Prevalence of mental health conditions and brain fog in people with long COVID: A systematic review and meta-analysis.

OBJECTIVE: Long COVID can include impaired cognition ('brain fog'; a term encompassing multiple symptoms) and mental health conditions. We performed a systematic review and meta-analysis to estimate their prevalence and to explore relevant factors associated with the incidence of impaired cognition and mental health conditions. METHODS: Searches were conducted in Medline and PsycINFO to cover the start of the pandemic until August 2023. Included studies reported prevalence of mental health conditions and brain fog in adults with long COVID after clinically-diagnosed or PCR-confirmed SARS-CoV-2 infection. FINDINGS: 17 studies were included, reporting 41,249 long COVID patients. Across all timepoints (3-24 months), the combined prevalence of mental health conditions and brain fog was 20·4% (95% CI 11·1%-34·4%), being lower among those previously hospitalised than in community-managed patients(19·5 vs 29·7% respectively; p = 0·047). The odds of mental health conditions and brain fog increased over time and when validated instruments were used. Odds of brain fog significantly decreased with increasing vaccination rates (p = ·000). CONCLUSIONS: Given the increasing prevalence of mental health conditions and brain fog over time, preventive interventions and treatments are needed. Research is needed to explore underlying mechanisms that could inform further research in development of effective treatments. The reduced risk of brain fog associated with vaccination emphasizes the need for ongoing vaccination programs.

Effectiveness and cost-effectiveness of a web-based cardiac rehabilitation programme for people with chronic stable angina: protocol for the ACTIVATE (Angina Controlled Trial Investigating the Value of the 'Activate your heart' Therapeutic E-intervention) randomised controlled trial.

INTRODUCTION: Chronic stable angina is common and disabling. Cardiac rehabilitation is routinely offered to people following myocardial infarction or revascularisation procedures and has the potential to help people with chronic stable angina. However, there is insufficient evidence of effectiveness and cost-effectiveness for its routine use in this patient group. The objectives of this study are to compare the effectiveness and cost-effectiveness of the 'Activate Your Heart' cardiac rehabilitation programme for people with chronic stable angina compared with usual care. METHODS AND ANALYSIS: ACTIVATE is a multicentre, parallel-group, two-arm, superiority, pragmatic randomised controlled trial, with recruitment from primary and secondary care centres in England and Wales and a target sample size of 518 (1:1 allocation; allocation sequence by minimisation programme with built-in random element). The study uses secure web-based allocation concealment. The two treatments will be optimal usual care (control) and optimal usual care plus the 'Activate Your Heart' web-based cardiac rehabilitation programme (intervention). Outcome assessment and statistical analysis will be performed blinded; participants will be unblinded. Outcomes will be measured at baseline and at 6 and 12 months' follow-up. Primary outcome will be the UK version of Seattle Angina Questionnaire (SAQ-UK), physical limitations domain at 12 months' follow-up. Secondary outcomes will be the remaining two domains of SAQ-UK, dyspnoea, anxiety and depression, health utility, self-efficacy, physical activity and the incremental shuttle walk test. All safety events will be recorded, and serious adverse events assessed to determine whether they are related to the intervention and expected. Concurrent economic evaluation will be cost-utility analysis from health service perspective. An embedded process evaluation will determine the mechanisms and processes that explain the implementation and impacts of the cardiac rehabilitation programme. ETHICS AND DISSEMINATION: North of Scotland National Health Service Research Ethics Committee approval, reference 21/NS/0115. Participants will provide written informed consent. Results will be disseminated by peer-reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN10054455.

Non-pharmacological interventions for the reduction and maintenance of blood pressure in people with prehypertension: a systematic review protocol.

INTRODUCTION: Prehypertension is defined as blood pressure that is above the normal range but not high enough to be classed as hypertension. Prehypertension is a warning of development of hypertension as well as a risk for cardiovascular disease, heart attack and stroke. In the UK, non-pharmacological interventions are recommended for prehypertension management but no reviews have focused on the effectiveness of these types of interventions solely in people with prehypertension. Therefore, the proposed systematic review will assess the clinical effectiveness and cost-effectiveness of non-pharmacological interventions in reducing or maintaining blood pressure in prehypertensive people. METHODS AND ANALYSIS: This systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The databases/trial registries that will be searched to identify relevant randomised controlled trials (RCTs) and economic evaluations include Medline, EMBASE, CINAHL, PsycINFO, CENTRAL, the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Cochrane Library, Scopus and the International HTA Database. Search terms have been identified by the team including an information specialist. Three reviewers will be involved in the study selection process. Risk of bias will be evaluated using the Cochrane risk-of-bias tool for RCTs and the Consensus Health Economic Criteria list for economic evaluations. Findings from the included studies will be tabulated and synthesised narratively. Heterogeneity will be assessed through visual inspection of forest plots and the calculation of the χ2 and I2 statistics and causes of heterogeneity will be assessed where sufficient data are available. If possible, we plan to investigate differential effects on specific subgroups and from different types of interventions using meta-regression. Where relevant, the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) will be used to assess the certainty of the evidence found. ETHICS AND DISSEMINATION: Ethical approval is not needed. Results will be published in a peer-reviewed journal, disseminated via the wider study website and shared with the study sites and participants. REGISTRATION DETAILS: The review is registered with PROSPERO (CRD420232433047).

Left ventricular hypertrophy and mortality in ethnic minority groups in the UK: e-ECHOES study.

OBJECTIVES: Hypertension is the key modifiable cardiovascular risk factor but is underdiagnosed, and its scale in South Asian and African-Caribbean communities is unknown. Left ventricular hypertrophy (LVH) is a measure of target organ damage in uncontrolled hypertension. The study assesses LVH prevalence in South Asian and African-Caribbean communities and its impact on mortality. METHOD: This study is based on the large prospective UK community Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES, age ≥45 years). Left ventricular mass index (LVMI) was calculated using echocardiography to establish LVH. The predictive value of LVH all-cause and cardiovascular mortality was assessed using Cox regression. RESULTS: The study included 3200 South Asians (age 59 ±â€Š10 years, 52% women, 45% had a history of hypertension, 5.8 ±â€Š1.0-year follow-up). LVH was found in 1568 (49%), of whom 45% did not have hypertension diagnosis. On Cox regression, LVH was independently associated with all-cause mortality [hazard ratio 1.38, 95% confidence interval (95% CI) 1.01-1.88], cardiovascular mortality (hazard ratio 2.64, 95% CI 1.21-3.73). The projected overall hypertension prevalence was 82%, undiagnosed hypertension prevalence 37%. The study included 1858 African-Caribbeans (age 62 ±â€Š12, 45% women, 45% had history of hypertension, 5.1 ±â€Š0.9-year follow-up). LVH was found in 1186 (64%), of whom 32% did not have hypertension diagnosis. LVH was borderline associated with all-cause mortality (hazard ratio 1.57, 95% CI 1.01-2.44), but not cardiovascular mortality (hazard ratio 1.82, 95% CI 0.80-4.16). The projected overall hypertension prevalence was 78.5%, and undiagnosed hypertension prevalence was 20.8%. CONCLUSION: UK South Asians and African-Caribbeans have a high prevalence of hypertension, which is often underdiagnosed and poorly controlled.

Exercised-based cardiac rehabilitation associates with lower all-cause mortality in patients with primary pulmonary hypertension.

Background: Despite pharmacological therapies to improve outcomes of pulmonary hypertension (PH), poor long-term survival remains. Exercised-based cardiac rehabilitation (ExCR) may be an alternative strategy to improve prognosis. Therefore, using an electronic medical record (EMR) database, the objective of this study was to compare mortality between patients with primary PH with ExCR vs. propensity-matched PH patients without ExCR. Methods: The retrospective analysis was conducted on February 15, 2023 using anonymized data within TriNetX, a global federated health research network. All patients were aged ≥18 years with primary PH recorded in EMRs with at least 1-year follow-up from ExCR. Using logistic regression models, patients with PH with an EMR of ExCR were 1:1 propensity score-matched with PH patients without ExCR for age, sex, race, and comorbidities, and cardiovascular care. Results: In total, 109,736 patients with primary PH met the inclusion criteria for the control group and 784 patients with primary PH met the inclusion criteria for the ExCR cohort. Using the propensity score-matched cohorts, 1-year mortality from ExCR was proportionally lower with 13.6% (n = 101 of 744 patients) in the ExCR cohort compared to 23.3% (n = 174 of 747 patients) in the controls (OR 0.52, 95% CI 0.40-0.68). Conclusion: The present study of 1,514 patients with primary PH suggests that ExCR is associated with 48% lower odds of 1-year mortality, when compared to propensity score-matched patients without ExCR.

Antihypertensive treatment in people of very old age with frailty: time for a paradigm shift?

The optimal management of hypertension in individuals aged 80 years or older with frailty remains uncertain due to multiple gaps in evidence. Complex health issues, polypharmacy, and limited physiological reserve make responding to antihypertensive treatments unpredictable. Patients in this age group may have limited life expectancy, so their quality of life should be prioritized when making treatment decisions. Further research is needed to identify which patients would benefit from more relaxed blood pressure targets and which antihypertensive medications are preferable or should be avoided. A paradigm shift is required in attitudes towards treatment, placing equal emphasis on deprescribing and prescribing when optimizing care. This review discusses the current evidence on managing hypertension in individuals aged 80 years or older with frailty, but further research is essential to address the gaps in knowledge and improve the care of this population.

Barriers to and facilitators of physical activity in adults living with and beyond cancer, with special emphasis on head and neck cancer: a systematic review of qualitative and mixed methods studies.

PURPOSE: Physical activity can improve health outcomes for cancer patients; however, only 30% of patients are physically active. This review explored barriers to and facilitators of physical activity promotion and participation in patients living with and beyond cancer. Secondary aims were to (1) explore similarities and differences in barriers and facilitators experienced in head and neck cancer versus other cancers, and (2) identify how many studies considered the influence of socioeconomic characteristics on physical activity behaviour. METHODS: CINAHL Plus, MEDLINE, PsycINFO, Scopus and Cochrane (CDSR) were searched for qualitative and mixed methods evidence. Quality assessment was conducted using the Mixed Methods Appraisal Tool and a Critical Appraisal Skills Programme Tool. Thematic synthesis and frequency of reporting were conducted, and results were structured using the Capability-Opportunity-Motivation-Behaviour model and Theoretical Domains Framework. RESULTS: Thirty qualitative and six mixed methods studies were included. Socioeconomic characteristics were not frequently assessed across the included studies. Barriers included side effects and comorbidities (physical capability; skills) and lack of knowledge (psychological capability; knowledge). Having a dry mouth or throat and choking concerns were reported in head and neck cancer, but not across other cancers. Facilitators included improving education (psychological capability; knowledge) on the benefits and safety of physical activity. CONCLUSION: Educating patients and healthcare professionals on the benefits and safety of physical activity may facilitate promotion, uptakeand adherence. Head and neck cancer patients experienced barriers not cited across other cancers, and research exploring physical activity promotion in this patient group is required to improve physical activity engagement.

Risk reduction intervention for raised blood pressure (REVERSE): protocol for a mixed-methods feasibility study.

INTRODUCTION: Around 40% of adults have pre-hypertension (blood pressure between 120-139/80-89), meaning they are at increased risk of developing hypertension and other cardiovascular disease-related conditions. There are limited studies on the management of pre-hypertension; however, guidance recommends that it should be focused on lifestyle modification rather than on medication. Self-monitoring of blood pressure could allow people to monitor and manage their risk status and may allow individuals to modify lifestyle factors. The purpose of this study is to determine the feasibility and acceptability, to both healthcare professionals and people with pre-hypertension, of blood pressure self-monitoring. METHODS AND ANALYSIS: A prospective, non-randomised feasibility study, with a mixed-methods approach will be employed. Eligible participants (n=114) will be recruited from general practices, pharmacies and community providers across Lancashire and South Cumbria. Participants will self-monitor their blood pressure at home for 6 months and will complete questionnaires at three timepoints (baseline, 6 and 12 months). Healthcare professionals and participants involved in the study will be invited to take part in follow-up interviews and a focus group. The primary outcomes include the willingness to engage with the concept of pre-hypertension, the acceptability of self-monitoring, and the study processes. Secondary outcomes will inform the design of a potential future trial. A cost-analysis and cost-benefit analysis will be conducted. ETHICS AND DISSEMINATION: Ethics approval has been obtained from London-Fulham NHS Research Ethics Committee, the University of Central Lancashire Health Ethics Review Panel and the HRA. The results of the study will be disseminated via peer-reviewed publications, feedback to service users and healthcare professionals, and to professional bodies in primary care and pharmacy. TRIAL REGISTRATION NUMBER: ISRCTN13649483.

Effects of different exercise types on quality of life for patients with atrial fibrillation: a systematic review and meta-analysis.

AIM: To investigate the effectiveness of exercise and the most effective types of exercise for patients with atrial fibrillation (AF) to improve health-related quality of life (HRQoL) and exercise capacity, and reduce AF burden, AF recurrence and adverse events. METHODS AND RESULTS: Systematic search in PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL Plus, and SPORTDiscus for randomized controlled trials (RCTs) and nonrandomized pre-post intervention studies investigating the effect of different types of exercise on AF patients. After exclusion, 12 studies (11 RCTs, 1 prepost) with a total of 670 participants were included. Exercise interventions consisted of aerobic exercise, aerobic interval training (AIT), Qigong, yoga, and exercise-based cardiac rehabilitation (CR). There were significant positive effects of exercise on general health {mean difference [MD] = 6.42 [95% confidence interval (CI): 2.90, 9.93]; P = 0.0003; I2 = 17%} and vitality [MD = 6.18 (95% CI: 1.94, 10.41); P = 0.004; I2 = 19%)] sub-scales of the Short Form 36-item questionnaire (SF-36). Qigong resulted in a significant improvement in the 6-min walk test [MD = 105.00m (95% CI: 19.53, 190.47)]. Exercise-based CR and AIT were associated with a significant increment in V̇O2peak, and AIT significantly reduced AF burden. Adverse events were few and one intervention-related serious adverse event was reported for exercise-based CR. CONCLUSION: Exercise led to improvements in HRQoL, exercise capacity, and reduced AF burden. The available exercise interventions for AF patients are few and heterogeneous. Future studies are needed for all types of exercise intervention in this patient group to (co-)develop an optimized exercise training intervention for AF patients.

Earlier cancer diagnosis in primary care: a feasibility economic analysis of ThinkCancer!

BACKGROUND: UK cancer survival rates are much lower compared with other high-income countries. In primary care, there are opportunities for GPs and other healthcare professionals to act more quickly in response to presented symptoms that might represent cancer. ThinkCancer! is a complex behaviour change intervention aimed at primary care practice teams to improve the timely diagnosis of cancer. AIM: To explore the costs of delivering the ThinkCancer! intervention to expedite cancer diagnosis in primary care. DESIGN & SETTING: Feasibility economic analysis using a micro-costing approach, which was undertaken in 19 general practices in Wales, UK. METHOD: From an NHS perspective, micro-costing methodology was used to determine whether it was feasible to gather sufficient economic data to cost the ThinkCancer! INTERVENTION: Owing to the COVID-19 pandemic, ThinkCancer! was mainly delivered remotely online in a digital format. Budget impact analysis (BIA) and sensitivity analysis were conducted to explore the costs of face-to-face delivery of the ThinkCancer! intervention as intended pre-COVID-19. RESULTS: The total costs of delivering the ThinkCancer! intervention across 19 general practices in Wales was £25 030, with an average cost per practice of £1317 (standard deviation [SD]: 578.2). Findings from the BIA indicated a total cost of £34 630 for face-to-face delivery. CONCLUSION: Data collection methods were successful in gathering sufficient health economics data to cost the ThinkCancer! INTERVENTION: Results of this feasibility study will be used to inform a future definitive economic evaluation alongside a pragmatic randomised controlled trial (RCT).

STIMULATE-ICP-Delphi (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways Delphi): Study protocol.

INTRODUCTION: As mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in delivering care for patients with multi-morbidity. The multi-system nature of Long COVID and its impact on physical and psychological health demands a more effective model of holistic, integrated care. The evolution of integrated care systems (ICSs) in the UK presents an important opportunity to explore areas of mutual benefit to LTC, multi-morbidity and Long COVID care. There may be benefits in comparing and contrasting ICPs for Long COVID with ICPs for other LTCs. METHODS AND ANALYSIS: This study aims to evaluate health services requirements for ICPs for Long COVID and their applicability to other LTCs including multi-morbidity and the overlap with medically not yet explained symptoms (MNYES). The study will follow a Delphi design and involve an expert panel of stakeholders including people with lived experience, as well as clinicians with expertise in Long COVID and other LTCs. Study processes will include expert panel and moderator panel meetings, surveys, and interviews. The Delphi process is part of the overall STIMULATE-ICP programme, aimed at improving integrated care for people with Long COVID. ETHICS AND DISSEMINATION: Ethical approval for this Delphi study has been obtained (Research Governance Board of the University of York) as have approvals for the other STIMULATE-ICP studies. Study outcomes are likely to inform policy for ICPs across LTCs. Results will be disseminated through scientific publication, conference presentation and communications with patients and stakeholders involved in care of other LTCs and Long COVID. REGISTRATION: Researchregistry: https://www.researchregistry.com/browse-the-registry#home/registrationdetails/6246bfeeeaaed6001f08dadc/.

STIMULATE-ICP-CAREINEQUAL (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways) study protocol: Defining usual care and examining inequalities in Long Covid support.

INTRODUCTION: Individuals with Long Covid represent a new and growing patient population. In England, fewer than 90 Long Covid clinics deliver assessment and treatment informed by NICE guidelines. However, a paucity of clinical trials or longitudinal cohort studies means that the epidemiology, clinical trajectory, healthcare utilisation and effectiveness of current Long Covid care are poorly documented, and that neither evidence-based treatments nor rehabilitation strategies exist. In addition, and in part due to pre-pandemic health inequalities, access to referral and care varies, and patient experience of the Long Covid care pathways can be poor. In a mixed methods study, we therefore aim to: (1) describe the usual healthcare, outcomes and resource utilisation of individuals with Long Covid; (2) assess the extent of inequalities in access to Long Covid care, and specifically to understand Long Covid patients' experiences of stigma and discrimination. METHODS AND ANALYSIS: A mixed methods study will address our aims. Qualitative data collection from patients and health professionals will be achieved through surveys, interviews and focus group discussions, to understand their experience and document the function of clinics. A patient cohort study will provide an understanding of outcomes and costs of care. Accessible data will be further analysed to understand the nature of Long Covid, and the care received. ETHICS AND DISSEMINATION: Ethical approval was obtained from South Central-Berkshire Research Ethics Committee (reference 303958). The dissemination plan will be decided by the patient and public involvement and engagement (PPIE) group members and study Co-Is, but will target 1) policy makers, and those responsible for commissioning and delivering Long Covid services, 2) patients and the public, and 3) academics.

'Function First': how to promote physical activity and physical function in people with long-term conditions managed in primary care? A study combining realist and co-design methods.

OBJECTIVES: To develop a taxonomy of interventions and a programme theory explaining how interventions improve physical activity and function in people with long-term conditions managed in primary care. To co-design a prototype intervention informed by the programme theory. DESIGN: Realist synthesis combining evidence from a wide range of rich and relevant literature with stakeholder views. Resulting context, mechanism and outcome statements informed co-design and knowledge mobilisation workshops with stakeholders to develop a primary care service innovation. RESULTS: A taxonomy was produced, including 13 categories of physical activity interventions for people with long-term conditions. ABRIDGED REALIST PROGRAMME THEORY: Routinely addressing physical activity within consultations is dependent on a reinforcing practice culture, and targeted resources, with better coordination, will generate more opportunities to address low physical activity. The adaptation of physical activity promotion to individual needs and preferences of people with long-term conditions helps affect positive patient behaviour change. Training can improve knowledge, confidence and capability of practice staff to better promote physical activity. Engagement in any physical activity promotion programme will depend on the degree to which it makes sense to patients and professions, and is seen as trustworthy. CO-DESIGN: The programme theory informed the co-design of a prototype intervention to: improve physical literacy among practice staff; describe/develop the role of a physical activity advisor who can encourage the use of local opportunities to be more active; and provide materials to support behaviour change. CONCLUSIONS: Previous physical activity interventions in primary care have had limited effect. This may be because they have only partially addressed factors emerging in our programme theory. The co-designed prototype intervention aims to address all elements of this emergent theory, but needs further development and consideration alongside current schemes and contexts (including implications relevant to COVID-19), and testing in a future study. The integration of realist and co-design methods strengthened this study.

Healthy eating and lifestyle in pregnancy (HELP): a cluster randomised trial to evaluate the effectiveness of a weight management intervention for pregnant women with obesity on weight at 12 months postpartum.

OBJECTIVE: To assess whether a weight management intervention for pregnant women with obesity was effective in reducing body mass index (BMI) 12 months after giving birth. METHODS: Pragmatic, cluster randomised controlled trial (RCT) with embedded cost-effectiveness analysis. 598 women with a BMI of ≥30 kg/m2 (between 12 and 20 weeks gestation) were recruited from 20 secondary care maternity units in England and Wales. BMI at 12 months postpartum was the primary outcome. A range of clinical and behavioural secondary outcomes were examined. INTERVENTIONS: Women attending maternity units randomised to intervention were invited to a weekly weight management group, which combined expertise from a commercial weight loss programme with clinical advice from midwives. Both intervention and control participants received usual care and leaflets on diet and physical activity in pregnancy. RESULTS: Mean (SD) BMI at 12 months postpartum was 36.0 kg/m2 (5.2) in the control group, and 37.5 kg/m2 (6.7) in the intervention group. After adjustment for baseline BMI, the intervention effect was -0.02 (95% CI -0.04 to 0.01). The intervention group had an improved healthy eating score (3.08, 95% CI 0.16 to 6.00, p < 0.04), improved fibre score (3.22, 1.07 to 5.37, p < 0.01) and lower levels of risky drinking at 12 months postpartum compared to the control group (OR 0.45, 0.27 to 0.74, p < 0.002). The net incremental monetary benefit was not statistically significantly different between arms, although the probability of the intervention being cost-effective was above 60%, at policy-relevant thresholds. CONCLUSIONS: There was no significant difference between groups on the primary outcome of BMI at 12 months. Analyses of secondary outcomes indicated improved healthy eating and lower levels of risky drinking. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25260464.

Protocol for a feasibility study incorporating a randomised pilot trial with an embedded process evaluation and feasibility economic analysis of ThinkCancer!: a primary care intervention to expedite cancer diagnosis in Wales.

BACKGROUND: Compared to the rest of Europe, the UK has relatively poor cancer outcomes, with late diagnosis and a slow referral process being major contributors. General practitioners (GPs) are often faced with patients presenting with a multitude of non-specific symptoms that could be cancer. Safety netting can be used to manage diagnostic uncertainty by ensuring patients with vague symptoms are appropriately monitored, which is now even more crucial due to the ongoing COVID-19 pandemic and its major impact on cancer referrals. The ThinkCancer! workshop is an educational behaviour change intervention aimed at the whole general practice team, designed to improve primary care approaches to ensure timely diagnosis of cancer. The workshop will consist of teaching and awareness sessions, the appointment of a Safety Netting Champion and the development of a bespoke Safety Netting Plan and has been adapted so it can be delivered remotely. This study aims to assess the feasibility of the ThinkCancer! intervention for a future definitive randomised controlled trial. METHODS: The ThinkCancer! study is a randomised, multisite feasibility trial, with an embedded process evaluation and feasibility economic analysis. Twenty-three to 30 general practices will be recruited across Wales, randomised in a ratio of 2:1 of intervention versus control who will follow usual care. The workshop will be delivered by a GP educator and will be adapted iteratively throughout the trial period. Baseline practice characteristics will be collected via questionnaire. We will also collect primary care intervals (PCI), 2-week wait (2WW) referral rates, conversion rates and detection rates at baseline and 6 months post-randomisation. Participant feedback, researcher reflections and economic costings will be collected following each workshop. A process evaluation will assess implementation using an adapted Normalisation Measure Development (NoMAD) questionnaire and qualitative interviews. An economic feasibility analysis will inform a future economic evaluation. DISCUSSION: This study will allow us to test and further develop a novel evidenced-based complex intervention aimed at general practice teams to expedite the diagnosis of cancer in primary care. The results from this study will inform the future design of a full-scale definitive phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04823559 .

Protocol for a definitive randomised controlled trial and economic evaluation of a community-based rehabilitation programme following hip fracture: fracture in the elderly multidisciplinary rehabilitation-phase III (FEMuR III).

INTRODUCTION: Proximal femoral (hip) fracture is common, serious and costly. Rehabilitation may improve functional recovery but evidence of effectiveness and cost-effectiveness are lacking. An enhanced rehabilitation intervention was previously developed and a feasibility study tested the methods used for this randomised controlled trial (RCT). The objectives are to compare the effectiveness and cost-effectiveness of the enhanced rehabilitation programme following surgical repair of proximal femoral fracture in older people compared with usual care. METHODS AND ANALYSIS: Protocol for phase III, parallel-group, two-armed, superiority, pragmatic RCT with 1:1 allocation ratio; allocation sequence by minimisation programme with a built-in random element; secure web-based allocation concealment. The two treatments will be usual care (control) and usual care plus an enhanced rehabilitation programme (intervention). The enhanced rehabilitation will consist of a patient-held information workbook, goal setting diary and up to six additional therapy sessions. Outcome assessment and statistical analysis will be performed blind; patient and carer participants will be unblinded. Outcomes will be measured at baseline, 17 and 52 weeks' follow-up. Primary outcome at 52 weeks will be the Nottingham Extended Activities of Daily Living scale. Secondary outcomes will measure anxiety and depression, health utility, cognitive status, hip pain intensity, falls self-efficacy, fear of falling, grip strength and physical function. Carer strain, anxiety and depression will be measured in carers. All safety events will be recorded, and serious adverse events will be assessed to determine whether they are related to the intervention and expected. Concurrent economic evaluation will be a cost-utility analysis from a health service and personal social care perspective. An embedded process evaluation will determine the mechanisms and processes that explain the implementation and impacts of the enhanced rehabilitation programme. ETHICS AND DISSEMINATION: National Health Service research ethics approval reference 18/NE/0300. Results will be disseminated by peer-reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN28376407; Pre-results registered on 23 November 2018.

Barriers and facilitators to deprescribing in primary care: a systematic review.

BACKGROUND: Managing polypharmacy is a challenge for healthcare systems globally. It is also a health inequality concern as it can expose some of the most vulnerable in society to unnecessary medications and adverse drug-related events. Care for most patients with multimorbidity and polypharmacy occurs in primary care. Safe deprescribing interventions can reduce exposure to inappropriate polypharmacy. However, these are not fully accepted or routinely implemented. AIM: To identify barriers and facilitators to safe deprescribing interventions for adults with multimorbidity and polypharmacy in primary care. DESIGN & SETTING: A systematic review of studies published from 2000, examining safe deprescribing interventions for adults with multimorbidity and polypharmacy. METHOD: A search of electronic databases: MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature (CINHAL), Cochrane, and Health Management Information Consortium (HMIC) from inception to 26 Feb 2019, using an agreed search strategy. This was supplemented by handsearching of relevant journals, and screening of reference lists and citations of included studies. RESULTS: In total, 40 studies from 14 countries were identified. Cultural and organisational barriers included: a culture of diagnosing and prescribing; evidence-based guidance focused on single diseases; a lack of evidence-based guidance for the care of older people with multimorbidities; and a lack of shared communication, decision-making systems, tools, and resources. Interpersonal and individual-level barriers included: professional etiquette; fragmented care; prescribers' and patients' uncertainties; and gaps in tailored support. Facilitators included: prudent prescribing; greater availability and acceptability of non-pharmacological alternatives; resources; improved communication, collaboration, knowledge, and understanding; patient-centred care; and shared decision-making. CONCLUSION: A whole systems, patient-centred approach to safe deprescribing interventions is required, involving key decision-makers, healthcare professionals, patients, and carers.