may allow hospitals to leverage communications and relationships within a high-stakes environment to improve service delivery.

You Cannot Function in "Overwhelm": Helping Primary Care Navigate the Slow End of the Pandemic.

GOAL: This study was developed to explicate underlying organizational factors contributing to the deterioration of primary care clinicians' mental health during the COVID-19 pandemic. METHODS: Using data from the Larry A. Green Center for the Advancement of Primary Health Care for the Public Good's national survey of primary care clinicians from March 2020 to March 2022, a multidisciplinary team analyzed more than 11,150 open-ended comments. Phase 1 of the analysis happened in real-time as surveys were returned, using deductive and inductive coding. Phase 2 used grounded theory to identify emergent themes. Qualitative findings were triangulated with the survey's quantitative data. PRINCIPAL FINDINGS: The clinicians shifted from feelings of anxiety and uncertainty at the start of the pandemic to isolation, lack of fulfillment, moral injury, and plans to leave the profession. The frequency with which they spoke of depression, burnout, and moral injury was striking. The contributors to this distress included crushing workloads, worsening staff shortages, and insufficient reimbursement. Consequences, both felt and anticipated, included fatigue and demoralization from the inability to manage escalating workloads. Survey findings identified responses that could alleviate the mental health crisis, namely: (1) measuring and customizing workloads based on work capacity; (2) quantifying resources needed to return to sufficient staffing levels; (3) promoting state and federal support for sustainable practice infrastructures with less administrative burden; and (4) creating patient visits of different lengths to rebuild relationships and trust and facilitate more accurate diagnoses. PRACTICAL APPLICATIONS: Attention to clinicians' mental health should be rapidly directed to on-demand, confidential mental health support so they can receive the care they need and not worry about any stigma or loss of license for accepting that help. Interventions that address work-life balance, workload, and resources can improve care, support retention of the critically important primary care workforce, and attract more trainees to primary care careers.

Resident worklife and wellness through the late phase of the pandemic: a mixed methods national survey study.

BACKGROUND: System contributors to resident burnout and well-being have been under-studied. We sought to determine factors associated with resident burnout and identify at risk groups. METHODS: We performed a US national survey between July 15 2022 and April 21, 2023 of residents in 36 specialties in 14 institutions, using the validated Mini ReZ survey with three 5 item subscales: 1) supportive workplace, 2) work pace/electronic medical record (EMR) stress, and 3) residency-specific factors (sleep, peer support, recognition by program, interruptions and staff relationships). Multilevel regressions and thematic analysis of 497 comments determined factors related to burnout. RESULTS: Of 1118 respondents (approximate median response rate 32%), 48% were female, 57% White, 21% Asian, 6% LatinX and 4% Black, with 25% PGY 1 s, 25% PGY 2 s, and 22% PGY 3 s. Programs included internal medicine (15.1%) and family medicine (11.3%) among 36 specialties. Burnout (found in 42%) was higher in females (51% vs 30% in males, p = 0.001) and PGY 2's (48% vs 35% in PGY-1 s, p = 0.029). Challenges included chaotic environments (41%) and sleep impairment (32%); favorable aspects included teamwork (94%), peer support (93%), staff support (87%) and program recognition (68%). Worklife subscales were consistently lower in females while PGY-2's reported the least supportive work environments. Worklife challenges relating to burnout included sleep impairment (adjusted Odds Ratio (aOR) 2.82 (95% CIs 1.94, 4.19), absolute risk difference (ARD) in burnout 15.9%), poor work control (aOR 2.25 (1.42, 3.58), ARD 12.2%) and chaos (aOR 1.73 (1.22, 2.47), ARD 7.9%); program recognition was related to lower burnout (aOR 0.520 (0.356, 0.760), ARD 9.3%). These variables explained 55% of burnout variance. Qualitative data confirmed sleep impairment, lack of schedule control, excess EMR and patient volume as stressors. CONCLUSIONS: These data provide a nomenclature and systematic method for addressing well-being during residency. Work conditions for females and PGY 2's may merit attention first.

Fast, accurate ranking of engineered proteins by target-binding propensity using structure modeling.

Deep-learning-based methods for protein structure prediction have achieved unprecedented accuracy, yet their utility in the engineering of protein-based binders remains constrained due to a gap between the ability to predict the structures of candidate proteins and the ability toprioritize proteins by their potential to bind to a target. To bridge this gap, we introduce Automated Pairwise Peptide-Receptor Analysis for Screening Engineered proteins (APPRAISE), a method for predicting the target-binding propensity of engineered proteins. After generating structural models of engineered proteins competing for binding to a target using an established structure prediction tool such as AlphaFold-Multimer or ESMFold, APPRAISE performs a rapid (under 1 CPU second per model) scoring analysis that takes into account biophysical and geometrical constraints. As proof-of-concept cases, we demonstrate that APPRAISE can accurately classify receptor-dependent vs. receptor-independent adeno-associated viral vectors and diverse classes of engineered proteins such as miniproteins targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike, nanobodies targeting a G-protein-coupled receptor, and peptides that specifically bind to transferrin receptor or programmed death-ligand 1 (PD-L1). APPRAISE is accessible through a web-based notebook interface using Google Colaboratory (https://tiny.cc/APPRAISE). With its accuracy, interpretability, and generalizability, APPRAISE promises to expand the utility of protein structure prediction and accelerate protein engineering for biomedical applications.

Understanding what leaders can do to facilitate healthcare workers' feeling valued: improving our knowledge of the strongest burnout mitigator.

AIM: Feeling valued is a striking mitigator of burnout yet how to facilitate healthcare workers (HCWs) feeling valued has not been adequately studied. This study discovered factors relating to HCWs feeling valued so leaders can mitigate burnout and retain their workforce. METHOD: The Coping with COVID-19 survey, initiated in March 2020 by the American Medical Association, was distributed to 208 US healthcare organisations. Of the respondents, 37 685 physicians, advanced practice clinicians, nurses, and other clinical staff answered questions that assessed burnout, intent to leave and whether they felt valued.Quantitative analysis looked at odds of burnout and intent to leave among the highest versus lowest feeling valued (FV) groups. Open-ended comments provided by 5559 respondents with high or low sense of FV were analysed to understand aspects of work life that contributed to FV. RESULTS: Of 37 685 respondents, 45% felt valued; HCWs who felt highly valued had 8.3 times lower odds of burnout and 10.2 lower odds of intent to leave than those who did not feel valued at all. Qualitative data identified six themes associated with FV: (1) physical safety, (2) compensation and pandemic-related finances, (3) transparent and frequent communication, (4) effective teamwork, (5) empathetic and respectful leaders, and (6) organisational support. CONCLUSION: This US study demonstrates that FV correlates with burnout and intent to leave, yet only 45% of HCWs feel valued. Six themes link to interventions leaders can follow to facilitate HCWs FV and potentially reduce burnout and increase retention for a challenged healthcare workforce.

Learning From a National Quality Improvement Collaborative for Brief Resolved Unexplained Events.

OBJECTIVE: In 2016, the American Academy of Pediatrics published the Brief Resolved Unexplained Event (BRUE) Clinical Practice Guideline (CPG). A multicenter quality improvement (QI) collaborative aimed to improve CPG adherence. METHODS: A QI collaborative of 15 hospitals aimed to improve testing adherence, the hospitalization of lower-risk infants, the correct use of diagnostic criteria, and risk classification. Interventions included CPG education, documentation practices, clinical pathways, and electronic medical record integration. By using medical record review, care of emergency department (ED) and inpatient patients meeting BRUE criteria was displayed via control or run charts for 3 time periods: pre-CPG publication (October 2015 to June 2016), post-CPG publication (July 2016 to September 2018), and collaborative (April 2019 to June 2020). Collaborative learning was used to identify and mitigate barriers to iterative improvement. RESULTS: A total of 1756 infants met BRUE criteria. After CPG publication, testing adherence improved from 56% to 64% and hospitalization decreased from 49% to 27% for lower-risk infants, but additional improvements were not demonstrated during the collaborative period. During the collaborative period, correct risk classification for hospitalized infants improved from 26% to 49% (ED) and 15% to 33% (inpatient) and the documentation of BRUE risk factors for hospitalized infants improved from 84% to 91% (ED). CONCLUSIONS: A national BRUE QI collaborative enhanced BRUE-related hospital outcomes and processes. Sites did not improve testing and hospitalization beyond the gains made after CPG publication, but they did shift the BRUE definition and risk classification. The incorporation of caregiver perspectives and the use of shared decision-making tools may further improve care.

Association of patient characteristics and insurance type with anti-obesity medications prescribing and fills.

AIM: To characterize factors associated with the receipt of anti-obesity medication (AOM) prescription and fill. MATERIALS AND METHODS: This retrospective cohort study used electronic health records from 1 January 2015 to 30 June 2023, in a large health system in Ohio and Florida. Adults with a body mass index ≥30 kg/m2 who attended ≥1 weight-management programme or had an initial AOM prescription between 1 July 2015 and 31 December 2022, were included. The main measures were a prescription for an AOM (naltrexone-bupropion, orlistat, phentermine-topiramate, liraglutide 3.0 mg and semaglutide 2.4 mg) and an AOM fill during the study follow-up. RESULTS: We identified 50 678 adults, with a mean body mass index of 38 ± 8 kg/m2 and follow-up of 4.7 ± 2.4 years. Only 8.0% of the cohort had AOM prescriptions and 4.4% had filled prescriptions. In the multivariable analyses, being a man, Black, Hispanic and other race/ethnicity (vs. White), Medicaid, traditional Medicare, Medicare Advantage, self-pay and other insurance types (vs. private insurance) and fourth quartile of the area deprivation index (vs. first quartile) were associated with lower odds of a new prescription. Hispanic ethnicity, being a man, Medicaid, traditional Medicare and Medicare Advantage insurance types, liraglutide and orlistat (vs. naltrexone-buproprion) were associated with lower odds of AOM fill, while phentermine-topiramate was associated with higher odds. Among privately insured individuals, the insurance carrier was associated with both the odds of AOM prescription and fill. CONCLUSIONS: Significant disparities exist in access to AOM both at the prescribing stage and getting the prescription filled based on patient characteristics and insurance type.

Human Papillomavirus Vaccination Status and Correlates Among Mid-Adult Women: Connecticut, USA, 2016-2019.

Background: In 2019, the CDC expanded their recommendations for human papillomavirus (HPV) vaccination beyond age 26 years to include shared clinical decision-making (SCDM) among adults aged 27-45 years ("mid-adults"). The purpose of this study was to describe HPV vaccination status among mid-adult women before the implementation of SCDM for HPV vaccination. Methods: A cross-sectional survey was conducted during 2016-2019 in Connecticut, United States, and enrolled women born in 1981 or later (birth cohorts eligible for HPV vaccination). This analysis was restricted to participants aged 27 years and older at the time of the survey. Correlates of vaccination status, sources of vaccine information, and reasons for not receiving the vaccine were examined. Results: Among 298 participants, 64.4% had not received HPV vaccine. Other than age (younger age was associated with being vaccinated), no other demographic or behavioral correlates were associated with vaccination. Compared with unvaccinated women, vaccinated women were more likely to have heard about the HPV vaccine from a doctor (odds ratio [OR] = 3.45, 95% confidence interval [CI]: 2.00-5.88) and less likely to have heard about it from television (OR = 0.23, 95% CI: 0.13-0.41). The main reasons for not being vaccinated were "vaccine not offered" (48%) and "too old" (40%). Conclusions: A majority of mid-adult women in this study were not previously vaccinated against HPV, signaling the large opportunity for SCDM with this population. This may be facilitated by ensuring health care providers and mid-adult women know about the availability and potential benefits of HPV vaccination to inform decision making.

Intrapyloric Botulinum Toxin Injection for Refractory Nausea and Vomiting in Pediatric Patients.

OBJECTIVES: Chronic nausea and vomiting may be associated with gastroparesis or other conditions. Poor mechanistic understanding of symptoms often precludes targeted therapy. Numerous case series suggest that intrapyloric botulinum toxin injection (IPBI) may be beneficial in treating gastroparesis and dyspepsia in children. We hypothesized that nausea, vomiting, and other symptoms, independent of gastroparesis, may improve with IPBI. We sought to identify gastric emptying (GE) and manometric patterns in IPBI responders versus nonresponders. METHODS: Electronic records of 25 pediatric patients who received IPBI for refractory nausea, vomiting, or both were retrospectively reviewed. We assessed symptom improvement post-IPBI and compared symptoms, GE, and antroduodenal manometry (ADM) findings between IPBI responders and nonresponders. RESULTS: At least one major symptom improved in 19 patients (76%) after IPBI. Of 22 patients completing a GE study, 14 had delayed GE with no significant difference between IPBI responders and nonresponders. Of 22 patients who underwent ADM, 18 had normal fasting peristalsis, 5 had postprandial antral hypomotility, 4 had neuropathic findings, and 19 had pylorospasm. IPBI responders, compared to nonresponders, demonstrated higher antral pressures with feeding ( P < 0.0001) and shorter duration of pylorospasm ( P = 0.0036). Antral pressures did not differ significantly with fasting or following motilin agonists. CONCLUSIONS: Our findings suggest that IPBI may have therapeutic benefit in pediatric patients with chronic nausea and/or vomiting, independent of gastroparesis. ADM findings of intact antral peristalsis and elevated antral pressures, in conjunction with efficacy of IPBI, support pyloric non-relaxation as a potential contributor to nausea and/or vomiting in pediatric patients.