Reprint of: 'A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance'.

The UK Medical Research Council's widely used guidance for developing and evaluating complex interventions has been replaced by a new framework, commissioned jointly by the Medical Research Council and the National Institute for Health Research, which takes account of recent developments in theory and methods and the need to maximise the efficiency, use, and impact of research.

Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM): protocol for a randomised feasibility trial.

INTRODUCTION: Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes. METHODS AND ANALYSIS: A multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control). The primary outcome of this feasibility trial will be to assess whether prespecified progression criteria (recruitment, retention, intervention adherence) are met to progress to the full randomised trial. The trial will be conducted across three UK sites and 60 people with MLTCs, defined as two or more LTCs, with at least one having evidence of the beneficial effect of exercise. The PERFORM intervention comprises an 8-week (twice a week for 6 weeks and once a week for 2 weeks) supervised rehabilitation programme of personalised exercise training and self-management education delivered by trained healthcare professionals followed by two maintenance sessions. Trial participants will be recruited over a 4.5-month period, and outcomes assessed at baseline (prerandomisation) and 3 months postrandomisation and include health-related quality of life, psychological well-being, symptom burden, frailty, exercise capacity, physical activity, sleep, cognition and serious adverse events. A mixed-methods process evaluation will assess acceptability, feasibility and fidelity of intervention delivery and feasibility of trial processes. An economic evaluation will assess the feasibility of data collection and estimate the costs of the PERFORM intervention. ETHICS AND DISSEMINATION: The trial has been given favourable opinion by the West Midlands, Edgbaston Research Ethics Service (Ref: 23/WM/0057). Participants will be asked to give full, written consent to take part by trained researchers. Findings will be disseminated via journals, presentations and targeted communications to clinicians, commissioners, service users and patients and the public. TRIAL REGISTRATION NUMBER: ISRCTN68786622. PROTOCOL VERSION: 2.0 (16 May 2023).

Estimating the prevalence and predictors of musculoskeletal disorders in Tanzania: a cross-sectional pilot study.

Introduction: musculoskeletal (MSK) disorders account for approximately 20% of all years lived with disability worldwide however studies of MSK disorders in Africa are scarce. This pilot study aimed to estimate the community-based prevalence of MSK disorders, identify predictors, and assess the associated disability in a Tanzanian population. Methods: a cross-sectional study was conducted in one village in the Kilimanjaro region from March to June 2019. The Gait, Arms, Legs, Spine (GALS) or paediatric GALS (pGALS) examinations were used during household and school visits. Individuals positive in GALS/pGALS screening were assessed by the regional examination of the musculoskeletal system (REMS) and Modified Health Assessment Questionnaire (MHAQ). Results: among the 1,172 individuals enrolled in households, 95 (8.1%, 95% CI: 6.6 - 9.8) showed signs of MSK disorders using the GALS/pGALS examination and 37 (3.2%, 95% CI: 2.2 - 4.3) using the REMS. Among 682 schools enrolled children, seven showed signs of MSK disorders using the GALS/pGALS examination (1.0%, 95% CI: 0.4 - 2.1) and three using the REMS (0.4%, 95% CI: 0.0 - 1.3). In the household-enrolled adult population, female gender and increasing age were associated with GALS and REMS-positive findings. Among GALS-positive adults, increasing age was associated with REMS-positive status and increasing MHAQ score. Conclusion: this Tanzanian study demonstrates a prevalence of MSK disorders and identifies predictors of MSK disorders comparable to those seen globally. These findings can inform the development of rheumatology services and interventions in Tanzania and the design of future investigations of the determinants of MSK disorders, and their impacts on health, livelihoods, and well-being.

Rapid ethnographic appraisal of community concepts of and responses to joint pain in Kilimanjaro, Tanzania.

INTRODUCTION: Musculoskeletal disorders, experienced as joint pain, are a significant global health problem, but little is known about how joint pain is categorised and understood in Tanzania. Understanding existing conceptualisations of and responses to joint pain is important to ensure both research and interventions are equitable and avoid biomedical imposition. METHODS: Rapid ethnographic appraisal was conducted in a periurban and rural community in Kilimanjaro, documenting language used to describe joint pain, ideas about causes, understandings of who experiences such pain, the impacts pain has and how people respond to it. We conducted 66 interviews with community leaders, traditional healers, community members and pharmacists.Photographs were taken and included in fieldnotes to supplement the interview data and develop thick descriptions. Data were analysed by constant comparison using QDA Miner software. RESULTS: Across the sample, dominant concepts of joint pain were named ugonjwa wa baridi, cold disease; ugonjwa wa uzee, old age disease; rimatizim, disease of the joints; and gauti, gout. Causes mentioned included exposure to the cold, old age, alcohol and red meat consumption, witchcraft, demons and injuries/falls. Age, gender and occupation were seen as important factors for developing joint pain. Perceived impacts of joint pain included loss of mobility, economic and family problems, developing new health conditions, death, reduction in sexual functioning and negative self-perceptions. Responses to joint pain blended biomedical treatments, herbal remedies, consultations with traditional healers and religious rituals. CONCLUSIONS: Conceptualisations of and responses to joint pain in the two communities were syncretic, mixing folk and biomedical practices. Narratives about who is affected by joint pain mirror emerging epidemiological findings, suggesting a strong 'lay epidemiology' in these communities. Anthropological methods can support the decolonisation of global health by decentring the imposition of English language biomedicine and pursuing synthetic, dignified languages of care.

Testing the feasibility of a co-designed intervention, comprising self-managed, home-based, exercise training with embedded behavioural support and compression therapy for people with venous leg ulcers receiving treatment at home (FISCU-II).

BACKGROUND: Venous leg ulcers (VLUs) heal slowly, are painful for patients and are costly for healthcare systems; they also affect patients' quality of life. Previous work suggests that supervised exercise training used in combination with compression therapy may offer clinical benefits. However, a large population of people with VLUs are unable to access such an intervention due to frailty and age. OBJECTIVES: To assess the feasibility of 'FISCU Home' (a co-designed, 12-week home-based self-managed lifestyle programme based on exercise and behaviour support) as an adjunct therapy to compression in people with VLUs. METHODS: Forty people with VLUs, receiving treatment at home, were recruited from community nursing and tissue viability teams, and via a newspaper advertisement. Participants were randomized 1 : 1 either to exercise with behaviour support (three times per week) plus compression therapy or compression only. The feasibility of the programme was assessed using progression criteria that included exercise attendance rate, loss to follow-up, patient preference(s) and adverse events (AEs). Baseline assessments were repeated at 12 weeks and 6 months. Secondary outcomes (i.e. ulcer recurrence, healing rate and healing time) were also documented at these intervals. Intervention and healthcare utilization costs were calculated. RESULTS: The study recruitment rate was 65%, while 75% of the exercise group participants attended all scheduled exercise sessions. All participants completed compression therapy. No serious AEs or exercise-related AEs were reported. Median (interquartile range) ulcer healing time was shorter in the exercise group [29 (7-108) vs. 42 (6-116) weeks]. CONCLUSIONS: The feasibility and acceptability of both a home- and exercise-based lifestyle intervention in conjunction with compression therapy and the study procedures are supported.

Evaluation of the Healthy Start voucher scheme on maternal vitamin use and child breastfeeding: a natural experiment using data linkage.

Background: Having a good start in life during pregnancy and infancy has been shown to be important for living both a healthy life and a longer life. Despite the introduction of many policies for the early-years age group, including voucher schemes, with the aim of improving nutrition, there is limited evidence of their impact on health. Objectives: To assess the effectiveness of the Healthy Start voucher scheme on infant, child and maternal outcomes, and to capture the lived experiences of the Healthy Start voucher scheme for low-income women. Design: This was a natural experiment study using existing data sets, linked to routinely collected health data sets, with a nested qualitative study of low-income women and an assessment of the health economics. Setting: Representative sample of Scottish children and UK children. Participants: Growing Up in Scotland cohort 2 (n = 2240), respondents to the 2015 Infant Feeding Study (n = 8067) and a sample of 40 participants in the qualitative study. Interventions: The Health Start voucher, a means-tested scheme that provides vouchers worth £3.10 per week to spend on liquid milk, formula milk, fruit and vegetables. Main outcome measures: Infant and child outcomes - breastfeeding initiation and duration; maternal outcomes - vitamin use pre and during pregnancy. Results: The exposed group were women receiving the Healthy Start voucher (R), with two control groups: eligible and not claiming the Healthy Start voucher (E) and nearly eligible. There was no difference in vitamin use during pregnancy for either comparison (receiving the Healthy Start voucher, 82%; eligible and not claiming the Healthy Start voucher, 86%; p = 0.10 vs. receiving the Healthy Start voucher, 87%; nearly eligible, 88%; p = 0.43) in the Growing Up in Scotland cohort. Proportions were similar for the Infant Feeding Study cohort (receiving the Healthy Start voucher, 89%; eligible and not claiming the Healthy Start voucher, 86%; p = 0.01 vs. receiving the Healthy Start voucher, 89%; nearly eligible, 87%; p = 0.01); although results were statistically significantly different, these were small effect sizes. There was no difference for either comparison in breastfeeding initiation or breastfeeding duration in months in Growing Up in Scotland, but there was a negative effect of the Healthy Start voucher in the Infant Feeding Survey. This contrast between data sets indicates that results are inconclusive for breastfeeding. The qualitative study found that despite the low monetary value the women valued the Healthy Start voucher scheme. However, the broader lives of low-income women are crucial to understand the constraints to offer a healthy diet. Limitations: Owing to the policy being in place, it was difficult to identify appropriate control groups using existing data sources, especially in the Infant Feeding Study. Conclusions: As the Healthy Start voucher scheme attempts to influence health behaviour, this evaluation can inform other policies aiming to change behaviour and use voucher incentives. The null effect of Healthy Start vouchers on the primary outcomes may be due to the value of the vouchers being insufficient to change the broader lives of low-income women to offer a healthy diet. Future work: The methods developed to undertake an economic evaluation alongside a natural experiment using existing data can be used to explore the cost-effectiveness of the Healthy Start voucher scheme. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 11, No. 11. See the NIHR Journals Library website for further project information.

United Kingdom governments have introduced many policies to support infants and their families. Most of these policies have not been evaluated in terms of health outcomes. Therefore, there is limited evidence for policy-makers about whether or not the right policies are in place to make a difference to the health of young children and their families. We investigated the impact of the Healthy Start voucher scheme (worth £3.10 per week to spend on milk, fruit and vegetables) on the health of low-income mothers, and their infants and young children, in particular vitamin use of mothers and breastfeeding of infants. Using survey data, there were high rates of vitamin use during pregnancy, but fewer women taking vitamins before pregnancy. There was no effect of Healthy Start vouchers on taking vitamins before or during pregnancy. There was inconclusive evidence of the effect of Healthy Start vouchers on breastfeeding, indicating that use of the vouchers does not discourage breastfeeding in women with low incomes. From interviews with mothers, we found that they valued the Healthy Start vouchers and understood the aims of the policy. Healthy Start vouchers were not mentioned in decision-making around breastfeeding. Women's choice to breast or formula feed was based on a range of other factors, such as support to breastfeed. They wanted to provide a healthy diet for their families, but owing to living on low incomes did not always manage it. Policy-makers still need more evidence about the effects of voucher schemes to improve the health of low-income mothers, and their infants and young children. The decision-makers require evidence to determine where to allocate limited resources. There is a need to improve support for low-income families to provide their families with a healthy diet.

Relationship of the SITLESS intervention on medication use in community-dwelling older adults: an exploratory study.

Background: Sedentary behavior (SB) and physical activity (PA) interventions in older adults can improve health outcomes. Problems related with aging include prevalent comorbidity, multiple non-communicable diseases, complaints, and resulting polypharmacy. This manuscript examines the relationship between an intervention aiming at reducing SB on medication patterns. Method: This manuscript presents a local sub-analysis of the SITLESS trial data on medication use. SITLESS was an exercise referral scheme (ERS) enhanced by self-management strategies (SMS) to reduce SB in community-dwelling older adults. We analyzed data from the ERS + SMS, ERS and usual care (UC) groups. Patient medication records were available at baseline and at the end of the intervention (4-month period) and were analyzed to explore the effect of SITLESS on medication patterns of use. Result: A sample of 75 participants was analyzed, mostly older overweight women with poor body composition scores and mobility limitations. There was a significant reduction of 1.6 medicines (SD = 2.7) in the ERS group (p < 0.01), but not in the UC or ERS + SMS groups. Differences were more evident in medicines used for short periods of time. Conclusion: The findings suggest that an exercise-based program enhanced by SMS to reduce SB might influence medication use for acute conditions but there is a need to further investigate effects on long-term medicine use in older adults.

Exploring the Feasibility of a Self-Managed Lifestyle Intervention, Based on Exercise and Behaviour Support, as an Adjunct Therapy to Compression: A Sub-Study Focusing on People with Venous Leg Ulcers and Early Neuro-Degenerative Diseases (FISCU-NDD).

BACKGROUND: The aim of this study was to adapt the "FISCU Home" intervention (a co-produced, self-managed and expert-supported lifestyle intervention comprising exercise and behaviour support aimed at people with Venous Leg Ulcers (VLUs), in a way that is suitable for the needs of people with combined VLUs and early-stage, Neuro-degenerative diseases (NDDs), and to explore its feasibility (e.g., estimate rates of recruitment and completion of sessions, calculate study adherence rates, assess participant satisfaction via participant interviews, and assess ease of data collection) within this clinical sub-group. METHODS: We recruited seven people belonging to this VLUs sub-group (e.g., people with early-stage dementia or Parkinson's), who were ≥18 years' old, had VLU(s) of diameter ≥1 cm, ABPI ≥ 0.8, had the ability to tolerate lower-leg compression and were receiving VLU treatment at home. In Phase 1, participants helped us adapt the intervention. In Phase 2 we carried out a 4-week "training crash-course". This consisted of three, 1 h, self-managed, exercise sessions per week (12 sessions in total), among the participants that completed the interviews. For Phase 3, we carried out post-interviews with all participants to investigate their study experiences, which were analysed using content analysis. RESULTS: All assessments were completed successfully (100% retention and assessment completion), with no exercise-related adverse events. All participants completed the 4-week intervention (100%; all sessions completed by all participants). CONCLUSION: Our findings suggest that the adapted intervention is feasible, enjoyable and well-received, and has the potential to provide clinical benefits to the participants.

Benefits, risks, barriers, and facilitators to cycling: a narrative review.

There is large potential to increase cycling participation worldwide. Participation in cycling is associated with lower risk of mortality from any cause, and incidence of cardiovascular disease and type 2 diabetes, as well as positive mental health and well-being. The largest potential for health gains likely to come from increasing participation amongst those who do not currently cycle regularly, rather than encouraging those who already cycle regularly to cycle more. Replacing car journeys with cycling can lead to reductions in air pollution emissions and lower pollutant exposure to the general population. Important gaps and uncertainties in the existing evidence base include: the extent to which the health benefits associated with cycling participation are fully causal due to the observational nature of much of the existing evidence base; the real-world economic cost-benefits of pragmatic interventions to increase cycling participation; and the most effective (combination of) approaches to increase cycling participation. To address these uncertainties, large-scale, long-term randomised controlled trials are needed to: evaluate the effectiveness, and cost-effectiveness, of (combinations of) intervention approaches to induce sustained long-term increases in cycling participation in terms of increases in numbers of people cycling regularly and number of cycling journeys undertaken, across a range of population demographic groups; establish the effects of such interventions on relevant outcomes related to health and wellbeing, economic productivity and wider societal impacts; and provide more robust quantification of potential harms of increasing cycling participation, such as collision risks.

Pilot study of a ketogenic diet in bipolar disorder.

BACKGROUND: 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. AIMS: To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

Trends of frequency, mortality and risk factors among patients admitted with stroke from 2017 to 2019 to the medical ward at Kilimanjaro Christian Medical Centre hospital: a retrospective observational study.

OBJECTIVE: The burden of stroke has increased in recent years worldwide, particularly in low-income and middle-income countries. In this study we aim to determine the number of stroke admissions, and associated comorbidities, at a referral hospital in Northern Tanzania. DESIGN: This was a retrospective observational study. SETTING: The study was conducted at a tertiary referral hospital, Kilimanjaro Christian Medical Centre (KCMC), in the orthern zone of Tanzania. PARTICIPANTS: The study included adults aged 18 years and above, who were admitted to the medical wards from 2017 to 2019. OUTCOME: The primary outcome was the proportion of patients who had a stroke admitted in the medical ward at KCMC and the secondary outcome was clinical outcome such as mortality. METHODS: We conducted a retrospective audit of medical records from 2017 to 2019 for adult patients admitted to the medical ward at KCMC. Data extracted included demographic characteristics, previous history of stroke and outcome of the admission. Factors associated with stroke were investigated using logistic regression. RESULTS: Among 7976 patients admitted between 2017 and 2019, 972 (12.2%) were patients who had a stroke. Trends show an increase in patients admitted with stroke over the 3 years with 222, 292 and 458 in 2017, 2018 and 2019, respectively. Of the patients who had a stroke, 568 (58.4%) had hypertension while 167 (17.2%) had diabetes mellitus. The proportion of admitted stroke patients aged 18-45 years, increased from 2017 (n=28, 3.4%) to 2019 (n=40, 4.3%). The in-hospital mortality related to stroke was 229 (23.6%) among 972 patients who had a stroke and female patients had 50% higher odds of death as compared with male patients (OR:1.5; CI 1.30 to 1.80). CONCLUSION: The burden of stroke on individuals and health services is increasing over time, which reflects a lack of awareness on the cause of stroke and effective preventive measures. Prioritising interventions directed towards the reduction of non-communicable diseases and associated complications, such as stroke, is urgently needed.

The co-design of an exercise-based, lifestyle intervention for people with venous leg ulcers; a self-care, expert-supported strategy for a chronic condition.

Exercise is recommended as an adjunct treatment, alongside compression therapy to increase venous leg ulcer (VLU) wound healing times, however, there are no published programmes available that support patients to exercise at home on their own. To develop an exercise-based lifestyle intervention that is feasible and acceptable to people with VLUs, a participatory approach was utilised. Clinicians, researchers, and people living with VLUs collaborated in the design of "FISCU Home". Two focus groups and nine interviews were conducted with people living with a VLU. Tissue viability nurses provided clinical expertise. Data was analysed through thematic analysis. Ten key themes were identified and incorporated into FISCU Home: (I) a condition-specific flexible programme, (II) personal assessment and tailored exercises, (III) tapered individualised support, (IV) short lower-intensity sessions, (V) chair-based options, (VI) falls prevention, (VII) accessible resources, (VIII) functional, compact, self-managed exercises, (IX) a behaviour change strategy, and (X) education. FISCU Home has integrated patients' needs and preferences with evidence-based principles and theory to create an exercise-based lifestyle intervention for people with VLUs. FISCU Home could provide a mainstream adjunct therapy in wound care and support the movement towards self-management.

"Mars Bar and a Tin of Red Bull Kept Me and My Patients Alive": Exploring Barriers to Healthy Eating through Facebook Comments of Shiftworkers.

The negative impact of an unhealthy diet on the shiftworker population has been well-documented. However, little evidence exists on the underlying reasons for unhealthy eating behaviours and the existing barriers to healthy eating withinshiftwork environments. This qualitative study investigated the dietary behaviours reported by shiftworkers through Facebook comments. Comments were collected if they were on public shiftworker-relevant posts pertaining to dietary news or dietary information on Facebook and were posted by self-identified shiftworkers, relatives of shiftworkers, or partners of shiftworkers. A thematic analysis of the 144 comments collected generated four categories that can be used to understand the motivations for eating behaviour on-shift: what shiftworkers eat, where food is sourced from, when food is eaten, and why certain foods are chosen. Results reveal motivations, attitudes, and both internal and external barriers to healthy eating behaviours, as well as similarities and differences across shiftwork industries. Recommendations for future research include further explorations on the link between scheduled eating (e.g., time-restricted eating) and shiftwork, the impact of a rotating shift arrangements on dietary health behaviours, and the impact of interpersonal relationships on shiftworker dietary choices. Understanding these motivations will inform strategies to promote healthy eating and help understand barriers for shiftworkers.

Comorbidity and health-related quality of life in people with a chronic medical condition in randomised clinical trials: An individual participant data meta-analysis.

BACKGROUND: Health-related quality of life metrics evaluate treatments in ways that matter to patients, so are often included in randomised clinical trials (hereafter trials). Multimorbidity, where individuals have 2 or more conditions, is negatively associated with quality of life. However, whether multimorbidity predicts change over time or modifies treatment effects for quality of life is unknown. Therefore, clinicians and guideline developers are uncertain about the applicability of trial findings to people with multimorbidity. We examined whether comorbidity count (higher counts indicating greater multimorbidity) (i) is associated with quality of life at baseline; (ii) predicts change in quality of life over time; and/or (iii) modifies treatment effects on quality of life. METHODS AND FINDINGS: Included trials were registered on the United States trials registry for selected index medical conditions and drug classes, phase 2/3, 3 or 4, had ≥300 participants, a nonrestrictive upper age limit, and were available on 1 of 2 trial repositories on 21 November 2016 and 18 May 2018, respectively. Of 124 meeting these criteria, 56 trials (33,421 participants, 16 index conditions, and 23 drug classes) collected a generic quality of life outcome measure (35 EuroQol-5 dimension (EQ-5D), 31 36-item short form survey (SF-36) with 10 collecting both). Blinding and completeness of follow up were examined for each trial. Using trials where individual participant data (IPD) was available from 2 repositories, a comorbidity count was calculated from medical history and/or prescriptions data. Linear regressions were fitted for the association between comorbidity count and (i) quality of life at baseline; (ii) change in quality of life during trial follow up; and (iii) treatment effects on quality of life. These results were then combined in Bayesian linear models. Posterior samples were summarised via the mean, 2.5th and 97.5th percentiles as credible intervals (95% CI) and via the proportion with values less than 0 as the probability (PBayes) of a negative association. All results are in standardised units (obtained by dividing the EQ-5D/SF-36 estimates by published population standard deviations). Per additional comorbidity, adjusting for age and sex, across all index conditions and treatment comparisons, comorbidity count was associated with lower quality of life at baseline and with a decline in quality of life over time (EQ-5D -0.02 [95% CI -0.03 to -0.01], PBayes > 0.999). Associations were similar, but with wider 95% CIs crossing the null for SF-36-PCS and SF-36-MCS (-0.05 [-0.10 to 0.01], PBayes = 0.956 and -0.05 [-0.10 to 0.01], PBayes = 0.966, respectively). Importantly, there was no evidence of any interaction between comorbidity count and treatment efficacy for either EQ-5D or SF-36 (EQ-5D -0.0035 [95% CI -0.0153 to -0.0065], PBayes = 0.746; SF-36-MCS (-0.0111 [95% CI -0.0647 to 0.0416], PBayes = 0.70 and SF-36-PCS -0.0092 [95% CI -0.0758 to 0.0476], PBayes = 0.631. CONCLUSIONS: Treatment effects on quality of life did not differ by multimorbidity (measured via a comorbidity count) at baseline-for the medical conditions studied, types and severity of comorbidities and level of quality of life at baseline, suggesting that evidence from clinical trials is likely to be applicable to settings with (at least modestly) higher levels of comorbidity. TRIAL REGISTRATION: A prespecified protocol was registered on PROSPERO (CRD42018048202).

Is education level, as a proxy for socio-economic position, related to device-measured and self-reported sedentary behavior in European older adults? A cross-sectional study from the SITLESS project.

Background: Sedentary behavior (SB) is a determinant of health in older adult people. Educational level is a primary driver of health disparities and is demonstrated to be a reliable measure of socioeconomic position. We aimed to examine the associations between educational level and self-reported along with device-measured SB in older adults living in Europe and the association of mentally active and passive SB domains with the educational level and gender in these associations. Methods: The design is cross-sectional. One thousand three hundred and sixty participants aged 65 and over (75.3±6.3 years old, 61.8% women) participated. Inclusion criteria were scored with the Short Physical Performance Battery. Variables that describe the sample were assessed with an interview, and device-measured SB was assessed with an accelerometer. SB was assessed with the Sedentary Behavior Questionnaire and an accelerometer. Multiple linear regression models were used to study the association between the level of education and SB. Results: Participants self-reported an average of 7.82 (SD: 3.02) daily waking hours of SB during weekend days, and the average of device-measured SB was 11.39 (1.23) h. Total mentally active SB (weekdays and weekends) was associated with the education level (p < 0.000). Participants were more sedentary during the week than during weekends, regardless of level of education (p < 0.000). Education level was significantly associated with self-reported mean hours per day in 46SB (p = 0.000; R=0.026; 95%CI). Conclusion: Low education level in older adults is associated with self-reported SB but not with objective SB measures.

Development and optimisation of a multi-component workplace intervention to increase cycling for the Cycle Nation Project.

The Cycle Nation Project (CNP) aimed to develop, test the feasibility of and optimize a multi-component individual-/social-level workplace-based intervention to increase cycling among office staff at a multinational bank (HSBC UK). To do this, we first explored barriers to cycling in a nationally-representative survey of UK adults, then undertook focus groups with bank employees to understand any context-specific barriers and ways in which these might be overcome. These activities led to identification of 10 individual-level, two social-level, and five organizational-level modifiable factors, which were mapped to candidate intervention components previously identified in a scoping review of cycling initiatives. Interviews with HSBC UK managers then explored the practicality of implementing the candidate intervention components in bank offices. The resultant pilot CNP intervention included 32 core components across six intervention functions (education, persuasion, incentivisation, training, environmental restructuring, enablement). Participants received a loan bike for 12-weeks (or their own bike serviced), and a 9-week cycle training course (condensed to 6 weeks for those already confident in basic cycling skills), including interactive information sharing activities, behavior change techniques (e.g., weekly goal setting), bike maintenance training, practical off-road cycling skill games and on-road group rides. Sessions were delivered by trained bank staff members who were experienced cyclists. The CNP pilot intervention was delivered across three sites with 68 participants. It was completed in two sites (the third site was stopped due to COVID-19) and was feasible and acceptable to both women and men and across different ethnicities. In addition, the CNP intervention was successful (at least in the short term) in increasing cycling by 3 rides/week on average, and improving perceptions of safety, vitality, confidence, and motivation to cycle. Following minor modifications, the long-term effectiveness and cost-effectiveness of the CNP intervention should be tested in a full-scale randomized controlled trial.

How do multiple long-term conditions impact on the cost-of-illness in early rheumatoid arthritis?

OBJECTIVE: Multiple long-term conditions (MLTCs) are prevalent in rheumatoid arthritis (RA) and associated with worse outcomes and greater economic burden. However, little is known about the impact of MLTCs on the cost-of-illness (COI) in early RA, including direct and indirect costs. The objective of this study was to quantify this impact on COI. METHODS: The Scottish Early Rheumatoid Arthritis study is a national cohort of adults with new-onset RA. Direct costs were estimated applying relevant unit costs to health resource utilisation; indirect costs were measured by productivity loss due to health conditions. Two-part models were used, adjusting for age, gender, baseline functional disability and health-related quality of life. The Charlson Comorbidity Index score was calculated using ICD-10 diagnoses. Individuals were defined as 'RA alone', 'RA plus LTC' and 'RA plus MLTCs' according to the number of coexisting LTCs. RESULTS: Data were available for 818 participants. Average annualised direct costs incurred by people with early RA plus MLTCs (£4444; 95% CI £3100 to £6371) were twice as, and almost five times higher than, those with a single LTC (£2184; 95% CI £1596 to £2997) and those without LTC (£919; 95% CI £694 to £1218), respectively. Indirect costs incurred by RA plus MLTCs (£842; 95% CI £377to £1521) were 3.1 times higher than RA alone (£530; 95% CI £273to £854). The relative proportion of direct costs increased with LTC category, ranging from 77.2% to 84.1%. In addition to increased costs with LTCs, costs also increased with age and were higher for men regardless of LTC category. CONCLUSIONS: MLTCs impact on COI early in the course of RA. The presence of LTCs is associated with significant increases in both direct and indirect costs among people with early RA.

Medium- and longer-term cardiovascular effects of e-cigarettes in adults making a stop-smoking attempt: a randomized controlled trial.

BACKGROUND: Smoking is a major risk factor for cardiovascular disease and smoking cessation reduces excess risk. E-cigarettes are popular for smoking cessation but there is little evidence on their cardiovascular health effect. Our objective was to compare the medium- and longer-term cardiovascular effects in smokers attempting to quit smoking using e-cigarettes with or without nicotine or prescription nicotine replacement therapy (NRT). METHODS: This was a single-center, pragmatic three-arm randomized (1:1:1) controlled trial, which recruited adult smokers (≥ 10 cigarettes/day), who were willing to attempt to stop smoking with support (n = 248). Participants were randomized to receive behavioral support with either (a) e-cigarettes with 18 mg/ml nicotine, (b) e-cigarettes without nicotine, and (c) NRT. Flow-mediated dilation (%FMD) and peak cutaneous vascular conductance (CVCmax) responses to acetylcholine (ACh) and sodium nitroprusside (SNP), mean arterial pressure (MAP), and other outcomes were recorded at baseline, 3, and 6 months after stopping smoking. Data were analyzed using generalized estimating equations (GEE). RESULTS: At 3- and 6-month follow-up, %FMD showed an improvement over baseline in all three groups (e.g., p < 0.0001 at 6 months). Similarly, ACh, SNP, and MAP improved significantly over baseline in all groups both at 3 and 6 months (e.g., ACh: p = 0.004, at 6 months). CONCLUSIONS: Smokers attempting to quit experienced positive cardiovascular impact after both a 3- and 6-month period. None of the groups (i.e., nicotine-containing and nicotine-free e-cigarettes or NRT) offered superior cardiovascular benefits to the others. TRIAL REGISTRATION: ClinicalTrials.gov NCT03061253 . Registered on 17 February 2017.

Cost-effectiveness of a programme to address sedentary behaviour in older adults: results from the SITLESS RCT.

BACKGROUND: This study details the within-trial economic evaluation and long-term economic model of SITLESS, a multi-country, three-armed randomized controlled trial comparing a combined intervention of exercise referral schemes (ERS) enhanced by self-management strategies (SMS) against ERS alone and usual care (UC). METHODS: A cost-utility analysis, conducted from the base-case perspective of the National Health Service and personal and social services, estimated the incremental cost per incremental quality-adjusted life year (QALY) and years in full capability (YFC). A secondary analysis combined the costs with a broad set of outcomes within a cost-consequence framework, from a societal perspective. A Markov-type decision-analytic model was developed to project short-term changes in physical activity to long-term outcomes and costs, over a 5- and 15-year time horizon. RESULTS: The results of the within-trial analysis show that SMS+ERS is highly likely to be cost-effective compared to ERS alone (ICER €4270/QALY), but not compared to UC. Participants allocated to the SMS+ERS group also showed an improvement in YFC compared to ERS alone and UC. The long-term analysis revealed that SMS+ERS is likely to be a cost-effective option compared to ERS and UC over a 5-year, but not with a 15-year horizon, being then dominated by ERS alone. CONCLUSION: This research provides new evidence that SMS is a cost-effective add-on to ERS strategies. This economic evaluation informs the case for further, cost-effective, refinement of lifestyle change programmes targeted to older adults, with the aim of ultimately reducing the impact of non-communicable diseases in this population.