King's College London

BACKGROUND Overweight and obesity greatly increase the risk of preeclampsia. There is a need to better risk-stratify these women in pregnancy and channel resources to those who can benefit most. METHODS Prospective observational study of 11 962 women with singleton pregnancies attending a routine assessment at 35+0 to 36+6 weeks’ gestation at King’s College Hospital, London, United Kingdom. Women were categorized by their body mass index at 11 to 13 weeks’ gestation as normal weight (18.5–24.9 kg/m ² ), overweight (25.0–29.9 kg/m ² ), or obese (≥30 kg/m ² ). We recorded maternal demographics, assessed uterine artery pulsatility index and ophthalmic artery peak systolic velocity ratio, and measured carotid-to-femoral pulse-wave velocity. Preeclampsia development was retrieved from medical records. Multivariable logistic regression was undertaken to examine determinants of preeclampsia. Mediation analysis was performed to assess causal relationships. RESULTS In this cohort, 28.4% were overweight and 17.9% were obese. Preeclampsia developed more often in overweight/obese (versus normal weight) women (6.0% versus 1.7%, respectively; P <0.001); women of Black and South Asian ethnicity were at particularly increased risk ( P =0.02 and 0.004, respectively). Determinants of preeclampsia development did not differ by body mass index. Mediation analysis suggested that the effect of overweight/obesity on preeclampsia development may be mediated partly by changes in maternal cardiovascular indices, particularly aortic stiffness (as reflected by carotid-to-femoral pulse-wave velocity, proportion mediated=72.6%). CONCLUSIONS Risk factors for term preeclampsia are largely similar between overweight/obese and normal-weight women, except for Black and South Asian women, who face a particularly high risk within the overweight/obese group. Maternal vascular assessment may serve as a valuable tool for stratifying the risk for term preeclampsia in these populations.

Background Participant Information Leaflets (PILs) are lengthy and increasingly complex, and could deter research participation. A shortened PIL may be more appealing as it is likely to provide a more a manageable volume of information. Previous research has found that shortened PILs are no less effective for recruitment outcomes, and we deemed it useful to replicate this in an online setting. We also decided to compare retention rates, given the potential for more information to increase participants’ motivation. Aim To evaluate the efficacy of a shortened vs standard-length PIL on trial recruitment and retention rates. Methods This two-arm study within a trial (SWAT) was embedded in a host randomised controlled trial (RCT)—IBD-BOOST. Potential participants were randomised to receive a standard-length or shortened PIL electronically for recruitment to the host RCT. An ethics committee approved potential participants being blinded to this randomisation. Primary outcome: The percentage of SWAT participants receiving the shortened vs standard PIL who were recruited to the RCT. Results Four thousand two hundred one participants were randomised to the standard-length (n = 2099) and shortened (n = 2102) PIL arms. Thirty-four email queries were received about the PILs—18 from those who received the standard and 16 from those receiving the shortened. Seven hundred eight SWAT participants were recruited to the RCT—333 (15.86%) who received the standard-length PIL and 375 (17.84%) who received the shortened (OR = 1.15, (95%CI = 0.98, 1.35), p = 0.09). Retention rates in the RCT were not statistically different between groups. Conclusion We did not find evidence of a significant difference between RCT recruitment and retention rates in participants randomised to the standard-length PIL compared with the shortened. It may be that a shortened PIL has the same effect on recruitment and retention outcomes, providing that the trial does not require extensive information for other reasons (e.g. safety). Therefore, it could be argued that researchers have a choice about how long to make PILs, perhaps with a link to more detail. Alternatively, given that there was no benefit of the shortened PIL, it may be worth comparing written PILs with other methods of conveying information to determine optimal means of encouraging participation and retention in decentralised trials. Host trial registration A randomised controlled trial of supported, online, self-management for symptoms of fatigue, pain and urgency/incontinence in people with inflammatory bowel disease: the IBD-BOOST trial (ISRCTN71618461 on ISRCTN registry).

Background Due to historical under-recognition of attention-deficit hyperactivity disorder (ADHD) among girls and women, little is known about female-specific factors that may affect individuals with ADHD, including those related to changes in ovarian hormones (e.g. across the menstrual cycle). Aims We investigated whether females with a self-reported clinical diagnosis of ADHD are more likely to experience premenstrual dysphoric disorder (PMDD). We also examined associations between PMDD and ADHD defined by a symptom and impairment threshold. Method Participants were aged between 18 and 34 years, were assigned female at birth and were recruited via Prolific.com ( n = 715). Participants self-reported clinician diagnosis of ADHD, depression and anxiety. ADHD symptoms were assessed via the Adult ADHD Self-Report Scale (ASRS), to which we applied a DSM-5-based symptom and impairment cut-off (‘ASRS-based ADHD’). PMDD symptoms were assessed via the Premenstrual Symptoms Screening Tool (PSST), which identifies provisional PMDD. Using Poisson regression models, we compared risk for provisional PMDD among females with ADHD (self-reported clinical diagnosis [ n = 102] or ASRS-based [ n = 229]) with a non-ADHD reference group ( n = 305). We additionally compared risk for provisional PMDD among individuals with ADHD and depression/anxiety diagnoses, ADHD only and a non-ADHD reference group. Results The prevalence of provisional PMDD was elevated among individuals with a self-reported clinical ADHD diagnosis (31.4%), and among participants with ASRS-based ADHD (41.1%), compared with the non-ADHD reference group (9.8%). Individuals with ASRS-based ADHD and depression and/or anxiety diagnoses were at highest risk for provisional PMDD (relative risk 4.53 [3.10, 6.61]) compared with the non-ADHD reference group. Conclusions Clinicians should be aware that individuals with a diagnosis of ADHD, or with high ADHD symptom levels, and who have a menstrual cycle may be more likely to experience PMDD. Future research should investigate the underlying mechanisms that link ADHD and disorders associated with hormonal sensitivity, such as PMDD.

Objective To investigate the patient, treatment and oncological prognostic factors for multiple mental well‐being outcomes in prostate cancer. Patient and Methods The MIND‐P study was a multi‐institutional prospective cohort study recruiting newly diagnosed prostate cancer patients for 12 months post‐diagnosis across eight centres. Periodic data collection evaluated mental, physical and social well‐being measures incorporating five mental well‐being outcomes selected based on prior research as important measures in patients with prostate cancer. This included depression, anxiety, fear of recurrence, body image, and masculinity. Treatment, patient, and oncological prognostic factors for developing significant well‐being symptoms were evaluated along with symptom trajectories. Results Of 300 patients recruited, 13.7% and 11.0% developed depression or anxiety symptoms, with 45.0% developing at least one significant mental well‐being symptom. Those undergoing hormone monotherapy had higher depression scores from 6 months post‐diagnosis (all p < 0.05), with prostatectomy patients having poorer body image and masculinity scores, when compared with surveillance patients (all p < 0.02). Metastatic disease at diagnosis was associated with increased depression, anxiety and fear of cancer recurrence. Patient factors for poorer mental well‐being included younger age, a previous psychiatric history, social deprivation, poorer baseline mental health symptoms and poorer baseline sexual and urinary function. Symptom trajectory analysis demonstrated the increasing symptom load in body image and masculine self‐esteem experienced post any active treatment modality, with more stable scores for other mental well‐being measures. Conclusion A high incidence of multiple mental well‐being issues was identified post‐diagnosis, highlighting their individual importance during follow‐up. Baseline mental and functional symptoms, a previous psychiatric history and stage at diagnosis appear to be particularly important prognostic factors for the development of significant symptoms. A comprehensive initial biopsychosocial assessment incorporating these could identify high‐risk patients for improved monitoring and subsequent support. ClinicalTrials.gov number ‐ NCT04647474.

Objective To explore the role of shared decision-making (SDM) in the implementation of evidence-based practice in women with chronic hypertension planning birth and investigate the barriers and the facilitators in the provision of antenatal care. Methods A multimethod multisite approach was used including case-note review (n=55) and structured observations (n=18) to assess the provision of third trimester antenatal care. The barriers and facilitators to implementation were identified from semistructured qualitative interviews with healthcare professionals (n=13) and pregnant women (n=14) using inductive thematic analysis. The findings were integrated and evaluated using the ‘Three Talk Model of Shared Decision-making’. Setting and participants Pregnant women with chronic hypertension, some with superimposed pre-eclampsia and their principal carers at three National Health Service hospital trusts. Results Healthcare professionals delivering care to pregnant women with high blood pressure were aligned with most communication practices (set out in the Calgary-Cambridge communication guide). Pregnant women with hypertension who described being engaged in shared decisions about birth developed a trusting relationship with their maternity team. Despite frequent caesarean section birth (52%) and early term birth (median gestation at delivery 38 weeks (IQR1 37 weeks, IQR3 39 weeks) identified by case-note review; integrated data (observations, case-note review and qualitative interviews) found pregnant women with high blood pressure were not regularly provided with personalised information based on what they would find helpful, encouraged to share their own thoughts or offered choice in relation to timing or mode of birth. Uncertainty regarding the evidence around optimal timing of birth was the main barrier identified by professionals. Facilitators included training for professionals in SDM, midwife-led antenatal classes for high-risk women and multiprofessional clinics. Conclusions Strategies to promote more widespread adoption of SDM are likely to improve the experiences of women with high blood pressure making decisions about childbirth.

Aims To determine the treatment effectiveness associated with mobile health‐delivered cognitive behavioural therapy for insomnia (mCBT‐I) interventions for adults with insomnia and to identify the potential characteristics associated with better treatment outcomes. Design A systematic review and meta‐analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA 2020) guidelines. Methods Seven English‐ and two Chinese‐language databases were searched, without restrictions on publication dates, up to July 2024. Reference lists of relevant reviews and grey literature were included in the search. Randomised controlled trials evaluating mCBT‐I in adults with insomnia and published in either English or Chinese were included in this meta‐analysis. A random‐effects model was used for data analysis, accompanied by additional subgroup analyses and meta‐regression. Results Sixteen studies involving 2146 participants were included in this meta‐analysis. mCBT‐I interventions were associated with significantly reduced insomnia symptoms and improved sleep quality at post intervention, at 1–3‐month follow‐up, and at 4–6‐month follow‐up. Interventions that included five components of CBT‐I, were delivered for 6 weeks or longer, and were conducted in a group format were linked to better treatment outcomes; the differences in other subgroup categories were not statistically significant. Studies involving participants with comorbid conditions showed a greater effect in reducing insomnia symptoms than those without such participants. In addition, mCBT‐I interventions delivered by healthcare professionals resulted in statistically larger effect sizes for improving sleep quality than self‐help regimens. Conclusions The systematic review and meta‐analysis identified the effectiveness of mCBT‐I in reducing insomnia symptoms and improving sleep quality and offered practical implications for the development of effective mCBT‐I interventions in clinical practice. However, future robust studies are needed to explore the long‐term effects of mCBT‐I interventions. Patient or Public Contribution No patient or public contribution. Trail Registration PROSPERO CRD: 42023454647

Background Adolescents and young adults (AYA) with asthma and allergies have unexpectedly high mortality and morbidity. A survey in 2019 amongst healthcare professionals (HCPs) in Europe highlighted significant gaps in transition care, which negatively impacts patients' outcomes. Since then, an evidence‐based guideline and practical toolbox for effective transition of AYA with asthma and allergies have been published. Aims To assess HCPs' perspectives, practice and challenges on transition care for AYA with asthma and allergies, including the impact of the recent guideline, potential differences across countries and changes since 2019. Methods Cross‐sectional online survey‐based study. European HCP managing AYA with allergies and/or asthma were invited to participate in May–June 2023. Results 511 responses were collected. Amongst respondents, 60%–70% were familiar with the guideline and toolbox, and found them helpful. At least for selected patients, 50%–85% of respondents adhered to some guideline recommendations and initiatives/resources for transition care such as simplifying medication regimes, seeing AYA on their own or producing transition reports. We observed improvements compared to 2019 in areas such as prioritising transition, training, assessment of psychosocial issues and transition readiness, access to other HCP, transfer and post‐transfer feedback systems. However, 20% of respondents had no transition process and around 50% had no transition‐specific elements. Sixty percent found transition care ‘very’ or ‘moderately challenging’, with transition not being prioritised, time constraints and limited expertise on psychosocial issues as leading problems. Significant differences were observed in transition practice across countries. Conclusion Despite improvement in training and approach towards transition care, challenges and limitations persist in effectively implementing evidence‐based guidelines. Raising greater awareness about the need for, and the positive impact of high‐quality transition care amongst policy‐makers, HCP, and patients/families remains a key priority to unlock resources for training and effective implementation at a national/international level.

The second Biomarkers of Aging Symposium, jointly hosted by the National Institute on Aging (NIA) Intramural Research Program and the Biomarkers of Aging Consortium (BAC) on September 12, 2024, in Baltimore, MD, convened leading researchers, clinicians, and stakeholders in the aging field to share new developments and discuss roadmaps to advance biomarkers of aging. This meeting report summarizes the highlights of this symposium and underscores the urgent need to understand longitudinal, complex, and heterogeneous processes of aging to unlock the full potential of aging biomarkers.

In this update, we discuss the pricing paradox of combination therapies in health technology assessment; examine the Inflation Reduction Act’s impact on pharmaceutical innovation and analyze the revised Dutch economic evaluation guidelines.

Objectives We created the Digital Activity and Feelings Inventory (DAFI) to measure youth digital activities and the psychological reactions they evoke, established its psychometric properties and tested its validity in predicting mental health relative to screen time estimates. Methods An initial pool of items was generated using the existing research on youth digital activity and mental health and further refined via consultations with experts and young people (online youth panel sessions, n = 14). The participants (n = 383, mean age = 19 years) completed the resulting DAFI alongside established measures of depression, anxiety, wellbeing, and screen time. The DAFI factor structure, reliability and predictive validity were tested. Results Exploratory factor analyses identified five digital activity subscales: Risky Content, Risky Interactions, Social Comparison, Leisure Activities and Social Engagement and three psychological reactions subscales: Negative Self‐Reactions, Negative Stress Reactions, and Positive Reactions. Internal consistency and test‐retest reliability were high. Social Comparison and Negative Self‐Reactions, but not screen time, independently predicted depression and anxiety symptoms. Positive Reactions, lack of Negative Self‐Reactions, lower screen time and Social Engagement predicted wellbeing. Conclusion The DAFI is a reliable measure of digital activities and associated psychological reactions and predicts youth mental health better than screen time.

Objective This study aimed to explore the diverse range of weight loss behaviors that extend beyond traditional diagnostic criteria, highlighting the variability in symptom presentation. Method We text mined free‐text responses from 1675 participants with anorexia nervosa, bulimia nervosa, or binge‐eating disorder in the Genetic Links to Anxiety and Depression (GLAD) Study and the Eating Disorders Genetics Initiative UK (EDGI UK). In secondary analyses, we investigated differences by eating disorder and gender. Results Frequently endorsed behaviors included structured diets (619 endorsements) and calorie counting (422 endorsements), but also less commonly considered behaviors like compression garments (147 endorsements) and self‐harm (88 endorsements). We identified four overarching themes: restriction‐based approaches, medical intervention, body manipulation, and food avoidance. The most frequently reported weight loss behaviors and resultant themes did not differ among eating disorders or genders, closely resembling those in the broader sample. Notably, 81 participants with binge‐eating disorder, which typically lacks the endorsement of recurrent compensatory behaviors, reported weight loss and compensatory behaviors. Discussion Our findings identify a crucial gap in current diagnostic assessments, which may hamper recognition and lead to underdiagnosis of eating disorders. By incorporating our insights into an inclusive assessment process that expects and accommodates novel behaviors, clinicians could capture a broader spectrum of behaviors, thus improving diagnostic accuracy. However, our sample homogeneity implies the need for more diverse samples. Our study contributes essential insights for enhancing diagnostic criteria.

Aim To analyze the gender stratified associations of individual and clustered unhealthy behaviors during early adolescence (i.e., 11 years) with internalizing and externalizing symptoms during mid- and late adolescence (i.e., 14 and 17 years). Methods We used data from the Millennium Cohort Study including 9127 (4642 girls) participants at 14 years of age and 6970 (3611 girls) at 17 years of age. Internalizing and externalizing symptoms were self-reported by the main caregiver using the Strengths and Difficulties Questionnaire at 11 years, 14 years, and 17 years. Depressive symptoms were estimated using the Mood and Feelings Questionnaire at 14 years. Psychological distress was assessed using the six-item Kessler psychological distress scale at 17 years. Unhealthy behaviors (i.e., low sports practice, elevated TV-viewing, daily soft drink consumption, < 2 portions/day of fruits, alcohol consumption and tobacco use) were assessed at 11years. We used negative binomial regression models, adjusting for potential confounders assessed at 11y. Results Clustering three or more unhealthy behaviors at 11 years was associated with higher depressive symptoms (Boys: incidence rate ratio, IRR: 1.35; 95% CI: 1.17–1.56; Girls: 1.23; 1.10–1.38) and peer problems (boys: 1.36; 1.17–1.56; girls: 1.22; 1.08–1.38) at 14 years in both genders, as well as emotional problems among boys. Similarly, clustering three or more unhealthy behaviors was associated with higher peer problems (boys: 1.33; 1.16–1.51; girls: 1.24; 1.08–1.42) and psychological distress (boys:1.14; 1.04–1.25; girls: 1.10; 1.02–1.30) at 17 years among both genders as well as emotional problems among boys. Despite the high prevalence emotional problems among girls in both waves, there was a linear trend of increasing risk of the outcome with the increase in the number of unhealthy behaviors. Low sports practice and TV viewing were the unhealthy behaviors most consistently associated with later mental health-related outcomes. Conclusion Clustering two or more unhealthy behaviors during early adolescence was associated with higher internalizing and depressive symptoms in mid-adolescence, as well as internalizing symptoms and psychological distress in late adolescence.

Plectin (PLEC) is a versatile linker protein expressed in nearly all mammalian tissues, interlinking various components of the cytoskeleton and anchoring the hemidesmosome to the intermediate filament network of basal keratinocytes. Variants in PLEC disrupt its function as a linker protein, resulting in epidermolysis bullosa simplex (EBS), a hereditary skin disorder characterized by blister formation and mechanical fragility. Additionally, EBS patients with PLEC variants often exhibit varying degrees of muscular dystrophy. In this study, we detail the genotype, phenotype, transmission electron microscopy (TEM), and immunofluorescence microscopy (IFM) findings of nine Taiwanese EBS patients with PLEC variants. The patients had 13 pathogenic variants, including two missense variants and one inframe variant. Analyzing muscle involvement, TEM, and IFM findings, we determined that the presence of at least one missense or inframe pathogenic variant was correlated with milder muscular dystrophy or a later onset. Using AlphaFold, we modeled the 3D protein structures to elucidate the structural and functional implications of these pathogenic variants.

Aims To examine if SARS‐CoV‐2 infection is associated with new‐onset type 1 diabetes in the post‐acute period in children and young people (CYP). Methods In this population cohort, we used data on all hospital activity in England to estimate type 1 diabetes incidence among CYP aged 0–17 exposed to SARS‐CoV‐2 between May 2020 and August 2022, from day 28 after a positive test for the following 6 months. We compared this with unexposed CYP who were hospitalized for elective procedures or following trauma during the pandemic, and in the 2 years prior to the pandemic (historic cohorts). We excluded CYP with prior chronic illnesses. We undertook Cox regression analyses adjusted for age, sex, ethnicity, deprivation and season of index date, and stratified by periods when different SARS‐CoV‐2 variants were dominant. Results There were 1,087,604 CYP in the exposed cohort, 143,748 in the trauma cohort, 253,368 in the elective cohort, 160,925 in the historic trauma cohort and 388,673 in the historic elective cohort. Hazard of developing type 1 diabetes was significantly higher among those exposed than unexposed CYP: 2.4 [1.58–3.64] relative to the trauma cohort, 2.9 [2.00–4.13] relative to the elective cohort, 4.2 [2.56–7.04] relative to the historic trauma cohort and 2.4 [1.81–3.10] relative to the historic elective cohort. Associations may be strongest during the Delta period. Conclusions SARS‐CoV‐2 infection is associated with subsequent incident type 1 diabetes in the 1–7 months after an acute infection in previously healthy CYP.

The importance of effective clinical leadership has been reflected in an increase in leadership development programmes. However, there remains a lack of consensus regarding the optimal structure, content and evaluation of such programmes. This review synthesised evidence from reviews of leadership development interventions for healthcare professionals published prior to October 2024, including content, methods, evaluation strategies and impact. Title, abstract and full-text screening were conducted in duplicate by two reviewers. Data extraction was piloted by two reviewers and conducted by a single reviewer. Quality appraisal was conducted using the Risk of Bias in Systematic Reviews tool by a single reviewer, with generative artificial intelligence serving as the second reviewer. 86 systematic and non-systematic reviews met inclusion criteria. Regarding educational methods, leadership training effectiveness was associated with experiential learning, mixed-methods approaches, coaching or mentoring, longitudinal designs, goal-setting, and 360-degree feedback. Group learning and interprofessional education were noted for fostering teamwork. Programmes tailored to participants’ needs and organisational contexts showed better outcomes. Content reported to be effective included interpersonal skills, self-awareness, emotional intelligence, leadership theory, communication and teamwork. Evaluations primarily relied on self-reported measures. Training outcomes were largely positive at the individual level, with participants reporting increased confidence and competence. Organisational and clinical outcomes were less frequently assessed. The long-term impact on patient outcomes and return on investment remains uncertain. Leadership development programmes were found to enhance individual competencies. However, evidence supporting long-term, system-wide impact remains limited due to reliance on self-reported evaluations and a lack of standardised evaluation approaches

Dakar is replete with incomplete houses that are often viewed pejoratively to denote the supposed ‘failure’ of African cities. However, this perspective occludes analyses of the popular economies and socialities emanating from these same structures. This article explores the everyday lives of property guardians (known locally as gardiens ) living in the unfinished diaspora-built homes of Ouakam, Dakar (Senegal). Combining a critical historical analysis of post-colonial and post-socialist land and property arrangements in Ouakam with three ethnographic vignettes, the article unravels everyday articulations of property on the ground and develops the notion of entanglement to explore how property is produced, enacted, negotiated and re-arranged by gardiens . It shows that a propertied landscape characterised by opacity paradoxically enables gardiens to hold their place in the city and argues that entanglement illuminates different registers of agency, prompting us to re-imagine the politics and possibilities of life in the interstices of property.

The last British Society for Rheumatology (BSR) guideline on the hot swollen joint (HSJ) was published in 2006. The guideline needs to be updated to provide a summary of the current evidence for investigating and managing a HSJ, with a particular focus on septic arthritis. This guideline is aimed at healthcare professionals in the UK who directly care for people presenting with an HSJ, including front-line clinicians (in general practice and the emergency department), rheumatologists, orthopaedic surgeons, infectious diseases physicians, nurses, physiotherapists, occupational therapists, hand therapists, pharmacists, other health professionals and people experiencing an HSJ. It will also be relevant to people with lived experience of the condition as well as organizations that support them in the public and private sectors, including charities and informal patient support groups. This guideline will be developed using the methods and processes outlined in the BSR Guideline Protocol. Here we provide a brief summary of the scope of the guideline update in development.