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Abstract Introduction Attacks on healthcare have been committed throughout the Syrian conflict in violation of International Humanitarian Law (IHL), contributing to the devastation of the country’s healthcare system. The conflict has also forcibly displaced over half of Syria’s pre-conflict population, 7.2 million of whom are internally displaced. In this retrospective analysis, we aim to assess the relationships between (1) healthcare attacks and general conflict and (2) healthcare attacks and forced displacement between 2016 and 2022. Methods Data on healthcare attacks, conflict events, and displacement were extracted from the Syrian American Medical Society (SAMS), Uppsala Conflict Data Project, and OCHA Türkiye, respectively. The analysis addresses three research questions: the associations between (1) healthcare attacks and conflict events, (2) healthcare attacks and conflict events in the week after an attack on a healthcare facility, and (3) healthcare attacks and forced displacement. For each, we used generalized additive models with a negative binomial distribution that also accounted for spatial and temporal factors. Results SAMS recorded a total of 541 attack events, comprising 650 attack rounds over 235 facilities between 2016 and 2022. Conflict events were significantly associated with healthcare attacks in the same week (IRR: 1.14, 95% CI 1.12–1.17), and healthcare attacks in one week were associated with a maximum of 1.44 greater risk (95% CI 1.08–1.91) of conflict events in the following week, even when accounting for general conflict levels in the previous weeks. Healthcare attacks were also significantly associated with increased displacement up to three months following the attacks. Discussion We find that healthcare facilities are not avoided during conflict (as obliged under IHL), and that healthcare attacks significantly precede an escalation of general conflict in the same area. Healthcare attacks are also significantly associated with displacement for months following the attacks, even when accounting for conflict levels. Based on these findings, we present a framework outlining one pathway through which healthcare attacks may contribute to larger conflict tactics. Our findings highlight the critical role of healthcare infrastructure in conflict and reaffirm calls to hold perpetrators of these attacks accountable.

Abstract Background Lipid disorders significantly increase cardiovascular disease (CVD) risk, the leading cause of mortality worldwide. Effective lipid management is critical for improving health outcomes. Traditional screening methods face challenges due to data complexity and the need for timely decision-making. Data visualization and dashboard technologies offer clear, actionable insights and supporting informed decision-making. This study investigates the use of these technologies in lipid management and their impacts on the quadruple aim of healthcare. Methods This scoping review followed the Joanna Briggs Institute (JBI) approach, focusing on studies involving dashboard technologies or data visualization in lipid management. A comprehensive search across multiple databases (Embase, Web of Science, PubMed, Scopus, CINAHL) and gray literature was conducted, including English-language publications from 2014 to 2024. Data were analyzed using quantitative descriptive and qualitative content analysis to evaluate the key features, clinical applications, and outcomes. Results Twenty-seven studies met the inclusion criteria, primarily focusing on dashboard utilization by physicians for managing diabetes and CVD, utilizing electronic medical records and clinical guidelines. Key analysis methods included comparing key performance indicators (KPIs) (85.2%) and trend analysis (74.1%). Lipid management workflows emphasized prevention (88.9%) and treatment planning (77.8%). Interventions included care packages (comprehensive sets of interventions for patient care), decision support systems, web-based tools, and mobile health solutions. Regarding Quadruple Aim outcomes: 12 studies focused on improving population health (8 positive, 4 no change), 9 on clinical outcomes (5 positive, 4 no change), 6 on provider work life (5 positive), 5 on patient experience (positive changes in education and time management), and 2 on cost reduction (1 positive, 1 negative). Conclusions Dashboards are important tools in managing lipid disorders in managing lipid disorders, integrating with educational tools, collaborative care models, and decision support systems. Although they are effective in enhancing population health and clinical experiences, their impact on patient outcomes and cost reduction requires further exploration. Future research should focus on detailed evaluations of dashboard impacts on patient outcomes and cost-effectiveness, emphasizing precision prevention of chronic diseases.

Abstract Background As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those subjects who responded to treatment, to build a more precise Phase 3 trial design for further investigation in likely responders. Results Subjects with mtDNA pathogenic variants or single large-scale mtDNA deletions represented 74% of the MMPOWER-3 population, with 70% in the mtDNA cohort having either single large-scale mtDNA deletions or MT-TL1 pathogenic variants. Most subjects in the nDNA cohort had pathogenic variants in genes required for mtDNA maintenance (mtDNA replisome), the majority of which were in POLG and TWNK. The mtDNA replisome post-hoc cohort displayed an improvement on the 6MWT, trending towards significant, in the elamipretide group when compared with placebo (25.2 ± 8.7 m versus 2.0 ± 8.6 m for placebo group; p = 0.06). The 6MWT results at week 24 in subjects with replisome variants showed a significant change in the elamipretide group subjects who had chronic progressive external ophthalmoplegia (CPEO) (37.3 ± 9.5 m versus − 8.0 ± 10.7 m for the placebo group; p = 0.0024). Pharmacokinetic (exposure–response) analyses in the nDNA cohort showed a weak positive correlation between plasma elamipretide concentration and 6MWT improvement. Conclusions Post hoc analyses indicated that elamipretide had a beneficial effect in PMM patients with mtDNA replisome disorders, underscoring the importance of considering specific genetic subtypes in PMM clinical trials. These data serve as the foundation for a follow-up Phase 3 clinical trial (NuPOWER) which has been designed as described in this paper to determine the efficacy of elamipretide in patients with mtDNA maintenance-related disorders. Classification of evidence Class I ClinicalTrials.gov identifier NCT03323749

Abstract Introduction The Irish Prostate Cancer Outcomes Research (IPCOR) Study collected longitudinal data on men newly diagnosed with Prostate Cancer (PC). Understanding the nuances of disease presentation is essential, considering the high incidence of PC in Ireland. This study aims to characterise disease presentation features, identify factors related to socio demographic disparities in presentation following opportunistic screening, and shed light on potential inequality challenges within Ireland’s healthcare structure. Methods Data were collected on demographics, diagnosis, and treatment of 6,816 men newly diagnosed with PC across 16 hospitals in the Republic of Ireland from February 2016 to January 2020. A complete case analysis was carried out, complemented by a sensitivity analysis for addressing sites with high rates of missing values. Multivariable logistic regression was conducted to examine the association between various predictor variables and the initial presentation to the urology clinic subsequent to opportunistic screening. Results A multivariable logistic regression model revealed that the type of hospital was a key determinant in post-opportunistic screening presentation, with patients in public hospitals 45.7% more likely to be presented following screening compared to those in private hospitals. Urban residents were 34% more likely to present following screening than rural ones. Age negatively influenced presentation following screening likelihood, decreasing by 3.4% yearly. Discussion Our research has highlighted the key features of PC presentation in Ireland, revealing potential inequalities affecting mainly urban populations, middle socioeconomic groups, and individuals with inadequate healthcare coverage. While the differences we observed in various groups may appear subtle and may indicate the success of the Rapid Access Prostate Clinics, they are still significant in pinpointing specific populations that require special attention. Conclusions By addressing these nuanced differences in access to healthcare, socioeconomic status, and urban versus rural residence and implementing tailored strategies, we can work towards closing disparity gaps in PC, ultimately leading to improved health outcomes and equity across all population segments.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations. There is little understanding of why some organs are specifically impacted in patients and the mechanisms of disease persistence remain unclear. While much work has been done characterizing the DNA methylation status in SLE, there is less information on histone modifications, a more dynamic epigenetic feature. This study identifies two histone marks of activation and the binding of p300 genome-wide in three cell types and three clinical subsets to better understand cell-specific effects and differences across clinical subsets. Results We examined 20 patients with SLE and 8 controls and found that individual chromatin marks varied considerably across T cells, B cells, and monocytes. When pathways were examined, there was far more concordance with conservation of TNF, IL-2/STAT5, and KRAS pathways across multiple cell types and ChIP data sets. Patients with cutaneous lupus and lupus nephritis generally had less dramatically altered chromatin than the general SLE group. Signals also demonstrated significant overlap with GWAS signals in a manner that did not implicate one cell type more than the others. Conclusions The pathways identified by altered histone modifications and p300 binding are pathways known to be important from RNA expression studies and recognized pathogenic mechanisms of disease. NFκB and classical inflammatory pathways were strongly associated with increased peak heights across all cell types but were the highest-ranking pathway for all three antibodies in monocytes according to fgsea analysis. IL-6 Jak/STAT3 signaling was the most significant pathway association in T cells marked by H3K27ac change. Therefore, each cell type experiences the disease process distinctly although in all cases there was a strong theme of classical inflammatory pathways. Importantly, this NFκB pathway, so strongly implicated in the patients with generalized SLE, was much less impacted in monocytes when cutaneous lupus was compared to the general SLE cohort and also less impacted in lupus nephritis compared to general SLE. These studies define important cell type differences and emphasize the breadth of the inflammatory effects in SLE.

Abstract Background In the United States (US), transgender women of color experience cyclical, interlocking systems of structural and institutional oppression rooted in racism and transphobia, which fuel economic vulnerability. Together, cycles of intersecting racism, transphobia, and economic vulnerability create conditions that give rise to extreme HIV inequities among transgender women of color. Microeconomic interventions — designed to improve financial standing by increasing income generation and access to financial resources through entrepreneurship, cash transfers, and training — have the potential to address structural factors underlying HIV inequities. Over the past few years, several trans-led organizations, including the Trans Sistas of Color Project, have integrated microeconomic strategies, specifically emergency assistance, into their programming. The aim of the current study is to conduct a pilot randomized controlled trial (RCT) to evaluate the feasibility and acceptability of a definitive subsequent RCT and explore initial evidence of an enhanced microeconomic intervention to increase income generation and improve HIV prevention and care continua outcomes. Methods This is a two-arm waitlist randomized controlled trial in which transgender women of color will be randomly allocated to either usual care that includes the Trans Sistas of Color Project’s existing microeconomic interventions, which includes the following: (1) US $250 in emergency assistance and (2) peer support to obtain legal gender affirmation (i.e., legal name and gender markers on identification documents) or the enhanced microeconomic intervention that includes usual care and will be enhanced to include the following: (1) 12 weekly educational group sessions on economic empowerment (i.e., job acquisition, income generation through micro-business, and financial literacy) and HIV prevention and care, (2) employment-focused mentoring, and (3) an unconditional grant (US $1200) for use towards acquiring self-led or formal employment. Participants in each condition will complete a baseline survey prior to randomization, a follow-up survey immediately following intervention completion, and 3-month survey after intervention completion. Participants will also complete qualitative exit interviews within 1 month of intervention completion for both conditions. Discussion This study will be one of the first US-based pilot randomized clinical trials that builds upon existing community-led solutions to economic vulnerability to address HIV inequities. Findings will provide the necessary groundwork to examine intervention effectiveness in a future large-scale trial. Trials registration NCT06212544. Protocol version September 25, 2024, version 2.

Abstract Politics as the exercise of power always influence public policies–which reflects the multifaceted nature of decision-making–but “using politics” as a motivation for self-serving interests of government leaders and their allies poses problems. This article reviews the impacts of COVID-19 on health systems of the Latin American and Caribbean region from a political lens. We highlight the overriding influence of politics in health policies, weak governance structures that became compromised, exacerbation of corruption, and breakdowns in the communication and trust between governments and their citizens. There are many factors that did not work well-or as expected. For instance, the poor predictive ability of the Global Health Security Index, which showed that pre-pandemic assessments were deeply naive to how health systems evidence and expertise are uniquely vulnerable to politics. We argue that there is an urgent need to rethink health policy and systems frameworks-including metrics-at national and global level. There is also a need for new global health governance arrangements. The expected solidarity and collaboration among countries was trumped by the rich countries practice of gauging essential resources and vaccines and applying health diplomacy to the rest of the world, and the unchecked power of commercial corporations producing essential medical supplies and vaccines.

Abstract Background In response to activated patient communities’ catalyzation, two significant efforts by the FDA to expedite treatments have now been in place for multiple decades. In 1983, the United States Congress passed the Orphan Drug Act to provide financial incentives for development of drugs for rare diseases. In 1992, partly in response to the HIV epidemic, the FDA implemented Accelerated Approval (AA) to expedite access to promising new therapies to treat serious conditions with unmet medical need based on surrogate marker efficacy while additional clinical data is confirmed. The uses of these regulatory approaches over time are assessed in this study. Methods The following U.S. FDA CDER published lists were used in this analysis: 1. all orphan designations and approvals; 2. all AA and their details updated through December 31, 2022; new molecular entities (NMEs). Results Orphan drug designations and approvals have increased several-fold over the past four decades. The largest increase recently has been in therapies targeting oncological diseases (comprised of both oncology and malignant hematology). Although orphan drug approvals based on NMEs are the minority of orphan drug designations, the count of approved orphan drug NMEs has increased in recent years. The characteristics of orphan drug approvals show notable differences by disease area with rare diseases and medical genetics (49%) having a relatively large fraction of orphan drug approvals with NMEs compared to the oncological diseases (32%). Similar to the use of orphan drug designation, oncological disease therapies have been the largest utilizers of AA. Many therapies targeting these diseases address unmet medical need and can leverage surrogate markers that have previously been used in similar trials. The timings of conversion of AA (confirmed or withdrawn) were assessed and found to be consistent across decades and to have some dependency upon the broad disease area (when assessed by three large groups: HIV conversions were fastest; followed by oncology; followed by all others). By the end of 2022, 98% of the first 105 (approved in 2010 or earlier) AA had been converted to confirmed or withdrawn. Conclusions Although the typical timings for AA to be confirmed or withdrawn has not changed significantly over the decades, the disease areas utilizing orphan drug designation and AA have changed significantly over time. Both programs have had increases in their use for therapies targeting oncological diseases. The re-use of surrogate markers for oncological diseases has been an advantage in a way that may not be scientifically feasible in many other disease areas that have greater differentiation across disease etiology. For non-oncological diseases, applicability of AA is, in part, dependent upon greater focus on characterization and acceptance of novel surrogate markers.

Abstract Background The Myositis Interstitial Lung Disease Nintedanib Trial (MINT) is a hybrid trial, which is enrolling patients both at local sites and remotely via a decentralised site. The trial will investigate the efficacy and safety of nintedanib in patients with progressive myositis-associated interstitial lung disease (MA-ILD). Methods/Design MINT is an exploratory, prospective randomised placebo-controlled trial. Eligible patients will have myositis and evidence of fibrosing ILD on high-resolution computed tomography (HRCT), be taking standard of care medications for myositis, and meet criteria for ILD progression within the prior 24 months based on decline in FVC, worsened fibrosis on HRCT, and/or worsened dyspnoea. Patients will be randomised 1:1 to receive nintedanib 150 mg twice daily or placebo for 12 weeks then open-label nintedanib for 12 weeks. Patients will be enrolled at local sites and a decentralised site. Most study visits will be completed remotely using telemedicine or digital health technologies. The primary endpoint is the change in Living with Pulmonary Fibrosis (L-PF) questionnaire dyspnoea domain score at week 12. Other endpoints include changes in other L-PF questionnaire domains, lung function, imaging, and physical activity, and assessment of adverse events. Data collected using remote versus clinic enrolment, and using home versus clinic spirometry, will be compared. Discussion MINT is an innovative, hybrid trial that will evaluate the effects of nintedanib on symptoms, quality of life, and ILD progression in patients with progressive MA-ILD and provide valuable information on the utility of decentralised recruitment and remote data collection in clinical trials. Trial registration Clinicaltrials.gov NCT05799755 (date of registration: 05/04/2023).

Abstract Alzheimer’s disease (AD) is a multifactorial disease with both genetic and environmental factors contributing to its etiology. Previous evidence has implicated disturbed insulin signaling as a key mechanism that plays a role in both neurodegenerative diseases such as AD and comorbid somatic diseases such as diabetes mellitus type 2 (DM2). In this study, we analysed available genome-wide association studies (GWASs) of AD and somatic insulin-related diseases and conditions (SID), i.e., DM2, metabolic syndrome and obesity, to identify genes associated with both AD and SID that could increase our insights into their molecular underpinnings. We then performed functional enrichment analyses of these genes. Subsequently, using (additional) GWAS data, we conducted shared genetic etiology analyses between AD and SID, on the one hand, and blood and cerebrospinal fluid (CSF) metabolite levels on the other hand. Further, integrating all these analysis results with elaborate literature searches, we built a molecular landscape of the overlap between AD and SID. From the landscape, multiple functional themes emerged, including insulin signaling, estrogen signaling, synaptic transmission, lipid metabolism and tau signaling. We also found shared genetic etiologies between AD/SID and the blood/CSF levels of multiple metabolites, pointing towards “energy metabolism” as a key metabolic pathway that is affected in both AD and SID. Lastly, the landscape provided leads for putative novel drug targets for AD (including MARK4, TMEM219, FKBP5, NDUFS3 and IL34) that could be further developed into new AD treatments.

Abstract Aim To describe where clinical information is contemporarily and commonly found in UK primary care, what is favoured by clinicians, and whether this is (1) publicly funded (2) has commercial potential conflicts of interest. Design and setting A mixed methods study, consisting of (1) site visits to general practices in Scotland, (2) online questionnaire, focused on UK general practice (3) analysis of materials cited by professionals. Methods Data about sources of clinical information used was obtained verbally, visually and via search histories on computers from visits. This was used to inform a questionnaire in which primary care clinicians in the four nations of the UK were invited to participate. This obtained data about the information sources used and preferred by clinicians. This information was searched for data about funding and conflicts of interest. Results Over 2022, four practices were visited. 337 clinicians, 280 of whom were general practitioners completed an online questionnaire. 136 different resources were identified. These were mainly websites but sources of information included colleagues, either in practice or through online networks, apps, local guidelines, health charities, and learning resources aimed at GPs. Of these, 70 were not publicly funded, and were a mixture of membership organisations, charities, or sponsored venues. Conclusions Primary care clinicians obtain information for themselves and patients from a wide variety of sources. Funding is from a variety of sources and some contain advertising and/or sponsorship, risking commercial bias. Protocol Pre-published at https://osf.io/wrzqk .

Abstract Background Multiple state and national health care organizations have invested in activities to screen for and address the health-related social needs (HRSNs) of their patients. However, patient perspectives concerning HRSN screening discussions and facilitated referrals to supports are largely unexplored. The main objectives of this study were to explore the ways in which Massachusetts Medicaid (MassHealth) members engage with their health care clinicians to discuss HRSNs, to identify common needs discussed, and to describe whether members feel these needs are being addressed by health care clinicians and staff. Methods The study team performed a cross-sectional, qualitative research study that included in-depth, open-ended interviews with 44 adult MassHealth members. Interviews were conducted between June and October 2022. Interviews were recorded, transcribed, and systematically coded for analysis, and common themes were reported. The data collected for this study were part of a larger independent evaluation of MassHealth’s 2017-2022 Section 1115 Demonstration that granted authority from CMS to implement health care delivery system reforms in Massachusetts. Results In this qualitative study of Medicaid members, some reportedly felt comfortable freely discussing all of their clinical and social needs with their health care clinicians, while others noted feelings of apprehension. Several members recalled being asked about their HRSNs in various clinical or community settings, while others did not. The majority of members endorsed having an unmet HRSN, including housing, nutrition, financial, or transportation issues, and many barriers to addressing these HRSNs were discussed. Finally, many members cited a preference for discussing HRSNs with community-based care coordinators and social workers at the community partner organizations rather than with their health care clinicians. Community-based care coordinators were lauded as essential facilitators in making the connection to necessary resources to help address HRSNs. Conclusions Study results highlight an opportunity to increase the effectiveness of HRSN screening and referral practices within the health care setting through relationship building between Medicaid members and diverse interdisciplinary care teams that include staff such as community health workers. Continued investment in cross-sector partnerships, screening workflows, and patient-clinician relationships may contribute to establishing an environment in which members can comfortably discuss HRSNs and connect with needed services to improve their health.

Abstract Background Prognostic models that identify individuals with chronic kidney disease (CKD) at greatest risk of developing kidney failure help clinicians to make decisions and deliver precision medicine. It is recognised that people with CKD usually have multiple long-term health conditions (multimorbidity) and often experience frailty. We undertook a systematic review to evaluate the representation and consideration of multimorbidity and frailty within CKD cohorts used to develop and/or validate prognostic models assessing the risk of kidney failure. Methods We identified studies that described derivation, validation or update of kidney failure prognostic models in MEDLINE, CINAHL Plus and the Cochrane Library—CENTRAL. The primary outcome was representation of multimorbidity or frailty. The secondary outcome was predictive accuracy of identified models in relation to presence of multimorbidity or frailty. Results Ninety-seven studies reporting 121 different kidney failure prognostic models were identified. Two studies reported prevalence of multimorbidity and a single study reported prevalence of frailty. The rates of specific comorbidities were reported in a greater proportion of studies: 67.0% reported baseline data on diabetes, 54.6% reported hypertension and 39.2% reported cardiovascular disease. No studies included frailty in model development, and only one study considered multimorbidity as a predictor variable. No studies assessed model performance in populations in relation to multimorbidity. A single study assessed associations between frailty and the risks of kidney failure and death. Conclusions There is a paucity of kidney failure risk prediction models that consider the impact of multimorbidity and/or frailty, resulting in a lack of clear evidence-based practice for multimorbid or frail individuals. These knowledge gaps should be explored to help clinicians know whether these models can be used for CKD patients who experience multimorbidity and/or frailty. Systematic review registration This review has been registered on PROSPERO (CRD42022347295).

Abstract Background Under Sect. 564 of the Federal Food, Drug, and Cosmetic Act, when the US Department of Health and Human Services Secretary issues a declaration based on one of four types of determinations, FDA may authorize an unapproved product or unapproved uses of an approved product for emergency use. It is unclear how much the public and health care providers understand about emergency use authorizations and how that understanding influences perceptions or behavioral intentions. The current study aimed to explore consumer and health care provider perceptions of emergency use authorizations and how promotion of emergency use authorizations has been investigated in the literature. Methods We conducted a scoping review via PubMed, Embase, Web of Science, and CINAHL for original research published in English from January 1, 2012, through November 10, 2022. We conducted surveillance of the literature through March 2023. Results We identified 13 studies reported in 14 publications that addressed public and health care provider attitudes, understanding, and behaviors with regard to products authorized under an emergency use authorization. We did not identify any articles describing research regarding the promotion of emergency use authorization products. Findings suggest gaps in understanding of emergency use authorizations, both for the public and health care providers. Findings also suggest the public and health care providers have concerns about safety or the lack of full FDA approval that may contribute to decreased willingness to receive treatments and vaccines under an emergency use authorization. Conclusions Future research should explore how emergency use authorizations have been promoted and how that promotion impacts public and health care provider perceptions.

Abstract Background Rural populations experience ongoing health inequities with disproportionately high morbidity and mortality rates, but digital health in rural settings is poorly studied. Our research question was: How does digital health influence healthcare outcomes in rural settings? The objective was to identify how digital health capability enables the delivery of outcomes in rural settings according to the quadruple aims of healthcare: population health, patient experience, healthcare costs and provider experience. Methods A multi-site qualitative case study was conducted with interviews and focus groups performed with healthcare staff (n = 93) employed in rural healthcare systems (n = 10) in the state of Queensland, Australia. An evidence-based digital health capability framework and the quadruple aims of healthcare served as classification frameworks for deductive analysis. Theoretical analysis identified the interrelationships among the capability dimensions, and relationships between the capability dimensions and healthcare outcomes. Results Seven highly interrelated digital health capability dimensions were identified from the interviews: governance and management; information technology capability; people, skills, and behaviours; interoperability; strategy; data analytics; consumer centred care. Outcomes were directly influenced by all dimensions except strategy. The interrelationship analysis demonstrated the influence of strategy on all digital health capability dimensions apart from data analytics, where the outcomes of data analytics shaped ongoing strategic efforts. Conclusions The study indicates the need to coordinate improvement efforts targeted across the dimensions of digital capability, optimise data analytics in rural settings to further support strategic decision making, and consider how consumer-centred care could influence digital health capability in rural healthcare services. Digital transformation in rural healthcare settings is likely to contribute to the achievement of the quadruple aims of healthcare if transformation efforts are supported by a clear, resourced digital strategy that is fit-for-purpose to the nuances of rural healthcare delivery.

Abstract Background Neuroinflammation is involved in the pathogenesis of almost every central nervous system disorder. As the brain’s innate immune cells, microglia fine tune their activity to a dynamic brain environment. Previous studies have shown that repeated bouts of peripheral inflammation can trigger long-term changes in microglial gene expression and function, a form of innate immune memory. Methods and results In this study, we used multiple low-dose lipopolysaccharide (LPS) injections in adult mice to study the acute cytokine, transcriptomic, and microglia morphological changes that contribute to the formation of immune memory in the frontal cortex, hippocampus, and striatum, as well as the long-term effects of these changes on behavior. Training and tolerance of gene expression was shared across regions, and we identified 3 unique clusters of DEGs (2xLPS-sensitive, 4xLPS-sensitive, LPS-decreased) enriched for different biological functions. 2xLPS-sensitive DEG promoters were enriched for binding sites for IRF and NFkB family transcription factors, two key regulators of innate immune memory. We quantified shifts in microglia morphological populations and found that while the proportion of ramified and rod-like microglia mostly remained consistent within brain regions and sexes with LPS treatment, there was a shift from ameboid towards hypertrophic morphological states across immune memory states and a dynamic emergence and resolution of events of microglia aligning end-to-end with repeated LPS. Conclusions Together, findings support the dynamic regulation of microglia during the formation of immune memories in the brain and support future work to exploit this model in brain disease contexts.

Abstract Background The Aboriginal health workforce has unique insights given their healthcare experience and interactions with their communities. The aims of this project were to explore their perceptions of hepatitis B related shame and ways to improve hepatitis B care in Aboriginal and Torres Strait Islander communities of Northern Territory’s Top End, Australia. Methods We conducted a qualitative study with guidance from the Menzies School of Health Research Infectious Diseases Indigenous Reference Group. The Aboriginal health workforce was asked to participate in semi-structured interviews exploring hepatitis B related shame and ways to improve hepatitis B care. Qualitative data were evaluated using reflexive thematic analysis. Results There were fifteen semi-structured interviews with participants representing eight different communities. The experience of shame was reported by the Aboriginal health workforce to be common for individuals diagnosed with hepatitis B and comprised feelings of fear related to transmitting the virus, to being isolated, and to being at fault. Shame was mediated by poor health literacy, communication, the lack of culturally safe spaces and was perpetuated by intersecting stereotypes. Improvements in care can be achieved by utilising the Aboriginal health workforce more effectively, improving communication and the availability of culturally safe spaces, emphasising community connection, and reframing hepatitis B as a chronic condition. Conclusions Hepatitis B related shame was an important issue and impactful in Aboriginal and Torres Strait Islander communities in the Top End of the Northern Territory. There were many facets to shame in these communities and it was mediated by several factors. The Aboriginal health workforce has emphasised several pathways to improve care and diminish the impact of shame, such as improving communication and the availability of culturally safe spaces.

Abstract Background Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. Methods We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. Results We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21–27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. Conclusions Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Abstract Background Digital health offers unprecedented opportunities to enhance health service delivery across vast geographic regions. However, these benefits can only be realized with effective capabilities and clinical leadership of the rural healthcare workforce. Little is known about how rural healthcare workers acquire skills in digital health, how digital health education or training programs are evaluated and the barriers and enablers for high quality digital health education and training. Objective To conduct a scoping review to identify and synthesize existing evidence on digital health education and training of the rural healthcare workforce. Inclusion criteria Sources that reported digital health and education or training in the healthcare workforce in any healthcare setting outside metropolitan areas. Methods We searched for published and unpublished studies written in English in the last decade to August 2023. The databases searched were PubMed, Embase, Scopus, CINAHL and Education Resources Information Centre. We also searched the grey literature (Google, Google Scholar), conducted citation searching and stakeholder engagement. The JBI Scoping Review methodology and PRISMA guidelines for scoping reviews were used. Results Five articles met the eligibility criteria. Two case studies, one feasibility study, one micro-credential and one fellowship were described. The mode of delivery was commonly modular online learning. Only one article described an evaluation, and findings showed the train-the-trainer model was technically and pedagogically feasible and well received. A limited number of barriers and enablers for high quality education or training of the rural healthcare workforce were reported across macro (legal, regulatory, economic), meso (local health service and community) and micro (day-to-day practice) levels. Conclusions Upskilling rural healthcare workers in digital health appears rare. Current best practice points to flexible, blended training programs that are suitably embedded with interdisciplinary and collaborative rural healthcare improvement initiatives. Future work to advance the field could define rural health informatician career pathways, address concurrent rural workforce issues, and conduct training implementation evaluations. Review registration number Open Science Framework: https://doi.org/10.17605/OSF.IO/N2RMX .

Abstract 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.

Abstract Background Prokaryotic microbes have impacted marine biogeochemical cycles for billions of years. Viruses also impact these cycles, through lysis, horizontal gene transfer, and encoding and expressing genes that contribute to metabolic reprogramming of prokaryotic cells. While this impact is difficult to quantify in nature, we hypothesized that it can be examined by surveying virus-encoded auxiliary metabolic genes (AMGs) and assessing their ecological context. Results We systematically developed a global ocean AMG catalog by integrating previously described and newly identified AMGs and then placed this catalog into ecological and metabolic contexts relevant to ocean biogeochemistry. From 7.6 terabases of Tara Oceans paired prokaryote- and virus-enriched metagenomic sequence data, we increased known ocean virus populations to 579,904 (up 16%). From these virus populations, we then conservatively identified 86,913 AMGs that grouped into 22,779 sequence-based gene clusters, 7248 (~ 32%) of which were not previously reported. Using our catalog and modeled data from mock communities, we estimate that ~ 19% of ocean virus populations carry at least one AMG. To understand AMGs in their metabolic context, we identified 340 metabolic pathways encoded by ocean microbes and showed that AMGs map to 128 of them. Furthermore, we identified metabolic “hot spots” targeted by virus AMGs, including nine pathways where most steps (≥ 0.75) were AMG-targeted (involved in carbohydrate, amino acid, fatty acid, and nucleotide metabolism), as well as other pathways where virus-encoded AMGs outnumbered cellular homologs (involved in lipid A phosphates, phosphatidylethanolamine, creatine biosynthesis, phosphoribosylamine-glycine ligase, and carbamoyl-phosphate synthase pathways). Conclusions Together, this systematically curated, global ocean AMG catalog and analyses provide a valuable resource and foundational observations to understand the role of viruses in modulating global ocean metabolisms and their biogeochemical implications. Video Abstract

Abstract Background Sexually transmitted infections (STIs) are a serious public health issue in many countries. Online postal self-sampling (OPSS) is increasingly used to test for STIs, a trend accelerated by the COVID-19 pandemic. There remains limited understanding of how service users experience OPSS and what leads them to access it over clinic-based services, or vice versa. This research seeks to address these gaps, by undertaking a large qualitative study which sits within the ASSIST study, a mixed-methods, realist evaluation of OPSS. Methods Participants were recruited via clinic-based and online sexual health services in three case study areas in England. Purposive sampling was used to over-represent populations disproportionately affected by poor sexual health: young people; people of colour; men who have sex with men; and trans and non-binary people. Semi-structured interviews were analysed using Levesque’s conceptual framework of access to healthcare. Results We interviewed 100 service users. Participants typically became aware of OPSS from sexual health services, the internet or word of mouth. Acceptability of OPSS was facilitated by the perceived privacy it offered over clinic-based services, which some participants found embarrassing to access. OPSS also enabled participants to overcome barriers to reaching clinic-based services, such as a lack of appointment availability, although difficulty obtaining OPSS kits in some areas undermined this. As all services in our case study areas were free to use, affordability did not significantly shape access, although OPSS enabled some participants to avoid costs associated with travelling to clinic-based services. Participants were usually able to engage with OPSS, finding it easy to use and reliable, although blood self-sampling was challenging for most. Participants valued the support offered by clinic-based services beyond STI testing, including the opportunity to access contraception or ask staff questions, and felt this was more appropriate when they had specific concerns about their sexual health, such as STI symptoms. Conclusions Our findings constitute one of the largest qualitative studies to have explored OPSS and offer valuable insights to providers. OPSS shapes access to STI testing in a number of ways, including facilitating access in many circumstances, but users also want to retain access to clinic-based services, particularly for when they believe they need support beyond STI testing.

Abstract Background Despite being high-achieving students, many medical students face academic challenges, particularly during their first year of study. Research indicates that self-regulated learning, involving metacognitive processes and adaptive strategies, can positively influence academic achievement. This study aimed to assess the early learning and study skills of first-year medical students in an international medical school with the goal of developing a learner-centered educational intervention to promote self-regulated learning. Methods We conducted a retrospective analysis of the Learning and Study Skills Inventory (LASSI) questionnaire that was administered annually each August to first-year medical students from 2019 to 2022. The distribution of students across different percentile ranges for each selected variable was determined for each year and all years collectively. Students were counted within distinct percentile brackets (50th and below, between 51st and 75th, and above 75th ) for each variable. Results A total of 147 students completed the LASSI questionnaire over the 4-year time period. Using academic resources was the greatest concern, with 67% of students in the 50th or below percentile, followed by selecting the main idea (56%), motivation (51%), and concentration (50%). Attitude scored highest across all cohorts, scoring between 21.55 ± 0.73 and 26.49 ± 0.34. In comparing mean scores of LASSI variables across all cohorts, attitude, motivation, test-taking strategies, time management, and the use of academic resources differed significantly (p

Abstract Background Self-reported health is a widely used health indicator in surveys and questionnaires. The measure gained attention when research identified its association with mortality in the 1970s and 1980s. The measure is also associated with morbidity and other health outcomes such as the utilisation of health services. Self-reported health is a particularly useful measure for young people because this age group is generally clinically healthy. However, it is known that many chronic conditions have long latency periods that are initiated early in life. Because of its predictive nature, self-reported health can be used to estimate young people’s current and future health. Despite its widespread use, however, self-reported health remains a poorly understood concept. This paper presents the protocol for a systematic review that will identify and synthesise qualitative studies that investigate the factors that are considered by young people when they assess their health, and when they talk about health overall. Methods The population of the review is young people aged 10–24 years, with or without health conditions. We will search the databases of MEDLINE (Ovid®), PsycINFO (APA PsycNet), ProQuest Sociology Collection, and Web of Science Core Collection™. We will also utilise techniques of reference checking and forward citation searching, as this strategy has been shown to result in a higher number of high-quality studies in social science systematic reviews. Google Scholar and Google Search were used during preliminary searches; Google Scholar will be utilised for forward citation searching. We will include studies written in English, German, or Finnish; there will be no lower date limit. One reviewer will screen all citations. A second reviewer will independently screen a sample of 20% of the abstracts. Data will be extracted by one researcher, two other researchers will independently review all data extracted, and quality appraisal will be completed by the first reviewer. We will utilise the Quality Framework for the appraisal of included articles and thematic synthesis of qualitative studies. Discussion The results of this systematic review will improve the understanding of the factors that are considered during the self-assessments of health; this will improve the interpretation of the results of quantitative research. Also, an improved understanding of the conceptualisation of health will inform the development of health policies and interventions that support young people’s health. Systematic review registration PROSPERO CRD42022367519.

Abstract In order to slow the spread of COVID-19, on March 23, 2020, a strict lockdown was implemented in the UK. This was followed by alternating periods of less restrictive lockdowns until most public health restrictions were lifted in the summer of 2021. While these measures were necessary, they significantly affected people’s daily activities, lifestyles, and mental well-being. This paper presents a longitudinal research study that focused on females aged 55 + in the UK, aiming to understand how COVID-19 and the subsequent 15-month period of lockdowns affected their lifestyles and emotions. The study collected data through online surveys, where respondents reported the frequency and mode of access to activities, and their positive and negative emotional experiences during distinct study phases that encompassed both lockdown and less strict periods. In contrast to previous studies highlighting vulnerabilities for females and the elderly during lockdowns, this research found that the studied group maintained an overall positive outlook throughout the study period and successfully adapted to the lockdowns by increasing their engagement in certain activities, in particular, activities like ‘getting active’. In addition, our findings indicate rapid adaptive behaviour change towards many online activities, such as cultural activities. However, the study also revealed negative emotions and a decrease in some activities during the second lockdown in 2020 and the subsequent lockdowns in 2021, underscoring the challenges inherent in prolonged periods of confinement. In addition, the study found negative affect associated with some activities, including working and studying from home. The findings provide valuable insights into how females aged over 55 coped with stressful circumstances, which can inform the development of resilient and mental health-conscious public health policies and responses in preparation for future pandemics or other hazards.

Abstract Background Epigenetic scores (EpiScores), reflecting DNA methylation (DNAm)-based surrogates for complex traits, have been developed for multiple circulating proteins. EpiScores for pro-inflammatory proteins, such as C-reactive protein (DNAm CRP), are associated with brain health and cognition in adults and with inflammatory comorbidities of preterm birth in neonates. Social disadvantage can become embedded in child development through inflammation, and deprivation is overrepresented in preterm infants. We tested the hypotheses that preterm birth and socioeconomic status (SES) are associated with alterations in a set of EpiScores enriched for inflammation-associated proteins. Results In total, 104 protein EpiScores were derived from saliva samples of 332 neonates born at gestational age (GA) 22.14 to 42.14 weeks. Saliva sampling was between 36.57 and 47.14 weeks. Forty-three (41%) EpiScores were associated with low GA at birth (standardised estimates |0.14 to 0.88|, Bonferroni-adjusted p-value

Abstract The COTAT (Collaborative Opioid Taper After Trauma) Study was a randomized trial of an opioid taper support program using a physician assistant (PA) to provide pain and opioid treatment guidance to primary care providers assuming care for adult patients with moderate to severe trauma discharged from a Level I trauma center on opioid therapy. Patients were recruited, assessed, and randomized individually by a surgery research recruitment team one to two days prior to discharge to home. Participants randomized to the opioid taper support program were contacted by phone within a few days of discharge by the PA interventionist to confirm enrollment and their primary care provider (PCP). The intervention consisted of PA support as needed to the PCP concerning pain and opioid care at weeks 1, 2, 4, 8, 12, 16, and 20 after discharge or until the PCP office indicated they no longer needed support or the patient had tapered off opioids. The PA was supervised by a pain physician-psychiatrist, a family physician, and a trauma surgeon. Patients randomized to usual care received standard hospital discharge instructions and written information on managing opioid medications after discharge. Trial results were analyzed using repeated measures analysis. 37 participants were randomized to the intervention and 36 were randomized to usual care. The primary outcomes of the trial were pain, enjoyment, general activity (PEG score) and mean daily opioid dose at 3 and 6 months after hospital discharge. Treatment was unblinded but assessment was blinded. No significant differences in PEG or opioid outcomes were noted at either time point. Physical function at 3 and 6 months and pain interference at 6 months were significantly better in the usual care group. No significant harms of the intervention were noted. COVID-19 (corona virus 2019) limited recruitment of high-risk opioid tolerant subjects, and limited contact between the PA interventionist and the participants and the PCPs. Our opioid taper support program failed to improve opioid and pain outcomes, since both control and intervention groups tapered opioids and improved PEG scores after discharge. Future trials of post-trauma opioid taper support with populations at higher risk of persistent opioid use are needed. This trial is registered at clinicaltrials.gov under NCT04275258 19/02/2020. This trial was funded by a grant from the Centers for Disease Control and Prevention to the University of Washington Harborview Injury Prevention & Research Center (R49 CE003087, PI: Monica S. Vavilala, MD). The funder had no role in the analysis or interpretation of the data.

Abstract Background Drug overdose deaths in the United States increased to historic levels in recent years, with provisional estimates indicating more than 111,000 deaths in the 12 months ending July 2023. In 2019, the Centers for Disease Control and Prevention’s Division of Overdose Prevention in collaboration with the National Association of City and County Health Officials, funded local health departments (LHDs) to work on overdose prevention activities. This paper aims to: 1) describe the overdose prevention activities that LHDs implemented during the four eighteen-month funding cycles; 2) identify programmatic successes and areas of opportunity for LHDs to consider when implementing future overdose prevention activities; and to 3) inform policy considerations and future overdose prevention programming at the local level. Methods We used programmatic data to identify overdose prevention activities implemented by 45 LHDs. Activities were double-coded according to the social-ecological model and the U.S. Department of Health and Human Services Overdose Prevention Strategies and Guiding Principles. We analyzed final codes to identify distribution and overlap of the Strategies and Guiding Principles across the social ecological model co-occurrences. Results Approximately 55.9% (n=123) of the 220 overdose prevention activities that were coded took place at the community level, 32.3% (n=71) at the individual level, 8.6% (n=19) at the relationship level, and 3.2% (n=7) at the policy level. Most of the activities were coded as coordination, collaboration, and integration (n=52, 23.6%), harm reduction (n=51, 23.1%), data and evidence (n=47, 21.4%) or reducing stigma (n=24, 10.9%). Few activities were related to primary prevention (n=14, 6.4%), equity (n=14, 6.4%), recovery support (n=11, 5.0%), and evidence-based treatment (n=7, 3.2%). Conclusions Localities have primarily implemented activities focused on the community and individual levels, with most of these centered around coordination, collaboration, and integration; harm reduction; or data and evidence. This study identified gaps in overdose prevention for LHDs related to treatment and health equity and that more interventions should be implemented at the relationship and policy levels. Continuing these efforts is important as LHDs explore opportunities to enhance and expand their work in various strategy areas across the social ecology. Findings from this study may be used to inform localities as they design and implement future overdose prevention activities.

Abstract Purpose Accurate perception of tactile stimuli is essential for performing and learning activities of daily living. Through this scoping review, we sought to summarize existing examination approaches for identifying tactile deficits at the upper extremity in individuals with stroke. The goal was to identify current limitations and future research needs for designing more comprehensive examination tools. Methods A scoping review was conducted in accordance with the Joanna Briggs Institute methodological framework and the PRISMA for Scoping Reviews (PRISMA-ScR) guidelines. A database search for tactile examination approaches at the upper extremity of individuals with stroke was conducted using Medline (Ovid), The Cochrane Library (Wiley), CINAHL Plus with Full Text (Ebsco), Scopus (Elsevier), PsycInfo (Ebsco), and Proquest Dissertations and Theses Global. Original research and review articles that involved adults (18 years or older) with stroke, and performed tactile examinations at the upper extremity were eligible for inclusion. Data items extracted from the selected articles included: if the examination was behavioral in nature and involved neuroimaging, the extent to which the arm participated during the examination, the number of possible outcomes of the examination, the type(s) of tactile stimulation equipment used, the location(s) along the arm examined, the peripheral nerves targeted for examination, and if any comparison was made with the non-paretic arm or with the arms of individuals who are neurotypical. Results Twenty-two articles met the inclusion criteria and were accepted in this review. Most examination approaches were behavioral in nature and involved self-reporting of whether a tactile stimulus was felt while the arm remained passive (i.e., no volitional muscle activity). Typically, the number of possible outcomes with these behavioral approaches were limited (2-3), whereas the neuroimaging approaches had many more possible outcomes ( $$>15$$ > 15 ). Tactile examinations were conducted mostly at the distal locations along the arm (finger or hand) without targeting any specific peripheral nerve. Although a majority of articles compared paretic and non-paretic arms, most did not compare outcomes to a control group of individuals who are neurotypical. Discussion Our findings noted that most upper extremity tactile examinations are behavioral approaches, which are subjective in nature, lack adequate resolution, and are insufficient to identify the underlying neural mechanisms of tactile deficits. Also, most examinations are administered at distal locations of the upper extremity when the examinee’s arm is relaxed (passive). Further research is needed to develop better tactile examination tools that combine behavioral responses and neurophysiological outcomes, and allow volitional tactile exploration. Approaches that include testing of multiple body locations/nerves along the upper extremity, provide higher resolution of outcomes, and consider normative comparisons with individuals who are neurotypical may provide a more comprehensive understanding of the tactile deficits occurring following a stroke.

Abstract Background Hepatitis B is endemic amongst the Australian Aboriginal population in the Northern Territory. A participatory action research project identified the lack of culturally appropriate education tools and led to the development of the “Hep B Story” app in the Aboriginal language Yolŋu Matha. This paper describes a formal evaluation of the app’s first version, which informed improvements and translation into a further ten Aboriginal languages. Methods The evaluation employed Participatory Action Research (PAR) principles to work within Indigenous research methodologies and prioritise Indigenous knowledge to improve the app iteratively. Semi-structured interviews and focus groups were conducted across the Northern Territory with 11 different language groups. Local Community Based Researchers and Aboriginal Research team members coordinated sessions. The recorded, translated conversations were transcribed verbatim and thematically analysed using an inductive and deductive approach. Results Between November 2018 and September 2020, 94 individuals from 11 language groups participated in 25 semi-structured interviews and 10 focus groups. All participants identified as Aboriginal. Most participants felt the app would be culturally appropriate for Aboriginal communities in the Northern Territory and improve knowledge surrounding hepatitis B. The information gathered from these interviews allowed for identifying five main themes: support for app, relationships, concept versus language, shame, and perceptions of images, along with errors that required modification. Conclusions A “real-life” evaluation of the app was comprehensively completed using a PAR approach blended with Indigenous research methods. This evaluation allowed us to develop an updated and enhanced version of the app before creating the additional ten language versions. An iterative approach alongside strong community engagement was pivotal in ensuring the app’s cultural safety and appropriateness. We recommend avoiding the use of knowledge-based evaluations in an Aboriginal setting to ensure relevant and culturally appropriate feedback is obtained.

Abstract Background As the opioid public health crisis evolves to include fentanyl and other potent synthetic opioids, more patients are admitted to the hospital with serious complications of drug use and frequently require higher levels of care, including intensive care unit (ICU) admission, for acute and chronic conditions related to opioid use disorder (OUD). This patient population poses a unique challenge when managing sedation and ensuring adequate ventilation while intubated given their high opioid requirements. Starting a patient on medications such as buprenorphine may be difficult for inpatient providers unfamiliar with its use, which may lead to undertreatment of patients with OUD, prolonged mechanical ventilation and length of stay. Methods We developed a 7-day buprenorphine low dose overlap initiation (LDOI) schedule for patients with OUD admitted to the ICU (Table 1). Buprenorphine tablets were split by pharmacists and placed into pre-made blister packs as a kit to be loaded into the automated medication dispensing machine for nursing to administer daily. An internal quality review validated the appropriate dosing of split-dose tablets. To simplify order entry and increase prescriber comfort with this new protocol, we generated an order set within our electronic health record software with prebuilt buprenorphine titration orders. This protocol was implemented alongside patient and healthcare team education and counseling on the LDOI process, with follow-up offered to all patients upon discharge. Results Here we report a series of 6 ICU patients started on buprenorphine using the LDOI schedule with split buprenorphine tablets. None of the 6 patients experienced precipitated withdrawal upon buprenorphine initiation using the LDOI schedule, and 5/6 patients were successfully extubated during the buprenorphine initiation. Four of six patients had a decrease in daily morphine milligram equivalents, with 3 patients transitioning to buprenorphine alone. Conclusion Initiating buprenorphine via LDOI was found to be successful in the development of a protocol for critically ill patients with OUD. We examined LDOI of buprenorphine in intubated ICU patients and found no events of acute precipitated withdrawal. This protocol can be used as a guide for other institutions seeking to start critically ill patients on medication treatment for OUD during ICU admission.

Abstract Background People living with, or caring for someone with, rare forms of dementia can encounter issues while obtaining a diagnosis and trying to access appropriate support. This can affect their wellbeing, quality of life, social relationships and employment status. This study makes use of an arts-based narrative approach to explore individual accounts of these experiences whilst also exploring how, in telling their stories, those affected by rare forms of dementia might invoke, and situate their stories in relation to, broader cultural narratives around dementia and illness. Methods Semi-structured interviews were conducted via video-conferencing software with participants (N = 27), living with, or caring for someone with, a rare forms of dementia. Participants used line drawings to depict their journey from initial symptoms to the present day, followed by prompts to verbally narrate their experiences. All interview transcripts and line drawings were subjected to narrative analysis. Four sets of transcripts and drawings were then subjected to more in-depth analysis. Results Analysis shed light on the struggles encountered by both care-partners and people with a diagnosis, while navigating a health and social care system that does not always understand their needs. This often led to individuals feeling isolated and unsupported. Accounts also depicted challenges to identity brought on by the process. The moment of diagnosis was also drawn in a complicated light. Individuals found comfort in gaining understanding, but felt fear at recognising upcoming challenges. Participants situated their own accounts against mainstream cultural narratives around what good support for cognitive impairment and dementia might look like, whilst also demonstrating the influential role they took on in pursuing the right care. Conclusions The use of line drawing, alongside narrative interviews, allowed participants to tell complicated, sometimes anachronistic, stories about difficult experiences, whilst also reflecting on, and attaching meaning to, them. These stories highlighted pressing gaps in healthcare services and shone a light on the various pieces of collective action individuals were engaged in in order to improve them. Finally, in modelling some elements of the participants’ service provision which were working, the narratives pointed to future directions services might move in.

Abstract Background For many countries, especially those outside the USA without incentive payments, implementing and maintaining electronic medical records (EMR) is expensive and can be controversial given the large amounts of investment. Evaluating the value of EMR implementation is necessary to understand whether or not, such investment, especially when it comes from the public source, is an efficient allocation of healthcare resources. Nonetheless, most countries have struggled to measure the return on EMR investment due to the lack of appropriate evaluation frameworks. Methods This paper outlines the development of an evidence-based digital health cost-benefit analysis (eHealth-CBA) framework to calculate the total economic value of the EMR implementation over time. A net positive benefit indicates such investment represents improved efficiency, and a net negative is considered a wasteful use of public resources. Results We developed a three-stage process that takes into account the complexity of the healthcare system and its stakeholders, the investment appraisal and evaluation practice, and the existing knowledge of EMR implementation. The three stages include (1) literature review, (2) stakeholder consultation, and (3) CBA framework development. The framework maps the impacts of the EMR to the quadruple aim of healthcare and clearly creates a method for value assessment. Conclusions The proposed framework is the first step toward developing a comprehensive evaluation framework for EMRs to inform health decision-makers about the economic value of digital investments rather than just the financial value.

Abstract Background Women living with HIV (WLWH) experience higher rates of intimate partner violence (IPV) compared to women without HIV, but there has been minimal research to date on the impact of the COVID-19 pandemic on the lived experiences of WLWH who are IPV survivors. Methods This is a secondary analysis of COVID-19 impact using baseline data from an ongoing, prospective, micro-longitudinal cohort study of HIV care engagement among WLWH who have experienced lifetime IPV. We measured the impact of COVID-19 along key domains (i.e., physical health, day-to-day life, sexual/relationship behavior, substance use, HIV care, mental health, financial status, and having conflict with partners). Using independent t-tests or Fisher’s exact tests, and Pearson’s chi-squared tests, we compared women with and without ongoing IPV across sociodemographic characteristics, psychiatric disorders, substance use, and COVID-19 impact domains. We then built separate multivariate linear regression models for each of the different COVID-19 impact domains; ongoing IPV exposure was the primary explanatory variable of interest. Results Enrolled participants (n = 84) comprised a group of women (mean age 53.6y; SD = 9.9) who were living with HIV for a mean 23.3 years (SD = 10), all of whom had experienced lifetime IPV. Among 49 women who were currently partnered, 79.6% (n = 39) reported ongoing IPV. There were no statistically significant differences between those experiencing ongoing IPV and those who were not (or not partnered) in terms of demographic characteristics, substance use, or mental health. In multivariate models, ongoing IPV exposure was not associated with any COVID-19 impact domain. Anxiety and depression, however, were associated with COVID-19-related physical health, HIV care, and relationship conflict. Hispanic ethnicity was significantly associated with COVID-19-related physical health. More severe cocaine and opioid use were also significantly associated with COVID-19-related impact on day-to-day life. Conclusions Among this sample of WLWH who are all lifetime IPV-survivors, nearly half had ongoing IPV exposure. The COVID-19 public health emergency period affected WLWH in varied ways, but impacts were most profound for women experiencing concurrent mental health and substance use problems. Findings have important implications for future interventions to improve women’s health and social outcomes.

Abstract Background Stillbirth rates remain a global priority and in Australia, progress has been slow. Risk factors of stillbirth are unique in Australia due to large areas of remoteness, and limited resource availability affecting the ability to identify areas of need and prevalence of factors associated with stillbirth. This retrospective cohort study describes lifestyle and sociodemographic factors associated with stillbirth in South Australia (SA), between 1998 and 2016. Methods All restigered births in SA between 1998 ad 2016 are included. The primary outcome was stillbirth (birth with no signs of life ≥ 20 weeks gestation or ≥ 400 g if gestational age was not reported). Associations between stillbirth and lifestyle and sociodemographic factors were evaluated using multivariable logistic regression and described using adjusted odds ratios (aORs). Results A total of 363,959 births (including 1767 stillbirths) were included. Inadequate antenatal care access (assessed against the Australian Pregnancy Care Guidelines) was associated with the highest odds of stillbirth (aOR 3.93, 95% confidence interval (CI) 3.41–4.52). Other factors with important associations with stillbirth were plant/machine operation (aOR, 1.99; 95% CI, 1.16–2.45), birthing person age ≥ 40 years (aOR, 1.92; 95% CI, 1.50–2.45), partner reported as a pensioner (aOR, 1.83; 95% CI, 1.12–2.99), Asian country of birth (aOR, 1.58; 95% CI, 1.19–2.10) and Aboriginal/Torres Strait Islander status (aOR, 1.50; 95% CI, 1.20–1.88). The odds of stillbirth were increased in regional/remote areas in association with inadequate antenatal care (aOR, 4.64; 95% CI, 2.98–7.23), birthing age 35–40 years (aOR, 1.92; 95% CI, 1.02–3.64), Aboriginal and/or Torres Strait Islander status (aOR, 1.90; 95% CI, 1.12–3.21), paternal occupations: tradesperson (aOR, 1.69; 95% CI, 1.17–6.16) and unemployment (aOR, 4.06; 95% CI, 1.41–11.73). Conclusion Factors identified as independently associated with stillbirth odds include factors that could be addressed through timely access to adequate antenatal care and are likely relevant throughout Australia. The identified factors should be the target of stillbirth prevention strategies/efforts. SThe stillbirth rate in Australia is a national concern. Reducing preventable stillbirths remains a global priority.

Abstract Background Action on the social determinants of health is important to strengthen primary health care and promote access among underserved populations. We report on findings from stakeholder consultations undertaken at one of the Canadian sites of the Innovative Models Promoting Access-to-Care Transformation (IMPACT) program, as part of the development of a best practice intervention to improve access to primary health care. The overarching objective of this qualitative study was to understand the processes, barriers, and facilitators to connect patients to health enabling community resources (HERs) to inform a patient navigation model situated in primary care. Methods Focus groups and interviews were conducted with primary care physicians, and community health and social service providers to understand their experiences in supporting patients in reaching HERs. Current gaps in access to primary health care and the potential of patient navigation were also explored. We applied Levesque et al., (2013) access framework to code the data and four themes emerged: (1) Approachability and Ability to Perceive, (2) Acceptability and Ability to Seek, (3) Availability and Accommodation, and Ability to Reach, and (4) Appropriateness. Results Determinants of access included patient and provider awareness of HERs, the nature of the patient-provider relationship, funding of HERs, integration of primary and community care services, and continuity of information. Participants’ perspectives about the potential scope and role of a patient navigator provided valuable insight for the development of the Access to Resources in the Community (ARC) navigation model and how it could be embedded in a primary care setting. Conclusion Additional consultation with key stakeholders in the health region is needed to gain a broader understanding of the challenges in caring for primary care patients with social barriers and how to support them in accessing community-based primary health care to inform the design of the ARC intervention.

Abstract Background Little is known about why patients with low back pain (LBP) respond differently to treatment, and more specifically, to a lumbar stabilization exercise program. As a first step toward answering this question, the present study evaluates how subgroups of patients who demonstrate large and small clinical improvements differ in terms of physical and psychological changes during treatment. Methods Participants (n = 110) performed the exercise program (clinical sessions and home exercises) over eight weeks, with 100 retained at six-month follow-up. Physical measures (lumbar segmental instability, motor control impairments, range of motion, trunk muscle endurance and physical performance tests) were collected twice (baseline, end of treatment), while psychological measures (fear-avoidance beliefs, pain catastrophizing, psychological distress, illness perceptions, outcome expectations) were collected at four time points (baseline, mid-treatment, end of treatment, follow-up). The participants were divided into three subgroups (large, moderate and small clinical improvements) based on the change of perceived disability scores. ANOVA for repeated measure compared well-contrasted subgroups (large vs. small improvement) at different times to test for SUBGROUP × TIME interactions. Results Statistically significant interactions were observed for several physical and psychological measures. In all these interactions, the large- and small-improvement subgroups were equivalent at baseline, but the large-improvement subgroup showed more improvements over time compared to the small-improvement subgroup. For psychological measures only (fear-avoidance beliefs, pain catastrophizing, illness perceptions), between-group differences reached moderate to strong effect sizes, at the end of treatment and follow-up. Conclusions The large-improvement subgroup showed more improvement than the small-improvement subgroup with regard to physical factors typically targeted by this specific exercise program as well as for psychological factors that are known to influence clinical outcomes.

Abstract 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.

Abstract Background Between 2020 and 2022, eight calves in a Nebraska herd (composite Simmental, Red Angus, Gelbvieh) displayed exercise intolerance during forced activity. In some cases, the calves collapsed and did not recover. Available sire pedigrees contained a paternal ancestor within 2–4 generations in all affected calves. Pedigrees of the calves’ dams were unavailable, however, the cows were ranch-raised and retained from prior breeding seasons, where bulls used for breeding occasionally had a common ancestor. Therefore, it was hypothesized that a de novo autosomal recessive variant was causative of exercise intolerance in these calves. Results A genome-wide association analysis utilizing SNP data from 6 affected calves and 715 herd mates, followed by whole-genome sequencing of 2 affected calves led to the identification of a variant in the gene PYGM (BTA29:g.42989581G > A). The variant, confirmed to be present in the skeletal muscle transcriptome, was predicted to produce a premature stop codon (p.Arg650*). The protein product of PYGM, myophosphorylase, breaks down glycogen in skeletal muscle. Glycogen concentrations were fluorometrically assayed as glucose residues demonstrating significantly elevated glycogen concentrations in affected calves compared to cattle carrying the variant and to wild-type controls. The absence of the PYGM protein product in skeletal muscle was confirmed by immunohistochemistry and label-free quantitative proteomics analysis; muscle degeneration was confirmed in biopsy and necropsy samples. Elevated skeletal muscle glycogen persisted after harvest, resulting in a high pH and dark-cutting beef, which is negatively perceived by consumers and results in an economic loss to the industry. Carriers of the variant did not exhibit differences in meat quality or any measures of animal well-being. Conclusions Myophosphorylase deficiency poses welfare concerns for affected animals and negatively impacts the final product. The association of the recessive genotype with dark-cutting beef further demonstrates the importance of genetics to not only animal health but to the quality of their product. Although cattle heterozygous for the variant may not immediately affect the beef industry, identifying carriers will enable selection and breeding strategies to prevent the production of affected calves.

Abstract Background Regular HIV and STI testing remain a cornerstone of comprehensive sexual health care. In this study, we examine the efficacy of Get Connected, a WebApp that combines test locators with personalized educational resources, in motivating young men who have sex with men (YMSM) to undergo regular HIV and STI testing. Methods Participants were randomly placed in one of two conditions. The first condition included the full version of GC (GC-PLUS), which included content tailored to users’ psychosocial characteristics (e.g., age, race/ethnicity, relationship status, HIV/STI testing history). The second condition served as our attention-control and only included the testing locator (GC-TLO) for HIV/STI testing services. Participants were recruited from three cities (Houston, Philadelphia, and Atlanta) characterized by high HIV incidence. Assessments were collected at 1, 3-, 6-, 9- and 12-month follow-ups. Results Both versions of GC were acceptable and efficacious in increasing routine HIV and STI testing over a 12-month period. 40% of the sample reported testing at least twice, with no main effects observed across the two intervention arms (OR = 1.11; 95% CI: 0.69, 1.80), p =.66). Greater intervention effects were observed among YMSM who engaged more frequently with the intervention, with regional differences observed. Conclusions Our findings underscore the need to cater to the diverse needs of YMSM through multilevel approaches. Broadly, mHealth HIV/STI testing interventions, such as Get Connected, would benefit from matching technologies to the local context to have the greatest impact. Trial Registration This study is registered on ClinicalTrials.gov (NCT03132415).

Abstract Background The study of biological age acceleration may help identify at-risk individuals and reduce the rising global burden of age-related diseases. Using DNA methylation (DNAm) clocks, we investigated biological aging in schizophrenia (SCZ), a mental illness that is associated with an increased prevalence of age-related disabilities and morbidities. In a whole blood DNAm sample of 1090 SCZ cases and 1206 controls across four European cohorts, we performed a meta-analysis of differential aging using three DNAm clocks (i.e., Hannum, Horvath, and Levine). To dissect how DNAm aging contributes to SCZ, we integrated information on duration of illness and SCZ polygenic risk, as well as stratified our analyses by chronological age and biological sex. Results We found that blood-based DNAm aging is significantly altered in SCZ independent from duration of the illness since onset. We observed sex-specific and nonlinear age effects that differed between clocks and point to possible distinct age windows of altered aging in SCZ. Most notably, intrinsic cellular age (Horvath clock) is decelerated in SCZ cases in young adulthood, while phenotypic age (Levine clock) is accelerated in later adulthood compared to controls. Accelerated phenotypic aging was most pronounced in women with SCZ carrying a high polygenic burden with an age acceleration of + 3.82 years (CI 2.02–5.61, P = 1.1E−03). Phenotypic aging and SCZ polygenic risk contributed additively to the illness and together explained up to 14.38% of the variance in disease status. Conclusions Our study contributes to the growing body of evidence of altered DNAm aging in SCZ and points to intrinsic age deceleration in younger adulthood and phenotypic age acceleration in later adulthood in SCZ. Since increased phenotypic age is associated with increased risk of all-cause mortality, our findings indicate that specific and identifiable patient groups are at increased mortality risk as measured by the Levine clock. Our study did not find that DNAm aging could be explained by the duration of illness of patients, but we did observe age- and sex-specific effects that warrant further investigation. Finally, our results show that combining genetic and epigenetic predictors can improve predictions of disease outcomes and may help with disease management in schizophrenia.

Abstract Background COVID-19 pneumonia causes hyperinflammatory response that culminates in acute respiratory syndrome (ARDS) related to increased multiorgan dysfunction and mortality risk. Antiviral-neutralizing immunoglobulins production reflect the host humoral status and illness severity, and thus, immunoglobulin (Ig) circulating levels could be evidence of COVID-19 prognosis. Methods The relationship among circulating immunoglobulins (IgA, IgG, IgM) and COVID-19 pneumonia was evaluated using clinical information and blood samples in a COVID-19 cohort composed by 320 individuals recruited during the acute phase and followed up to 4 to 8 weeks (n = 252) from the Spanish first to fourth waves. Results COVID-19 pneumonia development depended on baseline Ig concentrations. Circulating IgA levels together with clinical features at acute phase was highly associated with COVID-19 pneumonia development. IgM was positively correlated with obesity (ρb = 0.156, P = 0.020), dyslipemia (ρb = 0.140, P = 0.029), COPD (ρb = 0.133, P = 0.037), cancer (ρb = 0.173, P = 0.007) and hypertension (ρb = 0.148, P = 0.020). Ig concentrations at recovery phase were related to COVID-19 treatments. Conclusions Our results provide valuable information on the dynamics of immunoglobulins upon SARS-CoV-2 infection or other similar viruses.

Abstract Background Patients with schizophrenia (SZ) or bipolar disorder (BD) may have increased risk of complications from prescribed opioids, including opioid-induced respiratory depression. We compared prescription opioid pain medication dispensing for patients with SZ or BD versus controls over 5 years to assess dispensing trends. Methods This retrospective, observational study analysed US claims data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases for individuals aged 18–64 years with prevalent SZ or BD for years 2015–2019 compared with age- and sex-matched controls. Baseline characteristics, comorbidities, and medication use were assessed. Proportions of individuals dispensed prescription opioids chronically (ie, ≥70 days over a 90-day period or ≥ 6 prescriptions annually) or nonchronically (≥1 prescription, chronic definition not met) were assessed. Results In 2019, the Commercial and Medicaid databases contained records for 4773 and 30,179 patients with SZ and 52,780 and 63,455 patients with BD, respectively. Patients with SZ or BD had a higher prevalence of comorbidities, including pain, versus controls in each analysis year. From 2015 to 2019, among commercially insured patients with SZ, chronic opioid-dispensing proportions decreased from 6.1% (controls: 2.7%) to 2.3% (controls: 1.2%) and, for patients with BD, from 11.4% (controls: 2.7%) to 6.4% (controls: 1.6%). Chronic opioid dispensing declined in Medicaid-covered patients with SZ from 15.0% (controls: 14.7%) to 6.7% (controls: 6.0%) and, for patients with BD, from 27.4% (controls: 12.0%) to 12.4% (controls: 4.7%). Among commercially insured patients with SZ, nonchronic opioid dispensing decreased from 15.5% (controls: 16.4%) to 10.7% (controls: 11.0%) and, for patients with BD, from 26.1% (controls: 17.5%) to 20.0% (controls: 12.2%). In Medicaid-covered patients with SZ, nonchronic opioid dispensing declined from 22.5% (controls: 24.4%) to 15.1% (controls: 12.7%) and, for patients with BD, from 32.3% (controls: 25.9%) to 24.6% (controls: 13.6%). Conclusions The proportions of individuals dispensed chronic or nonchronic opioid medications each year were similar between commercially and Medicaid-insured patients with SZ versus controls and were higher for patients with BD versus controls. From 2015 to 2019, the proportions of individuals who were dispensed prescription opioids chronically or nonchronically decreased for patients with SZ or BD and controls.

Abstract Background Globally, emergency departments (EDs) are overcrowded and unable to meet an ever-increasing demand for care. The aim of this study is to comprehensively review and synthesise literature on potential solutions and challenges throughout the entire health system, focusing on ED patient flow. Methods An umbrella review was conducted to comprehensively summarise and synthesise the available evidence from multiple research syntheses. A comprehensive search strategy was employed in four databases alongside government or organisational websites in March 2023. Gray literature and reports were also searched. Quality was assessed using the JBI critical appraisal checklist for systematic reviews and research syntheses. We summarised and classified findings using qualitative synthesis, the Population-Capacity-Process (PCP) model, and the input/throughput/output (I/T/O) model of ED patient flow and synthesised intervention outcomes based on the Quadruple Aim framework. Results The search strategy yielded 1263 articles, of which 39 were included in the umbrella review. Patient flow interventions were categorised into human factors, management-organisation interventions, and infrastructure and mapped to the relevant component of the patient journey from pre-ED to post-ED interventions. Most interventions had mixed or quadruple nonsignificant outcomes. The majority of interventions for enhancing ED patient flow were primarily related to the 'within-ED' phase of the patient journey. Fewer interventions were identified for the 'post-ED' phase (acute inpatient transfer, subacute inpatient transfer, hospital at home, discharge home, or residential care) and the 'pre-ED' phase. The intervention outcomes were aligned with the aim (QAIM), which aims to improve patient care experience, enhance population health, optimise efficiency, and enhance staff satisfaction. Conclusions This study found that there was a wide range of interventions used to address patient flow, but the effectiveness of these interventions varied, and most interventions were focused on the ED. Interventions for the remainder of the patient journey were largely neglected. The metrics reported were mainly focused on efficiency measures rather than addressing all quadrants of the quadruple aim. Further research is needed to investigate and enhance the effectiveness of interventions outside the ED in improving ED patient flow. It is essential to develop interventions that relate to all three phases of patient flow: pre-ED, within-ED, and post-ED.

Abstract Background Impaired brain bioenergetics is a pathological hallmark of Alzheimer’s disease (AD) and is a compelling target for AD treatment. Patients with AD exhibit dysfunction in the brain creatine (Cr) system, which is integral in maintaining bioenergetic flux. Recent studies in AD mouse models suggest Cr supplementation improves brain mitochondrial function and may be protective of AD peptide pathology and cognition. Aims The Creatine to Augment Bioenergetics in Alzheimer’s disease (CABA) study is designed to primarily assess the feasibility of supplementation with 20 g/day of creatine monohydrate (CrM) in patients with cognitive impairment due to AD. Secondary aims are designed to generate preliminary data investigating changes in brain Cr levels, cognition, peripheral and brain mitochondrial function, and muscle strength and size. Methods CABA is an 8-week, single-arm pilot study that will recruit 20 patients with cognitive impairment due to AD. Participants attend five in-person study visits: two visits at baseline to conduct screening and baseline assessments, a 4-week visit, and two 8-week visits. Outcomes assessment includes recruitment, retention, and compliance, cognitive testing, magnetic resonance spectroscopy of brain metabolites, platelet and lymphocyte mitochondrial function, and muscle strength and morphology at baseline and 8 weeks. Discussion CABA is the first study to investigate CrM as a potential treatment in patients with AD. The pilot data generated by this study are pertinent to inform the design of future large-scale efficacy trials. Trial registration ClinicalTrials.gov, NCT05383833 , registered on 20 May 2022.

Abstract Background Simulation-based education (SBE) affords learners opportunities to develop communication skills, including those related to pediatrics. Feedback is an integral part of SBE, and while much research into feedback from multiple sources exists, the findings are mixed. The aim of this comparative study was to replicate some of this work in a novel area, pediatric medical education, to better understand how multisource feedback (self, educator, and simulated parent) may inform learning and curriculum design. Methods During their pediatric rotation, medical students participated in a consultation with a simulated parent, engaged in video-assisted self-reflection, and received feedback from both an educator and the simulated parent through an e-learning platform. The Pediatric Consultation Skills Assessment Tool (PCAT) was used for self-assessment and educator feedback, and the Consultation and Relational Empathy (CARE) measure was used for simulated parent feedback. Results Our results showed that high-performing students underrated their performance, and low-performing students overrated their performance. Feedback from multiple sources helps to identify both areas of weakness in student performance and areas of weakness in student self-appraisal. Overall, general areas of weakness identified for the learners related to making contingency plans and providing easy-to-understand explanations for simulated parents. Some simulated parent feedback did not align with educator and student ratings, highlighting the value of including the simulated parent perspective. Our findings question whether a third party can reliably judge the simulated parent’s level of understanding. Conclusion Multisource feedback allows students to develop layered insights into their performance and supports self-appraisal. Aggregating feedback through an e-learning platform allows educators to gain greater insights into the strengths and weakness of students and design a more tailored teaching plan to support student needs.

Abstract Background We identified that Stanford Health Care had a significant number of patients who after discharge are found by the utilization review committee not to meet Center for Mediare and Medicaid Services (CMS) 2-midnight benchmark for inpatient status. Some of the charges incurred during the care of these patients are written-off and known as Medicare 1-day write-offs. This study which aims to evaluate the use of a Best Practice Alert (BPA) feature on the electronic medical record, EPIC, to ensure appropriate designation of a patient’s hospitalization status as either inpatient or outpatient in accordance with Center for Medicare and Medicaid services (CMS) 2 midnight length of stay benchmark thereby reducing the number of associated write-offs. Method We incorporated a best practice alert (BPA) into the Epic Electronic Medical Record (EMR) that would prompt the discharging provider and the case manager to review the patients’ inpatient designation prior to discharge and change the patient’s designation to observation when deemed appropriate. Patients who met the inclusion criteria (Patients must have Medicare fee-for-service insurance, inpatient length of stay (LOS) less than 2 midnights, inpatient designation as hospitalization status at time of discharge, was hospitalized to an acute level of care and belonged to one of 37 listed hospital services at the time of signing of the discharge order) were randomized to have the BPA either silent or active over a three-month period from July 18, 2019, to October 18, 2019. Result A total of 88 patients were included in this study: 40 in the control arm and 48 in the intervention arm. In the intervention arm, 8 (8/48, 16.7%) had an inpatient status designation despite potentially meeting Medicare guidelines for an observation stay, comparing to 23 patients (23/40, 57.5%) patients in the control group (p = 0.001). The estimated number of write-offs in the control arm was 17 (73.9%, out of 23 inpatient patients) while in the intervention arm was 1 (12.5%, out of 8 inpatient patient) after accounting for patients who may have met inpatient criteria for other reasons based on case manager note review. Conclusion This is the first time to our knowledge that a BPA has been used in this manner to reduce the number of Medicare 1-day write-offs.

Abstract Background Understanding professionalism is an essential component of becoming a doctor in order to ensure the trust of patients and wider society. Integrally linked to the concept of professionalism is the importance of identifying and raising concerns to ensure high quality, safe patient care. It is recognised that medical students are uniquely placed to identify and report concerns given their frequent rotations through multiple clinical placements and their peer relationships and, in so doing, develop and enact their own medical professionalism. Although there is existing literature exploring medical students’ willingness to raise concerns about observed professionalism lapses, this has largely been in the context of clinical interactions. Medical students will however undoubtedly encounter concerning behaviours or attitudes in their fellow students, an area that has not specifically been reported upon. This study therefore set out to explore medical students’ willingness to report professionalism concerns they encounter both within and away from the clinical setting, particularly focusing on peer-related concerns. Methods 10 medical students, in later clinical years of a large UK medical school, volunteered to take part in in-depth semi-structured interviews. Interviews were recorded, transcribed and then analysed thematically to generate themes and subthemes to represent central organising concepts. Results Three broad themes were generated from the data. Hidden curricular effects including role models, hierarchical structures and the operational systems in place to raise concerns subconsciously influenced students’ decisions to raise concerns. Secondly, students offered a range of justifications to defend not taking action, including considering their own vulnerabilities and values alongside demonstrating empathy for perceived mitigating circumstances. The third theme highlighted the complex interplay of influencing factors that students considered when encountering professionalism issues in their peers including wider peer cohort effects and a desire to maintain individual peer-relationships. Conclusions Medical students will inevitably encounter situations where the professionalism of others is brought into question. However, despite clear curricular expectations to report such concerns, these findings demonstrate that students undergo a complex decision-making process in determining the threshold for reporting a concern through navigating a range of identified influencing factors. This study highlights the important role medical schools play in helping reduce the inner conflict experienced by medical students when raising concerns and in ensuring they provide supportive processes to empower their students to raise concerns as part their own developing professionalism.

Abstract Background Sustaining evidence-based practices (EBPs) is crucial to ensuring care quality and addressing health disparities. Approaches to identifying factors related to sustainability are critically needed. One such approach is Matrixed Multiple Case Study (MMCS), which identifies factors and their combinations that influence implementation. We applied MMCS to identify factors related to the sustainability of the evidence-based Collaborative Chronic Care Model (CCM) at nine Department of Veterans Affairs (VA) outpatient mental health clinics, 3–4 years after implementation support had concluded. Methods We conducted a directed content analysis of 30 provider interviews, using 6 CCM elements and 4 Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) domains as codes. Based on CCM code summaries, we designated each site as high/medium/low sustainability. We used i-PARIHS code summaries to identify relevant factors for each site, the extent of their presence, and the type of influence they had on sustainability (enabling/neutral/hindering/unclear). We organized these data into a sortable matrix and assessed sustainability-related cross-site trends. Results CCM sustainability status was distributed among the sites, with three sites each being high, medium, and low. Twenty-five factors were identified from the i-PARIHS code summaries, of which 3 exhibited strong trends by sustainability status (relevant i-PARIHS domain in square brackets): “Collaborativeness/Teamwork [Recipients],” “Staff/Leadership turnover [Recipients],” and “Having a consistent/strong internal facilitator [Facilitation]” during and after active implementation. At most high-sustainability sites only, (i) “Having a knowledgeable/helpful external facilitator [Facilitation]” was variably present and enabled sustainability when present, while (ii) “Clarity about what CCM comprises [Innovation],” “Interdisciplinary coordination [Recipients],” and “Adequate clinic space for CCM team members [Context]” were somewhat or less present with mixed influences on sustainability. Conclusions MMCS revealed that CCM sustainability in VA outpatient mental health clinics may be related most strongly to provider collaboration, knowledge retention during staff/leadership transitions, and availability of skilled internal facilitators. These findings have informed a subsequent CCM implementation trial that prospectively examines whether enhancing the above-mentioned factors within implementation facilitation improves sustainability. MMCS is a systematic approach to multi-site examination that can be used to investigate sustainability-related factors applicable to other EBPs and across multiple contexts.

Abstract Mass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed as a result of the interactions between proteins and metal-based species. However, with increasing resolution, dataset size, and species complexity, the time required to identify adducts and the error-prone nature of manual assignment have become limiting factors in MS analysis. AdductHunter is a open-source web-based analysis tool that automates the peak identification process using constraint integer optimization to find feasible combinations of protein and fragments, and dynamic time warping to calculate the dissimilarity between the theoretical isotope pattern of a species and its experimental isotope peak distribution. Empirical evaluation on a collection of 22 unique MS datasetsshows fast and accurate identification of protein-metal complex adducts in deconvoluted mass spectra.