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Abstract Ehlers-Danlos Syndrome (EDS) are a heterogeneous group of genetic connective tissue disorders, and typically manifests as weak joints that subluxate/dislocate, stretchy and/or fragile skin, organ/systems dysfunction, and significant widespread pain. Historically, this syndrome has been poorly understood and often overlooked. As a result, people living with EDS had difficulty obtaining an accurate diagnosis and appropriate treatment, leading to untold personal suffering as well as ineffective health care utilization. The GoodHope EDS clinic addresses systemic gaps in the diagnosis and treatment of EDS. This paper describes a leap forward—from lack of awareness, diagnosis, and treatment—to expert care that is tailored to meet the specific needs of patients with EDS. The GoodHope EDS clinic consists of experts from various medical specialties who work together to provide comprehensive care that addresses the multi-systemic nature of the syndrome. In addition, EDS-specific self-management programs have been developed that draw on exercise science, rehabilitation, and health psychology to improve physical and psychosocial wellbeing and overall quality of life. Embedded into the program are research initiatives to shed light on the clinical presentation, underlying mechanisms of pathophysiology, and syndrome management. We also lead regular educational activities for community health care providers to increase awareness and competence in the interprofessional management of EDS beyond our doors and throughout the province and country.

Abstract Background People experiencing homelessness access specialist palliative care late in their illness trajectory, if at all. There is also little evidence they receive generalist palliative care or are given opportunities to engage in Advance Care Planning. This qualitative study describes the central role of key workers in supporting access to healthcare in homeless communities and identifies implications for improving palliative care provision. Methods Qualitative data were collected via focus groups and individual interviews with staff working for a key provider of support and housing/accommodation for people experiencing homelessness in an urban area of Aotearoa New Zealand. Results The ability to provide palliative care for people experiencing homelessness is dependent upon supporting engagement with mainstream health services. It is here that we identified the key worker role as central due to the complex and expert work they undertake to facilitate healthcare access for their clients. As a result of the high burden of chronic conditions this community experiences, most of this work related to support managing serious conditions, as well as death and dying. Key workers often went ‘above and beyond’ to support their clients in engaging with mainstream health services, during outpatient appointments, hospital admissions and in emergency department settings. They felt clinicians in these settings did not recognise the knowledge they held about the person, or their skills in terms of providing trauma informed care. The inflexibility of current care provision, as well as people experiencing homelessness feeling stigmatised, and neither valued nor respected in these settings, also created barriers to receiving care. Conclusions New models of palliative care are required which recognise the central role of non-health care key support staff and engage them more actively in supporting people experiencing homelessness when they interact with mainstream health services. Such models will need to be responsive to the nature and complexity of palliative care need in this population and facilitate support for people who typically do not see healthcare spaces as safe. The trusted relationships key workers have developed over time are crucial resources for identifying palliative care need and supporting access to palliative care for people experiencing homelessness.

Abstract Introduction In low- and-middle-income-countries (LMICs) like Ghana, universal access to quality healthcare remains a mirage and this undermines achievement of sustainable development goal (SDG) 3. The SafeCare Quality Improvement (QI) programme is an initiative of PharmAccess Foundation, a Netherlands-based non-governmental organisation (NGO). In 2009 SafeCare QI programme was launched in Ghana to help address gaps in healthcare quality standards, leveraging existing local resources. Over 600 private and public healthcare facilities are currently enrolled in the programme and is being adopted for nation-wide rollout by government of Ghana and implementing partners. Objective This paper explored views and experiences of frontline health staff and policy makers on the SafeCare quality improvement programme in Ghana and how local resources were leveraged in its implementation. Methodology Design/setting: The evaluation was conducted in 53 private and public healthcare facilities from seven administrative regions of Ghana across the coastal, middle, and northern geopolitical belts. The regions are Ashanti (n = 12), Bono East (n = 8), Bono (n = 3), Greater Accra (n = 12), Oti (n = 4), Savannah (n = 8) and Western (n = 9). Sampling: Quota and purposive sampling techniques were used to sample the healthcare facilities in accordance with the study eligibility criteria. Total of 45 focus group discussions (FGDs) and 47 individual in-depth interviews (IDIs) were conducted among frontline staff and policy makers from government and private local partner institutions. Analysis: Group and individual interviews were audio recorded, transcribed verbatim and thematic content analysis done using Nvivo (version 12.0) software. Findings Overall, participants perceived the relevance and benefits of the SafeCare programme to be "very satisfactory" while the programme impact, rollout process and success were perceived to be "satisfactory". Quality healthcare standards were perceived to have improved in beneficiary health facilities due to participation in the SafeCare programme. Patient satisfaction, service utilisation and revenue generation in healthcare facilities were also attributed to the SafeCare programme. Proposals were made for harmonisation of existing QI assessment tools to mitigate duplications. Agreed data sharing protocols and interoperability with existing national database were also recommended to promote sustainability. Finally, low staff motivation, high workload, lack of financial and material resources were cited as potential impediments to full compliance with the SafeCare QI standards by healthcare facilities enrolled in the programme. Conclusions SafeCare QI programme has contributed to QI and adherence to patient safety standards in Ghana. Sustainability is however dependent on continuous government commitment as the programme gets adopted as a national QI programme. Overlaps in content of QI assessment tools ought to be addressed to promote efficiency without compromising quality standards. The SafeCare programme demonstrates that health systems in LMICs have the potential to attain acceptable quality healthcare standards when they take advantage of existing local resources, including private-public partnership (PPP) and peer-learning opportunities.

Abstract Background Transport injuries are a global public health concern, causing 1.35 million deaths and over 20 million non-fatal injuries annually. Low- and middle-income countries, particularly countries in Africa, are experiencing an increase in fatalities. Ghana and the Volta Region are not exempted from the burden, prompting targeted interventions. In the development of these interventions, epidemiological data analysis is needed to identify areas for action. This study aimed to analyze the distribution, trends, and incidence of transport-related injuries in the Volta Region of Ghana. Method Secondary data was analyzed to describe transport-related injury cases and deaths in the Volta Region of Ghana from 2019 to 2023. Transport-related injuries were obtained from the monthly out-patient morbidity report form whereas transport related deaths were obtained from the inpatient morbidity and mortality, and cause of death report forms. Descriptive data analyses were performed and reported as frequencies, proportions, ratios, and choropleth maps. Result Of the 33,415 transport-related injury cases reported between 2019 and 2023, 25 were fatal. The highest proportion of cases, 35.8% (35.3–36.4), was among persons aged 20–34 years. About 66.0% (65.5–66.5) of all the cases involved males. The cumulative incidence was 387 injuries per 100,000 population with the highest incidence recorded in 2021. The incidence of cases declined from 357 per 100,000 population in 2019 to 320 per 100,000 population in 2023. The death rate was stable over the period with the highest of 1.2 per 1000 recorded in 2019 and declined from 1.2 per 1000 in 2019 to 0.9 per 1000 in 2023. Most, 56% of the deaths were reported in district hospitals. Conclusion The study showed a decreasing trend in the incidence of transport injuries, but a steady mortality rate in the Volta Region. Young adults were the highest affected group. There is the need for increased road safety campaigns and further research.

Abstract Background Congenital heart defects can lead to right ventricular (RV) pressure-overload and heart failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) have been studied clinically as options to restore heart function in disease states. Many studies have indicated these cells act through paracrine mechanisms to prevent apoptosis, promote cellular function, and regulate gene/protein expression. We aimed to determine the proteomic response of diseased hearts to cell therapy. Methods We utilized a juvenile rat model of RV pressure overload created by banding the pulmonary artery (PAB). Two weeks post-banding, bone marrow-derived mesenchymal stromal cells (MSCs) and 3 populations of CPCs (nCPCs, cCPCs, ES-CPCs) were delivered to the RV free wall. RV function and cellular retention were measured for four weeks post-injection, at which point hearts were extracted and the RV was excised for liquid chromatography and tandem mass spectrometry. Resulting RV proteomes were compared and analyzed using systems biology and bioinformatics. Results Proteomic profiling identified 1156 total proteins from the RV, of which 5.97% were significantly changed after PAB. This disease-altered proteome was responsive to cellular therapy, with 72% of the PAB-altered proteome being fully or partially reversed by MSC therapy. This was followed by nCPCs (54%), ES-CPCs (52%), and cCPCs (39%). Systems biology and bioinformatics analysis showed MSC, nCPC, or ES-CPC cell therapy is associated with a decrease in predicted adverse cardiac effects. We also observed an effect of cell therapy on the non-altered RV proteome, however, this was associated with minor predicted pathological endpoints. Conclusions Our data indicate MSCs, ES-CPCs, and nCPCs significantly reverse the PAB-altered proteome towards a pre-disease state in our animal model. These results indicate cell-based therapies show promise in improving RV function after pressure overload through partial restoration of the disease-altered cardiac proteome.

Abstract Background The global burden of mental health disorders is on the increase, which has contributed to discussions on mitigation strategies. While mental health discourses in respect of access to services are still ongoing, there is limited focus on vulnerable groups. Deaf persons are at risk of exclusion from health services due to their unique modes of communication. In order to advocate for the inclusion of deaf persons in mental health services, there is a need for a study eliciting information on their knowledge about mental health and accessibility to services. Method The study was guided by a mixed-methods design and a two-phase data collection. In phase one, a questionnaire was distributed to 284 deaf persons to gather information on their knowledge of mental health conditions, causes, sources of information, and accessibility of services. Frequencies were used to report the trends identified in the data. Following this, an interview guide was designed based on the trends identified in the first phase to develop an in-depth insight into the experiences of deaf persons (n = 40) in respect of awareness and accessibility to mental health services. Results The results showed convergences and divergence between the qualitative and quantitative data. For instance, they were convergences between both datasets relative to knowledge on and causes of mental health conditions. Conclusion The study highlights the need for health policymakers to leverage the information gathered on the study participants’ knowledge to develop appropriate mental health training programmes for deaf persons.

Abstract Background Women from areas of social deprivation and minority ethnic groups are more likely to experience poor physical health and have higher rates of mental health problems relative to women from less socially disadvantaged groups. However, very little research has examined this in relation to perinatal anxiety. The current study aims to determine prevalence, risk factors and desire for treatment for perinatal anxiety in three regions of the UK with diverse regional characteristics. Methods Women completed measures of anxiety in early, mid-, late-pregnancy and postpartum. Participants were included from three regions of the UK: Region 1 = North East England & North Cumbria n = 512; Region 2 = London North Thames n = 665; Region 3 = West Midlands n = 705. Results Prevalence of perinatal anxiety was lower in Region 1 (OR 0.63 95% CI 0.45 to 0.89) and Region 2 (OR 0.72 95% CI 0.52 to 0.98) relative to Region 3. Analysis showed the effect of neighbourhood socioeconomic deprivation on perinatal anxiety differed by region. In more affluent regions, living in a deprived neighbourhood had a greater impact on perinatal anxiety than living in a deprived neighbourhood in a deprived region. Other factors associated with risk of anxiety in the perinatal period included physical health problems and identifying as being from ‘mixed or multiple’ ethnic groups. Conclusions Neighbourhood deprivation relative to regional deprivation is a better predictor of perinatal anxiety than either regional deprivation or neighbourhood deprivation alone. Women of mixed ethnic backgrounds and women with physical health problems may warrant more attention in terms of screening and support for perinatal anxiety. Self-reported desire for treatment was found to be low.

Abstract Background The use of insecticide-treated nets (ITNs) is a strategy recommended by the World Health Organization (WHO) for malaria prevention. In Nigeria, ITNs have been periodically distributed since 2007 through campaigns. Campaign activities and assets are typically tracked using either a paper-based or digital system. In 2017, a digital approach was introduced in Ondo state for tracking attendance at training sessions as part of the ITN campaign. Following the success of the 2017 introduction, subsequent campaigns planned to digitise other aspects of the campaign to improve accountability and efficiency of the ITN distribution. The COVID-19 pandemic posed additional challenges for the ITN distribution planned for 2021 and adaptations were made to the programme strategy to ensure the campaign could go ahead safely. This article presents lessons and experiences from the 2021 ITN distribution campaign in Ondo state, Nigeria. Methods The campaign used RedRose, a customised mobile application, to monitor the planning and delivery of the campaign, collect household information including training personnel and tracking the transfer of ITNs between distribution hubs and households. ITNs were delivered through a single-phase door-to-door distribution strategy. Results The campaign distributed 2,965,125 ITNs covering 1,057,577 households across Ondo state. The digital application was beneficial for monitoring the quality of implementation and tracking assets and staff to ensure safety.. The single-phase door-to-door approach was more convenient for households compared to fixed-point distribution but increased the workload for mobilization and distribution teams. Conclusions Single phase door-to-door strategy using digital tools was an effective method to increase coverage of ITNs while closely tracking the progress of distribution campaigns. High-quality population data are needed to further improve the planning and implementation of ITN campaigns and other health interventions.

Abstract Background Despite Ghana’s Persons with Disability Act, 2006 (Act 715) making provisions for access to healthcare services for adolescents with disabilities and their families, a corpus of literature has reported that persons with disabilities continue to face challenges in accessing healthcare services. However, the voices of adolescents with disabilities and their families are very scarce in such discourse. This study explored the experiences of adolescents with disabilities and their families in accessing healthcare services as per the provisions described in Ghana’s Act 715. Methods This study involved 45 participants, including 25 adolescents with disabilities and 20 family members from a municipality in Ghana. Employing a qualitative descriptive design, semi-structured interviews were conducted which was then analyzed thematically and interpreted using Critical Disability Theory. Results The study identified two major categories of barriers to healthcare access: environmental (socio-economic difficulties, poor built environment, unavailability of rehabilitation services) and systemic (cultural beliefs, poor support at healthcare facilities and inadequate healthcare legislative provisions for families of children with disabilities). Despite legal provisions for free healthcare, participants faced significant financial barriers, with specialist services often not covered by the National Health Insurance Scheme. Conclusions The study calls for policy adjustments to fully cover specialist care under Ghana’s National Health Insurance Scheme, establishment of local-level health assessment and resource centers, educational campaigns to change cultural perceptions, and training of healthcare workers to promote quality access to healthcare.

Abstract Background Sierra Leone faces a significant challenge in addressing HIV/AIDS, particularly among adolescent girls and young women. This age group is considered highly vulnerable due to biological factors and social inequalities. Understanding the prevalence of HIV testing in this demographic is crucial for designing effective prevention and treatment strategies. This study investigated the spatial distribution of HIV testing and its associated factors among adolescent girls and young women in Sierra Leone. Methods Data from the 2019 Sierra Leone Demographic and Health Survey was used for the study. The sample comprised 6,062 adolescent girls and young women between the ages of 15 and 24. Spatial autocorrelation and Moran’s I statistic were employed to analyze the spatial distribution of HIV testing. An analysis utilising mixed-effect multilevel binary logistic regression was performed to determine the factors associated with HIV testing. The findings were presented as adjusted odds ratios (aOR) and a 95% confidence interval (CI). Results The national prevalence of HIV testing among adolescents and young women in Sierra Leone was 42.1% [40.3,43.9]. Kailahun, Kambia, Tonkolil, some parts of the Western rural area, and Bonthe districts were found to be statistically significant hotspot for HIV testing. Whereas, Karene, Falaba, Bo, kenema, and some parts of Pujuhun were statistically cold spot districts. Adolescent girls and young women aged 20–24 [aOR = 1.63, 95% CI = 1.29, 2.07] had higher odds of HIV testing than those aged 15–19. Those with secondary/higher education [aOR = 1.87, 95% CI = 1.40, 2.51] had higher odds of HIV testing than those with no education. The odds of HIV testing was higher among adolescent girls and young women who use the Internet [aOR = 1.75, 95% CI = 1.32, 2.33] than those who did not use internet. Adolescent girls and young women with one [aOR = 16.56, 95% CI = 12.31, 22.29] and two or more parity [aOR = 16.37, 95% CI = 10.86, 24.68] had higher odds of HIV testing than those with no parity. The likelihood of HIV testing was higher among adolescent girls and young women who had sex below 18 [aOR = 4.54, 95% CI = 3.25, 6.34] and those who had sex at 18+ [aOR = 5.70, 95% CI = 3.84, 8.45] compared to those who had never had sex. Adolescent girls and young women who visited health facilities in the past 12 months [aOR = 1.82, 95% CI = 1.46, 2.26] had higher odds of HIV testing than those who did not. Conclusion Despite some positive trends, HIV testing rates among adolescent girls and young women in Sierra Leone remain moderate. Spatial autocorrelation analysis consistently revealed hotspots and cold spots for HIV testing, with Kailahun, Kambia, Tonkolil, some parts of the Western rural area, and Bonthe districts remaining persistent hotspots. Age, education, internet use, sexual history, parity, and healthcare access are significant factors influencing testing behaviour. To improve testing rates, the government and policymakers should prioritize educational campaigns, expand internet access, integrate HIV testing into routine healthcare, and address stigma associated with HIV.

Abstract Background Adult day programs aim to facilitate aging in place by supporting the health and well-being of persons with dementia and providing respite to their caregivers. However, studies on the effects of day programs are inconclusive, and we especially lack insights into the context conditions and mechanisms of day programs that may produce different outcomes for different groups of persons with dementia and their caregivers. Our objective was to conduct a realist review, synthesizing research on day programs to develop program theories explaining how and why day programs do or do not produce positive or negative outcomes for different groups of persons with dementia, and caregivers. Methods We identified 14 literature reviews (including 329 references published between 1975 and 2021) on adult day programs. From this initial pool of studies, we will include those that focused on day program attendees with dementia or meaningful cognitive impairment, and/or their caregivers, and that report how day program contexts (C) and mechanisms (M) bring about outcomes (O) for attendees and caregivers. We will extract CMO statements (i.e., narratives that explain how and why day programs do or do not bring about certain outcomes for whom and under what circumstances). Using additional focused searches, citation mapping, citation tracking, and discussions with our researcher and expert team members, we will identify additional references. CMO statements will be synthesized, transformed into hypotheses, and linked and visualized to form program theories. Using focus groups and the James Lind Alliance Priority Setting Partnership method, we will discuss and prioritize our CMO statements and refine our program theories with 32 experts (older adults, caregivers, Alzheimer societies, caregiver organizations, day program staff and managers, and health system and policy decision makers). Discussion By identifying essential elements and processes of day programs and related knowledge gaps, this study will generate much-needed knowledge to leverage the full potential of day programs so they can provide appropriate care, preventing premature institutionalization, and unnecessary acute and primary care use. This will ultimately improve the quality of life of persons with dementia and their caregivers, alleviate caregiver burden, and reduce social costs. Systematic review registration PROSPERO CRD42024504030

Abstract Artificial Intelligence (AI) is transforming systematic reviews (SRs) in health research by automating processes such as study screening, data extraction, and quality assessment. This perspective highlights recent advancements in AI tools that enhance efficiency and accuracy in SRs. It discusses the benefits, challenges, and future directions of AI integration, emphasising the need for human oversight to ensure the reliability of AI outputs in evidence synthesis and decision-making in healthcare.

Abstract Background The COVID-19 pandemic led to dramatic changes in the lives of children that impact cardiometabolic health. Cities and counties had varying policies with respect to school closure, recreational programs, and efforts to mitigate food insecurity and economic distress. Our objective was to evaluate changes in BMI-z score and prevalence of overweight/obesity prior to and during the pandemic among children in San Francisco, CA, where public schools were closed for 18-months. Methods This was an electronic medical record-based retrospective cohort study. We included 15,401 children, 4–17 years of age at study onset. Our exposure was time into each of three time periods: (1) March 2018-February 2019; (2) March 2019-February 2020; (3) March 2020-August 2021 (the pandemic period of school closure). Generalized estimating equations (GEE) were used to assess changes in BMI-z score and overweight/obesity across the three time periods. We assessed for effect modification by age-category, insurance status, and race/ethnicity. Results Mean BMI-z score increased by 0.06 per year in time period 2, the year prior to the pandemic (p

Abstract Background Sickle cell disease (SCD) is a genetic blood disorder characterized by a painful vaso-occlusive crisis due to the sickling of red blood cells in capillaries. Complications often lead to liver and renal dysfunctions, contributing to morbidity and mortality, particularly for children under 5. This systematic review and meta-analysis aimed to evaluate the liver and renal functions of people with SCD (HbSS) compared to those without it (HbAA) in Africa. Methods The protocol was registered with PROSPERO (CRD42022346771). We searched PubMed, Embase, Web of Science, and Google Scholar using the keywords “liver function”, “renal function”, “sickle cell disease”, and “Africa” on 6th May 2023 for peer-reviewed articles with abstracts in English. We included case-control studies comparing SCD (HbSS) with controls without hemoglobinopathies (HbAA). We used the random-effect model to calculate the pooled average values for the blood tests of people with SCD in RStudio version 4.2.2. Results Overall, 17 articles were analyzed from five African countries involving 1312 people with SCD and 1558 controls. The pooled mean difference of liver enzymes aspartate transaminase (AST) was 8.62 (95% CI − 2.99–20.23, I 2 = 97.0%, p 50%, there was substantial variation in the reported articles’ results. Systematic review registration PROSPERO CRD42022346771

Abstract Background Approximately, 10% of people report a penicillin allergy; however, more than 90% can safely undergo delabeling after a detailed history, oral challenge, or other investigations such as penicillin skin testing (PST). Although PST is the gold standard, the results can be heterogeneous, and awaiting specialist assessment may take an inordinate amount of time. Therefore, oral provocation challenge has become acceptable for individuals with low-risk penicillin allergy histories. There also appears to be an association with increased prevalence of adverse drug reaction reporting in female individuals, which may translate to penicillin allergy prevalence; however, the evidence has not been assessed through a sex and gender lens. This systematic review will identify and synthesize the findings from studies that report measures of effectiveness and safety of interventions aimed at delabeling penicillin allergies in low-risk individuals. Information related to sex and gender will be extracted, where available, to understand potential differences in allergy reporting and patient outcomes. Methods The Cochrane Handbook for Systematic Reviews of Interventions and the Centre for Review and Dissemination’s Guidance for Undertaking Reviews in Health Care will be used as frameworks for conducting this systematic review. The literature search will be conducted by a medical librarian (B. M. M.) and will consist of a search strategy to identify and retrieve published studies that meet our inclusion criteria. Studies that require penicillin skin testing (PST) as a step prior to other interventions will be excluded. Integrated knowledge translation involving co-design was carried out for this systematic review protocol creation. Data extraction will be conducted at four levels: (1) study level, (2) patient level, (3) intervention level, and (4) outcome level. A narrative descriptive synthesis of results and risk of bias of all included studies will be provided, and, if relevant, a meta-analysis will be performed. Discussion The dissemination of findings from this knowledge synthesis to various stakeholders is intended to inform on options for evidence-based interventions to aid in delabeling penicillin allergies in individuals with a low risk of experiencing a hypersensitivity reaction. Detailed reporting on the characteristics of delabeling interventions as well as the effectiveness of similar interventions will benefit policy makers considering the implementation of a penicillin allergy delabeling protocol. Additionally, findings from this systematic review will report on the current evidence regarding the role of sex and gender in both the prevalence and outcomes associated with the presence of penicillin allergies. Systematic review registration PROSPERO CRD42022336457.

Abstract Background Latency remains a major obstacle to finding a cure for HIV despite the availability of antiretroviral therapy. Due to virus dormancy, limited biomarkers are available to identify latent HIV-infected cells. Profiling of individual HIV-infected cells is needed to explore potential latency biomarkers and to study the mechanisms of persistence that maintain the HIV reservoir. Methods Single cell spatial transcriptomic characterization using the CosMx Spatial Molecular Imager platform was conducted to analyze HIV-infected cells in formalin-fixed paraffin-embedded sections of splenic tissue surgically obtained from an HIV-infected humanized mouse model. Regulation of over a thousand human genes was quantified in both viremic and aviremic specimens. In addition, in situ hybridization and immunohistochemistry were performed in parallel to identify HIV viral RNA- and p24-containing cells, respectively. Finally, initial findings from CosMx gene profiling were confirmed by isolating RNA from CD4 + T cells obtained from a person living with HIV on antiretroviral therapy following either PMA/Ionomycin or DMSO treatment. RNA was quantified using qPCR for a panel of targeted human host genes. Results Supervised cell typing revealed that most of the HIV-infected cells in the mouse spleen sections were differentiated CD4 + T cells. A significantly higher number of infected cells, 2781 (1.61%) in comparison to 112 (0.06%), and total HIV transcripts per infected cell were observed in viremic samples compared to aviremic samples, respectively, which was consistent with the data obtained from ISH and IHC. Notably, the expression of 55 genes was different in infected cells within tissue from aviremic animals compared to viremic. In particular, both spleen tyrosine kinase (SYK) and CXCL17, were expressed approximately 100-fold higher. This data was further evaluated against bulk RNA isolated from HIV-infected human primary CD4 + T cells. A nearly 6-fold higher expression of SYK mRNA was observed in DMSO-treated CD4 + T cells compared to those stimulated with PMA/Ionomycin. Conclusion This study found that the CosMx SMI platform is valuable for assessing HIV infection and providing insights into host biomarkers associated with HIV reservoirs. Higher relative expression of the SYK gene in aviremic-infected cells from the humanized mouse HIV model was consistent with levels found in CD4 + T cells of aviremic donors.

Abstract Purpose Understanding the technical efficiency of health facilities is essential for an optimal allocation of scarce resources to primary health sectors. The COVID-19 pandemic may have further undermined levels of efficiency in low-resource settings. This study takes advantage of 2019 and 2020 data on characteristics of health facilities, health services inputs and output to examine the levels and changes in efficiency of Ghanaian health facilities. The current study by using a panel dataset contributes to existing evidence, which is mostly based on pre-COVID-19 and single-period data. Methods The analysis is based on a panel dataset including 151 Ghanaian health facilities. Data Envelopement Analysis (DEA) technique was used to estimate the level and changes in efficiency of health facilities across two years.. Results The results show a net increase of 26% in inputs, influenced mostly by increases in temporary non-clinical staff (131%) and attrition of temporary clinical staff and permanent non-clinical staff, 40% and 54% respectively. There was also a net reduction in output of 34%, driven by a reduction in in-patient days (37%), immunization (11%), outpatients visits and laboratory test of 9%. Nowithstanding the COVID-19 pandemic, the results indicate that 59 (39%) of sampled health facilities in 2020 were efficient, compared to 48 (32%) in 2019. The results also indicate that smaller-sized health facilities were less likely to be efficient compared to relatively bigger health facilities. Conclusion Based on the findings, it will be essential to examine factors that accounted for efficiency improvements in some health facilities, to enable health facilities lagging behind to learn from those on the efficiency frontier. In addition, the findings emphasise the need for CHAG to work with health facility managers to optimise inputs allocation through a redistribution of staff. Most importantly, the findings are suggestive of the resilience of CHAG health facilities in responding to a health shock such as the COVID-19 pandemic.

Abstract Background Much policy attention focuses on increasing the supply of workers in the English NHS but there has been less attention paid to the rise in leavers. This paper seeks to explore how existing data sets can illuminate the decision-making of leavers and inform actions that could mitigate this. Method Secondary analysis of routinely collected data from 79 workforce projects in the UK (n = 46 339 participants) over a 4-year (2019–2023) period was undertaken. Free text data we extracted and analysed using content analysis, sentiment analysis and text mining. Inclusion criteria were those who stated they had resigned, had confirmed retirement date, and had secured employment elsewhere either within or without the sector but had not yet resigned. Exclusion criteria were those who had not indicated they were leaving or indicated intention to leave. These findings were then compared with themes from Herzberg’s work hygiene theory and Hoffat and Woods’s professional practice environment theory. Results Multiple reasons were given for leaving. Findings were congruent with Herzberg’s two factor work hygiene theory and demonstrate that leavers are driven by the inability to meet their intrinsic motivation to practice according to their professional standards as much as by terms and conditions. Leavers describe suboptimal professional practice environments which produce obstacles to achieving their work objectives and leaving their intrinsic motivation frustrated. Conclusion Whilst reasons for leaving differ between people, there is a relationship between intrinsic motivation (why they want to do the job) and the conditions in which they try to do the job. This study suggests that looking beyond the primary reason for leaving given in the national dataset could identify how the practice environment influences the decision.

Abstract Background Poor person-centered maternal care (PCMC) contributes to high maternal mortality and morbidity, directly and indirectly, through lack of, delayed, inadequate, unnecessary, or harmful care. While evidence on poor PCMC prevalence, as well as inequities, expanded in the last decade, there is still a significant gap in evidence-based interventions to address PCMC. We describe the protocol for a trial to test the effectiveness of the “Caring for Providers to Improve Patient Experience” (CPIPE) intervention, which includes five strategies, targeting provider stress and bias as intermediate factors to improve PCMC and address inequities. Methods The trial will assess the effect of CPIPE on PCMC, as well as on intermediate and distal outcomes, using a two-arm cluster randomized controlled trial in 40 health facilities in Migori and Homa Bay Counties in Kenya and Upper East and Northeast Regions in Ghana. Twenty facilities in each country will be randomized to 10 intervention and 10 control sites. The primary intervention targets are all healthcare workers who provide maternal health services. The intervention impact will be assessed among healthcare workers in the study health facilities and among women who give birth in the study health facilities. The primary outcome is PCMC measured with the PCMC scale, via multiple cross-sectional surveys of mothers who gave birth in the preceding 12 weeks in study facilities at baseline (prior to the intervention), midline (6 months after intervention start), and endline (12 months post-baseline) (N = 2000 across both countries at each time point). Additionally, 400 providers in the study facilities across both countries will be followed longitudinally at baseline, midline, and endline, to assess intermediate outcomes. The trial incorporates a mixed-methods design; survey data alongside in-depth interviews (IDIs) with healthcare facility leaders, providers, and mothers to qualitatively explore factors influencing the outcomes. Finally, we will collect process and cost data to assess intervention fidelity and cost-effectiveness. Discussion This trial will be the first to rigorously assess an intervention to improve PCMC that addresses both provider stress and bias and will advance the evidence base for interventions to improve PCMC and contribute to equity in maternal and neonatal health. Trial registration ClinicalTrials.gov: NCT06085105. Protocol version and date: v2-11-07-23

Abstract Background Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT. Methods Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement. Results All societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65–4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00). Conclusion The SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families.

Abstract Background Gastric cancer (GC), a molecularly heterogeneous disease, is the third leading cause of cancer death worldwide. The majority of GC cases worldwide occur in East Asia, predominantly China. Mutational Signature Framework offers an elegant approach to identify mutational processes present in tumors. Methods To identify mutational signature patterns, we conducted whole exome sequencing (WES) analysis in Chinese patients with GC. Mutect2 and MutsigCV were used to identify significantly mutated genes in 175 Chinese GC cases using paired tumor-normal tissues. We investigated mutational signatures using Catalogue of Somatic Mutations in Cancer (COSMIC) Version 2 (V2) and Version 3 (V3). Results We identified 104 mutated genes with P

Abstract Background Serious games are risk-free environments training various medical competencies, such as clinical reasoning, without endangering patients’ safety. Furthermore, serious games provide a context for training situations with unpredictable outcomes. Training these competencies is particularly important for healthcare professionals in emergency medicine. Methods Based on these considerations, we designed, implemented, and evaluated a serious game in form of an emergency department, containing the features of a virtual patient generator, a chatbot for medical history taking with self-formulated questions, artificially generated faces based on an artificial intelligence algorithm, and feedback for students. The development process was based on an already existing framework resulting in an iterative procedure between development and evaluation. The serious game was evaluated using the System Usability Scale and the User Experience Questionnaire. Results The System Usability Scale provided a substantial result for the usability. In terms of the user experience, four scales yielded positive results, whereas two scales yielded neutral results. Conclusion The evaluation of both usability and user experience yielded overall positive results, while simultaneously identifying potential areas for improvement. Further studies will address the implementation of additional game design elements, and testing student learning outcome.

Abstract Background Informed consent is the cornerstone of research ethics. One of its goals is that participants enter research with an understanding of what their participation entails. This paper is a study on how researchers understand the informed consent process. Previous studies have looked at this topic from a research participant perspective. However, few studies focus on the perspectives of the researchers. Therefore, this is an important paper that highlights an important issue (informed consent) from the perspective of those who administer it during research. Methods In-depth interviews were conducted with 18 researchers from 3 different research centers in Malawi working in clinical trials. The data was analyzed using open code utilizing the thematic approach to qualitative data. Results This study identified that researchers have good awareness of the role of informed consent, how important it is for participants to understand the given information and ways to adjust their practice accordingly when obtaining it in order to enhance participant understanding. According to the research staff, most participants do not really understand all the concepts of the study at the initial visit, they gain more understanding during subsequent visits. It was emphasized that the best method of facilitating informed consent is reading the informed consent to the participant, thus a face-to-face conversation. Long and complex informed consent was identified as one of the barriers to participant understanding of the informed consent. Shortening the informed consent form and having additional conversation with the participants was suggested as one way of improving participant comprehension. Conclusion Most of the participants understand much of the information during subsequent visits as you keep reminding them since informed consent is an ongoing process. Existing relationship or trust between a participant and a researcher, may influence participants’ decision and misguide their understanding on the purpose of the study. Adequate time should be allocated to informed consent discussions. Shortening the informed consent forms and having additional conversations with potential participants may help improve their understanding.

Abstract Background Depression and anxiety are prevalent after stroke and associated with poor outcomes. We previously co-developed a stroke-specific self-management intervention, HEADS: UP (Helping Ease Anxiety and Depression after Stroke). The two studies reported here aimed to test the feasibility and acceptability of the HEADS: UP course and supporting materials, and research processes ahead of a definitive trial. Methods We recruited community-dwelling stroke survivors (SS) ≥ 3 months post-stroke, with symptoms of mood disorder (Hospital Anxiety and Depression Scale ≥ 8). Participants could ‘enrol’ a family member/ ‘other’ to take part with them, if desired. Study 1 tested HEADS: UP delivered in-person, and informed optimisation of research processes and intervention delivery and materials. In a pragmatic response to Covid-related socialising restrictions, HEADS: UP was then adapted for online delivery, tested in Study 2. The primary outcome (both studies) was the feasibility (acceptability, fidelity) of the intervention and of research processes. Quantitative data (including patient-reported outcome measures (PROMs) assessing mood and quality of life) and qualitative data were collected pre-/post-intervention. Descriptive statistics were used to analyse quantitative data; a thematic framework approach was used to analyse qualitative data. Both studies received ethical approval prior to commencement. Results Study 1 Feasibility: 13 (59.1%) of 22 potentially eligible stroke survivors consented; aged 66 (median, interquartile range (IQR) 14); male (n = 9; 69%); 28 (IQR 34) months post-stroke. Of these, n = 10 (76.9%) completed PROMS pre-intervention; n = 6 (46.2%) post-intervention. Acceptability: Nine (69.2%) of the 13 participants attended ≥ 4 core intervention sessions. Aspects of screening and data collection were found to be burdensome. Study 2 Feasibility: SS n = 9 (41%) of 22 potentially eligible stroke survivors consented; aged 58 years (median; IQR 12); male (n = 4; 44.4%); 23 (IQR 34) months post-stroke. Of these, n = 5 (55.6%) completed PROMS pre-intervention; n = 5 (55.6%) post-intervention. Acceptability: Five (55.6%) of the 9 participants attended ≥ 4 core sessions. They found online screening and data collection processes straightforward.

Abstract Background Orthopedic injuries are serious and continue to be a concern for healthcare systems worldwide. Approximately 90% of the estimated traumatic injuries occur in low- and middle-income countries. In Kenya, there is a dearth of information on orthopedic injury patterns that could be used to prioritize injury prevention measures and to help hospital management teams allocate resources appropriately. The purpose of this study was to determine the epidemiology of orthopedic injuries admitted to Kenyatta National Hospital. Methods This was a retrospective cross-sectional study. Overall, 720 charts were reviewed. Data were analyzed using frequency distribution, pearson chi-square test and logistic regression. Results Overall, 85% were aged 15–64 years. Approximately 80% were male, married or single. Patients with primary or secondary education composed 72%. Road traffic accidents (59.4%) and falls (24.7%) were the most common mechanisms of injury. A total of 99.9% of the inpatients were Kenyans. Open injuries were 40.1%. Lower limb (67.4%) and upper limb (26.9%) injuries were the most common. Inpatients aged 15–24 years were 74% less likely to have upper limb injuries than those aged 0–14 years (p = 0.023). However, those aged 15–24 years were 19.250 times more likely to have spine injuries than those aged 0–14 years (p = 0.008). Males were 68.6% and 51.2% less likely to have pelvic injury and comorbidities, respectively, than females (p

Abstract Background Women’s intentions to use any contraceptive method are critical for better understanding their future needs and making them more likely to act on that intention. This study assessed the factors associated with the intention to use modern contraceptives among women of reproductive age in Benin. Methods This was a cross-sectional study that used the 2017–2018 Benin Demographic and Health Survey (BDHS). The study analyzed a weighted sample of 13, 582 women of reproductive age who were non-users of contraceptives. The intention to use contraceptives was the outcome variable. Multivariate logistic regression analysis was conducted to determine the factors associated with the intention to use contraceptives among women of reproductive age. The results were estimated using an adjusted odds ratios (aOR) with a 95% confidence interval (CI) and statistical significance set at p

Abstract Background Assisted living (AL) is an increasingly common residential setting for persons with dementia; yet concerns exist about sub-optimal care of this population in AL given its lower levels of staffing and services. Our objectives were to (i) examine associations between AL setting (dementia care vs. other), COVID-19 pandemic waves, and prevalent antipsychotic, antidepressant, anti-dementia, benzodiazepine, and anticonvulsant drug use among residents with dementia/cognitive impairment, and (ii) explore associations between resident and home characteristics and prevalent medication use. Methods We conducted a population-based, repeated cross-sectional study using linked clinical and health administrative databases for all publicly funded AL homes in Alberta, Canada, examined between January 2018 - December 2021. The quarterly proportion of residents dispensed a study medication was examined for each setting and period (pandemic vs. comparable historical [2018/2019 combined]) focusing on four pandemic waves (March-May 2020, September 2020-February 2021, March-May 2021, September-December 2021). Log-binomial GEE models estimated prevalence ratios (PR) for period (pandemic vs. historical periods), setting (dementia care vs. other) and period-setting interactions, adjusting for resident (age, sex) and home (COVID-19 cases, health region, ownership) characteristics. Results On March 1, 2020, there were 2,779 dementia care and 3,013 other AL residents (mean age 83, 69% female) with dementia/cognitive impairment. Antipsychotic use increased during waves 2–4 in both settings, but this was more pronounced in dementia care than other AL during waves 3 and 4 (e.g., adjusted [adj]PR 1.20, 95% CI 1.14–1.27 vs. adjPR 1.09, 95% CI 1.02–1.17, interaction p = 0.023, wave 3). Both settings showed a statistically significant but modest increase in antidepressant use and decrease in benzodiazepine use. For dementia care AL residents only, there was a statistically significant increase in gabapentinoid use during several waves (e.g., adjPR 1.32, 95% CI 1.10–1.59, wave 3). Other than a modest decrease in prevalent anti-dementia drug use for both settings in wave 2, no other significant pandemic effects were observed. Conclusions The persistence of the pandemic-associated increase in antipsychotic and antidepressant use in AL residents coupled with a greater increase in antipsychotic and gabapentinoid use for dementia care settings raises concerns about the attendant risks for residents with cognitive impairment.

Abstract Background COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear. Methods The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo. Results Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs. Conclusions In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants.

Abstract Background Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population. Methods We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 − 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression. Results For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 − 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 − 31.8 each), CIN1 (7.7%; 95% CI, 2.5 − 17.0) and micro-invasion (4.6%; 95% CI, 1.0 − 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 − 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 − 0.99; p = 0.025). Conclusion This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

Abstract Background Anxiety in pregnancy and postpartum is highly prevalent but under-recognised. To identify perinatal anxiety, assessment tools must be acceptable, relevant, and easy to use for women in the perinatal period. Methods To determine the acceptability and ease of use of anxiety measures to pregnant or postpartum women (n = 41) we examined five versions of four measures: the Generalised Anxiety Disorder scale (GAD) 2-item and 7-item versions; Whooley questions; Clinical Outcomes in Routine Evaluation (CORE-10); and Stirling Antenatal Anxiety Scale (SAAS). Cognitive interviews were used to examine ease of comprehension, judgement, retrieval and responding. Results All measures were acceptable. Some items were deemed less relevant to the perinatal period e.g., difficulties sleeping. Ease of comprehension, judgement, retrieval and responding varied, with all measures having strengths and weaknesses. The SAAS and CORE-10 had the lowest mean number of problematic components. The GAD had the highest mean number of problematic components​. Non-binary response options were preferred. Preferences for time frames (e.g. one week, one month) varied. Qualitative data provides in-depth information on responses to each measure. Conclusions Findings can be used to inform clinical guidelines and research on acceptable anxiety assessment in pregnancy and after birth.

Abstract Background Lucilia cuprina (Wiedemann, 1830) (Diptera: Calliphoridae) is the main causative agent of flystrike of sheep in Australia and New Zealand. Female flies lay eggs in an open wound or natural orifice, and the developing larvae eat the host’s tissues, a condition called myiasis. To improve our understanding of host-seeking behavior, we quantified gene expression in male and female antennae based on their behavior. Methods A spatial olfactometer was used to evaluate the olfactory response of L. cuprina mated males and gravid females to fresh or rotting beef. Antennal RNA-Seq analysis was used to identify sensory receptors differentially expressed between groups. Results Lucilia cuprina females were more attracted to rotten compared to fresh beef (> fivefold increase). However, males and some females did not respond to either type of beef. RNA-Seq analysis was performed on antennae dissected from attracted females, non-attracted females and males. Transcripts encoding sensory receptors from 11 gene families were identified above a threshold (≥ 5 transcript per million) including 49 ATP-binding cassette transporters (ABCs), two ammonium transporters (AMTs), 37 odorant receptors (ORs), 16 ionotropic receptors (IRs), 5 gustatory receptors (GRs), 22 odorant-binding proteins (OBPs), 9 CD36-sensory neuron membrane proteins (CD36/SNMPs), 4 chemosensory proteins (CSPs), 4 myeloid lipid-recognition (ML) and Niemann-Pick C2 disease proteins (ML/NPC2), 2 pickpocket receptors (PPKs) and 3 transient receptor potential channels (TRPs). Differential expression analyses identified sex-biased sensory receptors. Conclusions We identified sensory receptors that were differentially expressed between the antennae of both sexes and hence may be associated with host detection by female flies. The most promising for future investigations were as follows: an odorant receptor (LcupOR46) which is female-biased in L. cuprina and Cochliomyia hominivorax Coquerel, 1858; an ABC transporter (ABC G23.1) that was the sole sensory receptor upregulated in the antennae of females attracted to rotting beef compared to non-attracted females; a female-biased ammonia transporter (AMT_Rh50), which was previously associated with ammonium detection in Drosophila melanogaster Meigen, 1830. This is the first report suggesting a possible role for ABC transporters in L. cuprina olfaction and potentially in other insects. Graphical Abstract

Abstract Background During inpatient rehabilitation, physical therapists (PTs) often need to manually advance patients’ limbs, adding physical burden to PTs and impacting gait retraining quality. Different electromechanical devices alleviate this burden by assisting a patient’s limb advancement and supporting their body weight. However, they are less ideal for neuromuscular engagement when patients no longer need body weight support but continue to require assistance with limb advancement as they recover. The objective of this study was to determine the feasibility of using a hip flexion exosuit to aid paretic limb advancement during inpatient rehabilitation post-stroke. Methods Fourteen individuals post-stroke received three to seven 1-hour walking sessions with the exosuit over one to two weeks in addition to standard care of inpatient rehabilitation. The exosuit assistance was either triggered by PTs or based on gait events detected by body-worn sensors. We evaluated clinical (distance, speed) and spatiotemporal (cadence, stride length, swing time symmetry) gait measures with and without exosuit assistance during 2-minute and 10-meter walk tests. Sessions were grouped by the assistance required from the PTs (limb advancement and balance support, balance support only, or none) without exosuit assistance. Results PTs successfully operated the exosuit in 97% of sessions, of which 70% assistance timing was PT-triggered to accommodate atypical gait. Exosuit assistance eliminated the need for manual limb advancement from PTs. In sessions with participants requiring limb advancement and balance support, the average distance and cadence during 2-minute walk test increased with exosuit assistance by 2.2 ± 3.1 m and 3.4 ± 1.9 steps/min, respectively (p 0.339). Conclusions We incorporated a unilateral hip flexion exosuit into inpatient stroke rehabilitation in individuals with varying levels of impairments. The exosuit assistance removed the burden of manual limb advancement from the PTs and resulted in improved gait measures in some conditions. Future work will understand how to optimize controller and assistance profiles for this population.

Abstract Background Although road traffic injuries and deaths have decreased globally, there is substantial national and sub-national heterogeneity, particularly in low- and middle-income countries (LMICs). Ghana is one of few countries in Africa collecting comprehensive, spatially detailed data on motor vehicle collisions (MVCs). This data is a critical step towards improving roadway safety, as accurate and reliable information is essential for devising targeted countermeasures. Methods Here, we analyze 16 years of police-report data using emerging hot spot analysis in ArcGIS to identify hot spots with trends of increasing injury severity (a weighted composite measure of MVCs, minor injuries, severe injuries, and deaths), and counts of injuries, severe injuries, and deaths along major roads in urban and rural areas of Ghana. Results We find injury severity index sums and minor injury counts are significantly decreasing over time in Ghana while severe injury and death counts are not, indicating the latter should be the focus for road safety efforts. We identify new, consecutive, intensifying, and persistent hot spots on 2.65% of urban roads and 4.37% of rural roads. Hot spots are intensifying in terms of severity and frequency on major roads in rural areas. Conclusions A few key road sections, particularly in rural areas, show elevated levels of road traffic injury severity, warranting targeted interventions. Our method for evaluating spatiotemporal trends in MVC, road traffic injuries, and deaths in a LMIC includes sufficient detail for replication and adaptation in other countries, which is useful for targeting countermeasures and tracking progress.

Abstract Background Limited research has explored the effect of Circle of Willis (CoW) anatomy among blunt cerebrovascular injuries (BCVI) on outcomes. It remains unclear if current BCVI screening and scanning practices are sufficient in identification of concomitant COW anomalies and how they affect outcomes. Methods This retrospective cohort study included adult traumatic BCVIs at 17 level I-IV trauma centers (08/01/2017-07/31/2021). The objectives were to compare screening criteria, scanning practices, and outcomes among those with and without COW anomalies. Results Of 561 BCVIs, 65% were male and the median age was 48 y/o. 17% (n = 93) had a CoW anomaly. Compared to those with normal CoW anatomy, those with CoW anomalies had significantly higher rates of any strokes (10% vs. 4%, p = 0.04), ICHs (38% vs. 21%, p = 0.001), and clinically significant bleed (CSB) before antithrombotic initiation (14% vs. 3%, p

Abstract Background Chronic kidney disease (CKD) is a complex disorder that has become a high prevalence global health problem, with diabetes being its predominant pathophysiologic driver. Autosomal genetic variation only explains some of the predisposition to kidney disease. Variations in the mitochondrial genome (mtDNA) and nuclear-encoded mitochondrial genes (NEMG) are implicated in susceptibility to kidney disease and CKD progression, but they have not been thoroughly explored. Our aim was to investigate the association of variation in both mtDNA and NEMG with CKD (and related traits), with a particular focus on diabetes. Methods We used the UK Biobank (UKB) and UK-ROI, an independent collection of individuals with type 1 diabetes mellitus (T1DM) patients. Results Fourteen mitochondrial variants were associated with estimated glomerular filtration rate (eGFR) in UKB. Mitochondrial variants and haplogroups U, H and J were associated with eGFR and serum variables. Mitochondrial haplogroup H was associated with all the serum variables regardless of the presence of diabetes. Mitochondrial haplogroup X was associated with end-stage kidney disease (ESKD) in UKB. We confirmed the influence of several known NEMG on kidney disease and function and found novel associations for SLC39A13, CFL1, ACP2 or ATP5G1 with serum variables and kidney damage, and for SLC4A1, NUP210 and MYH14 with ESKD. The G allele of TBC1D32-rs113987180 was associated with higher risk of ESKD in patients with diabetes (OR:9.879; CI95%:4.440–21.980; P = 2.0E-08). In UK-ROI, AGXT2-rs71615838 and SURF1-rs183853102 were associated with diabetic nephropathies, and TFB1M-rs869120 with eGFR. Conclusions We identified novel variants both in mtDNA and NEMG which may explain some of the missing heritability for CKD and kidney phenotypes. We confirmed the role of MT-ND5 and mitochondrial haplogroup H on renal disease (serum variables), and identified the MT-ND5-rs41535848G variant, along with mitochondrial haplogroup X, associated with higher risk of ESKD. Despite most of the associations were independent of diabetes, we also showed potential roles for NEMG in T1DM.

Abstract Background Evolution of novelty is a central theme in evolutionary biology, yet studying the origins of traits with an apparently discontinuous origin remains a major challenge. Venom systems are a well-suited model for the study of this phenomenon because they capture several aspects of novelty across multiple levels of biological complexity. However, while there is some knowledge on the evolution of individual toxins, not much is known about the evolution of venom systems as a whole. One way of shedding light on the evolution of new traits is to investigate less specialised serial homologues, i.e. repeated traits in an organism that share a developmental origin. This approach can be particularly informative in animals with repetitive body segments, such as centipedes. Results Here, we investigate morphological and biochemical aspects of the defensive telopodal glandular organs borne on the posterior legs of venomous stone centipedes (Lithobiomorpha), using a multimethod approach, including behavioural observations, comparative morphology, proteomics, comparative transcriptomics and molecular phylogenetics. We show that the anterior venom system and posterior telopodal defence system are functionally convergent serial homologues, where one (telopodal defence) represents a model for the putative early evolutionary state of the other (venom). Venom glands and telopodal glandular organs appear to have evolved from the same type of epidermal gland (four-cell recto-canal type) and while the telopodal defensive secretion shares a great degree of compositional overlap with centipede venoms in general, these similarities arose predominantly through convergent recruitment of distantly related toxin-like components. Both systems are composed of elements predisposed to functional innovation across levels of biological complexity that range from proteins to glands, demonstrating clear parallels between molecular and morphological traits in the properties that facilitate the evolution of novelty. Conclusions The evolution of the lithobiomorph telopodal defence system provides indirect empirical support for the plausibility of the hypothesised evolutionary origin of the centipede venom system, which occurred through functional innovation and gradual specialisation of existing epidermal glands. Our results thus exemplify how continuous transformation and functional innovation can drive the apparent discontinuous emergence of novelties on higher levels of biological complexity.

Abstract Background Despite growing interest in workplace mental health interventions, evidence of their effectiveness is mixed. Implementation science offers a valuable lens to investigate the factors influencing successful implementation. However, evidence synthesis is lacking, especially for small-to-medium-sized enterprises (SMEs) and for specific work sectors. The objectives of this review are to establish the scope of research with explicit analysis of implementation aspects of workplace mental health interventions and to identify barriers and facilitators to implementation in general and within SMEs and selected sectors. Methods A systematic scoping review and meta-synthesis of mixed methods process evaluation research from 11 databases, with the evaluation of methodological quality (MMAT) and confidence in findings (CERQual), was conducted. We selected information-rich studies and synthesised them using domains within the Nielsen and Randall implementation framework: context, intervention activities, implementation; and mental models. Results We included 43 studies published between 2009 and 2022, of which 22 were rated as information-rich to be analysed for barriers and facilitators. Most studies were conducted in healthcare. Facilitators reflecting ‘high confidence’ included: relevant and tailored content, continuous and pro-active leadership buy-in and support, internal or external change agents/champions, assistance from managers and peers, resources, and senior-level experience and awareness of mental health issues. Healthcare sector-specific facilitators included: easy accessibility with time provided, fostering relationships, clear communication, and perceptions of the intervention. Stigma and confidentiality issues were reported as barriers overall. Due to the small number of studies within SMEs reported findings did not reach ‘high confidence’. A lack of studies in construction and Information and Communication Technology meant separate analyses were not possible. Conclusions There is dependable evidence of key factors for the implementation of workplace mental health interventions which should be used to improve implementation. However, there is a lack of studies in SMEs and in a larger variety of sectors. Systematic review registration Research Registry ( reviewregistry897 ).

Abstract Background Quality smoking data is crucial for assessing smoking-related health risk and eligibility for interventions related to that risk. Smoking information collected in primary care practices (PCPs) is a major data source; however, little is known about the PCP smoking data quality. This project compared PCP smoking data to that collected in the Māori and Pacific Abdominal Aortic Aneurysm (AAA) screening programme. Methods A two stage review was conducted. In Stage 1, data quality was assessed by comparing the PCP smoking data recorded close to AAA screening episodes with the data collected from participants at the AAA screening session. Inter-rater reliability was analysed using Cohen’s kappa scores. In Stage 2, an audit of longitudinal smoking status was conducted, of a subset of participants potentially misclassified in Stage 1. Data were compared in three groups: current smoker (smoke at least monthly), ex-smoker (stopped > 1 month ago) and never smoker (smoked

Abstract Background Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. Methods STORY follows 720 young people aged 16–25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings (‘Ōura ring’) unobtrusively measures individuals’ daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. Discussion By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.

Abstract Background Cameroon is one of the countries with the highest burden of malaria. Since 2018, there has been an ongoing conflict in the country, which has reduced access to healthcare for populations in affected regions, and little is known about the impact on access to malaria services. The objective of this study was to understand the current situation regarding access to malaria services in Cameroon to inform the design of interventions to remove barriers and encourage the use of available services. Methods A qualitative research study was carried out to understand the barriers preventing communities accessing care, the uptake of community health worker (CHW) services, and to gather perceptions on community engagement approaches, to assess whether these could be an appropriate mechanism to encourage uptake of community health worker (CHW) services. Twenty-nine focus group discussions and 11 in-depth interviews were carried out between May and July 2021 in two regions of Cameroon, Southwest and Littoral. Focus group discussions were held with CHWs and community members and semi-structured, in-depth interviews were conducted with key stakeholders including regional government staff, council staff, community leaders and community-based organisations. The data were analysed thematically; open, descriptive coding was combined with exploration of pre-determined investigative areas. Results The study confirmed that access to healthcare has become increasingly challenging in conflict-affected areas. Although the Ministry of Health are providing CHWs to improve access, several barriers remain that limit uptake of these services including awareness, availability, cost, trust in competency, and supply of testing and treatment. This study found that communities were supportive of community engagement approaches, particularly the community dialogue approach. Conclusion Communities in conflict-affected regions of Cameroon continue to have limited access to healthcare services, in part due to poor use of CHW services provided. Community engagement approaches can be an effective way to improve the awareness and use of CHWs. However, these approaches alone will not be sufficient to resolve all the challenges faced by conflict-affected communities when accessing health and malaria services. Additional interventions are needed to increase the availability of CHWs, improve the supply of diagnostic tests and treatments and to reduce the cost of treatment for all.

Abstract Importance Large-scale estimates of bronchopulmonary dysplasia (BPD) are warranted for adequate prevention and treatment. However, systematic approaches to ascertain rates of BPD are lacking. Objective To conduct a systematic review and meta-analysis to assess the prevalence of BPD in very low birth weight (≤ 1,500 g) or very low gestational age (

Abstract Background In the United States there are roughly three million births a year, ranging from cesarean to natural births. A major aspect of the birthing process is related to the healing environment, and how that helps or harms healing for the mother and child. Using the theoretical framework, Theory of Supportive Care Settings (TSCS), this study aimed to explore what is necessary to have a safe and sacred healing environment for mothers. Method This study utilized an updated Qualitative Interpretive Meta-synthesis (QIMS) design called QIMS-DTT [deductive theory testing] to answer the research question, What are mother’s experiences of environmental factors contributing to a supportive birthing environment within healthcare settings? Results Key terms were run through multiple databases, which resulted in 5,688 articles. After title and abstract screening, 43 were left for full-text, 12 were excluded, leaving 31 to be included in the final QIMS. Five main themes emerged from analysis: 1) Service in the environment, 2) Recognizing oneself within the birthing space, 3) Creating connections with support systems, 4) Being welcomed into the birthing space, and 5) Feeling safe within the birthing environment. Conclusions Providing a warm and welcoming birth space is crucial for people who give birth to have positive experiences. Providing spaces where the person can feel safe and supported allows them to find empowerment in the situation where they have limited control.

Abstract Background Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes. Methods A systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected. Results Six articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71–1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible. Conclusions This systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years. Systematic review registration PROSPERO CRD42022308006

Abstract The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs’ potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.

Abstract Background Autism spectrum disorder (ASD) is a lifelong neurological condition which results in social skill deficits, communication difficulties, and restrictive and repetitive behaviour. The difficulties associated with parenting children with ASD have been studied extensively, mainly from the perspectives of mothers. The extent of involvement of fathers in the raising of children with ASD has received limited scholarly attention, especially in non-Western contexts such as the United Arab Emirates. Objectives This study asked mothers to evaluate the involvement of fathers in the development of children with ASD. Methods In all, 240 mothers completed the Fathers’ Involvement in Development and Rehabilitation Scale, designed based on a review of literature on the construct of involvement, namely attitude, participation in training, and support domains. The data were subjected to computation of mean scores, multivariate analysis of variance, hierarchical regression, and moderation analyses. Results The results suggested that fathers held positive attitudes and provided substantial support to their children with ASD. However, mothers were ambivalent regarding the participation of fathers in training to support the development of their children. Differences were also observed between participants according to marital status, location, child gender, and ASD severity. Conclusion Recommendations for targeted training for fathers and other study implications are discussed.