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Ageing populations and improved survival, have contributed to a rise in the number of people living with multimorbidity, raising issues related to polypharmacy, treatment burden, competing priorities and poor coordination of care. Self-management programs are increasingly included as an essential component of interventions to improve outcomes in this population. However, an overview of how interventions supporting self-management in patients with multimorbidity is missing. This scoping review focused on mapping the literature on patient-centered interventions for people living with multimorbidity. We searched several databases, clinical registries, and grey literature for RCTs published between 1990–2019 describing interventions that supported self-management in people with multimorbidity. We included 72 studies that were found to be very heterogeneous when it comes to the population, delivery modes and modalities, intervention elements and facilitators. The results pointed to an extensive use of cognitive behavioral therapy as a basis for interventions, as well as behavior change theories and disease management frameworks. The most coded behavior change techniques stemmed from the categories Social Support, Feedback and monitoring and Goals and Planning. To allow for implementation of effective interventions in clinical practice, improved reporting of intervention mechanisms in RCTs is warranted. [ABSTRACT FROM AUTHOR]

Using a surrogate endpoint as a substitute for a patient-relevant final outcome enables randomised controlled trials (RCTs) to be conducted more efficiently. However, the use of surrogates remains controversial and there is currently no guideline for the reporting of RCTs using surrogate endpoints; therefore, we seek to develop SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) extensions to improve the reporting of these trials. We would like to invite interested individuals (trial methodologists, journal editors, healthcare industry, regulators and payers, and patient/public representative groups), particularly those with experience in the use of surrogate endpoints in trials. [ABSTRACT FROM AUTHOR]

Spinal cord stimulation (SCS) is increasingly used to treat painful diabetic neuropathy (PDN). At the time of a recent meta-analysis in this field, data were only available from randomized controlled trials (RCTs) of traditional low-frequency SCS (LF-SCS). However, outcomes from high-frequency 10 kHz SCS treatment are now available. Our study aimed to systematically review the contemporary evidence for SCS in patients with lower limb pain due to PDN and include an indirect comparison of the high- and low-frequency modalities. We searched the PubMed/CENTRAL databases up to 18 August 2022, for peer-reviewed RCTs of SCS that enrolled PDN patients with lower limb pain symptoms. The quality of the evidence was assessed with the Cochrane Risk of Bias tool. Using SCS treatment arm data from the RCTs, we indirectly compared the absolute treatment effect of 10 kHz SCS and LF-SCS. Results are presented in tables and forest plots. This systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Three RCTs met our eligibility criteria, including the recent 10 kHz SCS RCT (N = 216, 90 implanted) and 2 others that examined LF-SCS (N = 36, 17 implanted; N = 60, 37 implanted). Our analysis of 6-month data found clinically meaningful pain relief with each SCS modality. However, significantly greater pain reduction was identified for 10 kHz SCS over LF-SCS: average pain reduction in the 10 kHz SCS cohort was 73.7% compared with 47.5% in the pooled LF-SCS group (p < 0.0001). In the permanent implant subset, the 50% pain reduction responder rate was 83.3% in the 10 kHz SCS cohort versus 63.0% in the pooled LF-SCS group (p = 0.0072). The overall risk of bias of each included RCT was deemed high, mainly due to the absence of patient blinding. Our analysis indicates that paresthesia-free 10 kHz SCS can provide superior pain relief and responder rate over LF-SCS for managing PDN patients refractory to conventional medical management. [ABSTRACT FROM AUTHOR]

Background: The e-coachER trial aimed to determine whether adding web-based behavioural support to exercise referral schemes (ERS) increased long-term device-measured physical activity (PA) for patients with chronic conditions, compared to ERS alone, within a randomised controlled trial. This study explores the mechanisms of action of the e-coachER intervention using measures of the behaviour change processes integral to the intervention's logic model. Methods: Four hundred fifty adults with obesity, diabetes, hypertension, osteoarthritis or history of depression referred to an ERS were recruited in Plymouth, Birmingham and Glasgow. The e-coachER intervention comprising 7-Steps to Health was aligned with Self-Determination Theory and mapped against evidence-based behaviour change techniques (BCTs). Participants completed questionnaires at 0, 4, and 12 months to assess PA and self-reported offline engagement with core BCTs in day-to-day life (including action planning and self-monitoring) and beliefs relating to PA (including perceived importance, confidence, competence, autonomy and support). We compared groups at 4 and 12 months, controlling for baseline measures and other covariates. Mediation analysis using the product of coefficients method was used to determine if changes in process variables mediated intervention effects on moderate to vigorous physical activity (MVPA) recorded by accelerometer and self-report at 4- and 12-months. Results: The internal reliability (Cronbach's alpha) for all multi-item scales was > 0.77. At 4-months, those randomised to e-coachER reported higher levels of PA beliefs relating to importance (1.01, 95% confidence interval (CI): 0.42 to 1.61, p = 0.001), confidence (1.28, 95% CI: 0.57 to 1.98, p < 0.001), competence (1.61, 95% CI:.68 to 2.54, p = 0.001), availability of support (0.77, 95% CI: 0.07 to 1.48, p = 0.031), use of action planning (1.54, 95% CI: 0.23 to 2.85, p = 0.021) and use of self-monitoring (0.76, 95% CI: 0.19 to 1.32, p = 0.009) compared to ERS alone. There were no intervention effects on autonomous beliefs or perceived frequency of support, compared to ERS alone. At the 12-month follow-up, participants belief in the importance of PA was the only process measure to remain significantly higher in the e-coachER group when compared to ERS alone (0.75, 95% CI: 0.05 to 1.45). Intervention effects on perceived importance (2.52, 95% CI: 0.45 to 5.39), action planning (1.56, 95% CI: 0.10 to 3.54) and self-monitoring (1.92, 95% CI: 0.21 to 4.33) at 4-months significantly mediated change in accelerometer measured MVPA at 12-months (recorded in ≥ 10-min bouts). Conclusions: e-coachER led to some short-term changes in most process outcomes. Some of these processes also appeared to mediate e-coachER effects on changes in accelerometer measured MVPA. Further work should be carried out to understand how best to design and implement theoretically underpinned web-based physical activity promotion interventions within ERS. Trial registration: ISRCTN, ISRCTN15644451. Registered 12 February 2015. [ABSTRACT FROM AUTHOR]

Objective: This randomised controlled trial (RCT) aimed to investigate the effects of a simple cognitive task intervention on intrusive memories ("flashbacks") and associated symptoms following a traumatic event. Patients presenting to a Swedish emergency department (ED) soon after a traumatic event were randomly allocated (1:1) to the simple cognitive task intervention (memory cue + mental rotation instructions + computer game "Tetris" for at least 20 min) or control (podcast, similar time). We planned follow-ups at one-week, 1-month, and where possible, 3- and 6-months post-trauma. Anticipated enrolment was N = 148. Results: The RCT was terminated prematurely after recruiting N = 16 participants. The COVID-19 pandemic prevented recruitment/testing in the ED because: (i) the study required face-to-face contact between participants, psychology researchers, ED staff, and patients, incurring risk of virus transmission; (ii) the host ED site received COVID-19 patients; and (iii) reduced flow of patients otherwise presenting to the ED in non-pandemic conditions (e.g. after trauma). We report on delivery of study procedures, recruitment, treatment adherence, outcome completion (primary outcome: number of intrusive memories during week 5), attrition, and limitations. The information presented and limitations may enable our group and others to learn from this terminated study. Trial registration ClinicalTrials.gov: NCT04185155 (04-12-2019) [ABSTRACT FROM AUTHOR]

Objective: To determine whether adding web-based support (e-coachER) to an exercise referral scheme (ERS) increases objectively assessed physical activity (PA).Design: Multicentre trial with participants randomised to usual ERS alone (control) or usual ERS plus e-coachER (intervention).Setting: Primary care and ERS in three UK sites from 2015 to 2018.Participants: 450 inactive ERS referees with chronic health conditions.Interventions: Participants received a pedometer, PA recording sheets and a user guide for the web-based support. e-coachER interactively encouraged the use of the ERS and other PA options.Main Outcome Measures: Primary and key secondary outcomes were: objective moderate-to-vigorous PA (MVPA) minutes (in ≥10 min bouts and without bouts), respectively, after 12 months. Secondary outcomes were: other accelerometer-derived and self-reported PA measures, ERS attendance, EQ-5D-5L, Hospital Anxiety and Depression Scale and beliefs about PA. All outcomes were collected at baseline, 4 and 12 months. Primary analysis was an intention to treat comparison between intervention and control arms at 12-month follow-up.Results: There was no significant effect of the intervention on weekly MVPA at 12 months between the groups recorded in ≥10 min bouts (mean difference 11.8 min of MVPA, 95% CI: -2.1 to 26.0; p=0.10) or without bouts (mean difference 13.7 min of MVPA, 95% CI: -26.8 to 54.2; p=0.51) for 232 participants with usable data. There was no difference in the primary or secondary PA outcomes at 4 or 12 months.Conclusion: Augmenting ERS referrals with web-based behavioural support had only a weak, non-significant effect on MVPA.Trial Registration Number: ISRCTN15644451. [ABSTRACT FROM AUTHOR]

In the drive towards faster patient access to treatments, health technology assessment (HTA) agencies are increasingly faced with reliance on evidence from surrogate endpoints, leading to increased decision uncertainty. This study undertook an updated survey of methodological guidance for using surrogate endpoints across international HTA agencies. We reviewed HTA and economic evaluation methods guidance from European, Australian and Canadian HTA agencies. We considered how guidelines addressed the methods for handling surrogate endpoints, including (1) level of evidence, (2) methods of validation, and (3) thresholds of acceptability. Across the 73 HTA agencies surveyed, 29 (40%) had methodological guidelines that made specific reference to consideration of surrogate outcomes. Of the 45 methods documents analysed, the majority [27 (60%)] were non-technology specific, 15 (33%) focused on pharmaceuticals and three (7%) on medical devices. The principles of the European network for Health Technology Assessment (EUnetHTA) guidelines published in 2015 on the handling of surrogate endpoints appear to have been adopted by many European HTA agencies, i.e. preference for final patient-relevant outcomes and reliance on surrogate endpoints with biological plausibility and epidemiological evidence of the association between the surrogate and final endpoint. Only a small number of HTA agencies (UK National Institute for Care and Excellence; the German Institute for Medical Documentation and Information and Institute for Quality and Efficiency in Health Care; the Australian Pharmaceutical Benefits Advisory Committee; and the Canadian Agency for Drugs and Technologies in Health) have developed more detailed prescriptive criteria for the acceptance of surrogate endpoints, e.g. meta-analyses of randomised controlled trials showing strong association between the treatment effect on the surrogate and final outcomes. As the decision uncertainty associated with reliance on surrogate endpoints carries a risk to patients and society, there is a need for HTA agencies to develop more detailed methodological guidance for consistent selection and evaluation of health technologies that lack definitive final patient-relevant outcome evidence at the time of the assessment. [ABSTRACT FROM AUTHOR]

Background: Although there is trial evidence that complex interventions are effective for the self-management of heart failure, little evidence supports their effectiveness in routine practice. We used Social Practice Theory to guide a Type 1 Hybrid Trial: a mixed methods process evaluation of a complex intervention for heart failure. The objective of this paper is to explore the value of Social Practice Theory for implementation science.Methods: Social Practice Theory informed a mixed methods process evaluation of a multi-centre randomised controlled trial of a 12 week home-based intervention to optimise self-care support for people with heart failure and their caregivers - Rehabilitation EnAblement in Chronic Heart Failure (REACH-HF). Interviews were conducted with 19 people with heart failure and 17 caregivers at 4 months and 12 months after recruitment into the trial. Cases were constructed at the level of the individual, couple, facilitator and centre; and included multi-modal process and outcome data. Evaluative coding and subsequent within- and cross-case analyses enabled the development of a typology of relationships linking fidelity of intervention delivery and tailoring of content to individual needs and concerns. Social Practice Theory was used to interrogate the relationships between elements of the intervention and their implementation.Results: Of 216 trial participants, 107 were randomised to the intervention (REACH-HF plus usual care). The intervention was most effective when fidelity was high and delivery was tailored to the individual's needs, but less effective when both tailoring and fidelity were low. Theory-based analysis enabled us to model complex relationships between intervention elements (competencies, materials and meanings) and social context. The findings illustrate how intervention fidelity and tailoring are contextual and how the effectiveness of the REACH-HF intervention depended on both optimal alignment and implementation of these elements.Conclusion: The study demonstrates the utility of theory-based analysis which integrates data from multiple sources to highlight contexts and circumstances in which interventions work best. Social Practice Theory provides a framework for guiding and analysing the processes by which a complex intervention is evaluated in a clinical trial, and has the potential to guide context-specific implementation strategies for clinical practice.Trial Registration: ISRCTN, IISRCTN86234930 . Registered 13th November 2014. [ABSTRACT FROM AUTHOR]

Background: Caregivers frequently provide support to people living with long-term conditions. However, there is paucity of evidence of interventions that support caregivers in their role. Rehabilitation EnAblement in Chronic Heart Failure (REACH-HF) is a novel home-based, health-professional-facilitated, self-management programme for patients with heart failure (HF) and their caregivers. Methods: Based on the random allocation of individual adult patients with reduced ejection fraction (HFrEF) and left ventricular ejection fraction <45% within the past five years, the caregiver of patients was allocated to receive the REACH-HF intervention over 12 weeks (REACH-HF group) or not (control group). Caregiver outcomes were generic health-related quality of life (EQ-5D-5L), Family Caregiver Quality of Life Scale questionnaire (FamQol), Caregiver Burden Questionnaire HF (CBQ-HF), Caregiver Contribution to Self-care of HF Index questionnaire (CC-SCHFI) and Hospital Anxiety and Depression Scale (HADS). Outcomes were compared between groups at 4, 6 and 12 months follow-up. Twenty caregivers receiving REACH-HF were purposively selected for qualitative interviews at 4 and 12 months. Results: Compared with controls (44 caregivers), the REACH-HF group (53 caregivers) had a higher mean CC-SCHFI confidence score at 12 months (57.5 vs 62.8, adjusted mean difference: 9.3, 95% confidence interval: 1.8–16.8, p = 0.016). No significant between group differences were seen in other caregiver outcomes. Qualitative interviews showed that most caregivers who received the REACH-HF intervention made positive changes to how they supported the HF patient they were caring for, and perceived that they had increased their confidence in the caregiver role over time. Conclusion: Provision of the REACH-HF intervention for caregivers of HF patients improved their confidence of self-management and was perceived for some to be helpful in supporting their caregiver role. [ABSTRACT FROM AUTHOR]

Background: Standardised home-based pulmonary rehabilitation (PR) programmes offer an alternative model to centre-based supervised PR for which uptake is currently poor. We determined if a structured home-based unsupervised PR programme was non-inferior to supervised centre-based PR for participants with COPD.Methods: A total of 287 participants with COPD who were referred to PR (187 male, mean (SD) age 68 (8.86) years, FEV1% predicted 48.34 (17.92)) were recruited. They were randomised to either centre-based PR or a structured unsupervised home-based PR programme including a hospital visit with a healthcare professional trained in motivational interviewing, a self-management manual and two telephone calls. Fifty-eight (20%) withdrew from the centre-based group and 51 (18%) from the home group. The primary outcome was dyspnoea domain in the chronic respiratory disease questionnaire (Chronic Respiratory Questionnaire Self-Report; CRQ-SR) at 7 weeks. Measures were taken blinded. We undertook a modified intention-to-treat (mITT) complete case analysis, comparing groups according to original random allocation and with complete data at follow-up. The non-inferiority margin was 0.5 units.Results: There was evidence of significant gains in CRQ-dyspnoea at 7 weeks in both home and centre-based groups. There was inconclusive evidence that home-based PR was non-inferior to PR in dyspnoea (mean group difference, mITT: -0.24, 95% CI -0.61 to 0.12, p=0.18), favouring the centre group at 7 weeks.Conclusions: The standardised home-based programme provides benefits in dyspnoea. Further evidence is needed to definitively determine if the health benefits of the standardised home-based programme are non-inferior or equivalent to supervised centre-based rehabilitation.Trial Registration Number: ISRCTN81189044. [ABSTRACT FROM AUTHOR]

Background: We have developed a healthy lifestyles programme (HeLP) for primary school aged children (9-10 years), currently being evaluated in a definitive cluster randomised controlled trial. This paper descriptively presents the baseline characteristics of trial children (BMI, waist circumference, % body fat, diet and physical activity) by gender, cluster level socio-economic status, school size and time of recruitment into the trial.Methods: Schools were recruited from across the South West of England and allocated 1:1 to either intervention (HeLP) or control (usual practice) stratified by the proportion of children eligible for free school meals (FSM, <19%, ≥19%) and school size (one Year 5 class, >1 Year 5 class). The primary outcome is change in body mass index standard deviation score (BMI sds) at 24 months post-randomisation. Secondary outcomes are BMI sds at 18 months, waist circumference and percentage body fat sds at 18 and 24 months, proportion of children classified as underweight, overweight and obese at 18 and 24 months, physical activity (for a sub-sample) and food intake at 18 months.Results: At baseline 11.4% and 13.6% of children were categorised as overweight or obese respectively. A higher percentage of girls than boys (25.3% vs 24.8%) and children from schools in FSM category 2 (28.2% vs 23.2%) were overweight or obese. Children were consuming a mean (range) of 4.15 (0-13) energy dense snacks (EDS) and 3.23 (0-9) healthy snacks (HS) per day with children from schools in FSM category 2 consuming more EDS and negative food markers and less HS and positive food markers. Children spent an average 53.6 min per day (11.9 to 124.8) in MVPA and thirteen hours (779.3 min) per day (11 h to 15 h) doing less than 'light' intensity activity. Less than 5% of children achieved the Departments of Health's recommendation of 60 min of MVPA every day.Conclusion: We have excellent completeness of baseline data for all measures and have achieved compliance to accelerometry not seen before in other large scale studies. Our anthropometric baseline data is representative of local and national data for children this age and reflects the gender and socio-economic variations expected of children this age in relation to physical activity and weight status.Trial Registration: ISRCTN15811706 (1/05/2012). [ABSTRACT FROM AUTHOR]

Objective: The evidence for cardiac rehabilitation after valve surgery remains sparse. Current recommendations are therefore based on patients with ischaemic heart disease. The aim of this randomised clinical trial was to assess the effects of cardiac rehabilitation versus usual care after heart valve surgery.Methods: The trial was an investigator-initiated, randomised superiority trial (The CopenHeartVR trial, VR; valve replacement or repair). We randomised 147 patients after heart valve surgery 1:1 to 12 weeks of cardiac rehabilitation consisting of physical exercise and monthly psycho-educational consultations (intervention) versus usual care without structured physical exercise or psycho-educational consultations (control). Primary outcome was physical capacity measured by VO2 peak and secondary outcome was self-reported mental health measured by Short Form-36.Results: 76% were men, mean age 62 years, with aortic (62%), mitral (36%) or tricuspid/pulmonary valve surgery (2%). Cardiac rehabilitation compared with control had a beneficial effect on VO2 peak at 4 months (24.8 mL/kg/min vs 22.5 mL/kg/min, p=0.045) but did not affect Short Form-36 Mental Component Scale at 6 months (53.7 vs 55.2 points, p=0.40) or the exploratory physical and mental outcomes. Cardiac rehabilitation increased the occurrence of self-reported non-serious adverse events (11/72 vs 3/75, p=0.02).Conclusions: Cardiac rehabilitation after heart valve surgery significantly improves VO2 peak at 4 months but has no effect on mental health and other measures of exercise capacity and self-reported outcomes. Further research is needed to justify cardiac rehabilitation in this patient group.Trial Registration Number: NCT01558765, Results. [ABSTRACT FROM AUTHOR]

Background: The Healthy Lifestyles Programme (HeLP) trial is being conducted to determine whether a novel school-based intervention is effective and cost-effective in preventing obesity in 9-10 year-old children. This article describes the detailed statistical analysis plan for the HeLP trial, including an amendment (and rationale for amendment) made to originally planned sensitivity analyses. Methods and design: The HeLP trial is a definitive, pragmatic, superiority, cluster randomised controlled trial with two parallel groups and blinded outcome assessment. This update article describes in detail (1) the primary and secondary outcomes, (2) the statistical analysis principles (including which children will be included in each analysis, how the clustered nature of the study design will be accounted for, which covariates will be included in each analysis, how the results will be presented), (3) planned sensitivity analyses, planned subgroup analyses and planned adherence-adjusted analyses for the primary outcome, (4) planned analyses for the secondary outcomes and (e) planned longitudinal analyses. [ABSTRACT FROM AUTHOR]

Background: Differences in blood pressure between arms are associated with increased cardiovascular mortality in cohorts with established vascular disease or substantially elevated cardiovascular risk.Aim: To explore the association of inter-arm difference (IAD) with mortality in a community-dwelling cohort that is free of cardiovascular disease.Design and Setting: Cohort analysis of a randomised controlled trial in central Scotland, from April 1998 to October 2008.Method: Volunteers from Lanarkshire, Glasgow, and Edinburgh, free of pre-existing vascular disease and with an ankle-brachial index ≤0.95, had systolic blood pressure measured in both arms at recruitment. Inter-arm blood pressure differences were calculated and examined for cross-sectional associations and differences in prospective survival. Outcome measures were cardiovascular events and all-cause mortality during mean follow-up of 8.2 years.Results: Based on a single pair of measurements, 60% of 3350 participants had a systolic IAD ≥5 mmHg and 38% ≥10 mmHg. An IAD ≥5 mmHg was associated with increased cardiovascular mortality (adjusted hazard ratio [HR] 1.91, 95% confidence interval [CI] = 1.19 to 3.07) and all-cause mortality (adjusted HR 1.44, 95% CI = 1.15 to 1.79). Within the subgroup of 764 participants who had hypertension, IADs of ≥5 mmHg or ≥10 mmHg were associated with both cardiovascular mortality (adjusted HR 2.63, 95% CI = 0.97 to 7.02, and adjusted HR 2.96, 95% CI = 1.27 to 6.88, respectively) and all-cause mortality (adjusted HR 1.67, 95% CI = 1.05 to 2.66, and adjusted HR 1.63, 95% CI = 1.06 to 2.50, respectively). IADs ≥15 mmHg were not associated with survival differences in this population.Conclusion: Systolic IADs in blood pressure are associated with increased risk of cardiovascular events, including mortality, in a large cohort of people free of pre-existing vascular disease. [ABSTRACT FROM AUTHOR]

Introduction: Economically disadvantaged smokers not intending to stop may benefit from interventions aimed at reducing their smoking. This study assessed the effects of a behavioral intervention promoting an increase in physical activity versus usual care in a pilot randomized controlled trial.Methods: Disadvantaged smokers who wanted to reduce but not quit were randomized to either a counseling intervention of up to 12 weeks to support smoking reduction and increased physical activity (n = 49) or usual care (n = 50). Data at 16 weeks were collected for various smoking and physical activity outcomes. Primary analyses consisted of an intention to treat analysis based on complete case data. Secondary analyses explored the impact of handling missing data.Results: Compared with controls, intervention smokers were more likely to initiate a quit attempt (36 vs. 10%; odds ratio 5.05, [95% CI: 1.10; 23.15]), and a greater proportion achieved at least 50% reduction in cigarettes smoked (63 vs. 32%; 4.21 [1.32; 13.39]). Postquit abstinence measured by exhaled carbon monoxide at 4-week follow-up showed promising differences between groups (23% vs. 6%; 4.91 [0.80; 30.24]). No benefit of intervention on physical activity was found. Secondary analyses suggested that the standard missing data assumption of "missing" being equivalent to "smoking" may be conservative resulting in a reduced intervention effect.Conclusions: A smoking reduction intervention for economically disadvantaged smokers which involved personal support to increase physical activity appears to be more effective than usual care in achieving reduction and may promote cessation. The effect does not appear to be influenced by an increase in physical activity. [ABSTRACT FROM AUTHOR]

Background: Around 17% of people eligible for UK cardiac rehabilitation programmes following an acute coronary syndrome report moderate or severe depressive symptoms. While maximising psychological health is a core goal of cardiac rehabilitation, psychological care can be fragmented and patchy. This study tests the feasibility and acceptability of embedding enhanced psychological care, composed of two management strategies of proven effectiveness in other settings (nurse-led mental health care coordination and behavioural activation), within the cardiac rehabilitation care pathway.Methods/design: This study tests the uncertainties associated with a large-scale evaluation by conducting an external pilot trial with a nested qualitative study. We aim to recruit and randomise eight comprehensive cardiac rehabilitation teams (clusters) to intervention (embedding enhanced psychological care into routine cardiac rehabilitation programmes) or control (routine cardiac rehabilitation programmes alone) arms. Up to 64 patients (eight per team) identified with depressive symptoms upon initial assessment by the cardiac rehabilitation team will be recruited, and study measures will be administered at baseline (before starting rehabilitation) and at 5 months and 8 months post baseline. Outcomes include depressive symptoms, cardiac mortality and morbidity, anxiety, health-related quality of life and service resource use. Trial data on cardiac team and patient recruitment, and the retention and flow of patients through treatment will be used to assess intervention feasibility and acceptability. Qualitative interviews will be undertaken to explore trial participants' and cardiac rehabilitation nurses' views and experiences of the trial methods and intervention, and to identify reasons why patients declined to take part in the trial. Outcome data will inform a sample size calculation for a definitive trial.Discussion: The pilot trial and qualitative study will inform the design of a fully powered cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of the provision of enhanced psychological care within cardiac rehabilitation programmes.Trial Registration: ISRCTN34701576 (Registered 29 May 2014). [ABSTRACT FROM AUTHOR]

The article discusses an overview of systematic reviews of cardiac rehabilitation (CR) done by the medical research organization Cochrane Collaboration across several randomised controlled trials. Topics include findings of six Cochrane reviews of CR including exercise-based CR and psychological and education-based interventions, revealing a reduction in hospital admissions due to exercise-based CR, and limitations of the overview including the heterogeneity of populations and interventions.

Background: Depression is associated with physical inactivity, which may mediate the relationship between depression and a range of chronic physical health conditions. However, few interventions have combined a psychological intervention for depression with behaviour change techniques, such as behavioural activation (BA), to promote increased physical activity. Methods: To determine procedural and clinical uncertainties to inform a definitive randomised controlled trial (RCT), a pilot parallel-group RCT was undertaken within two Improving Access to Psychological Therapies (IAPT) services in South West England. We aimed to recruit 80 adults with depression and randomise them to a supported, written self-help programme based on either BA or BA plus physical activity promotion (BAcPAc). Data were collected at baseline and 4 months post-randomisation to evaluate trial retention, intervention uptake and variance in outcomes to inform a sample size calculation. Qualitative data were collected from participants and psychological wellbeing practitioners (PWPs) to assess the acceptability and feasibility of the trial methods and the intervention. Routine data were collected to evaluate resource use and cost. Results: Sixty people with depression were recruited, and a 73 % follow-up rate was achieved. Accelerometer physical activity data were collected for 64 % of those followed. Twenty participants (33 %) attended at least one treatment appointment. Interview data were analysed for 15 participants and 9 study PWPs. The study highlighted the challenges of conducting an RCT within existing IAPT services with high staff turnover and absences, participant scheduling issues, PWP and participant preferences for cognitive focussed treatment, and deviations from BA delivery protocols. The BAcPAc intervention was generally acceptable to patients and PWPs. Conclusions: Although recruitment procedures and data collection were challenging, participants generally engaged with the BAcPAc self-help booklets and reported willingness to increase their physical activity. A number of feasibility issues were identified, in particular the under-use of BA as a treatment for depression, the difficulty that PWPs had in adapting their existing procedures for study purposes and the instability of the IAPT PWP workforce. These problems would need to be better understood and resolved before proceeding to a full-scale RCT. [ABSTRACT FROM AUTHOR]

Background: Telephone triage represents one strategy to manage demand for face-to-face GP appointments in primary care. However, limited evidence exists of the challenges GP practices face in implementing telephone triage. We conducted a qualitative process evaluation alongside a UK-based cluster randomised trial (ESTEEM) which compared the impact of GP-led and nurse-led telephone triage with usual care on primary care workload, cost, patient experience, and safety for patients requesting a same-day GP consultation. The aim of the process study was to provide insights into the observed effects of the ESTEEM trial from the perspectives of staff and patients, and to specify the circumstances under which triage is likely to be successfully implemented. Here we report perspectives of staff. Methods: The intervention comprised implementation of either GP-led or nurse-led telephone triage for a period of 2-3 months. A qualitative evaluation was conducted using staff interviews recruited from eight general practices (4 GP triage, 4 Nurse triage) in the UK, implementing triage as part of the ESTEEM trial. Qualitative interviews were undertaken with 44 staff members in GP triage and nurse triage practices (16 GPs, 8 nurses, 7 practice managers, 13 administrative staff). Results: Staff reported diverse experiences and perceptions regarding the implementation of telephone triage, its effects on workload, and on the benefits of triage. Such diversity were explained by the different ways triage was organised, the staffing models used to support triage, how the introduction of triage was communicated across practice staff, and by how staff roles were reconfigured as a result of implementing triage. Conclusion: The findings from the process evaluation offer insight into the range of ways GP practices participating in ESTEEM implemented telephone triage, and the circumstances under which telephone triage can be successfully implemented beyond the context of a clinical trial. Staff experiences and perceptions of telephone triage are shaped by the way practices communicate with staff, prepare for and sustain the changes required to implement triage effectively, as well as by existing practice culture, and staff and patient behaviour arising in response to the changes made. [ABSTRACT FROM AUTHOR]

Background Challenges remain to find ways to support patients with depression who have low levels of physical activity (PA) to overcome perceived barriers and enhance the perceived value of PA for preventing future relapse. There is an evidence-base for behavioural activation (BA) for depression, which focuses on supporting patients to restore activities that have been avoided, but practitioners have no specific training in promoting PA. We aimed to design and evaluate an integrated BA and PA (BAcPAc) practitioner-led, written, self-help intervention to enhance both physical and mental health. Methods/design This study is informed by the Medical Research Council Complex Intervention Framework and describes a protocol for a pilot phase II randomised controlled trial (RCT) to test the feasibility and acceptability of the trial methods to inform a definitive phase III RCT. Following development of the augmented written self-help intervention (BAcPAc) incorporating behavioural activation with physical activity promotion, depressed adults are randomised to receive up to 12 sessions over a maximum of 4 months of either BAcPAc or behavioural activation alone within a written self-help format, which represents treatment as usual. The study is located within two 'Improving Access to Psychological Therapies' services in South West England, with both written self-help interventions supported by mental health paraprofessionals. Measures assessed at 4, 9, and 12 month follow-up include the following: CIS-R, PHQ-9, accelerometer recorded (4 months only) and self-reported PA, body mass index, blood pressure, Insomnia Severity Index, quality of life, and health and social care service use. Process evaluation will include analysis of recorded support sessions and patient and practitioner interviews. At the time of writing the study has recruited 60 patients. Discussion The feasibility outcomes will inform a definitive RCT to assess the clinical- and cost-effectiveness of the augmented BAcPAc written self-help intervention to reduce depression and depressive relapse, and bring about improvements across a range of physical health outcomes. [ABSTRACT FROM AUTHOR]

Background Cognitive behaviour therapy (CBT) is an effective treatment for depression. However, CBT is a complex therapy that requires highly trained and qualified practitioners, and its scalability is therefore limited by the costs of training and employing sufficient therapists to meet demand. Behavioural activation (BA) is a psychological treatment for depression that may be an effective alternative to CBT and, because it is simpler, might also be delivered by less highly trained and specialised mental health workers. Methods COBRA is a two-arm, non-inferiority, patient-level randomised controlled trial, including clinical, economic, and process evaluations comparing CBT delivered by highly trained professional therapists to BA delivered by junior professional or para-professional mental health workers to establish whether the clinical effectiveness of BA is non-inferior to CBT and if BA is cost effective compared to CBT. Four hundred and forty patients with major depressive disorder will be recruited through screening in primary care. We will analyse for non-inferiority in per-protocol and intention-to-treat populations. Our primary outcome will be severity of depression symptoms (Patient Health Questionnaire-9) at 12 months follow-up. Secondary outcomes will be clinically significant change and severity of depression at 18 months, and anxiety (General Anxiety Disorder-7 questionnaire) and health-related quality of life (Short-Form Health Survey-36) at 12 and 18 months. Our economic evaluation will take the United Kingdom National Health Service/Personal Social Services perspective to include costs of the interventions, health and social care services used, plus productivity losses. Costeffectiveness will explored in terms of quality-adjusted life years using the EuroQol-5D measure of health-related quality of life. Discussion The clinical and economic outcomes of this trial will provide the evidence to help policy makers, clinicians and guideline developers decide on the merits of including BA as a firstline treatment of depression. Trial registration Current Controlled Trials ISRCTN27473954. [ABSTRACT FROM AUTHOR]

Background: Chronic radicular pain can be effectively treated with spinal cord stimulation, but this therapy is not always sufficient for chronic back pain. Subcutaneous nerve stimulation (SQS) refers to the placement of percutaneous leads in the subcutaneous tissue within the area of pain. Case series data show that failed back surgery syndrome (FBSS) patients experience clinically important levels of pain relief following SQS and may also reduce their levels of analgesic therapy and experience functional well-being. However, to date, there is no randomized controlled trial evidence to support the use of SQS in FBSS. Methods/Design: The SubQStim study is a multicenter randomized controlled trial comparing SQS plus optimized medical management ('SQS arm') versus optimized medical management alone ('OMM arm') in patients with predominant back pain due to FBSS. Up to 400 patients will be recruited from approximately 33 centers in Europe and Australia and will be randomized 1:1 to the SQS or OMM arms. After 9 months, patients who fail to reach the primary outcome will be allowed to switch treatments. Patients will be evaluated at baseline (prior to randomization) and at 1, 3, 6, 9, 12, 18, 24, and 36 months after randomization. The primary outcome is the proportion of patients at 9 months with a ⩾50% reduction in back pain intensity compared to baseline. The secondary outcomes are: back and leg pain intensity score, functional disability, health-related quality of life, patient satisfaction, patient global impression of change, healthcare resource utilization/costs, cost-effectiveness analysis and adverse events. Outcomes arms will be compared between SQS and OMM arms at all evaluation points up to and including 9 months. After the 9-month assessment visit, the main analytic focus will be to compare within patient changes in outcomes relative to baseline. Discussion: The SubQStim trial began patient recruitment in November 2012. Recruitment is expected to close in late 2014. Trial registration: ClinicalTrials.gov NCT01711619 [ABSTRACT FROM AUTHOR]

Background: The RASCAL (Refractory Angina Spinal Cord stimulation and usuAL care) pilot study seeks to assess the feasibility of a definitive trial to assess if addition of spinal cord stimulation (SCS) to usual care is clinically superior and more cost-effective than usual care alone in patients with refractory angina. Methods/design: This is an external pilot, patient-randomized controlled trial. The study will take place at three centers in the United Kingdom - South Tees Hospitals NHS Foundation Trust (The James Cook University Hospital), Dudley Group of Hospitals NHS Foundation Trust, and Basildon and Thurrock University Hospitals NHS Foundation Trust. The subjects will be 45 adults with refractory angina, that is, limiting angina despite optimal anti-angina therapy, Canadian Cardiovascular Society Functional Classification Class III and IV, angiographically documented coronary artery disease not suitable for revascularization, satisfactory multidisciplinary assessment and demonstrable ischemia on functional testing. The study will be stratified by center, age and Canadian Cardiovascular Society Functional Classification. Interventions will involve spinal cord stimulation plus usual care ('SCS group') or usual care alone ('UC group'). Usual care received by both groups will include consideration of an education session with a pain consultant, trial of a transcutaneous electrical neurostimulation, serial thoracic sympathectomy and oral/systemic analgesics. Expected outcomes will be recruitment and retention rates; reasons for agreeing/declining participation; variability in primary and secondary outcomes (to inform power calculations for a definitive trial); and completion rates of outcome measures. Trial patient-related outcomes include disease-specific and generic health-related quality of life, angina exercise capacity, intake of angina medications, frequency of angina attacks, complications and adverse events, and satisfaction. Discussion: The RASCAL pilot trial seeks to determine the feasibility and design of a definitive randomized controlled trial comparing the addition of spinal cord stimulation to usual care versus usual care alone for patients with refractory angina. Fifteen patients have been recruited since recruitment opened in October 2011. The trial was originally scheduled to end in April 2013 but due to slow recruitment may have to be extended to late 2013. [ABSTRACT FROM AUTHOR]

BackgroundAlthough meta-analyses of randomized controlled trials (RCTs) of salt reduction report a reduction in the level of blood pressure (BP), the effect of reduced dietary salt on cardiovascular disease (CVD) events remains unclear.MethodsWe searched for RCTs with follow-up of at least 6 months that compared dietary salt reduction (restricted salt dietary intervention or advice to reduce salt intake) to control/no intervention in adults, and reported mortality or CVD morbidity data. Outcomes were pooled at end of trial or longest follow-up point.ResultsSeven studies were identified: three in normotensives, two in hypertensives, one in a mixed population of normo- and hypertensives and one in heart failure. Salt reduction was associated with reductions in urinary salt excretion of between 27 and 39 mmol/24 h and reductions in systolic BP between 1 and 4 mm Hg. Relative risks (RRs) for all-cause mortality in normotensives (longest follow-up-RR: 0.90, 95% confidence interval (CI): 0.58-1.40, 79 deaths) and hypertensives (longest follow-up RR 0.96, 0.83-1.11, 565 deaths) showed no strong evidence of any effect of salt reduction CVD morbidity in people with normal BP (longest follow-up: RR 0.71, 0.42-1.20, 200 events) and raised BP at baseline (end of trial: RR 0.84, 0.57-1.23, 93 events) also showed no strong evidence of benefit. Salt restriction increased the risk of all-cause mortality in those with heart failure (end of trial RR 2.59, 1.04-6.44, 21 deaths).We found no information on participant's health-related quality of life.ConclusionsDespite collating more event data than previous systematic reviews of RCTs (665 deaths in some 6,250 participants) there is still insufficient power to exclude clinically important effects of reduced dietary salt on mortality or CVD morbidity. Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small BP reduction achieved.A more detailed review has been published and will be updated in the Cochrane Database of Systematic Reviews [Taylor RS, Ashton KE, Moxham T, Hooper L, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease. Cochrane Database of Systematic Reviews (CDSR) 2011, Issue 7 (see www.thecochranelibrary.com for information). This is a version of a Cochrane review, which is available in The Cochrane Library. Cochrane systematic reviews are regularly updated to include new research, and in response to feedback from readers. The results of a Cochrane review can be interpreted differently, depending on people's perspectives and circumstances. Please consider the conclusions presented carefully. They are the opinions of review authors, and are not necessarily shared by The Cochrane Collaboration.American Journal of Hypertension (2011). doi:10.1038/ajh.2011.115 [ABSTRACT FROM AUTHOR]

Aims: Supervised exercise can benefit selected patients with heart failure, however the effectiveness of home-based exercise remains uncertain. We aimed to assess the effectiveness of a home-based exercise programme in addition to specialist heart failure nurse care. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Chronic back and leg pain conditions result in patients’ loss of function, reduced quality of life and increased costs to the society. Aims: To assess health-related quality of life (HRQoL) and cost implications of spinal cord stimulation plus non-surgical conventional medical management (SCS group) versus non-surgical conventional medical management alone (CMM group) in the management of neuropathic pain in patients with failed back surgery syndrome. Methods: A total of 100 patients were randomised to either the SCS or CMM group. Healthcare resource consumption data relating to screening, the use of the implantable generator in SCS patients, hospital stay, and drug and non-drug pain-related treatment were collected prospectively. Resource consumption was costed using UK and Canadian 2005–2006 national figures. HRQoL was assessed using the EuroQol-5D (EQ-5D) questionnaire. Costs and outcomes were assessed for each patient over their first 6-months of the trial. Results: The 6-month mean total healthcare cost in the SCS group (CAN$19,486; €12,653) was significantly higher than in the CMM group (CAN$3994; €2594), with a mean adjusted difference of CAN$15, 395 (€9997) (p <0.001). However, the gain in HRQoL with SCS over the same period of time was markedly greater in the SCS group, with a mean EQ-5D score difference of 0.25 [p <0.001] and 0.21 [p <0.001], respectively at 3- and 6-months after adjusting for baseline variables. Conclusions: The addition of SCS to CMM in patients with neuropathic leg and back pain results in higher costs to health systems but also generates important improvements in patients’ EQ-5D over the same period. [Copyright &y& Elsevier]

People receiving a renal transplant require long-term treatment with immunosuppressant drugs. Contemporary regimens usually include a calcineurin inhibitor (CI), either ciclosporin or tacrolimus, in conjunction with at least one other drug. The aim of this study was to review the economic literature relating to the choice of CIs in patients following renal transplantation, with the specific intention of highlighting the challenges in estimating their cost effectiveness. A systematic literature search and narrative analysis was carried out, and 12 studies of varying quality and complexity were reviewed. All of the studies compared ciclosporin, azathioprine and a corticosteroid (CAS) with tacrolimus, azathioprine and a corticosteroid (TAS) but only three also evaluated the costs and effects of other possible treatment regimens. A variety of different evaluative frameworks were employed, from single randomised controlled trial-based studies over relatively short-time periods (6 months) to more complex Bayesian modelling techniques. The studies were broadly consistent in concluding that TAS was more effective than CAS in terms of reducing the rate of acute rejection episodes. Of the studies that undertook decision modelling, all but one estimated that TAS was associated with better graft-related outcomes such as rejection-free life-years, patient-survival and QALYs. Six of the studies concluded that the healthcare costs associated with TAS were lower than those for CAS. A seventh study suggested that TAS was the least costly option if costs were considered over a relatively long time period (14 years). Only one study clearly concluded that CAS was more cost effective than TAS. Clinical evidence clearly shows that TAS is more effective than CAS in terms of reducing the incidence of acute rejection following renal transplantation. The majority of published economic evaluations suggest that TAS is also the more cost-effective option. However, the economic evaluations contained a number of methodological limitations, undermining the confidence that can be attached to their results. Future economic evaluations of the CIs, and immunosuppressants in general, should address these issues in order to produce more robust cost-effectiveness estimates. Most importantly, they should evaluate a wider range of potential treatment options. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To review the clinical and cost-effectiveness of spinal cord stimulation (SCS) in the management of patients with complex regional pain syndrome (CRPS) and identify the potential predictors of SCS outcome. Design: Systematic review of the literature and meta-regression. Methods: Electronic databases were searched for controlled and uncontrolled studies and economic evaluations relating to the use of SCS in patients with either CRPS type I or II. Results: One randomised controlled trial, 25 case series and one cost-effectiveness study were included. In the randomised controlled trial in type I CRPS patients, SCS therapy lead to a reduction in pain intensity at 24 months of follow-up (mean change in VAS score −2.0), whereas pain was unchanged in the control group (mean change in VAS score 0.0) (p <0.001). In the case series studies, 67% (95% CI 51%, 84%) of type I and type II CRPS patients implanted with SCS reported pain relief of at least 50% over a median follow-up period of 33 months. No statistically significant predictors of pain relief with SCS were observed in multivariate meta-regression analysis across studies. An economic analysis based on the randomised controlled trial showed a lifetime cost saving of approximately €58,470 (US$60,800) with SCS plus physical therapy compared with physical therapy alone. The mean cost per quality-adjusted life-year at 12-month follow-up was €22,580 (US$23,480). Conclusions: SCS appears to be an effective therapy in the management of patients with CRPS type I (Level A evidence) and type II (Level D evidence). Moreover, there is evidence to demonstrate that SCS is a cost-effective treatment for CRPS type I. [Copyright &y& Elsevier]

Background: Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. Methods: Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. Participants: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Data collected: exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. Results: Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p < 0.001). This difference in eligibility was primarily due to exclusion on the basis of language (i.e. the inability to speak English or Punjabi). Of those eligible, similar proportions were recruited from the different ethnic groups (white, South Asian and other). There was a marked difference in eligibility between people of Indian, Pakistani or Bangladeshi origin. Conclusion: Once eligible for this trial, people from different ethnic groups were recruited in similar proportions. The reason for ineligibility in the BRUM study was the inability to support the range of minority languages. [ABSTRACT FROM AUTHOR]

Introduction: Critical appraisal skills are believed to play a central role in an evidence-based approach to health practice. The aim of this study was to evaluate the effectiveness and costs of a critical appraisal skills educational intervention aimed at health care professionals. Methods: This prospective controlled trial randomized 145 self-selected general practitioners, hospital physicians, professions allied to medicine, and healthcare managers/administrators from the South West of England to a half-day critical appraisal skills training workshop (based on the model of problem-based small group learning) or waiting list control. The following outcomes were assessed at 6-months follow up: knowledge of the principles necessary for appraising evidence; attitudes towards the use of evidence about healthcare; evidence seeking behaviour; perceived confidence in appraising evidence; and ability to critically appraise a systematic review article. Results: At follow up overall knowledge score [mean difference: 2.6 (95% CI: 0.6 to 4.6)] and ability to appraise the results of a systematic review [mean difference: 1.2 (95% CI: 0.01 to 2.4)] were higher in the critical skills training group compared to control. No statistical significant differences in overall attitude towards evidence, evidence seeking behaviour, perceived confidence, and other areas of critical appraisal skills ability (methodology or generalizability) were observed between groups. Taking into account the workshop provision costs and costs of participants time and expenses of participants, the average cost of providing the critical appraisal workshops was approximately £250 per person. Conclusions: The findings of this study challenge the policy of funding 'one-off' educational interventions aimed at enhancing the evidence-based practice of health care professionals. Future evaluations of evidence-based practice interventions need to take in account this trial's negative findings and methodological difficulties. [ABSTRACT FROM AUTHOR]

Background: Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising because of an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post-surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesize that a comprehensive cardiac rehabilitation program can improve physical capacity and self-assessed mental health and reduce hospitalization and healthcare costs after heart valve surgery. Methods: This randomized clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients 1:1 to an intervention or a control group, using central randomization, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise and a psycho-educational intervention comprising five consultations. The primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. The secondary outcome is self-assessed mental health measured by the standardized questionnaire Short Form-36. Long-term healthcare utilization and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design will be used to evaluate qualitative and quantitative findings, encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. Conclusion: This randomized clinical trial will contribute with evidence of whether cardiac rehabilitation should be provided after heart valve surgery. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). [ABSTRACT FROM AUTHOR]

Objective: This two-site randomised trial compared the effectiveness of a voluntary sector-led, community-based diabetes prevention programme to a waiting-list control group at 6 months, and included an observational follow-up of the intervention arm to 12 months. Methods: Adults aged 18–75 years at increased risk of developing type 2 diabetes due to elevated blood glucose and being overweight were recruited from primary care practices at two UK sites, with data collected in participants' homes or community venues. Participants were randomised using an online central allocation service. The intervention, comprising the prototype "Living Well, Taking Control" (LWTC) programme, involved four weekly two-hour group sessions held in local community venues to promote changes in diet and physical activity, plus planned follow-up contacts at two, three, six, nine and 12 months alongside 5 hours of additional activities/classes. Waiting list controls received usual care for 6 months before accessing the programme. The primary outcome was weight loss at 6 months. Secondary outcomes included glycated haemoglobin (HbA1c), blood pressure, physical activity, diet, health status and well-being. Only researchers conducting analyses were blinded. Results: The target sample of 314 participants (157 each arm) was largely representative of local populations, including 44% men, 26% from ethnic minorities and 33% living in deprived areas. Primary outcome data were available for 285 (91%) participants (141 intervention, 144 control). Between baseline and 6 months, intervention participants on average lost more weight than controls (− 1.7 kg, 95% CI − 2.59 to − 0.85). Higher attendance was associated with greater weight loss (− 3.0 kg, 95% CI − 4.5 to − 1.5). The prototype LWTC programme more than doubled the proportion of participants losing > 5% of their body weight (21% intervention vs. 8% control, OR 2.83, 95% CI 1.36 to 5.90) and improved self-reported dietary behaviour and health status. There were no impacts on HbA1c, blood pressure, physical activity and well-being at 6 months and, amongst intervention participants, few further changes from six to 12-months (e.g. average weight re-gain 0.36 kg, 95% CI − 0.20 to 0.91). There were no serious adverse events but four exercise-related injuries were reported in the intervention arm. Conclusions: This voluntary sector-led diabetes prevention programme reached a broad spectrum of the population and had modest effects on weight-related outcomes, but limited impacts on other diabetes risk factors. Trial registration: Trial registration number: ISRCTN70221670, 5 September 2014 Funder (National Institute for Health Research School for Public Health Research) project reference number: SPHR-EXE-PES-COM. [ABSTRACT FROM AUTHOR]

Objectives: Transcatheter aortic valve implantation (TAVI) is often undertaken in the oldest frailest cohort of patients undergoing cardiac interventions. We plan to investigate the potential benefit of cardiac rehabilitation (CR) in this vulnerable population. Design: We undertook a pilot randomised trial of CR following TAVI to inform the feasibility and design of a future randomised clinical trial (RCT). Participants: We screened patients undergoing TAVI at a single institution between June 2016 and February 2017. Interventions: Participants were randomised post-TAVI to standard of care (control group) or standard of care plus exercise-based CR (intervention group). Outcomes: We assessed recruitment and attrition rates, uptake of CR, and explored changes in 6-min walk test, Nottingham Activities of Daily Living, Fried and Edmonton Frailty scores and Hospital Anxiety and Depression Score, from baseline (30 days post TAVI) to 3 and 6 months post randomisation. We also undertook a parallel study to assess the use of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the post-TAVI population. Results: Of 82 patients screened, 52 met the inclusion criteria and 27 were recruited (3 patients/month). In the intervention group, 10/13 (77%) completed the prescribed course of 6 sessions of CR (mean number of sessions attended 7.5, SD 4.25) over 6 weeks. At 6 months, all participants were retained for follow-up. There was apparent improvement in outcome scores at 3 and 6 months in control and CR groups. There were no recorded adverse events associated with the intervention of CR. The KCCQ was well accepted in 38 post-TAVI patients: mean summary score 72.6 (SD 22.6). Conclusions: We have demonstrated the feasibility of recruiting post-TAVI patients into a randomised trial of CR. We will use the findings of this pilot trial to design a fully powered multicentre RCT to inform the provision of CR and support guideline development to optimise health-related quality of life outcomes in this vulnerable population. Retrospectively registered 3rd October 2016 clinicaltrials.govNCT02921880. Trial registration: Clinicaltrials.Gov identifier NCT02921880 [ABSTRACT FROM AUTHOR]

The article discusses a randomised trial in London, England, which investigated the effect of adding five-element acupuncture to usual care for people who attend frequently with medically unexplained physical symptoms (MUPS). It notes that the addition of five-element acupuncture to usual care has a significant and sustained benefit for frequent attenders with MUPS. Improved wellbeing and individualised health status were also noted after the addition of five-element acupuncture consultations.

An abstract of the article "Treatment effect bias in randomised controlled trials using surrogate outcomes: a preliminary cohort study analysis," by Oriana Ciani and colleagues, is presented.

The article focuses on the study of whether treatment effects of randomised controlled trials in surrogate primary outcomes are different from final patient relevant primary outcomes or not. It is mentioned that advantage of surrogate outcomes are its short duration and size which reduces the cost of trials. It is concluded that surrogate primary outcomes trial are more likely to report larger treatment effects than trials reporting final patient relevant outcomes.

The article discusses a study which examined the effectiveness of interventions led by nurses in improving control of blood pressure in hypertensive people in Great Britain. Randomised controlled trials that compared any intervention intended to improve blood pressure delivered by nurses were identified by the authors. Based on the results of the systematic review and meta-analysis conducted, the authors supported structured algorithm driven care of hypertension provided by nurses and nurse prescribers.

Abstract: Spinal cord stimulation (SCS) has been suggested as a treatment option for patients with painful diabetic neuropathy (PDN). We conducted a systematic review and undertook a meta-analysis on individual patient data from randomised controlled trials (RCTs) to assess the effectiveness of SCS for the management of PDN. Electronic databases were searched from inception to May 2020 for RCTs of SCS for PDN. Searches identified 2 eligible RCTs (total of 93 patients with PDN) and 2 long-term follow-up studies of one of the RCTs. Individual patient data were obtained from the authors of one of these RCTs. Meta-analysis showed significant and clinically meaningful reductions in pain intensity for SCS compared with best medical therapy alone, pooled mean difference (MD) -3.13 (95% confidence interval [CI]: -4.19 to -2.08) on a 10-point scale at the 6-month follow-up. More patients receiving SCS achieved at least a 50% reduction in pain intensity compared with best medical therapy, pooled risk ratio 0.08 (95% CI: 0.02-0.38). Increases were observed for health-related quality of life assessed as EQ-5D utility score (pooled MD 0.16, 95% CI: 0.02-0.30) and visual analogue scale (pooled MD 11.21, 95% CI: 2.26-20.16). Our findings demonstrate that SCS is an effective therapeutic adjunct to best medical therapy in reducing pain intensity and improving health-related quality of life in patients with PDN. Large well-reported RCTs with long-term follow-up are required to confirm these results. [ABSTRACT FROM AUTHOR]

Abstract: Spinal cord stimulation (SCS) is an interventional nonpharmacologic treatment used for chronic pain and other indications. Methods for evaluating the safety and efficacy of SCS have evolved from uncontrolled and retrospective studies to prospective randomized controlled trials (RCTs). Although randomization overcomes certain types of bias, additional challenges to the validity of RCTs of SCS include blinding, choice of control groups, nonspecific effects of treatment variables (eg, paresthesia, device programming and recharging, psychological support, and rehabilitative techniques), and safety considerations. To address these challenges, 3 professional societies (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials, Institute of Neuromodulation, and International Neuromodulation Society) convened a meeting to develop consensus recommendations on the design, conduct, analysis, and interpretation of RCTs of SCS for chronic pain. This article summarizes the results of this meeting. Highlights of our recommendations include disclosing all funding source and potential conflicts; incorporating mechanistic objectives when possible; avoiding noninferiority designs without internal demonstration of assay sensitivity; achieving and documenting double-blinding whenever possible; documenting investigator and site experience; keeping all information provided to patients balanced with respect to expectation of benefit; disclosing all information provided to patients, including verbal scripts; using placebo/sham controls when possible; capturing a complete set of outcome assessments; accounting for ancillary pharmacologic and nonpharmacologic treatments in a clear manner; providing a complete description of intended and actual programming interactions; making a prospective ascertainment of SCS-specific safety outcomes; training patients and researchers on appropriate expectations, outcome assessments, and other key aspects of study performance; and providing transparent and complete reporting of results according to applicable reporting guidelines. [ABSTRACT FROM AUTHOR]

Spinal cord stimulation (SCS) is an established treatment of chronic neuropathic pain. Although a temporary SCS screening trial is widely used to determine whether a patient should receive permanent SCS implant, its evidence base is limited. We aimed to establish the clinical utility, diagnostic accuracy, and cost-effectiveness of an SCS screening trial. A multicentre single-blind, parallel two-group randomised controlled superiority trial was undertaken at 3 centres in the United Kingdom. Patients were randomised 1:1 to either SCS screening trial strategy (TG) or no trial screening strategy (NTG). Treatment was open label, but outcome assessors were masked. The primary outcome measure was numerical rating scale (NRS) pain at 6-month follow-up. Between June 2017 and September 2018, 105 participants were enrolled and randomised (TG = 54, NTG = 51). Mean numerical rating scale pain decreased from 7.47 at baseline (before SCS implantation) to 4.28 at 6 months in TG and from 7.54 to 4.49 in NTG (mean group difference: 0.2, 95% confidence interval [CI]: -1.2 to 0.9, P = 0.89). We found no difference between TG and NTG in the proportion of pain responders or other secondary outcomes. Spinal cord stimulation screening trial had a sensitivity of 100% (95% CI: 78-100) and specificity of 8% (95% CI: 1-25). The mean incremental cost-effectiveness ratio of TG vs NTG was £78,895 per additional quality-adjusted life-year gained. In conclusion, although the SCS screening trial may have some diagnostic utility, there was no evidence that an SCS screening TG provides superior patient outcomes or is cost-effective compared to a no trial screening approach. [ABSTRACT FROM AUTHOR]

Background Despite proven benefits of cardiac rehabilitation (CR), adherence to CR remains suboptimal. This trial aimed to assess the impact of the patient education ‘Learning and Coping Strategies’ (LC) on patient adherence to an eight-week CR program. Methods 825 patients with ischaemic heart disease or heart failure were open label randomised to either the LC arm (LC plus CR) or the control arm (CR alone) across three hospital units in Denmark. Both arms received same amount of training and education hours. LC consisted of individual clarifying interviews, participation of experienced patients as co-educators, situational, reflective and inductive teaching. The control arm received structured deductive teaching. The primary outcomes were patient adherence to at least 75% of the exercise training or education sessions. We tested for subgroup effects on the primary outcomes using interaction terms. The primary outcomes were compared across arms using logistic regression. Results More patients in the LC arm adhered to at least 75% of the exercise training sessions than control (80% versus 73%, adjusted odds ratio (OR):1.48; 95% CI:1.07 to 2.05, P = 0.018) and 75% of education sessions (79% versus 70%, adjusted OR:1.61, 1.17 to 2.22, P = 0.003). Some evidence of larger effects of LC on adherence was seen for patients with heart failure, low education and household income. Conclusions Addition of LC strategies improved adherence in rehabilitation both in terms of exercise training and education. Patients with heart failure, low levels of education and household income appear to benefit most from this adherence promoting intervention. Trial registration www.clinicaltrials.gov identifier NCT01668394 [ABSTRACT FROM AUTHOR]

Background Depression is a common, debilitating, and costly disorder. Many patients request psychological therapy, but the best-evidenced therapy—cognitive behavioural therapy (CBT)—is complex and costly. A simpler therapy—behavioural activation (BA)—might be as effective and cheaper than is CBT. We aimed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression. Methods In this randomised, controlled, non-inferiority trial, we recruited adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder from primary care and psychological therapy services in Devon, Durham, and Leeds (UK). We excluded people who were receiving psychological therapy, were alcohol or drug dependent, were acutely suicidal or had attempted suicide in the previous 2 months, or were cognitively impaired, or who had bipolar disorder or psychosis or psychotic symptoms. We randomly assigned participants (1:1) remotely using computer-generated allocation (minimisation used; stratified by depression severity [Patient Health Questionnaire 9 (PHQ-9) score of <19 vs ≥19], antidepressant use, and recruitment site) to BA from junior mental health workers or CBT from psychological therapists. Randomisation done at the Peninsula Clinical Trials Unit was concealed from investigators. Treatment was given open label, but outcome assessors were masked. The primary outcome was depression symptoms according to the PHQ-9 at 12 months. We analysed all those who were randomly allocated and had complete data (modified intention to treat [mITT]) and also all those who were randomly allocated, had complete data, and received at least eight treatment sessions (per protocol [PP]). We analysed safety in the mITT population. The non-inferiority margin was 1·9 PHQ-9 points. This trial is registered with the ISCRTN registry, number ISRCTN27473954. Findings Between Sept 26, 2012, and April 3, 2014, we randomly allocated 221 (50%) participants to BA and 219 (50%) to CBT. 175 (79%) participants were assessable for the primary outcome in the mITT population in the BA group compared with 189 (86%) in the CBT group, whereas 135 (61%) were assessable in the PP population in the BA group compared with 151 (69%) in the CBT group. BA was non-inferior to CBT (mITT: CBT 8·4 PHQ-9 points [SD 7·5], BA 8·4 PHQ-9 points [7·0], mean difference 0·1 PHQ-9 points [95% CI −1·3 to 1·5], p=0·89; PP: CBT 7·9 PHQ-9 points [7·3]; BA 7·8 [6·5], mean difference 0·0 PHQ-9 points [–1·5 to 1·6], p=0·99). Two (1%) non-trial-related deaths (one [1%] multidrug toxicity in the BA group and one [1%] cancer in the CBT group) and 15 depression-related, but not treatment-related, serious adverse events (three in the BA group and 12 in the CBT group) occurred in three [2%] participants in the BA group (two [1%] patients who overdosed and one [1%] who self-harmed) and eight (4%) participants in the CBT group (seven [4%] who overdosed and one [1%] who self-harmed). Interpretation We found that BA, a simpler psychological treatment than CBT, can be delivered by junior mental health workers with less intensive and costly training, with no lesser effect than CBT. Effective psychological therapy for depression can be delivered without the need for costly and highly trained professionals. [ABSTRACT FROM AUTHOR]

Background: Although recommended in guidelines for the management of coronary heart disease (CHD), concerns have been raised about the applicability of evidence from existing meta-analyses of exercise-based cardiac rehabilitation (CR).Objectives: The goal of this study is to update the Cochrane systematic review and meta-analysis of exercise-based CR for CHD.Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and Science Citation Index Expanded were searched to July 2014. Retrieved papers, systematic reviews, and trial registries were hand-searched. We included randomized controlled trials with at least 6 months of follow-up, comparing CR to no-exercise controls following myocardial infarction or revascularization, or with a diagnosis of angina pectoris or CHD defined by angiography. Two authors screened titles for inclusion, extracted data, and assessed risk of bias. Studies were pooled using random effects meta-analysis, and stratified analyses were undertaken to examine potential treatment effect modifiers.Results: A total of 63 studies with 14,486 participants with median follow-up of 12 months were included. Overall, CR led to a reduction in cardiovascular mortality (relative risk: 0.74; 95% confidence interval: 0.64 to 0.86) and the risk of hospital admissions (relative risk: 0.82; 95% confidence interval: 0.70 to 0.96). There was no significant effect on total mortality, myocardial infarction, or revascularization. The majority of studies (14 of 20) showed higher levels of health-related quality of life in 1 or more domains following exercise-based CR compared with control subjects.Conclusions: This study confirms that exercise-based CR reduces cardiovascular mortality and provides important data showing reductions in hospital admissions and improvements in quality of life. These benefits appear to be consistent across patients and intervention types and were independent of study quality, setting, and publication date. [ABSTRACT FROM AUTHOR]

Objectives: To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). Study Design And Setting: We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman ρ, surrogate threshold effect (STE), and R² were also estimated across predefined trial-level covariates. Results: We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman ρ ranged from 0.39 to 0.80, mean R² from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. Conclusion: None of the end points in this study were found to achieve the level of evidence (ie, mean Rtrial² > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy. [ABSTRACT FROM AUTHOR]