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Abstract Background During the first nine months of the COVID-19 emergency, patients were encouraged to use virtual versus clinic visits if in-person care was not deemed necessary by clinical staff. This study examined the association of spoken language preference and ethnicity with use of video versus phone virtual visits by US Latino and Chinese adult patients who got care in the same healthcare system. Methods We analyzed electronic health record data for four groups of adults aged 26-85y who had ≥ 1 primary or specialty care outpatient clinician visits during April-December 2020: 80,869 Latino adults preferring Spanish (LEP Latino); 214,765 Latino adults preferring English (non-LEP Latino); 23,430 Chinese adults preferring a Chinese dialect (LEP Chinese); and 49,710 Chinese adults preferring English (non-LEP Chinese). Prevalence of the following utilization outcomes were compared by language preference (LEP/non-LEP) within ethnicity and by ethnicity within language preference for four age subgroups (26-39y, 40-64y, 65-75y, and 76-85y): ≥ 1 virtual (video or phone) visit, ≥ 1 video visit, ≥ 1 phone visit, ≥ 1 clinic visit, video visits only, and phone visits only. We also compared ethnicity x language group differences within age subgroups using absolute difference and adjusted prevalence ratios derived from modified log-Poisson regression models that controlled for age and sex. Results Among virtual users, LEP Latino and Chinese adults were significantly less likely to use video visits and more likely to use phone visits than non-LEP Latino and Chinese adults in the same age strata. The LEP/non-LEP difference in video visit use was significantly larger among Latino than Chinese patients, with no similar ethnic group difference observed for phone visits. Within the LEP and non-LEP language groups, Chinese adults were significantly more likely than Latino adults to use video visits and less likely to use phone visits. Conclusions During the first nine months of the COVID-19 pandemic, uptake of video and phone virtual visits by Latino and Chinese adults significantly differed by LEP/non-LEP status within ethnicity and by ethnicity within LEP/non-LEP language group. These findings underscore the importance of disaggregating data by ethnicity and language preference when attempting to understand and study patient use of different virtual visit modalities.

Abstract Background Person-centred care is becoming increasingly recognised as an important element of palliative care. The current review syntheses evidence in relation to transitions in advanced cancer patients with palliative care needs. The review focuses on specific elements which will inform the Pal-Cycles programme, for patients with advanced cancer transitioning from hospital care to community care. Elements of transitional models for cancer patients may include, identification of palliative care needs, compassionate communication with the patient and family members, collaborative effort to establish a multi-dimensional treatment plan, review and evaluation of the treatment plan and identification of the end of life phase. Methods A scoping review of four databases (MEDLINE, EMBASE, CINAHL, PsycINFO) was conducted to identify peer-reviewed studies published from January 2013 to October, 2022. A further hand-search of references to locate additional relevant studies was also undertaken. Inclusion criteria involved cancer patients transitions of care with a minimum of two of components from those listed above. Studies were excluded if they were literature reviews, if transition of care was related to cancer survivors, involved non-cancer patients, had paediatric population, if the transition implied a change of therapy and or a lack of physical transit to a non-hospital place of care. This review was guided by Arksey and O’Malley’s framework and narrative synthesis was used. Results Out of 5695 records found, 14 records were selected. Transition models identified: increases in palliative care consultations, hospice referrals, reduction in readmission rates and the ability to provide end of life care at home. Transition models highlight emotional and spiritual support for patients and families. No uniform model of transition was apparent, this depends on the healthcare system where it is implemented. Conclusions The findings highlight the importance of collaboration, coordination and communication as central mechanisms for transitional model for patients with advanced cancer. This may require careful planning and will need to be tailored to the contexts of each healthcare system.

Background Patients living with life-limiting illnesses other than cancer constitute the majority of patients in need of palliative care globally, yet most previous systematic reviews of the cost impact of palliative care have not exclusively focused on this population. Reviews that tangentially looked at non-cancer patients found inconclusive evidence. Randomised controlled trials (RCTs) are the gold standard for treatment efficacy, while total health care costs offer a comprehensive measure of resource use. In the sole review of RCTs for non-cancer patients, palliative care reduced hospitalisations and emergency department visits but its effect on total health care costs was not assessed. The aim of this study is to review RCTs to determine the difference in costs between a palliative care approach and usual care in adult non-cancer patients with a life-limiting illness. Methods A systematic review using a narrative synthesis approach. The protocol was registered with PROSPERO prospectively (no. CRD42020191082). Eight databases were searched: Medline, CINAHL, EconLit, EMBASE, TRIP database, NHS Evidence, Cochrane Library, and Web of Science from inception to January 2023. Inclusion criteria were: English or German; randomised controlled trials (RCTs); adult non-cancer patients (> 18 years); palliative care provision; a comparator group of standard or usual care. Quality of studies was assessed using Drummond’s checklist for assessing economic evaluations. Results Seven RCTs were included and examined the following diseases: neurological (3), heart failure (2), AIDS (1) and mixed (1). The majority (6/7) were home-based interventions. All studies were either cost-saving (3/7) or cost-neutral (4/7); and four had improved outcomes for patients or carers and three no change in outcomes. Conclusions In a non-cancer population, this is the first systematic review of RCTs that has demonstrated a palliative care approach is cost-saving or at least cost-neutral. Cost savings are achieved without worsening outcomes for patients and carers. These findings lend support to calls to increase palliative care provision globally.

Abstract Background Adults and children with cancer are referred to palliative care infrequently or late. Oncologists often gatekeep these referrals. Social exchange theory is used to explain physician referral behaviour in various clinical settings. Its utility in a cancer palliative care setting is not known. Methods We used Karl Popper’s hypothetico-deductive approach to test the hypothesis. The hypothesis was that social exchange theory is a helpful framework for explaining oncologists’ palliative care referral behaviour in a cancer setting. The utility of the theoretical framework was tested against the empiric findings of a systematic review and original research. Results Most components of social exchange theory known to explain physician referral behaviour like beliefs about the provider or service, emotions triggered during the professional engagement, its symbolism and stigma, the complexity of the referral task, efforts needed to achieve it, its cost, benefit, and value were similar in a cancer setting. Empirical findings suggest that oncologists provided strategies and solutions to better palliative care integration instead of comparing their existing engagement with potential alternatives and choosing them. Conclusion Social exchange theory was found to be helpful in explaining oncologists’ palliative care referral behaviour. To further develop the social exchange theory based on the data used to test it, it is recommended to include feedback and solutions as a component of the theoretical framework alongside a comparison level for alternatives.

Abstract Introduction Melanoma, a deadly form of skin cancer, has witnessed a notable increase in incidence over the past decades. Despite advancements in treatment, it remains a significant cause of cancer mortality. Understanding demographic trends and variations in melanoma mortality is crucial for addressing disparities and implementing effective interventions. Methods Using the Centers for Disease Control Wide Ranging Online Data for Epidemiologic Research (CDC WONDER) database, we analyzed melanoma mortality data in the United States from 1999 to 2020. Data were stratified by demographic and regional variables, and age-adjusted mortality rates were calculated. Descriptive analysis was performed and Joinpoint regression analysis was employed to identify temporal trends. Results Between 1999 and 2020, there were 184,416 melanoma-related deaths in the United States Overall, the age-adjusted mortality rate declined from 2.7 to 2.0 per 100,000 people at a rate of -1.3% annually, with significant variations across demographic groups and regions. Men, non-Hispanic White individuals, and those aged > 65 experienced higher mortality rates. Non-Hispanic White individuals noted the steepest decrease in AAMR after 2013 at a rate of -6.1% annually. Disparities were seen by geographic density, with rural populations exhibiting higher mortality compared to their urban and suburban counterparts. Conclusion The study highlights a significant reduction in melanoma mortality in the U.S. since 2013, potentially attributed to advancements in diagnostic techniques such as dermoscopy and the introduction of immune checkpoint inhibitors. Disparities persist, particularly among rural populations. Targeted interventions focusing on increased screening and education are warranted to further mitigate melanoma mortality and address demographic disparities.

Abstract Background Palliative care provision should be driven by high quality research evidence. However, there are barriers to conducting research. Most research attention focuses on potential patient barriers; staff and organisational issues that affect research involvement are underexplored. The aim of this research is to understand professional and organisational facilitators and barriers to conducting palliative care research. Methods A mixed methods study, using an open cross-sectional online survey, followed by working groups using nominal group techniques. Participants were professionals interested in palliative care research, working as generalist/specialist palliative care providers, or palliative care research staff across areas of North West England. Recruitment was via local health organisations, personal networks, and social media in 2022. Data were examined using descriptive statistics and content analysis. Results Participants (survey n = 293, working groups n = 20) were mainly from clinical settings (71%) with 45% nurses and 45% working more than 10 years in palliative care. 75% were not active in research but 73% indicated a desire to increase research involvement. Key barriers included lack of organisational research culture and capacity (including prioritisation and available time); research knowledge (including skills/expertise and funding opportunities); research infrastructure (including collaborative opportunities across multiple organisations and governance challenges); and patient and public perceptions of research (including vulnerabilities and burdens). Key facilitators included dedicated research staff, and active research groups, collaborations, and networking opportunities. Conclusions Professionals working in palliative care are keen to be research active, but lack time, skills, and support to build research capabilities and collaborations. A shift in organisational culture is needed to enhance palliative care research capacity and collaborative opportunities across clinical and research settings.

Abstract Background Dignity is integral to palliative care. Illness can diminish it, causing hopelessness and the wish to hasten death. Yet, dignity is a complex multidimensional phenomenon, influenced by values and context. Understanding its varying interpretations can inform practice and policy. The aim of the study is to explore the understanding of dignity in adult patients with palliative care needs from a Lebanese perspective and how it is preserved during illness and while receiving health services. Design Qualitative interview study underpinned with a social constructionist lens. Fourteen patients recruited from home-based hospice and outpatient clinics in Lebanon. Data analysed using reflexive thematic analysis. Results Four themes were developed across all the interviews: (a) Dignity anchored through faith in God and religious practices; (b) Family support in maintaining physical, psychological wellbeing, and social connectedness; (c) Physical fitness, mental acuity, and healthy appearance through which patients may escape the stigma of disease, (d) accessible, equitable, and compassionate healthcare. Discussion Dignity is elusive and difficult to define but faith and religious beliefs play a significant contribution in this study. For the participants, illness is seen as a natural part of life that does not necessarily diminish dignity, but it is the illness related changes that potentially affect dignity. Findings show the importance of family and children in preserving dignity during illness and how their active presence provide a sense of pride and identity. Participants aspired to restore physical, social, and mental well-being to reclaim their dignity and normalize their lives. Challenges related to physical appearance, memory loss, vitality, and social stigma associated with illness diminished dignity. Accessible, equitable and compassionate healthcare services are also crucial in preserving dignity. Participants valued clear communication, respect, and empathy from healthcare providers and identified affordability of care essential for maintaining dignity. Conclusion Faith in God, and strong family ties are dominant elements to maintaining dignity in the Lebanese context. Relational connectedness with family, children or God is also a need in maintaining dignity in other communal countries with variations in emphasis. The study indicates that religious and cultural context shapes the needs and perceptions of dignity during illness. These findings are likely to be transferable to many Middle Eastern countries but also countries with strong religious and family ties globally.

Abstract Background Healthcare in care homes during the COVID-19 pandemic required a balance, providing treatment while minimising exposure risk. Policy for how residents should receive care changed rapidly throughout the pandemic. A lack of accessible data on care home residents over this time meant policy decisions were difficult to make and verify. This study investigates common patterns of healthcare utilisation for care home residents in relation to COVID-19 testing events, and associations between utilisation patterns and resident characteristics. Methods Datasets from County Durham and Darlington NHS Foundation Trust including secondary care, community care and a care home telehealth app are linked by NHS number used to define daily healthcare utilisation sequences for care home residents. We derive four 10-day sets of sequences related to Pillar 1 COVID-19 testing; before [1] and after [2] a resident’s first positive test and before [3] and after [4] a resident’s first test. These sequences are clustered, grouping residents with similar healthcare patterns in each set. Association of individual characteristics (e.g. health conditions such as diabetes and dementia) with healthcare patterns are investigated. Results We demonstrate how routinely collected health data can be used to produce longitudinal descriptions of patient care. Clustered sequences [1,2,3,4] are produced for 3,471 care home residents tested between 01/03/2020–01/09/2021. Clusters characterised by higher levels of utilisation were significantly associated with higher prevalence of diabetes. Dementia is associated with higher levels of care after a testing event and appears to be correlated with a hospital discharge after a first test. Residents discharged from inpatient care within 10 days of their first test had the same mortality rate as those who stayed in hospital. Conclusion We provide longitudinal, resident-level data on care home resident healthcare during the COVID-19 pandemic. We find that vulnerable residents were associated with higher levels of healthcare usage despite the additional risks. Implications of findings are limited by the challenges of routinely collected data. However, this study demonstrates the potential for further research into healthcare pathways using linked, routinely collected datasets.

Abstract Background Globally, children with cancer often experience delays in palliative care referral or are infrequently referred. Therefore, we conducted a qualitative study to gain insight from paediatric oncologists into what enables or deters palliative care referral. Strategic solutions to develop integrated palliative care was a critical study theme. In this paper, we have explained and interpreted these strategic solutions through the lens of feedback intervention theory. Methodology The study findings were interpreted using Kumar’s six-step approach that enabled systematic evaluation of a theory’s appropriateness and alignment with the researcher’s paradigm, methodology, and study findings. It also explained how theory informed analysis and elucidated challenges or the development of new models. The feedback intervention theory appraises the discrepancy between actual and desired goals and provides feedback to improve it. Results Strategic solutions generated from the study findings were coherent with the aspects elucidated in theory, like coping mechanisms, levels of feedback hierarchy, and factors determining the effect of the feedback intervention on performance. Paediatric oncologists suggested integrating palliative care providers in the team innocuously, improving communication between teams, relabelling palliative care as symptom control, and working with a skilled and accessible palliative care team. The paper proposes an infinite loop model developed from the study, which has the potential to foster integrated palliative care through excellent collaboration and continuous feedback. Conclusion Applying feedback intervention theory can bridge the gap between actual and desired practice for integrated cancer palliative care in paediatric oncology.

Abstract Aspergillus fumigatus is the leading causative agent of life-threatening invasive aspergillosis in immunocompromised individuals. One antifungal class used to treat Aspergillus infections is the fungistatic echinocandins, semisynthetic drugs derived from naturally occurring fungal lipopeptides. By inhibiting beta-1,3-glucan synthesis, echinocandins cause both fungistatic stunting of hyphal growth and repeated fungicidal lysis of apical tip compartments. Here, we uncover an endogenous mechanism of echinocandin tolerance in A. fumigatus whereby the inducible oxylipin signal 5,8-diHODE confers protection against tip lysis via the transcription factor ZfpA. Treatment of A. fumigatus with echinocandins induces 5,8-diHODE synthesis by the fungal oxygenase PpoA in a ZfpA dependent manner resulting in a positive feedback loop. This protective 5,8-diHODE/ZfpA signaling relay is conserved among diverse isolates of A. fumigatus and in two other Aspergillus pathogens. Our findings reveal an oxylipin-directed growth program—possibly arisen through natural encounters with native echinocandin producing fungi—that enables echinocandin tolerance in pathogenic aspergilli.

Abstract Background The disproportionate effect of COVID-19 on long term care facility (LTCF) residents has highlighted the need for clear, consistent guidance on the management of pandemics in such settings. As research exploring the experiences of LTCFs during the pandemic and the implications of mass hospital discharge, restricting staff movement, and limiting visitation from relatives are emerging, an in-depth review of policies, guidance and recommendations issued during this time could facilitate wider understanding in this area. Aims To identify policies, guidance, and recommendations related to LTCF staff and residents, in England issued by the government during the COVID-19 pandemic, developing a timeline of key events and synthesizing the policy aims, recommendations, implementation and intended outcomes. Method A scoping review of publicly available policy documents, guidance, and recommendations related to COVID-19 in LTCFs in England, identified using systematic searches of UK government websites. The main aims, recommendations, implementation and intended outcomes reported in included documents were extracted. Data was analysed using thematic synthesis following a three-stage approach: coding the text, grouping codes into descriptive themes, and development of analytical themes. Results Thirty-three key policy documents were included in the review. Six areas of recommendations were identified: infection prevention and control, hospital discharge, testing and vaccination, staffing, visitation and continuing routine care. Seven areas of implementation were identified: funding, collaborative working, monitoring and data collection, reducing workload, decision making and leadership, training and technology, and communication. Discussion LTCFs remain complex settings, and it is imperative that lessons are learned from the experiences during COVID-19 to ensure that future pandemics are managed appropriately. This review has synthesized the policies issued during this time, however, the extent to which such guidance was communicated to LTCFs, and subsequently implemented, in addition to being effective, requires further research. In particular, understanding the secondary effects of such policies and how they can be introduced within the existing challenges inherent to adult social care, need addressing.

Objectives: Financial strain has important consequences for patients, providers, and health care systems. However, there is currently no gold standard measure to screen for financial strain. This study compared the performance of 3 single-item screeners using a composite measure of financial strain as a “gold standard.” Methods: We conducted a secondary analysis of unweighted data from a 2021 survey of Kaiser Permanente Northern California health plan members comparing the percentages of adults who experienced financial strain based on 3 general single-item screeners, a screener specific to medical and dental health care use, and a composite financial strain measure. The study sample was comprised of 2734 non-Medicaid insured adults who answered all financial strain questions. Kappa statistics evaluating agreement of the 3 general screeners with the composite measure were calculated for the sample overall, by age group, and within age group, by 4 levels of income and 4 racial/ethnic subgroups. Results: Among 947 adults aged 35 to 65, 30.7% had just enough money or not enough money to make ends meet, 23.3% had a somewhat hard or hard time paying for basics, 18.8% had trouble paying for ≥1 type of expense, 20.5% had delayed/used less medical/dental care, and 41.5% had experienced financial strain based on the composite measure. Among 1787 adults aged 66 to 85, the percentages who screened positive on these measures were 22.7%, 19.4%, 12.9%, 19.8%, and 34.4%, respectively. Across the sample, by income categories and racial/ethnic groups, the making ends meet screener identified higher percentages of adults experiencing financial strain and performed better when compared with the composite measure than the hard to pay for the very basics and trouble paying for expenses screeners. Overall, substantial decreases in the percentages of adults who screened positive on the financial strain measures were seen as level of income increased. Within income categories, middle-aged adults were more likely than older adults to have experienced financial strain based on the composite and general single-item screeners. Conclusions: As social risk screening becomes part of the standard of care, it will be important to assess how well different brief screeners for financial strain perform with diverse patient populations.

Background: Korsakoff’s syndrome (KS) is a debilitating psychoneurological disorder that can occur in adults with alcohol use disorder (AUD). People with KS experience a sudden onset of symptoms including confabulation, anterograde and retrograde amnesias, apathy, issues with vision and gait, and lack of insight. Frequently an adult child of the parent with alcohol-induced KS becomes the caregiver, regardless of the status or quality of the relationship with their parent. While there is a rich literature base in the areas of adult children of parents with AUD and caregiving, there are no studies that have explored the experiences of adult children caring for a parent with alcohol-induced KS. This study aimed to explore the experiences of adult children who provide care for a parent or parental figure suffering from alcohol-induced Korsakoff syndrome (KS). Method: This study used a generic qualitative approach with thematic analysis using both in person and web-based video interview methods and field notes to address this gap in the literature. Eight individuals participated in the study, men (n=2) and women (n=6), with participants ranging in age from 31 to 43 years (average age 37 years). Results: Five themes emerged: addiction and the adult child, experiencing caregiver burden, experiencing a variety of emotions, professional healthcare experiences, and observations of symptoms. These themes emerged over seven anchor events in their caregiving experiences: interactions with their parent pre-diagnosis, parent’s medical emergency, hospitalization, diagnosis, housing, legal, and financial. Conclusion: The results provide a foundation for future research in the areas of KS, caregiving, and adult children of parents with AUD. They also provide a basis to inform the development of interventions with this population and demonstrate a need for more awareness of KS among healthcare professionals.

BackgroundTransgender and nonbinary (TNB) people experience economic and psychosocial inequities that make them more likely to be subject to financial and mental health harms exacerbated by the COVID-19 pandemic. Sustainable, multilevel interventions are needed to address these harms. The onset of the COVID-19 pandemic galvanized many TNB-led organizations to provide emergency financial and peer support for TNB people negatively impacted by the pandemic. However, the efficacy of these interventions has not been evaluated. The Creating Access to Resources and Economic Support (CARES) study seeks to assess the efficacy of feasible, acceptable, and community-derived interventions to reduce economic and psychological harms experienced by transgender people in the wake of the COVID-19 pandemic. ObjectiveThe study aims to (1) compare the efficacy of microgrants with peer mentoring with that of microgrants without peer mentoring in reducing psychological distress, (2) examine mechanisms by which microgrants with or without peer mentoring may impact psychological distress, and (3) explore participants’ intervention experiences and perceived efficacy. MethodsWe will enroll 360 TNB adults into an embedded, mixed methods, 3-arm, and 12-month randomized controlled trial. Participants will be randomized 1:1:1 to arm A (enhanced usual care), which will receive a single microgrant plus monthly financial literacy education, arm B (extended microgrants), which will receive enhanced usual care plus monthly microgrants, or arm C (peer mentoring), which will receive extended microgrants combined with peer mentoring. All intervention arms last for 6 months, and participants complete semiannual, web-based surveys at 0, 6, and 12 months as well as brief process measures at 3 and 6 months. A subset of 36 participants, 12 (33%) per arm, will complete longitudinal in-depth interviews at 3 and 9 months. ResultsFull recruitment began on January 8, 2024, and, as of July 26, 2024, a total of 138 participants have enrolled. Recruitment is expected to be completed no later than March 31, 2025, and the final study visit will take place in March 2026. ConclusionsThis national, web-based study will demonstrate whether an intervention tailored to reduce material hardship and improve peer support among TNB adults will reduce psychological distress. Its equitable, community-academic partnership will ensure the rapid dissemination of study findings. Trial RegistrationClinicalTrials.gov NCT05971160; https://clinicaltrials.gov/study/NCT05971160 International Registered Report Identifier (IRRID)DERR1-10.2196/63656

L’objet du présent article est de présenter les principaux résultats d’une démarche de recherche réalisée entre 2019 et 2022 avec l’appui du Conseil de recherche en sciences humaines du Canada (CRSH). La recherche portait sur l’étude comparative de dix fondations subventionnaires ayant adopté une posture d’intervention fondée sur le lieu (place-based philanthropy). Notre texte est divisé en trois grandes sections. La première se penche sur la philanthropie moderne. La deuxième présente le résultat de la méta-analyse qui a été réalisée au début de l’étude comparative. La troisième section expose les résultats de l’analyse comparative effectuée. Avant de conclure par un appel à l’action fondée sur le lieu, nous présentons les questions qui ont guidé notre collecte de données et validons ou invalidons nos hypothèses de travail.

IntroductionThe Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) is a North American learning health network focused on improving outcomes of children with juvenile idiopathic arthritis (JIA). JIA is a chronic autoimmune disease that can lead to morbidity related to persistent joint and ocular inflammation. PR-COIN has a shared patient registry that tracks twenty quality measures including ten outcome measures of which six are related to disease activity. The network's global aim, set in 2021, was to increase the percent of patients with oligoarticular or polyarticular JIA that had an inactive or low disease activity state from 76% to 80% by the end of 2023.MethodsTwenty-three hospitals participate in PR-COIN, with over 7,200 active patients with JIA. The disease activity outcome measures include active joint count, physician global assessment of disease activity, and measures related to validated composite disease activity scoring systems including inactive or low disease activity by the 10-joint clinical Juvenile Arthritis Disease Activity Score (cJADAS10), inactive or low disease activity by cJADAS10 at 6 months post-diagnosis, mean cJADAS10 score, and the American College of Rheumatology (ACR) provisional criteria for clinical inactive disease. Data is collated to measure network performance, which is displayed on run and control charts. Network-wide interventions have included pre-visit planning, shared decision making, self-management support, population health management, and utilizing a Treat to Target approach to care.ResultsFive outcome measures related to disease activity have demonstrated significant improvement over time. The percent of patients with inactive or low disease activity by cJADAS10 surpassed our goal with current network performance at 81%. Clinical inactive disease by ACR provisional criteria improved from 46% to 60%. The mean cJADAS10 score decreased from 4.3 to 2.6, and the mean active joint count declined from 1.5 to 0.7. Mean physician global assessment of disease activity significantly improved from 1 to 0.6.ConclusionsPR-COIN has shown significant improvement in disease activity metrics for patients with JIA. The network will continue to work on both site-specific and collaborative efforts to improve outcomes for children with JIA with attention to health equity, severity adjustment, and data quality.

The piRNA pathway is a conserved germline-specific small RNA pathway that ensures genomic integrity and continued fertility. In C. elegans and other nematodes, Type-I piRNAs are expressed from >10,000 independently transcribed genes clustered within two discrete domains of 1.5 and 3.5 MB on Chromosome IV. Clustering of piRNA genes contributes to their germline-specific expression, but the underlying mechanisms are unclear. We analyze isolated germ nuclei to demonstrate that the piRNA genomic domains are located in a heterochromatin-like environment. USTC (Upstream Sequence Transcription Complex) promotes strong association of nucleosomes throughout piRNA clusters, yet organizes the local nucleosome environment to direct the exposure of individual piRNA genes. Localization of USTC to the piRNA domains depends upon the ATPase chromatin remodeler ISW-1, which maintains high nucleosome density across piRNA clusters and ongoing production of piRNA precursors. Overall, this work provides insight into how chromatin states coordinate transcriptional regulation over large genomic domains, with implications for global genome organization.

IntroductionEnsuring high-quality race and ethnicity data within the electronic health record (EHR) and across linked systems, such as patient registries, is necessary to achieving the goal of inclusion of racial and ethnic minorities in scientific research and detecting disparities associated with race and ethnicity. The project goal was to improve race and ethnicity data completion within the Pediatric Rheumatology Care Outcomes Improvement Network and assess impact of improved data completion on conclusions drawn from the registry.MethodsThis is a mixed-methods quality improvement study that consisted of five parts, as follows: (1) Identifying baseline missing race and ethnicity data, (2) Surveying current collection and entry, (3) Completing data through audit and feedback cycles, (4) Assessing the impact on outcome measures, and (5) Conducting participant interviews and thematic analysis.ResultsAcross six participating centers, 29% of the patients were missing data on race and 31% were missing data on ethnicity. Of patients missing data, most patients were missing both race and ethnicity. Rates of missingness varied by data entry method (electronic vs. manual). Recovered data had a higher percentage of patients with Other race or Hispanic/Latino ethnicity compared with patients with non-missing race and ethnicity data at baseline. Black patients had a significantly higher odds ratio of having a clinical juvenile arthritis disease activity score (cJADAS10) of ≥5 at first follow-up compared with White patients. There was no significant change in odds ratio of cJADAS10 ≥5 for race and ethnicity after data completion. Patients missing race and ethnicity were more likely to be missing cJADAS values, which may affect the ability to detect changes in odds ratio of cJADAS ≥5 after completion.ConclusionsAbout one-third of the patients in a pediatric rheumatology registry were missing race and ethnicity data. After three audit and feedback cycles, centers decreased missing data by 94%, primarily via data recovery from the EHR. In this sample, completion of missing data did not change the findings related to differential outcomes by race. Recovered data were not uniformly distributed compared with those with non-missing race and ethnicity data at baseline, suggesting that differences in outcomes after completing race and ethnicity data may be seen with larger sample sizes.

Background Shared decision‐making (SDM) has the potential to improve hypertension care quality and equity. However, research lacks diverse representation and evidence about how race and ethnicity affect SDM. Therefore, this study aims to explore SDM in the context of hypertension management. Methods and Results Explanatory sequential mixed‐methods design was used. Quantitative data were sourced at baseline and 12‐month follow up from RICH LIFE (Reducing Inequities in Care of Hypertension: Lifestyle Improvement for Everyone) participants (n=1212) with hypertension. Qualitative data were collected from semistructured individual interviews, at 12‐month follow‐up, with participants (n=36) selected based on their SDM scores and blood pressure outcome. Patients were cross‐ categorized based on high or low SDM scores and systolic blood pressure reduction of ≥10 or

Abstract Background Care homes (long-term care facilities) were profoundly impacted early in the COVID-19 pandemic, both in terms of resident mortality and restrictions for infection control. This study investigated the impact on the emotional well-being of care home staff of challenges faced at this time, and the strategies used to manage them. Methods Semi-structured interviews conducted October 2020-June 2021 with care home staff and health service staff working with them explored the impact of the early waves of the COVID-19 pandemic (March 2020-June 2021). Interview data were analysed using reflexive thematic analysis. Results Interview participants were 16 care home staff and 10 health service staff. Analysis generated four key themes: 1)Anxiety and distress, 2)Overwhelming workload, 3)Pulling through; and 4)Resilience in a time of crisis. Care home staff experienced Anxiety and distress due to uncertainty of what to expect; witnessing illness and deaths of residents; concerns regarding their own health, and sometimes feeling their work was under-recognised. They also experienced an Overwhelming workload due to infection control measures, caring for sick residents and reduction in external healthcare support. Our theme of Pulling through reflects the peer support and problem-solving strategies with which care home staff managed the impact of the pandemic, along with a sense of responsibility and meaning towards their work. An overarching theme of Resilience in a time of crisis drew on the other three themes and describes how many staff managed, maintained, and often increased their work despite the challenges of the pandemic. Participants also described increasing emotional fatigue as the pandemic continued. Conclusions This paper builds on literature on the emotional impact of the pandemic on care home staff, also exploring ways that staff responded to this impact. These findings can help inform planning for future crises including disease outbreaks, and raise important questions for further work to develop pandemic preparedness in care homes and beyond. They also raise wider questions about the current cultural status of care work, which may have exposed care home staff to greater risk of distress, and which contrasts with the professionalism and responsibility shown by staff in response to pandemic challenges.

Abstract Background Over one-third of people living with HIV (PLH) in Ukraine are not on treatment. Index testing services, which link potentially exposed partners (named partners) of known PLH (index patients) with testing and treatment services, are being scaled in Ukraine and could potentially close this gap. Methods This retrospective study included patient data from 14,554 adult PLH who initiated antiretroviral treatment (ART) between October 2018 and May 2021 at one of 35 facilities participating in an intervention to strengthen index testing services. Mixed effects modified Poisson models were used to assess differences between named partners and other ART initiators, and an interrupted time series (ITS) analysis was used to assess changes in ART initiation over time. Results Compared to other ART initiators, named partners were significantly less likely to have a confirmed TB diagnosis (aRR = 0.56, 95% CI = 0.40, 0.77, p

We, the QUARTET Collaboration, propose an experiment to measure the nuclear charge radii of light elements with up to 20 times higher accuracy. These are essential both for understanding nuclear physics at low energies, and for experimental and theoretical applications in simple atomic systems. Such comparisons advance the understanding of bound-state quantum electrodynamics and are useful for searching for new physics beyond the Standard Model. The energy levels of muonic atoms are highly susceptible to nuclear structure, especially to the mean square charge radius. The radii of the lightest nuclei (with the atomic number, Z=1,2) have been determined with high accuracy using laser spectroscopy in muonic atoms, while those of medium mass and above were determined using X-ray spectroscopy with semiconductor detectors. In this communication, we present a new experiment, aiming to obtain precision measurements of the radii of light nuclei 3≤Z≤10 using single-photon energy measurements with cryogenic microcalorimeters; a quantum-sensing technology capable of high efficiency with outstanding resolution for low-energy X-rays.

Abstract Background Understanding why patients experience loss to follow-up (LTFU) is essential for TB control. This analysis examines the impact of travel distance to RR-TB treatment on LTFU, which has yet to be analyzed within South Africa. Methods We retrospectively analyzed 1436 patients treated for RR-TB at ten South African public hospitals. We linked patients to their residential ward using data reported to NHLS and maps available from the Municipal Demarcation Board. Travel distance was calculated from each patient’s ward centroid to their RR-TB treatment site using the georoute command in Stata. The relationship between LTFU and travel distance was modeled using multivariable logistic regression. Results Among 1436 participants, 75.6% successfully completed treatment and 24.4% were LTFU. The median travel distance was 40.96 km (IQR: 17.12, 63.49). A travel distance > 60 km increased odds of LTFU by 91% (p = 0.001) when adjusting for HIV status, age, sex, education level, employment status, residential locale, treatment regimen, and treatment site. Conclusion People living in KwaZulu-Natal and Eastern Cape travel long distances to receive RR-TB care, placing them at increased risk for LTFU. Policies that bring RR-TB treatment closer to patients, such as further decentralization to PHCs, are necessary to improve RR-TB outcomes.

Abstract Background Intimate partner violence (IPV) threatens the safety, health and quality of life of women worldwide. Comprehensive IPV interventions that are tailored, take a long-term view of women’s needs, including health concerns, and maximize choice and control, have the potential to effectively address heath and safety concerns. Few such interventions have been tested, including in the Canadian context. Methods A parallel randomized controlled trial of adult (age 19 + years), English-speaking, Canadian women with histories of IPV randomized either to iHEAL, a tailored health promotion intervention delivered by Registered Nurses over 6–7 months, or to community service information (usual care control). Primary (Quality of Life, PTSD symptoms) and secondary outcomes (Depression, Confidence in Managing Daily Life, Chronic Pain, IPV Severity) were measured at baseline and 6, 12 and 18 months post-intervention via an online survey. Generalized estimating equations were used to test for differences by study arm in intention-to-treat (full sample) and per protocol (1 + iHEAL visit) analyses focussing on short-term (immediately post-intervention) and longer-term (1 year post-intervention) effects. Selected process evaluation data were summarized using descriptive statistics. Results Of 331 women enrolled, 175 were randomized to iHEAL (135 who engaged in 1 + visits) and 156 to control. Women who received iHEAL showed significantly greater short-term improvement in Quality of Life compared to the control group, with these effects maintained 1 year later. Changes in PTSD Symptoms also differed significantly by group, with weaker initial effects that were stronger 1 year post-intervention. Significant moderate, short- and longer-term group effects were also observed for Depression and Confidence in Managing Daily Life. IPV Severity decreased for both groups, with significant immediate effects in favour of the intervention group that grew stronger 1 year post-intervention. There were no changes in Chronic Pain. Conclusion iHEAL is an effective, acceptable and safe intervention for diverse groups of women with histories of IPV. Trial results provide a foundation for implementation and ongoing evaluation in health care settings and systems. Delayed effects noted for PTSD Symptoms and IPV Severity suggest that longer-term assessment of these outcomes may be needed in trials of IPV interventions. Trial registration Clinicaltrials.gov ID NCT03573778 (Registered on June 29, 2018).

Goal: This paper introduces an automated post-traumatic stress disorder (PTSD) screening tool that could potentially be used as a self-assessment or inserted into routine medical visits to aid in PTSD diagnosis and treatment. Methods: With an emotion estimation algorithm providing arousal (excited to calm) and valence (pleasure to displeasure) levels through discourse, we select regions of the acoustic signal that are most salient for PTSD detection. Our algorithm was tested on a subset of data from the DVBIC-TBICoE TBI Study, which contains PTSD Check List Civilian (PCL-C) assessment scores. Results: Speech from low-arousal and positive-valence regions provide the highest discrimination for PTSD. Our model achieved an AUC (area under the curve) of 0.80 in detecting PCL-C ratings, outperforming models with no emotion filtering (AUC = 0.68). Conclusions: This result suggests that emotion drives the selection of the most salient temporal regions of an audio recording for PTSD detection.

Abstract Social recognition is crucial for survival in social species, and necessary for group living, selective reproduction, pair bonding, and dominance hierarchies. Mice and rats are the most commonly used animal models in social memory research, however current paradigms do not account for the complex social dynamics they exhibit in the wild. To assess the range of social memories being studied, we conducted a systematic analysis of neuroscience articles testing the social memory of mice and rats published within the past two decades and analyzed their methods. Our results show that despite these rodent’s rich social memory capabilities, the majority of social recognition papers explore short-term memories and short-term familiarity levels with minimal exposure between subject and familiar stimuli—a narrow type of social memory. We have identified several key areas currently understudied or underrepresented: kin relationships, mates, social ranks, sex variabilities, and the effects of aging. Additionally, reporting on social stimulus variables such as housing history, strain, and age, is limited, which may impede reproducibility. Overall, our data highlight large gaps in the diversity of social memories studied and the effects social variables have on social memory mechanisms.

Abstract Quiescence, a reversible state of cell-cycle arrest, is an important state during both normal development and cancer progression. For example, in glioblastoma (GBM) quiescent glioblastoma stem cells (GSCs) play an important role in re-establishing the tumour, leading to relapse. While most studies have focused on identifying differentially expressed genes between proliferative and quiescent cells as potential drivers of this transition, recent studies have shown the importance of protein oscillations in controlling the exit from quiescence of neural stem cells. Here, we have undertaken a genome-wide bioinformatic inference approach to identify genes whose expression oscillates and which may be good candidates for controlling the transition to and from the quiescent cell state in GBM. Our analysis identified, among others, a list of important transcription regulators as potential oscillators, including the stemness gene SOX2, which we verified to oscillate in quiescent GSCs. These findings expand on the way we think about gene regulation and introduce new candidate genes as key regulators of quiescence.

Abstract Background Children of substance-involved mothers are at especially high risk for exposure to adverse childhood experiences (ACEs) and poor mental health and development. Early interventions that support mothers, children, and the mother-child relationship have the greatest potential to reduce exposure to early adversity and the mental health problems associated with these exposures. Currently, there is a lack of evidence from the real-world setting demonstrating effectiveness and return on investment for intervention programs that focus on the mother-child relationship in children of substance-involved mothers. Methods One hundred substance-involved pregnant and/or parenting women with children between the ages of 0–6 years old will be recruited through the Breaking the Cycle and Maxxine Wright intervention programs, in Toronto, Ontario, Canada and Surrey, British Columbia, Canada, respectively. Children’s socioemotional development and exposure to risk and protective factors, mothers’ mental health and history of ACEs, and mother-child relationship quality will be assessed in both intervention programs. Assessments will occur at three time points: pre-intervention, 12-, and 24-months after engagement in the intervention program. Discussion There is a pressing need to identify interventions that promote the mental health of infants and young children exposed to early adversity. Bringing together an inter-disciplinary research team and community partners, this study aligns with national strategies to establish strong evidence for infant mental health interventions that reduce child exposure to ACEs and support the mother-child relationship. This study was registered with clinicaltrials.gov (NCT05768815) on March 14, 2023.

Abstract Background Bereavement experience is shaped by cultural and social contexts. No systematically constructed reviews were identified to explore the bereavement experience for people who are influenced by Chinese culture valuing filial piety and mutual dependence. This review aimed to systematically review the bereavement experience of Taiwanese family members living in Taiwan following an expected death. Methods MEDLINE, PsycINFO, CINAHL, China Academic Journal Database, and Chinese Electronic Periodical Services were searched with no date restrictions from inception to 20 October 2022. The methodological rigour of studies was assessed using Hawker’s appraisal tool. A narrative synthesis approach using Popay’s work was employed to synthesise the findings of the studies. Studies investigating Taiwanese family members’ bereavement experiences were included. We excluded papers studying bereavement through the death of a child. Results Searches retrieved 12,735 articles (after de-duplication), 17 of which met the inclusion criteria and were included for synthesis: English [9] and Chinese [8], published between 2006 and 2021. The studies varied in quality with scores ranging from 22 to 33 out of 36. The studies differed in the relationship between participants and the deceased, the bereaved time frames, and the definitions of bereavement. Most studies focussed on family members of cancer patients receiving specialist palliative care. Three bereavement theories and four tools were used. Risk factors of bereavement outcomes included family members feeling less prepared for death and deaths where palliative sedative therapy was used. Protective factors were higher caregiving burden and longer caregiving periods. Four themes regarding Taiwanese bereavement experience were generated: multiple impacts of death; problem-based coping strategies; importance of maintaining connections; influential religious beliefs and rituals. Conclusion Continuing the relationship with the deceased is a key element of Taiwanese bereavement experience and it is influenced by religious and cultural beliefs. Suppressing or hiding emotions during bereavement to connect with the deceased and maintain harmonious relationships needs to be acknowledged as culturally acceptable and encouraged by some religions in Taiwan. The findings could be potentially relevant for other Chinese populations, predominantly Buddhist countries or other East Asian societies. The role of preparing for death in bereavement outcomes is little understood and requires further research.

ABSTRACT Resistance to ceftazidime-avibactam (CZA) due to Klebsiella pneumoniae carbapenemase (KPC) variants is increasing worldwide. We characterized two CZA-resistant clinical Klebsiella pneumoniae strains by antimicrobial susceptibility test, conjugation assays, and WGS. Isolates belonged to ST258 and ST45, and produced a KPC-31 and a novel variant KPC-197, respectively. The novel KPC variant presents a deletion of two amino acids on the Ω-loop (del_168–169_EL) and an insertion of two amino acids in position 274 (Ins_274_DS). Continued surveillance of KPC variants conferring CZA resistance in Colombia is warranted.IMPORTANCELatin America and the Caribbean is an endemic region for carbapenemases. Increasingly high rates of Klebsiella pneumoniae carbapenemase (KPC) have established ceftazidime-avibactam (CZA) as an essential antimicrobial for the treatment of infections due to MDR Gram-negative pathogens. Although other countries in the region have reported the emergence of CZA-resistant KPC variants, this is the first description of such enzymes in Colombia. This finding warrants active surveillance, as dissemination of these variants could have devastating public health consequences.

Semblanza de Manuel Marí

Introduction: The prevalence of hypertension increases with age and differs by race and ethnicity. Among U.S. Asian adults, prevalence is higher for Filipino adults than for other major Asian subgroups, but whether this disparity exists across the adult lifespan is unknown. This study examined hypertension prevalence by age decade, comparing Filipino adults with South Asian, Chinese, Black, Hispanic, and White adults. Methods: This cross-sectional study used 2015–2016 electronic health record data from a Northern California integrated healthcare delivery system for 1,839,603 adults aged 30–79 years, including 128,124 Filipino adults. Hypertension was defined by diagnosis codes. Sex-specific prevalence was calculated by race and ethnicity overall and by 10-year age decade from ages 30–39 years to 70–79 years. The prevalence of hypertension among 5 racial and ethnic groups was compared within each decade (with Filipino as the reference), adjusting for age, English language, diabetes, smoking, and weight category. Results: Decade-specific prevalence of hypertension among Filipino men and women, respectively, was 9.7% and 8.5% for ages 30–39 years, 26.0% and 23.9% for ages 40–49 years, 45.9% and 44.4% for ages 50–59 years, 65.4% and 63.9% for ages 60–69 years, and 82.1% and 82.9% for ages 70–79 years. Across all age decades, hypertension prevalence among Filipino adults largely tracked with Black adults and was much higher than among South Asian, Chinese, White, and Hispanic adults. This pattern remained after adjusting for covariates, with the largest differences observed for adults aged

Ethyl 4-((11-(hexylamino)-11-oxoundecyl)oxy)benzoate was synthesized using 11-bromoundecanoic acid hexylamide and commercially available ethyl 4-hydroxybenzoate through a Williamson etherification synthesis. The structural characterization was performed using UV-Vis, FT-IR, 1H-NMR, 13C-NMR, and HRMS.

Objectives: Healthcare screening identifies factors that impact patient health and well-being. Hunger as a Vital Sign (HVS) is widely applied as a screening tool to assess food security. However, there are no common practice screening questions to identify patients who are nutrition insecure or acquire free food from community-based organizations. This study used self-reported survey data from a non-Medicaid insured adult population approximately one year after the start of the COVID-19 pandemic (2021). The survey examined the extent to which the HVS measure might have under-estimated population-level food insecurity and/or nutrition insecurity, as well as under-identified food and nutrition insecurity among patients being screened for social risks in the healthcare setting. Methods: Data from a 2021 English-only mailed/online survey were analyzed for 2791 Kaiser Permanente Northern California (KPNC) non-Medicaid insured members ages 35-85 years. Sociodemographics, financial strain, food insecurity, acquiring free food from community-based organizations, and nutrition insecurity were assessed. Data from respondents’ electronic health records were abstracted to identify adults with diet-related chronic health conditions. Data were weighted to the age × sex × racial/ethnic composition of the 2019 KPNC adult membership. Differences between groups were evaluated for statistical significance using adjusted prevalence ratios (aPRs) derived from modified log Poisson regression models. Results: Overall, 8.5% of participants reported moderate or high food insecurity, 7.7% had acquired free food from community-based organizations, and 13% had nutrition insecurity. Black and Latino adults were significantly more likely than White adults to have food insecurity (17.4% and 13.1% vs 5.6%, aPRs = 2.97 and 2.19), acquired free food from community-based organizations (15.1% and 15.3% vs 4.1%, aPRs = 3.74 and 3.93), nutrition insecurity (22.1% and 23.9% vs 7.9%, aPRs = 2.65 and 2.64), and food and nutrition insecurity (32.4% and 32.5% vs 12.3%, aPRs = 2.54 and 2.44). Almost 20% of adults who had been diagnosed with diabetes, prediabetes, ischemic CAD, or heart failure were food insecure and 14% were nutrition insecure. Conclusions: Expanding food-related healthcare screening to identify and assess food insecurity, nutrition insecurity, and use of community-based emergency food resources together is essential for supporting referrals that will help patients achieve optimal health.

Background: Efforts to better understand and improve letters of recommendation (LORs) in the resident selection process have identified unwritten rules and hidden practices that may limit their effectiveness. The objective of our study is to explore these unwritten rules and hidden practices more fully in one Canadian academic medical community. Methods: We conducted semi-structured, discourse-based interviews with 18 faculty members from the departments of Internal Medicine and Psychiatry at the University of Manitoba, Canada. Interviews were guided by sample LORs and were focused on experiences with either writing or reading LORs. We analyzed interviews using key concepts from genre theory and Aristotle’s appeals to ethos, logos, and pathos. Results: Participants described how the practices surrounding LORs are guided by unwritten rules. These practices contributed to writers’ use of visible strategies and textual silence to establish credibility, build a strong case, and appeal to readers. Readers rely on similar strategies, but not always as intended by the writers. Conclusions: The unwritten rules of one academic community can impede a nationally-facilitated resident selection process. Our findings highlight how critiques and potential improvements to LORs could benefit from considering the use of visible and invisible rhetorical strategies in specific contexts.

Introduction Information systems for community health have become increasingly sophisticated and evidence-based in the last decade and they are now the most widely used health information systems in many low-income and middle-income countries. This study aimed to establish consensus regarding key features and interoperability priorities for community health information systems (CHISs).Methods A Delphi study was conducted among a systematically selected panel of CHIS experts. This impressive pool of experts represented a range of leading global health institutions, with gender and regional balance as well as diversity in their areas of expertise. Through five rounds of iterative surveys and follow-up interviews, the experts established a high degree of consensus. We supplemented the Delphi study findings with a series of focus group discussions with 10 community health worker (CHW) leaders.Results CHISs today are expected to adapt to a wide range of local contextual requirements and to support and improve care delivery. While once associated with a single role type (CHWs), these systems are now expected to engage other end users, including patients, supervisors, clinicians and data managers. Of 30 WHO-classified digital health interventions for care providers, experts identified 23 (77%) as being important for CHISs. Case management and care coordination features accounted for more than one-third (14 of 37, 38%) of the core features expected of CHISs today, a higher proportion than any other category. The highest priority use cases for interoperability include CHIS to health management information system monthly reporting and CHIS to electronic medical record referrals.Conclusion CHISs today are expected to be feature-rich, to support a range of user roles in community health systems, and to be highly adaptable to local contextual requirements. Future interoperability efforts, such as CHISs in general, are expected not only to move data efficiently but to strengthen community health systems in ways that measurably improve care.

BackgroundWhile ecological momentary assessment (EMA) is commonly used to study social contexts and social influence in the real world, EMA almost exclusively relies on participant self-report of present circumstances, including the proximity to influential peers. There is the potential for developing a proximity sensing approach that uses small Bluetooth beacons and smartphone-based detection and data collection to collect information about interactions between individuals passively in real time. ObjectiveThis paper aims to describe the methods for evaluating the functionality and validity of a Bluetooth-based beacon and a smartphone app to identify when ≥2 individuals are physically proximal. MethodsWe will recruit 20 participants aged 18 to 29 years with Android smartphones to complete a 3-week study during which beacon detection and self-report data will be collected using a smartphone app (MEI Research). Using an interviewer-administered social network interview, participants will identify up to 3 peers of the same age who are influential on health behavior (alcohol use in this study). These peers will be asked to carry a Bluetooth beacon (Kontakt asset tag) for the duration of the study; each beacon has a unique ID that, when detected, will be recorded by the app on the participant’s phone. Participants will be prompted to respond to EMA surveys (signal-contingent reports) when a peer beacon encounter meets our criteria and randomly 3 times daily (random reports) and every morning (morning reports) to collect information about the presence of peers. In all reports, the individualized list of peers will be presented to participants, followed by questions about peer and participant behavior, including alcohol use. Data from multiple app data sets, including beacon encounter specifications, notification, and app logs, participant EMA self-reports and postparticipation interviews, and peer surveys, will be used to evaluate project goals. We will examine the functionality of the technology, including the stability of the app (eg, app crashes and issues opening the app), beacon-to-app detection (ie, does the app detect proximal beacons?), and beacon encounter notification when encounter criteria are met. The validity of the technology will be defined as the concordance between passive detection of peers via beacon-to-app communication and the participant’s EMA report of peer presence. Disagreement between the beacon and self-report data (ie, false negatives and false positives) will be investigated in multiple ways (ie, to determine if the reason was technology-related or participant compliance-related) using encounter data and information collected from participants and peers. ResultsParticipant recruitment began in February 2023, and enrollment was completed in December 2023. Results will be reported in 2025. ConclusionsThis Bluetooth-based technology has important applications and clinical implications for various health behaviors, including the potential for just-in-time adaptive interventions that target high-risk behavior in real time. International Registered Report Identifier (IRRID)DERR1-10.2196/50241

BackgroundMigraine has an increased prevalence in several immune disorders, but genetic cause-effect relationships remain unclear. Mendelian randomization (MR) was used in this study to explore whether immune diseases are causally associated with migraine and its subtypes.MethodsWe conducted a two-sample bidirectional multivariate Mendelian randomization study. Single-nucleotide polymorphisms (SNP) for six immune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1D), allergic rhinitis (AR), asthma and psoriasis, were used as genetic instrumental variables. Summary statistics for migraine were obtained from 3 databases: the International Headache Genetics Consortium (IHGC), UK Biobank, and FinnGen study. MR analyses were performed per outcome database for each exposure and subsequently meta-analyzed. Reverse MR analysis was performed to determine whether migraine were risk factors for immune diseases. In addition, we conducted a genetic correlation to identify shared genetic variants for these two associations.ResultsNo significant causal relationship was found between immune diseases and migraine and its subtypes. These results were robust with a series of sensitivity analyses. Using the linkage disequilibrium score regression method (LDSC), we detected no genetic correlation between migraine and immune diseases.ConclusionThe evidence from our study does not support a causal relationship between immune diseases and migraine. The mechanisms underlying the frequent comorbidity of migraine and several immune diseases need to be further elucidated.

BackgroundBoth alcohol consumption and HIV infection are associated with worse brain, cognitive, and clinical outcomes in older adults. However, the extent to which brain and cognitive dysfunction is reversible with reduction or cessation of drinking is unknown. ObjectiveThe 30-Day Challenge study was designed to determine whether reduction or cessation of drinking would be associated with improvements in cognition, reduction of systemic and brain inflammation, and improvement in HIV-related outcomes in adults with heavy drinking. MethodsThe study design was a mechanistic experimental trial, in which all participants received an alcohol reduction intervention followed by repeated assessments of behavioral and clinical outcomes. Persons were eligible if they were 45 years of age or older, had weekly alcohol consumption of 21 or more drinks (men) or 14 or more drinks (women), and were not at high risk of alcohol withdrawal. After a baseline assessment, participants received an intervention consisting of contingency management (money for nondrinking days) for at least 30 days followed by a brief motivational interview. After this, participants could either resume drinking or not. Study questionnaires, neurocognitive assessments, neuroimaging, and blood, urine, and stool samples were collected at baseline, 30 days, 90 days, and 1 year after enrollment. ResultsWe enrolled 57 persons with heavy drinking who initiated the contingency management protocol (mean age 56 years, SD 4.6 years; 63%, n=36 male, 77%, n=44 Black, and 58%, n=33 people with HIV) of whom 50 completed 30-day follow-up and 43 the 90-day follow-up. The planned study procedures were interrupted and modified due to the COVID-19 pandemic of 2020-2021. ConclusionsThis was the first study seeking to assess changes in brain (neuroimaging) and cognition after alcohol intervention in nontreatment-seeking people with HIV together with people without HIV as controls. Study design strengths, limitations, and lessons for future study design considerations are discussed. Planned analyses are in progress, after which deidentified study data will be available for sharing. Trial RegistrationClinicalTrials.gov NCT03353701; https://clinicaltrials.gov/study/NCT03353701 International Registered Report Identifier (IRRID)DERR1-10.2196/53684

Avascular necrosis of the femoral head is a debilitating condition that can lead to femoral head collapse. Core decompression with adjuvant cellular therapies, such as bone marrow aspirate concentrate, delays disease progression and improves outcomes. However, inconsistent results in the literature may be due to limitations in surgical technique and difficulty in targeting the necrotic lesions. Here, we present a surgical technique utilizing computed tomography-based three-dimensional modeling and instrument tracking to guide the therapy to the center of the lesion. This method minimizes the number of attempts to reach the lesion and confirms the three-dimensional positioning of the instrumentation within the lesion. Our technique may improve the outcomes of core decompression and adjuvant therapy and prevent or delay hip collapse in patients with femoral head avascular necrosis.

A síndrome de Turner (ST) ocorre em 1 a cada 2.000-4.000 meninas e pode afetar múltiplos órgãos ao longo de todos os estágios da vida, necessitando de cuidados multidisciplinares. Este protocolo de condutas na ST foi elaborado com base no Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting e no Turner syndrome: mechanisms and management, como sugestão a ser aprovada para uso no complexo do Hospital Universitário Walter Cantídio - HUWC. O protocolo descreve as manifestações clínicas da síndrome, os critérios para suspeição e indicação da análise cromossômica, os rastreios necessários no momento do diagnóstico e ao longo da vida e as recomendações para uso do hormônio de crescimento (GH) e para a terapia de reposição hormonal (TRH) nos casos confirmados.

La agroecología, como campo de aplicación multidisciplinar, se sustenta teórica y metodológicamente en varias disciplinas, pero su fundamento central es el conocimiento tradicional, el cual retoma principios ecológicos, sociales y económicos de las comunidades para favorecer los agroecosistemas y sus diversas formas de regulación. En el presente artículo se describen tres perspectivas de la agroecología, producto del análisis bibliométrico realizado por los autores, y que permite vislumbrar elementos a considerar en la enseñanza de las ciencias naturales, especialmente desde la escuela rural, con el fin de sugerir algunas posibilidades investigativas, pedagógicas y didácticas para su abordaje. La agroecología abre nuevas opciones de estudio e investigación en la escuela rural, concebida ésta como centro de convergencia cultural, está cobrando interés global, articulándose con procesos sociales y políticas públicas de numerosos países del mundo, con el fin de rescatar, visibilizar y valorar la sabiduría local como medio para proponer vías encaminadas para promover, entre otras cosas, la soberanía alimentaria, el cuidado del ambiente y la resiliencia de los agroecosistemas, de acuerdo con contextos históricos y geográficos específicos de las comunidades; para ello es esencial articular conocimientos, intereses, necesidades y saberes culturales ancestrales, tradicionales y locales desde la escuela rural.

Exogenous enzymes as alternatives to feed antibiotics in poultry has become an emerging research area with the emergence of antibiotic resistance. The objective was to evaluate the effects of diet medication (antibiotics) and β-glucanase (BGase) on digesta soluble β-glucan depolymerization, carbohydrate fermentation, and performance of coccidiosis-vaccinated broiler chickens fed wheat-based diets. A total of 1,782 broilers were raised on litter floor pens, and each treatment was assigned to 1 pen in each of the 9 rooms. The 3 dietary treatments were based on wheat as the sole grain (control, control + medication and control + 0.1% BGase), and the birds were fed the respective treatments ad libitum from 0 to 33 d. Treatments were arranged in a randomized complete block design and analyzed as a one-way ANOVA. Beta-glucanase reduced the peak molecular weight, weight average molecular weight (Mw) and maximum molecular weight for the smallest 10% β-glucan molecules (MW-10%) in ileal digesta at d 11 and 33, whereas diet medication reduced Mw and MW-10% at d 33 compared to the control (P

Purpose: Obtaining prior authorization (PA) before treatment is becoming increasingly burdensome in oncology, especially in radiation oncology. Here, we describe the impact of a strategic novel operational PA redesign to shorten authorization time and to improve patient access to cancer care at a large United States academic proton therapy center. We ask whether such a redesign may be replicable and adoptable across oncology centers. Materials and Methods: Our PA redesign strategy was based on a 3-tiered approach. Specifically, we (1) held payors accountable to legally backed timelines, (2) leveraged expertise on insurance policies and practices, and (3) updated the submission, appeal writing, and planning procedures for PA. Metrics were compared at the following 3 time points: 6 months before, at phase-in, and at 6 months after intervention. Results: In analyzing the impact of improving PA access to care, the percentage of approvals for commercial proton beam therapy improved by an absolute 30.6% postintervention (P < .001). The proportion of commercially insured patients treated with proton beam therapy also increased by 6.2%, and the number of new starts rose by 11.7 patients/mo. Overall patient census increased by 13 patients/d. Median authorization time was 1 week, and 90% of surveyed providers reported reduced PA burden and improved patient care. Conclusion: This is the first validated, comprehensive operational strategy to improve access to cancer therapy while reducing the burden of PA. This novel approach may be helpful for addressing barriers to PA in medical and surgical oncology because the redesign is predicated on laws that regulate PA across disciplines.

Abstract Production of secondary metabolites is controlled by a complicated regulatory network in eukaryotic cells. Several layers of regulators are involved in this process, ranging from pathway-specific regulation, to epigenetic control, to global regulation. Here, we discover that interaction of an RNA-binding protein CsdA with a regulator RsdA coordinates fungal secondary metabolism. Employing a genetic deletion approach and transcriptome analysis as well as metabolomics analysis, we reveal that CsdA and RsdA synergistically regulate fungal secondary metabolism comprehensively. Mechanistically, comprehensive genetic and biochemical studies prove that RsdA and CsdA co-localize in the nucleus and physically interact to achieve their functions. In particular, we demonstrate that CsdA mediates rsdA expression by binding specific motif “GUCGGUAU” of its pre-mRNA at a post-transcriptional level. We thus uncover a mechanism in which RNA-binding protein physically interacts with, and controls the expression level of, the RsdA to coordinate fungal secondary metabolism.

Purpose: Male breast cancer treatment involves multimodality therapy, including radiation therapy; nevertheless, few men have received proton therapy (PT) for it. Further, heart disease is an established leading cause of death in men, and radiation therapy heart dose correlates with cardiac toxicity, highlighting the need for cardiac-sparing radiation techniques. Thus, we provide a descriptive analysis of PT in a male breast cancer cohort. Patients and Methods: Men who received PT for localized breast cancer between 2012 and 2022 were identified from a prospective database. Toxicities were prospectively recorded by using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Results: Five male patients were identified. All had estrogen receptor (ER)–positive, Her2neu-negative disease and received adjuvant endocrine therapy. One had genetic testing positive for BRCA2, one had a variant of unknown significance (VUS) in the APC gene, and one had a VUS in MSH2. Median age was 73 years (range, 41–80). Baseline comorbidities included obesity (n = 1), diabetes (n = 1), hypertension (n = 4), history of deep vein thrombosis (n = 1), personal history of myocardial infarction (n = 3; 1 with a pacemaker), and a history of lung cancer (n = 1). All received PT to the left chest wall and comprehensive regional lymphatics. One received passive-scattering PT, and 4 received pencil beam scanning. One patient received a boost to the mastectomy incision via electrons. Median heart dose was 1 GyRBE (range, 0–1.0), median 0.1-cm3 dose to the left anterior descending artery was 7.5 GyRBE (range, 0–14.2), and median follow-up was 2 years (range, 0.75–6.5); no patient experienced a new cardiac event, and all remain free from breast cancer recurrence and progression. Conclusion: In a small case series for a rare diagnosis, PT to the chest wall and regional lymphatics, including internal mammary nodes, resulted in low cardiac exposure, high local regional disease control rates, and minimal toxicity. Proton therapy should be considered for treating men with breast cancer to achieve cardiac sparing.

Abstract Background In this evaluation, we aim to strengthen Routine Health Information Systems (RHIS) through the digitization of data quality assessment (DQA) processes. We leverage electronic data from the Kenya Health Information System (KHIS) which is based on the District Health Information System version 2 (DHIS2) to perform DQAs at scale. We provide a systematic guide to developing composite data quality scores and use these scores to assess data quality in Kenya. Methods We evaluated 187 HIV care facilities with electronic medical records across Kenya. Using quarterly, longitudinal KHIS data from January 2011 to June 2018 (total N = 30 quarters), we extracted indicators encompassing general HIV services including services to prevent mother-to-child transmission (PMTCT). We assessed the accuracy (the extent to which data were correct and free of error) of these data using three data-driven composite scores: 1) completeness score; 2) consistency score; and 3) discrepancy score. Completeness refers to the presence of the appropriate amount of data. Consistency refers to uniformity of data across multiple indicators. Discrepancy (measured on a Z-scale) refers to the degree of alignment (or lack thereof) of data with rules that defined the possible valid values for the data. Results A total of 5,610 unique facility-quarters were extracted from KHIS. The mean completeness score was 61.1% [standard deviation (SD) = 27%]. The mean consistency score was 80% (SD = 16.4%). The mean discrepancy score was 0.07 (SD = 0.22). A strong and positive correlation was identified between the consistency score and discrepancy score (correlation coefficient = 0.77), whereas the correlation of either score with the completeness score was low with a correlation coefficient of -0.12 (with consistency score) and -0.36 (with discrepancy score). General HIV indicators were more complete, but less consistent, and less plausible than PMTCT indicators. Conclusion We observed a lack of correlation between the completeness score and the other two scores. As such, for a holistic DQA, completeness assessment should be paired with the measurement of either consistency or discrepancy to reflect distinct dimensions of data quality. Given the complexity of the discrepancy score, we recommend the simpler consistency score, since they were highly correlated. Routine use of composite scores on KHIS data could enhance efficiencies in DQA at scale as digitization of health information expands and could be applied to other health sectors beyondHIV clinics.

IntroductionSuicide and suicide clusters within Native American Reservation communities are devastating to the entire community and increase individuals’ risk for suicide over the lifespan. The objective of this paper is to describe the Indigenous community-based participatory research protocol implemented in partnership with the Fort Belknap Indian Community in Montana, United States. The study protocol was developed to understand suicide risk and protective factors, and community-derived solutions, in a reservation community with history of a suicide cluster and high rates of youth suicide.MethodsIn this mixed-methods study, qualitative data from youth, adults, and service providers and quantitative data from 200 adolescents and young adults (aged 14–24 years) were collected in Fort Belknap, Montana from May – December of 2022. Qualitative data were collected first via in-depth interviews and focus groups. Survey questions included validated and pre-tested measures of factors youth experience across socio-ecological levels. Thematic analysis was applied to the qualitative data; and logistic regression models were used to examine relationships within the quantitative data.DiscussionThis study will add a multi-dimensional perspective to our current understanding of (1) risk and protective factors for suicide, community-derived postvention solutions, and insights on community assets, and (2) the current health and psychosocial status of youth in the Fort Belknap community. This study may serve as an exemplar of co-created, culturally safe solutions designed to address mental health resource gaps. Next steps include development of a suicide crisis response tool kit and a culturally aligned postvention intervention that will enhance individual, family, and community survivance.

Abstract Monitoring subnational healthcare quality is important for identifying and addressing geographic inequities. Yet, health facility surveys are rarely powered to support the generation of estimates at more local levels. With this study, we propose an analytical approach for estimating both temporal and subnational patterns of healthcare quality indicators from health facility survey data. This method uses random effects to account for differences between survey instruments; space-time processes to leverage correlations in space and time; and covariates to incorporate auxiliary information. We applied this method for three countries in which at least four health facility surveys had been conducted since 1999 – Kenya, Senegal, and Tanzania – and estimated measures of sick-child care quality per WHO Service Availability and Readiness Assessment (SARA) guidelines at programmatic subnational level, between 1999 and 2020. Model performance metrics indicated good out-of-sample predictive validity, illustrating the potential utility of geospatial statistical models for health facility data. This method offers a way to jointly estimate indicators of healthcare quality over space and time, which could then provide insights to decision-makers and health service program managers.