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Background The quality of school-based sex and relationships education (SRE) is variable in the UK. Digitally-based interventions can usefully supplement teacher-delivered lessons and positively impact sexual health knowledge. Designed to address gaps in core SRE knowledge, STASH (Sexually Transmitted infections And Sexual Health) is a peer-led social network intervention adapted from the successful ASSIST (A Stop Smoking in Schools Trial) model, and based on Diffusion of Innovation theory. This paper describes how the STASH intervention was developed and refined. Methods Drawing on the Six Steps in Quality Intervention Development (6SQuID) framework, we tested a provisional programme theory through three iterative stages -: 1) evidence synthesis; 2) intervention co-production; and 3) adaptation - which incorporated evidence review, stakeholder consultation, and website co-development and piloting with young people, sexual health specialists, and educators. Multi-method results were analysed in a matrix of commonalities and differences. Results Over 21 months, intervention development comprised 20 activities within the three stages. 1) We identified gaps in SRE provision and online resources (e.g. around sexual consent, pleasure, digital literacy), and confirmed critical components including the core ASSIST peer nomination process, the support of schools, and alignment to the national curriculum. We reviewed candidate social media platforms, ruling out all except Facebook on basis of functionality restrictions which precluded their use for our purposes. 2) Drawing on these findings, as well as relevant behaviour change theories and core elements of the ASSIST model, we co-developed new content with young people and other stakeholders, tailored to sexual health and to delivery via closed Facebook groups, as well as face-to-face conversations. 3) A pilot in one school highlighted practical considerations, including around peer nomination, recruitment, awareness raising, and boundaries to message sharing. From this, a revised STASH intervention and programme theory were co-developed with stakeholders. Conclusions STASH intervention development required extensive adaptation from the ASSIST model. Although labour intensive, our robust co-development approach ensured that an optimised intervention was taken forward for feasibility testing. Evidencing a rigorous approach to operationalising existing intervention development guidance, this paper also highlights the significance of balancing competing stakeholder concerns, resource availability, and an ever-changing landscape for implementation. Trial registration ISRCTN97369178.

Background Although missed appointments in healthcare have been an area of concern for policy, practice and research, the primary focus has been on reducing single ‘situational’ missed appointments to the benefit of services. Little attention has been paid to the causes and consequences of more ‘enduring’ multiple missed appointments in primary care and the role this has in producing health inequalities. Methods We conducted a realist review of the literature on multiple missed appointments to identify the causes of ‘missingness.’ We searched multiple databases, carried out iterative citation-tracking on key papers on the topic of missed appointments and identified papers through searches of grey literature. We synthesised evidence from 197 papers, drawing on the theoretical frameworks of candidacy and fundamental causation. Results Missingness is caused by an overlapping set of complex factors, including patients not identifying a need for an appointment or feeling it is ‘for them’; appointments as sites of poor communication, power imbalance and relational threat; patients being exposed to competing demands, priorities and urgencies; issues of travel and mobility; and an absence of choice or flexibility in when, where and with whom appointments take place. Conclusions Interventions to address missingness at policy and practice levels should be theoretically informed, tailored to patients experiencing missingness and their identified needs and barriers; be cognisant of causal domains at multiple levels and address as many as practical; and be designed to increase safety for those seeking care.

The number of people living with multiple long-term conditions (MLTC or multimorbidity) is increasing. There have been national and international calls for more and better research in this clinical area. This systematic review will assess the methodological approaches, risk of bias and standards of reporting of the included trials. This study will benchmark current methodological practice and identify areas for improvement. MEDLINE, Scopus, CINAHL, CENTRAL and the International Research Community in Multimorbidity database will be searched from January 1999 to identify randomised controlled trials conducted with the aim of improving health outcomes for people living with MLTCs. Study screening, data extraction and the risk of bias assessment will be conducted independently by two reviewers. Data to be extracted will include study descriptors, design and analysis characteristics, methodological quality, bias and standard of reporting. A narrative synthesis will be conducted to summarise current methodological practice and to identify areas for improvement. Ethical approval is not required. The results of the review will be published in a peer-reviewed journal and shared via conferences and webinars. PROSPERO registration number: CRD42024595925.

Background Age-friendly communities are designed to support older adults in staying healthy, active, and engaged in society as they age. While the built environment plays an important role in their wellbeing, little is known about what shapes older adults’ views of community age-friendliness. This study explored how mid-to-older aged adults perceive community age-friendliness, and how these perceptions influence ageing in place. Methods Semi-structured interviews (in-person/online) were conducted with 21 community-dwelling adults (55–75 years; mean age 65.0 ± 5.5) from two Scottish local authorities with high deprivation (September 2023 – March 2024). Guided by maps of their local area, barriers and facilitators to community age-friendliness were charted to the WHO Age-Friendly Cities, Place Standard and Ageing in Place frameworks, and perceptions of localness were explored. Results Participants varied in physical activity, frailty, and loneliness levels, and experienced declining community age-friendliness. Physical barriers included neglected facilities, poorly accessible homes and spaces, and environmental hazards. Social barriers included declining access to social spaces due to rising costs, reduced hours and service closures. Service-related barriers included digital exclusion, ageism, safety concerns and reduced healthcare access. Perceptions of localness were shaped by (i) accessible and preferred transport options, with local areas shrinking as health declines; (ii) distance to essential services; and (iii) places where participants had social ties. Conclusions The perceived deterioration of local places underpins a decline of community age-friendliness. To support older adults to age well, policymakers must consider the effects of declining mobility, access to- and closure -of essential facilities for older adults.

Background Early childhood education and care (ECEC) settings offer a potentially cost-effective and sustainable solution for ensuring children have opportunities to meet physical activity (PA) and sedentary time (ST) guidelines. This paper systematically reviewed the association between childcare environment and practice and children’s PA and ST. Methods Three electronic databases were searched, and citation tracking of eligible studies performed between June–July 2020 (updated March 2022). Studies were eligible when (i) participants attended ECEC settings, (ii) they reported the association between use of outdoor space, including factors of time, availability, play, size and equipment, and children’s device-measured PA and ST, and (iii) where applicable, they compared the exposure to use of indoor space. Risk of bias was assessed using the Critical Appraisal Skills Program (CASP) tools. A synthesis was performed using effect direct plots and charts to visualise effect sizes. Results Of 1617 reports screened, 29 studies met the inclusion criteria. Studies provided data on outdoor versus indoor time ( n  = 9; 960 children), outdoor versus indoor play ( n  = 3; 1104 children), outdoor play space ( n  = 19; 9596 children), outdoor space use external to ECEC ( n  = 2; 1148 children), and portable ( n  = 7; 2408 children) and fixed ( n  = 7; 2451 children) outdoor equipment. Time spent outdoors versus indoors was associated with increased moderate-to-vigorous PA (MVPA), light PA (LPA) and total PA, while the association with ST was inconclusive. The mean (standard deviation) levels of outdoor MVPA (4.0 ± 3.2 to 18.6 ± 5.6 min/h) and LPA (9.9 ± 2.6 to 30.8 ± 11.8 min/h) were low, and ST high (30.0 ± 6.5 to 46.1 ± 4.3 min/h). MVPA levels doubled when children played outdoors versus indoors. Outdoor play space, and outdoor portable equipment, were associated with increased MVPA. A dose-response relationship for outdoor play area size was observed, demonstrating increased MVPA with areas ≥505m 2 (5436 ft 2 ), but no further increases when areas were > 900m 2 (9688 ft 2 ). No studies reported on injuries in outdoor settings. Conclusions ECEC policies and practices should promote not only outdoor time but also the availability of resources such as portable play equipment and sufficient size of outdoor play areas that enable children to be physically active for sustained periods while outdoors. Systematic review registration International prospective register of systematic reviews (PROSPERO) Registration Number: CRD42020189886.

Background Identifying clusters of multiple long-term conditions (MLTCs), also known as multimorbidity, and their associated burden may facilitate the development of effective and cost-effective targeted healthcare strategies. This study aimed to identify clusters of MLTCs and their associations with long-term health-related quality of life (HRQoL) in two UK population-based cohorts. Methods Age-stratified clusters of MLTCs were identified at baseline in UK Biobank ( n  = 502,363, 54.6% female) and UKHLS ( n  = 49,186, 54.8% female) using latent class analysis (LCA). LCA was applied to people who self-reported ≥ 2 LTCs (from n  = 43 LTCs [UK Biobank], n  = 13 LTCs [UKHLS]) at baseline, across four age-strata: 18–36, 37–54, 55–73, and 74 + years. Associations between MLTC clusters and HRQoL were investigated using tobit regression and compared to associations between MLTC counts and HRQoL. For HRQoL, we extracted EQ-5D index data from UK Biobank. In UKHLS, SF-12 data were extracted and mapped to EQ-5D index scores using a standard preference-based algorithm. HRQoL data were collected at median 5 (UKHLS) and 10 (UK Biobank) years follow-up. Analyses were adjusted for available sociodemographic and lifestyle covariates. Results LCA identified 9 MLTC clusters in UK Biobank and 15 MLTC clusters in UKHLS. Clusters centred around pulmonary and cardiometabolic LTCs were common across all age groups. Hypertension was prominent across clusters in all ages, while depression featured in younger groups and painful conditions/arthritis were common in clusters from middle-age onwards. MLTC clusters showed different associations with HRQoL. In UK Biobank, clusters with high prevalence of painful conditions were consistently associated with the largest deficits in HRQoL. In UKHLS, clusters of cardiometabolic disease had the lowest HRQoL. Notably, negative associations between MLTC clusters containing painful conditions and HRQoL remained significant even after adjusting for number of LTCs. Conclusions While higher LTC counts remain important, we have shown that MLTC cluster types also have an impact on HRQoL. Health service delivery planning and future intervention design and risk assessment of people with MLTCs should consider both LTC counts and MLTC clusters to better meet the needs of specific populations.

Background Bipolar disorder is a serious mental illness, which requires new strategies for prevention and management. Recent evidence suggests that a ketogenic diet may be an effective intervention. This research aimed to explore the feasibility and acceptability of a ketogenic diet intervention for bipolar disorder, fidelity to its behavioural components and the experiences of the participants and research clinicians involved. Methods A mixed-methods process evaluation was conducted. Semi-structured telephone interviews were carried out with 15 participants 1–2 months after completing a 6–8 week modified ketogenic diet intervention, and 4 research clinicians from the study team following the completion of data collection. Data were thematically analysed. Fidelity checklists completed by research dietitians were analysed using descriptive count and percentage statistics. Findings are reported post-hoc, following the analysis and publication of the main pilot study findings. Reporting was guided by the COREQ checklist. Results Five themes were identified in the qualitative data: (1) ‘ Encouraging entry and supporting exit’ (e.g. recognising and managing participants’ varied motives and expectations, including around weight loss and symptom alleviation); (2) ‘ Challenging but potentially transformational ,’ which reflects that while it can be difficult to initiate and maintain a ketogenic diet day-to-day, many participants perceived physical and psychological benefits (e.g. significant weight loss, mood stability and enhanced ability to focus); (3) ‘Intervention facilitators ,’ including a range of behavioural (e.g. goal setting), social (e.g. family and dietitians) and technological (e.g. apps for monitoring) support mechanisms; (4) ‘Intervention barriers’ (e.g. dietary preferences, concerns about the diet and its impact, the testing burden and capacity of the delivery team); and (5) ‘The wider context’ (e.g. the cost of living and sociocultural expectations) was a crucial factor explaining differential experiences. Overall, descriptive analyses indicated moderate-to-good fidelity to the behaviour change components of the study. Conclusion We provide novel insight into the experiences of people living with bipolar disorder initiating and following a ketogenic diet, as well as those of research clinicians who support the intervention. Future trials may benefit from increased clinical research capacity, better-defined entry and exit routes, additional interpersonal support, and greater understanding of how social and societal factors impact participation. Trial registration Study registration number: ISRCTN61613198 (02/03/22).

Children and adolescents commonly suffer from sleep and circadian rhythm disturbances, which may contribute to poorer mental health and wellbeing during this critical developmental phase. Many studies however rely on self-reported sleep measures. This study assessed whether accelerometry data collection was feasible within the school setting as a method for investigating the extent of sleep and circadian disruption, and associations with subjective wellbeing, in Scotland. Fourteen days of wrist-worn accelerometry data were collected from 69 pupils, aged 10–14 years. Objective measures of sleep timing, sleep duration and circadian rest-activity patterns were derived. Questionnaires assessed subjective sleep timing, depressive symptoms, and experiences of wearing the accelerometer. Pupils slept on average less than 8 hours per night, failing to meet standard age-specific recommendations. Sleep timing was later and duration longer on weekends compared to weekdays (B = 0.87, 95% confidence interval (CI) 0.70, 1.04; B = 0.49, 95% CI 0.29, 0.69), indicating social jetlag. Lower daytime activity was correlated with higher depressive symptoms ( r = -0.84, p = 0.008). Compared to primary school pupils, secondary pupils had shorter sleep window duration and lower circadian relative amplitude. Over half of participants reported some discomfort/inconvenience wearing the accelerometer. These data highlight that inadequate sleep is prevalent in this sample of schoolchildren. Future, larger scale investigations will examine in more detail the associations between sleep, circadian function and physical activity with mental health and wellbeing.

Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date. To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder. Euthymic individuals with bipolar disorder were recruited to a 6-8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198. Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6-8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication). The recruitment and retention of euthymic individuals with bipolar disorder to a 6-8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder. To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes. Euthymic individuals with bipolar disorder ( = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention. Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg ( < 0.001), mean body mass index fell by 1.5 kg/m ( < 0.001) and mean systolic blood pressure fell by 7.4 mmHg ( < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data ( = 14), there was a positive correlation between daily ketone levels and self-rated mood ( = 0.21, < 0.001) and energy ( = 0.19 < 0.001), and an inverse correlation between ketone levels and both impulsivity ( = -0.30, < 0.001) and anxiety ( = -0.19, < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex ( = 0.025) and fell by 13.6% in the posterior cingulate cortex ( = <0.001). These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.