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Shortly after the first case of SARS-CoV-2 was diagnosed a public health emergency (PHE) was declared and a multi-agency response was initiated within the US federal government to create and propagate testing capacity. As part of this response, an unprecedented program designated Rapid Acceleration of Diagnostics (RADx) Tech was established by the National Institutes of Health (NIH) to facilitate the development of point-of-care tests for the COVID-19. The RADx Tech Clinical Studies Core (CSC), located at the University of Massachusetts Chan Medical School (UMass Chan), with partnering academic, private, and non-governmental organizations around the country, was tasked with developing clinical studies to support this work. This manuscript details development of a biorepository specifically focused on the collection and storage of samples designed for diagnostic platform development. It highlights the unified collection and annotation process that enabled gathering a diverse set of samples. This diversity encompasses the geography and backgrounds of the participants as well as sample characteristics such as variant type and RT-PCR cycle threshold (CT) value of the corresponding reference sample on a uniform clinical reference platform., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the UMass Chan Institutional Review Board reference number [H00022475]. Informed consent for participation was obtained from all participants. In the case of pediatric participants, informed consent was obtained from the parent or legal guardian as well as assent from the child. Clinical trial number: not applicable. Consent for publication Not applicable. Competing interests The views expressed in this article are those of the authors and do not necessarily represent the views of the National Institute of Biomedical Imaging and Bioengineering; the National Heart, Lung, and Blood Institute; the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services., (© 2024. The Author(s).)

Maize is the most grown feed crop in the United States. Due to wind storms and other factors, 5% of maize falls over annually. The longitudinal shear modulus of maize stalk tissues is currently unreported and may have a significant influence on stalk failure. To better understand the causes of this phenomenon, maize stalk material properties need to be measured so that they can be used as material constants in computational models that provide detailed analysis of maize stalk failure. This study reports longitudinal shear modulus of maize stalk tissue through repeated torsion testing of dry and fully mature maize stalks. Measurements were focused on the two tissues found in maize stalks: the hard outer rind and the soft inner pith. Uncertainty analysis and comparison of multiple methodologies indicated that all measurements are subject to low error and bias. The results of this study will allow researchers to better understand maize stalk failure modes through computational modeling. This will allow researchers to prevent annual maize loss through later studies. This study also provides a methodology that could be used or adapted in the measurement of tissues from other plants such as sorghum, sugarcane, etc., (© 2024. The Author(s).)

Background: The experiences of GPs in Australia highlight key considerations regarding workload demands, remuneration incentives and the practical implications of working in regions with high ethnic density. This exploration helps to understand the elements that influence GPs delivery of care, particular for refugee women who exhibit disproportionately higher rates of chronic pain. This qualitative study explored the experiences of GPs providing care for refugee women living with chronic pain., Methods: Semi-structured interviews were undertaken with 10 GPs (9 female and 1 male) practicing across metropolitan Melbourne, Australia. GPs were recruited via purposive sampling and a snowballing strategy. Participants work experience ranged from one to 32 years. Audio recordings of the interviews were transcribed verbatim and stored in qualitative data Nvivo 12 software for coding. Transcripts of interviews were analysed thematically using a phenomenological approach., Results: Three overarching themes were identified: (1) meeting the needs of refugee women living with chronic pain; (2) the role of the GP; and (3) the challenges of the health care system. These themes reflected the complexity of consultations which arose, in part, from factors such as trust, the competencies of clinician's and the limitations posed by time, funding and interpreter use., Conclusion: GPs acknowledged the uniqueness of refugee women's chronic pain needs and whilst doctors welcomed care, many were often challenged by the complex nature of consultations. Those that worked in settings that aligned with refugee women's needs highlighted the importance of cultivating culturally safe clinical environments and listening to their patients' stories. However, system level challenges such as time, funding and resource constraints created significant challenges for GPs. Exploring GPs experiences allows for a better understanding of how vectors of disadvantage intersect in health care and highlights the need to better support doctors to improve health care provision for refugee women living with chronic pain., (© 2024. The Author(s).)

Objectives: This study aims to compare the efficacy of remote versus in-person training strategies to teach ultrasound guided knee arthrocentesis using formalin embalmed cadavers., Methods: 30 first-year medical student participants were randomly assigned to remote or in-person training groups. Pre- and post- training surveys were used to evaluate participant's self-confidence in their ability to perform the procedure. Participants were asked to watch a 30-minute training video and then attend a skills training workshop. The workshops consisted of 20 min of hands-on instruction followed by a skills assessment., Results: Following training, participant self-confidence increased significantly across all survey items in both groups (p = 0.0001). No significant changes in participant self-confidence were detected between the groups. Skills and knowledge-related metrics did not differ significantly between the groups with the exception of the "knowledge of instruments" variable., Conclusions: Our data suggests that remote ultrasound-guided procedure training, although logistically complex, is a viable alternative to traditional in-person learning techniques even for a notoriously hands on skill like ultrasound guided knee arthrocentesis. Novice first-year medical student operators in the remote-training group were able to significantly increase their confidence and demonstrate competency in a manner statistically indistinguishable from those trained in-person. These results support the pedagogical validity of using remote training to teach ultrasound guided procedures which could have implications in rural and global health initiatives where educational resources are more limited., (© 2024. The Author(s).)

Background: Although natural rubber latex remains dominant as the primary manufacturing material for male condoms synthetic materials first introduced in the early 1990s address many of the limitations of latex including the risk of allergies. Polyurethane elastomers allow condoms to be made significantly thinner to provide greater sensitivity and encourage greater use of condoms for contraception and STI prophylaxis. The primary objective of this Study was to evaluate the breakage, slippage and acceptability of two ultra-thin polyurethane condoms against a thin control latex male condom, designated latex C, in a randomized, cross over, masked, non-inferiority study. The condom designated Polyurethane A was designed for markets where 52/53 mm wide latex condoms are preferred whereas the condom designated Polyurethane B was designed for markets where the smaller 49 mm wide latex condom is preferred., Methods: The Study was designed to meet the requirements specified in ISO 29943-1: 2017 and FDA guidelines for clinical studies on synthetic condoms. It was conducted by two Essential Access Health centres, one in Northern California and the other in Southern California. Sexually active heterosexual couples (300) aged between 18 and 45 years were recruited to use three sets of five condoms in a block randomized order, recording breakage, slippage and acceptability after each use. A total of 252 couples contributed 2405 evaluable condom uses per protocol for the Condom A versus Latex C comparison (1193 Polyurethane A plus 1212 Latex C), and 247 couples provided 2335 evaluable condom uses per protocol for the Condom B versus Latex C comparison (1142 Polyurethane B plus 1193 Latex C). Only condoms used for vaginal intercourse were included in the analysis., Findings: Although the total failure rates (breakage and slippage) for the polyurethane condoms were higher than for the control Latex C condom, all condoms performed extremely well with low failure rates compared to similar condom studies. Condom Polyurethane A met the noninferiority requirements specified in ISO 23409:2011 relative to Latex C, the control NR latex condom, in the full Study population. While condom Polyurethane B did not meet the noninferiority requirement for the full Study population, it did meet the noninferiority requirement when analysis was restricted to the intended population (men with penis lengths ≤ 170 mm). Trial registration The Study is registered with ClinicalTrials.gov, NCT04622306, Protocol Reference SAGCS 2, initial release date 11/02/2020., (© 2024. The Author(s).)

Background: Tuberculosis (TB), a major cause of disease and antimicrobial resistance, is spread via aerosols. Aerosols have diagnostic potential and airborne-microbes other than Mycobacterium tuberculosis complex (MTBC) may influence transmission. We evaluated whether PneumoniaCheck (PMC), a commercial aerosol collection device, captures MTBC and the aeromicrobiome of people with TB., Methods: PMC was done in sputum culture-positive people (≥ 30 forced coughs each, n = 16) pre-treatment and PMC air reservoir (bag, corresponding to upper airways) and filter (lower airways) washes underwent Xpert MTB/RIF Ultra (Ultra) and 16S rRNA gene sequencing (sequencing also done on sputum). In a subset (n = 6), PMC microbiota (bag, filter) was compared to oral washes and bronchoalveolar lavage fluid (BALF)., Findings: 54% (7/13) bags and 46% (6/14) filters were Ultra-positive. Sequencing read counts and microbial diversity did not differ across bags, filters, and sputum. However, microbial composition in bags (Sphingobium-, Corynebacterium-, Novosphingobium-enriched) and filters (Mycobacterium-, Sphingobium-, Corynebacterium-enriched) each differed vs. sputum. Furthermore, sequencing only detected Mycobacterium in bags and filters but not sputum. In the subset, bag and filter microbial diversity did not differ vs. oral washes or BALF but microbial composition differed. Bags vs. BALF were Sphingobium-enriched and Mycobacterium-, Streptococcus-, and Anaerosinus-depleted (Anaerosinus also depleted in filters vs. BALF). Compared to BALF, none of the aerosol-enriched taxa were enriched in oral washes or sputum., Interpretation: PMC captures aerosols with Ultra-detectable MTBC and MTBC is more detectable in aerosols than sputum by sequencing. The aeromicrobiome is distinct from sputum, oral washes and BALF and contains differentially-enriched lower respiratory tract microbes., (© 2024. The Author(s).)

Background: In Australia, university clinical programs rely heavily on external healthcare professionals to provide a range of authentic clinical training and professional development opportunities for students. There is, however, a limited understanding of the factors that motivate these professionals to be educators and whether this varies across different healthcare disciplines within Australia. As the demand for clinical placements continues to increase, it is critical for the ongoing success of these programs that universities identify both the barriers associated with teaching and the benefits that enhance job satisfaction., Methods: A two-part questionnaire was emailed to 849 external healthcare educators teaching predominantly in Medicine, Medical Imaging, and Optometry programs at Deakin University. Part-one surveyed the socio-demographics, perceived benefits, and barriers to teaching, plus the utilisation of entitlements offered by the university. Part-two was modelled on Dybowski and Harendza's validated Physician Teaching Motivation Questionnaire (PTMQ) and adapted to an Australian audience., Results: Overall, 776 out of the 849 questionnaires were considered in the final participant pool. The response rate for part-one was 19.7% (n = 153/776) and 18.3% (n = 142/776) for part-two. Across all professions, altruism was the primary source of motivation for teaching in Deakin University's healthcare programs. Medical Imaging educators placed a higher value on career-related teaching aspects compared to those in Medicine and Optometry (p < 0.003). The resources and benefits associated with teaching were generally perceived to be of minimal importance. External healthcare educators most commonly reported that there were no barriers to teaching (41.3%, n = 78) however, increased workloads and time constraints were the next most likely factors to affect teaching participation (31.8%, n = 60)., Conclusion: Our validated adaptation of the PTMQ successfully targeted healthcare professions not focussed on by Dybowski and Harendza. Altruistic motivation was the overarching theme for why Australian external healthcare educators contribute to teaching with some differences in career-driven motivation additionally acknowledged. Despite there being no key benefits or barriers to teaching participation, universities must remain cognisant of the factors that influence the recruitment and retention of external healthcare educators and how to optimise these for the ongoing success and sustainability of their teaching programs., (© 2024. The Author(s).)

Background: Implementation of the World Health Organization (WHO) recommended Advanced HIV Disease screening package, remains poor in most settings with limited resources. More than 50% of newly diagnosed-HIV clients are missed on screening as a result of implementation barriers. It is important to mitigate the existing barriers and leverage enablers' inorder to maximize uptake of the advanced HIV disease screening. This study aimed to identify strategies for scaling up implementation of advanced HIV disease screening among newly HIV-diagnosed clients in pre-ART phase using a Consolidated Framework for Implementation Research-Expert Recommendation for Implementing Change (CFIR-ERIC) guiding tool., Methods: A qualitative study was conducted at Rumphi district hospital in Malawi (August - September, 2023). Two sessions of Focus group discussions (FDGs) involving key stakeholders were facilitated to identify specific strategies following the initial study on exploration of barriers and facilitators of advanced HIV disease screening package. Participants comprised healthcare providers, purposively selected from key hospital departments. A deductive approach was used to analyze FDG transcripts where emerging themes were mapped with ERIC list of strategies. CFIR-ERIC Matching tool version 1.0, was used to generate an output of the most to least expert-endorsed Level 1 and Level 2 strategies., Findings: About 25 key healthcare workers participated in FDGs. Overall, 6 Level 1 strategies (≥ 50% expert endorsement score) and 4 Level 2 strategies (≥ 20%, ≤ 49% expert endorsement score) were identified, targeting barriers associated with availability of resources, intervention complexity, access to knowledge and information, communication; and implementation leads. Most of the reported strategies were cross-cutting and aimed at enhancing clinical knowledge of the intervention (distributing training materials, educational meetings), developing stakeholders' interrelations (network weaving) as well as improving clinical workflow (environmental restructuring). Use of evaluative and iterative strategies such as monthly data collection for evaluation were also recommended as part of continuous improvement while an AHD coordinator was recommended to be formally appointed inorder to spearhead coordination of AHD screening services., Conclusion: Through the involvement of key stakeholders and the use of CFIR-ERIC matching tool, this study has identified cross-cutting strategies that if well implemented, can help to mitigate contextual barriers and leverage enablers for an improved delivery of AHD screening package., (© 2024. The Author(s).)

Background: Stroke affects long-term physical and cognitive function; many survivors report unmet health needs, such as pain or depression. A hospital-led follow-up service designed to address ongoing health problems may avoid unplanned readmissions and improve quality of life., Methods: This paper outlines the protocol for a registry-based, randomised controlled trial with allocation concealment of participants and outcome assessors. Based on an intention-to-treat analysis, we will evaluate the feasibility, acceptability, potential effectiveness and cost implications of a new tailored, codesigned, hospital-led follow-up service for people within 6-12 months of stroke. Participants (n = 100) from the Australian Stroke Clinical Registry who report extreme health problems on the EuroQol EQ-5D-3L survey between 90 and 180 days after stroke will be randomly assigned (1:1) to intervention (follow-up service) or control (usual care) groups. All participants will be independently assessed at baseline and 12-14-week post-randomisation. Primary outcomes for feasibility are the proportion of participants completing the trial and for intervention participants the proportion that received follow-up services. Acceptability is satisfaction of clinicians and participants involved in the intervention. Secondary outcomes include effectiveness: change in extreme health problems (EQ-5D-3L), unmet needs (Longer-term Unmet Needs questionnaire), unplanned presentations and hospital readmission, functional independence (modified Rankin Scale) and cost implications estimated from self-reported health service utilisation and productivity (e.g. workforce participation). To inform future research or implementation, the design contains a process evaluation including clinical protocol fidelity and an economic evaluation., Discussion: The results of this study will provide improved knowledge of service design and implementation barriers and facilitators and associated costs and resource implications to inform a future fully powered effectiveness trial of the intervention., Trial Registration: ACTRN12622001015730pr., Trial Sponsor: Florey Institute of Neuroscience and Mental Health, 245 Burgundy Street, Heidelberg, VIC, 3084, PH: +61 3 9035 7032., (© 2024. The Author(s).)

Background: Retained surgical items (RSI) are preventable events that pose a significant risk to patient safety. Current strategies for preventing RSIs rely heavily on manual instrument counting methods, which are prone to human error. This study evaluates the feasibility and performance of a deep learning-based computer vision model for automated surgical tool detection and counting., Methods: A novel dataset of 1,004 images containing 13,213 surgical tools across 11 categories was developed. The dataset was split into training, validation, and test sets at a 60:20:20 ratio. An artificial intelligence (AI) model was trained on the dataset, and the model's performance was evaluated using standard object detection metrics, including precision and recall. To simulate a real-world surgical setting, model performance was also evaluated in a dynamic surgical video of instruments being moved in real-time., Results: The model demonstrated high precision (98.5%) and recall (99.9%) in distinguishing surgical tools from the background. It also exhibited excellent performance in differentiating between various surgical tools, with precision ranging from 94.0 to 100% and recall ranging from 97.1 to 100% across 11 tool categories. The model maintained strong performance on a subset of test images containing overlapping tools (precision range: 89.6-100%, and recall range 97.2-98.2%). In a real-time surgical video analysis, the model maintained a correct surgical tool count in all non-transition frames, with a median inference speed of 40.4 frames per second (interquartile range: 4.9)., Conclusion: This study demonstrates that using a deep learning-based computer vision model for automated surgical tool detection and counting is feasible. The model's high precision and real-time inference capabilities highlight its potential to serve as an AI safeguard to potentially improve patient safety and reduce manual burden on surgical staff. Further validation in clinical settings is warranted., (© 2024. The Author(s).)

Background: Evaluations of continuing professional development programs typically focus on short-term knowledge and skill acquisition. There is a need for more comprehensive program evaluation methods that assess a broader range of impacts and can elicit how and why these outcomes occurred. We conducted a qualitative study to investigate the impacts of a multidisciplinary, online health professional postgraduate degree and to gain insights into the factors that led to these impacts., Methods: Participants were graduates of the University of Melbourne's Master of Cancer Sciences who could participate in an online interview. Semi-structured, qualitative interviews were conducted exploring a broad range of impacts, including changes in professional practice and career trajectory since graduation, and how the degree influenced these impacts. Data were analysed inductively., Results: Fifteen participants (female: 80%, 31-50 years old: 67%) from a range of professions were interviewed. A number of major themes were uncovered. Impacts on career trajectory included expanded career horizons (e.g. increased role diversity and complexity), and increased confidence in their professional identity. Impacts on professional practice included individual improvements in patient care and research, as well as changes in organisational practice. Factors identified as leading to these impacts were: (i) active, interactive and interprofessional learning; (ii) networking, informal mentoring, and role-modelling; and (iii) support at multiple levels., Conclusion: This study provides preliminary evidence of the positive impact of a Master of Cancer Sciences on graduate career trajectory and professional practice. In addition, the inductive methodology enabled identification of the curricular features (both planned and emergent) that influenced these impacts, facilitating potential transferability of learnings to other teaching programs., (© 2024. The Author(s).)

Background: Well-built housing limits mosquito entry and can reduce malaria transmission. The association between community-level housing and malaria burden in Uganda was assessed using data from randomly selected households near 64 health facilities in 32 districts., Methods: Houses were classified as 'improved' (synthetic walls and roofs, eaves closed or absent) or 'less-improved' (all other construction). Associations between housing and parasitaemia were made using mixed effects logistic regression (individual-level) and multivariable fractional response logistic regression (community-level), and between housing and malaria incidence using multivariable Poisson regression., Results: Between November 2021 and March 2022, 4.893 children aged 2-10 years were enrolled from 3.518 houses; of these, 1.389 (39.5%) were classified as improved. Children living in improved houses had 58% lower odds (adjusted odds ratio = 0.42, 95% CI 0.33-0.53, p < 0.0001) of parasitaemia than children living in less-improved houses. Communities with > 67% of houses improved had a 63% lower parasite prevalence (adjusted prevalence ratio 0.37, 95% CI 0.19-0.70, p < 0.0021) and 60% lower malaria incidence (adjusted incidence rate ratio 0.40, 95% CI 0.36-0.44, p < 0.0001) compared to communities with < 39% of houses improved., Conclusions: Improved housing was strongly associated with lower malaria burden across a range of settings in Uganda and should be utilized for malaria control., (© 2024. The Author(s).)

Microtubule targeting agents (MTAs) are commonly prescribed to treat cancers and predominantly kill cancer cells in mitosis. Significantly, some MTA-treated cancer cells escape death in mitosis, exit mitosis and become malignant polyploid giant cancer cells (PGCC). Considering the low number of cancer cells undergoing mitosis in tumor tissues, killing them in interphase may represent a favored antitumor approach. We discovered that ST-401, a mild inhibitor of microtubule (MT) assembly, preferentially kills cancer cells in interphase as opposed to mitosis, a cell death mechanism that avoids the development of PGCC. Single cell RNA sequencing identified mRNA transcripts regulated by ST-401, including mRNAs involved in ribosome and mitochondrial functions. Accordingly, ST-401 induces a transient integrated stress response, reduces energy metabolism, and promotes mitochondria fission. This cell response may underly death in interphase and avoid the development of PGCC. Considering that ST-401 is a brain-penetrant MTA, we validated these results in glioblastoma cell lines and found that ST-401 also reduces energy metabolism and promotes mitochondria fission in GBM sensitive lines. Thus, brain-penetrant mild inhibitors of MT assembly, such as ST-401, that induce death in interphase through a previously unanticipated antitumor mechanism represent a potentially transformative new class of therapeutics for the treatment of GBM., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has profoundly impacted individuals, society, and healthcare organisations worldwide. Recent international research suggests that concerns, needs, and experiences of healthcare workers (HCWs) have evolved throughout the pandemic. This longitudinal qualitative study explored the evolving views and experiences of Victorian healthcare workers (HCWs) and organisational key personnel during the coronavirus disease (COVID-19) pandemic., Methods: We recruited participants from the Coronavirus in Victorian Health and Aged care workers (COVIC-HA) study cohort. We conducted two rounds of semi-structured interviews with HCWs and organisational key personnel from three different healthcare settings (hospital, aged care and primary care) in Victoria, Australia, in May-July 2021 and May-July 2022. Data were analysed thematically using trajectory and recurrent cross-sectional approaches, guided by a temporal change framework., Results: Twelve HCWs and five key personnel from various professional roles participated in interviews at both timepoints. Expected themes derived from mid-2021 interviews (navigating uncertainty, maintaining service delivery, and addressing staff needs) evolved over time. Concerns shifted from personal health and safety to workforce pressures, contributing to HCW burnout and fatigue and ongoing mental health support needs. New themes emerged from mid-2022 interviews, including managing ongoing COVID-19 impacts and supporting the healthcare workforce into the future. Clear and consistent communication, stable guidelines and forward-looking organisational responses were considered crucial., Conclusions: Our longitudinal qualitative study highlighted the evolving impact of the COVID-19 pandemic on HCWs' perceptions, health and wellbeing and uncovered long-term sector vulnerabilities. Analysing HCW experiences and key personnel insights over time and across different pandemic phases provided crucial insights for policymakers to protect the healthcare workforce. Findings emphasise the need for proactive strategies that prioritise HCWs' wellbeing and workforce sustainability. Policy makers must invest in HCW health and wellbeing initiatives alongside healthcare system improvements to ensure resilience and capacity to meet future challenges., Trial Registration: This study was approved through the Victorian Streamlined Ethical Review Process (SERP: Project Number 68,086) and registered with ANZCTR (ACTRN12621000533897) on 6 May 2021., (© 2024. The Author(s).)

Objectives: To predict the dental caries outcomes in young adults from a set of longitudinally-obtained predictor variables and identify the most important predictors using machine learning techniques., Methods: This study was conducted using the Iowa Fluoride Study dataset. The predictor variables - sex, mother's education, family income, composite socio-economic status (SES), caries experience at ages 9, 13, and 17, and the cumulative estimates of risk and protective factors, including fluoride, dietary, and behavioral variables from ages 5-9, 9-13, 13-17, and 17-23 were used to predict the age 23 D 2+ MFS count. The following machine learning models (LASSO regression, generalized boosting machines (GBM), negative binomial (NegGLM), and extreme gradient boosting models (XGBOOST)) were compared under 5-fold cross validation with nested resampling techniques., Results: The prevalence of cavitated level caries experience at age 23 (mean D 2+ MFS count) was 4.75. The predictive analysis found LASSO to be the best performing model (compared to GBM, NegGLM, and XGBOOST), with a root mean square error (RMSE) of 0.70, and coefficient of determination (R 2 ) of 0.44. After dichotomization of the predicted and observed values of the LASSO regression, the classification results showed accuracy, precision, recall, and ROC AUC of 83.7%, 85.9%, 93.1%, 68.2%, respectively. Previous caries experience at age 13 and age 17 and sugar-sweetened beverages intakes at age 13 and age 17 were found to be the four most important predictors of cavitated caries count at age 23., Conclusion: Our machine learning model showed high accuracy and precision in the prediction of caries in young adults from a longitudinally-obtained predictor variables. Our model could, in the future, after further development and validation with other diverse population data, be used by public health specialists and policy-makers as a screening tool to identify the risk of caries in young adults and apply more targeted interventions. However, data from a more diverse population are needed to improve the quality and generalizability of caries prediction., (© 2024. The Author(s).)

We conducted secondary data analysis using a biobehavioral survey dataset of 1538 MSM from Zimbabwe. Survey participants were screened for the four symptoms suggestive of tuberculosis infection using the WHO TB screening algorithm. Results: All participants experienced at least one symptom suggestive of tuberculosis. 40% of HIV-positive MSM reported having had a cough in the last month and 13% of them experienced unexpected weight loss. The prevalence of experiencing any of the four TB symptoms amongst HIV-positive MSM was 23%. Contribution There is an urgent need for active TB case finding and treatment amongst HIV-positive MSM in Zimbabwe. Clinicians will need to ensure that MSM who need TB testing receive it timeously., (© 2024. The Author(s).)

Background: Stenotrophomonas maltophilia is a gram-negative bacteria known for causing opportunistic and nosocomial infections in humans. S. maltophilia is an emerging pathogen of concern due to it's increasing prevalence, diverse disease spectrum, intrinsic multi-drug resistance and high mortality rates in immunocompromised individuals. S. maltophilia is a rare cause of neonatal sepsis associated with significant morbidity and mortality. The bacterium's multi-drug resistance poses a considerable challenge for treatment, with various mechanisms contributing to its resistance., Case Presentation: We report a case involving a 40-h-old male African neonate who exhibited symptoms of neonatal sepsis. The blood culture revealed Stenotrophomonas maltophilia, which was sensitive to ciprofloxacin and gentamicin but resistant to other antibiotics. Lumbar puncture for CSF could not be done because the father declined. We treated the newborn with the empirical first-line antibiotics as per the national guideline intravenous ampicillin and gentamicin for six days, and the child recovered fully with a repeated negative blood culture., Conclusions: This report describes a neonatal sepsis case caused by S. maltophilia, a multi-drug resistant bacteria and a rare cause of neonatal sepsis. We report that early detection of the bacterial and antimicrobial management based on local antibiogram data may be essential for successful patient's management., (© 2024. The Author(s).)

Background: The United States (US) continues to experience unprecedented rates of overdose mortality and there is increased need to identify effective harm reduction practices. Research from Canada describes cannabis donation through harm reduction agencies as an adjunctive strategy to mitigate the negative consequences of more harmful drugs. This case study describes the operational logistics, feasibility, and potential benefits of a cannabis donation program that was operated through a harm reduction program in rural Michigan., Case Presentation: We applied a community driven research approach to gather information from harm reduction program staff about the implementation and evolution of cannabis donation efforts in Michigan. We also examined 20-months (September 2021 through May 2023) of administrative data from a cannabis company to compare the sale and donation of cannabis products. Ten cannabis-experienced harm reduction clients received cannabis donations, with clinical staff determining client interest and appropriateness, and providing weekly pick-up or delivery. To expand product availability and sustainability, we examined administrative data from a commercialcannabis company that volunteered to provide donations. This administrative data suggests that while flower products constitute most of the adult and medical sales, edible, oil, and topical products predominated donations. Further, cost analysis suggests that donations represent only 1% of total gross sales and account for much less than the expected yearly donation amount., Conclusions: Research suggests there is potential to reduce alcohol and drug use related harms of more dangerous substances through substitution with cannabis. This case study is the first to document cannabis donation as a harm reduction practice in the US and suggests potential for sustainability dependent on state laws. Findings from this case study provide a starting point for inquiry into cannabis donation as a harm reduction strategy in the US; future research is needed to fully understand the individual-level outcomes, public health impacts, necessary legal regulations, and best practices for cannabis donation programs through harm reduction organizations., (© 2024. The Author(s).)

Background: Lack of Cytomegalovirus (CMV) knowledge among healthcare professionals has been proven to be the main threat to pregnant women's awareness, preventing them from reducing the risk of infection. The aims of this study were to assess the knowledge and practices of French-speaking Swiss perinatal professionals in terms of CMV prevention, as well as the sociodemographic-professional factors that influence them., Methods: This observational study used a cross-sectional design to collect data-via an anonymous electronic questionnaire in French distributed to gynecologists-obstetricians, general practitioners and midwives via various channels: e-mails and social networks of partner centers, professional associations, and conferences. The 41-item questionnaire collected data on sociodemographic and professional characteristics, general CMV knowledge, national recommendation knowledge and prevention practices. Univariable and multivariable analyses were performed., Results: A total of 110 gynecologist-obstetricians, 5 general practitioners and 226 midwives participated in the study. While more than 80% of practitioners were familiar with protective hygiene measures, significant gaps were highlighted concerning the transmission routes, as well as the signs of short- and long-term congenital CMV infection. Regarding practice, 63.3% of participants provided information on CMV to their patients, mainly during the first antenatal visit. Among those who did not, lack of knowledge and forgetfulness were the two main reasons cited. Concerning systematic screening, 45.7% of participants offered it to their patients, and 37.3% only offered it to "at risk" groups. The existence of national guidelines on CMV was known by 62.0% of participants. Multivariable analysis revealed that working as a gynecologist-obstetrician was independently associated with higher score of preventive practices, while performing ultrasound or preconception consultations was independently associated with a higher score of general CMV knowledge, and working in a university hospital was independently associated with a higher score of Swiss recommendation knowledge. A level of training higher than the basic medical or midwifery diploma and participation in fetal medicine symposia both promote a higher score of CMV knowledge and prevention practices in line with current recommendations., Conclusion: This study confirms the significant gaps in CMV knowledge among French-speaking Swiss caregivers along with the heterogeneity of their prevention practices. To raise awareness among pregnant women and reduce the burden of congenital CMV infections, improving professional knowledge through access to specific training and standardizing practices should be a national priority., (© 2024. The Author(s).)

Background: In low- and middle-income countries countries, millions of deaths occur annually from household air pollution (HAP), pulmonary tuberculosis (PTB), and HIV-infection. However, it is unknown whether HAP influences PTB risk among people living with HIV-infection., Methods: We conducted a case-control study among 1,277 HIV-infected adults in Bukavu, eastern Democratic Republic of Congo (February 2018 - March 2019). Cases had current or recent (<5y) PTB (positive sputum smear or Xpert MTB/RIF), controls had no PTB. Daily and lifetime HAP exposure were assessed by questionnaire and, in a random sub-sample (n=270), by 24-hour measurements of personal carbon monoxide (CO) at home. We used multivariable logistic regression to examine the associations between HAP and PTB., Results: We recruited 435 cases and 842 controls (median age 41 years, [IQR] 33-50; 76% female). Cases were more likely to be female than male (63% vs 37%). Participants reporting cooking for >3h/day and ≥2 times/day and ≥5 days/week were more likely to have PTB (aOR 1·36; 95%CI 1·06-1·75) than those spending less time in the kitchen. Time-weighted average 24h personal CO exposure was related dose-dependently with the likelihood of having PTB, with aOR 4·64 (95%CI 1·1-20·7) for the highest quintile [12·3-76·2 ppm] compared to the lowest quintile [0·1-1·9 ppm]., Conclusion: Time spent cooking and personal CO exposure were independently associated with increased risk of PTB among people living with HIV. Considering the high burden of TB-HIV coinfection in the region, effective interventions are required to decrease HAP exposure caused by cooking with biomass among people living with HIV, especially women., (© 2024. The Author(s).)

Although the introduction of the IL-1 and IL-6 inhibiting biologics in 2012 has revolutionized the treatment and markedly improved outcomes for many patients with SJIA, about 20% of these patients continue to have active disease, have markedly decreased quality of life and high disease activity as well as treatment-related morbidity and mortality. There is a clear need to define these disease states, and then use these definitions as the basis for further studies into the prevalence, clinical features, and pathophysiologic mechanisms. While such patients are most likely to benefit from novel therapies, they are very difficult to enroll in the ongoing clinical trials given the unique features of their disease and large numbers of background medications. The discussions at the NextGen 2022 conference focused on strategies to overcome these obstacles and accelerate studies in refractory SJIA., (© 2023. The Author(s).)

It has been increasingly recognized that there is a subset of patients with refractory systemic JIA, who have failed all available medications and may benefit from HSCT. The increasing experience with HSCT in SJIA, suggests that despite the complicated post-HSCT course, short-term, the transplanted patients either achieved SJIA remission or reduced burden of disease. Longer follow-up, however, is needed to better define the long-term outcomes. The discussion at the NextGen 2022 conference was focused on the optimal timing for the procedure, the need for a good control of inflammatory SJIA activity prior to HSCT, and the role of the reduced intensity conditioning regimens as there was a remote concern that such regimens might increase the risk of SJIA relapse after the transplantation. There was unanimous agreement about the importance of long-term registries to address these questions., (© 2023. The Author(s).)

Senecavirus A (SVA) causes vesicular disease in swine and has been responsible for a rampant increase in the yearly number of foreign animal disease investigations conducted in the United States. Diagnostic investigations for SVA are typically performed by sampling animals individually, which is labor-intensive and stressful. Developing an alternative aggregate sampling method would facilitate the detection of this virus at the population level. In a preliminary study, SVA was detected in processing fluids (PF) collected in a breeding herd before and after outbreak detection. The objective of this study was to estimate the average number of weeks PF remain SVA-positive after an SVA outbreak. Ten farrow-to-wean breeding herds volunteered to participate in this studyby longitudinally collecting PF samples after an SVA outbreak was detected and submitting samples for RT-rtPCR testing. The PF samples from the 10 farms were SVA-positive for an average of 11.8 weeks after the outbreak. Here, we show that testing of PF may be a cost-effective method to detect SVA and help halt its spread in SVA-endemic regions., (© 2024. The Author(s).)

Background: One in five children with an intellectual disability in the UK display behaviours that challenge. Despite associated impacts on the children themselves, their families, and services, little research has been published about how best to design, organise, and deliver health and care services to these children. The purpose of this study was to describe how services are structured and organised ("service models") in England for community-based health and care services for children with intellectual disability who display behaviours that challenge., Methods: Survey data about services were collected from 161 eligible community-based services in England. Staff from 60 of these services were also interviewed. A combination of latent class and descriptive analysis, coupled with consultation with family carers and professionals was used to identify and describe groupings of similar services (i.e., "service models")., Results: The latent class analysis, completed as a first step in the process, supported a distinction between specialist services and non-specialist services for children who display behaviours that challenge. Planned descriptive analyses incorporating additional study variables were undertaken to further refine the service models. Five service models were identified: Child and Adolescent Mental Health Services (CAMHS) (n = 69 services), Intellectual Disability CAMHS (n = 28 services), Children and Young People Disability services (n = 25 services), Specialist services for children who display behaviours that challenge (n = 27 services), and broader age range services for children and/or adolescents and adults (n= 12 services)., Conclusions: Our analysis led to a typology of five service models for community health and care services for children with intellectual disabilities and behaviours that challenge in England. Identification of a typology of service models is a first step in building evidence about the best provision of services for children with intellectual disabilities who display behaviours that challenge. The methods used in the current study may be useful in research developing service typologies in other specialist fields of health and care., Study Registration: Trial Registration: Current Controlled Trials ISRCTN88920546, Date assigned 05/07/2022., (© 2023. The Author(s).)

Objectives: Osteoarthritis (OA) is a joint disease with a heritable component. Genetic loci identified via genome-wide association studies (GWAS) account for an estimated 26.3% of the disease trait variance in humans. Currently, there is no method for predicting the onset or progression of OA. We describe the first use of the Collaborative Cross (CC), a powerful genetic resource, to investigate knee OA in mice, with follow-up targeted multi-omics analysis of homologous regions of the human genome., Methods: We histologically screened 275 mice for knee OA and conducted quantitative trait locus (QTL) mapping in the complete cohort (> 8 months) and the younger onset sub-cohort (8-12 months). Multi-omic analysis of human genetic datasets was conducted to investigate significant loci., Results: We observed a range of OA phenotypes. QTL mapping identified a genome-wide significant locus on mouse chromosome 19 containing Glis3, the human equivalent of which has been identified as associated with OA in recent GWAS. Mapping the younger onset sub-cohort identified a genome-wide significant locus on chromosome 17. Multi-omic analysis of the homologous region of the human genome (6p21.32) indicated the presence of pleiotropic effects on the expression of the HLA - DPB2 gene and knee OA development risk, potentially mediated through the effects on DNA methylation., Conclusions: The significant associations at the 6p21.32 locus in human datasets highlight the value of the CC model of spontaneous OA that we have developed and lend support for an immune role in the disease. Our results in mice also add to the accumulating evidence of a role for Glis3 in OA., (© 2023. The Author(s).)

Background and Objectives: Because much of the work in academic medicine is done by committee, early career URiM faculty, are often asked to serve on multiple committees, including diversity work that may not be recognized as important. They may also be asked to serve on committees to satisfy a diversity "check box," and may be asked more often than their non-URiM peers to serve in this capacity. We sought to describe the committee experiences of early career URiM faculty, hypothesizing that they may see committee service as a minority tax., Methods: Participants in the Leadership through Scholarship Fellowship (LTSF) were asked to share their experiences with committee service in their careers after participating in a faculty development discussion. Their responses were analyzed and reported using qualitative, open, axial, and abductive reasoning methods., Results: Four themes, with eight sub-themes (in parenthesis), emerged from the content analysis of the LTSF fellows responses to the prompt: Time commitment (Timing of committee work and lack of protected time for research and scholarship), URiM Committee service (Expectation that URiM person will serve on committees and consequences for not serving), Mentoring issues (no mentoring regarding committee service, faculty involvement is lacking and the conflicting nature of committee work) and Voice (Lack of voice or acknowledgement)., Conclusions: Early career URiM faculty reported an expectation of serving on committees and consequences for not serving related to their identity, but other areas of committee service they shared were not connected to their URiM identity. Because most of the experiences were not connected to the LTSF fellows' URiM identity, this group has identified areas of committee service that may affect all early career faculty. More research is necessary to determine how committee service affects URiM and non-URiM faculty in academic family medicine., (© 2023. The Author(s).)

Background: Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment., Methods: To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics modalities., Results: Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection., Conclusion: This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs., (© 2023. People´s Military Medical Press.)

Background: Improving oncology-specific knowledge and skills of healthcare professionals is critical for improving the outcomes of people with cancer. Many current postgraduate education offerings may be inaccessible to busy professionals, contain minimal consumer input or do not focus on the multidisciplinary nature of cancer care. In response to these needs, a Master of Cancer Sciences degree was developed. Our aim is to describe the development of the Master of Cancer Sciences., Methods: We describe the development of the Master of Cancer Sciences, including its theoretical and its pedagogical underpinnings., Results: Our approach to curriculum design was guided by Kern's Six-Step Approach to Medical Curriculum and underpinned by the Seven Principles of Online Learning. These approaches were further underpinned by the Cognitive Theory of Multimedia Learning which informed our approach to audio and visual information design. The pedagogy is interactive, experiential, interprofessional and importantly, includes consumers as educators. In practice, learning activities include peer feedback, multidisciplinary team meeting simulations, group work and clinical role plays. The online environment was visually shaped through infographics, high-quality educational videos and gamification., Conclusion: We have designed a Master of Cancer Sciences that is one of the first wholly online, cancer-specific Masters' programs. Its industry-led curriculum using evidence-based pedagogical choices utilises a range of novel digital formats and integrates the consumer perspective to provide a holistic overview of the field. Quantitative and qualitative evaluation of learning outcomes is ongoing., (© 2023. The Author(s).)

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children, causing significant morbidity. Despite the dramatic improvement in treatment, many patients do not achieve complete remission, and biomarkers for subclinical disease, flares, and response to treatment are lacking. Neutrophils and neutrophil extracellular traps (NETs) play key roles in the pathogenesis of autoimmune and inflammatory conditions. In this study, we characterized neutrophil enzyme activity and NETs formation in oligoarticular and polyarticular JIA and explored their association with disease activity., Methods: Neutrophils from 6 healthy controls and 7 patients with oligoarticular and polyarticular JIA were freshly isolated at time of diagnosis and after glucocorticoid intra-articular injection. Enzymatic activity of neutrophil granular enzymes was monitored by colorimetry and PMA-activated NETs formation was assessed using fluorescent microscopy., Results: In this pilot and feasibility study, we revealed that NETs were significantly increased in oligoarticular JIA patients at time of diagnosis compared to healthy controls. Anti-inflammatory treatment using intra-articular steroid injection normalized NETs formation in these patients. Correlation between NETs formation and clinical Juvenile Activity Disease Activity Score-10 (cJADAS-10) was linear and significant (P = 0.007) in oligo but not in poly JIA patients., Conclusions: This is the first study exploring the link of NETs formation with oligo and poly JIA activity. We demonstrated a statistically significant linear correlation between cJADAS-10 and NETs formation in oligo but not in poly JIA patients. Hence, we suggest that NETs may reflect clinical disease activity in JIA, and may serve as a putative biomarker. Further work is needed to validate these initial results and determine the dynamics of NETs formation in JIA., (© 2023. The Author(s).)

Background: Practitioners' perceptions of patients with obesity and obesity management shape their engagement in obesity care delivery. This study aims to describe practitioners' perceptions, experiences and needs in managing patients with obesity, determine the extent of weight stigma among health practitioners, and identify the factors associated with negative judgment towards patients with obesity., Methods: A cross-sectional online survey was conducted from May to August 2022 with health practitioners commonly involved in obesity management in Peninsular Malaysia, including doctors in primary care, internal medicine and bariatric surgery, and allied health practitioners. The survey explored practitioners' perceptions, barriers and needs in managing obesity, and evaluated weight stigma using the Universal Measures of Bias - Fat (UMB Fat) questionnaire. Multiple linear regression analysis was used to identify demographic and clinical-related factors associated with higher negative judgment towards patients with obesity., Results: A total of 209 participants completed the survey (completion rate of 55.4%). The majority (n = 196, 94.3%) agreed that obesity is a chronic disease, perceived a responsibility to provide care (n = 176, 84.2%) and were motivated to help patients to lose weight (n = 160, 76.6%). However, only 22% (n = 46) thought their patients were motivated to lose weight. The most frequently reported barriers to obesity discussions were short consultation time, patients' lack of motivation, and having other, more important, concerns to discuss. Practitioners needed support with access to multi-disciplinary care, advanced obesity training, financing, comprehensive obesity management guidelines and access to obesity medications. The mean (SD) of the UMB Fat summary score was 2.99 (0.87), with the mean (SD) domain scores ranging between 2.21 and 4.36 (1.06 to 1.45). No demographic and clinical-related factors were significantly associated with negative judgment from the multiple linear regression analyses., Conclusion: Practitioners in this study considered obesity a chronic disease. While they had the motivation and capacity to engage in obesity management, physical and social opportunities were the reasons for not discussing obesity with their patients. Practitioners needed more support to enhance their capability and opportunity to engage with obesity management. Weight stigma in healthcare settings in Malaysia should be addressed, given the possibility of hindering weight discussions with patients., (© 2023. The Author(s).)

Background: Refugee women exhibit some of the highest rates of chronic pain yet the diversity and challenges of health care systems across countries pose numerous challenges for refugee women trying to access quality health care., Objective: We sought to explore the experiences of Assyrian refugee women seeking care for chronic pain., Methods: Semi-structured interviews (face-to-face and virtual) were undertaken with 10 Assyrian women of refugee background living in Melbourne, Australia. Audio recordings and field notes of interviews were collected and themes were identified using a phenomenological approach. Women were required to be conversant in English or Arabic and willing to use a translator if necessary., Results: We identified five major themes of women's experiences accessing care for chronic pain: (1) the story of pain; (2) the experience of help seeking in Australia and home country; (3) factors shaping the ability to access appropriate care; (4) support seeking systems; and (5) influence of culture and gender roles., Conclusion: Exploring refugee women's experience of seeking care for chronic pain reinforces the need to explore hard to reach population's perspectives in research and helps to understand how vectors of disadvantage may intersect. For successful integration into health care systems of host countries, particularly for complex conditions such as chronic pain, there is a need to work with women community members to develop programs that are culturally aligned to enhance access pathways to care., (© 2023. The Author(s).)

The COVID-19 pandemic represents an unprecedented challenge for clinical research. The Pneumococcal Vaccine Schedules (PVS) study is a non-inferiority, interventional trial in which infants resident in 68 geographic clusters are randomised to two different schedules for pneumococcal vaccination. From September 2019 onwards, all infants resident in the study area became eligible for trial enrolment at all Expanded Programme on Immunisation (EPI) clinics in the study area. Surveillance for clinical endpoints is conducted at all 11 health facilities in the study area. PVS is conducted as a collaboration between the Medical Research Council Unit The Gambia (MRCG) at LSHTM and the Gambian Ministry of Health (MoH). The COVID-19 pandemic caused many disruptions to PVS. MRCG instructed interventional studies that participant enrolment be suspended on 26 March 2020, and a public health emergency was declared in The Gambia on 28 March 2020. Enrolment in PVS restarted on 1 July 2020 and was suspended again on 5 August 2020 after The Gambia experienced a sharp increase in COVID-19 cases in late July 2020 and restarted again on 1 September 2020. During periods of suspended enrolment of infants at EPI clinics, PVS continued safety surveillance at health facilities, albeit with disruptions. During the periods of suspended enrolment, infants who had been enrolled before 26 March 2020 continued to receive the PCV schedule to which they had been randomly allocated based on their village of residence, whereas all other infants received the standard PCV schedule. Throughout 2020 and 2021, the trial faced numerous technical and operational challenges: disruption to MoH delivery of EPI services and clinical care at health facilities; episodes of staff illness and isolation; disruption of MRCG transport, procurement, communications and human resource management; and also a range of ethical, regulatory, sponsorship, trial monitoring and financial challenges. In April 2021, a formal review concluded that the pandemic had not compromised the scientific validity of PVS and that the trial should continue as per protocol. The continuing challenges that COVID-19 poses to PVS, and other clinical trials will persist for some time., (© 2023. The Author(s).)

Background: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration., Methods: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR 1 YF 1 ), MMR followed by YF vaccine four weeks later (MMR 1 YF 2 ), or YF followed by MMR vaccine four weeks later (YF 1 MMR 2 ). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests., Results: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR 1 YF 1 group versus 96.3% in the MMR 1 YF 2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR 1 YF 1 versus 94.7% MMR 1 YF 2 , a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR 1 YF 1 versus 97.9% MMR 1 YF 2 , a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR 1 YF 1 versus 97.5% YF 1 MMR 2 , a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted., Conclusion: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration., Trial Registration: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Peppers, bell and chile, are a culturally and economically important worldwide. Domesticated Capsicum spp. are distributed globally and represent a complex of valuable genetic resources., Objectives: Explore population structure and diversity in a collection of 467 peppers representing eight species, spanning the spectrum from highly domesticated to wild using 22,916 SNP markers distributed across the twelve chromosomes of pepper., Results: These species contained varied levels of genetic diversity, which also varied across chromosomes; the species also differ in the size of genetic bottlenecks they have experienced. We found that levels of diversity negatively correlate to levels of domestication, with the more diverse being the least domesticated., (© 2023. The Author(s).)

Background: The distribution of the duration that clinical cases of COVID-19 occupy hospital beds (the 'length of stay') is a key factor in determining how incident caseloads translate into health system burden. Robust estimation of length of stay in real-time requires the use of survival methods that can account for right-censoring induced by yet unobserved events in patient progression (e.g. discharge, death). In this study, we estimate in real-time the length of stay distributions of hospitalised COVID-19 cases in New South Wales, Australia, comparing estimates between a period where Delta was the dominant variant and a subsequent period where Omicron was dominant., Methods: Using data on the hospital stays of 19,574 individuals who tested positive to COVID-19 prior to admission, we performed a competing-risk survival analysis of COVID-19 clinical progression., Results: During the mixed Omicron-Delta epidemic, we found that the mean length of stay for individuals who were discharged directly from ward without an ICU stay was, for age groups 0-39, 40-69 and 70 +, respectively, 2.16 (95% CI: 2.12-2.21), 3.93 (95% CI: 3.78-4.07) and 7.61 days (95% CI: 7.31-8.01), compared to 3.60 (95% CI: 3.48-3.81), 5.78 (95% CI: 5.59-5.99) and 12.31 days (95% CI: 11.75-12.95) across the preceding Delta epidemic (1 July 2021-15 December 2021). We also considered data on the stays of individuals within the Hunter New England Local Health District, where it was reported that Omicron was the only circulating variant, and found mean ward-to-discharge length of stays of 2.05 (95% CI: 1.80-2.30), 2.92 (95% CI: 2.50-3.67) and 6.02 days (95% CI: 4.91-7.01) for the same age groups., Conclusions: Hospital length of stay was substantially reduced across all clinical pathways during a mixed Omicron-Delta epidemic compared to a prior Delta epidemic, contributing to a lessened health system burden despite a greatly increased infection burden. Our results demonstrate the utility of survival analysis in producing real-time estimates of hospital length of stay for assisting in situational assessment and planning of the COVID-19 response., (© 2023. The Author(s).)

Background: Despite new and better treatments for juvenile dermatomyositis (JDM), not all patients with moderate severity disease respond adequately to first-line therapy. Those with refractory disease remain at higher risk for disease and glucocorticoid-related complications. Biologic disease-modifying antirheumatic drugs (DMARDs) have become part of the arsenal of treatments for JDM. However, prospective comparative studies of commonly used biologics are lacking., Methods: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM biologics workgroup met in 2019 and produced a survey assessing current treatment escalation practices for JDM, including preferences regarding use of biologic treatments. The cases and questions were developed using a consensus framework, requiring 80% agreement for consensus. The survey was completed online in 2020 by CARRA members interested in JDM. Survey results were analyzed among all respondents and according to years of experience. Chi-square or Fisher's exact test was used to compare the distribution of responses to each survey question., Results: One hundred twenty-one CARRA members responded to the survey (denominators vary for each question). Of the respondents, 88% were pediatric rheumatologists, 85% practiced in the United States, and 43% had over 10 years of experience. For a patient with moderately severe JDM refractory to methotrexate, glucocorticoids, and IVIG, approximately 80% of respondents indicated that they would initiate a biologic after failing 1-2 non-biologic DMARDs. Trials of methotrexate and mycophenolate were considered necessary by 96% and 60% of respondents, respectively, before initiating a biologic. By weighed average, rituximab was the preferred biologic over abatacept, tocilizumab, and infliximab. Over 50% of respondents would start a biologic by 4 months from diagnosis for patients with refractory moderately severe JDM. There were no notable differences in treatment practices between respondents by years of experience., Conclusion: Most respondents favored starting a biologic earlier in disease course after trialing up to two conventional DMARDs, specifically including methotrexate. There was a clear preference for rituximab. However, there remains a dearth of prospective data comparing biologics in refractory JDM. These findings underscore the need for biologic consensus treatment plans (CTPs) for refractory JDM, which will ultimately facilitate comparative effectiveness studies and inform treatment practices., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Methods used to sample mosquitoes are important to consider when estimating entomologic metrics. Human landing catches (HLCs) are considered the gold standard for collecting malaria vectors. However, HLCs are labour intensive, can expose collectors to transmission risk, and are difficult to implement at scale. This study compared alternative methods to HLCs for collecting Anopheles mosquitoes in eastern Uganda., Methods: Between June and November 2021, mosquitoes were collected from randomly selected households in three parishes in Tororo and Busia districts. Mosquitoes were collected indoors and outdoors using HLCs in 16 households every 4 weeks. Additional collections were done indoors with prokopack aspirators, and outdoors with pit traps, in these 16 households every 2 weeks. CDC light trap collections were done indoors in 80 households every 4 weeks. Female Anopheles mosquitoes were identified morphologically and Anopheles gambiae sensu lato were speciated using PCR. Plasmodium falciparum sporozoite testing was done with ELISA., Results: Overall, 4,891 female Anopheles were collected, including 3,318 indoors and 1,573 outdoors. Compared to indoor HLCs, vector density (mosquitoes per unit collection) was lower using CDC light traps (4.24 vs 2.96, density ratio [DR] 0.70, 95% CIs 0.63-0.77, p < 0.001) and prokopacks (4.24 vs 1.82, DR 0.43, 95% CIs 0.37-0.49, p < 0.001). Sporozoite rates were similar between indoor methods, although precision was limited. Compared to outdoor HLCs, vector density was higher using pit trap collections (3.53 vs 6.43, DR 1.82, 95% CIs 1.61-2.05, p < 0.001), while the sporozoite rate was lower (0.018 vs 0.004, rate ratio [RR] 0.23, 95% CIs 0.07-0.75, p = 0.008). Prokopacks collected a higher proportion of Anopheles funestus (75.0%) than indoor HLCs (25.8%), while pit traps collected a higher proportion of Anopheles arabiensis (84.3%) than outdoor HLCs (36.9%)., Conclusion: In this setting, the density and species of mosquitoes collected with alternative methods varied, reflecting the feeding and resting characteristics of the common vectors and the different collection approaches. These differences could impact on the accuracy of entomological indicators and estimates of malaria transmission, when using the alternative methods for sampling mosquitos, as compared to HLCs., (© 2022. The Author(s).)

Background: In partnership with a Nehiyawak (Plains Cree) community of Maskwacîs,central Alberta (Canada), we implemented an Indigenous-led intervention to provide experiential learning opportunities for perinatal health care providers (HCPs) and staff. Our objective was to capture the impact of participating in cultural safety learning opportunities on perceived self-awareness for HCPs and staff to provide enhanced culturally informed care., Methods: Perinatal HCPs and staff who work regularly with Indigenous women from our partnering community took part in a series of experiential learning activities designed by a Community Advisory Committee. We used an explanatory sequential mixed methods approach informed by community-based participatory research. We compared Cultural Intelligence Scale (CQS) and Maskwacîs-Specific Cultural Scale (MSCS) scores pre- and post-intervention using non-parametrical statistical analysis (Wilcoxon signed rank test). Post-intervention, we conducted a qualitative description study using semi-structured interviews. Qualitative data was analyzed using thematic analysis., Results: A total of 17 participants completed pre- and post-intervention questionnaires. Responses indicated a shift in perceived cultural and community knowledge and comfort levels, with positive gains in overall mean scores for both the CQS (p = 0.01) and MSCS (p = 0.01). Nine participants completed qualitative interviews. Overall, participants felt better equipped to provide more culturally informed care to their patients post-intervention., Conclusion: An Indigenous-led experiential learning intervention was effective in enhancing overall perceived cultural awareness and preparedness to provide culturally informed care for perinatal HCPs and staff. This study provides evidence for fostering relationships between Indigenous communities and health systems toward enhanced perinatal care., (© 2022. The Author(s).)

Background: In 2020-2021, long-lasting insecticidal nets (LLINs) were distributed nationwide in Uganda during the COVID-19 pandemic. A cross-sectional survey was conducted in 12 districts to evaluate the impact of the campaign 1-5 months after LLIN distribution., Methods: During April-May 2021, households were randomly selected from target areas (1-7 villages) surrounding 12 government-run health facilities established as Malaria Reference Centres; at least 50 households were enrolled per cluster. Outcomes included household ownership of LLINs distributed through the universal coverage campaign (UCC) (at least one UCC LLIN), adequate coverage of UCC LLINs (at least one UCC LLIN per 2 residents), and use of LLINs (resident slept under a LLIN the previous night). Multivariate logistic regression models were used to identify household- and individual-level factors associated with outcomes, controlling for clustering around health facilities., Results: In total, 634 households, with 3342 residents and 1631 bed-nets, were included. Most households (93.4%) owned at least 1 UCC LLIN, but only 56.8% were adequately covered by UCC LLINs. In an adjusted analysis, the factor most strongly associated with adequate coverage by UCC LLINs was fewer household residents (1-4 vs 7-14; adjusted odds ratio [aOR] 12.96, 95% CI 4.76-35.26, p < 0.001; 5-6 vs 7-14 residents; aOR 2.99, 95% CI 1.21-7.42, p = 0.018). Of the 3166 residents of households that owned at least one UCC LLIN, only 1684 (53.2%) lived in adequately covered households; 89.9% of these used an LLIN the previous night, compared to 1034 (69.8%) of 1482 residents living in inadequately covered households. In an adjusted analysis, restricted to residents of inadequately covered households, LLIN use was higher in children under-five than those aged 5-15 years (aOR 3.04, 95% CI 2.08-4.46, p < 0.001), and higher in household heads than distantly-related residents (aOR 3.94, 95% CI 2.38-6.51, p < 0.001)., Conclusions: Uganda's 2021-21 campaign was successful, despite the COVID-19 pandemic. In future campaigns, strategies should be adopted to ensure high LLIN coverage, particularly for larger households. A better understanding of the drivers of LLIN use within households is needed to guide future interventions, educational messages, and behaviour change communication strategies; school-aged children and distantly-related residents appear vulnerable and could be targeted., (© 2022. The Author(s).)

Objective: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants., Methods: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path&#95;MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path&#95;MMR carriers who were first- or second-degree relatives of Lynch syndrome probands., Results: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path&#95;MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path&#95;MSH2 50% and 39%; for path&#95;MSH6 13% and 17% and for path&#95;PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups., Conclusions: Prospectively observed CRC incidences (PLSD) in path&#95;MLH1 and path&#95;MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path&#95;MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path&#95;PMS2 carriers subjected to colonoscopy, but not significantly so., (© 2022. The Author(s).)

Background: For people living with dementia (PLWD) the overuse of potentially inappropriate medications (PIMs) remains a persistent problem. De-prescribing trials in the elderly have mixed results. Clinician champions may be uniquely suited to lead efforts to address this challenge. Here we describe the study protocol for a 24-month embedded pragmatic cluster-randomized clinical trial within two accountable care organizations (ACOs) of such a clinician champion intervention. The specific aims are to (1) assess the effectiveness of a clinician champion on de-implementing PIMs in PLWD, (2) determine if the intervention is associated with a reduction in emergency department (ED) visits and hospitalizations attributed to a fall, and (3) examine five implementation outcomes: appropriateness, feasibility, fidelity, penetration, and equity., Methods/design: Two ACOs agreed to participate: United States Medical Management (USMM) and Oschner Health System. The unit of randomization will be the primary care clinic. A clinician champion will be recruited from each of the intervention clinics to participate in a 6-month training program and then work with clinicians and staff in their clinic for 12 months to reduce the use of PIMs in their PLWD population. For aims 1 and 2, Medicare claims data will be used to assess outcomes. The outcome for aim #1 will be medication possession rates per quarter, for the three therapeutic classes of PIMs among patients with dementia in intervention clinics versus control clinics. For aim #2, we will assess the incidence of falls using a previously validated algorithm. For both aims 1 and 2, we will construct hierarchical models with time period observations nested within patient using generalized estimating equations (GEE) with robust standard errors. The key variable of interest will be the treatment indicator assigned based on practice. For aim #3, we will conduct qualitative thematic analysis of documentation by the clinician champions in their project workbooks to evaluate the five implementation outcomes., Discussion: This embedded pragmatic trial will add to our existing knowledge regarding the effectiveness of a clinician champion strategy to de-prescribe potentially inappropriate medication among patients with dementia as well as its appropriateness, feasibility, fidelity, penetration, and equity., Trial Registration: Clinicaltrials.gov NCT05359679 , Registered May 4, 2022., (© 2022. The Author(s).)

Background: Road traffic injuries (RTIs), primarily musculoskeletal in nature, are the leading cause of unintentional injury worldwide, incurring significant individual and societal burden. Investigation of a large representative cohort is needed to validate early identifiable predictors of long-term work incapacity post-RTI. Therefore, up until two years post-RTI we aimed to: evaluate absolute occurrence of return-to-work (RTW) and occurrence by injury compensation claimant status; evaluate early factors (e.g., biopsychosocial and injury-related) that influence RTW longitudinally; and identify factors potentially modifiable with intervention (e.g., psychological distress and pain)., Methods: Prospective cohort study of 2019 adult participants, recruited within 28 days of a non-catastrophic RTI, predominantly of mild-to-moderate severity, in New South Wales, Australia. Biopsychosocial, injury, and compensation data were collected via telephone interview within one-month of injury (baseline). Work status was self-reported at baseline, 6-, 12-, and 24-months. Analyses were restricted to participants who reported paid work pre-injury (N = 1533). Type-3 global p-values were used to evaluate explanatory factors for returning to 'any' or 'full duties' paid work across factor subcategories. Modified Poisson regression modelling was used to evaluate factors associated with RTW with adjustment for potential covariates., Results: Only ~ 30% of people with RTI returned to full work duties within one-month post-injury, but the majority (76.7%) resumed full duties by 6-months. A significant portion of participants were working with modified duties (~ 10%) or not working at all (~ 10%) at 6-, 12-, and 24-months. Female sex, low education, low income, physically demanding occupations, pre-injury comorbidities, and high injury severity were negatively associated with RTW. Claiming injury compensation in the fault-based scheme operating at the time, and early identified post-injury pain and psychological distress, were key factors negatively associated with RTW up until two years post-injury., Conclusions: Long-term work incapacity was observed in 20% of people following RTI. Our findings have implications that suggest review of the design of injury compensation schemes and processes, early identification of those at risk of delayed RTW using validated pain and psychological health assessment tools, and improved interventions to address risks, may facilitate sustainable RTW., Trial Registration: This study was registered prospectively with the Australian New Zealand Clinical Trials Registry (ACTRN12613000889752)., (© 2022. The Author(s).)

Background: Residential Medication Management Review (RMMR) is a subsidized comprehensive medicines review program for individuals in Australian residential aged care facilities (RACFs). This study examined weekly trends in medicines use in the four months before and after an RMMR and among a comparison group of residents who did not receive an RMMR., Methods: This retrospective cohort study included individuals aged 65 to 105 years who first entered permanent care between 1/1/2012 and 31/12/2016 in South Australia, Victoria, or New South Wales, and were taking at least one medicine. Individuals with an RMMR within 12 months of RACF entry were classified into one of three groups: (i) RMMR within 0 to 3 months, (ii) 3 to 6 months, or (iii) within 6 to 12 months of RACF entry. Individuals without RMMRs were included in the comparison group. Weekly trends in the number of defined daily doses per 1000 days were determined in the four months before and after the RMMR (or assigned index date in the comparison group) for 14 medicine classes., Results: 113909 individuals from 1979 RACFs were included, of whom 55021 received an RMMR. Across all three periods examined, decreased use of statins and proton pump inhibitors was observed post-RMMR in comparison to those without RMMRs. Decreases in calcium channel blockers, benzodiazepines/zopiclone, and antidepressants were observed following RMMR provision in the 3-6 and 6-12 months after RACF entry. Negligible changes in antipsychotic use were also observed following an RMMR in the 6-12 months after RACF entry by comparison to those without RMMRs. No changes in use of opioids, ACE inhibitors/sartans, beta blockers, loop diuretics, oral anticoagulants, or medicines for osteoporosis, diabetes or the cognitive symptoms of dementia were observed post-RMMR., Conclusions: For six of the 14 medicine classes investigated, modest changes in weekly trends in use were observed after the provision of an RMMR in the 6-12 months after RACF entry compared to those without RMMRs. Findings suggest that activities such as medicines reconciliation may be prioritized when an RMMR is provided on RACF entry, with deprescribing more likely after an RMMR the longer a resident has been in the RACF., (© 2022. The Author(s).)

Background: The development of resistance by Plasmodium falciparum to anti-malarial drugs impedes any benefits of the drug. In addition, absence or delayed availability of current anti-malarial drugs in remote areas has the potential to results to parasite escape and continuous transmission., Case Presentation: The case of a 29-year old pregnant woman from Biase Local Government Area in Cross River State Nigeria presenting with febrile illness and high body temperature of 38.7 °C was reported. She looked pale and vomited twice on arrival at the health facility. Her blood smear on the first day of hospitalization was positive for P. falciparum by RDT, microscopy (21,960 parasite/µl) and real-time PCR, with a PCV of 18%. She was treated with 600 mg intravenous quinine in 500 ml of 5% Dextrose/0.9% Saline 8-hourly for 24 h. On the second day of hospitalization, she complained of weakness, persistent high-grade fever and vaginal bleeding. A bulging amnion from an extended cervix was observed. Following venous blood collection for laboratory investigations, 600 µg of misoprostol was inserted into the posterior fornix of her vagina as part of her obstetric care. Parenteral quinine was discontinued, and she was given full therapeutic regimen of artemether-lumefantrine 80/480 mg tablets to be taken for 3 days beginning from the second day. Her blood samples on the second and third day of hospitalization remained positive for P. falciparum by all three diagnostic methods. Single nucleotide polymorphism (SNP) assay on all three P. falciparum isolates revealed the presence of variants associated with multiple drug resistant markers., Discussion: Infecting P. falciparum isolates may have been resistant to initial quinine treatment resulting from parasite cross-resistance with other quinoline associated resistant markers such as 86Y and 184 F., Conclusions: Therefore, the likely transmission of similarly resistant parasites in the study area calls for reinforcement of interventions and adherence to current World Health Organization guidelines in administering only approved drugs to individuals in order to mitigate parasite escape and eventual transmission to other susceptible individuals., (© 2022. The Author(s).)

Background: Distribution of long-lasting insecticide treated nets (LLINs) is the most widely used intervention for the prevention of malaria but recall and social desirability biases may lead to challenges in accurately measuring use of bednets. SmartNet is a remote electronic monitor that provides objective measurements of bednet use over weeks at a time. Assessing local acceptability is important when implementing innovative global health technologies such as SmartNet. This study draws on established models such as the Technology Acceptance Model (TAM) and Theoretical Framework of Acceptability (TFA) to assess acceptability of SmartNet in Ugandan households., Methods: Semi-structured qualitative interviews were conducted at weeks one and six following installation of SmartNet in ten households in Western Uganda. Heads-of-households answered open-ended questions addressing the main acceptability domains of the TFA and TAM models (i.e. perceived ease of use, ethicality, etc.). Responses were digitally recorded, transcribed, coded and analyzed using a thematic analysis approach., Results: Seven out of ten households interviewed reported no difference in use between SmartNet and a standard LLIN. Households stated the large size, soft fabric, and the efficacy of SmartNet relative to a standard LLIN contributed to perceived usefulness and perceived ease of use. Opportunity costs of the novel monitoring system expressed by households included difficulty washing nets and dislike of blinking lights on the device. Barriers to SmartNet use focused on questions of the ethics of bednet use monitoring, discomfort with technical aspects of the device and a poor understanding of its function amongst others in the community. However, explaining SmartNet to other community members resolved these concerns and often resulted in interest and acceptance among peers., Conclusion: Objective monitoring of bednet use with SmartNet appears acceptable to these households in Uganda. Use of SmartNet seems to be similar to behaviors around use of standard LLINs. Viewpoints on many aspects of SmartNet were generally favorable. Concerns around ethicality of bednet monitoring are present and indicate the need for continuing community education. The device will continue to be optimized to make it more acceptable to users and to accurately reflect standard LLIN use to improve our understanding of prevention behaviors in malaria endemic settings., (© 2022. The Author(s).)

Background: Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species., Methods: This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb<5g/dl and <7g/dl) and/or the risk for blood transfusion, the incidence risk of ≥ 25% fall in haemoglobin with and without haemoglobinuria, and the incidence risk of ≥ 25% fall in haemoglobin to under 7g/dl with and without haemoglobinuria., Discussion: This study evaluates the potential benefit of a universal radical cure for both P. vivax and P. falciparum in different endemic locations. If found safe and effective universal radical cure could represent a cost-effective approach to clear otherwise unrecognised P. vivax infections and hence accelerate P. vivax elimination., Trial Registration: NCT03916003 . Registered on 12 April 2019., (© 2022. The Author(s).)