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Abstract Many studies have described the diversity of Austronesian-speaking Taiwanese people to shed more light on their origin and their connection with the “Out of Taiwan” migrations. However, the genetic relationship between the non-Austronesian-speaking groups of Taiwan and the populations of continental Asia is still unclear. Here, we studied the diversity of mtDNA in 767 non-Austronesian speakers from 16 locations in Taiwan using partial sequencing obtained from the hypervariable segment I (HVS-I) and coding regions 8,001-9,000 and 9.801–10,900 and 85 complete mtDNA genome sequences. Bayesian analysis of population structure was used to examine their relationship with over 3662 individuals representing indigenous groups of Taiwan, continental East Asia, Japan, and Island Southeast Asia. The whole analysis identified 278 haplotypes. Complete genomes revealed 62 novel subhaplogroups, of which 31 were exclusive to Taiwan. Estimates of coalescence times of all subhaplogroups showed peaks of diversification greater than 5.0 kya, likely characterizing gene flow from continental East Asian groups but not excluding in situ Taiwanese ancestry. Furthermore, a significant number of clades exclusive to non-Austronesian speakers of Taiwan (NAN_Tw) showed coalescence peaks between 1.0 and 2.6 kya, suggesting possible late Neolithic to early metal age settlements of NAN_Tw and local expansion in Taiwan.

Abstract Background Despite attempts in retracing the history of the Thao people in Taiwan using folktales, linguistics, physical anthropology, and ethnic studies, their history remains incomplete. The heritage of Thao has been associated with the Pazeh Western plains peoples and several other mountain peoples of Taiwan. In the last 400 years, their culture and genetic profile have been reshaped by East Asian migrants. They were displaced by the Japanese and the construction of a dam and almost faced extinction. In this paper, genetic information from mitochondrial DNA (mtDNA), Histoleucocyte antigens (HLA), and the non-recombining Y chromosome of 30 Thao individuals are compared to 836 other Taiwan Mountain and Plains Aborigines (TwrIP & TwPp), 384 Non-Aboriginal Taiwanese (non-TwA) and 149 Continental East Asians. Results The phylogeographic analyses of mtDNA haplogroups F4b and B4b1a2 indicated gene flow between Thao, Bunun, and Tsou, and suggested a common ancestry from 10,000 to 3000 years ago. A claim of close contact with the heavily Sinicized Pazeh of the plains was not rejected and suggests that the plains and mountain peoples most likely shared the same Austronesian agriculturist gene pool in the Neolithic. Conclusions Having been moving repeatedly since their arrival in Taiwan between 6000 and 4500 years ago, the Thao finally settled in the central mountain range. They represent the last plains people whose strong bonds with their original culture allowed them to preserve their genetic heritage, despite significant gene flow from the mainland of Asia. Representing a considerable contribution to the genealogical history of the Thao people, the findings of this study bear on ongoing anthropological and linguistic debates on their origin.

Abstract: The Xga and CD99 antigens of the human Xg blood group system show a unique and sex-specific phenotypic relationship. The phenotypic relationship is believed to result from transcriptional coregulation of the XG and CD99 genes, which span the pseudoautosomal boundary of the X and Y chromosomes. However, the molecular genetic background responsible for these blood groups has remained undetermined. During the present investigation, we initially conducted a pilot study aimed at individuals with different Xga/CD99 phenotypes; this used targeted next-generation sequencing of the genomic areas relevant to XG and CD99. This was followed by a large-scale association study that demonstrated a definite association between a single nucleotide polymorphism (SNP) rs311103 and the Xga/CD99 blood groups. The G and C genotypes of SNP rs311103 were associated with the Xg(a+)/CD99H and Xg(a−)/CD99L phenotypes, respectively. The rs311103 genomic region with the G genotype was found to have stronger transcription-enhancing activity by reporter assay, and this occurred specifically with erythroid-lineage cells. Such activity was absent when the same region with the C genotype was investigated. In silico analysis of the polymorphic rs311103 genomic regions revealed that a binding motif for members of the GATA transcription factor family was present in the rs311103[G] region. Follow-up investigations showed that the erythroid GATA1 factor is able to bind specifically to the rs311103[G] region and markedly stimulates the transcriptional activity of the rs311103[G] segment. The present findings identify the genetic basis of the erythroid-specific Xga/CD99 blood group phenotypes and reveal the molecular background of their formation.

Following publication of the original article [1], we have been notified that Additional file 3 was published with track changes.

Maternal–fetal ABO incompatibility is one of the causes of neonatal hyperbilirubinemia. We postulate that hemoglobin (Hb), hematocrit (Hct), and red blood cell (RBC) values for cord blood units (CBUs) are lower and erythroblast values higher for maternal–fetal ABO incompatible dyads than for compatible dyads. Objective: We investigated the relationship between Hb, Hct, RBC, and erythroblast CBU values and maternal–fetal ABO blood type compatibility. Methods: Mothers having blood group O who gave birth to infants with blood group A, B, or AB were classified as Group I. According to baby’s blood group, the members of Group I were further divided into AO (baby group A, mother group O), BO (baby group B, mother group O), and ABO (baby group AB, mother group O) subgroups. Mothers having blood group A who gave birth to infants with blood group B or AB and mothers having blood group B who gave birth to infants with blood group A or AB were classified as Group II. All other maternal–fetal blood type pairs were considered ABO compatible and were classified as Group III. We compared mean Hb, Hct, RBC, and erythroblast values for the infants’ CBUs among these three groups including the subgroups of Group I. Results: Group I had lower mean Hb, Hct, and RBC values than Group II and Group III (both p

Background: Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease predominantly occurring in females of childbearing age. Late onset SLE patients are uncommon and have different clinical and laboratory characteristics compared with younger patients. Methods: For further investigation of this subgroup, we retrospectively reviewed and analyzed 19 SLE patients with disease onset at age 60 years or older (Group A) collected from 1998 to 2008 in the computerized database of outpatients and inpatients of our hospital. For comparison, 50 SLE patients with disease onset between 15 and 40 years (Group B) were also selected using a simple random sampling method during the same period from the same database. Results: When compared with Group B, Group A had: (1) a decreased ratio of female to male; (2) a longer lag time from disease onset to diagnosis; (3) higher rates of renal insufficiency and mortality; and (4) lower immunologic disorder rates, including anti-double-stranded DNA antibody, anti-ribonucleoprotein antibody and hypocomplementemia. The main cause of death in both groups was septic shock. Conclusion: The clinical and laboratory features were found to be different between Groups A and B. Late onset SLE patients had a more insidious onset, a longer lag time from disease onset to diagnosis and, therefore, a higher mortality rate. Thus, this particular subgroup of SLE patients should be afforded greater attention to avoid delays in diagnosis or misdiagnosis.

Aneurysmal subarachnoid hemorrhage (SAH) is a highly morbid and fatal condition with high rate of cognitive impairment and negative impact in quality of life among survivors. Delayed cerebral infarction (DCI) is one the major factors for these negative outcomes. In this study we compared the circulating microRNA profiles of SAH patients and healthy individuals, and the circulating microRNA profiles of SAH patients with and without DCI.Peripheral blood samples on Day 7 after the onset of SAH were subjected to microarray analysis with Affymetrix miRNA 3.0 array and quantitative PCR analysis. SAH patients with (N = 20) and without DCI (N = 20) and Healthy controls (N = 20) were included for analyses.We demonstrated that 99 miRNAs were found to be dysregulated in the SAH patient group with DCI. 81 miRNAs were upregulated and 18 were downregulated. Findings from KEGG pathway analysis showed that miRNAs and target genes for axon guidance and TGF-beta signaling were involved, implying that the resulted differential miRNA expression pattern reflect the results of SAH instead of etiology of the disease. miR-132-3p and miR-324-3p showed distinctive upregulations in qPCR [miR-132: 9.5 fold (95%CI: 2.3 to 16.7) in DCI group and 3.4 fold (95%CI: 1.0 to 5.8) in Non-DCI group; miR-324: 4924 fold (95%CI: 2620 to 7228) in DCI group and 4545 fold (95%CI: 2408 to 6683) in non-DCI group]. However, there were no significant differences in fold changes between SAH patients with and without DCI [fold change ratios (mean+/-SD): 2.7+/-4.2 and 1.1+/-1.1 for miRNA-132 and miRNA-324].Our study demonstrated that as compared to healthy control, miR-132 and miR-324 showed a upregulation in both SAH DCI and Non-DCI groups. However, the differences between the SAH DCI and non-DCI groups were not statistically significant.

BACKGROUND: Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR] = 1.33, Bonferroni corrected combined P [P(Bc)] = 1.17 x 10⁻²), DPB1*05:01 (OR = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR = 0.62, P(Bc) = 1.97 x 10⁻²), DRB1*15:01 (OR = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR = 2.63, P(Bc) = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. CONCLUSIONS/SIGNIFICANCE: These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation.

Genetic affinities between aboriginal Taiwanese and populations from Oceania and Southeast Asia have previously been explored through analyses of mitochondrial DNA (mtDNA), Y chromosomal DNA, and human leukocyte antigen loci. Recent genetic studies have supported the "slow boat" and "entangled bank" models according to which the Polynesian migration can be seen as an expansion from Melanesia without any major direct genetic thread leading back to its initiation from Taiwan. We assessed mtDNA variation in 640 individuals from nine tribes of the central mountain ranges and east coast regions of Taiwan. In contrast to the Han populations, the tribes showed a low frequency of haplogroups D4 and G, and an absence of haplogroups A, C, Z, M9, and M10. Also, more than 85% of the maternal lineages were nested within haplogroups B4, B5a, F1a, F3b, E, and M7. Although indicating a common origin of the populations of insular Southeast Asia and Oceania, most mtDNA lineages in Taiwanese aboriginal populations are grouped separately from those found in China and the Taiwan general (Han) population, suggesting a prevalence in the Taiwanese aboriginal gene pool of its initial late Pleistocene settlers. Interestingly, from complete mtDNA sequencing information, most B4a lineages were associated with three coding region substitutions, defining a new subclade, B4a1a, that endorses the origin of Polynesian migration from Taiwan. Coalescence times of B4a1a were 13.2 +/- 3.8 thousand years (or 9.3 +/- 2.5 thousand years in Papuans and Polynesians). Considering the lack of a common specific Y chromosomal element shared by the Taiwanese aboriginals and Polynesians, the mtDNA evidence provided here is also consistent with the suggestion that the proto-Oceanic societies would have been mainly matrilocal.

Abstract Background In the UK, Health and Wellbeing Strategies (JHWS) were introduced to identify and help address the health needs of local communities. JHWS translate a borough’s Joint Strategic Needs assessment into actionable outcomes and prioritises areas of focus, but the content and approach of JHWS may vary across different local authorities (LAs) due to demographic and priority differences. Objective Characterise the key health and wellbeing components of existing and emerging health and wellbeing strategies of 33 local authorities in London. Design Scoping review study with content assessment. Methods An online search was conducted to identify JHWS documents. This search was supplemented with outreach to health and wellbeing boards to ensure that the latest documents were retrieved. A set of 62 health and wellbeing themes and words to be captured spanning 13 categories was developed by a team of researchers, and data collection was independently carried out by two researchers. Occurrences of words in the strategy documents were recorded, and a configuration matrix was created and used to determine data trends across the local authorities. A broad search of the context in which the search terms appeared was also performed to understand the trends. Results Thirty-three JHWS were analysed to identify key search term frequencies. The analysis encompassed strategies from 2015 to 2030, ranging from 7 to 94 pages. Mental health and youth terms emerged as the two top priorities across all strategies. Other frequent terms were related to access to healthcare, inequality, employment, smoking, housing, carers, and elderly individuals. Conversely, terms related to dental health, pollution, nutrition, sexual health, green spaces, breastfeeding, and climate were less cited. Conclusion This analysis provides insights into regional health priorities and a comprehensive overview of health and wellbeing strategies across London's local authorities. Despite certain limitations, the findings offer valuable insights for local authorities' strategic planning and future research.

Abstract Background Nowadays, stabilization splints for the management of bruxism and temporomandibular disorders (TMD) can be produced utilizing a digital workflow comprising a digital impression of the teeth, digital splint design, and computer-aided manufacturing of the splints. The latter is usually a milling process, however, more recently 3D printing gained popularity due to its better cost and time efficiency. It remains unknown whether 3D printed stabilization splints are inferior to milled splints regarding clinical outcomes. Methods This clinical trial assesses the non-inferiority of 3D printed occlusal splints compared to milled occlusal splints in a monocentric prospective randomized single-blinded crossover trial with two cohorts. One cohort includes 20 participants with bruxism, the other 20 participants with pain-related TMD, i.e., myalgia, myofascial pain, or arthralgia of the jaw muscles/the temporomandibular joint(s) diagnosed according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Michigan-type stabilization splints are fabricated in a digital workflow by milling or 3D printing using CE-marked materials within their intended purpose. The participants wear a milled and a 3D printed splint in a randomized order for 3 months each, with follow-up visits after 2 weeks and 3 months. Investigated outcome parameters are oral health-related quality of life (OHRQoL) evaluated by the Oral Health Impact Profile (OHIP-G14), participant satisfaction as rated on a visual analog scale, therapeutic efficacy, and technical result of the splints. In this context, therapeutic efficacy means antagonist wear and—in the TMD group—reduction of pain/disability assessed by the Graded Chronic Pain Scale (GCPS v2.0) and clinical assessment following the DC/TMD standard, while technical outcome measures splint fit, wear and fracture rate. Discussion The trial will provide important information on the clinical outcome of 3D printed stabilization splints in comparison to milled splints and will, therefore, enable an evidence-based decision in favor of or against a manufacturing process. This, in turn, will guarantee for a maximum of the patient’s OHRQoL during splint therapy, therapeutic efficacy, and longevity of the splints. Trial registration German Clinical Trials Register (DRKS) DRKS00033904. Registered on March 15, 2024.

Background: The integration of work coaches (WCs) and disability employment advisors (DEAs) into General Practitioner (GP) practices in the UK aims to address the interplay between health and employment by facilitating access to employment support, especially to people with disabilities and health conditions affecting their ability to work. This study seeks to explore the perspectives and perceptions of WCs, DEAs and GPs regarding the benefits and challenges of embedding WCs and DEAs in GP practices. Methods: Data was collected between May and July 2023 through semi-structured interviews with four GPs, four WCs and four DEAs working in NHS GP practices. The interviews were audio-recorded, transcribed verbatim and thematically analysed using the Thematic Framework method. Emergent themes were pre-structured and classified as perceived benefits, barriers and challenges or drivers and strategies. Results: The integration of WCs & DEAs within GP practices was perceived by respondents as fostering a direct collaboration between professionals as well as a greater openness of patients which benefited patients, WCs/DEAs and GPs. While all respondents emphasised the various benefits, they also identified several barriers and challenges. The implementation stage was perceived as particularly challenging, especially by WCs and DEAs, whereas the lack of human, financial and logistical resources hindered the service beyond this stage. Several strategies and drivers to support the service were identified, including the importance of receiving support from all professionals involved as well as making the service visible to both healthcare professionals and patients. Conclusion: Embedding WCs and DEAs in GP practices emerges as a promising approach which can benefit patients, GPs and WCs/DEAs. Exploring patients' perspectives directly is crucial to fully assess this type of service and identify any additional challenges and benefits.

Background Family interactions, which are always multi-faceted, are complicated further by family members with disabilities. In resource-poor settings, policies and programmes that address the needs of and challenges faced by families are often inaccessible or unavailable. Approximately 13% of the families in Tanzania have at least one member with a disability, yet family-centred research on caring for disabled children and adolescents is scarce in this context. Objective The aim is to explore the needs and challenges faced by families that care for children and adolescents with physical disabilities in the Kilimanjaro Region of north-eastern Tanzania. Methods This qualitative study had a constructivist grounded-theory design. In-depth interviews, using a semi-structured interview guide based on the social-capital framework, were conducted with 12 female participants aged between 24 and 80. A conceptual model of family needs, inspired by Maslow’s hierarchy of needs, informed the analysis. Results Challenging needs were grouped into five categories, which were linked to Maslow’s hierarchy of needs and related to the central concept of ‘adaptive adjustment’: (1) ‘barely surviving’; (2) ‘safety needs in jeopardy’; (3) ‘sociocultural protection’; (4) ‘self-esteem far beyond reach’, and (5) ‘dreaming of self-actualisation’. Conclusion Families caring for children and adolescents with physical disabilities in north-eastern Tanzania have needs that extend beyond the available and accessible resources. Families can adjust and adapt by avoiding certain situations, accepting the reality of their circumstances and exploring alternative ways of coping. A sustainable support system, including social networks, is essential for meeting basic needs and ensuring safety.

Background: Non-prescribed anabolic androgenic steroid (AAS) use is associated with AAS-induced hypogonadism (ASIH), and metabolic, cardiovascular, and mental health risks. Symptoms of ASIH (fatigue, depression, anxiety, sexual dysfunction) are hard to endure following cessation, but there is no consensus on whether endocrine treatment should be used to treat ASIH. This proof-of-concept study aims to explore safety of off-label clomiphene citrate therapy, whether the treatment will reduce the symptoms of androgen deficiency, and to study changes in health risks after cessation. Methods: In this open-labeled non-randomized off-label hormone intervention pilot study, we shall include males with AAS dependence intending to cease use. The 16-week intervention included clomiphene citrate, transdermal testosterone gel for the first four weeks and optional human chorionic gonadotropin (hCG) from week 4 if low treatment response. Measures of physical and mental health will be examined from ongoing AAS use, during the intervention, and at 6- and 12 months post cessation. Change in self-reported symptoms of hypogonadism and other withdrawal symptoms will be compared with data from a group of men who ended AAS use temporarily without the medical intervention. The study may provide valuable clinical insights and may be used to inform the design of future intervention studies.

Introduction: Right hemicolectomy (RHC) remains the treatment standard for goblet cell adenocarcinoma (GCA), despite limited evidence supporting survival benefit. This study aims to explore factors influencing surgical management and survival outcomes among patients treated with RHC or appendicectomy using NCRAS (UK) and SEER (USA) data. Methods: A retrospective analysis was conducted using 998 (NCRAS) and 1703 (SEER) cases. Factors influencing procedure type were explored using logistic regression analyses. Overall survival (OS) probabilities and Kaplan–Meier (KM) plots were generated using KM analysis and the log-rank test compared survival between groups. Cox regression analyses were performed to assess hazard ratios. Results: The NCRAS analysis revealed that age and regional stage disease were determinants of undergoing RHC, with all age groups showing similar odds of receiving RHC, excluding the 75+ age group. The SEER analysis revealed tumour size > 2 cm, and receipt of chemotherapy were determinants of undergoing RHC, unlike the distant stage, which was associated with appendicectomy. Surgery type was not a significant predictor of OS in both analyses. In NCRAS, age and stage were significant predictors of OS. In SEER, age, stage, and Black race were significant predictors of worse OS. Conclusions: The study shows variations in the surgical management of GCA, with limited evidence to support a widespread recommendation for RHC.

Congenital adrenal hyperplasia (CAH) is one of the most common inherited rare endocrine disorders. This case report presents two female siblings with delayed diagnosis of non-classical CAH 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2D/HSD3B2) despite early hospital admission and apparent CAH manifestations such as infections, hirsutism, menstrual disturbances, and PCOS phenotype. Initially, sister 1 was misdiagnosed with PCOS and then 11-hydroxylase deficiency (CYP11B1), based on ultrasound, biochemical findings, and negative genetic testing for 21-hydroxylase deficiency (CYP21A2). Additional diagnostic workup was performed when sister 2 also presented with symptoms of androgen excess. Genetic testing for CAH/steroid disorders finally revealed that both siblings were compound heterozygous for two variants in the HSD3B2 gene: a frameshift variant, c.558dup, p.(Thr187Hisfs*17) and a novel missense variant, c.65T>C, p.(Leu22Ser). A Synacthen test showed an insufficient cortisol increase. In vitro studies of the variants in a cell model revealed loss of function for the p.(Thr187Hisfs*17) and partial activity for p.(Leu22Ser) confirming non-classic CAH. Overlapping symptomatology and lack of specialized knowledge on steroid biosynthesis and associated rarest forms of CAH may explain the delayed diagnosis. However, with newer diagnostic methods comprising a less biased approach, very rare forms of non-classical CAH may no longer be overlooked in the future.

Burn mass casualty event occurrences are rare but will place significant burdens on any burn unit or healthcare system. Effective disaster preparedness plays a significant role in mitigating the aftermath of a burn mass casualty. The aim of this study was to assess the resource requirements during the initial two weeks of a burn mass casualty event. Eight patients in a burn mass casualty event were simulated using the Emergo Train System®. These simulated patients were matched with real historical patients treated in our burn centre, and their resource requirements were analysed. An average of eight staff is required to care for a patient per day along with almost 75 h of operating time (excluding anaesthesia and turnover time). A substantial quantity of consumables was used in the first two weeks. This study has demonstrated the substantial material consumption and staff requirements in the first two weeks of management in a burn mass casualty event. Such findings will offer valuable insight for disaster preparedness planning and resource management strategies.

IntroductionCaring for physically disabled children, particularly in contexts where resources are often insufficient or absent, exposes primary carers to significant psychological strain. The lack of structured mechanisms to address this psychological burden poses a considerable threat to the wellbeing of both carers and the children with disabilities under their care. However, research on the psychological wellbeing of carers in Tanzania is scarce. This study aimed to evaluate the psychological wellbeing and symptoms of anxiety and depression, along with associated factors, of carers of children, and adolescents with physical disabilities in the Kilimanjaro region.MethodsA cross-sectional survey was conducted from November 2020 to June 2021 in the Kilimanjaro region, involving 212 carers. The Swahili versions of the WHO-5 Wellbeing Index and Hopkins Symptoms Check List-25 were used to assess psychological wellbeing and symptoms of anxiety and depression. Data were analysed using IBM SPSS Statistics V.28. Multivariable linear and binary logistic regression were used to assess the associations.ResultsMore than four fifths (81%) of the carers were parents, and most of these parents were mothers (92%). Of the 212 carers, more than half (51%) exhibited poor psychological wellbeing, 42% had symptoms of anxiety, and 38% symptoms of depression. Notably, poor psychological wellbeing was significantly associated with symptoms of anxiety and depression. Results of a multivariable regression analysis indicated that extended family support was associated with better psychological wellbeing and lower odds of symptoms of anxiety and depression. A higher estimated monthly income was associated with better psychological wellbeing, and lower odds of symptoms of depression. Access to rehabilitation for the child was associated with improved psychological wellbeing and decreased likelihood of symptoms of anxiety.ConclusionMany carers of children, and adolescents with physical disabilities in Tanzania are at high risk of having poor psychological wellbeing, and symptoms of anxiety and depression. Support from extended-family networks is crucial in promoting good psychological wellbeing. The government in Tanzania should improve rehabilitation services, especially in disadvantaged rural areas, and integrate mental-health screening for carers in both rehabilitation programmes and primary healthcare.

Objectives The global prevalence of mental health disorders has risen significantly since the beginning of the COVID-19 pandemic. The pandemic has additionally caused disruption to mental health services, leading to a shift from in-person to remote service delivery. Given its long-term impact, it has become critical to evaluate whether changes in health delivery during the pandemic have had an effect on prescribing patterns for commonly prescribed psychotropic drugs. This study aims to assess the impact of the COVID-19 pandemic on changes in psychotropic prescribing patterns in adults, as well as differences in prescribing in different healthcare delivery approaches across various geographical contexts.Design and eligibility requirements Systematic review of cohort, interrupted time-series and cross-sectional studies examining prescribing trends for at least one commonly prescribed psychotropic drug during and after COVID-19 in accessing care remotely or face to face between 1 January 2020 and 17 June 2022.Data sources MEDLINE, EMBASE, CINAHL, HMIC and PsycINFO databases were searched in addition to citation chaining of relevant reviews.Extraction and analysis Study screening, data extraction and quality assessment were completed by two independent reviewers. The PECO strategy was used to devise the systematic review and findings were synthesised narratively.Results 16 studies were eligible for inclusion. Studies documenting changes in psychotropic prescribing trends provided very conflicting findings. There were no stark differences in prescribing outcomes between different healthcare delivery methods (ie, face-to-face consultations vs remote consultations). A noteworthy finding was that the prescribing rate of benzodiazepines was higher in women than men. No particular trends were observed for the prescription rates of hypnotics, antidepressants or antipsychotics.Conclusions Findings support mixed trends in the prescription of psychotropic medications in a range of settings, hindering conclusive statements on COVID-19’s impact on prescribing. In areas where remote consultations are in use, more comprehensive research is required to assess the safety of prescribing in these settings to inform public health policy and assess if the observed trends in our systematic review persist over time (given the increased consideration of remote and telehealth care in delivering services), particularly the safe and effective deployment of these services.

Abstract Background Libraries in the UK have evolved from traditional book-lending institutions into dynamic community hubs, This study aims to explore the potential of libraries to act as community hubs to promote mental and physical health and wellbeing of community-dwelling adults, drawing on insights from both library users and library staff in England. Design A mixed-method, cross-sectional study using online survey and interviews with community-dwelling adults and library staff. Methods We collected data using a 14-item electronic survey and interviews with library users and staff to gauge perceptions. Descriptive statistics and thematic analysis were used to identify key trends and emergent themes. Results We included 605 respondents from the survey and interviewed 12 library users and staff. Libraries remain popular and are considered a ‘safe place by members of the community, regardless of their frequency of service usage irrespective of whether they are frequent users of services. However, a lack of awareness among library users about community-facing services could act as a hurdle to improving community health and wellbeing. Targeted engagement with residents is needed to increase awareness of libraries’ services, including community interventions to help tackle loneliness and inequalities in digital and health literacy. Library staff often did not feel involved in important decision-making. Various barriers, drivers and practical recommendations were identified to leverage libraries as hubs to promote community health and wellbeing. Conclusion Libraries already offer a variety of resources that directly or indirectly support the health and wellbeing of community-dwelling adults and young people. However, public awareness of these services is limited. As we navigate post-pandemic recovery, libraries can serve as platforms for community engagement, fostering resilience, mental health support and reducing social isolation. Recognising libraries’ untapped potential can lead to healthier communities and improved wellbeing.

Abstract Background Even prior to the advent of the COVID-19 pandemic, there was ample evidence that loneliness and social isolation negatively impacted physical and mental health, employability, and are a financial burden on the state. In response, there has been significant policy-level attention on tackling loneliness. The objective of this scoping review was to conduct a loneliness policy landscape analysis across 52 countries of the UN European country groups. Our policy analysis sought to highlight commonalities and differences between the different national approaches to manage loneliness, with the goal to provide actionable recommendations for the consideration of policymakers wishing to develop, expand or review existing loneliness policies. Methods We searched governmental websites using the Google search engine for publicly available documents related to loneliness and social isolation. Seventy-eight documents were identified in total, from which 23 documents were retained. Exclusion of documents was based on predetermined criteria. A structured content analysis approach was used to capture key information from the policy documents. Contextual data were captured in a configuration matrix to highlight common and unique themes. Results We could show that most policies describe loneliness as a phenomenon that was addressed to varying degrees in different domains such as social, health, geographical, economic and political. Limited evidence was found regarding funding for suggested interventions. We synthesised actionable recommendations for the consideration of policy makers focusing on the use of language, prioritisation of interventions, revisiting previous campaigns, sharing best practice across borders, setting out a vision, evaluating interventions, and the need for the rapid and sustainable scalability of interventions. Conclusions Our study provides the first overview of the national loneliness policy landscape, highlighting the increasing prioritisation of loneliness and social isolation as a major public health and societal issue. Our findings suggest that policymakers can sustain this momentum and strengthen their strategies by incorporating rigorous, evidence-based intervention evaluations and fostering international collaborations for knowledge sharing. We believe that policymakers can more effectively address loneliness by directing funds to develop and implement interventions that impact the individual, the community and society.

Abstract Background It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). Methods This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. Results Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes. Conclusions Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. Trial registration details Not applicable.

Abstract Background Antidiabetic medication adherence is a key aspect for successful control of type 2 diabetes mellitus (T2DM). This systematic review aims to provide an overview of the associations between socioeconomic factors and antidiabetic medication adherence in individuals with T2DM. Methods A study protocol was established using the PRISMA checklist. A primary literature search was conducted during March 2022, searching PubMed, Embase, Web of Science, as well as WorldCat and the Bielefeld Academic Search Engine. Studies were included if published between 1990 and 2022 and included individuals with T2DM. During primary screening, one reviewer screened titles and abstracts for eligibility, while in the secondary screening, two reviewers worked independently to extract the relevant data from the full-text articles. Results A total of 15,128 studies were found in the primary search, and 102 were finally included in the review. Most studies found were cross-sectional (72) and many investigated multiple socioeconomic factors. Four subcategories of socioeconomic factors were identified: economic (70), social (74), ethnical/racial (19) and geographical (18). The majority of studies found an association with antidiabetic medication adherence for two specific factors, namely individuals’ insurance status (10) and ethnicity or race (18). Other important factors were income and education. Conclusions A large heterogeneity between studies was observed, with many studies relying on subjective data from interviewed individuals with a potential for recall bias. Several socioeconomic groups influencing medication adherence were identified, suggesting potential areas of intervention for the improvement of diabetes treatment adherence and individuals’ long-term well-being.

Abstract Background It has been reported that caseload midwifery, which implies continuity of midwifery care during pregnancy, childbirth, and the postnatal period, improves the outcomes for the mother and child. The aim of this study was to review benefits and risks of caseload midwifery, compared with standard care comparable to the Swedish setting where the same midwife usually provides antenatal care and the checkup postnatally, but does not assist during birth and the first week postpartum. Methods Medline, Embase, Cinahl, and the Cochrane Library were searched (Nov 4th, 2021) for randomized controlled trials (RCTs). Retrieved articles were assessed and pooled risk ratios calculated when possible, using random-effects meta-analyses. Certainty of evidence was assessed according to GRADE. Results In all, 7,594 patients in eight RCTs were included, whereof five RCTs without major risk of bias, including 5,583 patients, formed the basis for the conclusions. There was moderate certainty of evidence for little or no difference regarding the risk of Apgar ≤ 7 at 5 min, instrumental birth, and preterm birth. There was low certainty of evidence for little or no difference regarding the risk of perinatal mortality, neonatal intensive care, perineal tear, bleeding, and acute caesarean section. Caseload midwifery may reduce the overall risk of caesarean section. Regarding breastfeeding after hospital discharge, maternal mortality, maternal morbidity, health-related quality of life, postpartum depression, health care experience/satisfaction and confidence, available studies did not allow conclusions (very low certainty of evidence). For severe child morbidity and Apgar ≤ 4 at 5 min, there was no literature available. Conclusions When caseload midwifery was compared with models of care that resembles the Swedish one, little or no difference was found for several critical and important child and maternal outcomes with low-moderate certainty of evidence, but the risk of caesarean section may be reduced. For several outcomes, including critical and important ones, studies were lacking, or the certainty of evidence was very low. RCTs in relevant settings are therefore required.

Abstract Background Our ability to self-care can play a crucial role in the prevention, management and rehabilitation of diverse conditions, including chronic non-communicable diseases. Various tools have been developed to support the measurement of self-care capabilities of healthy individuals, those experiencing everyday self-limiting conditions, or one or more multiple long-term conditions. We sought to characterise the various non-mono-disease specific self-care measurement tools for adults as such a review was lacking. Objective The aim of the review was to identify and characterise the various non-mono-disease specific self-care measurement tools for adults. Secondary objectives were to characterise these tools in terms of their content, structure and psychometric properties. Design Scoping review with content assessment. Methods The search was conducted in Embase, PubMed, PsycINFO and CINAHL databases using a variety of MeSH terms and keywords covering 1 January 1950 to 30 November 2022. Inclusion criteria included tools assessing health literacy, capability and/or performance of general health self-care practices and targeting adults. We excluded tools targeting self-care in the context of disease management only or indicated to a specific medical setting or theme. We used the Seven Pillars of Self-Care framework to inform the qualitative content assessment of each tool. Results We screened 26,304 reports to identify 38 relevant tools which were described in 42 primary reference studies. Descriptive analysis highlighted a temporal shift in the overall emphasis from rehabilitation-focused to prevention-focused tools. The intended method of administration also transitioned from observe-and-interview style methods to the utilisation of self-reporting tools. Only five tools incorporated questions relevant to the seven pillars of self-care. Conclusions Various tools exist to measure individual self-care capability, but few consider assessing capability against all seven pillars of self-care. There is a need to develop a comprehensive, validated tool and easily accessible tool to measure individual self-care capability including the assessment of a wide range of self-care practices. Such a tool could be used to inform targeted health and social care interventions.

Congenital adrenal hyperplasia (CAH) is a recessive condition t hat affects the adrenal glands. Despite life-long replacement therapy with glucocorticoids and mineralocorticoids, adult patients with CAH often experience impaired gonadal function. In pubertal boys and in men with CAH, circulating testosterone is produced by the adrenal glands as well as the testicular, steroidogenic cells. In this European two-center study, we evaluated the function of Leydig and Sertoli cells in 61 boys and men with CAH, primarily due to 21-hydroxylase deficiency. Despite conventional hormone replacement therapy, our results indicated a significant reduction in serum concentrations of both Leydig cel l-derived hormones (i.e. insulin-like factor 3 (INSL3) and testosterone) and Sertoli cell-derived hormones (i.e. inhibin B and anti-Müllerian hormone) in adult males with CAH. Serum concentrations of INSL3 were particularly reduced in those with testicular adrenal rest tumors. To our knowledge, this is the first study to evaluate circulating INSL3 as a candi date biomarker to monitor Leydig cell function in patients with CAH.

BackgroundThe COVID-19 pandemic led to the implementation of a national policy of shielding to safeguard clinically vulnerable patients. To ensure consistent care for high-risk patients with hypertension, NHS England introduced the BP@home initiative to enable patients to self-monitor their blood pressure by providing them with blood pressure monitors. This study aimed to identify barriers and facilitators to the implementation of the initiative based on the experience and perspectives of programme managers and healthcare professionals (HCPs) involved in its implementation in London.Methods and findingsWe conducted five semi-structured focus groups and one individual interview with a total of 20 healthcare professionals involved at different levels and stages in the BP@home initiative across four of the five London Integrated Care Systems (ICSs). All focus groups and interviews were audio-recorded, transcribed and analysed thematically following the Framework Method. Respondents reported being challenged by the lack of adequate IT, human and financial resources to support the substantial additional workload associated with the programme. These issues resulted in and reinforced the differential engagement capacities of PCNs, practices and patients, thus raising equity concerns among respondents. However respondents also identified several facilitators, including the integration of the eligibility criteria into the electronic health record (EHR), especially when combined with the adoption of practice-specific, pragmatic and opportunistic approaches to the onboarding of patients. Respondents also recommended the provision of blood pressure monitors (BPMs) on prescription, additional funding and training based on needs assessment, the incorporation of BP@home into daily practice and simplification of IT tools, and finally the adoption of a person-centred care approach. Contextualised using the second iteration of the Consolidated Framework for Implementation Research (CFIR), these findings support key evidence-based recommendations to help streamline the implementation of the BP@home initiative in London's primary care setting.ConclusionsPrograms such as BP@Home are likely to become more common in primary care. To successfully support HCPs' aim to care for their hypertensive patients, their implementation must be accompanied by additional financial, human and training resources, as well as supported task-shifting for capacity building. Future studies should explore the perspectives of HCPs based in other parts of the UK as well as patients' experiences with remote monitoring of blood pressure.

Introduction Sexual violence (SV) is highly prevalent among university campuses across the globe, despite of several initiatives implemented to address it. Several studies have been published focusing on various aspects of SV on campuses. However, no review has been retrieved from the Joanna Briggs Institute (JBI) Database, Cochrane Library or Ovid examining evidence synthesis on prevalence, risk factors, victims and perpetrators, policies, laws and universities responses to SV in sub-Saharan Africa (SSA). This review aims to map the existing literature on SV victimisation among university students in SSA, related response strategies, and identify gaps in the evidence.Methods and analysis This review will follow JBI guidelines and will be conducted from 1 July 2023 to 31 December 2023. A team of five reviewers will screen eligible documents and articles for relevance from various data sources including electronic databases such as MEDLINE, EMBASE, PsycINFO, CINAHL, Google Scholar, PubMed and websites for government and agencies. Standard information for each study will be collected and a common analytical framework for all the primary documents will be conducted.Ethics and dissemination This review will involve analysis of published data only and therefore does not require ethics approval. The results will be published in a peer-reviewed journal.Registration This review has been registered with the Open Science Framework.

Background Social-emotional ability is important for overall health and wellbeing in early childhood. Recognizing preschool children in need of extra support, especially those living in unfavourable conditions, can have immediate positive effects on their health and benefit their wellbeing in the long-term. Objectives The aim of this study is to investigate whether there are social inequalities in preschool children’s social-emotional problems, and whether inequalities differ between boys and girls. Method This study utilized repeated measures from cross-sectional population-based surveys of three-year old children (2014–2018). The final study population comprised of 9,099 children which was 61% of all the eligible children in Västerbotten County during the study period. The Ages and Stages Questionnaires: Social-Emotional (ASQ:SE) 36-month interval was used to measure children’s social-emotional ability. Social inequalities were studied with respect to parents’ income, education, and place of birth, for which data was obtained from Statistics Sweden. Multiple logistic and ordered regressions were used. Results Among 3-year-olds, social-emotional problems were more common in the most vulnerable social groups, i.e. parents in the lowest income quintile (OR: 1.45, p

Abstract Background Abnormal birth weight – small for gestational age (SGA) and large for gestational age (LGA) – are important indicators for newborn health. Due to changes in lifestyle in recent decades, it is essential to keep up-to-date with the latest information on maternal factors linked to abnormal birth weight. The aim of this study is to investigate SGA and LGA in relation to maternal individual, lifestyle and socioeconomic characteristics. . Methods This is a register-based cross-sectional study. Self-reported data from Sweden’s Salut Programme maternal questionnaires (2010–2014) were linked with records in the Swedish Medical Birth Register (MBR). The analytical sample comprised 5089 singleton live births. A Swedish standard method using ultrasound-based sex-specific reference curves defines the abnormality of birth weight in MBR. Univariable and multivariable logistic regressions were used to examine crude and adjusted associations between abnormal birth weights and maternal individual, lifestyle and socioeconomic characteristics. A sensitivity analysis, using alternative definitions of SGA and LGA under the percentile method, was undertaken. Results In multivariable logistic regression, maternal age and parity were associated with LGA (aOR = 1.05, CI = 1.00, 1.09) and (aOR = 1.31, CI = 1.09, 1.58). Maternal overweight and obesity were strongly associated with LGA (aOR = 2.28, CI = 1.47, 3.54) and (aOR = 4.55, CI = 2.85, 7.26), respectively. As parity increased, the odds of delivering SGA babies decreased (aOR = 0.59, CI = 0.42, 0.81) and preterm deliveries were associated with SGA (aOR = 9.46, CI = 5.67, 15.79). The well-known maternal determinants of abnormal birthweight, such as unhealthy lifestyles and poor socioeconomic factors, were not statistically significant in this Swedish setting. Conclusions The main findings suggest that multiparity, maternal pre-pregnancy overweight and obesity are strong determinants for LGA babies. Public health interventions should address modifiable risk factors, especially maternal overweight and obesity. These findings suggest that overweight and obesity is an emerging public health threat for newborn health. This might also result in the intergenerational transfer of overweight and obesity. These are important messages for public health policy and decision making.

Abstract Background Recreational use of anabolic-androgenic steroids (AAS) is a public health concern world-wide associated with a range of physical and psychological side effects. Still, people who use AAS tend to be reluctant to seek treatment. This study aims to explore use characteristics, treatment-seeking behaviour, side effects and associated health concerns among men with AAS use. Methods The study includes cross-sectional self-report data from 90 men with a current or previous use of AAS exceeding 12 months, where 41 (45.6%) had sought treatment at least once during their lifetime, and 49 (54.4%) had not. Health service engagement was examined with descriptive statistics on reasons for contacting health services, transparency about AAS use, satisfaction with health services and reasons for not seeking treatment. Furthermore, experienced side effects and health concerns were compared between the treatment seeking and the non-treatment seeking group, using two-sample t-tests and Chi2 or Fisher exact tests for numerical and categorical variables, respectively. Results All 90 AAS-using men reported side effects from AAS use. Treatment seekers were significantly younger, experienced more side effects including gynecomastia, excessive sweating, fatigue, depression and anxiety, and expressed more concern for testosterone deficiency. Preventive health check-up was the most common reason for seeking treatment (n = 22, 53.7%), and 38 men (93%) were transparent about AAS use during consultations with health professionals. The main reported reasons for not seeking healthcare services were that the experienced side effects were not considered to be of treatment demanding nature (n = 39, 79.6%) and the belief that healthcare providers had scarce knowledge about AAS use and its health impacts (n = 12, 24.5%). Conclusions Reluctance to seek treatment among people who use AAS, despite having associated side effects and health concerns, may contribute to continued health risks. It is important to fill the knowledge gap on how to reach and treat this new patient group, and policy makers and treatment providers need to be educated on how to meet their treatment needs.

Key points We surveyed 1177 community dwelling adults to explore the use of lifestyle medicine approaches to tackle ED. Univariable and multivariable logistic regression was used to explore the association of ED with health and lifestyle factors. We collected data on how ED was addressed in general practice and to identify the best rated strategy to tackle the condition. A key limitation was lack of follow-up using personal interview component to explore individual drivers and barriers for the routine adoption of lifestyle behaviour modification to tackle ED. Structured education about the impact of lifestyle behaviour modification and how this could influence the appearance or trajectory of ED could help improve personal choice.

The ratio between luteinizing hormone (LH) and follicle-stimulating hormone (FSH) has previously been described as an excellent marker of sex in healthy infants. However, LH/ FSH remains not fully described in patients with differences of sex development (DSD). The aim was therefore to describe LH/FSH in infants with DSD. This was a retrospective study of DSD patients, all aged 0–1.2 years. In total, 87 infants with DSD and at least one serum sample per infant were included. Longitudinal samples from single patients were included whenever possible. Serum LH/FSH ratios in these patients were plotted against recently published age-related and sex-dimorphic cutoffs. Overall, LH/FSH sometimes corresponded to assigned sex without any obvious pattern in terms of diagnoses. LH/FSH corresponded to the biological sex in all patients with Turner or Klinefelter syndrome. In patients with 46,XX or 46,XY DSD (except congenital adrenal hyperplasia (CAH)), the ratios did not correspond to the assigned sex in all cases and were interchangeably within the male and female range. In patients with CAH, the ratio corresponded to biological sex (based on sex chromosomes) in some cases but also ranged across the cutoffs. In the 15 patients with 45,X/46,XY mosaicism, the LH/FSH ratios corresponded to the assigned sex in all cases (12 were raised as males, 3 as females) and at all time points in cases with multiple sampling. While this study describes LH/FSH in infants with DSD, the exact clinical role of the ratio in the management of these patients remains to be further elucidated.

Abstract Background Generalised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20–40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE. Methods This was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90. Results A total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89–1.19); p = 0.58]. There were no between-group differences for secondary outcomes. Conclusions VPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15. Trial registration No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Abstract REM sleep without atonia (RSWA) is a key feature for the diagnosis of rapid eye movement (REM) sleep behaviour disorder (RBD). We introduce RBDtector, a novel open-source software to score RSWA according to established SINBAR visual scoring criteria. We assessed muscle activity of the mentalis, flexor digitorum superficialis (FDS), and anterior tibialis (AT) muscles. RSWA was scored manually as tonic, phasic, and any activity by human scorers as well as using RBDtector in 20 subjects. Subsequently, 174 subjects (72 without RBD and 102 with RBD) were analysed with RBDtector to show the algorithm’s applicability. We additionally compared RBDtector estimates to a previously published dataset. RBDtector showed robust conformity with human scorings. The highest congruency was achieved for phasic and any activity of the FDS. Combining mentalis any and FDS any, RBDtector identified RBD subjects with 100% specificity and 96% sensitivity applying a cut-off of 20.6%. Comparable performance was obtained without manual artefact removal. RBD subjects also showed muscle bouts of higher amplitude and longer duration. RBDtector provides estimates of tonic, phasic, and any activity comparable to human scorings. RBDtector, which is freely available, can help identify RBD subjects and provides reliable RSWA metrics.