Simon Briscoe

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

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

Using realist review to inform intervention development: methodological illustration and conceptual platform for collaborative care in offender mental health

BackgroundThis paper reports how we used a realist review, as part of a wider project to improve collaborative mental health care for prisoners with common mental health problems, to develop a conceptual platform. The importance of offenders gaining support for their mental health, and the need for practitioners across the health service, the criminal justice system, and the third sector to work together to achieve this is recognised internationally. However, the literature does not provide coherent analyses of how these ambitions can be achieved. This paper demonstrates how a realist review can be applied to inform complex intervention development that spans different locations, organisations, professions, and care sectors.MethodsWe applied and developed a realist review for the purposes of intervention development, using a three-stage process. (1) An iterative database search strategy (extending beyond criminal justice and offender health) and groups of academics, practitioners, and people with lived experience were used to identify explanatory accounts (n = 347). (2) From these accounts, we developed consolidated explanatory accounts (n = 75). (3) The identified interactions between practitioners and offenders (within their organisational, social, and cultural contexts) were specified in a conceptual platform. We also specify, step by step, how these explanatory accounts were documented, consolidated, and built into a conceptual platform. This addresses an important methodological gap for social scientists and intervention developers about how to develop and articulate programme and implementation theory underpinning complex interventions.ResultsAn integrated person-centred system is proposed to improve collaborative mental health care for offenders with common mental health problems (near to and after release) by achieving consistency between the goals of different sectors and practitioners, enabling practitioners to apply scientific and experiential knowledge in working judiciously and reflectively, and building systems and aligning resources that are centred on offenders’ health and social care needs.ConclusionsAs part of a broader programme of work, a realist review can make an important contribution to the specification of theoretically informed interventions that have the potential to improve health outcomes. Our conceptual platform has potential application in related systems of health and social care where integrated, and person-centred care is a goal.

Understanding the challenge of weight loss maintenance: a systematic review and synthesis of qualitative research on weight loss maintenance

ABSTRACT Behaviour change interventions can be effective in helping people to lose weight, but weight is often regained. Effective interventions are required to prevent this. We conducted a systematic review and synthesis of qualitative research on people’s experiences of weight loss maintenance. We searched bibliographic databases for qualitative studies about the experience of currently or previously overweight adults trying to maintain weight loss. We thematically synthesised study findings to develop a model of weight loss maintenance. Twenty six studies from five countries with 710 participants were included. The model developed through our synthesis proposes that making the behaviour changes required for weight loss maintenance generates psychological ‘tension’ due to the need to override existing habits, and incompatibility of the new behaviours with the fulfilment of psychological needs. Successful maintenance involves management or resolution of this tension. Management of tension can be achieved through self-regulation, renewing of motivation and managing external influences, although this can require constant effort. Resolution may be achieved through changing habits, finding non-obesogenic methods for addressing needs, and potentially through change in self-concept. Implications for the development of weight loss maintenance interventions are explored.

The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model.

BACKGROUND Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). OBJECTIVE To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). DATA SOURCES The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. REVIEW METHODS The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed indication (based on start dose administered) were included in the review. None of the RCTs were completely aligned with current European Union licenses. The results suggest a clinical benefit from ESAs for anaemia-related outcomes and an improvement in HRQoL scores. The impact of ESAs on AEs and survival remains highly uncertain, although point estimates are lower, confidence intervals are wide and not statistically significant. Base-case incremental cost-effectiveness ratios (ICERs) for ESA treatment compared with no ESA treatment ranged from £ 19,429 to £ 35,018 per QALY gained, but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs, including the possibility of overall health disbenefit. All ICERs were sensitive to survival and cost. LIMITATIONS The relative effectiveness of ESAs was not addressed; all ESAs were assumed to have equivalent efficacy. No studies were completely aligned with their European labelling beyond the starting dose evaluated. There is questionable generalisability given that the included trials were published >20 years ago and there have been many changes to chemotherapy as well as to the quality of supportive treatment. Trial quality was moderate or poor and there was considerable unexplained heterogeneity for a number of outcomes, particularly survival, and evidence of publication bias. Adjustments were not made to account for multiple testing. CONCLUSIONS ESAs could be cost-effective when used closer to licence, but there is considerable uncertainty, mainly because of unknown impacts on overall survival. STUDY REGISTRATION This study is registered as PROSPERO CRD42013005812. FUNDING The National Institute for Health Research Health Technology Assessment programme.

What is the clinical effectiveness and cost-effectiveness of conservative interventions for tendinopathy? An overview of systematic reviews of clinical effectiveness and systematic review of economic evaluations

BACKGROUND Lateral elbow tendinopathy (LET) is a common complaint causing characteristic pain in the lateral elbow and upper forearm, and tenderness of the forearm extensor muscles. It is thought to be an overuse injury and can have a major impact on the patients social and professional life. The condition is challenging to treat and prone to recurrent episodes. The average duration of a typical episode ranges from 6 to 24 months, with most (89%) reporting recovery by 1 year. OBJECTIVES This systematic review aims to summarise the evidence concerning the clinical effectiveness and cost-effectiveness of conservative interventions for LET. DATA SOURCES A comprehensive search was conducted from database inception to 2012 in a range of databases including MEDLINE, EMBASE and Cochrane Databases. METHODS AND OUTCOMES We conducted an overview of systematic reviews to summarise the current evidence concerning the clinical effectiveness and a systematic review for the cost-effectiveness of conservative interventions for LET. We identified additional randomised controlled trials (RCTs) that could contribute further evidence to existing systematic reviews. We searched MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Web of Science, The Cochrane Library and other important databases from inception to January 2013. RESULTS A total of 29 systematic reviews published since 2003 matched our inclusion criteria. These were quality appraised using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist; five were considered high quality and evaluated using a Grading of Recommendations, Assessment, Development and Evaluation approach. A total of 36 RCTs were identified that were not included in a systematic review and 29 RCTs were identified that had only been evaluated in an included systematic review of intermediate/low quality. These were then mapped to existing systematic reviews where further evidence could provide updates. Two economic evaluations were identified. LIMITATIONS The summary of findings from the review was based only on high-quality evidence (scoring of > 5 AMSTAR). Other limitations were that identified RCTs were not quality appraised and dichotomous outcomes were also not considered. Economic evaluations took effectiveness estimates from trials that had small sample sizes leading to uncertainty surrounding the effect sizes reported. This, in turn, led to uncertainty of the reported cost-effectiveness and, as such, no robust recommendations could be made in this respect. CONCLUSIONS Clinical effectiveness evidence from the high-quality systematic reviews identified in this overview continues to suggest uncertainty as to the effectiveness of many conservative interventions for the treatment of LET. Although new RCT evidence has been identified with either placebo or active controls, there is uncertainty as to the size of effects reported within them because of the small sample size. Conclusions regarding cost-effectiveness are also unclear. We consider that, although updated or new systematic reviews may also be of value, the primary focus of future work should be on conducting large-scale, good-quality clinical trials using a core set of outcome measures (for defined time points) and appropriate follow-up. Subgroup analysis of existing RCT data may be beneficial to ascertain whether or not certain patient groups are more likely to respond to treatments. STUDY REGISTRATION This study is registered as PROSPERO CRD42013003593. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Interventions to improve antimicrobial prescribing of doctors in training: the IMPACT (IMProving Antimicrobial presCribing of doctors in Training) realist review

Introduction Antimicrobial resistance has been described as a global crisis—more prudent prescribing is part of the solution. Behaviour change interventions are needed to improve prescribing practice. Presently, the literature documents that context impacts on prescribing decisions, yet insufficient evidence exists to enable researchers and policymakers to determine how local tailoring should take place. Doctors in training are an important group to study, being numerically the largest group of prescribers in UK hospitals. Unfortunately very few interventions specifically targeted this group. Methods and analysis Our project aims to understand how interventions to change antimicrobial prescribing behaviours of doctors in training produce their effects. We will recruit a project stakeholder group to advise us throughout. We will synthesise the literature using the realist review approach—a form of theory-driven interpretive systematic review approach often used to make sense of complex interventions. Interventions to improve antimicrobial prescribing behaviours are complex—they are context dependent, have long implementation chains, multiple non-linear interactions, emergence and depend on human agency. Our review will iteratively progress through 5 steps: step 1—Locate existing theories; step 2—Search for evidence; step 3—Article selection; step 4—Extracting and organising data; and step 5—Synthesising the evidence and drawing conclusions. Data analysis will use a realist logic of analysis to describe and explain what works, for whom, in what circumstances, in what respects, how and why to improve antimicrobial prescribing behaviour of doctors in training. Ethics and dissemination Ethical approval was not required for our review. Our dissemination strategy will be participatory and involve input from our stakeholder group. Tailored project outputs will be targeted at 3 audiences: (1) doctors in training; (2) clinical supervisors/trainers and medical educators; and (3) policy, decision makers, regulators and royal societies.

How do older people describe their sensory experiences of the natural world? A systematic review of the qualitative evidence

BackgroundDespite the increased scholarly interest in the senses and sensory experiences, the topic of older people’s sensory engagement with nature is currently under researched. This paper reviews and synthesises qualitative research evidence about how older people, including those living with dementia, describe their sensory engagement with the natural world.MethodsTen databases were searched from 1990 to September 2014: MEDLINE (Ovid), MEDLINE-in-Process (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), GreenFILE (EBSCO), ProQuest Sociology, ASSIA (ProQuest), International Bibliography of the Social Sciences (ProQuest); HMIC (Ovid); Social Policy and Practice (Ovid). Forward and backward citation chasing of included articles was conducted; 20 organizations were contacted to identify unpublished reports. Screening was undertaken independently by two reviewers.ResultsTwenty seven studies were included. Thematic analysis revealed that descriptions of sensory experiences are encompassed within six themes: descriptions from ‘the window’; sensory descriptions that emphasise vision; descriptions of ‘being in nature’; descriptions of ‘doing in nature’; barriers to sensory engagement; and meanings of being and doing in nature.ConclusionsOlder people derive considerable pleasure and enjoyment from viewing nature, being and doing in nature which, in turn has a positive impact on their wellbeing and quality of life. Future research could usefully explore how sensory engagement with nature could be used to stimulate reminiscences of places and people, and evoke past sensory experiences to enrich everyday life and maintain a sense of self.The protocol was registered with PROSPERO (CRD42015020736).

Web searching for systematic reviews: a case study of reporting standards in the UK Health Technology Assessment programme

Identifying literature for a systematic review requires searching a variety of sources. The main sources are typically bibliographic databases. Web searching using search engines and websites may be used to identify grey literature. Searches should be reported in order to ensure transparency and reproducibility. This study assesses the reporting of web searching for systematic reviews carried out by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (UK). The study also makes recommendations about reporting web searching for systematic reviews in order to achieve a reasonable level of transparency and reproducibility. Systematic reviews were identified by searching the HTA database via the Centre for Reviews and Dissemination (CRD) website. Systematic reviews were included in the study if they made reference to searching the web using either search engines or websites. A data-extraction checklist was designed to record how web searching was reported. The checklist recorded whether a systematic review reported: the names of search engines or websites; the dates they were searched; the search terms; the results of the searches; and, in the case of websites, whether a URL was reported. 554 HTA reports published between January 2004 and December 2013 were identified. 300 of these reports are systematic reviews, of which 108 report web searching using either a search engine or a website. Overall, the systematic reviews assessed in the study exhibit a low standard of web search reporting. In the majority of cases, the only details reported are the names of websites (n = 54) or search engines (n = 33). A small minority (n = 6) exhibit the highest standard of web search reporting. Most web search reporting in systematic reviews carried out on the UK HTA programme is not detailed enough to ensure transparency and reproducibility. Transparency of reporting could be improved by adhering to a reporting standard such as the standard detailed in the CRD systematic reviews methods guidance. Reproducibility is harder to achieve due to the frequency of changes to websites and search engines.

The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation.

BACKGROUND Colorectal cancer is the fourth most commonly diagnosed cancer in the UK after breast, lung and prostate cancer. People with metastatic disease who are sufficiently fit are usually treated with active chemotherapy as first- or second-line therapy. Targeted agents are available, including the antiepidermal growth factor receptor (EGFR) agents cetuximab (Erbitux®, Merck Serono UK Ltd, Feltham, UK) and panitumumab (Vecitibix®, Amgen UK Ltd, Cambridge, UK). OBJECTIVE To investigate the clinical effectiveness and cost-effectiveness of panitumumab in combination with chemotherapy and cetuximab in combination with chemotherapy for rat sarcoma (RAS) wild-type (WT) patients for the first-line treatment of metastatic colorectal cancer. DATA SOURCES The assessment included a systematic review of clinical effectiveness and cost-effectiveness studies, a review and critique of manufacturer submissions, and a de novo cohort-based economic analysis. For the assessment of effectiveness, a literature search was conducted up to 27 April 2015 in a range of electronic databases, including MEDLINE, EMBASE and The Cochrane Library. REVIEW METHODS Studies were included if they were randomised controlled trials (RCTs) or systematic reviews of RCTs of cetuximab or panitumumab in participants with previously untreated metastatic colorectal cancer with RAS WT status. All steps in the review were performed by one reviewer and checked independently by a second. Narrative synthesis and network meta-analyses (NMAs) were conducted for outcomes of interest. An economic model was developed focusing on first-line treatment and using a 30-year time horizon to capture costs and benefits. Costs and benefits were discounted at 3.5% per annum. Scenario analyses and probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS The searches identified 2811 titles and abstracts, of which five clinical trials were included. Additional data from these trials were provided by the manufacturers. No data were available for panitumumab plus irinotecan-based chemotherapy (folinic acid + 5-fluorouracil + irinotecan) (FOLFIRI) in previously untreated patients. Studies reported results for RAS WT subgroups. First-line treatment with anti-EGFR therapies in combination with chemotherapy appeared to have statistically significant benefits for patients who are RAS WT. For the independent economic evaluation, the base-case incremental cost-effectiveness ratio (ICER) for RAS WT patients for cetuximab plus oxaliplatin-based chemotherapy (folinic acid + 5-fluorouracil + oxaliplatin) (FOLFOX) compared with FOLFOX was £104,205 per quality-adjusted life-year (QALY) gained; for panitumumab plus FOLFOX compared with FOLFOX was £204,103 per QALY gained; and for cetuximab plus FOLFIRI compared with FOLFIRI was £122,554 per QALY gained. The ICERs were sensitive to treatment duration, progression-free survival, overall survival (resected patients only) and resection rates. LIMITATIONS The trials included RAS WT populations only as subgroups. No evidence was available for panitumumab plus FOLFIRI. Two networks were used for the NMA and model, based on the different chemotherapies (FOLFOX and FOLFIRI), as insufficient evidence was available to the assessment group to connect these networks. CONCLUSIONS Although cetuximab and panitumumab in combination with chemotherapy appear to be clinically beneficial for RAS WT patients compared with chemotherapy alone, they are likely to represent poor value for money when judged by cost-effectiveness criteria currently used in the UK. It would be useful to conduct a RCT in patients with RAS WT. STUDY REGISTRATION This study is registered as PROSPERO CRD42015016111. FUNDING The National Institute for Health Research Health Technology Assessment programme.

N of 1 trials and the optimal individualisation of drug treatments: a systematic review protocol

BackgroundGuidelines and evidence-based drug treatment recommendations are usually based on the results of clinical trials, which have limited generalisability in routine clinical settings due to their restrictive eligibility criteria. These trials are also conducted in ideal and rigorously controlled settings. N of 1 trials, which are single patient multiple crossover studies, offer a means of increasing the evidence base and individualising care for individuals in clinical practice. This systematic review of the N of 1 drug treatment trial aims to investigate its usefulness for achieving optimal individualised patient care.MethodsThe following databases will be searched for relevant articles: MEDLINE, EMBASE, PsycINFO (all via Ovid), AMED, CINAHAL (via EBSCO), The Cochrane Library (including CENTRAL, NHS EED, and DARE), and Web of Science (Thomson Reuters). Supplementary searches will include ongoing trial databases and organisational websites. All N of 1 trials in which patients have been treated with a drug will be considered. Outcomes will include information on the clinical usefulness of N of 1 trials—i.e. achievement of optimal individualised care, health-care utilisation of patients, frequently used practices, experiences of clinical care or participation in N of 1 trials, adherence to treatment plan, and unwanted effects of the treatment. Screening of included papers will be undertaken independently by two reviewers, while data extraction and the quality of reporting will be conducted by one reviewer and checked by another. Both quantitative and qualitative summaries will be reported using appropriate methods.DiscussionThis review will provide new insights into the clinical utility of N of 1 drug trials in helping participants find the most acceptable treatment as defined by patients and clinicians based on the selected outcome measures and the perspectives of participants involved in such trials. Findings from this review will inform the development of a stakeholder workshop and guidance to help physicians find the optimum therapy for their patients and will help guide future research on N of 1 trials.Systematic review registrationPROSPERO CRD42016032452