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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Primate-conserved carbonic anhydrase IV and murine-restricted LY6C1 enable blood-brain barrier crossing by engineered viral vectors.

The blood-brain barrier (BBB) presents a major challenge for delivering large molecules to study and treat the central nervous system. This is due in part to the scarcity of targets known to mediate BBB crossing. To identify novel targets, we leverage a panel of adeno-associated viruses (AAVs) previously identified through mechanism-agnostic directed evolution for improved BBB transcytosis. Screening potential cognate receptors for enhanced BBB crossing, we identify two targets: murine-restricted LY6C1 and widely conserved carbonic anhydrase IV (CA-IV). We apply AlphaFold-based in silico methods to generate capsid-receptor binding models to predict the affinity of AAVs for these identified receptors. Demonstrating how these tools can unlock target-focused engineering strategies, we create an enhanced LY6C1-binding vector, AAV-PHP.eC, that, unlike our prior PHP.eB, also works in Ly6a-deficient mouse strains such as BALB/cJ. Combined with structural insights from computational modeling, the identification of primate-conserved CA-IV enables the design of more specific and potent human brain-penetrant chemicals and biologicals, including gene delivery vectors.

Exploring relationships between physician stress, burnout, and diagnostic elements in clinician notes.

OBJECTIVES: To understand the relationship between stressful work environments and patient care by assessing work conditions, burnout, and elements of the diagnostic process. METHODS: Notes and transcripts of audiotaped encounters were assessed for verbal and written documentation related to psychosocial data, differential diagnosis, acknowledgement of uncertainty, and other diagnosis-relevant contextual elements using 5-point Likert scales in seven primary care physicians (PCPs) and 28 patients in urgent care settings. Encounter time spent vs time needed (time pressure) was collected from time stamps and clinician surveys. Study physicians completed surveys on stress, burnout, and work conditions using the Mini-Z survey. RESULTS: Physicians with high stress or burnout were less likely to record psychosocial information in transcripts and notes (psychosocial information noted in 0% of encounters in 4 high stress/burned-out physicians), whereas low stress physicians (n=3) recorded psychosocial information consistently in 67% of encounters. Burned-out physicians discussed a differential diagnosis in only 31% of encounters (low counts concentrated in two physicians) vs. in 73% of non-burned-out doctors' encounters. Burned-out and non-burned-out doctors spent comparable amounts of time with patients (about 25 min). CONCLUSIONS: Key diagnostic elements were seen less often in encounter transcripts and notes in burned-out urgent care physicians.

Using Rapid-Cycle Change to Improve COVID-19 Vaccination Strategy in Primary Care.

During the COVID-19 pandemic, misinformation and distrust exacerbated disparities in vaccination rates by race and ethnicity throughout the United States. Primary care, public health systems, and community health centers have shifted their vaccination outreach strategies toward these disparate, unvaccinated populations. To support primary care, we developed the SAVE Sprint model for implementing rapid-cycle change to improve vaccination rates by overcoming community outreach barriers and workforce limitations. Participants were recruited for the 10-week SAVE Sprint program through partnerships with the National Association of Community Health Centers (NACHC) and the Resilient American Communities (RAC) Initiative. The majority of the participants were from community health centers. Data were evaluated during the program through progress reports and surveys, and interviews conducted three months post-intervention were recorded, coded, and analyzed. The SAVE Sprint model of rapid-cycle change exceeded participants' expectations and led to improvements in patient education and vaccination among their vulnerable populations. Participants reported building new skills and identifying strategies for targeting specific populations during a public health emergency. However, participants reported that planning for rapid-pace change and trust-building with community partners prior to a health care crisis is preferable and would make navigating an emergency easier.

Improving diagnosis: adding context to cognition.

BACKGROUND: The environment in which clinicians provide care and think about their patients is a crucial and undervalued component of the diagnostic process. CONTENT: In this paper, we propose a new conceptual model that links work conditions to clinician responses such as stress and burnout, which in turn impacts the quality of the diagnostic process and finally patient diagnostic outcomes. The mechanism for these interactions critically depends on the relationship between working memory (WM) and long-term memory (LTM), and ways WM and LTM interactions are affected by working conditions. SUMMARY: We propose a conceptual model to guide interventions to improve work conditions, clinician reactions and ultimately diagnostic process, accuracy and outcomes. OUTLOOK: Improving diagnosis can be accomplished if we are able to understand, measure and increase our knowledge of the context of care.

Delivering High-Quality Primary Care Requires Work That Is Worthwhile for Medical Assistants.

Medical assistants are core members of the primary care team, but health care organizations struggle to hire and retain them amid the ongoing exodus of health care workers as part of the "Great Resignation." To sustain a stable and engaged workforce of medical assistants, we argue that efforts to hire and retain them should focus on making their work worthwhile. Work that is worthwhile includes adequate pay, benefits, and job security, but additionally enables employees to experience a sense of contribution, growth, social connectedness, and autonomy. We highlight opportunities during team huddles, the rooming of patients, and career development where the work of medical assistants can be made worthwhile. We also connect these components to the work design literature to show how clinic managers and supervising clinicians can promote worthwhile work through decision-making and organizational climate. Going beyond financial compensation, these components target the latent occupational needs of medical assistants and are likely to forge employee-employer relationships that are mutually valued and sustained over time.

Conceptual Framework for Integrating Family Caregivers Into the Health Care Team: A Scoping Review.

More than 80% of family care partners of older adults are responsible for coordinating care between and among providers; yet, their inclusion in the health care delivery process lacks recognition, coordination, and standardization. Despite efforts to include care partners (e.g., through informal or formal proxy access to their care recipient's patient portal), policies and procedures around care partner inclusion are complex and inconsistently implemented. We conducted a scoping review of peer-reviewed articles published from 2015 to 2021 and reviewed a final sample of 45 U.S.-based studies. Few articles specifically examine the inclusion of care partners in health care teams; those that do, do not define or measure care partner inclusion in a standardized way. Efforts to consider care partners as "partners" rather than "visitors" require further consideration of how to build health care teams inclusive of care partners. Incentives for health care organizations and providers to practice inclusive team-building may be required.

Burnout Among Missouri Primary Care Clinicians in 2021: Roadmap for Recovery?

Rates of burnout among clinicians have been exacerbated by the COVID-19 (COVID)pandemic. A survey of Missouri primary care professionals at federally qualified health centers was conducted during a COVID surge in August 2021 to assess burnout, stress, and job satisfaction as well as if respondents had sought assistance for burnout or attended resiliency training. Despite respondents reporting rates of burnout (56%) that exceed those reported nationally (48%), only 17% sought help for burnout. Most (81%) had not attended resiliency training; of those who did, 16% said sessions "make me feel less alone," while an equivalent number found sessions not useful, identifying an absence of resources within their organization. Comments focused on the need for dedicated time to receive support, including time to seek assistance during working hours, time to take breaks, and time for self-care. The data suggest one path forward to remediate burnout: provide the workforce with time to access support.