One size does not fit all - Application of accelerometer thresholds in chronic disease

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record National Institute for Health Research (NIHR

Exercise-based rehabilitation for heart failure: systematic review and meta-analysis

This is the final version of the article. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVE: To update the Cochrane systematic review of exercise-based cardiac rehabilitation (CR) for heart failure. METHODS: A systematic review and meta-analysis of randomised controlled trials was undertaken. MEDLINE, EMBASE and the Cochrane Library were searched up to January 2013. Trials with 6 or more months of follow-up were included if they assessed the effects of exercise interventions alone or as a component of comprehensive CR programme compared with no exercise control. RESULTS: 33 trials were included with 4740 participants predominantly with a reduced ejection fraction (<40%) and New York Heart Association class II and III. Compared with controls, while there was no difference in pooled all-cause mortality between exercise CR with follow-up to 1 year (risk ratio (RR) 0.93; 95% CI 0.69 to 1.27, p=0.67), there was a trend towards a reduction in trials with follow-up beyond 1 year (RR 0.88; 0.75 to 1.02, 0.09). Exercise CR reduced the risk of overall (RR 0.75; 0.62 to 0.92, 0.005) and heart failure-specific hospitalisation (RR 0.61; 0.46 to 0.80, 0.0004) and resulted in a clinically important improvement in the Minnesota Living with Heart Failure questionnaire (mean difference: -5.8 points, -9.2 to -2.4, 0.0007). Univariate meta-regression analysis showed that these benefits were independent of the type and dose of exercise CR, and trial duration of follow- up, quality or publication date. CONCLUSIONS: This updated Cochrane review shows that improvements in hospitalisation and health-related quality of life with exercise-based CR appear to be consistent across patients regardless of CR programme characteristics and may reduce mortality in the longer term. An individual participant data meta-analysis is needed to provide confirmatory evidence of the importance of patient subgroup and programme level characteristics (eg, exercise dose) on outcome.This publication presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-1210-12004)

"Flogging dead horses": evaluating when have clinical trials achieved sufficiency and stability? A case study in cardiac rehabilitation

<p>Abstract</p> <p>Background</p> <p>Most systematic reviews conclude that another clinical trial is needed. Measures of sufficiency and stability may indicate whether this is true.</p> <p>Objectives: To show how evidence accumulated on centre-based versus home-based cardiac rehabilitation, including estimates of sufficiency and stability</p> <p>Methods</p> <p>Systematic reviews of clinical trials of home versus centre-based cardiac rehabilitation were used to develop a cumulative meta-analysis over time. We calculated the standardised mean difference (SMD) in effect, confidence intervals and indicators of sufficiency and stability. Sufficiency refers to whether the meta-analytic database adequately demonstrates that an intervention works - is statistically superior to another. It does this by assessing the number of studies with null results that would be required to make the meta-analytic effect non-statistically significant. Stability refers to whether the direction and size of the effect is stable as new studies are added to the meta-analysis.</p> <p>Results</p> <p>The standardised mean effect difference reduced over fourteen comparisons from a non-significant difference favouring home-based cardiac rehabilitation to a very small difference favouring hospital (SMD -0.10, 95% CI -0.32 to 0.13). This difference did not reach the sufficiency threshold (failsafe ratio 0.039 < 1) but did achieve the criteria for stability (cumulative slope 0.003 < 0.005).</p> <p>Conclusions</p> <p>The evidence points to a relatively small effect difference which was stable but not sufficient in terms of the suggested thresholds. Sufficiency should arguably be based on substantive significance and decided by patients. Research on patient preferences should be the priority. Sufficiency and stability measures are useful tools that need to be tested in further case studies.</p

Factors Associated with Objectively Assessed Physical Activity Levels of Heart Failure Patients

This is the final version. Available on open access from Longdom Publishing via the DOI in this recordAim: To determine the level of objectively measured moderate-to-vigorous physical activity (MVPA) in patients with heart failure (HF), and to assess the association between MVPA and patient sociodemographic, exercise capacity, and health status factors. Methods: Baseline MVPA data was available in 247 HF patients with 7-day wrist-worn accelerometry from two randomized controlled trials. Associations between MVPA and patient sociodemographic, exercise capacity, and health status factors were assessed using univariate and multivariable linear regression models. Results: 247 patients (28% female, mean age 71 ± 10 years) with HF with reduced ejection fraction (n=198) and preserved ejection fraction (n=49) were included in the analysis. Average MVPA was 283. 3 min/week and ranged widely from a minimum of 0 mins/week to maximum of 2626. 7 mins/week (standard deviation: 404. 1 mins/week). 111 (45%) of patients had a level of PA that met current guidelines of at least 150 minutes/week of MVPA. Multivariable regression showed patient’s age, body mass index, employment status, smoking status, New York Heart Association class, NT-proBNP and exercise capacity to be strongly associated (p<0. 001) with the level of MVPA (p<0. 001). Conclusion: Whilst 45% of HF patients had objectively measured levels of MVPA that met current PA recommendations, we observed a wide range in the level of MVPA across this patient sample. As a number of factors were found to be associated with MVPA our findings provide important information for future interventions aiming to increase MVPA in HF patients.University of ExeterNational Institute for Health Research (NIHR

Home-based versus centre-based cardiac rehabilitation: Abridged Cochrane systematic review and meta-analysis

Objective: To update the Cochrane review comparing the effects of home-based and supervised centre-based cardiac rehabilitation (CR) on mortality and morbidity, quality of life, and modifiable cardiac risk factors in patients with heart disease. Methods: Systematic review and meta-analysis. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and CINAHL were searched up to October 2014, without language restriction. Randomised trials comparing home-based and centre-based CR programmes in adults with myocardial infarction, angina, heart failure or who had undergone coronary revascularisation were included. Results: 17 studies with 2172 patients were included. No difference was seen between home-based and centre-based CR in terms of: mortality (relative risk (RR) 0.79, 95% CI 0.43 to 1.47); cardiac events; exercise capacity (mean difference (MD) −0.10, −0.29 to 0.08); total cholesterol (MD 0.07 mmol/L, −0.24 to 0.11); low-density lipoprotein cholesterol (MD −0.06 mmol/L, −0.27 to 0.15); triglycerides (MD −0.16 mmol/L, −0.38 to 0.07); systolic blood pressure (MD 0.2 mm Hg, −3.4 to 3.8); smoking (RR 0.98, 0.79 to 1.21); health-related quality of life and healthcare costs. Lower high-density lipoprotein cholesterol (MD −0.07 mmol/L, −0.11 to −0.03, p=0.001) and lower diastolic blood pressure (MD −1.9 mm Hg, −0.8 to −3.0, p=0.009) were observed in centre-based participants. Home-based CR was associated with slightly higher adherence (RR 1.04, 95% CI 1.01 to 1.07). Conclusions: Home-based and centre-based CR provide similar benefits in terms of clinical and health-related quality of life outcomes at equivalent cost for those with heart failure and following myocardial infarction and revascularisation

Rehabilitation Enablement in Chronic Heart Failure—a facilitated self-care rehabilitation intervention in patients with heart failure with preserved ejection fraction (REACH-HFpEF) and their caregivers:rationale and protocol for a single-centre pilot randomised controlled trial

This is the final version of the article. Available from the publisher via the DOI in this record.INTRODUCTION: The Rehabilitation EnAblement in CHronic Heart Failure in patients with Heart Failure (HF) with preserved ejection fraction (REACH-HFpEF) pilot trial is part of a research programme designed to develop and evaluate a facilitated, home-based, self-help rehabilitation intervention to improve self-care and quality of life (QoL) in heart failure patients and their caregivers. We will assess the feasibility of a definitive trial of the REACH-HF intervention in patients with HFpEF and their caregivers. The impact of the REACH-HF intervention on echocardiographic outcomes and bloodborne biomarkers will also be assessed. METHODS AND ANALYSIS: A single-centre parallel two-group randomised controlled trial (RCT) with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention) or usual care alone (control) in 50 HFpEF patients and their caregivers. The REACH-HF intervention comprises a REACH-HF manual with supplementary tools, delivered by trained facilitators over 12 weeks. A mixed methods approach will be used to assess estimation of recruitment and retention rates; fidelity of REACH-HF manual delivery; identification of barriers to participation and adherence to the intervention and study protocol; feasibility of data collection and outcome burden. We will assess the variance in study outcomes to inform a definitive study sample size and assess methods for the collection of resource use and intervention delivery cost data to develop the cost-effectiveness analyses framework for any future trial. Patient outcomes collected at baseline, 4 and 6 months include QoL, psychological well-being, exercise capacity, physical activity and HF-related hospitalisation. Caregiver outcomes will also be assessed, and a substudy will evaluate impact of the REACH-HF manual on resting global cardiovascular function and bloodborne biomarkers in HFpEF patients. ETHICS AND DISSEMINATION: The study is approved by the East of Scotland Research Ethics Service (Ref: 15/ES/0036). Findings will be disseminated via journals and presentations to clinicians, commissioners and service users. TRIAL REGISTRATION NUMBER: ISRCTN78539530; Pre-results .This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-1210-12004). NB, CA, CJG and RST are also supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust; KJ by CLAHRC West Midlands and SS by CLAHRC East-Midlands. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Healt

Impact of exercise-based cardiac rehabilitation in patients with heart failure (ExTraMATCH II) on mortality and hospitalisation:an individual-patient data meta-analysis of randomised trials

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordAIMS: To undertake an individual patient data (IPD) meta-analysis to assess the impact of exercise-based cardiac rehabilitation (ExCR) in patients with heart failure (HF) on mortality and hospitalisation, and differential effects of ExCR according to patient characteristics: age, sex, ethnicity, New York Heart Association functional class, ischaemic aetiology, ejection fraction, and exercise capacity. METHODS AND RESULTS: Randomised trials of exercise training for at least 3 weeks compared with no exercise control with 6-month follow-up or longer, providing IPD time to event on mortality or hospitalisation (all-cause or HF-specific). IPD were combined into a single dataset. We used Cox proportional hazards models to investigate the effect of ExCR and the interactions between ExCR and participant characteristics. We used both two-stage random effects and one-stage fixed effect models. IPD were obtained from 18 trials including 3912 patients with HF with reduced ejection fraction. Compared to control, there was no statistically significant difference in pooled time to event estimates in favour of ExCR although confidence intervals (CIs) were wide [all-cause mortality: hazard ratio (HR) 0.83, 95% CI 0.67-1.04; HF-specific mortality: HR 0.84, 95% CI 0.49-1.46; all-cause hospitalisation: HR 0.90, 95% CI 0.76-1.06; and HF-specific hospitalisation: HR 0.98, 95% CI 0.72-1.35]. No strong evidence was found of differential intervention effects across patient characteristics. CONCLUSION: Exercise-based cardiac rehabilitation did not have a significant effect on the risk of mortality and hospitalisation in HF with reduced ejection fraction. However, uncertainty around effect estimates precludes drawing definitive conclusions.This work is supported by UK National Institute for Health Research funding (HTA 15/80/30)

Process evaluation of a randomised pilot trial of home-based rehabilitation compared to usual care in patients with heart failure with preserved ejection fraction and their caregiver’s

Background: Whilst heart failure (HF) with preserved ejection fraction (HFpEF) affects almost 50 percent of the HF population, evidence-based treatment options remain limited. However, there is growing evidence of the potential value of exercise-based cardiac rehabilitation. This study reports the process evaluation of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) intervention for HFpEF patients and their caregivers conducted as part of the REACH-HFpEF pilot trial. Methods: Process evaluation sub-study parallel to a single centre (Tayside, Scotland) randomised controlled pilot trial with qualitative assessment of both intervention fidelity delivery and HFpEF patients’ and caregivers’ experiences. The REACH-HF intervention consisted of self-help manual for patients and caregivers, facilitated over 12 weeks by trained healthcare professionals. Interviews were conducted following completion of intervention in a purposeful sample of 15 HFpEF patients and 7 caregivers. Results: Qualitative information from the facilitator interactions and interviews identified three key themes for patients and caregivers: (1) understanding their condition, (2) emotional consequences of HF, and (3) patients’ and caregivers’ responses to the REACH-HF intervention. The differing professional backgrounds demonstrate the possibility of delivering REACH-HF by either existing HF or cardiac rehabilitation services of a combination of the two. Conclusions: The REACH-HF home-based facilitated intervention for HFpEF appears feasible and well accepted model for delivery of a cardiac rehabilitation intervention, with the potential to address key unmet needs of patients and their caregivers who are often excluded from service provision and current CR programmes. Results of this study will inform a recently funded full multicentre randomised clinical trial

Randomised trials comparing different healthcare settings : an exploratory review of the impact of pre-trial preferences on participation, and discussion of other methodological challenges

BACKGROUND: We recently published a systematic review of different healthcare settings (such as outpatient, community or home) for administering intravenous chemotherapy, and concluded that performing conventionally designed randomised trials was difficult. The main problems were achieving adequate trial accrual rates and recruiting a study population which adequately represented the target population of interest. These issues stemmed from the fact that potential participants may have had pre-trial perceptions about the trial settings they may be allocated; such preferences will sometimes be strong enough for patients to decline an invitation to participate in a trial. A patient preference trial design (in which patients can choose, or be randomised to, an intervention) may have obviated these recruitment issues, although none of the trials used such a design. METHODS: In order to gain a better understanding of the broader prevalence and extent of these preference issues (and any other methodological challenges), we undertook an exploratory review of settings trials in any area of healthcare treatment research. We searched The Cochrane Library and Google Scholar and used snowballing methods to identify trials comparing different healthcare settings. RESULTS: Trial accrual was affected by patient preferences for a setting in 15 of the 16 identified studies; birth setting trials were the most markedly affected, with between 68 % and 85 % of eligible women declining to participate specifically because of preference for a particular healthcare setting. Recruitment into substance abuse and chemotherapy setting studies was also notably affected by preferences. Only four trials used a preference design: the proportion of eligible patients choosing to participate via a preference group ranged from between 33 % and 67 %. CONCLUSIONS: In trials of healthcare settings, accrual may be seriously affected by patient preferences. The use of trial designs which incorporate a preference component should therefore strongly be considered. When designing such trials, investigators should consider settings to be complex interventions, which are likely to have linked components which may be difficult to control for. Careful thought is also needed regarding the choice of comparator settings and the most appropriate outcome measures to be used

Acceptability, Feasibility and Preliminary Evaluation of a Novel, Personalised, Home based Physical Activity Intervention for Chronic Heart Failure (Active-at-Home-HF)::A Pilot Study

Purpose: Less than 10% of heart failure patients in the UK participate in cardiac rehabilitation programmes. The present pilot study evaluated feasibility, acceptability and physiological effects of a novel, personalised, home-based physical activity intervention in chronic heart failure. Methods: Twenty patients (68±7 years old, 20% females) with stable chronic heart failure due to reduced left ventricular ejection fraction (31±8 %) participated in a single group, pilot study assessing the feasibility and acceptability of a 12-week personalised home-based physical activity intervention aiming to increase daily number of steps by 2000 from baseline (Active-at-Home-HF). Patients completed cardiopulmonary exercise testing with non-invasive gas exchange and haemodynamic measurements and quality of life questionnaire pre- and post-intervention. Patients were supported weekly via telephone and average weekly step count data collected using pedometers. Results: 43 patients were screened and 20 recruited into the study. Seventeen patients (85%) completed the intervention, and 15 (75%) achieved the target step count. Average step count per day increased significantly from baseline to 3 weeks by 2546 (5108±3064 to 7654±3849 P=0.03, n=17), and was maintained until week 12 (9022±3942). Following completion of the intervention, no adverse events were recorded, quality of life improved by 4 points (26±18 vs. 22±19). Peak exercise stroke volume increased by 19% (127±34 vs 151±34 m/beat, P=0.05), while cardiac index increased by 12% (6.8±1.5 vs. 7.6±2.0 L/min/m2, P=0.19). Workload and oxygen consumption at anaerobic threshold also increased by 16% (49±16 vs. 59±14 watts, P=0.01) and 10% (11.5±2.9 vs. 12.8±2.2 ml/kg/min, P=0.39). Conclusion: The Active-at-Home-HF intervention is feasible, acceptable and effective for increasing physical activity in CHF. It may lead to improvements in quality of life, exercise tolerance and haemodynamic function