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.

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.

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.

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.

Addressing Symptom Burden and Palliative Care Needs in Cystic Fibrosis: A Narrative Review of the Literature.

Among people with cystic fibrosis (CF), illness burden is multifaceted, and symptoms may fluctuate in intensity across a lifespan. Caregivers of people with CF may also experience distressing symptoms. Recent developments in CF care, including the availability of highly effective modulator therapies (HEMTs) and new palliative care guidelines promoting palliative care screening may help alleviate symptoms. The objective of this review was to present a narrative view of the recent literature on symptom burden in CF, new screening approaches informed by the Cystic Fibrosis Foundation (CFF) palliative care guidelines, and early data from studies examining the impact of HEMTs on CF symptom burden. A review of the relevant literature was conducted using Google Scholar and PubMed. Included articles covered approaches to burden assessment in CF and other chronic illnesses, epidemiology of CF symptom burden, the impact of HEMTs on symptom burden, and the CFF palliative care guidelines. A primary palliative care model implementing the CFF guidelines was also described. Results of this review show that while recent developments in CF care have led to a reduction in physical symptoms, mental health symptoms remain prevalent. Ongoing screening and triage can ensure that physical symptoms, psychological symptoms, social needs, practical problems, and communication concerns are addressed by care teams.

Primary Care Physician Leadership in Top Ranked US Hospitals.

This assessment of the "top hospitals" in the US according to 4 leading rankings reveals only 4 to 7% of represented CEOs are primary care physicians by training. Greater attention to leadership development from primary care residency through health system practice is needed to avoid diminishing primary care's critical role and salutary global benefits.

What do rural young people want from their mental health service.

INTRODUCTION: Rural young people have high rates of mental illness and low rates of help-seeking making it crucial to extend research about service improvement in rural and remote Australia. OBJECTIVE: To describe what rural young people want from their headspace service, and what rural headspace clinicians understand they provide. DESIGN: This study used a qualitative methodology with reflexive thematic analysis to analyse participant interviews and systematically derive common themes. FINDINGS: Thirteen participants were interviewed comprising young people aged 16 to 18 years who had accessed one of three rural headspace services, together with clinicians working in those services. Key themes for both young people and clinicians comprised accessibility, flexibility, engagement, safety, youth-focus, and evidence-based treatment although there were some differences of emphasis amongst themes. There was also an additional theme for young people of awareness, and for clinicians of caring. DISCUSSION: The results supported that what young people were seeking was largely consistent with what headspace clinicians were providing. There were however some specific issues relevant to service provision in a rural context such as increased awareness of services, the need to focus on evidenced based interventions, and better promotion in schools and the local community. Service gaps such as unmet needs for young people with higher risk who might fall outside of agency requirements were also identified. CONCLUSION: Results of this study help inform better service delivery and increased awareness for mental health of young people in rural communities to improve access and outcomes.

Burnout Among Hospitalists During the Early COVID-19 Pandemic: a National Mixed Methods Survey Study.

BACKGROUND  : Hospitalist physician stress was exacerbated by the pandemic, yet there have been no large scale studies of contributing factors. OBJECTIVE: Assess remediable components of burnout in hospitalists. PARTICIPANTS, STUDY DESIGN AND MEASURES: In this Coping with COVID study, we focused on assessment of stress factors among 1022 hospital-based clinicians surveyed between April to December 2020. We assessed variables previously associated with burnout (anxiety/depression due to COVID-19, work overload, fear of exposure or transmission, mission/purpose, childcare stress and feeling valued) on 4 point Likert scales, with results dichotomized with the top two categories meaning "present"; burnout was assessed with the Mini Z single item measure (top 3 choices = burnout). Quantitative analyses utilized multilevel logistic regression; qualitative analysis used inductive and deductive methods. These data informed a conceptual model. KEY RESULTS: Of 58,408 HCWs (median response rate 32%), 1022 were hospital-based clinicians (906 (89%) physicians; 449 (44%) female; 469 (46%) White); 46% of these hospital-based clinicians reported burnout. Work overload was associated with almost 5 times the odds of burnout (OR 4.9, 95% CIs 3.67, 6.85, p < 0.001), and those with anxiety or depression had 4 times the odds of burnout (OR 4.2, CIs 3.21, 7.12, p < 0.001), while those feeling valued had half the burnout odds (OR 0.43, CIs 0.31, 0.61, p < 0.001). Regression models estimated 42% of burnout variance was explained by these variables. In open-ended comments, leadership support was helpful, with "great leadership" represented by transparency, regular updates, and opportunities to ask questions. CONCLUSIONS: In this national study of hospital medicine, 2 variables were significantly related to burnout (workload and mental health) while two variables (feeling valued and leadership) were likely mitigators. These variables merit further investigation as means of reducing burnout in hospital medicine.

Dose-dependent effects of GAT107, a novel allosteric agonist-positive allosteric modulator (ago-PAM) for the α7 nicotinic cholinergic receptor: a BOLD phMRI and connectivity study on awake rats.

Background: Alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonists have been developed to treat schizophrenia but failed in clinical trials due to rapid desensitization. GAT107, a type 2 allosteric agonist-positive allosteric modulator (ago-PAM) to the α7 nAChR was designed to activate the α7 nAChR while reducing desensitization. We hypothesized GAT107 would alter the activity of thalamocortical neural circuitry associated with cognition, emotion, and sensory perception. Methods: The present study used pharmacological magnetic resonance imaging (phMRI) to evaluate the dose-dependent effect of GAT107 on brain activity in awake male rats. Rats were given a vehicle or one of three different doses of GAT107 (1, 3, and 10 mg/kg) during a 35 min scanning session. Changes in BOLD signal and resting state functional connectivity were evaluated and analyzed using a rat 3D MRI atlas with 173 brain areas. Results: GAT107 presented with an inverted-U dose response curve with the 3 mg/kg dose having the greatest effect on the positive BOLD volume of activation. The primary somatosensory cortex, prefrontal cortex, thalamus, and basal ganglia, particularly areas with efferent connections from the midbrain dopaminergic system were activated as compared to vehicle. The hippocampus, hypothalamus, amygdala, brainstem, and cerebellum showed little activation. Forty-five min post treatment with GAT107, data for resting state functional connectivity were acquired and showed a global decrease in connectivity as compared to vehicle. Discussion: GAT107 activated specific brain regions involved in cognitive control, motivation, and sensory perception using a BOLD provocation imaging protocol. However, when analyzed for resting state functional connectivity there was an inexplicable, general decrease in connectivity across all brain areas.

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits.

The impact of physician leadership development on behaviour and work-related changes.

In this article, we present findings from a retrospective survey of 117 physician leadership development program graduates at the Sauder School of Business at the University of British Columbia in Vancouver. The survey was designed to assess how the program contributed to graduates' leadership development, specifically in terms of behaviour change and work-related changes. The themes resulting from the analysis of the open-ended questions reflected that the program led to changes in graduates' leadership behaviour and their ability to lead change in their respective organizations. The study highlighted the benefits of investment in training for physician leaders to advance transformation and improvement initiatives in a changing world.

Disparities in Pediatric Specialty Referral Scheduling and Completion.

OBJECTIVE: To estimate differences in scheduled and completed specialty referrals by race, ethnicity, language for care, and insurance type. STUDY DESIGN: We studied a retrospective cohort of 38 334 specialty referrals to a large children's hospital between March 2019 and March 2021. We included referrals for patients with primary care clinics within 5 miles of the hospital. We examined whether the odds of and time to scheduled and completed referrals differed by patient sociodemographic characteristics. RESULTS: Of all referrals, 62% were scheduled and 54% were completed. Referral completion rates were lower for patients with Black race (45%), Native Hawaiian/Pacific Islander race (48%), Spanish language (49%), and public insurance (47%). Odds of scheduled and completed referral were lower for Asian (aOR scheduled: 0.94, [95% CI: 0.89, 0.99]; aOR completed: 0.92 [0.87, 0.97]), Black (aOR scheduled: 0.86 [0.79, 0.94]; aOR completed: 0.80 [0.73, 0.87]), and publicly insured patients (aOR scheduled: 0.71 [0.66, 0.75]; aOR completed: 0.70 [0.66, 0.75]). Time to scheduled and completed referral was longer for Black (adjusted hazard ratio [aHR] scheduled: 0.93 [0.88, 0.98]; aHR completed: 0.93 [0.87, 0.99]) and publicly insured patients (aHR scheduled: 0.85 [0.82, 0.88]; aHR completed: 0.84 [0.80, 0.87]) and families with a language other than English (aHR scheduled: 0.66 [0.62, 0.70]; aHR completed: 0.92 [0.86, 0.99]). CONCLUSIONS: Within a geographically homogenous pediatric population, the odds and time to scheduled and completed specialty referrals differed by sociodemographic characteristics, suggesting the effects of discrimination. To improve access equity, health care organizations need clear and consistent referral workflows and more comprehensive metrics for access.

How does work environment relate to diagnostic quality? A prospective, mixed methods study in primary care.

OBJECTIVES: The quest to measure and improve diagnosis has proven challenging; new approaches are needed to better understand and measure key elements of the diagnostic process in clinical encounters. The aim of this study was to develop a tool assessing key elements of the diagnostic assessment process and apply it to a series of diagnostic encounters examining clinical notes and encounters' recorded transcripts. Additionally, we aimed to correlate and contextualise these findings with measures of encounter time and physician burnout. DESIGN: We audio-recorded encounters, reviewed their transcripts and associated them with their clinical notes and findings were correlated with concurrent Mini Z Worklife measures and physician burnout. SETTING: Three primary urgent-care settings. PARTICIPANTS: We conducted in-depth evaluations of 28 clinical encounters delivered by seven physicians. RESULTS: Comparing encounter transcripts with clinical notes, in 24 of 28 (86%) there was high note/transcript concordance for the diagnostic elements on our tool. Reliably included elements were red flags (92% of notes/encounters), aetiologies (88%), likelihood/uncertainties (71%) and follow-up contingencies (71%), whereas psychosocial/contextual information (35%) and mentioning common pitfalls (7%) were often missing. In 22% of encounters, follow-up contingencies were in the note, but absent from the recorded encounter. There was a trend for higher burnout scores being associated with physicians less likely to address key diagnosis items, such as psychosocial history/context. CONCLUSIONS: A new tool shows promise as a means of assessing key elements of diagnostic quality in clinical encounters. Work conditions and physician reactions appear to correlate with diagnostic behaviours. Future research should continue to assess relationships between time pressure and diagnostic quality.

Identifying odds of bloodstream infection in repaired silastic central venous catheters in a pediatric population.

Background: Silicone central venous catheters (CVCs) that weaken or rupture are reparable using a commercial repair kit. A literature review exploring bloodstream infections in repaired CVCs identified many findings indicating low or no increased risk of infection. This study aimed to understand pediatric patients' risk of bloodstream infection with repaired Hickman or Broviac catheters. Methods: A matched retrospective case-control study examined central line-associated bloodstream infection (CLABSI) or bacteremia in two separately matched cohorts of patients with silicone-type catheters. Controls were patients with CVCs selected from 2016 to 2019 and were matched to cases based on age group (older or younger than 3 years). Conditional logistic regression models calculated odds ratios (OR), with 95% confidence intervals (CI) representing the odds of a line repair occurring 30 days before an event among cases versus controls. Results: In 61 CLABSI cases and 104 controls, the OR of exposure to a line repair was 0.43; 95% CI, 0.05-3.87, P = 0.45. In comparing 49 bacteremia cases to 109 controls, the OR of exposure to a line repair was 6.69; 95% CI, 0.69-8, P = 0.10. Conclusions: The frequency of CVC repair was relatively low. Associations between repair and infection were not detected in either cohort; however, odds of line repair exposure appeared to be higher in bacteremia cases (a trend not observed in the CLABSI cohort). More extensive studies examining the demographic and clinical characteristics of the CVC repair population will be critical for improving outcomes.

Primary care physician leaders' perspectives on opportunities and challenges in healthcare leadership: a qualitative study.

BACKGROUND: There is an increasing demand for physicians to assume leadership roles in hospitals, health systems, clinics and community settings, given the documented positive outcomes of physician leadership and the systemic shifts towards value-based care. The purpose of this study is to examine how primary care physicians (PCPs) perceive and experience leadership roles. Better understanding how PCPs perceive leadership affords the opportunity to influence changes in primary care training in order to more adequately prepare and support physicians for current and future leadership roles. METHODS: This study used qualitative interviews, conducted from January to May 2020. The participants included 27 PCPs, recruited via the Harvard Medical School Center for Primary Care newsletters and through snowball sampling techniques. Participants worked in 22 different organisations, including major urban health systems, corporate pharmacy, public health departments and academic medical centres. RESULTS: Using content analysis and qualitative comparative analysis methodologies, three major themes and seven subthemes emerged from the interviews. The primary themes included the advantage PCPs have in leadership positions, the lack of leadership training and development, and disincentives to leading. CONCLUSIONS: While PCPs perceive primary care to hold a unique position that would incline them towards leadership, the lack of training and other noted disincentives are barriers to leadership. Therefore, health organisations should seek to invest in, better train and promote PCPs in leadership.

Diminished Neuronal ESCRT-0 Function Exacerbates AMPA Receptor Derangement and Accelerates Prion-Induced Neurodegeneration.

Endolysosomal defects in neurons are central to the pathogenesis of prion and other neurodegenerative disorders. In prion disease, prion oligomers traffic through the multivesicular body (MVB) and are routed for degradation in lysosomes or for release in exosomes, yet how prions impact proteostatic pathways is unclear. We found that prion-affected human and mouse brain showed a marked reduction in Hrs and STAM1 (ESCRT-0), which route ubiquitinated membrane proteins from early endosomes into MVBs. To determine how the reduction in ESCRT-0 impacts prion conversion and cellular toxicity in vivo, we prion-challenged conditional knockout mice (male and female) having Hrs deleted from neurons, astrocytes, or microglia. The neuronal, but not astrocytic or microglial, Hrs-depleted mice showed a shortened survival and an acceleration in synaptic derangements, including an accumulation of ubiquitinated proteins, deregulation of phosphorylated AMPA and metabotropic glutamate receptors, and profoundly altered synaptic structure, all of which occurred later in the prion-infected control mice. Finally, we found that neuronal Hrs (nHrs) depletion increased surface levels of the cellular prion protein, PrPC, which may contribute to the rapidly advancing disease through neurotoxic signaling. Taken together, the reduced Hrs in the prion-affected brain hampers ubiquitinated protein clearance at the synapse, exacerbates postsynaptic glutamate receptor deregulation, and accelerates neurodegeneration.SIGNIFICANCE STATEMENT Prion diseases are rapidly progressive neurodegenerative disorders characterized by prion aggregate spread through the central nervous system. Early disease features include ubiquitinated protein accumulation and synapse loss. Here, we investigate how prion aggregates alter ubiquitinated protein clearance pathways (ESCRT) in mouse and human prion-infected brain, discovering a marked reduction in Hrs. Using a prion-infection mouse model with neuronal Hrs (nHrs) depleted, we show that low neuronal Hrs is detrimental and markedly shortens survival time while accelerating synaptic derangements, including ubiquitinated protein accumulation, indicating that Hrs loss exacerbates prion disease progression. Additionally, Hrs depletion increases the surface distribution of prion protein (PrPC), linked to aggregate-induced neurotoxic signaling, suggesting that Hrs loss in prion disease accelerates disease through enhancing PrPC-mediated neurotoxic signaling.