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Background There is a lack of international consensus regarding the prescription of high-intensity interval training (HIIT) for people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). Aims To assess the clinical effectiveness and safety of low-volume HIIT compared with moderate-intensity steady-state (MISS) exercise training for people with CAD. Methods and results We conducted a multi-centre RCT, recruiting 382 patients from 6 outpatient CR centres. Participants were randomized to twice-weekly HIIT (n = 187) or MISS (n = 195) for 8 weeks. HIIT consisted of 10 × 1 min intervals of vigorous exercise (>85% maximum capacity) interspersed with 1 min periods of recovery. MISS was 20–40 min of moderate-intensity continuous exercise (60–80% maximum capacity). The primary outcome was the change in cardiorespiratory fitness [peak oxygen uptake (VO2 peak)] at 8 week follow-up. Secondary outcomes included cardiovascular disease risk markers, cardiac structure and function, adverse events, and health-related quality of life. At 8 weeks, VO2 peak improved more with HIIT (2.37 mL.kg−1.min−1; SD, 3.11) compared with MISS (1.32 mL.kg−1.min−1; SD, 2.66). After adjusting for age, sex, and study site, the difference between arms was 1.04 mL.kg−1.min−1 (95% CI, 0.38 to 1.69; P = 0.002). Only one serious adverse event was possibly related to HIIT. Conclusions In stable CAD, low-volume HIIT improved cardiorespiratory fitness more than MISS by a clinically meaningful margin. Low-volume HIIT is a safe, well-tolerated, and clinically effective intervention that produces short-term improvement in cardiorespiratory fitness. It should be considered by all CR programmes as an adjunct or alternative to MISS. Trial registration ClinicalTrials.gov: NCT02784873. https://clinicaltrials.gov/ct2/show/NCT02784873.

IntroductionPeople with psychosis tend to have smaller social networks than both people in the general population and other people with long-term health conditions. Small social networks are associated with poor quality of life. Preliminary evidence suggests that coaching patients to increase their social contacts may be effective. In this study, we assessed whether structured social coaching improves the quality of life of patients with psychosis (primary outcome) compared with an active control group, receiving information on local social activities.Methods and analysisA structured social coaching intervention was developed based on the literature and refined through stakeholder involvement. It draws on principles from motivational interviewing, solution focused therapy and structured information giving. It is provided over a 6-month period and can be delivered by a range of different mental health professionals. Its effectiveness and cost-effectiveness are assessed in a randomised controlled trial, compared with an active control group, in which participants are given an information booklet on local social activities. Participants are aged 18 or over, have a primary diagnosis of a psychotic disorder (International Classification of Disease: F20–29) and capacity to provide informed consent. Participants are assessed at baseline and at 6, 12 and 18 months after individual randomisation. The primary outcome is quality of life at 6 months (Manchester Short Assessment of Quality of Life). We hypothesise that the effects on quality of life are mediated by an increase in social contacts. Secondary outcomes are symptoms, social situation and time spent in social activities. Costs and cost-effectiveness analyses will consider service use and health-related quality of life.Ethics and disseminationNational Health Service REC London Hampstead (19/LO/0088) provided a favourable opinion. Findings will be disseminated through a website, social media, scientific papers and user-friendly reports, in collaboration with a lived experience advisory panel.Trial registration numberISRCTN15815862.

Overstating the impact of interventions through incomplete or inaccurate reporting can lead to inappropriate scale-up of interventions with low impact. Accurate reporting of the impact of interventions is of great importance in global health research to protect scarce resources. In global health, the cluster randomised trial design is commonly used to evaluate complex, multicomponent interventions, and outcomes are often binary. Complete reporting of impact for binary outcomes means reporting both relative and absolute measures. We did a systematic review to assess reporting practices and potential to overstate impact in contemporary cluster randomised trials with binary primary outcome. We included all reports registered in the Cochrane Central Register of Controlled Trials of two-arm parallel cluster randomised trials with at least one binary primary outcome that were published in 2017. Of 73 cluster randomised trials, most (60 [82%]) showed incomplete reporting. Of 64 cluster randomised trials for which it was possible to evaluate, most (40 [63%]) reported results in such a way that impact could be overstated. Care is needed to report complete evidence of impact for the many interventions evaluated using the cluster randomised trial design worldwide.

Background Periodontal intrabony defects are usually treated surgically with the aim of increasing attachment and bone levels and reducing risk of progression. However, recent studies have suggested that a minimally invasive non-surgical therapy (MINST) leads to considerable clinical and radiographic defect depth reductions in intrabony defects. The aim of this study is to compare the efficacy of a modified MINST approach with a surgical approach (modified minimally invasive surgical therapy, M-MIST) for the treatment of intrabony defects. Methods This is a parallel-group, single-centre, examiner-blind non-inferiority randomised controlled trial with a sample size of 66 patients. Inclusion criteria are age 25–70, diagnosis of periodontitis stage III or IV (grades A to C), presence of ≥ 1 ‘intrabony defect’ with probing pocket depth (PPD) > 5 mm and intrabony defect depth ≥ 3 mm. Smokers and patients who received previous periodontal treatment to the study site within the last 12 months will be excluded. Patients will be randomly assigned to either the modified MINST or the M-MIST protocol and will be assessed up to 15 months following initial therapy. The primary outcome of the study is radiographic intrabony defect depth change at 15 months follow-up. Secondary outcomes are PPD and clinical attachment level change, inflammatory markers and growth factors in gingival crevicular fluid, bacterial detection, gingival inflammation and healing (as measured by geometric thermal camera imaging in a subset of 10 test and 10 control patients) and patient-reported outcomes. Discussion This study will produce evidence about the clinical efficacy and potential applicability of a modified MINST protocol for the treatment of periodontal intrabony defects, as a less invasive alternative to the use of surgical procedures. Trial registration ClinicalTrials.gov, NCT03797807. Registered on 9 January 2019.

BackgroundBefriending by volunteers has the potential to reduce the frequent social isolation of patients with schizophrenia and thus improve health outcomes. However, trial-based evidence for its effectiveness is limited.AimsTo conduct a randomised controlled trial of befriending for patients with schizophrenia or related disorders.MethodPatients were randomised to a befriending programme for 1 year or to receive information about social activities only (trial registration: ISRCTN14021839). Outcomes were assessed masked to allocation at the end of the programme; at 12 months and at a 6-month follow-up. The primary outcome was daily time spent in activities (using the Time Use Survey (TUS)) with intention-to-treat analysis.ResultsA total of 124 patients were randomised (63 intervention, 61 active control) and 92 (74%) were followed up at 1 year. In the intervention group, 49 (78%) met a volunteer at least once and 31 (49%) had more than 12 meetings. At 1 year, mean TUS scores were more than three times higher in both groups with no significant difference between them (adjusted difference 8.9, 95% CI −40.7 to 58.5, P = 0.72). There were no significant differences in quality of life, symptoms or self-esteem. However, patients in the intervention group had significantly more social contacts than those in the control group at the end of the 12-month period. This difference held true at the follow-up 6 months later.ConclusionsAlthough no difference was found on the primary outcome, the findings suggest that befriending may have a lasting effect on increasing social contacts. It may be used more widely to reduce the social isolation of patients with schizophrenia.

BackgroundEffective programmes to help children manage their weight are required. ‘Families for Health’ focuses on a parenting approach, designed to help parents develop their parenting skills to support lifestyle change within the family. Families for Health version 1 showed sustained reductions in mean body mass index (BMI) z-score after 2 years in a pilot project.ObjectiveThe aim was to evaluate its effectiveness and cost-effectiveness in a randomised controlled trial (RCT).DesignThe trial was a multicentre, investigator-blind RCT, with a parallel economic and process evaluation, with follow-up at 3 and 12 months. Randomisation was by family unit, using a 1 : 1 allocation by telephone registration, stratified by three sites, with a target of 120 families.SettingThree sites in the West Midlands, England, UK.ParticipantsChildren aged 6–11 years who were overweight (≥ 91st centile BMI) or obese (≥ 98th centile BMI), and their parents/carers. Recruitment was via referral or self-referral.InterventionsFamilies for Health version 2 is a 10-week, family-based community programme with parallel groups for parents and children, addressing parenting, lifestyle, social and emotional development. Usual care was the treatment for childhood obesity provided within each locality.Main outcome measuresJoint primary outcome measures were change in children’s BMI z-score and incremental cost per quality-adjusted life-year (QALY) gained at 12 months’ follow-up (QALYs were calculated using the European Quality of Life-5 Dimensions Youth version). Secondary outcome measures included changes in children’s waist circumference, percentage body fat, physical activity, fruit/vegetable consumption and quality of life. Parents’ BMI and mental well-being, family eating/activity, parent–child relationships and parenting style were also assessed. The process evaluation documented recruitment, reach, dose delivered, dose received and fidelity, using mixed methods.ResultsThe study recruited 115 families (128 children; 63 boys and 65 girls), with 56 families randomised to the Families for Health arm and 59 to the ‘usual-care’ control arm. There was 80% retention of families at 3 months (Families for Health, 46 families; usual care, 46 families) and 72% retention at 12 months (Families for Health, 44 families; usual care, 39 families). The change in BMI z-score at 12 months was not significantly different in the Families for Health arm and the usual-care arm [0.114, 95% confidence interval (CI) –0.001 to 0.229;p = 0.053]. However, within-group analysis showed that the BMI z-score was significantly reduced in the usual-care arm (–0.118, 95% CI –0.203 to –0.034;p = 0.007), but not in the Families for Health arm (–0.005, 95% CI –0.085 to 0.078;p = 0.907). There was only one significant difference between groups for secondary outcomes. The economic evaluation, taking a NHS and Personal Social Services perspective, showed that mean costs 12 months post randomisation were significantly higher for Families for Health than for usual care (£998 vs. £548;p ConclusionsFamilies for Health was neither effective nor cost-effective for the management of obesity in children aged 6–11 years, in comparison with usual care. Further exploration of the wide range of responses in BMI z-score in children following the Families for Health and usual-care interventions is warranted, focusing on children who had a clinically significant benefit and those who showed a worse outcome with treatment. Further research could focus on the role of parents in the prevention of obesity, rather than treatment.Trial registrationCurrent Controlled Trials ISRCTN45032201.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 1. See the NIHR Journals Library website for further project information.

Background: Periodontal intrabony defects are usually treated surgically with the aim to increase attachment and bone levels and reduce risk of progression. However, recent studies have suggested that a minimally-invasive non-surgical therapy (MINST) leads to considerable clinical and radiographic defect depth reductions in intrabony defects. The aim of this study is to compare the efficacy of a modified MINST approach with a surgical approach (modified minimally-invasive surgical therapy, M-MIST) for the treatment of intrabony defects. Methods: This is a parallel-group single-centre examiner-blind non-inferiority randomised controlled trial with a sample size of 66 patients. Inclusion criteria are age 25-70, diagnosis of periodontitis stage III or IV (grades A to C), presence of ≥1 ‘intrabony defect’ with probing pocket depth (PPD) >5 mm and intrabony defect depth ≥3mm. Smokers and patients who received previous periodontal treatment to the study site within the last 12 months will be excluded. Patients will be randomly assigned to either the modified MINST or the M-MIST protocol and will be assessed up to 15 months following initial therapy. The primary outcome of the study is radiographic intrabony defect depth change at 15 months follow-up. Secondary outcomes are PPD and clinical attachment loss (CAL) change, inflammatory markers and growth factors in gingival crevicular fluid, bacterial detection, gingival inflammation and healing (as measured by geometric/thermal camera imaging in a subset of 10 test and 10 control patients) and patient-reported outcomes. Discussion: This study will produce evidence about the clinical efficacy and potential applicability of a modified MINST protocol for the treatment of periodontal intrabony defects, as a less invasive alternative to the use of surgical procedures. Trial registration: This study was registered on clinicaltrials.gov NCT03797807 (date registered: 9 January 2019). Keywords: Periodontitis, intrabony defect, minimally-invasive, quality of life, bone

BACKGROUND It is unclear whether patients with specific subgingival microbiological profiles benefit more from adjunctive systemic antibiotics. AIMS To answer the question: "What is the clinical benefit in periodontitis patients taking adjunctive systemic antimicrobials to non-surgical therapy, depending on pre-treatment detection of periodontopathogenic bacteria?" MATERIALS AND METHODS A search was conducted in four electronic databases for randomized controlled trials reporting clinical outcomes following adjunctive antibiotic therapy for patients divided by baseline microbiological profiles. RESULTS The initial search resulted in 643 papers, reduced to five after screening and author contact. Four of these studies were suitable for a fixed effects two-stage individual participant data meta-analysis adjusted for baseline data. Collectively, adjunctive amoxicillin and metronidazole yielded superior clinical results (measured as reduction of PPDs) compared to placebo. No significant differences were detected for the effect of adjunctive antibiotics by the detection of Aggregatibacter actinomycetemcomitans on PPDs ≥ 5 mm (WMD = 1.16, 95% CI [-5.37, 7.68], I2 = 37.8%) or other clinical outcomes. All included studies had low risk of bias. CONCLUSION There is no evidence to suggest that baseline detection of periodontopathogenic bacteria should be used as criterion for prescribing adjunctive antibiotics, although only limited information on microbial data and specific antimicrobials was available for analysis.

Objective Evaluating effectiveness and cost-effectiveness of ‘Families for Health V2′ (FFH) compared with usual care (UC).\ud \ud Design Multicentre randomised controlled trial (RCT) (investigators blinded, families unblinded) and economic evaluation. Stratified randomisation by family; target of 120 families.\ud \ud Setting Three National Health Service Primary Care Trusts in West Midlands, England.\ud \ud Participants Overweight or obese (≥91st or ≥98th centile body mass index (BMI)) children aged 6–11 years and their parents/carers, recruited March 2012–February 2014.\ud \ud Interventions FFH; a 10-week community-based family programme addressing parenting, lifestyle change and social and emotional development. UC; usual support for childhood obesity at each site.\ud \ud Main outcome measures Primary outcomes were 12-months change in children's BMI z-score and incremental cost per quality-adjusted life-year gained (QALY). Secondary outcomes included changes in children's physical activity, fruit and vegetable consumption and quality of life, parents' BMI and mental well-being, family eating/activity, parent-child relationships and parenting style.\ud \ud Results 115 families (128 children) were randomised to FFH (n=56) or UC (n=59). There was no significant difference in BMI z-score 12-months change (0.114, 95% CI −0.001 to 0.229, p=0.053; p=0.026 in favour of UC with missing value multiple imputation). One secondary outcome, change in children's waist z-score, was significantly different between groups in favour of UC (0.15, 95% CI 0.00 to 0.29). Economic evaluation showed that mean costs were significantly higher for FFH than UC (£998 vs £548, p

AimsCardiac resynchronisation therapy (CRT) is effective treatment for selected patients with heart failure (HF) but has ~30% non-response rate. We evaluated whether specific biomarkers can predict outcome.MethodsA prospective single-centre pilot study of consecutive unselected patients undergoing CRT for HF between November 2013 and December 2015 evaluating cardiac extracellular matrix biomarkers and micro-ribonucleic acid (miRNA) expression before and after CRT assessing ability to predict functional response and survival. Each underwent three assessments (pre-implant, 6 weeks and 6 months postimplant) including: New York Heart Association (NYHA) class, echocardiography, electrocardiography, 6 min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Plasma markers of cardiac fibrosis assessed were: N-terminal pro-peptides of collagen I and III, collagen I C-terminal telopeptides (CTx) and matrix metalloproteinases (MMP-2 and MMP-9) as well as a panel of miRNAs (miRNA-21, miRNA-30d, miRNA-122, miRNA-133a, miRNA-210 and miRNA-486).ResultsA total of 52 patients were recruited; mean age (±SD) was 72.4±9.4 years; male=43 (82.7%), ischaemic aetiology=30 (57.7%), mean QRS duration=166.4±23.5 ms, left bundle branch block (LBBB) morphology = 39 (75.0%), mean NYHA=2.7±0.6, 6MWT=238.8±130.6 m, MLHFQ=46.4±21.3 and left ventricular ejection fraction (LVEF)=24.3%±8.0%. Mean follow-up=1.7±0.3 and 5.8±0.7 months. There were 27 (55.1%) functional responders (3 no definable 6-month response; 2 missed assessments and 1 long-term lead displacement). No marker predicted response, however, CTx and LBBB trended most towards predicting functional response.ConclusionNo specific biomarkers reached significance for predicting functional response to CRT. CTx showed a trend towards predicting response and warrants further study.Trial registration numberNCT02541773.

Pilot studies and other small clinical trials are often conducted but serve a variety of purposes and there is little consensus on their design. One paradigm that has been suggested for the design of such studies is Bayesian decision theory. In this article, we review the literature with the aim of summarizing current methodological developments in this area. We find that decision-theoretic methods have been applied to the design of small clinical trials in a number of areas. We divide our discussion of published methods into those for trials conducted in a single stage, those for multi-stage trials in which decisions are made through the course of the trial at a number of interim analyses, and those that attempt to design a series of clinical trials or a drug development programme. In all three cases, a number of methods have been proposed, depending on the decision maker’s perspective being considered and the details of utility functions that are used to construct the optimal design. EU project InSPiRe (Innovative methodology for small populations research); FP HEALTH 2013 – 602144

BACKGROUND Patients with advanced chronic kidney disease (CKD) experience complex functional and structural changes of the cardiopulmonary and musculoskeletal system. This results in reduced exercise tolerance, quality of life and ultimately premature death. We investigated the relationship between subjective measures of health related quality of life and objective, standardised functional measures for cardiovascular and pulmonary health. METHODS Between April 2010 and January 2013, 143 CKD stage-5 or CKD5d patients (age 46.0±1.1y, 62.2% male), were recruited prospectively. A control group of 83 healthy individuals treated for essential hypertension (HTN; age 53.2±0.9y, 48.22% male) were recruited at random. All patients completed the SF-36 health survey questionnaire, echocardiography, vascular tonometry and cardiopulmonary exercise testing. RESULTS Patients with CKD had significantly lower SF-36 scores than the HTN group; for physical component score (PCS; 45.0 vs 53.9, p

Objective Cardiac resynchronisation therapy (CRT) is an effective therapy for selected patients with heart failure (HF); however, a significant non-response rate exists. We examined current evidence on extracellular cardiac matrix (ECM) biomarkers in predicting response following CRT. Methods Complete literature review of PubMed, Ovid SP MEDLINE, Cochrane Library and TRIP, reference lists, international cardiology conferences and ongoing studies between December 1999 and December 2015 conducted according to prospectively registered study selection and analysis criteria (PROSPERO:CRD42016025864) was performed. All observational and randomised control trials (RCT) were included if they tested prespecified ECM biomarkers’ ability to predict CRT response. Risk of bias assessment and data extraction determined pooling of included studies was not feasible due to heterogeneity of the selected studies. Results A total of 217 studies were screened; six (five prospective cohort and one RCT substudy) were included in analysis with 415 participants in total. Study sizes varied (n=55–260), cohort characteristics contrasted (male: 67.8%–83.6%, ischaemic aetiology: 40.2%–70.3%) and CRT response definitions differed (three clinical/functional, three echocardiographic). Consistent observation in all ECM biomarker behaviour before and after CRT implantation was not observed between studies. Lower type I and type III collagen synthesis biomarkers (N-terminal propeptides of type I and III procollagens) expression demonstrated replicated ability to predict reverse left ventricular remodelling. Conclusion Collagen synthesis biomarkers offer the most potential as ECM biomarkers for predicting CRT response. Heterogeneity between these studies was large and limited the ability to pool and compare results numerically. Use of different response definitions was one of the biggest challenges.

Background: The potential of technology to aid integration of care delivery systems is being explored in a range of contexts across a variety of conditions in the United Kingdom. Prostate cancer is the most common cancer in UK men. With a 10-year survival rate of 84%, there is a need to explore innovative methods of care that are integrated between primary health care providers and specialist teams in order to address long-term consequences of the disease and its treatment as well as to provide continued monitoring for recurrence. Objective: Our aim was to test the feasibility of a randomized controlled trial to compare a model of prostate cancer continuing and follow-up care integration, underpinned by digital technology, with usual care in terms of clinical and cost-effectiveness, patient-reported outcomes, and experience. Methods: A first phase of the study has included development of an online adaptive prostate specific Holistic Needs Assessment system (HNA), training for primary care-based nurses, training of an IT peer supporter, and interviews with health care professionals and men with prostate cancer to explore views of their care, experience of technology, and views of the proposed intervention. In Phase 2, men in the intervention arm will complete the HNA at home to help identify and articulate concerns and share them with their health care professionals, in both primary and specialist care. Participants in the control arm will receive usual care. Outcomes including quality of life and well-being, prostate-specific concerns, and patient enablement will be measured 3 times over a 9-month period. Results: Findings from phase 1 indicated strong support for the intervention among men, including those who had had little experience of digital technology. Men expressed a range of views on ways that the online system might be used within a clinical pathway. Health care professionals gave valuable feedback on how the output of the assessment might be presented to encourage engagement and uptake by clinical teams. Recruitment to the second phase of the study, the feasibility trial, commenced March 2017. Conclusions: To our knowledge, this study is the first in the United Kingdom to trial an online holistic needs assessment for men with prostate cancer, with data shared between patients and primary and secondary care providers. This study addresses recommendations in recent policy documents promoting the importance of data sharing and enhanced communication between care providers as a basis for care integration. We anticipate that this model of care will ultimately provide important benefits for both patients and the National Health Service. Trial Registration: International Standard Randomized Controlled Trial Number (ISRCTN): 31380482; http://www.isrctn.com/ISRCTN31380482 (Archived by WebCite at http://www.webcitation.org/6s8I42u5N) [JMIR Res Protoc 2017;6(7):e147]

Introduction: Current international guidelines for cardiac rehabilitation (CR) advocate moderate-intensity exercise training (MISS, moderate-intensity steady state). This recommendation predates significant advances in medical therapy for coronary heart disease (CHD) and may not be the most appropriate strategy for the ‘modern’ patient with CHD. High-intensity interval training (HIIT) appears to be a safe and effective alternative, resulting in greater improvements in peak oxygen uptake (VO2 peak). To date, HIIT trials have predominantly been proof-of-concept studies in the laboratory setting and conducted outside the UK. The purpose of this multicentre randomised controlled trial is to compare the effects of HIIT and MISS training in patients with CHD attending UK CR programmes. \ud \ud Methods and analysis: This pragmatic study will randomly allocate 510 patients with CHD to 8 weeks of twice weekly HIIT or MISS training at 3 centres in the UK. HIIT will consist of 10 high-intensity (85–90% peak power output (PPO)) and 10 low-intensity (20–25% PPO) intervals, each lasting 1 min. MISS training will follow usual care recommendations, adhering to currently accepted UK guidelines (ie, >20 min continuous exercise at 40–70% heart rate reserve). Outcome measures will be assessed at baseline, 8 weeks and 12 months. The primary outcome for the trial will be change in VO2 peak as determined by maximal cardiopulmonary exercise testing. Secondary measures will assess physiological, psychosocial and economic outcomes. \ud \ud Ethics and dissemination: The study protocol V.1.0, dated 1 February 2016, was approved by the NHS Health Research Authority, East Midlands— Leicester South Research Ethics Committee (16/EM/ 0079). Recruitment will start in August 2016 and will be completed in June 2018. Results will be published in peer-reviewed journals, presented at national and international scientific meetings and are expected to inform future national guidelines for exercise training in UK CR. Trial registration number: NCT02784873; pre-results.

The pattern and global burden of disease has evolved considerably over the last two decades, from primarily communicable, maternal, and perinatal causes to non-communicable disease (NCD). Cardiovascular disease (CVD) has become the single most important and largest cause of NCD deaths worldwide at over 50%. The World Health Organisation (WHO) estimates that 17.6 million people died of CVD worldwide in 2012. Proportionally, this accounts for an estimated 31.43% of global mortality, with ischaemic heart disease (IHD) accounting for approximately 7.4 million deaths, 13.2% of the total. IHD was also the greatest single cause of death in 2000, accounting for an estimated 6.0 million deaths. The global burden of CVD falls, principally, on the low and middle-income (LMI) countries, accounting for over 80% of CVD deaths. Individual populations face differing challenges and each population has unique health burdens, however, CVD remains one of the greatest health challenges both nationally and worldwide.

It is well known that socio-economic status is a strong predictor of screening attendance, with women of higher socioeconomic status more likely to attend breast cancer screening. We investigated whether socio-economic status was related to the detection of cancer at breast screening centres. In two separate projects we combined UK data from the population census, the screening information systems, and the cancer registry. Five years of data from all 81 screening centres in the UK was collected. Only women who had previously attended screening were included. The study was given ethical approval by the University of Warwick Biomedical Research Ethics committee reference SDR-232-07- 2012. Generalised linear models with a log-normal link function were fitted to investigate the relationship between predictors and the age corrected cancer detection rate at each centre. We found that screening centres serving areas with lower average socio-economic status had lower cancer detection rates, even after correcting for the age distribution of the population. This may be because there may be a correlation between higher socio-economic status and some risk factors for breast cancer such as nullparity (never bearing children). When applying adjustment for age, ethnicity and socioeconomic status of the population screened (rather than simply age) we found that SDR can change by up to 0.11.

Patients with advanced chronic kidney disease (CKD) experience complex functional and structural changes of the cardiopulmonary and musculoskeletal system. This results in reduced exercise tolerance, quality of life and ultimately premature death. We investigated the relationship between subjective measures of health related quality of life and objective, standardised functional measures for cardiovascular and pulmonary health.Between April 2010 and January 2013, 143 CKD stage-5 or CKD5d patients (age 46.0±1.1y, 62.2% male), were recruited prospectively. A control group of 83 healthy individuals treated for essential hypertension (HTN; age 53.2±0.9y, 48.22% male) were recruited at random. All patients completed the SF-36 health survey questionnaire, echocardiography, vascular tonometry and cardiopulmonary exercise testing.Patients with CKD had significantly lower SF-36 scores than the HTN group; for physical component score (PCS; 45.0 vs 53.9, p0.001) and mental component score (MCS; 46.9 vs. 54.9, p0.001). CKD subjects had significantly poorer exercise tolerance and cardiorespiratory performance compared with HTN (maximal oxygen uptake; VO2peak 19.9 vs 25.0ml/kg/min, p0.001). VO2peak was a significant independent predictor of PCS in both groups (CKD: b = 0.35, p = 0.02 vs HTN: b = 0.27, p = 0.001). No associations were noted between PCS scores and echocardiographic characteristics, vascular elasticity and cardiac biomarkers in either group. No associations were noted between MCS and any variable. The interaction effect of study group with VO2peak on PCS was not significant (ΔB = 0.08; 95%CI -0.28-0.45, p = 0.7). However, overall for a given VO2peak, the measured PCS was much lower for patients with CKD than for HTN cohort, a likely consequence of systemic uremia effects.In CKD and HTN, objective physical performance has a significant effect on quality of life; particularly self-reported physical health and functioning. Therefore, these quality of life measures are indeed a good reflection of physical health correlating highly with objective physical performance measures.

Growing interest in stratified medicine is leading to increasing importance of subgroup analyses in confirmatory clinical trials. Conventionally, confirmatory clinical trials either focus on a subgroup identified in advance or assess subgroup effects once the trial is completed. The focus of this article is methodology for adaptive clinical trials that both identify whether a treatment is particularly effective in a predefined subgroup, potentially enabling alteration of recruitment, and assess the effectiveness in the subgroup and/or whole population. Methods for such adaptive trials are described and compared, and the logistical and regulatory issues associated with such approaches are discussed.

OBJECTIVE: Little is known about the processes and factors that account for maintenance, with several theories existing that have not been subject to many empirical tests. The aim of this study was to test how well theoretical constructs derived from the Health Action Process Approach, Rothman's theory of maintenance, and Verplanken's approach to habitual behavior predicted maintenance of attendance at walking groups. METHOD: 114 participants, who had already attended walking groups in the community for at least 3 months, completed a questionnaire assessing theoretical constructs regarding maintenance. An objective assessment of attendance over the subsequent 3 months was gained. Multilevel modeling was used to predict maintenance, controlling for clustering within walking groups. RESULTS: Recovery self-efficacy predicted maintenance, even after accounting for clustering. Satisfaction with social outcomes, satisfaction with health outcomes, and overall satisfaction predicted maintenance, but only satisfaction with health outcomes significantly predicted maintenance after accounting for clustering. Self-reported habitual behavior did not predict maintenance despite mean previous attendance being 20.7 months. CONCLUSIONS: Recovery self-efficacy, and satisfaction with health outcomes of walking group attendance appeared to be important for objectively measured maintenance, whereas self-reported habit appeared not to be important for maintenance at walking groups. The findings suggest that there is a need for intervention studies to boost recovery self-efficacy and satisfaction with outcomes of walking group attendance, to assess impact on maintenance.

Exercise intolerance is an important comorbidity in patients with CKD. Anaerobic threshold (AT) determines the upper limits of aerobic exercise and is a measure of cardiovascular reserve. This study investigated the prognostic capacity of AT on survival in patients with advanced CKD and the effect of kidney transplantation on survival in those with reduced cardiovascular reserve. Using cardiopulmonary exercise testing, cardiovascular reserve was evaluated in 240 patients who were waitlisted for kidney transplantation between 2008 and 2010, and patients were followed for ≤5 years. Survival time was the primary endpoint. Cumulative survival for the entire cohort was 72.6% (24 deaths), with cardiovascular events being the most common cause of death (54.2%). According to Kaplan–Meier estimates, patients with AT

BackgroundInterventions to promote mental well-being can bring benefits to the individual and to society. The Internet can facilitate the large-scale and low-cost delivery of individually targeted health promoting interventions. ObjectiveTo evaluate the effectiveness of a self-directed Internet-delivered cognitive-behavioral skills training tool in improving mental well-being in a population sample. MethodsThis was a randomized trial with a waiting-list control. Using advertisements on a national health portal and through its mailing list, we recruited 3070 participants aged 18 or over, resident in England, and willing to give their email address and access a fully automated Web-based intervention. The intervention (MoodGYM) consisted of 5 interactive modules that teach cognitive-behavioral principles. Participants in the intervention arm received weekly email reminders to access the intervention. The control group received access to the intervention after the trial was completed and received no specific intervention or email reminders. Outcomes were assessed by using self-completion questionnaires. The primary outcome was mental well-being measured with the Warwick-Edinburgh Mental Well-being Scale (WEMWBS). Secondary outcomes were Center for Epidemiologic Studies Depression scale (CES-D) depression scores, Generalized Anxiety Disorder 7-item scale (GAD-7) anxiety scores, EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life scores, physical activity, and health service use. All outcomes were measured at baseline, and at 6- and 12-week follow-ups. ResultsA total of 1529 (49.80%) participants completed final follow-up at 12 weeks. Retention was 73.11% (1123/1536) in the control arm and 26.47% (406/1534) in the intervention arm. No relationship between baseline measures and withdrawal could be established. The analysis of WEMWBS mental well-being scores using a linear mixed model for repeated measures showed no difference between intervention and control group at baseline (difference –0.124 points, 95% CI –0.814 to 0.566), and significant improvements for the intervention group at 6 weeks (2.542 points, 95% CI 1.693-3.390) and at 12 weeks (2.876 points, 95% CI 1.933-3.819). The model showed a highly significant (P

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is\ud able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if\ud functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients.\ud \ud Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed\ud CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial\ud applanation tonometry were performed.\ud \ud Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were\ud desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced\ud anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and\ud in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating-\ud characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and\ud desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU\ud admission.\ud \ud Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a\ud preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the\ud potential to predict perioperative morbidity in kidney transplant recipients.

Background:\ud Effective programs to help children manage their weight are required. Families for Health focuses on a parenting approach, designed to help parents develop their parenting skills to support lifestyle change within the family. Families for Health V1 showed sustained reductions in overweight after 2 years in a pilot evaluation, but lacks a randomized controlled trial (RCT) evidence base.\ud \ud Methods/design:\ud This is a multi-center, investigator-blind RCT, with parallel economic evaluation, with a 12-month follow-up. The trial will recruit 120 families with at least one child aged 6 to 11 years who is overweight (≥91st centile BMI) or obese (≥98th centile BMI) from three localities and assigned randomly to Families for Health V2 (60 families) or the usual care control (60 families) groups. Randomization will be stratified by locality (Coventry, Warwickshire, Wolverhampton).\ud Families for Health V2 is a family-based intervention run in a community venue. Parents/carers and children attend parallel groups for 2.5 hours weekly for 10 weeks. The usual care arm will be the usual support provided within each NHS locality.\ud A mixed-methods evaluation will be carried out. Child and parent participants will be assessed at home visits at baseline, 3-month (post-treatment) and 12-month follow-up. The primary outcome measure is the change in the children’s BMI z-scores at 12 months from the baseline. Secondary outcome measures include changes in the children’s waist circumference, percentage body fat, physical activity, fruit/vegetable consumption and quality of life. The parents’ BMI and mental well-being, family eating/activity, parent–child relationships and parenting style will also be assessed.\ud Economic components will encompass the measurement and valuation of service utilization, including the costs of running Families for Health and usual care, and the EuroQol EQ-5D health outcomes. Cost-effectiveness will be expressed in terms of incremental cost per quality-adjusted life year gained. A de novo decision-analytic model will estimate the lifetime cost-effectiveness of the Families for Health program.\ud Process evaluation will document recruitment, attendance and drop-out rates, and the fidelity of Families for Health delivery. Interviews with up to 24 parents and children from each arm will investigate perceptions and changes made.\ud \ud Discussion:\ud \ud This paper describes our protocol to assess the effectiveness and cost-effectiveness of a parenting approach for managing childhood obesity and presents challenges to implementation.\ud \ud Trial registration: Current Controlled Trials ISRCTN45032201

Background Higher levels of mental wellbeing and positive psychological functioning have been associated with better physical functioning at older ages, better self-rated health (SRH), reductions in neuroendocrine, inflammatory and cardiovascular activity, and decreased risk of mortality in healthy and diseased populations. Nevertheless there is no data available on levels of mental wellbeing for the majority of populations worldwide. We aimed to describe the levels of mental wellbeing and evaluate any factors associated on the basis of socio-demographic, health, lifestyle and environmental variables reported by residents of Coventry, UK. Methods Stratified random cross-sectional survey conducted in Coventry, UK, between December 2009 and January 2010. We collected data from 3750 participants of the Coventry Household Survey, a biennial survey conducted by face to face interviews. The survey contained 45 questions asking about the environment, work and training, health, wellbeing and demographics. We calculated the levels of wellbeing as measured by the Warwick Edinburgh Mental Well-being Scale (WEMWBS), which is a positively worded, 14-question, Likert-type scale ranging from 14 to 70. Using simple and then multiple linear regression, we evaluated potential factors associated with mental wellbeing and compared them by gender, ethnicity, age, socioeconomic status and deprivation level. Results The survey was representative of the underlying population. Mean WEMWBS score was 51.2 (52 for men and 50.5 for women). After adjusting for socio-demographic variables, the following variables were associated with mental wellbeing: Self-rated health, sleep quality, ethnicity, fruit and vegetable consumption, home satisfaction, and night-time neighbourhood safety. The strongest associations were observed between mental wellbeing and self-rated health (B=6.13; 95% CI 4.63 to 7.62) and sleep quality (B=4.24; 95% CI 3.26 to 5.22). Levels of mental wellbeing were significantly different between age groups, gender, ethnicity, education level, and employment status. While deprivation level was significant in the simple linear regression, it was not strong enough to be included in the final multiple regression model- a surprising finding given prior research in social inequalities. Conclusions Self-rated health, sleep quality and fruit and vegetable consumption showed the strongest associations with mental wellbeing levels, while significant differences were also observed socio-demographically. Deprivation level was not strongly associated with mental wellbeing in our study. Subjective perceptions of health and wellbeing are complex and interrelated. More accurate descriptions of population levels of mental wellbeing may allow us to make some headway towards understanding an increasingly relevant factor for public health practice and policy.

Psychotic disorders carry social and economic costs for sufferers and society. Recent evidence highlights the risk posed by urban upbringing and social deprivation in the genesis of paranoia and psychosis. Evidence based psychological interventions are often not offered because of a lack of therapists. Virtual reality (VR) environments have been used to treat mental health problems. VR may be a way of understanding the aetiological processes in psychosis and increasing psychotherapeutic resources for its treatment. We developed a high-fidelity virtual reality scenario of an urban street scene to test the hypothesis that virtual urban exposure is able to generate paranoia to a comparable or greater extent than scenarios using indoor scenes. Participants (n=32) entered the VR scenario for four minutes, after which time their degree of paranoid ideation was assessed. We demonstrated that the virtual reality scenario was able to elicit paranoia in a nonclinical, healthy group and that an urban scene was more likely to lead to higher levels of paranoia than a virtual indoor environment. We suggest that this study offers evidence to support the role of exposure to factors in the urban environment in the genesis and maintenance of psychotic experiences and symptoms. The realistic high-fidelity street scene scenario may offer a useful tool for therapists.

Background Recruitment to trials evaluating the effectiveness of childhood obesity management interventions is challenging. We report our experience of recruitment to the Families for Health study, a randomised controlled trial evaluating the effectiveness of a family-based community programme for children aged 6–11 years, versus usual care. We evaluated the effectiveness of active recruitment (contacting eligible families directly) versus passive recruitment (informing the community through flyers, public events, media). Methods Initial approaches included passive recruitment via the media (newspapers and radio) and two active recruitment methods: National Child Measurement Programme (letters to families with overweight children) and referrals from health-care professionals. With slow initial recruitment, further strategies were employed, including active (e.g. targeted letters from general practices) and passive (e.g. flyers, posters and public events) methods. At first enquiry from a potential participant, families were asked where they heard about the study. Further quantitative (questionnaire) and qualitative data (one-to-one interviews with parents/carers), were collected from recruited families at baseline and 3-month follow-up and included questions about recruitment. Results In total, 194 families enquired about Families for Health, and 115 (59.3 %) were recruited and randomised. Active recruitment yielded 85 enquiries, with 43 families recruited (50.6 %); passive recruitment yielded 99 enquiries with 72 families recruited (72.7 %). Information seen at schools or GP surgeries accounted for over a quarter of enquiries (28.4 %) and over a third (37.4 %) of final recruitment. Eight out of ten families who enquired this way were recruited. Media-led enquiries were low (5 %), but all were recruited. Children of families recruited actively were more likely to be Asian or mixed race. Despite extensive recruitment methods, the trial did not recruit as planned, and was awarded a no-cost extension to complete the 12-month follow-up. Conclusions The higher number of participants recruited through passive methods may be due to the large number of potential participants these methods reached and because participants may see the information more than once. Recruiting to a child obesity treatment study is complex and it is advisable to use multiple recruitment strategies, some aiming at blanket coverage and some targeted at families with children who are overweight. Trial registration Current Controlled Trials ISRCTN45032201 (Date: 18 August 2011) Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1062-x) contains supplementary material, which is available to authorized users.

Importance: Restitution of kidney function by transplant confers a survival benefit in patients with end-stage renal disease. Investigations of mechanisms involved in improved cardiovascular survival have relied heavily on static measures from echocardiography or cardiac magnetic resonance imaging and have provided conflicting results to date. Objectives: To evaluate cardiovascular functional reserve in patients with end-stage renal disease before and after kidney transplant and to assess functional and morphologic alterations of structural-functional dynamics in this population. Design, Setting, and Participants: This prospective, nonrandomized, single-center, 3-arm, controlled cohort study, the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study, included patients with stage 5 chronic kidney disease (CKD) who underwent kidney transplant (KTR group), patients with stage 5 CKD who were wait-listed and had not undergone transplant (NTWC group), and patients with hypertension only (HTC group) seen at a single center from April 1, 2010, to January 1, 2013. Patients were followed up longitudinally for up to 1 year after kidney transplant. Clinical data collection was completed February 2014. Data analysis was performed from June 1, 2014, to March 5, 2015. Further analysis on baseline and prospective data was performed from June 1, 2017, to July 31, 2019. Main Outcomes and Measures: Cardiovascular functional reserve was objectively quantified using state-of-the-art cardiopulmonary exercise testing in parallel with transthoracic echocardiography. Results: Of the 253 study participants (mean [SD] age, 48.5 [12.7] years; 141 [55.7%] male), 81 were in the KTR group, 85 in the NTWC group, and 87 in the HTC group. At baseline, mean (SD) maximum oxygen consumption (V̇O2max) was significantly lower in the CKD groups (KTR, 20.7 [5.8] mL · min-1 · kg-1; NTWC, 18.9 [4.7] mL · min-1 · kg-1) compared with the HTC group (24.9 [7.1] mL · min-1 · kg-1) (P

Background: \ud Patients with chronic kidney failure (CKF) experience impaired functional cardiovascular reserve with reduced oxygen consumption at peak exercise (Vo2peak). No studies have examined whether this is related to impaired cardiovascular compliance as a consequence of loss of adaptive structural alterations, resulting from chronic uremia or hypertension.\ud \ud Study Design: \ud Prospective matched-cohort study.\ud \ud Setting & Participants: \ud We assessed CKF in parallel with patients with essential hypertension but without cardiovascular disease. Patients with CKF were either scheduled for kidney transplantation or transplant waitlisted. 80 patients with CKF and 80 with essential hypertension matched in age, sex, and body mass index were evaluated. 61 patients with CKF (76.3%) were dialysis dependent.\ud \ud Predictor: \ud CKF versus essential hypertension without cardiovascular disease.\ud \ud Measurements & Outcomes: \ud Vo2peak was measured during maximal exercise testing. 2-dimensional echocardiography and arterial applanation tonometry were performed prior to exercise testing. To evaluate for the difference in Vo2peak between study groups, statistically significant predictors of Vo2peak in multiple regression models were additionally assessed by fitting models comprising the interaction term of patient group with the predictor variable of interest.\ud \ud Results: \ud Vo2peak was significantly lower in patients with CKF than those with essential hypertension (18.8 vs 24.5 mL/min·kg; P < 0.001). Independent predictors of Vo2peak for CKF included left ventricular (LV) filling pressure (E/mean e′; unstandardized regression coefficient: change in Vo2peak [in mL/min·kg] per 1-unit change of variable = −5.1) and pulse wave velocity (−4.0); in essential hypertension, these were LV mass index (0.2), LV end-diastolic volume index (0.4), peak heart rate (0.2), and pulse wave velocity (−8.8). The interaction effect of Vo2peak between patient groups with LV mass index (P < 0.001), LV end-diastolic volume index (P < 0.001), and peak heart rate (P < 0.01) were significantly stronger in the hypertension group, whereby higher values led to greater Vo2peak.\ud \ud Limitations: \ud Skeletal muscle strength was not assessed.\ud \ud Conclusion: \ud This study suggests that maladaptive LV changes, as well as blunted chronotropic response, are important mechanistic factors resulting in reduced cardiovascular reserve in patients with CKF, beyond predominantly vascular changes associated with hypertension.

ObjectivesLow-frequency electrical muscle stimulation (LF-EMS) may have the potential to reduce breathlessness and increase exercise capacity in the chronic heart failure population who struggle to adhere to conventional exercise. The study’s aim was to establish if a randomised controlled trial of LF-EMS was feasible.Design and settingDouble blind (participants, outcome assessors), randomised study in a secondary care outpatient cardiac rehabilitation programme.ParticipantsPatients with severe heart failure (New York Heart Association class III–IV) having left ventricular ejection fraction InterventionsParticipants were randomised (remotely by computer) to 8 weeks (5×60 mins per week) of either LF-EMS intervention (4 Hz, continuous, n=30) or sham placebo (skin level stimulation only, n=30) of the quadriceps and hamstrings muscles. Participants used the LF-EMS straps at home and were supervised weeklyOutcome measuresRecruitment, adherence and tolerability to the intervention were measured during the trial as well as physiological outcomes (primary outcome: 6 min walk, secondary outcomes: quadriceps strength, quality of life and physical activity).ResultsSixty of 171 eligible participants (35.08%) were recruited to the trial. 12 (20%) of the 60 patients (4 LF-EMS and 8 sham) withdrew. Forty-one patients (68.3%), adhered to the protocol for at least 70% of the sessions. The physiological measures indicated no significant differences between groups in 6 min walk distance(p=0.13) and quality of life (p=0.55) although both outcomes improved more with LF-EMS.ConclusionPatients with severe heart failure can be recruited to and tolerate LF-EMS studies. A larger randomised controlled trial (RCT) in the advanced heart failure population is technically feasible, although adherence to follow-up would be challenging. The preliminary improvements in exercise capacity and quality of life were minimal and this should be considered if planning a larger trial.Trial registration numberISRCTN16749049