Understanding the processes underpinning IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) in primary care: study protocol for a process evaluation within a cluster randomised controlled implementation trial.

BACKGROUND: Providing supported self-management for people with asthma can reduce the burden on patients, health services and wider society. Implementation, however, remains poor in routine clinical practice. IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) is a UK-wide cluster randomised implementation trial that aims to test the impact of a whole-systems implementation strategy, embedding supported asthma self-management in primary care compared with usual care. To maximise opportunities for sustainable implementation beyond the trial, it is necessary to understand how and why the IMP2ART trial achieved its clinical and implementation outcomes. METHODS: A mixed-methods process evaluation nested within the IMP2ART trial will be undertaken to understand how supported self-management was implemented (or not) by primary care practices, to aid interpretation of trial findings and to inform scaling up and sustainability. Data and analysis strategies have been informed by mid-range and programme-level theory. Quantitative data will be collected across all practices to describe practice context, IMP2ART delivery (including fidelity and adaption) and practice response. Case studies undertaken in three to six sites, supplemented by additional interviews with practice staff and stakeholders, will be undertaken to gain an in-depth understanding of the interaction of practice context, delivery, and response. Synthesis, informed by theory, will combine analyses of both qualitative and quantitative data. Finally, implications for the scale up of asthma self-management implementation strategies to other practices in the UK will be explored through workshops with stakeholders. DISCUSSION: This mixed-methods, theoretically informed, process evaluation seeks to provide insights into the delivery and response to a whole-systems approach to the implementation of supported self-management in asthma care in primary care. It is underway at a time of significant change in primary care in the UK. The methods have, therefore, been developed to be adaptable to this changing context and to capture the impact of these changes on the delivery and response to research and implementation processes.

Implementing psychological interventions delivered by respiratory professionals for people with COPD. A stakeholder interview study.

Implementing psychological interventions in healthcare services requires an understanding of the organisational context. We conducted an interview study with UK National Health Service stakeholders to understand the barriers and facilitators for implementing psychological interventions for people with chronic obstructive pulmonary disorder (COPD). We used TANDEM as an exemplar intervention; a psychological intervention recently evaluated in a randomised controlled trial. Twenty participants providing care and/or services to people with COPD were purposively sampled from NHS primary/secondary care, and commissioning organisations. Participants were recruited via professional networks and referrals. Verbatim transcripts of semi-structured interviews were analysed using thematic analysis. Four themes were identified: (1) Living with COPD and emotional distress affects engagement with physical and psychological services; (2) Resource limitations affects service provision in COPD; (3) Provision of integrated care is important for patient well-being; and (4) Healthcare communication can be an enabler or a barrier to patient engagement. People need support with physical and psychological symptoms inherent with COPD and healthcare should be provided holistically. Respiratory healthcare professionals are considered able to provide psychologically informed approaches, but resources must be available for training, staff supervision and service integration. Communication between professionals is vital for clear understanding of an intervention's aims and content, to facilitate referrals and uptake. There was widespread commitment to integrating psychological and physical care, and support of respiratory healthcare professionals' role in delivering psychological interventions but significant barriers to implementation due to concerns around resources and cost efficiency. The current study informs future intervention development and implementation.

Exercise training as a novel primary treatment for localised prostate cancer: a multi-site randomised controlled phase II study.

Alternative management strategies for localised prostate cancer are required to reduce morbidity and overtreatment. The aim of this study was to evaluate the feasibility, safety and acceptability of exercise training (ET) with behavioural support as a primary therapy for low/intermediate risk localised prostate cancer. Men with low/intermediate-risk prostate cancer were randomised to 12 months of ET or usual care with physical activity advice (UCwA) in a multi-site open label RCT. Feasibility included acceptability, recruitment, retention, adherence, adverse events and disease progression. Secondary outcomes included quality of life and cardiovascular health indices. Of the 50 men randomised to ET (n = 25) or UCwA (n = 25), 92% (n = 46) completed 12 month assessments. Three men progressed to invasive therapy (two in UCwA). In the ET group, men completed mean: 140 mins per week for 12 months (95% CI 129,152 mins) (94% of target dose) at 75% Hrmax. Men in the ET group demonstrated improved body mass (mean reduction: 2.0 kg; 95% CI -2.9,-1.1), reduced systolic (mean: 13 mmHg; 95%CI 7,19) and diastolic blood pressure (mean:8 mmHg; 95% CI 5,12) and improved quality of life (EQ.5D mean:13 points; 95% CI 7,18). There were no serious adverse events. ET in men with low/intermediate risk prostate cancer is feasible and acceptable with a low progression rate to radical treatment. Early signals on clinically relevant markers were found which warrant further investigation.

Implementation fidelity of a self-management course for epilepsy: method and assessment.

BACKGROUND: Complex interventions such as self-management courses are difficult to evaluate due to the many interacting components. The way complex interventions are delivered can influence the effect they have for patients, and can impact the interpretation of outcomes of clinical trials. Implementation fidelity evaluates whether complex interventions are delivered according to protocol. Such assessments have been used for one-to-one psychological interventions; however, the science is still developing for group interventions. METHODS: We developed and tested an instrument to measure implementation fidelity of a two-day self-management course for people with epilepsy, SMILE(UK). Using audio recordings, we looked at adherence and competence of course facilitators. Adherence was assessed by checklists. Competence was measured by scoring group interaction, an overall impression score and facilitator "didacticism". To measure "didacticism", we developed a novel way to calculate facilitator speech using computer software. Using this new instrument, implementation fidelity of SMILE(UK) was assessed on three modules of the course, for 28% of all courses delivered. RESULTS: Using the instrument for adherence, scores from two independent raters showed substantial agreement with weighted Kappa of 0.67 and high percent agreement of 81.2%. For didacticism, the results from both raters were highly correlated with an intraclass coefficient of 0.97 (p < 0.0001). We found that the courses were delivered with a good level of adherence (> 50% of scored items received the maximum of 2 points) and high competence. Groups were interactive (mean score: 1.9-2.0 out of 2) and the overall impression was on average assessed as "good". Didacticism varied from 42% to 93% of total module time and was not associated with the other competence scores. CONCLUSION: The instrument devised to measure implementation fidelity was reproducible and easy to use. The courses for the SMILE(UK) study were delivered with a good level of adherence to protocol while not compromising facilitator competence. TRIAL REGISTRATION: ISRCTN57937389 .

Randomized clinical trial of sacral versus percutaneous tibial nerve stimulation in patients with faecal incontinence.

BACKGROUND: Sacral nerve stimulation (SNS) is a well established therapy for faecal incontinence (FI). Percutaneous tibial nerve stimulation (PTNS) is a newer, less invasive, treatment. The effectiveness and acceptability of these treatments have not been compared systematically. METHODS: An investigator-blinded randomized pilot trial of PTNS versus SNS with a parallel qualitative study was performed. Quantitative clinical outcomes and qualitative data from patient interviews were collected for both interventions. RESULTS: Forty patients (39 women; mean age 59 years) met the eligibility criteria; 23 were randomized to receive SNS and 17 to PTNS. Fifteen patients progressed to permanent SNS implantation and 16 received a full course of PTNS. Within-group effect sizes were marginally greater for SNS than for PTNS on available-case analysis. Mean(s.d.) FI episodes per week at baseline, and 3 and 6 months of follow-up were: 11·4(12·0), 4·0(4·0) and 4·9(6·9) respectively for SNS compared with 10·6(11·2), 5·8(6·9) and 6·3(6·9) for PTNS. Mean(s.d.) Cleveland Clinic Incontinence Score values at baseline, and 3 and 6 months were: 16·2(3·0), 11·1(5·2) and 10·4(5·6) for SNS versus 15·1(2·7), 11·7(4·4) and 12·1(5·2) for PTNS. Improvement of at least 50 per cent in FI episodes per week at 6 months was seen in 11 of 18 patients in the SNS group compared with seven of 15 in the PTNS group. Effect estimates for SNS with chronic implanted stimulation were larger (10 of 15 patients at 6 months). Disease-specific and generic quality-of-life improvements complemented clinical outcome data. Qualitative analysis of interview data suggested that both treatments had high acceptability amongst patients. CONCLUSION: In the short term, both SNS and PTNS provide some clinical benefit to patients with FI. Registration numbers: 2010-018728-15 and 10479 (http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=10479).

Protocol for an HTA report: Does therapeutic writing help people with long-term conditions? Systematic review, realist synthesis and economic modelling.

INTRODUCTION: Long-term medical conditions (LTCs) cause reduced health-related quality of life and considerable health service expenditure. Writing therapy has potential to improve physical and mental health in people with LTCs, but its effectiveness is not established. This project aims to establish the clinical and cost-effectiveness of therapeutic writing in LTCs by systematic review and economic evaluation, and to evaluate context and mechanisms by which it might work, through realist synthesis. METHODS: Included are any comparative study of therapeutic writing compared with no writing, waiting list, attention control or placebo writing in patients with any diagnosed LTCs that report at least one of the following: relevant clinical outcomes; quality of life; health service use; psychological, behavioural or social functioning; adherence or adverse events. Searches will be conducted in the main medical databases including MEDLINE, EMBASE, PsycINFO, The Cochrane Library and Science Citation Index. For the realist review, further purposive and iterative searches through snowballing techniques will be undertaken. Inclusions, data extraction and quality assessment will be in duplicate with disagreements resolved through discussion. Quality assessment will include using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data synthesis will be narrative and tabular with meta-analysis where appropriate. De novo economic modelling will be attempted in one clinical area if sufficient evidence is available and performed according to the National Institute for Health and Care Excellence (NICE) reference case.

Systematic review of tibial nerve stimulation to treat faecal incontinence.

BACKGROUND: Two forms of tibial nerve stimulation are used to treat faecal incontinence (FI): percutaneous (PTNS) and transcutaneous (TTNS) tibial nerve stimulation. This article critically appraises the literature on both procedures. METHODS: A systematic review was performed adhering to the PRISMA framework. A comprehensive literature search was conducted, with systematic methodological quality assessment and data extraction. Summary measures for individual outcome variables are reported. RESULTS: Twelve articles met eligibility criteria; six related to PTNS, five to TTNS, and one to both procedures. These included ten case series and two randomized clinical trials (RCTs). Case series were evaluated using the National Institute for Health and Care Excellence quality assessment for case series, scoring 3-6 of 8. RCTs were evaluated using the Jadad score, scoring 4 of a possible 5 marks, and the Cochrane Collaboration bias assessment tool. From one RCT and case series reports, the success rate of PTNS, based on the proportion of patients who achieved a reduction in weekly FI episodes of at least 50 per cent, was 63-82 per cent, and that of TTNS was 0-45 per cent. In an RCT of TTNS versus sham, no patient had a reduction in weekly FI episodes of 50 per cent or more, whereas in an RCT of PTNS versus TTNS versus sham, 82 per cent of patients undergoing PTNS, 45 per cent of those having TTNS, and 13 per cent of patients in the sham group had treatment success. CONCLUSION: PTNS and TTNS result in significant improvements in some outcome measures; however, TTNS was not superior to sham stimulation in a large, adequately powered, RCT. As no adequate RCT of PTNS versus sham has been conducted, conclusions cannot be drawn regarding this treatment.

Interventions to improve exercise behaviour in sedentary people living with and beyond cancer: a systematic review.

BACKGROUND: To systematically review the effects of interventions to improve exercise behaviour in sedentary people living with and beyond cancer. METHODS: Only randomised controlled trials (RCTs) that compared an exercise intervention to a usual care comparison in sedentary people with a homogeneous primary cancer diagnosis, over the age of 18 years were eligible. The following electronic databases were searched: Cochrane Central Register of Controlled Trials MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; SportDiscus; PEDro from inception to August 2012. RESULTS: Fourteen trials were included in this review, involving a total of 648 participants. Just six trials incorporated prescriptions that would meet current recommendations for aerobic exercise. However, none of the trials included in this review reported intervention adherence of 75% or more for a set prescription that would meet current aerobic exercise guidelines. Despite uncertainty around adherence in many of the included trials, the interventions caused improvements in aerobic exercise tolerance at 8-12 weeks (SMD=0.73, 95% CI=0.51-0.95) in intervention participants compared with controls. At 6 months, aerobic exercise tolerance is also improved (SMD=0.70, 95% CI=0.45-0.94), although four of the five trials had a high risk of bias; hence, caution is warranted in its interpretation. CONCLUSION: Expecting the majority of sedentary survivors to achieve the current exercise guidelines is likely to be unrealistic. As with all well-designed exercise programmes, prescriptions should be designed around individual capabilities and frequency, duration and intensity or sets, repetitions, intensity of resistance training should be generated on this basis.

Exercise for depression in care home residents: a randomised controlled trial with cost-effectiveness analysis (OPERA).

BACKGROUND: Many older people living in care homes (long term residential care or nursing homes) are depressed. Exercise is a promising non-drug intervention for preventing and treating depression in this population. OBJECTIVE: To evaluate the impact of a 'whole-home' intervention, consisting of training for residential and nursing home staff backed up with a twice-weekly, physiotherapist-led exercise class on depressive symptoms in care home residents. DESIGN: A cluster randomised controlled trial with a cost-effectiveness analysis to compare (1) the prevalence of depression in intervention homes with that in control homes in all residents contributing data 12 months after homes were randomised (cross-sectional analysis); (2) the number of depressive symptoms at 6 months between intervention and control homes in residents who were depressed at pre-randomisation baseline assessment (depressed cohort comparison); and (3) the number of depressive symptoms at 12 months between intervention and control homes in all residents who were present at pre-randomisation baseline assessment (cohort comparison). SETTING: Seventy-eight care homes in Coventry and Warwickshire and north-east London. PARTICIPANTS: Care home residents aged ≥ 65 years. INTERVENTIONS: Control intervention: Depression awareness training programme for care home staff. Active intervention: A 'whole-home' exercise intervention, consisting of training for care home staff backed up with a twice-weekly, physiotherapist-led exercise group. MAIN OUTCOME MEASURES: Geriatric Depression Scale-15, proxy European Quality of Life-5 Dimensions (EQ-5D), cost-effectiveness from an National Health Service perspective, peripheral fractures and death. RESULTS: We recruited a total of 1054 participants. Cross-sectional analysis: We obtained 595 Geriatric Depression Scale-15 scores and 724 proxy EQ-5D scores. For the cohort analyses we obtained 765 baseline Geriatric Depression Scale-15 scores and 776 proxy EQ-5D scores. Of the 781 who we assessed prior to randomisation, 765 provided a Geriatric Depression Scale-15 score. Of these 374 (49%) were depressed and constitute our depressed cohort. Resource-use and quality-adjusted life-year data, based on proxy EQ-5D, were available for 798 residents recruited prior to randomisation. We delivered 3191 group exercise sessions with 31,705 person attendances and an average group size of 10 (5.3 study participants and 4.6 non-study participants). On average, our participants attended around half of the possible sessions. No serious adverse events occurred during the group exercise sessions. In the cross-sectional analysis the odds for being depressed were 0.76 [95% confidence interval (CI) 0.53 to 1.09] lower in the intervention group at 12 months. The point estimates for benefit for both the cohort analysis (0.13, 95% CI -0.33 to 0.60) and depressed cohort (0.22, 95% CI -0.52 to 0.95) favoured the control intervention. There was no evidence of differences in fracture rates or mortality (odds ratio 1.07, 95% CI 0.79 to 1.48) between the two groups. There was no evidence of differences in the other outcomes between the two groups. Economic analysis: The additional National Health Service cost of the OPERA intervention was £374 per participant (95% CI -£655 to £1404); the mean difference in quality-adjusted life-year was -0.0014 (95% CI -0.0728 to 0.0699). The active intervention was thus dominated by the control intervention, which was more effective and less costly. CONCLUSION: The results do not support the use of a whole-home physical activity and moderate-intensity exercise programme to reduce depression in care home residents. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43769277. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 18. See the Health Technology Assessment programme website for further project information.

Self-management education programmes by lay leaders for people with chronic conditions.

BACKGROUND: Lay-led self-management programmes are becoming widespread in the attempt to promote self-care for people with chronic conditions. OBJECTIVES: To assess systematically the effectiveness of lay-led self-management programmes for people with chronic conditions. SEARCH STRATEGY: We searched: the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2005, Issue 1), MEDLINE (January 1986 to May 2006), EMBASE (January 1986 to June 2006), AMED (January 1986 to June 2006), CINAHL (January 1986 to June 2006), DARE (1994 to July 2006, National Research Register (2000 to July 2006), NHS Economic Evaluations Database (1994 to July 2006), PsycINFO (January 1986 to June 2006), Science Citation Index (January 1986 to July 2006), reference lists and forward citation tracking of included studies. We contacted principal investigators and experts in the field. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing structured lay-led self-management education programmes for chronic conditions against no intervention or clinician-led programmes. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Results of RCTs were pooled using a random-effects model with standardised mean differences (SMDs) or weighted mean differences (WMDs) for continuous outcomes. MAIN RESULTS: We included seventeen trials involving 7442 participants. The interventions shared similar structures and components but studies showed heterogeneity in conditions studied, outcomes collected and effects. There were no studies of children and adolescents, only one study provided data on outcomes beyond six months, and only two studies reported clinical outcomes. PRIMARY OUTCOMES: Health status: There was a small, statistically-significant reduction in: pain (11 studies, SMD -0.10 (95% confidence interval (CI) -0.17 to -0.04)); disability (8 studies, SMD -0.15 (95% CI -0.25 to -0.05); and fatigue (7 studies, SMD -0.16 (95% CI -0.23 to -0.09); and small, statistically-significant improvement in depression (6 studies, SMD -0.16 95% CI -0.24 to -0.07). There was a small (but not statistically- or clinically-significant) improvement in psychological well-being (5 studies; SMD -0.12 (95% CI -0.33 to 0.09)); but no difference between groups for health-related quality of life (3 studies; WMD -0.03 (95% CI -0.09 to 0.02). Six studies showed a statistically-significant improvement in self-rated general health (WMD -0.20 (95% CI -0.31 to -0.10). Health behaviours: 7 studies showed a small, statistically-significant increase in self-reported aerobic exercise (SMD -0.20 (95% CI -0.27 to -0.12)) and a moderate increase in cognitive symptom management (4 studies, WMD -0.55 ( 95% CI -0.85 to -0.26)). Healthcare use: There were no statistically-significant differences between groups in physician or general practitioner attendance (9 studies; SMD -0.03 (95% CI -0.09 to 0.04)). There were also no statistically-significant differences between groups for days/nights spent in hospital (6 studies; WMD -0.32 (95% CI -0.71 to 0.07)). Self-efficacy: (confidence to manage condition) showed a small statistically-significant improvement (10 studies): SMD -0.30, 95% CI -0.41 to -0.19. No adverse events were reported in any of the studies. AUTHORS' CONCLUSIONS: Lay-led self-management education programmes may lead to small, short-term improvements in participants' self-efficacy, self-rated health, cognitive symptom management, and frequency of aerobic exercise. There is currently no evidence to suggest that such programmes improve psychological health, symptoms or health-related quality of life, or that they significantly alter healthcare use. Future research on such interventions should explore longer term outcomes, their effect on clinical measures of disease and their potential role in children and adolescents.

Body mass, weight control behaviours, weight perception and emotional well being in a multiethnic sample of early adolescents.

OBJECTIVE: To investigate weight perception, dieting and emotional well being across the range of body mass index (BMI) in a population-based multiethnic sample of early adolescents. DESIGN: Cross-sectional population-based survey. SUBJECTS: In total, 2789 adolescents 11-14 years of age from three highly deprived regional authorities in East London, in 2001. MEASUREMENTS: Data were collected by student-completed questionnaire on weight perception, dieting history, mental and physical health, health behaviours, social capital and sociodemographic factors. Height and weight were measured by trained researchers. Overweight was defined as BMI > or =85th centile and obesity as BMI > or =98th centile. Underweight was defined as BMI< or =15th centile. RESULTS: In all, 73% were from ethnic groups other than white British. Valid BMI were available for 2522 subjects (90.4%) of whom 14% were obese. Only 20% of overweight boys and 51% of overweight girls assessed their weight accurately. Accuracy of weight perception did not vary between ethnic groups. In all, 42% of girls and 26% of boys reported current dieting to lose weight. Compared with white British teenagers, a history of dieting was more common among Bangladeshi, Indian and mixed ethnicity boys and less likely among Pakistani girls. Self-esteem was not associated with BMI in girls but was significantly lower in obese boys than those of normal weight (P=0.02). Within ethnic subgroups, self-esteem was significantly lower in overweight white British boys (P=0.03) and obese Bangladeshi boys (P=0.01) and Bangladeshi girls (P=0.04), but significantly higher in obese black African girls (P=0.01) than those of normal weight. Obese young people had a higher prevalence of psychological distress (P=0.04), except among Bangladeshi teenagers, where overweight and obese young people had less psychological distress than those of normal weight (P=0.02). Birth outside the UK was associated with reduced risk of obesity in girls (P=0.02) but not with history of dieting, weight perception or psychological factors in either gender. CONCLUSION: High levels of current dieting for weight control and inaccurate perception of body mass are common across all ethnic groups. However, dieting history and the associations of obesity with self-esteem and psychological distress vary between ethnic groups. Interventions to prevent or treat obesity in black or minority ethnicity groups must consider cultural differences in the relationship between body mass, self-esteem and psychological distress.

Illicit and traditional drug use among ethnic minority adolescents in East London.

OBJECTIVES: To explore ethnic variations in the use of illicit and traditional drugs, and the association of indicators of acculturation with drug use among an ethnically diverse representative sample of early adolescents in East London. STUDY DESIGN: A cross-sectional questionnaire survey. METHODS: Confidential questionnaires were used to assess 2789 male and female pupils in years 7 and 9, aged 11-14 years old, from a representative sample of 28 secondary schools in East London. RESULTS: In total, 10.8% reported having ever tried illicit drugs and 7.3% reported ever using cannabis. Compared with white British adolescents, cannabis use in the previous month was significantly higher amongst black Caribbean adolescents. Lifetime cannabis use was significantly higher amongst black Caribbean and mixed ethnicity young people, but was lower amongst Bangladeshi, Indian and Pakistani adolescents. Living in UK for 5 years or less markedly reduced the risk of lifetime and recent cannabis use when controlled for ethnicity and social class. Glue or solvent use was reported in 3.2% of adolescents, with use significantly higher amongst Bangladeshi young people. Lifetime paan use was reported by 14.1% of the sample, and was almost completely confined to South Asian or mixed ethnicities. CONCLUSIONS: Ethnic differences in illicit drug use were found in the study population, and significant differences were found between ethnic groups often identified as 'black.' Further research is needed in understanding cultural-specific risk and protective factors in different ethnic groups, and the importance of cultural identity in mediating health risk behaviors. The high use of paan and glue/gas/solvents by Bangladeshi young people poses an unappreciated public health problem that may require targeted interventions.

Application of thermophilic enzymes in commercial biotransformation processes.

Biocatalysis is a useful tool in the provision of chiral technology and extremophilic enzymes are just one component in that toolbox. Their role is not always attributable to their extremophilic properties; as with any biocatalyst certain other criteria should be satisfied. Those requirements for a useful biocatalyst will be discussed including issues of selectivity, volume efficiency, security of supply, technology integration, intellectual property and regulatory compliance. Here we discuss the discovery and commercialization of an L-aminoacylase from Thermococcus litoralis, the product of a LINK project between Chirotech Technology and the University of Exeter. The enzyme was cloned into Escherichia coli to aid production via established mesophilic fermentation protocols. A simple downstream process was then developed to assist in the production of the enzyme as a genetically modified-organism-free reagent. The fermentation and downstream processes are operated at the 500 litre scale. Characterization of the enzyme demonstrated a substrate preference for N-benzoyl groups over N-acetyl groups. The operational parameters have been defined in part by substrate-concentration tolerances and also thermostability. Several examples of commercial biotransformations will be discussed including a process that is successful by virtue of the enzyme's thermotolerance.