Evidence for exercise-based interventions across 45 different long-term conditions: an overview of systematic reviews.

Background: Almost half of the global population face significant challenges from long-term conditions (LTCs) resulting in substantive health and socioeconomic burden. Exercise is a potentially key intervention in effective LTC management. Methods: In this overview of systematic reviews (SRs), we searched six electronic databases from January 2000 to October 2023 for SRs assessing health outcomes (mortality, hospitalisation, exercise capacity, disability, frailty, health-related quality of life (HRQoL), and physical activity) related to exercise-based interventions in adults (aged >18 years) diagnosed with one of 45 LTCs. Methodological quality was assessed using AMSTAR-2. International Prospective Resister of Systematic Reviews (PROSPERO) ID: CRD42022319214. Findings: Forty-two SRs plus three supplementary RCTs were included, providing 990 RCTs in 936,825 people across 39 LTCs. No evidence was identified for six LTCs. Predominant outcome domains were HRQoL (82% of SRs/RCTs) and exercise capacity (66%); whereas disability, mortality, physical activity, and hospitalisation were less frequently reported (≤25%). Evidence supporting exercise-based interventions was identified in 25 LTCs, was unclear for 13 LTCs, and for one LTC suggested no effect. No SRs considered multimorbidity in the delivery of exercise. Methodological quality varied: critically-low (33%), low (26%), moderate (26%), and high (12%). Interpretation: Exercise-based interventions improve HRQoL and exercise capacity across numerous LTCs. Key evidence gaps included limited mortality and hospitalisation data and consideration of multimorbidity impact on exercise-based interventions. Funding: This study was funded by the National Institute for Health and Care Research (NIHR; Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)-NIHR202020).

Association of latent class analysis-derived multimorbidity clusters with adverse health outcomes in patients with multiple long-term conditions: comparative results across three UK cohorts.

Background: It remains unclear how to meaningfully classify people living with multimorbidity (multiple long-term conditions (MLTCs)), beyond counting the number of conditions. This paper aims to identify clusters of MLTCs in different age groups and associated risks of adverse health outcomes and service use. Methods: Latent class analysis was used to identify MLTCs clusters in different age groups in three cohorts: Secure Anonymised Information Linkage Databank (SAIL) (n = 1,825,289), UK Biobank (n = 502,363), and the UK Household Longitudinal Study (UKHLS) (n = 49,186). Incidence rate ratios (IRR) for MLTC clusters were computed for: all-cause mortality, hospitalisations, and general practice (GP) use over 10 years, using <2 MLTCs as reference. Information on health outcomes and service use were extracted for a ten year follow up period (between 01st Jan 2010 and 31st Dec 2019 for UK Biobank and UKHLS, and between 01st Jan 2011 and 31st Dec 2020 for SAIL). Findings: Clustering MLTCs produced largely similar results across different age groups and cohorts. MLTC clusters had distinct associations with health outcomes and service use after accounting for LTC counts, in fully adjusted models. The largest associations with mortality, hospitalisations and GP use in SAIL were observed for the "Pain+" cluster in the age-group 18-36 years (mortality IRR = 4.47, hospitalisation IRR = 1.84; GP use IRR = 2.87) and the "Hypertension, Diabetes & Heart disease" cluster in the age-group 37-54 years (mortality IRR = 4.52, hospitalisation IRR = 1.53, GP use IRR = 2.36). In UK Biobank, the "Cancer, Thyroid disease & Rheumatoid arthritis" cluster in the age group 37-54 years had the largest association with mortality (IRR = 2.47). Cardiometabolic clusters across all age groups, pain/mental health clusters in younger groups, and cancer and pulmonary related clusters in older age groups had higher risk for all outcomes. In UKHLS, MLTC clusters were not significantly associated with higher risk of adverse outcomes, except for the hospitalisation in the age-group 18-36 years. Interpretation: Personalising care around MLTC clusters that have higher risk of adverse outcomes may have important implications for practice (in relation to secondary prevention), policy (with allocation of health care resources), and research (intervention development and targeting), for people living with MLTCs. Funding: This study was funded by the National Institute for Health and Care Research (NIHR; Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)-NIHR202020).

Are cardiac rehabilitation pathways influenced by diabetes: A cohort study.

BACKGROUND: Cardiac rehabilitation (CR) is recommended following acute coronary syndrome (ACS). Diabetes is a common long-term condition associated with ACS, and the inclusion of these patients in CR has been less studied. This study examines the referral, uptake, and completion rates in the CR pathway for ACS patients with and without diabetes to identify potential barriers in the CR pathway. METHODS: The study included patients aged 18 or above who were discharged after a diagnosis of ACS in the Central Denmark Region between 1 September 2017 and 31 August 2018. Diabetes information was obtained from three sources. Logistic regression models were used to examine the associations between having diabetes and the three outcomes: non-referral, non-uptake and non-completion. Results were reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: A total of 2447 patients were eligible for the study, of which 457 (18.7%) had diabetes. Only non-uptake was found to be significantly associated with diabetes after adjustment for prespecified variables (OR = 1.38, 95% CI 1.01-1.90). Associations for non-referral (OR = 1.11, 95% CI 0.87-1.41) and non-completion (OR = 1.06, 95 %CI 0.73-1.53) were not found to be statistically significant between ACS patients with diabetes and those without diabetes. CONCLUSION: This study highlights a significant disparity in the uptake of CR between patients with and without diabetes following ACS, demonstrating that patients with diabetes require early promotion and increased assistance to enrol in CR.

What are the determinants of change in walking fitness in patients with a history of depression following cardiac rehabilitation?

AIMS: This study aims to investigate the demographic, clinical and service level factors determining change in walking fitness in cardiac rehabilitation (CR) patients with a history of depression following the CR programme. METHODS AND RESULTS: National Audit of Cardiac Rehabilitation (NACR) clinical data were used to identify 1476 patients with a history of depression who had their pre and post incremental shuttle walk test (ISWT) recorded between 1st Jan 2016 and 31st Jan 2020. A multiple linear regression was conducted to examine the determinants of change in walking fitness (m) following CR. Mean age was 61 (SD 10.45) and mean ISWT distance at baseline and outcome were 352.06m (SD 169.48) and 463.43m (SD 197.65), respectively. Multivariate analysis revealed that change in walking distance reduced by 1.6m for each year increase in age at baseline (P < 0.001). Females and unemployed patients had less improvement in walking fitness (23.1m and 21.5m, respectively). Having a body mass index >30 was associated with lower improvement (24.2m, p < 0.001), while physically active patients had 14.6m higher change. Higher baseline ISWT quintiles were associated with less improvement, and increased waiting time to start CR was associated with reduced change in walking fitness following CR. CONCLUSION: Older age, female gender, unemployment, higher baseline BMI, longer waiting time, and lower physical activity were associated with reduced walking fitness improvement in patients with a history of depression. Targeted intervention and prompt access to CR can optimize outcomes.

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).

Cardiac rehabilitation for children and young people (CardioActive): protocol for a single-blind randomised feasibility and acceptability study of a centre-based cardiac rehabilitation programme versus usual care in 11-16 years with heart conditions.

BACKGROUND: Congenital heart conditions are among the most common non-communicable diseases in children and young people (CYP), affecting 13.9 million CYP globally. While survival rates are increasing, support for young people adjusting to life with a heart condition is lacking. Furthermore, one in three CYP with heart conditions also experiences anxiety, depression or adjustment disorder, for which little support is offered. While adults are offered cardiac rehabilitation (CR) to support their mental and physical health, this is not offered for CYP.One way to overcome this is to evaluate a CR programme comprising exercise with mental health support (CardioActive; CA) for CYP with heart conditions. The exercise and mental health components are informed by the metacognitive model, which has been shown to be effective in treating anxiety and depression in CYP and associated with improving psychological outcomes in adult CR. METHOD AND ANALYSIS: The study is a single-blind parallel randomised feasibility trial comparing a CR programme (CA) plus usual care against usual care alone with 100 CYP (50 per arm) aged 11-16 diagnosed with a heart condition. CA will include six group exercise, lifestyle and mental health modules. Usual care consists of routine outpatient management. Participants will be assessed at three time points: baseline, 3-month (post-treatment) and 6-month follow-up. Primary outcomes are feasibility and acceptability (ie, referral rates, recruitment and retention rates, attendance at the intervention, rate of return and level of completion of follow-up data). Coprimary symptom outcomes (Strength and Difficulties Questionnaire and Paediatric Quality of Life) and a range of secondary outcomes will be administered at each time point. A nested qualitative study will investigate CYP, parents and healthcare staff views of CR and its components, and staff's experience of delivering CA. Preliminary health economic data will be collected to inform future cost-effectiveness analyses. Descriptive data on study processes and clinical outcomes will be reported. Data analysis will follow intention to treat. Qualitative data will be analysed using thematic analysis and the theoretical framework of acceptability. ETHICS AND DISSEMINATION: Ethical approval was granted on 14 February 2023 by the Greater Manchester East Research Ethics Committee (22/NW/0367). The results will be disseminated through peer-reviewed journals, conference presentations and local dissemination. TRIAL REGISTRATION NUMBER: ISRCTN50031147; NCT05968521.

Screening for - and prevalence of - anxiety and depression in cardiac rehabilitation in the post-COVID era. An observational study.

BACKGROUND: Approximately 20-30% of patients with a cardiac disease suffer from anxiety and/or depression, leading to poor health outcomes. To identify this subgroup, clinical guidelines recommend screening for anxiety and depression in cardiac rehabilitation (CR). It is unknown how screening practice is delivered post-COVID. METHODS: This observational study used data from the National Audit of Cardiac Rehabilitation from April 2018-March 2022. Descriptive statistics were used to assess screening rates and prevalence, while a multivariate logistic regression model was performed to analyse determinants for screening for anxiety and depression among patients participating in cardiac rehabilitation. RESULTS: The population consisted of 245,705 patients, where 128,643 (52.4%) were screened and 117,062 (47.6%) were not. Patients attending CR during first year of COVID-19 were less likely to be screened. Patients with female gender, living alone, non-white ethnicity, living in the most deprived areas, current smoking, and physical inactivity were less likely to be screened, while patients who were revascularized, having an objective physical fitness test, and attending a certified CR center were more likely to be screened. For patients attending CR during COVID-19, the prevalence of anxiety and depression decreased significantly. For anxiety the prevalence dropped from 34.4% to 15.8%, for depression the prevalence dropped from 33.5% to 16.5%. CONCLUSION: CR service provision was negatively impacted during COVID-19, leading to much lower screening for anxiety and depression in the CR setting. Prevalence of anxiety and depression decreased during COVID-19 for this population, possibly because psychologically affected patients refrained from attending CR.

Standardised Exercise Prescription for Patients with Chronic Coronary Syndrome and/or Heart Failure: A Consensus Statement from the EXPERT Working Group.

Whereas exercise training, as part of multidisciplinary rehabilitation, is a key component in the management of patients with chronic coronary syndrome (CCS) and/or congestive heart failure (CHF), physicians and exercise professionals disagree among themselves on the type and characteristics of the exercise to be prescribed to these patients, and the exercise prescriptions are not consistent with the international guidelines. This impacts the efficacy and quality of the intervention of rehabilitation. To overcome these barriers, a digital training and decision support system [i.e. EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool], i.e. a stepwise aid to exercise prescription in patients with CCS and/or CHF, affected by concomitant risk factors and comorbidities, in the setting of multidisciplinary rehabilitation, was developed. The EXPERT working group members reviewed the literature and formulated exercise recommendations (exercise training intensity, frequency, volume, type, session and programme duration) and safety precautions for CCS and/or CHF (including heart transplantation). Also, highly prevalent comorbidities (e.g. peripheral arterial disease) or cardiac devices (e.g. pacemaker, implanted cardioverter defibrillator, left-ventricular assist device) were considered, as well as indications for the in-hospital phase (e.g. after coronary revascularisation or hospitalisation for CHF). The contributions of physical fitness, medications and adverse events during exercise testing were also considered. The EXPERT tool was developed on the basis of this evidence. In this paper, the exercise prescriptions for patients with CCS and/or CHF formulated for the EXPERT tool are presented. Finally, to demonstrate how the EXPERT tool proposes exercise prescriptions in patients with CCS and/or CHF with different combinations of CVD risk factors, three patient cases with solutions are presented.

Improved clinical outcomes in response to a 12-week blended digital and community-based long-COVID-19 rehabilitation programme.

Introduction: Two million people in the UK are experiencing long COVID (LC), which necessitates effective and scalable interventions to manage this condition. This study provides the first results from a scalable rehabilitation programme for participants presenting with LC. Methods: 601 adult participants with symptoms of LC completed the Nuffield Health COVID-19 Rehabilitation Programme between February 2021 and March 2022 and provided written informed consent for the inclusion of outcomes data in external publications. The 12-week programme included three exercise sessions per week consisting of aerobic and strength-based exercises, and stability and mobility activities. The first 6 weeks of the programme were conducted remotely, whereas the second 6 weeks incorporated face-to-face rehabilitation sessions in a community setting. A weekly telephone call with a rehabilitation specialist was also provided to support queries and advise on exercise selection, symptom management and emotional wellbeing. Results: The 12-week rehabilitation programme significantly improved Dyspnea-12 (D-12), Duke Activity Status Index (DASI), World Health Orginaisation-5 (WHO-5) and EQ-5D-5L utility scores (all p < 0.001), with the 95% confidence intervals (CI) for the improvement in each of these outcomes exceeding the minimum clinically important difference (MCID) for each measure (mean change [CI]: D-12: -3.4 [-3.9, -2.9]; DASI: 9.2 [8.2, 10.1]; WHO-5: 20.3 [18.6, 22.0]; EQ-5D-5L utility: 0.11 [0.10, 0.13]). Significant improvements exceeding the MCID were also observed for sit-to-stand test results (4.1 [3.5, 4.6]). On completion of the rehabilitation programme, participants also reported significantly fewer GP consultations (p < 0.001), sick days (p = 0.003) and outpatient visits (p = 0.007) during the previous 3 months compared with baseline. Discussion: The blended and community design of this rehabilitation model makes it scalable and meets the urgent need for an effective intervention to support patients experiencing LC. This rehabilitation model is well placed to support the NHS (and other healthcare systems worldwide) in its aim of controlling the impacts of COVID-19 and delivering on its long-term plan. Clinical trial registration: https://www.isrctn.com/ISRCTN14707226, identifier 14707226.

Optimal outcomes from cardiac rehabilitation are associated with longer-term follow-up and risk factor status at 12 months: An observational registry-based study.

AIM: The purpose of Cardiac Rehabilitation (CR) is to promote and reduce risk factors in the short and long term, however, the latter has, to date, been poorly evaluated. We explored characteristics associated with provision and outcomes of a long-term assessment in CR. METHOD: Data from the UK National Audit of CR between April 2015 and March 2020 was used. Programmes were selected if they had an established mechanism and routine methodology to collect the 12-month assessments. Risk factors pre and post phase II CR and at the 12-month assessment were explored; BMI ≤30, ≥150 min of physical activity per week, hospital anxiety and depression scale (HADS) scores <8. The data came from 32 programmes, 24,644 patients with coronary heart disease. Patients being in at least one optimal risk factor stage throughout phase II CR (OR = 1.43 95% CI 1.28 to 1.59) or successfully reaching an optimal stage during phase II CR (OR = 1.61 95% CI 1.44 to 1.80) had an increased likelihood of being assessed at 12 months compared to those who did not. Patients being in the optimal stage upon completion of phase II CR had an increased likelihood of still being in the optimal stage at 12 months. Most prominent was BMI; (OR = 14.6 (95% CI 11.1 to 19.2) for patients reaching an optimal stage throughout phase II CR. CONCLUSION: Being in an optimal stage upon routine CR completion could be an overlooked predictor in the provision of a long-term CR service and prediction of longer-term risk factor status.

A randomised controlled, feasibility study to establish the acceptability of early outpatient review and early cardiac rehabilitation compared to standard practice after cardiac surgery and viability of a future large-scale trial (FARSTER).

OBJECTIVE: To determine the acceptability and feasibility of delivering early outpatient review following cardiac surgery and early cardiac rehabilitation (CR), compared to standard practice to establish if a future large-scale trial is achievable. METHODS: A randomised controlled, feasibility trial with embedded health economic evaluation and qualitative interviews, recruited patients aged 18-80 years from two UK cardiac centres who had undergone elective or urgent cardiac surgery via a median sternotomy. Eligible, consenting participants were randomised 1:1 by a remote, centralised randomisation service to postoperative outpatient review 6 weeks after hospital discharge, followed by CR commencement from 8 weeks (control), or postoperative outpatient review 3 weeks after hospital discharge, followed by commencement of CR from 4 weeks (intervention). The primary outcome measures related to trial feasibility including recruitment, retention, CR adherence, and acceptability to participants/staff. Secondary outcome measures included health-rated quality of life using EQ-5D-5L, NHS resource-use, Incremental Shuttle Walk Test (ISWT) distance, 30- and 90-day mortality, surgical site complications and hospital readmission rates. RESULTS: Fifty participants were randomised (25 per group) and 92% declared fit for CR. Participant retention at final follow-up was 74%; completion rates for outcome data time points ranged from 28 to 92% for ISWT and 68 to 94% for follow-up questionnaires. At each time point, the mean ISWT distance walked was greater in the intervention group compared to the control. Mean utility scores increased from baseline to final follow-up by 0.202 for the intervention (0.188 control). Total costs were £1519 for the intervention (£2043 control). Fifteen participants and a research nurse were interviewed. Many control participants felt their outpatient review and CR could have happened sooner; intervention participants felt the timing was right. The research nurse found obtaining consent for willing patients challenging due to discharge timings. CONCLUSION: Recruitment and retention rates showed that it would be feasible to undertake a full-scale trial subject to some modifications to maximise recruitment. Lower than expected recruitment and issues with one of the clinical tests were limitations of the study. Most study procedures proved feasible and acceptable to participants, and professionals delivering early CR. TRIAL REGISTRATION: ISRCTN80441309 (prospectively registered on 24/01/2019).

Factors associated with new-onset depressive symptoms in patients starting cardiac rehabilitation: Pre-COVID-19 and COVID-19 period comparison.

OBJECTIVE: We aim to: 1) investigate whether starting cardiac rehabilitation (CR) during the COVID-19 period was influential on new-onset depressive symptoms, 2) examine the relationship between sociodemographic and medical factors with the new-onset of depressive symptoms before and during the COVID-19 period in UK patients commencing CR. METHODS: The national audit of cardiac rehabilitation (NACR) data were used and the two years of data before COVID-19 and during COVID-19 were analysed (Feb,2018 - Nov,2021). Hospital Anxiety and Depression Scale measurement was used to assess depressive symptoms. Bivariate analysis and logistic regression were conducted to examine the influence of the COVID-19 period on new-onset depressive symptoms and the patient characteristics associated with it. RESULTS: 71055 patients screened for new-onset depressive symptoms were included in the analysis. Based on multivariate analysis, patients commencing CR during COVID-19 were 8% more likely to have new onset depressive symptoms compared to patients commencing before COVID-19. Smoking (OR: 1.26, 95%CI: 1.11, 1.43), physical inactivity (OR: 1.86, 95%CI: 1.74, 1.98), high anxiety (OR: 1.45, 95%CI: 1.44, 1.46), being male (OR: 1.21, 95%CI: 1.12, 1.30), single (OR: 1.25, 95%CI: 1.16, 1.35), having comorbidities of arthritis, diabetes, chronic bronchitis, emphysema, claudication (OR range: 1.19 to 1.60), receiving CABG treatment (OR: 1.47, 95%CI: 1.25, 1.73), and having heart failure (OR: 1.33, 95%CI: 1.19, 1.48) were the factors associated with having new-onset depressive symptoms at the start of CR. CONCLUSION: Our findings have shown that starting CR during the COVID-19 period was associated with increased odds of having new-onset depressive symptoms.

Research priorities relating to the delivery of cardiovascular prevention and rehabilitation programmes: results of a modified Delphi process.

OBJECTIVE: The purpose of this British Association for Cardiovascular Prevention and Rehabilitation (BACPR) research priority setting project (PSP) was to identify a top 10 list of priority research questions for cardiovascular prevention and rehabilitation (CVPR). METHODS: The PSP was facilitated by the BACPR clinical study group (CSG), which integrates as part of the British Heart Foundation Clinical Research Collaborative. Following a literature review to identify unanswered research questions, modified Delphi methods were used to engage CVPR-informed expert stakeholders, patients, partners and conference delegates in ranking the relevance of research questions during three rounds of an anonymous e-survey. In the first survey, unanswered questions from the literature review were ranked and respondents proposed additional questions. In the second survey, these new questions were ranked. Prioritised questions from surveys 1 and 2 were incorporated in a third/final e-survey used to identify the top 10 list. RESULTS: From 459 responses across the global CVPR community, a final top 10 list of questions were distilled from an overall bank of 76 (61 from the current evidence base and a further 15 from respondents). These were grouped across five broad categories: access and remote delivery, exercise and physical activity, optimising programme outcomes, psychosocial health and impact of the pandemic. CONCLUSIONS: This PSP used a modified Delphi methodology to engage the international CVPR community to generate a top 10 list of research priorities within the field. These prioritised questions will directly inform future national and international CVPR research supported by the BACPR CSG.

Home-based cardiac rehabilitation and physical activity in people with heart failure: a secondary analysis of the REACH-HF randomised controlled trials.

OBJECTIVES: To quantify the impact of a home-based cardiac rehabilitation intervention (Rehabilitation Enablement in Chronic Heart Failure (REACH-HF)) on objectively assessed physical activity (PA) of patients with heart failure (HF) and explore the extent by which patient characteristics are associated with a change in PA. DESIGN: Secondary analysis of randomised controlled trial data. SETTING: Five centres in the UK. PARTICIPANTS: 247 patients with HF (mean age 70.9±10.3 years; 28% women). INTERVENTIONS: REACH-HF versus usual care (control). PRIMARY AND SECONDARY OUTCOME MEASURES: PA was assessed over 7 days via GENEActiv triaxial accelerometer at baseline (pre-randomisation), post-intervention (4 months) and final follow-up (6-12 months). Using HF-specific intensity thresholds, intervention effects (REACH-HF vs control) on average min/day PA (inactivity, light PA and moderate-to-vigorous PA (MVPA)) over all days, week days and weekend days were examined using linear regression analysis. Multivariable regression was used to explore associations between baseline patient characteristics and change in PA. RESULTS: Although there was no difference between REACH-HF and control groups in 7-day PA levels post-intervention or at final follow-up, there was evidence of an increase in weekday MVPA (10.9 min/day, 95% CI: -2.94 to 24.69), light PA (26.9 min/day, 95% CI: -0.05 to 53.8) and decreased inactivity (-38.31 min/day, 95% CI: -72.1 to -4.5) in favour of REACH-HF. Baseline factors associated with an increase in PA from baseline to final follow-up were reduced MVPA, increased incremental shuttle walk test distance, increased Hospital Anxiety and Depression Scale anxiety score and living with a child >18 years (p<0.05). CONCLUSIONS: While participation in the REACH-HF home-based cardiac rehabilitation intervention did not increase overall weekly activity, patient's behaviour patterns appeared to change with increased weekday PA levels and reduced inactivity. Baseline PA levels were highly predictive of PA change. Future focus should be on robust behavioural changes, improving overall levels of objectively assessed PA of people with HF. TRIAL REGISTRATION NUMBERS: ISRCTN78539530 and ISRCTN86234930.

Cost-effectiveness of home-based cardiac rehabilitation: a systematic review.

OBJECTIVE: Centre-based cardiac rehabilitation (CR) is recognised as cost-effective for individuals following a cardiac event. However, home-based alternatives are becoming increasingly popular, especially since COVID-19, which necessitated alternative modes of care delivery. This review aimed to assess whether home-based CR interventions are cost-effective (vs centre-based CR). METHODS: Using the MEDLINE, Embase and PsycINFO databases, literature searches were conducted in October 2021 to identify full economic evaluations (synthesising costs and effects). Studies were included if they focused on home-based elements of a CR programme or full home-based programmes. Data extraction and critical appraisal were completed using the NHS EED handbook, Consolidated Health Economic Evaluation Reporting Standards and Drummond checklists and were summarised narratively. The protocol was registered on the PROSPERO database (CRD42021286252). RESULTS: Nine studies were included in the review. Interventions were heterogeneous in terms of delivery, components of care and duration. Most studies were economic evaluations within clinical trials (8/9). All studies reported quality-adjusted life years, with the EQ-5D as the most common measure of health status (6/9 studies). Most studies (7/9 studies) concluded that home-based CR (added to or replacing centre-based CR) was cost-effective compared with centre-based options. CONCLUSIONS: Evidence suggests that home-based CR options are cost-effective. The limited size of the evidence base and heterogeneity in methods limits external validity. There were further limitations to the evidence base (eg, limited sample sizes) that increase uncertainty. Future research is needed to cover a greater range of home-based designs, including home-based options for psychological care, with greater sample sizes and the potential to acknowledge patient heterogeneity.

Metacognitive therapy home-based self-help for anxiety and depression in cardiovascular disease patients in the UK: A single-blind randomised controlled trial.

BACKGROUND: Anxiety and depression in cardiac rehabilitation (CR) are associated with greater morbidity, mortality, and increased healthcare costs. Current psychological interventions within CR have small effects based on low-quality studies of clinic-based interventions with limited access to home-based psychological support. We tested the effectiveness of adding self-help metacognitive therapy (Home-MCT) to CR in reducing anxiety and depression in a randomised controlled trial (RCT). METHODS AND FINDINGS: We ran a single-blind, multi-centre, two-arm RCT. A total of 240 CR patients were recruited from 5 NHS-Trusts across North West England between April 20, 2017 and April 6, 2020. Patients were randomly allocated to Home-MCT+CR (n = 118, 49.2%) or usual CR alone (n = 122, 50.8%). Randomisation was 1:1 via randomised blocks within hospital site, balancing arms on sex and baseline Hospital Anxiety and Depression Scale (HADS) scores. The primary outcome was the HADS total score at posttreatment (4-month follow-up). Follow-up data collection occurred between August 7, 2017 and July 20, 2020. Analysis was by intention to treat. The 4-month outcome favoured the MCT intervention group demonstrating significantly lower end of treatment scores (HADS total: adjusted mean difference = -2.64 [-4.49 to -0.78], p = 0.005, standardised mean difference (SMD) = 0.38). Sensitivity analysis using multiple imputation (MI) of missing values supported these findings. Most secondary outcomes also favoured Home-MCT+CR, especially in reduction of post-traumatic stress symptoms (SMD = 0.51). There were 23 participants (19%) lost to follow-up in Home-MCT+CR and 4 participants (3%) lost to follow-up in CR alone. No serious adverse events were reported. The main limitation is the absence of longer term (e.g., 12-month) follow-up data. CONCLUSION: Self-help home-based MCT was effective in reducing total anxiety/depression in patients undergoing CR. Improvement occurred across most psychological measures. Home-MCT was a promising addition to cardiac rehabilitation and may offer improved access to effective psychological treatment in cardiovascular disease (CVD) patients. TRIAL REGISTRATION: NCT03999359.

Exercise rehabilitation in COPD and heart failure: comparison of two national audits.

Background: Pulmonary (PR) and cardiac rehabilitation (CR) are recommended in the management of chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF); the impact of coexisting COPD and CHF on completion and outcomes of rehabilitation programmes is unknown. We examined enrolment, completion and clinical outcomes of CR and PR in adults with COPD, CHF and coexisting COPD and CHF. Methods: The National Audit of CR and National COPD Audit Programme: clinical audits of PR were analysed (211 PR and 237 CR programmes); adults with a diagnosis of CHF, COPD or coexisting COPD and CHF were identified (COPD+CHF or CHF+COPD according to database). Propensity matching was conducted (age, sex, body mass index and functional status) between COPD+CHF and COPD, and CHF+COPD and CHF. Group by time interaction was examined using mixed 2×2 analysis of variance. Results: Those with CHF+COPD had lower enrolment and completion of CR compared to those with CHF; there were no differences in PR enrolment or completion between the two groups. Adults with COPD made a significantly larger gain in the incremental shuttle walk test compared to adults with COPD+CHF following PR (59.3 m versus 37.4 m); the improvements following CR were similar (CHF 77.3 m versus CHF+COPD 58.3 m). Similar improvements were made in the 6-min walk test following CR (CHF 45.1 m versus CHF+COPD 38.8 m) and PR (COPD 48.2 m versus COPD+CHF 44.0 m). Comparable improvements in quality of life and mood state were made following CR and PR, regardless of diagnosis. Conclusion: We have demonstrated that multi-morbid adults benefit from exercise-based rehabilitation, yet efforts are needed to promote completion. These findings support group-based, tailored, multi-morbid exercise rehabilitation.

Discrete choice experiment to investigate preferences for psychological intervention in cardiac rehabilitation.

OBJECTIVE: Cardiac rehabilitation (CR) is offered to people who recently experienced a cardiac event, and often comprises of exercise, education and psychological care. This stated preference study aimed to investigate preferences for attributes of a psychological therapy intervention in CR. METHODS: A discrete choice experiment (DCE) was conducted and recruited a general population sample and a trial sample. DCE attributes included the modality (group or individual), healthcare professional providing care, information provided prior to therapy, location and the cost to the National Health Service (NHS). Participants were asked to choose between two hypothetical designs of therapy, with a separate opt-out included. A mixed logit model was used to analyse preferences. Cost to the NHS was used to estimate willingness to pay (WTP) for aspects of the intervention design. RESULTS: Three hundred and four participants completed the DCE (general public sample (n=262, mean age 47, 48% female) and trial sample (n=42, mean age 66, 45% female)). A preference for receiving psychological therapy was demonstrated by both samples (general population WTP £1081; 95% CI £957 to £1206). The general population appeared to favour individual therapy (WTP £213; 95% CI £160 to £266), delivered by a CR professional (WTP £48; 9% % CI £4 to £93) and with a lower cost (ß=-0.002; p<0.001). Participants preferred to avoid options where no information was received prior to starting therapy (WTP -£106; 95% CI -£153 to -£59). Results for the location attribute were variable and challenging to interpret. CONCLUSIONS: The study demonstrates a preference for psychological therapy as part of a programme of CR, as participants were more likely to opt-in to therapy. Results indicate that some aspects of the delivery which may be important to participants can be tailored to design a psychological therapy. Preference heterogeneity is an issue which may prevent a 'one-size-fits-all' approach to psychological therapy in CR.

Levels of depressive symptoms in cardiac patients attending cardiac rehabilitation with a history of depression: pre Covid-19 and Covid-19 period comparison.

BACKGROUND: The large-scale changes in cardiac rehabilitation (CR) programme delivery in response to COVID-19 has led to diminished provision. The influence of these service changes on the depression symptoms of patients in CR programmes is unknown. Our study investigated the extent of depressive symptoms prior to and during the COVID-19 periods in patients with a previous history of depression at the start of CR. METHODS: Use of Registry routine practice data, National Audit of Cardiac Rehabilitation (NACR), from COVID-19 period Feb 2020 and Jan 2021, as well as pre COVID-19 period Feb 2019 and Jan 2020, was extracted. Depressive symptoms were defined according to Hospital Anxiety and Depression Score ≥ 8. Chi-square tests and independent samples t-tests were used to investigate baseline characteristics. Additionally, a binary logistic regression to examine the factors associated with high levels of depressive symptoms. RESULTS: In total 3661 patients with a history of depression were included in the analysis. Patients attending CR during COVID-19 were found to be 11% more likely to have high levels of acute depressive symptoms compared to patients attending CR prior to COVID-19. Physical inactivity, increased anxiety, a higher total number of comorbidities, increased weight, and living in the most deprived areas were statistically significant factors associated with high levels of acute depressive symptoms at the start of CR following multivariate adjustments. CONCLUSION: Our research suggests that following a cardiac event patients with prior history of depression have high levels of acute depressive symptoms at CR baseline assessment. This finding exists in both the pre Covid-19 and Covid-19 periods in patients with a history of depression.

A Single Domain Shark Antibody Targeting the Transferrin Receptor 1 Delivers a TrkB Agonist Antibody to the Brain and Provides Full Neuroprotection in a Mouse Model of Parkinson's Disease.

Single domain shark antibodies that bind to the transferrin receptor 1 (TfR1) on brain endothelial cells have been used to shuttle antibodies and other cargos across the blood brain barrier (BBB) to the brain. For these studies the TXB4 brain shuttle was fused to a TrkB neurotrophin receptor agonist antibody. The TXB4-TrkB fusion retained potent agonist activity at its cognate receptor and after systemic administration showed a 12-fold increase in brain levels over the unmodified antibody. Only the TXB4-TrkB antibody fusion was detected within the brain and localized to TrkB positive cells in the cortex and tyrosine hydroxylase (TH) positive dopaminergic neurons in the substantia nigra pars compacta (SNc), where it was associated with activated ERK1/2 signaling. When tested in the 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease (PD), TXB4-TrkB, but not the unmodified antibody, completely prevented the 6-OHDA induced death of TH positive neurons in the SNc. In conclusion, the fusion of the TXB4 brain shuttle allows a TrkB agonist antibody to reach neuroprotective concentrations in the brain parenchyma following systemic administration.