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Stage at diagnosis is one of the key factors determining survival rates of gynaecological cancers. Rapid access pathways were developed in the UK nearly two decades ago, aimed at diagnosing cancers at an earlier stage. Also known as cancer pathways, these consist of standardised referral methods to specialist clinics, where patients undergo diagnostic investigations, receive results and commence treatment swiftly. National cancer waiting time targets exist in conjunction with these pathways and have evolved in recent years to place an emphasis on confirming or excluding cancer within shorter timeframes. In this article we shall consider these UK-based pathways and targets in more detail, along with the challenges hospital trusts face in meeting them. We shall also outline the investigations required to diagnose the four most common gynaecological cancers - uterine, ovarian, cervical and vulval. [ABSTRACT FROM AUTHOR]

This paper reports on an investigation into female academics' experiences of living and working through the COVID‐19 pandemic in the United Kingdom (UK). A diary, diary‐interview method (DDIM) was used to gather qualitative data from 25 participants about their lives during the period March 2020–September 2021 and diary and interview data have since been curated and published in an open access digital archive. The paper argues firstly that in recording and interpreting change over time in the context of the COVID‐19 pandemic, the methodology constitutes a qualitative longitudinal research (QLLR) approach. Secondly, that the method has the capacity to convey temporal disruption and complexity, aligned with notions of crisis as fast, slow and ongoing. Thirdly, that Nixon's theorising of 'slow violence' can be used to frame the impacts of the pandemic as gradual, unseen and banal despite potentially negative implications for female academics' career progression. Finally, the paper argues that gathering this data through DDIM and publishing it in a publicly accessible digital archive represents a necessary form of witness with the potential to be utilised for future interventions. This paper reports on an investigation using a diary, diary‐interview method (DDIM) into female academics' experiences of living and working through the COVID‐19 pandemic in the United Kingdom (UK). The paper argues that DDIM has the capacity to convey temporal disruption and complexity, aligned with notions of crisis as fast, slow and ongoing. Nixon's theorising of 'slow violence' is used to frame a consideration of the pandemic's longer‐term, negative implications for female academics' career progression. [ABSTRACT FROM AUTHOR]

OBJECTIVES. We reviewed the use of social media and its influence on rhinoplasty decisions. MATERIAL AND METHODS. The literature survey was performed in PubMed, EBSCO, UpToDate, and ProQuest Central databases of Kırıkkale University and Google and Google Scholar databases. RESULTS. Networking features available through social media sites allow users to discover and share countless photos, videos and links from their desktops and mobile devices. In the United Kingdom, over 55% of facial plastic surgeons reported that their cosmetic patients were inspired to look better in selfies. 53.4% of respondents felt that TV shows promoting plastic surgery impacted the popularity of such procedures, and 65.0% of respondents believed that social media had a similar effect. Males reported being much less satisfied with surgery than females and were less specific about why they were unhappy. One-third of patients regularly looked for information about rhinoplasty on social media. Less than a third were affected by celebrities who had rhinoplasty for cosmetic reasons. However, over three percent believed the social media ads portraying rhinoplasty as a safe surgical procedure. CONCLUSION. We concluded that social media platforms play a significant role for the decision to undergo rhinoplasty and postoperative patient satisfaction. [ABSTRACT FROM AUTHOR]

Aim: This systematic review aimed to summarise the factors influencing women's engagement with, retention in and completion of substance abuse treatment since new national guidance was introduced in the United Kingdom in 2017 to assess potential barriers to service provision. Subjects and methods: Systematic reviews were conducted across two key databases using defined keywords to identify relevant journal articles. These were then graded by two independent reviewers before being selected for inclusion. The studies that were included focused on women over the age of 18 involved in community specialist substance misuse services for opiate, crack cocaine and/or alcohol addiction. Results: Twelve studies were identified, published between January 2017 until March 2020 (three cohort design, two cross-sectional and seven qualitative). Several barriers to female drug treatment were identified, including stigmatisation, disproportionate female roles in families, fear of children's services detaining their children and growing mistrust between clinicians and drug-users. Conclusions: The study found that services are struggling to cope with reduced government funds and increased demand resulting in shorter appointment times, quick turnover of staff and difficulty in accessing appointments at primary care centres and specialist services. Improving outcomes in engagement, retention and completion could be achieved by adding services such as integrated mental health treatments, parenting interventions and stress-reducing therapies and recruiting more female counsellors so women feel more comfortable discussing their previous traumas. [ABSTRACT FROM AUTHOR]

Introduction: Menopause is a key workplace issue. Many women will experience symptoms through their later working life. The ambulance service constitutes an employment setting that, dependent on the roles of female staff, can impact on the severity of menopause symptoms and experiences (Prothero et al., 2021). This study aimed to explore female ambulance staff experiences of the menopause transition and suggest ways to improve support offerings. Methods: A qualitative interpretive approach was adopted, involving 12 UK ambulance services. Participants were identified via purposive sampling, and semi-structured interviews were conducted from February to July 2022 via an online platform or telephone. Recordings were transcribed verbatim and analysed using an inductive thematic approach. Results: Twenty-two female participants, aged between 42 and 62 years, were interviewed, and represented all phases of the menopause: peri-menopause (n = 9); menopause (n = 5); post-menopause (n = 3); and unsure (n = 5). Fourteen participants had front-line (patient-facing) or emergency operation centre-based roles, while seven were employed in service support roles. Ten themes were identified: impact on work role; awareness and preparedness for menopause transition; personal impact of symptoms; desired support; appropriate sickness and menopause policy; managerial development; compassion and dignity; impact of working environment; impact on safety; and lack of choice. Lack of understanding and support from colleagues and line managers were identified as the key issues. This is included under the managerial development and compassion and dignity themes. Conclusions: The varying range of menopausal symptoms and their severity impacted on women’s performance at work. The experience of working while going through the menopause could be challenging. Employers should adopt a menopause policy which includes training and awareness for all staff, and suitable for front-line as well as service support staff. There is a need to create a culture where the menopause is not taboo, and women feel able to talk about their symptoms. [ABSTRACT FROM AUTHOR]

Appropriate breast support is recommended in sport; however, what constitutes appropriate support is complex, individual and often sports specific, particularly in elite sport given the wear duration. This intervention educated, assessed and advised elite British female athletes on breasts and bras; those with unresolved issues engaged in bespoke bra interventions. Following educational workshops (n = 80), breast/bra surveys (n = 60), individual bra assessments (n = 37); a rower, shooter, and hockey player participated in the bespoke bra intervention. Eighty-three per cent of athletes rated their breast/bra knowledge as ≤average. Fifty-one per cent experienced breast pain, affecting performance for 29%; seven used medication and one surgery to relieve symptoms. In individual bra assessments most wore ill-fitting, unsupportive bras and wanted bra advice. Bespoke bra interventions eliminated breast pain: for the rower, improved breast position and spine rotation; for the shooter, repositioned tissue and improved performance; and for the hockey player, accommodated smart devices. Whilst bespoke bra development is challenging, most elite athlete breast/bra issues are resolved via education, advice and fitting. [ABSTRACT FROM AUTHOR]

Background: The unadjusted gender pay gap in general practice is reported to be 33.5%. This reflects partly the differential rate at which women become partners, but evidence exploring gender differences in GPs' career progression is sparse. Aim: To explore factors affecting uptake of partnership roles, focusing particularly on gender differences. Design and setting: Convergent mixed-methods research design using data from UK GPs. Method: Secondary analysis of qualitative interviews and social media analysis of UK GPs' Twitter commentaries, which informed the conduct of asynchronous online focus groups. Findings were combined using methodological triangulation. Results: The sample comprised 40 GP interviews, 232 GPs tweeting about GP partnership roles, and seven focus groups with 50 GPs. Factors at individual, organisational, and national levels influence partnership uptake and career decisions of both men and women GPs. Desire for work–family balance (particularly childcare responsibilities) presented the greatest barrier, for both men and women, as well as workload, responsibility, financial investment, and risk. Greater challenges were, however, reported by women, particularly regarding balancing work–family lives, as well as prohibitive working conditions (including maternity and sickness pay) and discriminatory practices perceived to favour men and full-time GPs. Conclusion: There are some long-standing gendered barriers that continue to affect the career decisions of women GPs. The relative attractiveness of salaried, locum, or private roles in general practice appears to discourage both men and women from partnerships presently. Promoting positive workplace cultures through strong role models, improved flexibility in roles, and skills training could potentially encourage greater uptake. [ABSTRACT FROM AUTHOR]

In the UK, more women are studying medicine than men, most of whom have experienced sexism, yet these experiences are under-researched. This qualitative study explores female medical students' experiences of sexism on placement, impacts sustained, barriers and facilitators encountered upon reporting. A total of 17 semi-structured interviews were conducted, employing purposive sampling, snowball sampling and an inductive thematic analysis. A qualitative methodology was underpinned by the feminist social constructionist theory. Four themes were identified: 1—experiences of sexism, comprising physical and verbal harassment and microaggressions; 2—negative impacts of sexist encounters ranged from psychosocial to repercussions on learning and development; 3—systemic and attitudinal barriers to reporting; 4—recommendations to tackle sexism shaped by the views and experiences of female medical student participants. Female medical students experienced wide-ranging sexism which negatively impacted their wellbeing with negative repercussions for their training and development. The barriers to reporting need to be urgently addressed, and systems, policies and processes need to be over-hauled to sensitively, effectively and equitably manage and provide justice to students who experience and report sexism. Students need to be empowered to respond, report and be offered psychological safety in doing so. Attitudes and practices which are complicit in sustaining sexism need to be challenged and changed. [ABSTRACT FROM AUTHOR]

Objective: review of scientific literature of a descriptive nature that provides an update on useful concepts for the diagnosis and timely treatment of Hypothyroidism. Brief description: Hypothyroidism in the United Kingdom presented 2%, in the United States it has a prevalence of 1.3% and in Latin America its incidence is up to 10% of the population, the most affected age group are women, the Secondary hypothyroidism and subclinical hypothyroidism affects older women between 60 and 65 years of age, unlike secondary hypothyroidism that harms women between 30 and 50 years of age more, this higher prevalence is associated with physiological and hormonal changes, on the contrary, Congenital Hypothyroidism It commonly harms neonates, in conclusion, each of these categories generate alterations in the hypothalamic-pituitary axis, which leads to a low production and secretion of Thyrotropin (TSH), and simultaneously decrease its biological activity in the thyroid gland. Conclusions: hypothyroidism is a pathology that may or may not present symptoms, if a long-term constant examination is not carried out, it can affect the life of the individual, therefore, it is important to keep updated in order to detect it in time for its correct treatment in patient benefit. The population most likely to develop it is from developing countries due to the lack of iodine in the diet, hypothyroidism can be classified into four categories, congenital hypothyroidism, primary hypothyroidism, secondary hypothyroidism, subclinical hypothyroidism and each of them reduces biological activity in the thyroid gland. Through this review, the incidence and prevalence of hypothyroidism in recent years was disclosed, the age group prevalent in people over 70 years of age, especially in the female gender, as far as its treatment depends on the type of hypothyroidism diagnosed. [ABSTRACT FROM AUTHOR]

Objective: To determine treatment options (myomectomy vs. uterine artery embolization (UAE)) for women wishing to avoid hysterectomy. Methods: A multicenter randomized controlled trial was conducted on 254 women and data were collected on fibroid‐specific quality of life (UFS‐QOL), loss of menstrual blood, and pregnancy. Results: At 4 years, the mean difference in the UFS‐QOL was 5.0 points (95% confidence interval (CI) −1.4 to 11.5; P = 0.13) in favor of myomectomy. This was not statistically significant as it was at 2 years. There were no differences in bleeding scores, rates of amenorrhea, or heavy bleeding. Of those who were still menstruating, the majority reported regular or fairly regular periods: 36 of 48 (75%) in the UAE group and 30 of 39 (77%) in the myomectomy group. Twelve women after UAE and six women after myomectomy became pregnant (4 years) with seven and five live births, respectively (hazard ratio 0.48, 95% CI 0.18–1.28). There was no difference between the levels of hormones associated with the uterine reserve in each group. Conclusion: Leiomyoma are common in reproductive‐aged women, causing heavy menses and subfertility. Among women with uterine fibroids, myomectomy resulted in better fibroid‐related quality of life at 4 years, compared with UAE but the treatments decreased menstrual bleeding equally. There was also no significant difference in the impact of treatment on ovarian reserve. Synopsis: Women with uterine fibroids were randomized between uterine artery embolization and myomectomy. Quality of life was greater in the myomectomy group at 2 years, but neither menstrual blood loss nor markers of ovarian function differed. [ABSTRACT FROM AUTHOR]

The inclusion of girls and women in sport at all levels depends on single sex categories for most sports from puberty onwards, because of the biological differences between the sexes. Most sport is, by definition, competitive; involving invasion games, teams, leagues, races, competitions and sometimes rankings, from foundation to excellence. Girls and women are underrepresented, particularly in traditional sport, as recognised by the UK Sports Councils and most governing bodies of sport. This paper uses feminist philosophy: Lister on androcentric citizenship, and Fraser on justice as balance, framing, recognition, representation and redistribution. It investigates the impact on the inclusion of girls and women, of eligibility policies adopting 'self-identification of gender' guidelines for the inclusion of transgender people in sport, at participation rather than elite levels. It explores fairness and equality as incorporated in law in the 2010 Equality Act in Britain, and contributes to 'equality evidence' available to the UK Sports Councils and GBS. These bodies are charged with developing fair and inclusive evidence-based eligibility criteria, in sports participation settings, for both girls and women, and transgender people. [ABSTRACT FROM AUTHOR]

International research suggests that female veterans may experience gender‐specific barriers to accessing veteran‐specific care. This is the first UK study to report an exploratory qualitative investigation of the provision of health and social care support for female veterans and whether this support meets their needs. The research team carried out 13 virtual semi‐structured interviews between October and November 2020, with representatives from statutory and third sector organisations that provide support to UK female veterans. Ethical approval was obtained from the Anglia Ruskin University School of Education and Social Care Research Ethics Committee. The authors identified four overarching themes and nine sub‐themes in a thematic analysis following the framework outlined by Braun and Clarke (2006). The findings of this study suggest that practitioners from statutory and third sector organisations perceive the UK veteran support sector as male‐dominated and male‐targeted, with a lack of consideration for female veterans' needs. Participants reported a lack of engagement with veteran‐specific services by female veterans and suggested that women either do not identify with the 'veteran' label or do not feel comfortable accessing male‐dominated veteran‐specific services. The need for specific services for female veterans split participant opinion, with most of those who were female veterans themselves highlighting the importance of 'safe spaces' for women, particularly those who had experienced gender‐based violence during military service. Others felt that the veteran support sector currently lacked evidence of women's unique support needs, and an examination of current provision was required. The authors recommend a thorough assessment of UK female veterans' health and social care needs, alongside development of training and guidance for health and social care professionals, to ensure that veteran services are adequately developed, tailored and targeted with women's needs in mind. [ABSTRACT FROM AUTHOR]

The coronavirus, COVID-19 pandemic spread across the globe in 2020, with an initial high case mortality in those requiring intensive care treatment due to serious complication. A vaccine programme was quickly developed and currently the UK is one of highest double vaccinated and boosted countries in the world. Despite tremendous efforts by the UK, new cases of COVID-19 are still occurring, due to viral mutation. A major problem associated with COVID-19 is the large a-symptomatic spread within the population. Little investigation into the a-symptomatic population has been carried out and therefore we pose that the residual effects of a-symptomatic infection is still largely unknown. Prior to mass vaccination, a multi-phased single cohort study of IgM and IgG COVID-19 antibody prevalence and the associated haemostatic changes were assessed in a Welsh cohort of 739 participants, at three time points. Positive antibody participants with age and gender matched negative antibody controls were assessed at 0, 3 and 6 months. Antibody positive females appeared to have lower antibody responses in comparison to their a-symptomatic male counterparts. Despite this initial testing showed a unique significant increase in TRAP-6-induced platelet aggregation, prothrombin time (PT) and clot initiation time. Despite coagulation parameters beginning to return to normal at 3 months, significant decreases are observed in both haemoglobin and haematocrit levels. The production of extracellular vesicles (EV) was also determined in this study. Although the overall number of EV does not change throughout the study, at the initial 0 months' time point a significant increase in the percentage of circulating pro-coagulant platelet derived EV is seen, which does not appear to be related to the extent of platelet activation in the subject. We conclude that early, but reversible changes in haemostatic pathways within the a-symptomatic, female, antibody positive COVID-19 individuals are present. These changes may be key in identifying a period of pro-coagulative risk for a-symptomatic female patients. [ABSTRACT FROM AUTHOR]

This study (1) assessed the impact different stages of the menstrual cycle has on experienced football performance and exercise ability (2) identified the experienced barriers to football participation menstruation presents in amateur women footballers. An online survey was used. The inclusion criteria were non-professional, women currently experiencing regular menstrual cycles, ≥18 years, ≥60 min football/week in the UK. Descriptive statistics were performed on quantitative data and thematic analysis of the open-ended questions. 127 responses were included. Most of the respondents were aged between 18–25 (89%), Caucasian (83%) and competing in Universities Leagues (69%). Menstruation was reported to "never" limit football playing in 17%, "sometimes" in 47%, "rarely" in 25% and "always" in 10% of respondents. The majority (73%) reported one or more barriers menstruation present to football participation. Following thematic analysis, 165 meaning units, 23 themes and seven categories were identified. Confidence and aerobic capacity/endurance were identified to be the aspects most negatively impacted during the pre-menstrual and menstrual stages. Confidence is likely to be negatively impacted due to the barriers identified. Thus, recommendations on how to reduce these through education of players and involved staff, at the club and the FA level have been made. [ABSTRACT FROM AUTHOR]

Background and Objectives: The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of these outcomes. We aimed to investigate whether the associations between BCS and stroke, LLD, and dementia risks are independent of genetic predisposition for these conditions and quantify the effect of healthy lifestyle across genetic risk distributions for these outcomes., Methods: Using the UK Biobank (UKB) prospective cohort study, we computed baseline BCSs and polygenic scores to estimate genetic predisposition for stroke and LLD and APOE ε allele status to stratify dementia risk. As for outcomes again in UKB, we measured incidence of stroke, LLD, and dementia. We used multivariate Cox proportional hazard models to assess associations between BCS, genetic predisposition, and these outcomes. We also conducted stratified and interaction analyses to estimate the incidence of these outcomes across quartiles of genetic risk and BCS., Results: We included 368,340 UKB participants (median age 58 years (interquartile range 51-63 years), 46.3% male). Independent of genetic risk, a 5-point increase in BCS corresponded to lowered hazards of stroke (hazard ratio [HR] 0.70, 95% CI 0.68-0.73), LLD (HR 0.65, 95% CI 0.63-0.67), and dementia (HR 0.82, 95% CI 0.78-0.85). Incidences of all 3 outcomes were higher among participants with high genetic risk of these outcomes. However, these increased risks were offset for individuals with a higher BCS (incidence rates per 1,000 person-years were 2.76 vs 1.19 for stroke, 7.34 vs 4.46 for LLD, and 3.64 vs 2.05 for dementia, when comparing low and high BCS)., Discussion: Across different genetic predispositions for stroke, LLD, and dementia, healthier lifestyle behaviors are protective for brain health, demonstrating the nondeterminism of genetic risk. Furthermore, differences in BCS behave as aggregate risk estimators of all 3 outcomes. Further work is needed to prospectively investigate the utility and performance of the BCS as a targeted intervention in populations at elevated genetic risk of age-related brain disease.

Background and Objectives: Mounting evidence points to a strong connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association's Life's Essential 8 (LE8) constitutes a research and public health construct capturing key determinants of cardiovascular health. However, the overall effect of the LE8 on global, clinically relevant metrics of brain health is still unknown. We tested the hypothesis that worse LE8 profiles are associated with higher composite risk of the most important clinical endpoints related to poor brain health., Methods: We conducted a two-stage (discovery and replication) prospective study using data from the UK Biobank (UKB) and All of Us (AoU), 2 large population studies in the United Kingdom and the United States, respectively. The primary exposure was the LE8 score, a validated tool that captures 8 modifiable cardiovascular risk factors (blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration), organized in 3 categories (optimal, intermediate, and poor). The primary outcome was a composite of stroke, dementia, or late-life depression. We evaluated associations using multivariable Cox proportional hazard models., Results: The discovery stage included 316,127 UKB participants (mean age 56, 52% female). Over a mean (SD) follow-up time of 4.9 (0.4) years, the unadjusted risk of the composite outcome was 0.7% (95% CI 0.61-0.74), 1.2% (95% CI 1.11-1.22), and 1.8% (95% CI 1.70-1.91) in participants with optimal, intermediate, and poor cardiovascular health, respectively ( p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health hazard ratio [HR], 1.37; 95% CI 1.24-1.52, and poor vs optimal cardiovascular health HR, 2.11; 95% CI 1.88-2.36, p trend <0.001). The replication stage included 68,407 AoU participants (mean age 56, 60% female). Over a mean (SD) follow-up time of 2.9 (1.41) years, the unadjusted risk of the composite outcome was 2.8% (95% CI 2.49-3.05), 6% (95% CI 5.76-6.22), and 9.7% (95% CI 9.24-10.24) in participants with optimal, intermediate, and poor cardiovascular health, respectively ( p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health, HR 1.35; 95% CI 1.21-1.51, and poor vs optimal cardiovascular health, HR 1.94; 95% CI 1.72-2.18; p trend <0.001)., Discussion: Among middle-aged adults enrolled in 2 large population studies, poor cardiovascular health profiles were associated with two-fold higher risk of developing a composite outcome that captures the most important diseases related to poor brain health. Because the evaluated risk factors are all modifiable, our findings highlight the potential brain health benefits of using the Life's Essential 8 to guide cardiovascular health optimization.

The relationship between depression and severe non-alcoholic fatty liver disease (NAFLD) has not been clearly defined. We conducted a longitudinal cohort study and a two-sample Mendelian randomization (MR) analysis to assess the association of depression with severe NAFLD risk. We used individual data from the UK Biobank study with 481,181 participants, and summary data from published genome-wide association studies. The association between depression and severe NAFLD was assessed using Cox proportional hazards regression analysis. Two-sample MR for depression with NAFLD was conducted, the principal analysis employed the inverse variance weighted (IVW) approach. In the observational study, after a median follow-up of 13.46 years, 4,563 participants had severe NAFLD. In multivariable-adjusted model, participants with depression had an increased risk of severe NAFLD (hazards ratio:1.21, 95% confidence interval (CI):1.09-1.34), as compared to those without depression. In subgroup analyses, the association between depression and severe NAFLD risk was generally observed across different subgroups. For the MR, result also showed that genetically predicted depression was causally associated with a higher risk of NAFLD (odds ratio:1.55, 95%CI:1.10-2.19) in IVW. Our study revealed a prospective association of depression with severe NAFLD, thus potentially necessitating clinical monitoring of individuals with depression for severe NAFLD., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval The UK Biobank study has approval from the North West Multi-centre Research Ethics Committee, all methods were performed in accordance with the relevant guidelines and regulations, and all participants provided written informed consent. As our MR study was based on publicly available data, no additional ethical approval or consent was required., (© 2024. The Author(s).)

Background: Whether genetic susceptibility to cardiovascular diseases (CVDs) enhances the vulnerability to adverse cardiovascular outcomes by air pollution is unknown. We assessed the combined effect of air pollution and genetic predispositions on CVD risk., Methods and Results: From the UK Biobank cohort, we selected genetically unrelated White British participants without CVD. Levels of ambient particulate matter with a diameter of <2.5 μm (PM 2.5 ) and <10 μm were estimated using land use regression models. An individual's genetic predisposition to CVDs was determined by polygenic risk scores for coronary artery disease, myocardial infarction, stroke, ischemic stroke, heart failure, and atrial fibrillation. We stratified mortality and CVD risk by PM 2.5 exposure across high and low genetic risk groups. A total of 249 082 participants (aged 56.9±8.0 years, 46.8% men) were followed for a median of 10.8 years. The combined effect of PM 2.5 exposure and the genetic predisposition of CVD demonstrated the highest risk of cardiovascular death in the high genetic risk group with the greatest PM 2.5 exposure (adjusted hazard ratios ranging from 1.73 to 2.12 across the polygenic risk score of each CVD). The combination of higher exposure to ambient PM 2.5 and high genetic risk was associated with higher incidence of all CVDs, although no significant interactions were observed between genetic risk and PM 2.5 exposure on cardiovascular death or CVD events., Conclusions: A combination of greater PM 2.5 exposure and higher genetic predisposition to particular CVDs was modestly associated with elevated risks of cardiovascular death and CVDs. Not only alleviating PM 2.5 exposure in the general population but also implementing individualized preventive approach for those at high genetic risk might be beneficial.

Background: Percutaneous coronary intervention (PCI) of the left main coronary artery (LMCA) for stable angina has steadily increased. Outcomes stratified by sex are inconclusive and limited. We assessed sex-based trends and differences in clinical outcomes among patients with stable angina who received LMCA PCI., Methods and Results: We retrospectively collected data on patients with stable angina who underwent LMCA PCI (2006-2022) from the UK national PCI registry. The primary outcome of interest was inpatient mortality. Secondary outcomes were major bleeding and major cardiovascular and cerebral events. Multivariate logistic regression was used to assess adjusted odds ratio for outcome of interest. Of the 24 271 LMCA PCI performed, 5497 (22.7%) were in women. Women were older than men (median 72.7 versus 70.4) and less likely to have their PCI via radial access (50.3% versus 58.9%). More women had PCI guided by intravascular ultrasound (43.4% versus 41.2%). Women had significantly lower comorbid burden than men. Higher prevalence of chronic renal failure (6.72% versus 4.77%), smoking history (61.47% versus 45.68%), diabetes (27.36% versus 25.74%), prior myocardial infarction (45.36% versus 35.89%), and prior coronary artery bypass grafting (42.13% versus 30.34%) was observed in men than in women, respectively; P value <0.005 for all. Women had higher adjusted mortality (adjusted odds ratio, 1.63 [95% CI, 1.1-2.3]) and major bleeding events (adjusted odds ratio, 2.07 [95% CI, 1.19-3.59]). Although odds of major cardiovascular and cerebral events (adjusted odds ratio, 1.27[95% CI, 0.9-1.6]) were higher in women, it was not statistically significant., Conclusions: Despite being less comorbid, women had a significant increase in their mortality and major bleeding events following LMCA PCI. A sex-tailored approach considering age, intravascular imaging, and vascular access may improve outcomes.

Background: There is currently limited evidence comparing the association between metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic fatty liver disease (NAFLD), and the risk of peripheral artery disease (PAD). This study aims to analyze the associations of MAFLD and NAFLD with incident PAD., Methods and Results: Two longitudinal studies, the UKB (UK Biobank) study (n=372 216) and the ARIC (Atherosclerosis Risk in Communities) study (n=4681), categorized participants into MAFLD/non-MAFLD groups and NAFLD/non-NAFLD groups. Subsequently, participants were classified into 4 groups: non-fatty liver disease, MAFLD-only, NAFLD-only, and both MAFLD and NAFLD groups. Cox proportional hazard model estimated associations of MAFLD/NAFLD status, subtypes, and liver fibrosis severity with PAD risk. The MAFLD group had a higher risk of incident PAD compared with the non-MAFLD group, and similarly, the NAFLD group had a higher risk compared with the non-NAFLD group. Among these 4 groups, the MAFLD-only group had the strongest association with the risk of incident PAD, while the NAFLD-only group was not independently associated. Diabetic MAFLD subtype was significantly associated with increased PAD risk, and higher level of liver fibrosis scores correlated with elevated PAD risk., Conclusions: Both MAFLD and NAFLD are significantly associated with an increased incidence of PAD, with stronger associations in MAFLD and diabetic MAFLD population. These findings emphasize that the need for screening and prevention strategies for PAD in this high-risk population is warranted. The assessment of MAFLD and its subtypes should be considered as an integral component of cardiovascular risk assessment.

Background: Mosaic loss of chromosome Y (mLOY) in leukocytes of men reflects genomic instability from aging, smoking, and environmental exposures. A similar mosaic loss of chromosome X (mLOX) occurs among women. However, the associations between mLOY, mLOX, and risk of incident heart diseases are unclear., Methods and Results: We estimated associations between mLOY, mLOX, and risk of incident heart diseases requiring hospitalization, including atrial fibrillation, myocardial infarction, ischemic heart disease, cardiomyopathy, and heart failure. We analyzed 190 613 men and 224 853 women with genotyping data from the UK Biobank. Among these participants, there were 37 037 men with mLOY and 13 978 women with mLOX detected using the Mosaic Chromosomal Alterations caller. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs of each incident heart disease in relation to mLOY in men and mLOX in women. Additionally, Mendelian randomization was conducted to estimate causal associations. Among men, detectable mLOY was associated with elevated risk of atrial fibrillation (HR, 1.06 [95% CI, 1.03-1.11]). The associations were apparent in both never smokers (HR, 1.07 [95% CI, 1.01-1.14]) and ever smokers (HR, 1.05 [95% CI, 1.01-1.11]) as well as men aged >60 and ≤60 years. Mendelian randomization analyses supported causal associations between mLOY and atrial fibrillation (HR MR-PRESSO , 1.15 [95% CI, 1.13-1.18]). Among postmenopausal women, we found a suggestive inverse association between detectable mLOX and atrial fibrillation risk (HR, 0.90 [95% CI, 0.83-0.98]). However, associations with mLOY and mLOX were not found for other heart diseases., Conclusions: Our findings suggest that mLOY and mLOX reflect sex-specific biological processes or exposure profiles related to incident atrial fibrillation requiring hospitalization.

Background: Frontline health care staff are frequently exposed to traumatic events as part of their work. Although this study commenced before the emergence of COVID-19, levels of exposure were heightened by the pandemic. Many health care staff members report intrusive memories of such events, which can elicit distress, affect functioning, and be associated with posttraumatic stress disorder symptoms in the long term. We need evidence-based interventions that are brief, preventative, nonstigmatizing, suitable for the working lives of frontline health care staff, and effective for repeated trauma exposure. A brief, guided imagery-competing task intervention involving a trauma reminder cue and Tetris gameplay may hold promise in this regard, given evidence that it can prevent and reduce the number of intrusive memories following trauma across various settings., Objective: This case series aims to investigate the impact of a brief imagery-competing task intervention on the number of intrusive memories, general functioning, and symptoms of posttraumatic stress, anxiety, and depression, and examine the feasibility and acceptability of the intervention for UK National Health Service frontline health care staff. The intervention was delivered with guidance from a clinical psychologist., Methods: We recruited 12 clinical staff from the UK National Health Service, specifically from emergency departments, the intensive care unit, and the ambulance service. We evaluated the intervention using an AB single-case experimental design, where the baseline (A) was the monitoring-only phase and the postintervention (B) period was the time after the intervention was first administered. Methods were adapted once the COVID-19 pandemic began., Results: There was a decrease (59%) in the mean number of intrusive memories per day from baseline (mean 1.29, SD 0.94) to postintervention (mean 0.54, SD 0.51). There was a statistically significant reduction in the number of intrusive memories from baseline to postintervention, as shown by an aggregated omnibus analysis with a small effect size (τ-U=-0.38; P<.001). Depression, anxiety, and posttraumatic stress symptoms all significantly reduced from preintervention to postintervention. Participants also reported improvements in functioning based on both quantitative and qualitative measures. The intervention was feasible to deliver and rated as acceptable by participants., Conclusions: These preliminary findings suggest that this brief therapist-guided imagery-competing task intervention offers a potential approach to mitigating the impact of work-related traumatic events in frontline health care staff, both during a pandemic and beyond. Randomized controlled trials will be an important next step., (©Veronika Kubickova, Craig Steel, Michelle L Moulds, Marie Kanstrup, Sally Beer, Melanie Darwent, Liza Keating, Emily A Holmes, Lalitha Iyadurai. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 18.11.2024.)

Objectives: To identify suitable patients for glaucoma home monitoring and explore clinicians' perceptions of the possible benefits and risks of home monitoring within the National Health Service., Design: An online survey composed of open-ended and closed-ended questions., Setting: Secondary care., Participants: Glaucoma specialists registered with the UK and Eire Glaucoma Society., Outcome Measures: Agreement with clinical scenarios., Results: The estimated response rate was 68% (n=49). Of 49 participants, 92% (n=45) were consultant ophthalmologists and 71% (n=35) had over 10-year experience. There was a poor agreement regarding an ideal glaucoma patient for home monitoring, with only one scenario achieving over 60% agreement. Most participants believed that home monitoring would be most suitable for low-risk scenarios, rather than high-risk, due to fear of missing progression. In relation to acceptability, key facilitators included the potential to increase healthcare capacity and promote patient safety. However, low clinician trust in equipment reliability and fear of patient harm were reported as concerns., Conclusions: There was no clear consensus on which patients would benefit most from glaucoma home monitoring. While many clinicians believe home monitoring may enhance healthcare, there were also many concerns about the technologies themselves. Further work to address clinician concerns is warranted., Research Registry Registration Number: 6213., Competing Interests: Competing interests: AJK has received funding from the pharmaceutical industry for contributions to Advisory Boards and conference organisers for attendance/speaking at conferences. AJK is also chairman/trustee of Glaucoma UK. AT has received funding from the pharmaceutical industry for contributions to consulting, lectures and/or presentations, and advisory board participation. AT is also a member of the European Glaucoma Society executive committee., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA., Objectives: To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD., Methods: We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits., Results: We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively)., Conclusions: This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up., Competing Interests: Conflicts of interest The full conflicts of interest statement is provided in Appendix 3., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Objectives: Most people who have experienced sexual violence (SV) will disclose the event(s) to someone. Key recipients of disclosure are those working in healthcare. Telling someone in healthcare about experiences of SV can be an important step in accessing necessary medical care and being signposted to other services. While recognising healthcare settings are a key place for people to seek support, evidence is lacking about how best to create a safe environment for disclosure to take place, how services can make changes to better facilitate this experience and what changes matter most., Design: This study used a realist approach to identify mechanisms that facilitate safe and supported disclosure. Data were generated through three focus groups with Sexual and Reproductive Health Services healthcare professionals in the UK, and one-to-one interviews with survivors of SV who attended healthcare settings (n=18)., Results: The analysis found that service users needed to feel empowered and recognised as appropriate candidates for care in the material used to promote sexual healthcare services after SV. This promotional material needs to address rape myths, stereotypes and silence surrounding SV, to ensure that all individuals and especially those from diverse groups are empowered to access care. Three fundamental mechanisms for safe and supported disclosure were identified: being listened to, being validated and having choice. Trauma-informed care was identified as being essential for implementing these mechanisms. Healthcare professionals who were confident and competent regarding enquiry about SV and response to disclosures of SV were key., Conclusions: The development of services that are conducive to the disclosure of SV is needed to provide better support for those who have experienced SV and are ready to seek support. Use of appropriate promotional material, specific staff training and a trauma-informed approach are key elements to improve services., Competing Interests: Competing interests: JDR reports personal fees from GSK Pharma, Hologic Diagnostics, Mycovia and Janssen Pharma, as well as ownership of shares in GSK Pharma and AstraZeneca Pharma; is author of the UK and European Guidelines on Pelvic Inflammatory Disease; is a member of the European Sexually Transmitted Infections Guidelines Editorial Board; and is a member of the National Institute for Health Research (NIHR) Funding Committee (Health Technology Assessment Programme). He is an NIHR journals editor and associate editor of Sexually Transmitted Infections journal. He is an officer of the International Union against Sexually Transmitted Infections (treasurer) and a charity trustee of the Sexually Transmitted Infections Research Foundation., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Alopecia areata (AA) is an immune-mediated form of hair loss that can occur at any age, often with a significant mental health burden., Objectives: We aimed to provide estimates of the lifetime incidence of AA, and the impacts on mental health, healthcare utilization and work-related outcomes, assessing variation across major sociodemographic subgroups., Methods: AA cases were identified in primary care from the UK population-based Oxford-Royal College of General Practitioners Research and Surveillance Centre database (2009-2018). Lifetime incidence of AA was estimated at age 80 years using modified time-to-event models with age as the timescale, overall and stratified by sex, ethnicity, deprivation and geography. Mental health, healthcare utilization and work-related outcomes were assessed in the 2 years after AA diagnosis compared with matched unaffected controls, and stratified by the same sociodemographic subgroups., Results: During the study period, 6961 people developed AA. Overall lifetime incidence of AA was 2.11% [95% confidence interval (CI) 2.06-2.16]. Females had a higher lifetime incidence (2.35%, 95% CI 2.28-2.43) than males (1.88%, 95% CI 1.81-1.94). Lifetime incidence was higher in those of Asian ethnicity (5.87%, 95% CI 5.51-6.24), Other (4.5%, 95% CI 3.63-5.31), Mixed (4.4%, 95% CI 3.50-5.37) and Black (3.0%, 95% CI 2.63-3.42) ethnicity, compared with White ethnicity (1.7%, 95% CI 1.68-1.80). Lifetime incidence was highest in those with the greatest deprivation: most-deprived quintile (2.92%, 95% CI 2.77-3.07) compared with least-deprived (1.68%, 95% CI 1.59-1.78). Across sociodemographic subgroups, people with AA of Black ethnicity were most likely to have anxiety (adjusted odds ratio vs. matched controls 2.92, 95% CI 1.71-4.91), and had the greatest risk of time off work (adjusted hazard ratio vs. matched controls 2.54, 95% CI 1.80-3.56)., Conclusions: AA affects around 1 in 50 people over their lifetime. The incidence and impact of AA on mental health and work outcomes is highest in ethnic groups other than White. Clinicians should be aware of the marked heterogeneity in the incidence and impact of AA, and support targeted healthcare to groups at the highest risk of alopecia and its consequences., Competing Interests: Conflicts of interest ART has no competing interest to declare. CT is a principal and (national) chief investigator on the Pfizer-funded ALLEGRO clinical trials in alopecia areata; CT provides consulting services to Pfizer, and has received speaker fees from Leo Pharma. JN, RR and MC are employees and shareholders of Pfizer Ltd. AGM provides consultancy for Manentia and Pfizer., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Psoriatic disease (PsD) is closely associated with cardiovascular (CV) disease. The Life's Essential 8 (LE8) score is a new metric to assess CV health (CVH), where a higher score indicates better CVH. However, the longitudinal association between LE8 score and the risk of PsD remains uncertain., Objectives: To investigate, in a cohort study, the association between LE8 score, genetic susceptibility and the risk of PsD., Methods: This cohort study included 261 642 participants in the UK Biobank without PsD at baseline. LE8 comprises eight indicators: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose and blood pressure. Cox proportional hazard models were used to examine the association between participants' LE8 scores, genetic risk of PsD and the risk of PsD. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated., Results: During an average follow-up of 12.3 years, 1501 participants developed PsD. Compared with participants with low LE8 scores, the HRs of developing PsD for those with moderate and high LE8 scores were 0.51 (95% CI 0.43-0.59) and 0.34 (95% CI 0.27-0.42) after adjustments, respectively. Dose-response analysis revealed a linear negative association between continuous LE8 score and the risk of developing PsD (P < 0.001), with no evidence of nonlinear association detected. Genetic susceptibility to PsD did not modify this association (P-interaction = 0.63). Subgroup analyses revealed that women had a more pronounced beneficial association between LE8 scores and PsD risk (P-interaction = 0.02)., Conclusions: Our study suggests that a higher LE8 score, regardless of genetic risk, is associated with a lower risk of PsD, particularly in women. Consequently, maintaining good CVH status is recommended to prevent PsD and assess associated risks., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To assess the prevalence and severity of paruresis ('shy bladder syndrome') in a population of university staff and students and to determine if there was any relationship between demographics, self-esteem, presence of social anxiety disorders and negative toilet experiences and paruresis., Design: We undertook an anonymised cross-sectional online survey using Microsoft Forms. We invited participants aged 18 and over to complete the survey which included demographic information; any pre-existing medically or self-diagnosed anxiety-related conditions; Shy Bladder Scale (SBS); Rosenberg Self-Esteem Scale (RSES) and questions about using school toilets in their younger life. We defined 'mild' and 'severe' paruresis based on total SBS cut-off scores of greater than or equal to 31 and greater than or equal to 40. We calculated prevalence of paruresis, and explored differences in self-esteem, school toilet experience and social anxiety disorders between individuals with and without paruresis. Multivariable logistic regression was used to determine which variables had any influence on having a 'mild' and 'severe' paruresis diagnosis., Setting: We distributed the survey to all staff and students via their university email address as well as promoting the survey on university social media sites., Results: We received responses from 356 individuals. Most participants (237, 66.6%) were within the 18-30 year age category and most (277, 77.8%) were white. There were 221 (62.1%) females, 119 (33.4%) males and 16 (4.5%) other genders. The prevalence of 'mild' paruresis was 25.8% and of 'severe' paruresis 14.9% in this sample. 73.0% indicated that they had at least one medically or self-diagnosed anxiety disorder. There was a statistically significant difference in the total SBS score between individuals with and without an existing anxiety disorder (8 vs 19, <0.001). The adjusted odds of 'mild' paruresis were higher for men than women (OR 3.39; 95% CI 1.90 to 6.06), lower for those with a lower RSES score (OR 0.90; 95% CI 0.85 to 0.96), lower for those for a lower school toilet experience score (OR 0.88; 95% CI 0.78 to 0.99) and higher for those with at least one anxiety disorder (OR 3.164; 95% CI 1.52 to 6.59). The adjusted odds of 'severe' paruresis were higher for men than women (OR 2.60; 95% CI 1.32 to 5.12), lower for those with a lower RSES score (OR 0.90; CI 0.84 to 0.97) and higher for those with at least one anxiety disorder (OR 2.99 (1.18-7.56))., Conclusion: Large organisations should consider measures to help manage anxiety and improve toilet experiences. These could include resources and signposting to manage anxiety disorders and single-occupancy toilets and toilets in quiet areas to limit anxiety associated with shy bladder syndrome., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Healthcare systems data (HCSD) could improve the efficiency of clinical trials, but their accuracy and validity are uncertain. Our objective was to assess the accuracy of HCSD as the sole method of outcome detection in the REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) compared with adjudicated questionnaire follow-up and compare estimates of treatment effect., Methods: RESTART was a prospective, open, assessor-blind, parallel-group randomised controlled trial (RCT) of antiplatelet therapy after intracerebral haemorrhage (ICH) in the UK. We included 496 (92%) of 537 RESTART participants, who were resident in England or Scotland at randomisation. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. RESTART used annual questionnaires to detect its primary outcome (recurrent ICH) and secondary outcome (a composite of haemorrhagic or ischemic major adverse cardiovascular events [MACE]) over a median of 2.0 years; an independent adjudication committee verified outcomes using medical records and brain imaging. We obtained ICD10-coded HCSD on hospital admissions and deaths in England and Scotland to identify primary and secondary outcomes. We compared HCSD with a reference standard of adjudicated outcomes. We estimated the effects of antiplatelet therapy using HCSD alone in a Cox proportional hazards model adjusted for minimisation variables., Results: In the original RESTART trial, 31 people experienced a primary outcome event. HCSD had sensitivity of 84% (95% CI 66 to 95%) and positive predictive value of 68% (51 to 82%) for recurrent ICH. HCSD estimated an effect of antiplatelet therapy (adjusted hazard ratio [aHR] 0.51, 95% CI 0.27 to 0.98; p = 0.044) that was almost identical to adjudicated outcomes (aHR 0.51, 95% CI 0.25 to 1.03; p = 0.060). HCSD had sensitivity of 84% (76 to 91%) and positive predictive value of 78% (69 to 85%) for MACE, on which HCSD estimated an effect of antiplatelet therapy (aHR 0.81, 95% CI 0.56 to 1.16; p = 0.247) that was similar to adjudicated outcomes (aHR 0.65, 95% CI 0.44 to 0.95; p = 0.025)., Conclusions: In a RCT of antiplatelet therapy for people with ICH, HCSD was reasonably accurate and provided similar estimates of treatment effect compared with adjudicated outcomes., Trial Registration: ISRCTN71907627 . Registered on 25 April 2013., Competing Interests: Declarations Ethics approval and consent to participate The Scotland A research ethics committee approved RESTART before recruitment began (reference 12/SS/0138). The funding application and trial protocol pre-specified that HCSD would be collected alongside other methods to identify outcome events, for which participants gave consent. Consent for publication Not applicable—no identifying images or other personal or clinical details of participants are presented. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Reduced muscle mass has been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, it remains unclear whether decreased muscle mass is a risk factor for ALS or a consequence of motor neuron degeneration. Recently, serum creatinine-to-cystatin C ratio (CCR) have emerged as promising biomarkers for assessing muscle mass. We aimed to explore the association between CCR and the incidence of ALS using data from the UK Biobank. Between 2006 and 2010, 446,945 participants were included in the baseline. CCR was calculated as the ratio of serum creatinine to cystatin C. Cox regression models were used to analyze the relationship between CCR and ALS incidence. Furthermore, subgroup analyses were conducted to investigate potential covariates in these relationships. After adjusting for all covariates, the multivariate Cox regression analysis revealed a significant association between decreased CCR and an increased risk of ALS (hazard ratio (HR) = 0.990, 95% confidence interval (CI): 0.982-0.999, P = 0.026). Participants were stratified into groups based on CCR tertiles. Compared with participants in the highest tertiles of CCR, those in the lowest (HR = 1.388, 95% CI: 1.032-1.866, P = 0.030) and medium tertiles (HR = 1.348, 95% CI: 1.045-1.739, P = 0.021) had an increased risk of ALS incidence. Subgroup analysis showed that the relationship between CCR and ALS incidence was particularly significant among participants aged < 65 years (CCR tertile 1: HR = 1.916, 95% CI: 1.366-2.688, P < 0.001; CCR tertile 2: HR = 1.699, 95% CI: 1.267-2.278, P < 0.001). The present results demonstrate that lower CCR is significantly associated with a higher risk of ALS., Competing Interests: Competing interests The authors declare no competing interests. Ethical declarations All participants have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted., (© 2024. The Author(s).)

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., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki. Ethical approval was received from the National Health Service West of Scotland Research Ethics Service (WoSREC 3. reference 20/WS/0065), Health Research Authority (Reference IRAS 274901) and City, University of London (Reference ETH1920-0572). Informed consent to participate was obtained from all of the participants in the study. Consent for publication Not applicable. Competing interests A.S., H.C. and M.M. developed and published one of the measures employed in this study, the Stirling Antenatal Anxiety Scale (SAAS)., (© 2024. The Author(s).)

Background: The relationship between serum urea concentration and cancer in patients with metabolic syndrome (MetS) remains unclear. This study aimed to investigate the association between serum urea concentration and 16 site-specific cancers, overall cancer incidence, and cancer mortality in individuals with MetS., Methods: We analysed the data of 108,284 individuals with MetS obtained from the UK Biobank. The Cox proportional hazards model was used to determine the association between serum urea concentration at recruitment and cancer. The Benjamini-Hochberg correction was used to account for multiple comparisons., Results: Over the median follow-up period of 11.86 years, 18,548 new incident cases of cancer were documented. There were inverse associations of urea concentration with overall cancer incidence, and the incidence of oesophageal and lung cancers, with respective hazard ratios (95% confidence intervals) [HR (95% CI)] for the highest (Q4) vs lowest (Q1) urea quartiles of 0.95 (0.91-0.99), 0.68 (0.50-0.92), and 0.76 (0.64-0.90). However, high serum urea concentrations increased the male prostate cancer risk (HR 1.15; 95% CI 1.02-1.30). Although the Cox model indicated a protective effect of higher urea levels against stomach (HR 0.67; 95% CI 0.45-0.98; p = 0.040; FDR 0.120) and colorectal cancer (HR 0.86; 95% CI 0.74-0.99; p = 0.048; FDR 0.123), no strong evidence of association was found after applying the Benjamin-Hochberg correction. Moreover, across the median follow-up period of 13.77 years for cancer mortality outcome, 5034 cancer deaths were detected. An "L-shaped" nonlinear dose-response relationship between urea concentration and cancer mortality was discovered (p-nonlinear < 0.001), and the HR (95% CI) for urea concentration Q4 vs Q1 was 0.83 (0.77-0.91)., Conclusions: Serum urea concentration can be considered as a valuable biomarker for evaluating cancer risk in individuals with MetS, potentially contributing to personalised cancer screening and management strategies., Competing Interests: Declarations Ethics approval and consent to participate The UK Biobank was approved by the Research Ethics Committees of the Northwest Multi-Centre (reference no. 16/NW/0274). All the study participants signed an informed consent form. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The teratogenic potential of valproate in pregnancy is well established; however, evidence regarding the long-term safety of other antiseizure medications (ASMs) during pregnancy remains limited. Using routinely collected primary care data from the UK and nationwide Swedish registries to create a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in pregnancy, we show that those exposed to valproate were more likely to receive a diagnosis of autism, intellectual disability, and ADHD, when compared to children not exposed to ASMs. Additionally, children exposed to topiramate were 2.5 times more likely to be diagnosed with intellectual disability (95% CI: 1.23-4.98), and those exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05-1.48) and 1.30 times more likely to be diagnosed with intellectual disability (95% CI: 1.01-1.69). There was little evidence that children exposed to lamotrigine in pregnancy were more likely to receive neurodevelopmental diagnoses. While further research is needed, these findings may support considering safer treatment alternatives well before conception when clinically appropriate., Competing Interests: Competing interests T.T. has received support to the EURAP pregnancy registry from Accord, Eisai, GSK, UCB, Bial, Sanofi, GW Pharma, Teva, Angelini Pharma, Zentiva, SF Group, Glenmark and personal fees from Eisai, Sanofi, UCB and Angelini Pharma outside the submitted work. BL reports receiving consulting fees from Beasley Allen Law Firm, Patterson Belknap Webb & Tyler LLP and AlphaSights. None of the above entities had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The remaining authors have no conflicts of interest., (© 2024. The Author(s).)

The influence of air pollution on dynamic changes in clinical state from healthy to atrial fibrillation (AF), further AF-related complications and ultimately, death are unclear. We aimed to investigate the relationships between air pollution and the occurrence and progression trajectories of AF. We retrieved 442,150 participants free of heart failure (HF), myocardial infarction (MI), stroke and dementia at baseline from UK Biobank. Exposures to air pollution for each transition stage were estimated at the geocoded residential address of each participant using the bilinear interpolation approach. The outcomes were incident AF, complications, and death. Multi-stage models were used to evaluate the associations between air pollution and dynamic progression of AF. Over a 12.6-year median follow-up, a total of 21,670 incident AF patients were identified, of whom, 4103 developed complications and 1331 died. PM 2.5 , PM 10 , NO x and NO 2 were differentially positively associated, while O 3 was negatively associated with risks of progression trajectories of AF. PM 2.5 exposure was significantly associated with an increased risk of progression. The associations of PM 2.5 , PM 10 , NO x , and NO 2 on incident AF were generally more pronounced compared to other transitions. The cumulative transition probabilities were generally higher in individuals with higher exposure levels of PM 2.5 , PM 10 , NO x , and NO 2 and lower exposure to O 3 . Air pollution could potentially have a role in increasing the risk of both the occurrence and progression of AF, emphasizing the significance of air pollution interventions in both the primary prevention of AF and the management of AF-related outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. GYHL is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 899871. Other authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Maternal smoking during pregnancy (MSDP) is significantly linked to the short- or long-term health of offspring. However, little research has examined whether MSDP affect the aging rate of offspring., Methods: This study used questionnaires to determine out whether the participants' mothers smoked when they were pregnant. For evaluating aging rate, we used the following several outcome measures: telomere length, frailty index, cognitive function, homeostatic dysregulation score, KDM-age, age-related hospitalization rate, premature death, and life expectancy., Result: After adjusting for covariates, we found that the offspring of the MSDP group had significantly shorter telomere length in adulthood by 0.8 % (β = -0.008,95%CI:-0.009 to -0.006) compared with non-MSDP group. Compared to the non-MSDP group, participants in MSDP group showed higher levels of homeostatic dysregulation (β = 0.015,95%CI: 0.007-0.024) and were frailer (β = 0.008,95%CI:0.007-0.009). The KDM age increased by 0.100 due to MSDP (β = 0.100,95 % CI:0.018-0.181), and the age acceleration of KDM algorithm also increases significantly (β = 0.101, 95%CI:0.020-0.183). Additionally, we found that the risk of aging-related hospitalizations was significantly higher than the non-MSDP group by 10.4 %(HR = 1.104,95%CI:1.066-1.144). Moreover, MSDP group had a 12.2 % increased risk of all-cause premature mortality (HR = 1.122,95%CI:1.064-1.182) and a significant risk of lung cancer-specific premature mortality increased by 55.4 %(HR = 1.554,95%CI:1.346-1.793). In addition, participants in the MSDP group had significantly decreased cognitive function and shorter life expectancies than those in non-MSDP group., Conclusion: Our findings indicated a significant association between MSPD and accelerated aging, elevated hospitalization rates, increased premature mortality rates, and reduced life expectancies in offspring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Biliary tract cancer (BTC) is a rare and aggressive malignancy with increasing incidence. Most BTC cases are diagnosed with metastatic disease which carries a 5-year survival rate of <5%. Physical activity, diet, and obesity might be associated with BTC risk, but studies have been limited particularly in African descendants. We addressed this knowledge gap by evaluating associations of BTC risk with obesity, physical activity, and dietary intakes in 723,326 adult participants in four cohort studies conducted in China, the United Kingdom, and the United States. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) in each cohort; results were combined using meta-analysis. All cohorts had ≥11 median follow-up years with 839 incident BTC cases combined. BTC risk was positively associated with body mass index (BMI) and waist-to-hip ratio (WHR) whereas physical activity, fruit intake, and fish intake were inversely associated. HR and (95% CI) comparing BMI >35.0 to 18.5-24.9: 1.71 (1.26, 2.31), p-trend <.0001; comparing BMI-adjusted WHR top to bottom quartile: 1.20 (0.94, 1.53), p-trend = .05; comparing ≥15-0 metabolic equivalent task-hours/week 0.76 (0.61, 0.94), p-trend = .009; comparing highest to lowest intake tertile for fruit and fish 0.79 (0.66, 0.95), p-trend = .01; 0.82 (0.68, 0.98), p-trend = .04, respectively. Associations were, in general, similar across ancestry groups. Our study provides strong evidence for important roles of obesity, diet, and physical activity in BTC etiology and stresses the need for lifestyle modification to combat the rising incidence of this fatal malignancy., (© 2024 UICC.)

Background: Research in recent years has increasingly highlighted the relationship between exposure to potentially morally injurious events (PMIEs) and poor mental health outcomes. Human trafficking survivors often report exposure to many traumatic and PMIEs and given the complexities of trafficking exploitation, survivors may be especially vulnerable to moral injury. Despite this, no research has investigated experiences of PMIEs and moral injury in human trafficking survivors. The objective was to explore survivors' experiences of PMIEs, the impact of PMIEs on wellbeing and functioning and the factors that may influence outcomes following PMIEs., Method: Participants were seven human trafficking survivors from diverse backgrounds who had settled in the UK. In-depth semi-structured interviews were conducted via telephone. Data were analysed using thematic analysis., Results: Human trafficking survivors were found to experience multiple PMIEs, including transgressive acts committed by others and betrayal by trusted loved ones or those in positions of authority. Experiencing PMIEs contributed towards considerable psychological distress, including intense feelings of shame, anger and worthlessness, and negatively impacted survivors daily functioning. Formal support, especially practical help (e.g. warm clothing) and social support groups, were experienced as particularly beneficial., Conclusions: This study provides some of the first evidence that human trafficking survivors may be vulnerable to moral injury and indicates the impact that exposure to PMIEs can have on functioning. Future work is needed to ensure that statutory organisations consider the potential for causing moral injury when interacting with human trafficking survivors and clinical care teams are equipped to provide tailored guidance and support., Competing Interests: Declarations Ethical approval King’s College London Research Ethics Committee (HR-20/21-18272). Human ethics and consent to participate All participants provided informed consent to participate. This study was reviewed and approved by King’s College London Research Ethics Committee (HR-20/21-18272) in accordance with the Declaration of Helsinki. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications., Objectives: To describe the clinical outcomes of XLA patients in the United Kingdom and Hong Kong and evaluate current treatment strategies., Methods: Patients with a definitive diagnosis of XLA were included in this cross-sectional and retrospective analysis of clinical health outcomes. Data pertaining to diagnosis, infection incidence, IgG trough levels and lung function were collected and analysed., Results: 99 patients with a median age of 29.02 years (IQR 12.83-37.41) and a total follow up of 1922 patient years, were included this study. The median age at diagnosis was 3.30 years (IQR 1.04-8.38) which decreased over time (p = 0.004). 40% of the cohort had radiological evidence of bronchiectasis. Risk of bronchiectasis was not significantly associated with clinical infection incidence (p = 0.880) or IgG trough levels (p = 0.407). Two patients demonstrated novel complications, namely persistent norovirus infection, leading to haemopoietic stem cell transplantation (HSCT)., Conclusions: Despite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy., Competing Interests: Declarations Competing Interests Ben Shillitoe has received travel grants from Pharming and speaker fees from TakedaTomaz Garcez has Consulting, advisory work and educational support from BioCryst, CSL Behring, KalVista, Novartis, Octapharma, Pharming and Takeda.Jaime S Rosa Duque received a conference sponsorship from Merck Sharp & Dohme in 2023Yu Lung Lau chairs the Scientific Committee on Vaccine Preventable Diseases of the Hong Kong Government. The remaining authors have no COIs to delcare., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Physicians play an important role in management and governance of healthcare systems, yet many lack formal leadership training and skills. Despite leadership training through placements in wards at a graduate level, this should take place early on (undergraduate level), to lay the foundations for future physicians to consider a career choice in leadership positions long before entering practice. The fundamentals of leadership and management should be incorporated in the medical curriculum, with input from experts in the area such that relevant concepts are appropriately adapted with a healthcare context., Methods: We developed a pilot leadership and management module for undergraduate medical students, drawing from sources such as the UK National Health System and General Medical Council, primary literature, and undergraduate business school curricula. Students in their clinical years (4-6) of an undergraduate, six-year medical degree, were invited to participate in five 2-hour online sessions. Participants completed a questionnaire before and after module completion to assess whether individual perspectives on 22 skills relevant to leadership knowledge, and their self-rated competence in each one, changed following module attendance., Results: Sixteen medical students participated in the study. Module attendance resulted in mean self-reported competence increase in 18 of the 22 skills, with "inspire others", "public speaking", "coding and billing", "risk management" and "conflict resolution" displaying the largest positive change. Free-text comments provided encouraging feedback regarding the module and its contents, and the teaching method of such skills (case-studies or more applied scenarios, as opposed to taught lectures)., Conclusions: The positive changes in student perceptions and self-reported competence in leadership skills that are not traditionally included in the undergraduate medical curriculum, but are part of the business curriculum, further support the importance of inter-professional learning. Our findings are expected to inform the development of a module that could be incorporated in undergraduate medical curricula as part of future research with larger sample size and objective measures of skill competence., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Cyprus National Bioethics Committee (protocol number: ΕΕΒΚ/ΕΠ/2022.01.39). Participation was voluntary and written consent was obtained. This study does not have a Clinical Trial Number (CTN) as it does not meet the criteria for a clinical trial. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Almost 40% of the Nobel-Prize-winning discoveries in medicine are made by physician-scientists, who are a driving force in the evolving medical, academic and research landscape. However, their training has few defined milestones. To be effective clinicians, educators and researchers, they need to maintain and hone skills, often via continuous professional development (CPD) activities covering different domains. They have recurrently been described as an endangered species. Yet, warnings and recommendations across several decades did not stop the declining number of physician-scientists, which is now a chronic issue. This is further exacerbated by a lack of resources and support, especially after the COVID-19 pandemic., Methods: We administered a questionnaire called Positive and Negative Affect Schedule (PANAS-GEN) to get an initial emotional snapshot before performing individual semi-structured interviews with five physician-scientists in neurology working in the United Kingdom. We explored the key factors they balance before selecting CPD activities, along with their views on compulsory CPD events and assessments. We investigated their general feelings towards compulsory and non-compulsory CPD, how they felt the night before and the morning of the events, and the perceived consequences attending these have on their learning., Results: In our study, physician-scientists tend to choose training in their area of expertise but would enjoy exploring more if they had more time. The CPD choice was chiefly driven by speakers and topics, followed by learning needs. They disputed the utility of the current assessments, which are often seen as box-ticking exercises. While frustration, hostility and negative feelings were voiced for the compulsory ones, other CPD activities were welcomed with excitement, curiosity and a sense of adventure. Enthusiasm and excitement were felt the night before and the morning of the non-compulsory ones. CPD events were perceived to positively affect further learning, with the most immediate consequences being reading an article, networking or interacting with the speakers., Discussion: This is the first study exploring the key factors driving a group of physician-scientists while selecting CPD activities and investigating their feelings and emotions related to CPD attendance. More engaging and less box-ticking CPD should be on the cards, along with an adequate evaluation of these activities. It is essential to increase enthusiasm, which can facilitate engagement, and decrease frustration surrounding compulsory CPD activities. We still know too little about the role of emotions in learning, especially about CPD. Future studies should investigate the emotional side of learning across different career stages to restore the leaky pipeline and create a tailored environment with benefits for each of the three sides of the physician-scientist's identity: the clinical, the research, and the academic., Competing Interests: Declarations Ethics approval and consent to participate All methods were carried out in accordance with relevant guidelines and regulations. This work received ethical approval from the relevant Education Ethics Review Process at Imperial College London. Informed consent to participate was obtained from all the study participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Physical inactivity is an ongoing problem throughout the lifespan. For older people, inactivity has a negative impact on wellbeing, which worsened during the COVID-19 pandemic. Digital technologies can be employed to encourage uptake of social and physical activity through remotely delivered interventions to improve wellbeing, however, we need to understand older people's perceptions and experiences of using digital technologies before implementing these interventions., Aims: To explore the perceptions and experiences of older people on the use of digital technologies during the COVID-19 pandemic., Methods: Qualitative semi-structured interviews were conducted with 16 community dwelling older people from Hertfordshire, United Kingdom who were all programme participants in a remotely delivered mind-body physical activity programme called Positive Movement. Interviews were conducted before programme participation. The audio recorded interviews were transcribed and analysed using thematic analysis., Results: Four themes emerged from the data. The perceived impact of COVID-19 on social contact, perceived impact of COVID-19 on mental wellbeing, using digital platforms for health or exercise and using digital platforms for social contact., Discussion: Participants reported reduced social contact due to COVID-19. Most participants reported using digital technologies for social inclusion rather than health reasons, and there were mixed views on the willingness to use digital technologies for physical activity., Conclusion: Digital technologies offered a lifeline during COVID-19 to maintain social contact and their use was found acceptable by older people. Digital platforms such as Zoom can be further employed to conduct remotely delivered interventions with the aim to increase uptake of social and physical activity interventions within this population., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical standard Study approved by the Ethical Committee at the University of Bedfordshire (IHREC939). Informed consent Participants gave their informed consent. No identifiable details are included. All respondents aware of the intention to publish findings., (© 2024. The Author(s).)

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a newly recognized syndrome mediated by anti-platelet factor 4 antibodies induced by Covid-19 adenovirus-vectored vaccines including ChAdOx1 nCoV-19 and Ad26.COV2.S. This study validated a proposed Brighton Collaboration case definition for VITT. A data collection form was developed and used to capture the variations in VITT criteria and assess their level of diagnostic certainty from adjudicated positive VITT case datasheets in Germany (n = 71), UK (n = 220), Australia (n = 203), and Taiwan (n = 56). We observed high prevalence of each component of the proposed VITT definition in positive cases (84%-100%), except for the occurrence of thrombosis or thromboembolism criterion in only 34% of VITT cases in Taiwan. The sensitivity of this proposed definition was 100% for Germany and UK, 92% for Australia, and 89% for Taiwan cases. These findings support the validity of this case definition for VITT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H. Tran reports project grant funding support outside of the submitted work from AstraZeneca and Sanofi. W.-I. Huang is a member of the national enhanced passive Covid-19 vaccine safety surveillance team in Taiwan. J. Buttery has served as an independent data monitoring committee member for CEPI SPEAC, GSK, Serum Institute of India, SK Biosciences and Clover Vaccines. His employer Murdoch Children’s Research Institute is compensated for his time. A. Greinacher reports grants and non-financial support from Aspen, Boehringer Ingelheim, MSD, Bristol Myers Squibb (BMS), Paringenix, Bayer Healthcare, Gore Inc., Rovi, Sagent, Biomarin/Prosensa, personal fees from Aspen, Boehringer Ingelheim, MSD, Macopharma, BMS, Chromatec, Werfen, nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, GTH e.V. outside the submitted work. No other authors report conflicts of interest. Parts of the German results reported have been obtained in a study conducted by Universitätsmedizin Greifswald under service contract No. EMA/2021/17/TDA. The views expressed are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its Committees or Working Parties. The Taiwan VITT case information was based on data provided by the Vaccine Adverse Event Reporting System, operated by Taiwan Centers for Disease Control., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics., Design: A population-based longitudinal cohort study using real-time user data., Setting: 35 specialised long COVID clinics in the UK., Participants: 4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022., Main Outcome Measures: Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses., Results: The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was -0.86 (95% CI -1.32, -0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost., Conclusions: Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme., Competing Interests: Competing interests: KB's research portfolio is partly funded by National Institute for Health & and Care Research (NIHR) Applied Research Collaboration Wessex. HG reports working as a clinical safety officer for Living With. JRH reports receiving personal fees and fees to institution for honorariums and consultancy payments from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Takeda, and also sponsorship for attending meetings from AstraZeneca and GlaxoSmithKline. PP reports grants from the Medical Research Council and NIHR outside the submitted work. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Haemophilia is a rare bleeding disorder caused by a deficient or absent clotting factor, leading to frequent bleeding. Multiple intravenous (IV) infusions have been the standard prophylactic treatment; however, newer treatment options involve less frequent subcutaneous (SC) injections. To inform future health economic evaluations, this study applied the time trade-off (TTO) method for estimation of utilities associated with haemophilia treatment for both people with the disease and potential caregivers., Methods: Using the TTO method, utilities were estimated through two online surveys distributed in the UK, Canada and the US. In survey 1 (S1), adults from the general population aged 18 years and above evaluated health states as if they were living with haemophilia themselves and were receiving treatment for the condition. In survey 2 (S2), adults from the general population with a child under the age of 15 years evaluated health states as if they were treating their child for haemophilia. The surveys assessed the following treatment aspects: frequency of treatment, treatment device and injection site reactions., Results: In total, 812, 739 and 703 respondents completed S1 and 712, 594 and 527 completed S2 in the UK, Canada and the US, respectively. In both surveys, the treatment device was associated with the largest impact on utilities for both people with haemophilia and caregivers. Monthly SC injections with a prefilled pen-device were associated with a significant utility gain compared with SC injections with a syringe and IV infusions. In S1, a lower treatment frequency was preferred in all three countries, while in S2, a lower treatment frequency was preferred only in the UK. Avoiding injection site reactions was associated with a significant utility gain in both surveys, but only in the UK and Canada., Conclusions: The study suggests that the administration of haemophilia treatment in particular has an impact on utilities for both people and caregivers living with the disease. Thus, less complex and time-consuming treatment devices are expected to improve health-related quality of life. This can be further modified additively by less frequent administration. These results can inform future health economic analyses of haemophilia and haemophilia treatment., Competing Interests: Declarations Ethics approval and consent to participate This study was not a clinical trial, did not include patients and did not gather biological or human samples or identifiable personal information, and ethical review board approval was therefore not required. All respondents gave consent to participate before answering the surveys. Consent for publication Not applicable. Competing interests Medical writing support was provided by AO and CY from EY Godkendt Revisionspartnerselskab, Denmark, and funded by Novo Nordisk. Publication review support was provided by AXON Communications, London, UK, and funded by Novo Nordisk. MLW and MNW are employees of Novo Nordisk, and MLW owns stocks in Novo Nordisk. AO and CY received funding for performing the study and medical writing support but were not paid for their role as author., (© 2024. The Author(s).)

Background: Knowledge sharing is a crucial part of any knowledge management implementation. It refers to sharing skills and experience among team members in an organization. In a health care setting, sharing knowledge, whether tacit or explicit, is important and can lead to better health care services. In medical imaging departments, knowledge sharing can be of particular importance. There are several factors that affect knowledge-sharing practices in medical imaging departments: individual, departmental, and technological. Evaluating the importance of these factors and understanding their use can help with improving knowledge-sharing practices in medical imaging departments., Objective: We aimed to assess the level of motivation, identify current knowledge-sharing tools, and evaluate factors affecting knowledge sharing in the medical imaging departments of 2 cancer centers, The Christie, United Kingdom, and the Kuwait Cancer Control Center (KCCC)., Methods: A concurrent mixed methods study was conducted through nonprobability sampling techniques between February 1, 2023, and July 30, 2023. Semistructured interviews were used to validate the results of the quantitative analysis. Data were collected using an electronic questionnaire that was distributed among health care professionals in both cancer centers using Qualtrics. Semistructured interviews were conducted online using Microsoft Teams. The quantitative data were analyzed using the Qualtrics MX software to report the results for each question, whereas the qualitative data were analyzed using a thematic approach with codes classified through NVivo., Results: In total, 56 respondents from the KCCC and 29 from The Christie participated, with a 100% response rate (56/56, 100% and 29/29, 100%, respectively) based on the Qualtrics survey tool. A total of 59% (17/29) of health care professionals from The Christie shared their knowledge using emails and face-to-face communication as their main tools on a daily basis, and 57% (32/56) of health care professionals from the KCCC used face-to-face communication for knowledge sharing. The mean Likert-scale score of all the components that assessed the factors that affected knowledge-sharing behaviors fell between "somewhat agree" and "strongly agree" in both centers, excepting extrinsic motivation, which was rated as "neither agree nor disagree." This was similar to the results related to incentives. It was shown that 52% (15/29) of health care professionals at The Christie had no incentives to encourage knowledge-sharing practices. Therefore, establishing clear policies to manage incentives is important to increase knowledge-sharing practices., Conclusions: This study offered an evaluation of factors that affect knowledge sharing in 2 cancer centers. Most health care professionals were aware of the importance of knowledge-sharing practices in enhancing health care services. Several challenges were identified, such as time constraints, a lack of staff, and the language barrier, which limit knowledge-sharing practices. Therefore, establishing a clear policy for knowledge sharing is vital to practicing knowledge-sharing behaviors and facing any challenges that limit this practice., (©Maryam Almashmoum, James Cunningham, John Ainsworth. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 13.11.2024.)

Mendelian Randomization studies indicate that BMI contributes to various diseases, but it's unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement. Similar attenuation was observed for chronic kidney disease and stroke, though results varied. Findings were consistent across sexes, except for myocardial infarction. Residual effects may result from temporal BMI changes, pleiotropy, measurement error, non-linear relationships, non-collapsibility, or confounding. The attenuation extent of BMI genetic risk score on disease associations suggests the potential impact of reducing BMI on disease risk., Competing Interests: Competing interests G.E., G.T., V.S., F.Z., H.Helgason, T.O., S.R., V.T., M.O.U., G.S., A.S.S., H.E., H.M.A., G.A.J., A.H., S.G., U.S., H.K.A., D.O.A., G.B., H.S., T.T., P.S., U.T., H.Holm, D.F.G. and K.S. are employees of deCODE Genetics/Amgen Inc. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Fraud and sexual harassment have been haunting academia for years. While the scientific community proposed strategies to overcome misconduct in research, the problem of sexual harassment seems unresolved. One reason for this might be a difference between men and women in the perception of the moral character and competence of sexual harassers. Across four studies (N = 3776), in the UK and the US, men judged the sexual harasser as less immoral than women (Studies 1, 2, and 3a), even though sexual harassment was considered more harmful than fraud (Study 2). Consequently, men demanded less punishment for sexual harassers than women (Studies 1 and 2). This gender difference was not explained by moral rationalization (Study 3a). Further, a sexual harasser was judged as more competent than a fraudster but in an academic, not business, context (Studies 1 and 2). This effect was driven by the moral decoupling process, which participants used to separate competence judgments from moral judgments (Study 3b). Overall, these results suggest that in the academic context, gender interests most likely shape moral and punishment judgments towards sexual harassers, while the decoupling process allows both genders to perceive them as competent and immoral at the same time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Miazek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Helicobacter pylori is a prevalent infection that may complicate pregnancy, but evidence remains limited, controversial and may not apply to all pregnant women., Objective: This study aims to evaluate whether Helicobacter pylori is a risk factor for adverse pregnancy outcomes and to identify vulnerable subpopulations., Study Design: Multiplex serology was utilized to measure blood levels of immunoglobulin G against eight Helicobacter pylori antigens in 1372 pregnant women from three European birth cohorts: BiB (United Kingdom), Rhea (Greece) and INMA (Spain). Outcomes of interest included gestational diabetes mellitus, gestational hypertension, preeclampsia, preterm birth and small for gestational age neonates, as well as prenatal anxiety and depression. Adjusted logistic regression models were used to evaluate the association between Helicobacter pylori seropositivity (overall and by antigen) and antigen specific antibody levels with the outcomes. We examined effect modification of the associations by ethnicity., Results: Helicobacter pylori seropositivity was detected in 18.8% (258/1372) of pregnant women. Preeclampsia was the least common outcome (26/830). Helicobacter pylori seropositivity was associated with the development of two or more adverse pregnancy outcomes (gestational hypertension, gestational diabetes, preterm birth, small gestational age and preeclampsia) [OR:1.32 (95% CI: 1.06-1.65), p-value: 0.01], especially in women with high antibody levels to OMP antigen [OR: 2.12 (95% CI: 1.62-2.76), p-value: 0.001]. Women with high antibody levels to Helicobacter pylori antigens GroEL and NapA were more likely to develop preeclampsia [OR: 2.34 (95% CI: 1.10-8.82), p-value: 0.03; OR: 4.09 (95% CI: 1.4-11.93), p-value 0.01)]. Helicobacter pylori seropositivity increased the odds of developing any hypertensive disorder during pregnancy among women of western ethnicity (948/1372) [OR:3.35 (95% CI: 1.29-8.74), p-value 0.03]., Conclusion: Our study suggests that Helicobacter pylori seropositivity is a risk factor for multiple adverse pregnancy outcomes and particularly in women of western origin for hypertensive disorders during pregnancy. Moreover, pathogen specific characteristics reflected in the antibody responses against OMP, GroEL and NapA seem to determine disease associations., Competing Interests: Declarations Ethics approval and consent to participate All studies received approval from the ethics committees of the centers involved and written informed consent was obtained from all participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The adverse effects of early-life tobacco smoke exposure on chronic kidney disease (CKD) risk remain unclear. This study aimed to investigate the associations of early-life tobacco smoke exposure with CKD incidence in adulthood, and further explore the modification effects of physical activity (PA)., Methods: A total of 352,883 participants were included from the UK Biobank. The information on early-life tobacco smoke exposure was assessed by employing in utero tobacco smoke exposure and age of smoking initiation. Weekly moderate-to-vigorous physical activity (MVPA) was calculated for each individual. Cox proportional hazard regression was fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CKD risk, and to investigate the modification effects of MVPA., Results: CKD incidence significantly increased in participants with in utero tobacco smoke exposure (HR: 1.08, 95% CI: 1.04, 1.12). Compared with never-smokers, we found a monotonic increase in the risk of CKD with smoking initiation across adulthood (HR: 1.21, 95% CI: 1.16, 1.27), adolescence (HR: 1.29, 95% CI: 1.24, 1.35), and childhood (HR: 1.34, 95% CI: 1.25, 1.43) (P trend < 0.001). Additionally, we identified joint cumulative effects of MVPA and early-life tobacco smoke exposure on incident CKD. Compared with never-smokers with recommended MVPA, prenatal or childhood tobacco smokers without recommended MVPA had the highest CKD risk, and the HRs (95% CIs) were 1.17 (1.10, 1.24) and 1.51 (1.36, 1.68), respectively., Conclusions: Early-life tobacco smoke exposure may contribute to CKD incidence in adulthood, and the observed associations could be modified by MVPA. These findings provide important information on CKD prevention in the participant's early life while urging a more rapid and powerful need for tobacco control among pregnant couples, children, and adolescents., Competing Interests: Declarations Ethics approval and consent to participate Ethical approval was obtained from the North West Multi-Center Research Ethics Committee (reference: 11/NW/0382). All participants were well-informed and signed informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Placement interventions, characterised by greater availability and more prominent positioning of healthy food products in supermarkets and other food stores, are associated with healthier patterns of purchasing and diet. The WRAPPED intervention study is a natural experiment that aims to evaluate a supermarket placement intervention to improve fruit and vegetable sales, household purchasing and the dietary quality of women and their children. Process evaluation, alongside the evaluation of outcomes, is essential to understand how interventions are implemented, under what circumstances they are effective, and their mechanisms of impact. This study aimed to assess the implementation of the WRAPPED placement intervention., Methods: The study adopted a convergent mixed-methods design. Quantitative data extracted from study store planograms (visual representation of stores and product placement) before and after intervention implementation were used to assess the positioning of fresh fruit and vegetables in the first aisle from the front entrance (intervention dose). The availability of fresh fruit and vegetables in each study store was examined from stock-keeping unit (SKU) figures before and after intervention implementation. An intervention implementation survey (IIS) completed with store managers and senior supervisors before and 1- and 6-months post-intervention implementation enabled examination of the context across study stores. Semi-structured interviews with store managers and senior supervisors provided qualitative data about store staff experiences and perceptions of the intervention between 6-months post-intervention implementation., Results: The placement intervention was implemented with close adherence to the study protocol. There were marked differences, post-intervention implementation, in the positioning of fresh fruit and vegetables in intervention stores compared with control stores: median distance in intervention stores was 8.0 m (IQR 5.0 to 10.0) compared with 23.8 m (IQR 21.0 to 30.0) in control stores (P < 0.0001). The availability of varieties of fresh fruit and vegetables increased in intervention stores post-intervention compared with control stores: median (IQR) among intervention stores was 72 (51, 84) compared with 56.5 (50, 62) in control stores (P = 0.03). The mean change from baseline to post-implementation in number of different fruit and vegetables available in intervention stores was 15.3 (SD 16.7) (P = 0.01). IIS and interview data demonstrated little difference between intervention and store contexts over time. Reinforcing factors for intervention implementation included: head-office leadership, store staff views and attitudes and increased awareness of the importance of offering healthy food in prominent locations within stores., Conclusion: This study demonstrated that placement interventions which promote fresh fruit and vegetables to customers in discount supermarkets can be implemented effectively. These findings are encouraging for the implementation of national food policies which modify retail environments to improve population purchasing and dietary patterns., Trial Registration: NCT03573973; Pre-results., Competing Interests: Declarations Ethical approval Ethical approval for the study was given by University of Southampton Faculty of Medicine ethics committee (Ethics ID 20986.A9). The study abided by the Declaration of Helsinki, Research Governance Framework for Health and Social Care and Data Protection regulations. The Consolidated criteria for Reporting Qualitative research (COREQ) were used to report qualitative research methods used in this study. Competing interests No funding was received from the supermarket involved in this study and all analyses were conducted independently, without involvement of supermarket staff. We, the authors, have read the journal’s policy and JB, CV, SC, PD, HP and WL have no conflicts of interest to declare., (© 2024. The Author(s).)