Background:
For systematic reviews to be rigorous, deliverable and useful they need a well-defined review question. Scoping for a review also requires the specification of clear inclusion criteria and planned synthesis methods. Guidance is lacking on how to develop these, especially within the context of undertaking rapid and responsive systematic reviews to inform health services and health policy.

Objective:
This report describes and discusses the experiences of review scoping of three commissioned research centres that conducted evidence syntheses to inform health and social care organisation, delivery and policy in the UK, between 2017 and 2020.

Data sources:
Researcher recollection, project meeting minutes, e-mail correspondence with stakeholders, and scoping searches; from allocation of a review topic through to review protocol agreement.

Methods:
We produced eight descriptive case studies of selected reviews from the three teams. From these we identified key issues that shape the processes of scoping and question formulation for evidence synthesis. The issues were then discussed and lessons drawn.

Findings:
Across the eight diverse case studies we identified 14 recurrent issues that were important in shaping the scoping processes and formulating a review’s questions. These were ‘consultative issues’, relating to securing input from review commissioners, policy customers, experts, patients and other stakeholders: managing and deciding priorities; reconciling different priorities/perspectives; achieving buy-in and engagement; educating the end-user about synthesis processes and products, and; managing stakeholder expectations. There were ‘interface issues’ relating to the interaction between review team and potential review users: identifying the niche/gap and optimising value; assuring and balancing rigour/reliability/relevance, and; assuring transferability/applicability of study evidence to specific policy/service user contexts. There were also ‘technical issues’ associated with the methods and conduct of the review: choosing the method(s) of synthesis; balancing fixed versus fluid review questions/components/definitions; taking stock of what research already exists; Mapping vs Scoping vs Reviewing; scoping/relevance as a continuous process not just at initial stage, and; calibrating general versus specific and broad versus deep coverage of topics.

Limitations:
As a retrospective joint reflection by review teams on their experiences of scoping processes, this report is not based on prospectively collected research data. Also, our evaluations were not externally validated by, for example, policy and service evidence users or patients and the public.

Conclusions:
We have summarised our reflections on scoping from this programme of reviews as 14 common issues and 28 practical ‘lessons learned’. Effective scoping of rapid, responsive reviews extends beyond information exchange and technical procedures for specifying a ‘gap’ in the evidence. These considerations work alongside social processes, in particular the building of relationships and shared understanding between reviewers, research commissioners and potential review users that may be reflective of consultancy, negotiation, and co-production models of research and information use.

Funding:
Commissioned by the National Institute of Health Research Heath Services and Delivery Research programme as NIHR132708 (including work from Award IDs:. 16/47/11, 16/47/17, 16/47/22).

Background
Mental health problems are common among children and young people in the UK. They are experienced in different ways for some young people from ethnic minority backgrounds. Furthermore, those from ethnic minority backgrounds often have greater difficulties accessing mental health support, variable levels of engagement with services, and may prefer different support to their White British peers.
Objective
To describe the nature and scope of qualitative research about the experiences of children and young people from ethnic minority backgrounds in seeking or obtaining care or support for mental health problems.
Data sources
We searched seven bibliographic databases (ASSIA, CINAHL, MEDLINE, PsycInfo, HMIC, Social Policy and Practice, and Web of Science) using relevant terms [23 June 2021].
Methods
The scoping review included qualitative research about young people’s experiences of seeking or engaging with services or support for mental health problems. Included studies were: published from 2012 onwards, from the UK, were about those aged 10 to 24 years and were from ethnic minority backgrounds (i.e. not White British). Study selection, data extraction and quality assessment (with ‘Wallace’ criteria) were conducted by two reviewers. We provide a descriptive summary of the aims, scope, sample, methods and quality of the included studies, and selected presentation of authors’ findings (i.e. no formal synthesis).
Findings
From 5335 unique search records, we included 26 papers or reports describing 22 diverse qualitative studies. Most of the studies were well conducted and clearly described.
There were studies of refugees/asylum seekers (5 studies), university students (4), and studies among young people experiencing particular mental health problems (14; some studies appear in multiple categories): schizophrenia or psychosis (3), eating disorders (3), post-traumatic stress disorder (3; in asylum seekers), substance misuse (2) self-harm (2), and obsessive compulsive disorder (1). There were also three studies in ethnic minority young people who were receiving particular treatments (CBT, multi-systemic therapy for families, and a culturally adapted family-based talking therapy).
Most studies had been conducted with young people or their parents from a range of different ethnic backgrounds. However, nine studies were conducted in particular ethnic groups: asylum-seekers from Afghanistan (2), Black and South Asian (2), Black African and Black-Caribbean (2), South Asian (1), Pakistani or Bangladeshi (1), and Orthodox Jewish (1).
The studies suggested a range of factors that influence care-seeking and access to mental health care, in terms of the beliefs and knowledge of young people and their parents, the design and promotion of services, and the characteristics of care professionals. Poor access was attributed to a lack of understanding of mental health problems, lack of information about services, lack of trust in care professionals, social stigma, and cultural expectations about mental resilience.
Limitations
As a rapid scoping review there was only basic synthesis of the research findings.
Future work
Future research about young people from ethnic minorities could cover a wider range of ethnic minorities, sample and analyse separately experiences from particular ethnic minorities, cover those accessing different services for different needs, and adopt multiple perspectives (e.g. service user, carer, clinician, service management).
Review protocol was pre-registered with Open Science Framework at: https://osf.io/wa7bf/

Abstract
. Background
. Increasing pressure to publicise research findings and generate impact, alongside an expectation from funding bodies to go beyond publication within academic journals, has generated interest in alternative methods of science communication.
. Our aim is to describe our experience of using a variety of creative communication tools, reflect on their use in different situations, enhance learning and generate discussion within the systematic review community.
.
. Methods
. Over the last 5 years, we have explored several creative communication tools within the systematic review process and beyond to extend dissemination beyond traditional academic mechanisms.
. Central to our approach is the co-production of a communication plan with potential evidence users which facilitates (i) the identification of key messages for different audiences, (ii) discussion of appropriate tools to communicate key messages and (iii) exploration of avenues to share them. We aim to involve evidence users in the production of a variety of outputs for each research project cognisant of the many ways in which individuals engage with information.
.
. Results
. Our experience has allowed us to develop an understanding of the benefits and challenges of a wide range of creative communication tools. For example, board games can be a fun way of learning, may flatten power hierarchies between researchers and research users and enable sharing of large amounts of complex information in a thought provoking way, but they are time and resource intensive both to produce and to engage with. Conversely, social media shareable content can be quick and easy to produce and to engage with but limited in the depth and complexity of shareable information.
.
. Discussion
. It is widely recognised that most stakeholders do not have time to invest in reading large, complex documents; creative communication tools can be a used to improve accessibility of key messages. Furthermore, our experience has highlighted a range of additional benefits of embedding these techniques within our project processes e.g. opening up two-way conversations with end-users of research to discuss the implications of findings.
.

OBJECTIVE: the academic and scientific community has reacted at pace to gather evidence to help and inform about COVID-19. Concerns have been raised about the quality of this evidence. The aim of this review was to map the nature, scope and quality of evidence syntheses on COVID-19 and to explore the relationship between review quality and the extent of researcher, policy and media interest. DESIGN AND SETTING: a meta-research: systematic review of reviews. INFORMATION SOURCES: PubMed, Epistemonikos COVID-19 evidence, the Cochrane Library of Systematic Reviews, the Cochrane COVID-19 Study Register, EMBASE, CINAHL, Web of Science Core Collection and the WHO COVID-19 database, searched between 10 June 2020 and 15 June 2020. ELIGIBILITY CRITERIA: Any peer-reviewed article reported as a systematic review, rapid review, overview, meta-analysis or qualitative evidence synthesis in the title or abstract addressing a research question relating to COVID-19. Articles described as meta-analyses but not undertaken as part of a systematic or rapid review were excluded. STUDY SELECTION AND DATA EXTRACTION: Abstract and full text screening were undertaken by two independent reviewers. Descriptive information on review type, purpose, population, size, citation and attention metrics were extracted along with whether the review met the definition of a systematic review according to six key methodological criteria. For those meeting all criteria, additional data on methods and publication metrics were extracted. RISK OF BIAS: for articles meeting all six criteria required to meet the definition of a systematic review, AMSTAR-2 ((A MeaSurement Tool to Assess systematic Reviews, version 2.0) was used to assess the quality of the reported methods. RESULTS: 2334 articles were screened, resulting in 280 reviews being included: 232 systematic reviews, 46 rapid reviews and 2 overviews. Less than half reported undertaking critical appraisal and a third had no reproducible search strategy. There was considerable overlap in topics, with discordant findings. Eighty-eight of the 280 reviews met all six systematic review criteria. of these, just 3 were rated as of moderate or high quality on AMSTAR-2, with the majority having critical flaws: only a third reported registering a protocol, and less than one in five searched named COVID-19 databases. Review conduct and publication were rapid, with 52 of the 88 systematic reviews reported as being conducted within 3 weeks, and a half published within 3 weeks of submission. Researcher and media interest, as measured by altmetrics and citations, was high, and was not correlated with quality. DISCUSSION: This meta-research of early published COVID-19 evidence syntheses found low-quality reviews being published at pace, often with short publication turnarounds. Despite being of low quality and many lacking robust methods, the reviews received substantial attention across both academic and public platforms, and the attention was not related to the quality of review methods. INTERPRETATION: Flaws in systematic review methods limit the validity of a review and the generalisability of its findings. Yet, by being reported as 'systematic reviews', many readers may well regard them as high-quality evidence, irrespective of the actual methods undertaken. The challenge especially in times such as this pandemic is to provide indications of trustworthiness in evidence that is available in 'real time'. PROSPERO REGISTRATION NUMBER: CRD42020188822.

Aim: This systematic review identifies, appraises and synthesizes the evidence on the provision of fundamental nursing care to hospitalized patients with a highly infectious virus and the effectiveness of adaptations to overcome barriers to care. Design: Systematic review. Data Sources: in July 2020, we searched Medline, PsycINFO (OvidSP), CINAHL (EBSCOhost), BNI (ProQuest), WHO COVID-19 Database (https://search.bvsalud.org/) MedRxiv (https://www.medrxiv.org/), bioRxiv (https://www.biorxiv.org/) and also Google Scholar, TRIP database and NICE Evidence, forwards citation searching and reference checking of included papers, from 2016 onwards. Review Methods: We included quantitative and qualitative research reporting (i) the views, perceptions and experiences of patients who have received fundamental nursing care whilst in hospital with COVID-19, MERS, SARS, H1N1 or EVD or (ii) the views, perceptions and experiences of professional nurses and non-professionally registered care workers who have provided that care. We included review articles, commentaries, protocols and guidance documents. One reviewer performed data extraction and quality appraisal and was checked by another person. Results: of 3086 references, we included 64 articles; 19 empirical research and 45 review articles, commentaries, protocols and guidance documents spanning five pandemics. Four main themes (and 11 sub-themes) were identified. Barriers to delivering fundamental care were wearing personal protective equipment, adequate staffing, infection control procedures and emotional challenges of care. These barriers were addressed by multiple adaptations to communication, organization of care, staff support and leadership. Conclusion: to prepare for continuation of the COVID-19 pandemic and future pandemics, evaluative studies of adaptations to fundamental healthcare delivery must be prioritized to enable evidence-based care to be provided in future. Impact: Our review identifies the barriers nurses experience in providing fundamental care during a pandemic, highlights potential adaptations that address barriers and ensure positive healthcare experiences and draws attention to the need for evaluative research on fundamental care practices during pandemics.

OBJECTIVE: to explore and map the findings of prior research priority-setting initiatives related to improving the health and well-being of older adults. DESIGN: Scoping review. DATA SOURCES: Searched MEDLINE, EMBASE, AgeLine, CINAHL and PsycINFO databases from January 2014 to 26 April 2021, and the James Lind Alliance top 10 priorities. ELIGIBILITY CRITERIA: We included primary studies reporting research priorities gathered from stakeholders that focused on ageing or the health of older adults (≥60 years). There were no restrictions by setting, but language was limited to English and French. DATA EXTRACTION AND SYNTHESIS: We used a modified Reporting Guideline for Priority Setting of Health Research (REPRISE) guideline to assess the transparency of the reported methods. Population-intervention-control-outcome (PICO) priorities were categorised according to their associated International Classification of Health Interventions (ICHI) and International Classification of Functioning (ICF) outcomes. Broad research topics were categorised thematically. RESULTS: Sixty-four studies met our inclusion criteria. The studies gathered opinions from various stakeholder groups, including clinicians (n=56 studies) and older adults (n=35), and caregivers (n=24), with 75% of the initiatives involving multiple groups. None of the included priority-setting initiatives reported gathering opinions from stakeholders located in low-income or middle-income countries. of the priorities extracted, 272 were identified as broad research topics, while 217 were identified as PICO priorities. PICO priorities that involved clinical outcomes (n=165 priorities) and interventions concerning health-related behaviours (n=59) were identified most often. Broad research topics on health services and systems were identified most often (n=60). Across all these included studies, the reporting of six REPRISE elements was deemed to be critically low. CONCLUSION: Future priority setting initiatives should focus on documenting a more detailed methodology with all initiatives eliciting opinions from caregivers and older adults to ensure priorities reflect the opinions of all key stakeholder groups.

BACKGROUND: Collaborative working between academic institutions and those who provide health and social care has been identified as integral in order to produce acceptable, relevant, and timely research, and for outputs to be useful and practical to implement. The ExCHANGE Collaboration aims to bring together researchers and people working, living in and visiting care homes to build capacity, share and mobilise knowledge, and identify key areas for future research. This paper describes an embedded, formative, realist and theory-driven evaluation which aims to gather information about how successful the ExCHANGE Collaboration is perceived to be in achieving its aims. An existing realist programme theory from the literature - Closer Collaboration - will be supplemented by two substantive theories: Co-production and Knowledge Brokering. This will result in an initial programme theory which will be tested by this formative evaluation to refine understanding of how the ExCHANGE Collaboration works. METHODS: the evaluation will employ mixed qualitative methods, including: analysis of documents such as feedback forms, Knowledge Broker journal/diary, event attendance records, risk and issues logs and other relevant paperwork gathered as part of project delivery; observations of events/activities; and interviews with care home providers and staff, care home residents, residents' family members, and researchers who are involved in the project (both project design/delivery, and also attendance or involvement in project activities/events). Framework Analysis will be used to interpret the data collected; analysis will be strategic, by focusing on particular key areas of importance in the developing theory of how the ExCHANGE Collaboration might achieve change. RESULTS: the results of this study are expected to be published in 2022. DISCUSSION: This evaluation will investigate how successful the ExCHANGE Collaboration is perceived to be in achieving its aims, in what way, in which contexts, and how this may differ for those involved. It will do this by testing an initial programme theory about how the collaboration works, for whom, under which circumstances, and in what way. Findings will be shared through written publication, an end of project learning event for those involved/interested in the project, and a lay summary to be made publically available.

IntroductionPatient experience of nursing care is correlated with safety, clinical effectiveness, care quality, treatment outcomes and service use. Effective nursing care includes actions to develop nurse–patient relationships and deliver physical and psychosocial care to patients. The high risk of transmission of the SARS-CoV-2 virus compromises nursing care. No evidence-based nursing guidelines exist for patients infected with SARS-CoV-2, leading to potential variations in patient experience, outcomes, quality and costs.Methods and analysiswe aim to recruit 840 in-patient participants treated for infection with the SARS-CoV-2 virus from 14 UK hospitals, to a cluster randomised controlled trial, with embedded process and economic evaluations, of care as usual and a fundamental nursing care protocol addressing specific areas of physical, relational and psychosocial nursing care where potential variation may occur, compared with care as usual. Our coprimary outcomes are patient-reported experience (Quality from the Patients’ Perspective; Relational Aspects of Care Questionnaire); secondary outcomes include care quality (pressure injuries, falls, medication errors); functional ability (Barthell Index); treatment outcomes (WHO Clinical Progression Scale); depression Patient Health Questionnaire-2 (PHQ-2), anxiety General Anxiety Disorder-2 (GAD-2), health utility (EQ5D) and nurse-reported outcomes (Measure of Moral Distress for Health Care Professionals). For our primary analysis, we will use a standard generalised linear mixed-effect model adjusting for ethnicity of the patient sample and research intensity at cluster level. We will also undertake a planned subgroup analysis to compare the impact of patient-level ethnicity on our primary and secondary outcomes and will undertake process and economic evaluations.Ethics and disseminationResearch governance and ethical approvals are from the UK National Health Service Health Research Authority Research Ethics Service. Dissemination will be open access through peer-reviewed scientific journals, study website, press and online media, including free online training materials on the Open University’s FutureLearn web platform.Trial registration numberISRCTN13177364; Pre-results.

The need to improve care for people living with dementia in the hospital setting has long been recognised. Person-centred care has the potential to improve the experience of care for persons living with dementia and their carers, and has been shown to improve the experiences of hospital staff caring for the persons living with dementia, however it remains challenging to deliver in a time- and task-focussed acute care setting. This commentary suggests that to embed person-centred care across the hospital environment, cultural changes are needed at organisational and ward levels. In particular there needs to be: leadership that supports and advocates for workforce capacity to recognise and meet both psychological and physical needs of people living with dementia, promotion of physical environments that support familiarisation and social interactions, an inclusive approach to carers and the development of a culture of sharing knowledge and information across hierarchies and roles. An evidence-based set of pointers for service change are described which highlight institutional and environmental practices and processes that need to be addressed in order for person-centred care to become part of routine care.

Background: By 2030, the global population of people older than 60 years is expected to be higher than the number of children under 10 years, resulting in major health and social care system implications worldwide. Without a supportive environment, whether social or built, diminished functional ability may arise in older people. Functional ability comprises an individual's intrinsic capacity and people's interaction with their environment enabling them to be and do what they value. Objectives: This evidence and gap map aims to identify primary studies and systematic reviews of health and social support services as well as assistive devices designed to support functional ability among older adults living at home or in other places of residence. Search Methods: We systematically searched from inception to August 2018 in: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, CINAHL, PsycINFO, AgeLine, Campbell Library, ASSIA, Social Science Citation Index and Social Policy & Practice. We conducted a focused search for grey literature and protocols of studies (e.g. ProQuest Theses and Dissertation Global, conference abstract databases, Help Age, PROSPERO, Cochrane and Campbell libraries and ClinicalTrials.gov). Selection Criteria: Screening and data extraction were performed independently in duplicate according to our intervention and outcome framework. We included completed and on-going systematic reviews and randomized controlled trials of effectiveness on health and social support services provided at home, assistive products and technology for personal indoor and outdoor mobility and transportation as well as design, construction and building products and technology of buildings for private use such as wheelchairs, and ramps. Data Collection and Analysis: We coded interventions and outcomes, and the number of studies that assessed health inequities across equity factors. We mapped outcomes based on the International Classification of Function, Disability and Health (ICF) adapted categories: intrinsic capacities (body function and structures) and functional abilities (activities). We assessed methodological quality of systematic reviews using the AMSTAR II checklist. Main Results: After de-duplication, 10,783 records were screened. The map includes 548 studies (120 systematic reviews and 428 randomized controlled trials). Interventions and outcomes were classified using domains from the International Classification of Function, Disability and Health (ICF) framework. Most systematic reviews (n = 71, 59%) were rated low or critically low for methodological quality. The most common interventions were home-based rehabilitation for older adults (n = 276) and home-based health services for disease prevention (n = 233), mostly delivered by visiting healthcare professionals (n = 474). There was a relative paucity of studies on personal mobility, building adaptations, family support, personal support and befriending or friendly visits. The most measured intrinsic capacity domains were mental function (n = 269) and neuromusculoskeletal function (n = 164). The most measured outcomes for functional ability were basic needs (n = 277) and mobility (n = 160). There were few studies which evaluated outcome domains of social participation, financial security, ability to maintain relationships and communication. There was a lack of studies in low- and middle-income countries (LMICs) and a gap in the assessment of health equity issues. Authors' Conclusions: There is substantial evidence for interventions to promote functional ability in older adults at home including mostly home-based rehabilitation for older adults and home-based health services for disease prevention. Remotely delivered home-based services are of greater importance to policy-makers and practitioners in the context of the COVID-19 pandemic. This map of studies published prior to the pandemic provides an initial resource to identify relevant home-based services which may be of interest for policy-makers and practitioners, such as home-based rehabilitation and social support, although these interventions would likely require further adaptation for online delivery during the COVID-19 pandemic. There is a need to strengthen assessment of social support and mobility interventions and outcomes related to making decisions, building relationships, financial security, and communication in future studies. More studies are needed to assess LMIC contexts and health equity issues.

BACKGROUND: Guidance on provision of care for people with dementia states that occupation people find meaningful is essential for well-being; however, definitions of 'meaningful occupation' are often broad, with intrinsic meaning coming from within the person rather than the activity, leading to an inconsistent understanding of its purpose. OBJECTIVES: This study aimed to create a conceptual framework depicting the types of meaning that are seen as stemming from occupation. METHOD: Six electronic databases were searched (CINAHL, PubMed Central, PsycINFO, Embase, AMED, ASSIA) using a pre-specified search strategy to identify qualitative studies relating to meaningful occupation for people living with dementia. From 114 eligible full-text articles, six qualitative studies were identified as sufficiently rich, topically relevant and explicit in their definition of meaningful activity. A further 14 were purposefully sampled for their ability to refute or advance the emerging conceptual framework. The synthesis is based on meta-ethnography and is reported following eMERGe guidance. RESULTS: We found the fundamental purpose of occupation is to support the person living with dementia to feel they are living a meaningful and fulfilling life. Three overlapping concepts were identified: (i) catalytic environment, (ii) meaningful life and (iii) occupation as a tool. CONCLUSION: the framework proposes how occupation could support meaning in multiple ways and considers how these forms of meaning were influenced by the worldviews and values of the individual, and context in which they were experienced. IMPLICATIONS FOR PRACTICE: the conceptual framework offers a consistent theoretical grounding with which to measure effectiveness of meaningful occupation for people living with dementia.

OBJECTIVES: to describe and reflect on the methods and influence of involvement of young people with lived experience within a complex evidence synthesis. STUDY DESIGN AND SETTING: Linked syntheses of quantitative and qualitative systematic reviews of evidence about interventions to improve the mental health of children and young people (CYP) with long-term physical conditions (LTCs). METHODS: Involvement was led by an experienced patient and public involvement in research lead. Young people with long-term physical conditions and mental health issues were invited to join a study-specific Children and Young People's Advisory Group (CYPAG). The CYPAG met face to face on four occasions during the project with individuals continuing to contribute to dissemination following report submission. RESULTS: Eight young people joined the CYPAG. Their views and experiences informed (a) a systematic review evaluating the effectiveness of interventions intended to improve the mental health of CYP with LTCs, (b) a systematic review exploring the experiences of interventions intended to improve the mental well-being of CYP with LTCs and (c) an overarching synthesis. The CYPAG greatly contributed to the team's understanding and appreciation of the wider context of the research. The young people found the experience of involvement empowering and felt they would use the knowledge they had gained about the research process in the future. CONCLUSION: Creating an environment that enabled meaningful engagement between the research team and the CYPAG had a beneficial influence on the young people themselves, as well as on the review process and the interpretation, presentation and dissemination of findings.

BACKGROUND: an increasingly high number of patients admitted to hospital have dementia. Hospital environments can be particularly confusing and challenging for people living with dementia (Plwd) impacting their wellbeing and the ability to optimize their care. Improving the experience of care in hospital has been recognized as a priority, and non-pharmacological interventions including activity interventions have been associated with improved wellbeing and behavioral outcomes for Plwd in other settings. This systematic review aimed at evaluating the effectiveness of activity interventions to improve experience of care for Plwd in hospital. METHODS: Systematic searches were conducted in 16 electronic databases up to October 2019. Reference lists of included studies and forward citation searching were also conducted. Quantitative studies reporting comparative data for activity interventions delivered to Plwd aiming to improve their experience of care in hospital were included. Screening for inclusion, data extraction and quality appraisal were performed independently by two reviewers with discrepancies resolved by discussion with a third where necessary. Standardized mean differences (SMDs) were calculated where possible to support narrative statements and aid interpretation. RESULTS: Six studies met the inclusion criteria (one randomized and five non-randomized uncontrolled studies) including 216 Plwd. Activity interventions evaluated music, art, social, psychotherapeutic, and combinations of tailored activities in relation to wellbeing outcomes. Although studies were generally underpowered, findings indicated beneficial effects of activity interventions with improved mood and engagement of Plwd while in hospital, and reduced levels of responsive behaviors. Calculated SMDs ranged from very small to large but were mostly statistically non-significant. CONCLUSIONS: the small number of identified studies indicate that activity-based interventions implemented in hospitals may be effective in improving aspects of the care experience for Plwd. Larger well-conducted studies are needed to fully evaluate the potential of this type of non-pharmacological intervention to improve experience of care in hospital settings, and whether any benefits extend to staff wellbeing and the wider ward environment.

BACKGROUND: Medication mismanagement is a major cause of both hospital admission and nursing home placement of frail older adults. Medication reviews by community pharmacists aim to maximise therapeutic benefit but also minimise harm. Pharmacist-led medication reviews have been the focus of several systematic reviews, but none have focussed on the home setting. REVIEW METHODS: to determine the effectiveness of pharmacist home visits for individuals at risk of medication-related problems we undertook a systematic review and meta-analysis of randomised controlled trials (RCTs). Thirteen databases were searched from inception to December 2018. Forward and backward citation of included studies was also performed. Articles were screened for inclusion independently by two reviewers. Randomised controlled studies of home visits by pharmacists for individuals at risk of medication-related problems were eligible for inclusion. Data extraction and quality appraisal were performed by one reviewer and checked by a second. Random-effects meta-analyses were performed where sufficient data allowed and narrative synthesis summarised all remaining data. RESULTS: Twelve RCTs (reported in 15 articles), involving 3410 participants, were included in the review. The frequency, content and purpose of the home visit varied considerably. The data from eight trials were suitable for meta-analysis of the effects on hospital admissions and mortality, and from three trials for the effects on quality of life. Overall there was no evidence of reduction in hospital admissions (risk ratio (RR) of 1.01 (95%CI 0.86 to 1.20, I2 = 69.0%, p = 0.89; 8 studies, 2314 participants)), or mortality (RR of 1.01 (95%CI 0.81 to 1.26, I2 = 0%, p = 0.94; 8 studies, 2314 participants)). There was no consistent evidence of an effect on quality of life, medication adherence or knowledge. CONCLUSION: a systematic review of twelve RCTs assessing the impact of pharmacist home visits for individuals at risk of medication related problems found no evidence of effect on hospital admission or mortality rates, and limited evidence of effect on quality of life. Future studies should focus on using more robust methods to assess relevant outcomes.

AbstractMulticomponent peri-operative interventions offer to accelerate patient recovery and improve cost-effectiveness. The recent National Institute of Health Research-commissioned evidence synthesis review by Nunns et al. considers the effectiveness and cost-effectiveness of all types of multicomponent interventions for older adults undergoing elective inpatient surgery. Enhanced recovery programmes (ERPs) were the most commonly evaluated intervention. An association between ERPs and decreased length of stay was observed, whilst complication rates and time to recovery were static or sometimes reduced. Important areas which lack research in the context of ERPs are patient-reported outcome measures, patients with complex needs and assessment of factors pertaining to successful ERP implementation. The next generation of ERP studies should seek to develop our understanding in these key areas.

Under-identification of mental health difficulties (MHD) in children and young people contributes to the significant unmet need for mental health care. School-based programmes have the potential to improve identification rates. This systematic review aimed to determine the feasibility of various models of school-based identification of MHD. We conducted systematic searches in Medline, Embase, PsycINFO, ERIC, British Education Index, and ASSIA using terms for mental health combined with terms for school-based identification. We included studies that assessed feasibility of school-based identification of students in formal education aged 3-18 with MHD, symptomatology of MHD, or exposed to risks for MHD. Feasibility was defined in terms of (1) intervention fit, (2) cost and resource implications, (3) intervention complexity, flexibility, manualisation, and time concerns, and (4) adverse events. Thirty-three studies met inclusion criteria. The majority focused on behavioural and socioemotional problems or suicide risk, examined universal screening models, and used cross-sectional designs. In general, school-based programmes for identifying MHD aligned with schools' priorities, but their appropriateness for students varied by condition. Time, resource, and cost concerns were the most common barriers to feasibility across models and conditions. The evidence base regarding feasibility is limited, and study heterogeneity prohibits definitive conclusions about the feasibility of different identification models. Education, health, and government agencies must determine how to allocate available resources to make the widespread adoption of school-based identification programmes more feasible. Furthermore, the definition and measurement of feasibility must be standardised to promote any future comparison between models and conditions.

BACKGROUND: Missed hospital outpatient appointments is a commonly reported problem in healthcare services around the world; for example, they cost the National Health Service (NHS) in the UK millions of pounds every year and can cause operation and scheduling difficulties worldwide. In 2002, the World Health Organization (WHO) published a report highlighting the need for a model of care that more readily meets the needs of people with chronic conditions. Patient-initiated appointment systems may be able to meet this need at the same time as improving the efficiency of hospital appointments. OBJECTIVES: to assess the effects of patient-initiated appointment systems compared with consultant-led appointment systems for people with chronic or recurrent conditions managed in secondary care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and six other databases. We contacted authors of identified studies and conducted backwards and forwards citation searching. We searched for current/ongoing research in two trial registers. Searches were run on 13 March 2019. SELECTION CRITERIA: We included randomised trials, published and unpublished in any language that compared the use of patient-initiated appointment systems to consultant-led appointment systems for adults with chronic or recurrent conditions managed in secondary care if they reported one or more of the following outcomes: physical measures of health status or disease activity (including harms), quality of life, service utilisation or cost, adverse effects, patient or clinician satisfaction, or failures of the 'system'. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references at title/abstract stage and full-text stage using prespecified inclusion criteria. We resolved disagreements though discussion. Two review authors independently completed data extraction for all included studies. We discussed and resolved discrepancies with a third review author. Where needed, we contacted authors of included papers to provide more information. Two review authors independently assessed the risk of bias using the Cochrane Effective Practice and Organisation of Care 'Risk of bias' tool, resolving any discrepancies with a third review author. Two review authors independently assessed the certainty of the evidence using GRADE. MAIN RESULTS: the 17 included randomised trials (3854 participants; mean age 41 to 76 years; follow-up 12 to 72 months) covered six broad health conditions: cancer, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, psoriasis and inflammatory bowel disease. The certainty of the evidence using GRADE ratings was mainly low to very low. The results suggest that patient-initiated clinics may make little or no difference to anxiety (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.68 to 1.12; 5 studies, 1019 participants; low-certainty evidence) or depression (OR 0.79 95% CI 0.51 to 1.23; 6 studies, 1835 participants; low-certainty evidence) compared to the consultant-led appointment system. The results also suggest that patient-initiated clinics may make little or no difference to quality of life (standardised mean difference (SMD) 0.12, 95% CI 0.00 to 0.25; 7 studies, 1486 participants; low-certainty evidence) compared to the consultant-led appointment system. Results for service utilisation (contacts) suggest there may be little or no difference in service utilisation in terms of contacts between the patient-initiated and consultant-led appointment groups; however, the effect is not certain as the rate ratio ranged from 0.68 to 3.83 across the studies (median rate ratio 1.11, interquartile (IQR) 0.93 to 1.37; 15 studies, 3348 participants; low-certainty evidence). It is uncertain if service utilisation (costs) are reduced in the patient-initiated compared to the consultant-led appointment groups (8 studies, 2235 participants; very low-certainty evidence). The results suggest that adverse events such as relapses in some conditions (inflammatory bowel disease and cancer) may have little or no reduction in the patient-initiated appointment group in comparison with the consultant-led appointment group (MD -0.20, 95% CI -0.54 to 0.14; 3 studies, 888 participants; low-certainty evidence). The results are unclear about any differences the intervention may make to patient satisfaction (SMD 0.05, 95% CI -0.41 to 0.52; 2 studies, 375 participants) because the certainty of the evidence is low, as each study used different questions to collect their data at different time points and across different health conditions. Some areas of risk of bias across all the included studies was consistently high (i.e. for blinding of participants and personnel and blinding of outcome assessment, other areas were largely of low risk of bias or were affected by poor reporting making the assessment unclear). AUTHORS' CONCLUSIONS: Patient-initiated appointment systems may have little or no effect on patient anxiety, depression and quality of life compared to consultant-led appointment systems. Other aspects of disease status and experience also appear to show little or no difference between patient-initiated and consultant-led appointment systems. Patient-initiated appointment systems may have little or no effect on service utilisation in terms of service contact and there is uncertainty about costs compared to consultant-led appointment systems. Patient-initiated appointment systems may have little or no effect on adverse events such as relapse or patient satisfaction compared to consultant-led appointment systems.

Background
Being in hospital can be particularly confusing and challenging not only for people living with dementia, but also for their carers and the staff who care for them. Improving the experience of care for people living with dementia in hospital has been recognised as a priority.
Objectives
To understand the experience of care in hospital for people living with dementia, their carers and the staff who care for them and to assess what we know about improving the experience of care.
Review methods
We undertook three systematic reviews: (1) the experience of care in hospital, (2) the experience of interventions to improve care in hospital and (3) the effectiveness and cost-effectiveness of interventions to improve the experience of care. Reviews 1 and 2 sought primary qualitative studies and were analysed using meta-ethnography. Review 3 sought comparative studies and economic evaluations of interventions to improve experience of care. An interweaving approach to overarching synthesis was used to integrate the findings across the reviews.
Data sources
Sixteen electronic databases were searched. Forwards and backwards citation chasing, author contact and grey literature searches were undertaken. Screening of title and abstracts and full texts was performed by two reviewers independently. A quality appraisal of all included studies was undertaken.
Results
Sixty-three studies (reported in 82 papers) were included in review 1, 14 studies (reported in 16 papers) were included in review 2, and 25 studies (reported in 26 papers) were included in review 3. A synthesis of review 1 studies found that when staff were delivering more person-centred care, people living with dementia, carers and staff all experienced this as better care. The line of argument, which represents the conceptual findings as a whole, was that ‘a change of hospital culture is needed before person-centred care can become routine’. From reviews 2 and 3, there was some evidence of improvements in experience of care from activities, staff training, added capacity and inclusion of carers. In consultation with internal and external stakeholders, the findings from the three reviews and overarching synthesis were developed into 12 DEMENTIA CARE pointers for service change: key institutional and environmental practices and processes that could help improve experience of care for people living with dementia in hospital.
Limitations
Few of the studies explored experience from the perspectives of people living with dementia. The measurement of experience of care across the studies was not consistent. Methodological variability and the small number of intervention studies limited the ability to draw conclusions on effectiveness.
Conclusions
The evidence suggests that, to improve the experience of care in hospital for people living with dementia, a transformation of organisational and ward cultures is needed that supports person-centred care and values the status of dementia care. Changes need to cut across hierarchies and training systems to facilitate working patterns and interactions that enable both physical and emotional care of people living with dementia in hospital. Future research needs to identify how such changes can be implemented, and how they can be maintained in the long term. To do this, well-designed controlled studies with improved reporting of methods and intervention details to elevate the quality of available evidence and facilitate comparisons across different interventions are required
Study registration
This study is registered as PROSPERO CRD42018086013
Funding
This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research Vol. 8, No. 43. See the NIHR Journals Library website for further project information. Additional funding was provided by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

BACKGROUND: Children and young people with long-term physical health conditions are at increased risk of experiencing mental health and well-being difficulties. However, there is a lack of research that explores the experiences of and attitudes towards interventions aiming to improve their mental health and well-being. This systematic review seeks to address this gap in the literature by exploring what children and young people with long-term conditions, their caregivers, and health practitioners perceive to be important aspects of interventions aiming to improve their mental health and well-being. METHODS: an information specialist searched five academic databases using predefined criteria for qualitative evaluations of interventions aiming to improve the mental health or well-being of children with long-term physical conditions. Reviewers also performed supplementary citation and grey literature searches. Two reviewers independently screened titles, abstracts, and full texts that met the inclusion criteria and conducted data extraction and quality assessment. Meta-ethnography was used to synthesize the findings. RESULTS: Screening identified 60 relevant articles. We identified five overarching constructs through the synthesis: (a) Getting in and Staying In, (b) Therapeutic Foundation, (c) Social Support, (d) a Hopeful Alternative, and (e) Empowerment. The line of argument that links these constructs together indicates that when interventions can provide an environment that allows young people to share their experiences and build empathetic relationships, it can enable participants to access social support and increase feelings of hope and empowerment. CONCLUSION: These findings may provide a framework to inform the development of mental health interventions for this population and evaluate existing interventions that already include some of the components or processes identified by this research. Further research is needed to establish which of the constructs identified by the line of argument are most effective in improving the mental well-being of young people living with long-term conditions.

BACKGROUND: Robopets are small animal-like robots which have the appearance and behavioural characteristics of pets. OBJECTIVE: to bring together the evidence of the experiences of staff, residents and family members of interacting with robopets and the effects of robopets on the health and well-being of older people living in care homes. DESIGN: Systematic review of qualitative and quantitative research. DATA SOURCES: We searched 13 electronic databases from inception to July 2018 and undertook forward and backward citation chasing. METHODS: Eligible studies reported the views and experiences of robopets from residents, family members and staff (qualitative studies using recognised methods of qualitative data collection and analysis) and the effects of robopets on the health and well-being of care home residents (randomised controlled trials, randomised crossover trials and cluster randomised trials). Study selection was undertaken independently by two reviewers. We used the Wallace criteria and the Cochrane Risk of Bias tool to assess the quality of the evidence. We developed a logic model with stakeholders and used this as a framework to guide data extraction and synthesis. Where appropriate, we used meta-analysis to combine effect estimates from quantitative studies. RESULTS: Nineteen studies (10 qualitative, 2 mixed methods and 7 randomised trials) met the inclusion criteria. Interactions with robopets were described as having a positive impact on aspects of well-being including loneliness, depression and quality of life by residents and staff, although there was no corresponding statistically significant evidence from meta-analysis for these outcomes. Meta-analysis showed evidence of a reduction in agitation with the robopet "Paro" compared to control (-0.32 [95% CI -0.61 to -0.04, p = 0.03]). Not everyone had a positive experience of robopets. CONCLUSIONS: Engagement with robopets appears to have beneficial effects on the health and well-being of older adults living in care homes, but not all chose to engage. Whether the benefits can be sustained are yet to be investigated. IMPLICATIONS FOR PRACTICE: Robopets have the potential to benefit people living in care homes, through increasing engagement and interaction. With the robopet acting as a catalyst, this engagement and interaction may afford comfort and help reduce agitation and loneliness.

This is a protocol for a Campbell Evidence and Gap Map. The objectives are to identify and assess the available evidence on health, social care and technological interventions to improve functional ability among older adults.

Introduction: Sleep positioning systems are often prescribed as part of a 24-hour postural management programme for children and adults with neurodisabilities. In a search for evidence of effectiveness for children with cerebral palsy a recent Cochrane review found two randomised controlled trials. This review aims to appraise a broader set of studies including any neurological diagnosis and users of all ages to inform therapists about the quality of the evidence underlying practice. Method: a comprehensive search for all peer-reviewed studies that evaluated the use of sleep positioning systems was conducted in MEDLINE, EMBASE, CINAHL, Cochrane Library databases, BNI, HMIC, PEDro, OTSeeker and clinical trials registries. Disability organisations, manufacturers and colleagues worldwide were also contacted. Titles were screened for relevance by two reviewers. Data were extracted into bespoke quantitative or qualitative forms by one reviewer and checked by a second. Findings were analysed into simple themes. Results: a total of 14 studies were eligible for inclusion; all were small and most were of low quality. Inferences of benefits cannot be made from the literature but also no harm was found. Conclusions: the body of evidence supporting practice remains small and mostly of low quality. Therapists should remain cautious when presenting the benefits to families.

The aim of this systematic review was to explore the effects and experiences of parent-to-parent support in neonatal intensive care from the perspectives of those giving, receiving, or implementing support. Electronic database searches (14 databases; February 2018) were supplemented with forward and backward citation chasing. Study selection, data extraction and quality appraisal were performed independently by two reviewers. Fourteen studies (6 quantitative and 8 qualitative) met our inclusion criteria. Four major themes were identified in the qualitative literature: ‘trust’, ‘hope’, ‘information’, and ‘connecting’. Quantitative studies showed parent-to-parent support increased perceptions of support, reduced maternal stress, and increased mothers' confidence in the ability to care for their baby. Whilst the rich qualitative evidence suggested mostly positive experiences of parent-to-parent support from all perspectives, robust trial evidence was lacking. Furthermore, differences in models for implementing parent-to-parent support provided limited opportunities to develop recommendations to guide best practice. The protocol for this study was registered on PROSPERO, registration number CRD42018090569.

BACKGROUND: in the last 2 decades, several studies have examined the association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children and shown conflicting results. AIM: This systematic review aimed to assess the evidence for an association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children. We also sought to assess whether levothyroxine treatment for maternal thyroid hormone insufficiency improves child neurodevelopment outcomes. METHODS: We performed systematic literature searches in MEDLINE, EMBASE, PSYCinfo, CINAHL, AMED, BNI, Cochrane, Scopus, Web of Science, GreyLit, Grey Source and Open Grey (latest search: March 2017). We also conducted targeted web searching and performed forwards and backwards citation chasing. Meta-analyses of eligible studies were carried out using the random-effects model. RESULTS: We identified 39 eligible articles (37 observational studies and 2 randomized controlled trials [RCT]). Meta-analysis showed that maternal subclinical hypothyroidism and hypothyroxinaemia are associated with indicators of intellectual disability in offspring (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.20 to 3.83, P = .01, and OR 1.63, 95% CI 1.03 to 2.56, P = .04, respectively). Maternal subclinical hypothyroidism and hypothyroxinaemia were not associated with attention deficit hyperactivity disorder, and their effect on the risk of autism in offspring was unclear. Meta-analysis of RCTs showed no evidence that levothyroxine treatment for maternal hypothyroxinaemia or subclinical hypothyroidism reduces the incidence of low intelligence quotient in offspring. LIMITATIONS: Although studies were generally of good quality, there was evidence of heterogeneity between the included observational studies (I2 72%-79%). CONCLUSION: Maternal hypothyroxinaemia and subclinical hypothyroidism may be associated with intellectual disability in offspring. Currently, there is no evidence that levothyroxine treatment, when initiated 8- to 20-week gestation (mostly between 12 and 17 weeks), for mild maternal thyroid hormone insufficiency during pregnancy reduces intellectual disability in offspring.

BACKGROUND: Parents of babies admitted to neonatal units experience an arduous emotional journey. Feelings of helplessness, fear, sadness, guilt, grief and anger are common. These feelings can lead to anxiety, depression and post-traumatic stress which may persist long after discharge from the unit. Support from a parent with first-hand experience able to empathise with problems and challenges may help. This systematic review will identify quantitative and qualitative evidence to address the role of parent-to-parent support interventions for families of babies cared for in neonatal units, and combine the findings in an integrated synthesis. METHODS: We are working in collaboration with a study-specific Parent Advisory Group (PAG) of parents who have relevant and varied lived experience of having a baby in neonatal care and those who have been involved in providing peer support. With the PAG, we will carry out a systematic review bringing together all existing research on parent-to-parent support for parents of babies cared for in neonatal units. This will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol has been produced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol extension (PRISMA-P). We have co-produced a plain language protocol summary with the PAG which details the different stages of the project, and this is available via our website ( http://clahrc-peninsula.nihr.ac.uk/research/parent-to-parent-support ) for anyone interested in learning more about the detail of the project. DISCUSSION: all outputs will be available on the NIHR CLAHRC South West Peninsula (PenCLAHRC) website and promoted via PenCLAHRC networks as well as organisations that have been contacted throughout the project. PAG members will be involved in writing and reviewing the academic paper and final report and in co-producing dissemination products such as plain language summaries. The PAG will influence the main conclusions of the systematic review, aid interpretation and help to communicate results in the most appropriate ways. We will hold an impact conference with representatives from neonatal units, national neonatal networks, commissioners of services and parents to discuss what the findings mean for clinical practice and service provision. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018090569.

OBJECTIVES: Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. METHODS: We carried out a systematic review of randomised controlled trials (RCTs) in eleven databases and 2 trials registries from inception to June 2016. An update search was run in November 2017. All screening was performed by 2 independent reviewers. Included studies were appraised using the Cochrane risk of bias tool and the evidence assessed using GRADE. We included any dietary, pharmacological or psychosocial intervention for RAP, defined by Apley or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria, in children and adolescents. RESULTS: We included 55 RCTs, involving 3572 children with RAP (21 dietary, 15 pharmacological, 19 psychosocial, and 1 multiarm). We found probiotic diets, cognitive-behavioural therapy (CBT) and hypnotherapy were reported to reduce pain in the short-term and there is some evidence of medium term effectiveness. There was insufficient evidence of effectiveness for all other dietary interventions and psychosocial therapies. There was no robust evidence of effectiveness for pharmacological interventions. CONCLUSIONS: Overall the evidence base for treatment decisions is poor. These data suggest that probiotics, CBT, and hypnotherapy could be considered as part of holistic management of children with RAP. The evidence regarding relative effectiveness of different strains of probiotics is currently insufficient to guide clinical practice. The lack of evidence of effectiveness for any drug suggests that there is little justification for their use outside of well-conducted clinical trials. There is an urgent need for high-quality RCTs to provide evidence to guide management of this common condition.

BACKGROUND: Numerous risk factors for dementia are well established, though the causal nature of these associations remains unclear. OBJECTIVE: to systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or dementia. METHODS: We searched five databases from inception to February 2017 and conducted citation searches including MR studies investigating the association between any risk factor and global cognitive function, all-cause dementia or dementia subtypes. Two reviewers independently assessed titles and abstracts, full-texts, and study quality. RESULTS: We included 18 MR studies investigating education, lifestyle factors, cardiovascular factors and related biomarkers, diabetes related and other endocrine factors, and telomere length. Studies were of predominantly good quality, however eight received low ratings for sample size and statistical power. The most convincing causal evidence was found for an association of shorter telomeres with increased risk of Alzheimer's disease (AD). Causal evidence was weaker for smoking quantity, vitamin D, homocysteine, systolic blood pressure, fasting glucose, insulin sensitivity, and high-density lipoprotein cholesterol. Well-replicated associations were not present for most exposures and we cannot fully discount survival and diagnostic bias, or the potential for pleiotropic effects. CONCLUSIONS: Genetic evidence supported a causal association between telomere length and AD, whereas limited evidence for other risk factors was largely inconclusive with tentative evidence for smoking quantity, vitamin D, homocysteine, and selected metabolic markers. The lack of stronger evidence for other risk factors may reflect insufficient statistical power. Larger well-designed MR studies would therefore help establish the causal status of these dementia risk factors.

BACKGROUND: There are no disease-modifying treatments for dementia. There is also no consensus on disease modifying outcomes. We aimed to produce the first evidence-based consensus on core outcome measures for trials of disease modification in mild-to-moderate dementia. METHODS AND FINDINGS: We defined disease-modification interventions as those aiming to change the underlying pathology. We systematically searched electronic databases and previous systematic reviews for published and ongoing trials of disease-modifying treatments in mild-to-moderate dementia. We included 149/22,918 of the references found; with 81 outcome measures from 125 trials. Trials involved participants with Alzheimer's disease (AD) alone (n = 111), or AD and mild cognitive impairment (n = 8) and three vascular dementia. We divided outcomes by the domain measured (cognition, activities of daily living, biological markers, neuropsychiatric symptoms, quality of life, global). We calculated the number of trials and of participants using each outcome. We detailed psychometric properties of each outcome. We sought the views of people living with dementia and family carers in three cities through Alzheimer's society focus groups. Attendees at a consensus conference (experts in dementia research, disease-modification and harmonisation measures) decided on the core set of outcomes using these results. Recommended core outcomes were cognition as the fundamental deficit in dementia and to indicate disease modification, serial structural MRIs. Cognition should be measured by Mini Mental State Examination or Alzheimer's Disease Assessment Scale-Cognitive Subscale. MRIs would be optional for patients. We also made recommendations for measuring important, but non-core domains which may not change despite disease modification. LIMITATIONS: Most trials were about AD. Specific instruments may be superseded. We searched one database for psychometric properties. INTERPRETATION: This is the first review to identify the 81 outcome measures the research community uses for disease-modifying trials in mild-to-moderate dementia. Our recommendations will facilitate designing, comparing and meta-analysing disease modification trials in mild-to-moderate dementia, increasing their value. TRIAL REGISTRATION: PROSPERO no. CRD42015027346.

Introduction: the association between history of coronary artery bypass graft surgery (CABG) and dementia risk remains unclear. Methods: We conducted a prospective cohort analysis using data on 3155 elderly adults free from prevalent dementia from the US population-based Cardiovascular Health Study (CHS) with adjudicated incident all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia. Results: in the CHS, the hazard ratio (HR) for all-cause dementia was 1.93 [95% confidence interval (CI), 1.36-2.74] for those with CABG history compared with those with no CABG history after adjustment for potential confounders. Similar HRs were observed for AD (HR=1.71; 95% CI, 0.98-2.98), VaD (HR=1.42; 95% CI, 0.56-3.65), and mixed dementia (HR=2.73; 95% CI, 1.55-4.80). The same pattern of results was observed when these CHS findings were pooled with a prior prospective study, the pooled HRs were 1.96 (95% CI, 1.42-2.69) for all-cause dementia, 1.71 (95% CI, 1.04-2.79) for AD and 2.20 (95% CI, 0.78-6.19) for VaD. Discussion: Our results suggest CABG history is associated with long-term dementia risk. Further investigation is warranted to examine the causal mechanisms which may explain this relationship or whether the association reflects differences in coronary artery disease severity.

BACKGROUND: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. OBJECTIVES: to agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). DATA SOURCES: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. REVIEW METHODS: the project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. RESULTS: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. LIMITATIONS: Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network. CONCLUSIONS: Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. FUTURE WORK: We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. STUDY REGISTRATION: the project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. FUNDING: the National Institute for Health Research Health Technology Assessment programme.

BACKGROUND: This is an update of the original Cochrane review, last published in 2009 (Huertas-Ceballos 2009). Recurrent abdominal pain (RAP), including children with irritable bowel syndrome, is a common problem affecting between 4% and 25% of school-aged children. For the majority of such children, no organic cause for their pain can be found on physical examination or investigation. Many dietary inventions have been suggested to improve the symptoms of RAP. These may involve either excluding ingredients from the diet or adding supplements such as fibre or probiotics. OBJECTIVES: to examine the effectiveness of dietary interventions in improving pain in children of school age with RAP. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE, Embase, eight other databases, and two trials registers, together with reference checking, citation searching and contact with study authors, in June 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing dietary interventions with placebo or no treatment in children aged five to 18 years with RAP or an abdominal pain-related, functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We grouped dietary interventions together by category for analysis. We contacted study authors to ask for missing information and clarification, when needed. We assessed the quality of the evidence for each outcome using the GRADE approach. MAIN RESULTS: We included 19 RCTs, reported in 27 papers with a total of 1453 participants. Fifteen of these studies were not included in the previous review. All 19 RCTs had follow-up ranging from one to five months. Participants were aged between four and 18 years from eight different countries and were recruited largely from paediatric gastroenterology clinics. The mean age at recruitment ranged from 6.3 years to 13.1 years. Girls outnumbered boys in most trials. Fourteen trials recruited children with a diagnosis under the broad umbrella of RAP or functional gastrointestinal disorders; five trials specifically recruited only children with irritable bowel syndrome. The studies fell into four categories: trials of probiotic-based interventions (13 studies), trials of fibre-based interventions (four studies), trials of low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diets (one study), and trials of fructose-restricted diets (one study).We found that children treated with probiotics reported a greater reduction in pain frequency at zero to three months postintervention than those given placebo (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.98 to -0.12; 6 trials; 523 children). There was also a decrease in pain intensity in the intervention group at the same time point (SMD -0.50, 95% CI -0.85 to -0.15; 7 studies; 575 children). However, we judged the evidence for these outcomes to be of low quality using GRADE due to an unclear risk of bias from incomplete outcome data and significant heterogeneity.We found that children treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (odds ratio (OR) 1.63, 95% CI 1.07 to 2.47; 7 studies; 722 children). The estimated number needed to treat for an additional beneficial outcome (NNTB) was eight, meaning that eight children would need to receive probiotics for one to experience improvement in pain in this timescale. We judged the evidence for this outcome to be of moderate quality due to significant heterogeneity.Children with a symptom profile defined as irritable bowel syndrome treated with probiotics were more likely to experience improvement in pain at zero to three months postintervention than those given placebo (OR 3.01, 95% CI 1.77 to 5.13; 4 studies; 344 children). Children treated with probiotics were more likely to experience improvement in pain at three to six months postintervention compared to those receiving placebo (OR 1.94, 95% CI 1.10 to 3.43; 2 studies; 224 children). We judged the evidence for these two outcomes to be of moderate quality due to small numbers of participants included in the studies.We found that children treated with fibre-based interventions were not more likely to experience an improvement in pain at zero to three months postintervention than children given placebo (OR 1.83, 95% CI 0.92 to 3.65; 2 studies; 136 children). There was also no reduction in pain intensity compared to placebo at the same time point (SMD -1.24, 95% CI -3.41 to 0.94; 2 studies; 135 children). We judged the evidence for these outcomes to be of low quality due to an unclear risk of bias, imprecision, and significant heterogeneity.We found only one study of low FODMAP diets and only one trial of fructose-restricted diets, meaning no pooled analyses were possible.We were unable to perform any meta-analyses for the secondary outcomes of school performance, social or psychological functioning, or quality of daily life, as not enough studies included these outcomes or used comparable measures to assess them.With the exception of one study, all studies reported monitoring children for adverse events; no major adverse events were reported. AUTHORS' CONCLUSIONS: Overall, we found moderate- to low-quality evidence suggesting that probiotics may be effective in improving pain in children with RAP. Clinicians may therefore consider probiotic interventions as part of a holistic management strategy. However, further trials are needed to examine longer-term outcomes and to improve confidence in estimating the size of the effect, as well as to determine the optimal strain and dosage. Future research should also explore the effectiveness of probiotics in children with different symptom profiles, such as those with irritable bowel syndrome.We found only a small number of trials of fibre-based interventions, with overall low-quality evidence for the outcomes. There was therefore no convincing evidence that fibre-based interventions improve pain in children with RAP. Further high-quality RCTs of fibre supplements involving larger numbers of participants are required. Future trials of low FODMAP diets and other dietary interventions are also required to facilitate evidence-based recommendations.

BACKGROUND: the need to better understand implementing evidence-informed dementia care has been recognised in multiple priority-setting partnerships. The aim of this scoping review was to give an overview of the state of the evidence on implementation and dissemination of dementia care, and create a systematic evidence map. METHODS: We sought studies that addressed dissemination and implementation strategies or described barriers and facilitators to implementation across dementia stages and care settings. Twelve databases were searched from inception to October 2015 followed by forward citation and grey literature searches. Quantitative studies with a comparative research design and qualitative studies with recognised methods of data collection were included. Titles, abstracts and full texts were screened independently by two reviewers with discrepancies resolved by a third where necessary. Data extraction was performed by one reviewer and checked by a second. Strategies were mapped according to the ERIC compilation. RESULTS: Eighty-eight studies were included (30 quantitative, 34 qualitative and 24 mixed-methods studies). Approximately 60% of studies reported implementation strategies to improve practice: training and education of professionals (94%), promotion of stakeholder interrelationships (69%) and evaluative strategies (46%) were common; financial strategies were rare (15%). Nearly 70% of studies reported barriers or facilitators of care practices primarily within residential care settings. Organisational factors, including time constraints and increased workload, were recurrent barriers, whereas leadership and managerial support were often reported to promote implementation. Less is known about implementation activities in primary care and hospital settings, or the views and experiences of people with dementia and their family caregivers. CONCLUSION: This scoping review and mapping of the evidence reveals a paucity of robust evidence to inform the successful dissemination and implementation of evidence-based dementia care. Further exploration of the most appropriate methods to evaluate and report initiatives to bring about change and of the effectiveness of implementation strategies is necessary if we are to make changes in practice that improve dementia care.

Background: Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children. Objectives: to determine the effectiveness of pharmacological interventions for RAP in children of school age. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies. Selection criteria: Randomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life. Data collection and analysis: Two review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results. Main results: This review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies. Authors' conclusions: There is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.

BACKGROUND: This review supersedes the original Cochrane review first published in 2008 (Huertas-Ceballos 2008).Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. No organic cause for this pain can be found on physical examination or investigation for the majority of such children. Although many children are managed by reassurance and simple measures, a large range of psychosocial interventions involving cognitive and behavioural components have been recommended. OBJECTIVES: to determine the effectiveness of psychosocial interventions for reducing pain in school-aged children with RAP. SEARCH METHODS: in June 2016 we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the references of identified studies and relevant reviews. SELECTION CRITERIA: Randomised controlled trials comparing psychosocial therapies with usual care, active control, or wait-list control for children and adolescents (aged 5 to 18 years) with RAP or an abdominal pain-related functional gastrointestinal disorder defined by the Rome III criteria were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Five review authors independently selected studies, assessed them for risk of bias, and extracted relevant data. We also assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: This review includes 18 randomised controlled trials (14 new to this version), reported in 26 papers, involving 928 children and adolescents with RAP between the ages of 6 and 18 years. The interventions were classified into four types of psychosocial therapy: cognitive behavioural therapy (CBT), hypnotherapy (including guided imagery), yoga, and written self-disclosure. The studies were carried out in the USA, Australia, Canada, the Netherlands, Germany, and Brazil. The majority of the studies were small and short term; only two studies included more than 100 participants, and only five studies had follow-up assessments beyond six months. Small sample sizes and the degree of assessed risk of performance and detection bias in many studies led to the overall quality of the evidence being rated as low to very low for all outcomes.For CBT compared to control, we found evidence of treatment success postintervention (odds ratio (OR) 5.67, 95% confidence interval (CI) 1.18 to 27.32; Z = 2.16; P = 0.03; 4 studies; 175 children; very low-quality evidence), but no evidence of treatment success at medium-term follow-up (OR 3.08, 95% CI 0.93 to 10.16; Z = 1.85; P = 0.06; 3 studies; 139 children; low-quality evidence) or long-term follow-up (OR 1.29, 95% CI 0.50 to 3.33; Z = 0.53; P = 0.60; 2 studies; 120 children; low-quality evidence). We found no evidence of effects of intervention on pain intensity scores measured postintervention (standardised mean difference (SMD) -0.33, 95% CI -0.74 to 0.08; 7 studies; 405 children; low-quality evidence), or at medium-term follow-up (SMD -0.32, 95% CI -0.85 to 0.20; 4 studies; 301 children; low-quality evidence).For hypnotherapy (including studies of guided imagery) compared to control, we found evidence of greater treatment success postintervention (OR 6.78, 95% CI 2.41 to 19.07; Z = 3.63; P = 0.0003; 4 studies; 146 children; low-quality evidence) as well as reductions in pain intensity (SMD -1.01, 95% CI -1.41 to -0.61; Z = 4.97; P < 0.00001; 4 studies; 146 children; low-quality evidence) and pain frequency (SMD -1.28, 95% CI -1.84 to -0.72; Z = 4.48; P < 0.00001; 4 studies; 146 children; low-quality evidence). The only study of long-term effect reported continued benefit of hypnotherapy compared to usual care after five years, with 68% reporting treatment success compared to 20% of controls (P = 0.005).For yoga therapy compared to control, we found no evidence of effectiveness on pain intensity reduction postintervention (SMD -0.31, 95% CI -0.67 to 0.05; Z = 1.69; P = 0.09; 3 studies; 122 children; low-quality evidence).The single study of written self-disclosure therapy reported no benefit for pain.There was no evidence of effect from the pooled analyses for any type of intervention on the secondary outcomes of school performance, social or psychological functioning, and quality of daily life.There were no adverse effects for any of the interventions reported. AUTHORS' CONCLUSIONS: the data from trials to date provide some evidence for beneficial effects of CBT and hypnotherapy in reducing pain in the short term in children and adolescents presenting with RAP. There was no evidence for the effectiveness of yoga therapy or written self-disclosure therapy. There were insufficient data to explore effects of treatment by RAP subtype.Higher-quality, longer-duration trials are needed to fully investigate the effectiveness of psychosocial interventions. Identifying the active components of the interventions and establishing whether benefits are sustained in the long term are areas of priority. Future research studies would benefit from employing active control groups to help minimise potential bias from wait-list control designs and to help account for therapist and intervention time.

BACKGROUND: Healthcare professionals throughout the developed world report higher levels of sickness absence, dissatisfaction, distress, and "burnout" at work than staff in other sectors. There is a growing call for the 'triple aim' of healthcare delivery (improving patient experience and outcomes and reducing costs; to include a fourth aim: improving healthcare staff experience of healthcare delivery. A systematic review commissioned by the United Kingdom's (UK) Department of Health reviewed a large number of international healthy workplace interventions and recommended five whole-system changes to improve healthcare staff health and wellbeing: identification and response to local need, engagement of staff at all levels, and the involvement, visible leadership from, and up-skilling of, management and board-level staff. OBJECTIVES: This systematic review aims to identify whole-system healthy workplace interventions in healthcare settings that incorporate (combinations of) these recommendations and determine whether they improve staff health and wellbeing. METHODS: a comprehensive and systematic search of medical, education, exercise science, and social science databases was undertaken. Studies were included if they reported the results of interventions that included all healthcare staff within a healthcare setting (e.g. whole hospital; whole unit, e.g. ward) in collective activities to improve physical or mental health or promote healthy behaviours. RESULTS: Eleven studies were identified which incorporated at least one of the whole-system recommendations. Interventions that incorporated recommendations to address local need and engage the whole workforce fell in to four broad types: 1) pre-determined (one-size-fits-all) and no choice of activities (two studies); or 2) pre-determined and some choice of activities (one study); 3) a wide choice of a range of activities and some adaptation to local needs (five studies); or, 3) a participatory approach to creating programmes responsive and adaptive to local staff needs that have extensive choice of activities to participate in (three studies). Only five of the interventions included substantial involvement and engagement of leadership and efforts aimed at up-skilling the leadership of staff to support staff health and wellbeing. Incorporation of more of the recommendations did not appear to be related to effectiveness. The heterogeneity of study designs, populations and outcomes excluded a meta-analysis. All studies were deemed by their authors to be at least partly effective. Two studies reported statistically significant improvement in objectively measured physical health (BMI) and eight in subjective mental health. Six studies reported statistically significant positive changes in subjectively assessed health behaviours. CONCLUSIONS: This systematic review identified 11 studies which incorporate at least one of the Boorman recommendations and provides evidence that whole-system healthy workplace interventions can improve health and wellbeing and promote healthier behaviours in healthcare staff.

This systematic review and synthesis of qualitative research explored contextual factors relevant to non-pharmacological interventions for Attention Deficit Hyperactivity Disorder (ADHD) in schools. We conducted meta-ethnography to synthesise 34 studies, using theories of stigma to further develop the synthesis. Studies suggested that the classroom context requiring pupils to sit still, be quiet and concentrate could trigger symptoms of ADHD, and that symptoms could then be exacerbated through informal/formal labelling and stigma, damaged self-perceptions and resulting poor relationships with staff and pupils. Influences of the school context on symptoms of ADHD were often invisible to teachers and pupils, with most attributions made to the individual pupil and/or the pupil's family. We theorise that this ‘invisibility’ is at least partly an artefact of stigma, and that the potential for stigma for ADHD to seem ‘natural and right’ in the context of schools needs to be taken into account when planning any intervention.

OBJECTIVES: to evaluate the effectiveness of behaviour changing interventions targeting ordering of thyroid function tests. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE and the Cochrane Database up to May 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies evaluating the effectiveness of behaviour change interventions aiming to reduce ordering of thyroid function tests. Randomised controlled trials (RCTs), non-randomised controlled studies and before and after studies were included. There were no language restrictions. STUDY APPRAISAL AND SYNTHESIS METHODS: 2 reviewers independently screened all records identified by the electronic searches and reviewed the full text of any deemed potentially relevant. Study details were extracted from the included papers and their methodological quality assessed independently using a validated tool. Disagreements were resolved through discussion and arbitration by a third reviewer. Meta-analysis was not used. RESULTS: 27 studies (28 papers) were included. They evaluated a range of interventions including guidelines/protocols, changes to funding policy, education, decision aids, reminders and audit/feedback; often intervention types were combined. The most common outcome measured was the rate of test ordering, but the effect on appropriateness, test ordering patterns and cost were also measured. 4 studies were RCTs. The majority of the studies were of poor or moderate methodological quality. The interventions were variable and poorly reported. Only 4 studies reported unsuccessful interventions but there was no clear pattern to link effect and intervention type or other characteristics. CONCLUSIONS: the results suggest that behaviour change interventions are effective particularly in reducing the volume of thyroid function tests. However, due to the poor methodological quality and reporting of the studies, the likely presence of publication bias and the questionable relevance of some interventions to current day practice, we are unable to draw strong conclusions or recommend the implementation of specific intervention types. Further research is thus justified. TRIAL REGISTRATION NUMBER: CRD42014006192.

BACKGROUND: the benefits of end-user involvement in health-care research are widely recognized by research agencies. There are few published evaluations of end-user involvement in systematic reviews. OBJECTIVES: (i) Describe end-user involvement in a complex mixed-methods systematic review of ADHD in schools, (ii) reflect on the impact of end-user involvement, (iii) highlight challenges and benefits experienced and (iv) provide suggestions to inform future involvement. METHODS: End-users were involved in all stages of the project, both as authors and as members of an advisory group. In addition, several events were held with groups of relevant end-users during the project. RESULTS: End-user input (i) guided the direction of the research, (ii) contributed to a typology of interventions and outcomes, (iii) contributed to the direction of data analysis and (iv) contributed to the robustness of the syntheses by demonstrating the alignment of interim findings with lived experiences. Challenges included (i) managing expectations, (ii) managing the intensity of emotion, (iii) ensuring that involvement was fruitful for all not just the researcher, (iv) our capacity to communicate and manage the process and (v) engendering a sense of involvement amongst end-users. CONCLUSIONS: End-user involvement was an important aspect of this project. To minimize challenges in future projects, a recognition by the project management team and the funding provider that end-user involvement even in evidence synthesis projects is resource intensive is essential to allow appropriate allocation of time and resources for meaningful engagement.

© 2016 SEBDA School-based non-pharmacological interventions are an important part of the treatment of attention-deficit/hyperactivity disorder (ADHD). We aimed to systematically review qualitative literature relating to the experience of and attitudes towards school-based non-pharmacological interventions for ADHD. Systematic searches of 20 electronic databases were undertaken. Reviewers screened titles, abstracts and full reports of studies, before extracting data and critically appraising 33 included papers. Studies were synthesised using meta-ethnographic methods. Four-key interrelated themes were identified: (1) individualising interventions, (2) structure of interventions, (3) barriers to effectiveness, (4) perceived moderators and impact of interventions. The perceived effectiveness of interventions used in school settings is reported to vary. Therefore, flexible, tailored interventions ought to hold potential. However, highly individualised interventions may negatively affect children with ADHD. Findings point to the need for school-based interventions to take into account the wider school context, as well as core symptoms of ADHD.

Educational policy and the school effectiveness movement often involve rhetoric about the benefit of parent involvement in schools, but high quality relationships between parents and teachers are not always straightforwardly achieved, and this may be particularly true for parents of children presenting with academic problems and/or Social, Emotional and Behavioural Difficulties (SEBD). A systematic review of qualitative research was conducted to explore the school-related experiences of parents of pupils diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). Six studies reported in seven papers met the inclusion criteria. High quality parent—teacher relationships were found to be the exception, with mothers feeling silenced and criticised. Findings show commonalities with wider research about parents, but identify additional grounds for conflict resulting from parental blame for a pupils’ disruptive behaviour, and the ambivalent nature of the concept of ADHD.

AIM/BACKGROUND: to describe the two-stage prioritization process being used by the UK National Institute for Health Research's Collaboration for Leadership in Applied Health Research and Care for the South-West Peninsula (or PenCLAHRC) - a joint health service and university partnership and reflect on implications for the wider context of priority setting in health-care research. METHOD: PenCLAHRC's process establishes the priorities of Stakeholders including service users across a regional health system for locally relevant health services research and implementation. Health research questions are collected from clinicians, academics and service users in Devon and Cornwall (UK) using a web-based question formulation tool. There is a two-stage prioritization process which uses explicit criteria and a wide Stakeholder group, including service users to identify important research questions relevant to the south-west peninsula locality. RESULTS: to date, a wide variety of health research topics have been prioritized by the PenCLAHRC Stakeholders. The research agenda reflects the interests of academics, clinicians and service users in the local area. Potential challenges to implementation of the process include time constraints, variable quality of questions (including the language of research) and initiating and maintaining engagement in the process. Shared prioritization of local health research needs can be achieved between Stakeholders from a wide range of perspectives. CONCLUSIONS: the processes developed have been successful and, with minor changes, will continue to be used during subsequent rounds of prioritization. Engagement of Stakeholders in establishing a research agenda encourages the most relevant health questions to be asked and may improve implementation of research findings and take up by service users.

Background
Health services are increasingly focused on measuring and monitoring outcomes, particularly those that reflect patients’ priorities. To be meaningful, outcomes measured should be valued by patients and carers, be consistent with what health professionals seek to achieve, and be robust in terms of measurement properties.

The aim of this study was (i) to seek a shared vision between families and clinicians regarding key aspects of health as outcomes, beyond mortality and morbidity, for children with neurodisability, and (ii) to appraise which multidimensional patient reported outcome measures (PROMs) could be used to assess salient health domains.

Methods
Relevant outcomes were identified from (i) qualitative research with children and young people with neurodisability and parent carers, (ii) Delphi survey with health professionals, and (iii) systematic review of PROMs. The International Classification of Functioning Disability and Health provided a common language to code aspects of health. A subset of stakeholders participated in a prioritisation meeting incorporating a Q-sorting task to discuss and rank aspects of health.

Results
A total of 33 pertinent aspects of health were identified. Fifteen stakeholders from the qualitative and Delphi studies participated in the prioritisation meeting: 3 young people, 5 parent carers, and 7 health professionals. Aspects of health that emerged as more important for families and targets for health professionals were: communication, emotional wellbeing, pain, sleep, mobility, self-care, independence, mental health, community and social life, behaviour, toileting and safety. Whilst available PROMs measure many aspects of health in the ICF, no single PROM captures all the key domains prioritised as for children and young people with neurodisability. The paucity of scales for assessing communication was notable.

Conclusions
We propose a core suite of key outcome domains for children with neurodisability that could be used in evaluative research, audit and as health service performance indicators. Future work could appraise domain-specific PROMs for these aspects of health; a single measure assessing the key aspects of health that could be applied across paediatric neurodisability remains to be developed.

Objective: This overarching synthesis brings together the findings of four systematic reviews including 138 studies focused on non-pharmacological interventions for ADHD used in school settings. These reviews considered the effectiveness of school-based interventions for ADHD, attitudes towards and experience of school-based interventions for ADHD, and the experience of ADHD in school settings. Method: We developed novel methods to compare the findings across these reviews inductively and deductively. Results: Key contextual issues that may influence the effectiveness and implementation of interventions include the relationships that pupils with ADHD have with their teachers and peers, the attributions individuals make about the etiology of ADHD, and stigma related to ADHD or intervention attendance. Conclusion: Although we found some positive effects for some outcomes and intervention categories, heterogeneity in effect size estimates and research evidence suggests a range of diverse contextual factors potentially moderate the implementation and effectiveness of school based interventions for ADHD.

BACKGROUND: Metabolic factors are increasingly recognized to play an important role in the pathogenesis of Alzheimer's disease and dementia. Abnormal parathyroid hormone (PTH) levels play a role in neuronal calcium dysregulation, hypoperfusion and disrupted neuronal signaling. Some studies support a significant link between PTH levels and dementia whereas others do not. METHODS: We conducted a systematic review through January 2014 to evaluate the association between PTH and parathyroid conditions, cognitive function and dementia. Eleven electronic databases and citation indexes were searched including Medline, Embase and the Cochrane Library. Hand searches of selected journals, reference lists of primary studies and reviews were also conducted along with websites of key organizations. Two reviewers independently screened titles and abstracts of identified studies. Data extraction and study quality were performed by one and checked by a second reviewer using predefined criteria. A narrative synthesis was performed due to the heterogeneity of included studies. RESULTS: the twenty-seven studies identified were of low and moderate quality, and challenging to synthesize due to inadequate reporting. Findings from six observational studies were mixed but suggest a link between higher serum PTH levels and increased odds of poor cognition or dementia. Two case-control studies of hypoparathyroidism provide limited evidence for a link with poorer cognitive function. Thirteen pre-post surgery studies for primary hyperparathyroidism show mixed evidence for improvements in memory though limited agreement in other cognitive domains. There was some degree of cognitive impairment and improvement postoperatively in observational studies of secondary hyperparathyroidism but no evident pattern of associations with specific cognitive domains. CONCLUSIONS: Mixed evidence offers weak support for a link between PTH, cognition and dementia due to the paucity of high quality research in this area.

© 2014 SEBDA. Childhood psychiatric disorders are associated with a wide range of adverse outcomes including poor academic attainment. For some children these difficulties are recognised through school Special Educational Need procedures (SEN) but many others may remain unidentified and/or unsupported. In Britain, government data suggests disproportionate representation of children with a SEN among children permanently excluded from school. This review asks whether school-aged children with impairing psychopathology were more likely to be excluded from school than those without. Databases covering education, social sciences, psychology and medicine were searched, experts were contacted and bibliographies of key papers were hand-searched. Studies were included if the population covered school-aged children, and if validated diagnostic measures had been used to assess psychopathology. Children with impairing psychopathology had greater odds of exclusion compared to the rest of the school-age population: odds ratios range from 1.13 (95% CI: 0.55–2.33) to 45.6 (95% CI: 3.8–21.3). These findings however need to be considered in light of the paucity of the literature and methodological weaknesses discussed.

This is the protocol for a review and there is no abstract. The objectives are as follows: to examine the effectiveness of dietary interventions for RAP in children of school age.

OBJECTIVE: Elderly residents with dementia commonly exhibit increased agitation at mealtimes. This interferes with eating and can be distressing for both the individual and fellow residents. This review examines the effectiveness of mealtime interventions aimed at improving behavioral symptoms in elderly people living with dementia in residential care. DESIGN: Systematic review. DATA SOURCES: Medline, PsycINFO, Embase, HMIC, AMED (OvidSP); CDSR, CENTRAL, DARE (Cochrane Library, Wiley); CINAHL (EBSCOhost); British Nursing Index (NHS Evidence); ASSIA (ProQuest); Social Science Citation Index (Web of Knowledge); EThOS (British Library); Social Care Online and OpenGrey from inception to November 2012. Forward and backward citation chases, hand searches of other review articles identified in the search, and key journals. TYPES OF STUDY: all comparative studies were included. Articles were screened for inclusion independently by 2 reviewers. Data extraction and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. Data were not suitable for meta-analysis so narrative synthesis was carried out. RESULTS: a total of 6118 articles were identified in the original search. Eleven articles were finally included. Mealtime interventions were categorized into 4 types: music, changes to food service, dining environment alteration, and group conversation. Study quality was poor, making it difficult to reach firm conclusions. Although all studies showed a trend in favor of the intervention, only 6 reported a statistically significant improvement in behavioral symptoms. Four studies suggest cumulative or lingering effects of music on agitated and aggressive behaviors. CONCLUSION: There is some evidence to suggest that mealtime interventions improve behavioral symptoms in elderly people with dementia living in residential care, although weak study designs limit the generalizability of the findings. Well designed, controlled trials are needed to further understand the utility of mealtime interventions in this setting.

Objective: to determine the effectiveness of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on psychological and physical outcomes for people with vascular disease. Design: Systematic review and meta-analysis of randomised controlled trials. Data sources: AMED, CINAHL, EMBASE, British Nursing Index, Medline, Web of Science, PsycINFO, Cochrane Database of Systematic Reviews, Central, Social Sciences Citation Index, Social Policy and Practice, and HMIC from inception to January 2013. Review methods: Articles were screened for inclusion independently by two reviewers. Data extraction and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. Random-effects meta-analyses were performed. Results: Nine articles (from eight original randomised controlled trials) met eligibility criteria and were included in the final review. In total, 578 participants were enrolled across the trials, with participants presenting with prehypertension/hypertension (n. = 3 trials), type 1 or 2 diabetes (n. = 2), heart disease (n. = 2) and stroke (n. = 1). Meta-analyses, using standardised mean differences, showed evidence of reductions in stress (- 0.36; 95% CI - 0.67 to - 0.09; p. = 0.01), depression (- 0.35; 95% CI - 0.53 to - 0.16; p. = 0.003) and anxiety (- 0.50; 95% CI - 0.70 to - 0.29; p. < 0.001). Effects on physical outcomes (blood pressure, albuminuria, stress hormones) were mixed. Conclusion: Whilst populations with vascular disease appear to derive a range of psychological benefits from MBSR/MBCT intervention, the effects on physical parameters of disease are not yet established. More robust studies, with longer term follow-up, are required to ascertain full effectiveness of such intervention. © 2014.

BACKGROUND: Antipsychotic medications are commonly used to manage the behavioral and psychological symptoms of dementia. Several large studies have demonstrated an association between treatment with antipsychotics and increased morbidity and mortality in people with dementia. AIMS: to assess the effectiveness of interventions used to reduce inappropriate prescribing of antipsychotics to the elderly with dementia in residential care. METHOD: Systematic searches were conducted in 12 electronic databases. Reference lists of all included studies and forward citation searching using Web of Science were also conducted. All quantitative studies with a comparative research design and studies in which recognized methods of qualitative data collection were used were included. Articles were screened for inclusion independently by 2 reviewers. Data extraction and quality appraisal were performed by 1 reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. RESULTS: Twenty-two quantitative studies (reported in 23 articles) were included evaluating the effectiveness of educational programs (n = 11), in-reach services (n = 2), medication review (n = 4), and multicomponent interventions (n = 5). No qualitative studies meeting our inclusion criteria were identified. Eleven studies were randomized or controlled in design; the remainder were uncontrolled before and after studies. Beneficial effects were seen in 9 of the 11 studies with the most robust study design with reductions in antipsychotic prescribing levels of between 12% and 20%. Little empirical information was provided on the sustainability of interventions. CONCLUSION: Interventions to reduce inappropriate prescribing of antipsychotic medications to people with dementia resident in care homes may be effective in the short term, but longer more robust studies are needed. For prescribing levels to be reduced in the long term, the culture and nature of care settings and the availability and feasibility of nondrug alternatives needs to be addressed.

BACKGROUND: Limited attention has been paid in the literature to multiple component fall prevention interventions that comprise two or more fixed combinations of fall prevention interventions that are not individually tailored following a risk assessment. The study objective was to determine the effect of multiple component interventions on fall rates, number of fallers and fall-related injuries among older people and to establish effect sizes of particular intervention combinations. METHODS: Medline, EMBASE, CINAHL, PsychInfo, Cochrane, AMED, UK Clinical Research Network Study Portfolio, Current Controlled Trials register and Australian and New Zealand Clinical Trials register were systematically searched to August 2013 for randomised controlled trials targeting those aged 60 years and older with any medical condition or in any setting that compared multiple component interventions with no intervention, placebo or usual clinical care on the outcomes reported falls, number that fall or fall-related injuries. Included studies were appraised using the Cochrane risk of bias tool. Estimates of fall rate ratio and risk ratio were pooled across studies using random effects meta-analysis. Data synthesis took place in 2013. RESULTS: Eighteen papers reporting 17 trials were included (5034 participants). There was a reduction in the number of people that fell (pooled risk ratio = 0.85, 95% confidence interval (95% CI) 0.80 to 0.91) and the fall rate (pooled rate ratio = 0.80, 95% CI 0.72 to 0.89) in favour of multiple component interventions when compared with controls. There was a small amount of statistical heterogeneity (I(2) =20%) across studies for fall rate and no heterogeneity across studies examining number of people that fell. CONCLUSIONS: This systematic review and meta-analysis of randomised controlled trials found evidence that multiple component interventions that are not tailored to individually assessed risk factors are effective at reducing both the number of people that fall and the fall rate. This approach should be considered as a service delivery option.

This is the protocol for a review and there is no abstract. The objectives are as follows: to determine the effectiveness of pharmacological interventions for RAP in children of school age.

This is the protocol for a review and there is no abstract. The objectives are as follows: to determine the effectiveness of psychosocial interventions for RAP in children of school age.

Childhood psychiatric disorders are associated with a wide range of adverse outcomes including poor academic attainment. For some children these difficulties are recognised through school Special Educational Need procedures (SEN) but many others may remain unidentified and/or unsupported. In Britain, government data suggests disproportionate representation of children with a SEN among children permanently excluded from school. This review asks whether school-aged children with impairing psychopathology were more likely to be excluded from school than those without. Databases covering education, social sciences, psychology and medicine were searched, experts were contacted and bibliographies of key papers were hand-searched. Studies were included if the population covered school-aged children, and if validated diagnostic measures had been used to assess psychopathology. Children with impairing psychopathology had greater odds of exclusion compared to the rest of the school-age population: odds ratios range from 1.13 (95% CI: 0.55-2.33) to 45.6 (95% CI: 3.8-21.3). These findings however need to be considered in light of the paucity of the literature and methodological weaknesses discussed. © 2014 © 2014 SEBDA.

OBJECTIVE: to examine the impact of gardens and outdoor spaces on the mental and physical well-being of people with dementia who are resident in care homes and understand the views of people with dementia, their carers, and care home staff on the value of gardens and outdoor spaces. DESIGN: Systematic review. METHODS: Fourteen databases were searched from inception to February 2013. Forward and backward citation chasing of included articles was conducted; 38 relevant organizations were contacted to identify unpublished reports. Titles, abstracts, and full texts were screened independently by 2 reviewers in a 2-stage process and were discussed with a third reviewer where necessary. Results were synthesized narratively. RESULTS: Seventeen studies were included: 9 quantitative, 7 qualitative, and 1 mixed methods. The quantitative studies were of poor quality but suggested decreased levels of agitation were associated with garden use. The views and experiences of the garden are discussed in relation to themes of how the garden was used, nature of interactions, impact/effect of the gardens, mechanisms/how the garden was thought to have an effect, and negatives (such as perception of the garden as a hazard and the limited staff time). CONCLUSION: There are promising impacts on levels of agitation in care home residents with dementia who spend time in a garden. Future research would benefit from a focus on key outcomes measured in comparable ways with a separate focus on what lies behind limited accessibility to gardens within the residential care setting.

The need to improve the nutrition of the elderly living in long term care has long been recognised, but how this can best be achieved, and whether (and which) intervention is successful in reducing morbidity is less well understood. The aim of this systematic review was to determine the effectiveness of mealtime interventions for the elderly living in residential care. Mealtime interventions were considered as those that aimed to change/improve the mealtime routine, practice, experience or environment. Following comprehensive searches, review and appraisal, 37 articles were included. Inadequate reporting in over half of the articles limited data quality appraisal. Mealtime interventions were categorised into five types: changes to food service, food improvement, dining environment alteration, staff training and feeding assistance. Meta-analysis found inconsistent evidence of effects on body weight of changes to food service (0.5 kg; 95% CI: -1.1 to 2.2; p=0.51), food improvement interventions (0.4 kg; 95% CI: -0.8 to 1.7; p=0.50) or alterations to dining environment (1.5 kg; 95% CI: -0.7 to 2.8; p=0.23). Findings from observational studies within these intervention types were mixed, but generally positive. Observational studies also found positive effects on food/caloric intake across all intervention types, though meta-analyses of randomised studies showed little evidence of any effects on food/caloric intake in food improvement studies (-5 kcal; 95% CI: -36 to 26; p=0.74). There was some evidence of an effect on daily energy intakes within dining environment studies (181 kcal/day, 95% CI: -5 to 367, p=0.06). The need to improve the nutrition of the elderly living in residential long term care is well recognised. This review found some evidence that simple intervention around various aspects of mealtime practices and the mealtime environment can result in favourable nutritional outcomes. Further large scale pragmatic trials, however, are still required to establish full efficacy of such interventions.

Background
Volunteering has been advocated by the United Nations, and American and European governments as a way to engage people in their local communities and improve social capital, with the potential for public health benefits such as improving wellbeing and decreasing health inequalities. Furthermore, the US Corporation for National and Community Service Strategic Plan for 2011–2015 focused on increasing the impact of national service on community needs, supporting volunteers’ wellbeing, and prioritising recruitment and engagement of underrepresented populations. The aims of this review were to examine the effect of formal volunteering on volunteers’ physical and mental health and survival, and to explore the influence of volunteering type and intensity on health outcomes.

Methods
Experimental and cohort studies comparing the physical and mental health outcomes and mortality of a volunteering group to a non-volunteering group were identified from twelve electronic databases (Cochrane Library, Medline, Embase, PsychINFO, CINAHL, ERIC, HMIC, SSCI, ASSIA, Social Care Online, Social Policy and Practice) and citation tracking in January 2013. No language, country or date restrictions were applied. Data synthesis was based on vote counting and random effects meta-analysis of mortality risk ratios.

Results
Forty papers were selected: five randomised controlled trials (RCTs, seven papers); four non-RCTs; and 17 cohort studies (29 papers). Cohort studies showed volunteering had favourable effects on depression, life satisfaction, wellbeing but not on physical health. These findings were not confirmed by experimental studies. Meta-analysis of five cohort studies found volunteers to be at lower risk of mortality (risk ratio: 0.78; 95% CI: 0.66, 0.90). There was insufficient evidence to demonstrate a consistent influence of volunteering type or intensity on outcomes.

Conclusion
Observational evidence suggested that volunteering may benefit mental health and survival although the causal mechanisms remain unclear. Consequently, there was limited robustly designed research to guide the development of volunteering as a public health promotion intervention. Future studies should explicitly map intervention design to clear health outcomes as well as use pragmatic RCT methodology to test effects.

BACKGROUND:: Adherence to a Mediterranean diet has been associated with lower risk of various age-related diseases including dementia. Although narrative reviews have been published, no systematic review has synthesized studies on the association between Mediterranean diet adherence and cognitive function or dementia. METHODS:: We conducted a systematic review of 11 electronic databases (including Medline) of published articles up to January 2012. Reference lists, selected journal contents, and relevant websites were also searched. Study selection, data extraction, and quality assessment were performed independently by two reviewers using predefined criteria. Studies were included if they examined the association between a Mediterranean diet adherence score and cognitive function or dementia. RESULTS:: Twelve eligible papers (11 observational studies and one randomized controlled trial) were identified, describing seven unique cohorts. Despite methodological heterogeneity and limited statistical power in some studies, there was a reasonably consistent pattern of associations. Higher adherence to Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline, and reduced risk of Alzheimer disease in nine out of 12 studies, whereas results for mild cognitive impairment were inconsistent. CONCLUSIONS:: Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Further studies would be useful to clarify the association with mild cognitive impairment and vascular dementia. Long-term randomized controlled trials promoting a Mediterranean diet may help establish whether improved adherence helps to prevent or delay the onset of Alzheimer disease and dementia. © 2013 Lippincott Williams & Wilkins.

BACKGROUND: the cost to the NHS of missed or inappropriate hospital appointments is considerable. Alternative methods of appointment scheduling might be more flexible to patients' needs without jeopardising health and service quality. The objective was to systematically review evidence of patient initiated clinics in secondary care on patient reported outcomes among patients with chronic/recurrent conditions. METHODS: Seven databases were searched from inception to June 2013. Hand searching of included studies references was also conducted. Studies comparing the effects of patient initiated clinics with traditional consultant led clinics in secondary care for patients with long term chronic or recurrent diseases on health related quality of life and/or patient satisfaction were included. Data was extracted by one reviewer and checked by a second. Results were synthesised narratively. RESULTS: Seven studies were included in the review, these covered a total of 1,655 participants across three conditions: breast cancer, inflammatory bowel disease and rheumatoid arthritis. Quality of reporting was variable. Results showed no significant differences between the intervention and control groups for psychological and health related quality of life outcomes indicating no evidence of harm. Some patients reported significantly more satisfaction using patient-initiated clinics than usual care (p

This is the protocol for a review and there is no abstract. The objectives are as follows: to assess the effects of patient-initiated appointment systems compared with usual care in people with chronic or recurrent conditions managed in the secondary care setting. In particular, we are interested in whether these appointment systems can effectively manage disease without causing harm to patients and whether costs related to the provision of the service can be reduced compared with usual care.

AIM: to review the qualitative and quantitative evidence of the benefits of peer support for parents of children with disabling conditions in the context of health, well-being, impact on family, and economic and service implications. METHOD: We comprehensively searched multiple databases. Eligible studies evaluated parent-to-parent support and reported on the psychological health and experience of giving or receiving support. There were no limits on the child's condition, study design, language, date, or setting. We sought to aggregate quantitative data; findings of qualitative studies were combined using thematic analysis. Qualitative and quantitative data were brought together in a narrative synthesis. RESULTS: Seventeen papers were included: nine qualitative studies, seven quantitative studies, and one mixed-methods evaluation. Four themes were identified from qualitative studies: (1) shared social identity, (2) learning from the experiences of others, (3) personal growth, and (4) supporting others. Some quantitative studies reported a positive effect of peer support on psychological health and other outcomes; however, this was not consistently confirmed. It was not possible to aggregate data across studies. No costing data were identified. CONCLUSION: Qualitative studies strongly suggest that parents perceive benefit from peer support programmes, an effect seen across different types of support and conditions. However, quantitative studies provide inconsistent evidence of positive effects. Further research should explore whether this dissonance is substantive or an artefact of how outcomes have been measured.

BACKGROUND: Routine follow-up following uncomplicated surgery is being delivered by telephone in some settings. Telephone consultations may be preferable to patients and improve outpatient resource use. We aimed to compare the effectiveness of telephone consultations with face to face follow-up consultations, in patients discharged from hospital following surgery. METHODS: Seven electronic databases (including Medline, Embase and PsycINFO) were searched from inception to July 2011. Comparative studies of any design in which routine follow-up via telephone was compared with face to face consultation in patients discharged from hospital after surgery were included. Study selection, data extraction and quality appraisal were performed independently by two reviewers with consensus reached by discussion and involvement of a third reviewer where necessary. RESULTS: Five papers (four studies; 865 adults) met the inclusion criteria. The studies were of low methodological quality and reported dissimilar outcomes precluding any formal synthesis. CONCLUSIONS: There has been very little comparative evaluation of different methods of routine follow-up care in patients discharged from hospital following surgery. Further work is needed to establish a role for telephone consultation in this patient group.

BACKGROUND: Missed or inappropriate hospital appointments cost the UK National Health Service millions of pounds each year and delay treatment for other patients. Innovative methods of appointment scheduling that are more flexible to patient needs, may improve service quality and preserve resources. METHODS: a systematic review of the evidence for the clinical effectiveness of patient initiated clinics in managing long term care for people with chronic or recurrent conditions in secondary care. Seven databases were searched including MEDLINE, Embase and PsycINFO (using the OVID interface), the Cochrane Library of Systematic Reviews and CENTRAL, Science Citation Index Expanded, Social Sciences Citation Index, and Conference Proceedings Citation Index (via the Web of Science interface) from inception to June 2013. Studies comparing patient initiated clinics with traditional consultant-led clinics in secondary care for people with long term chronic or recurrent diseases were included. Included studies had to provide data on clinical or resource use outcomes. Data were extracted and checked by two reviewers using a piloted, standardised data extraction form. RESULTS: Eight studies (n = 1927 individuals) were included. All were conducted in the UK. There were few significant differences in clinical outcomes between the intervention and control groups. In some instances, using the patient initiated clinics model was associated with savings in time and resource use. The risk of harm from using the patient initiated clinic model of organising outpatient care is low. Studies with longer follow-up periods are needed to assess the long term costs and the ongoing risk of potential harms. CONCLUSIONS: the UK policy context is ripe for evidence-based, patient-centred services to be implemented, especially where the use of health care resources can be optimised without reducing the quality of care. Implementation of patient initiated clinics should remain cautious, with importance placed on ongoing evaluation of long term outcomes and costs.

BACKGROUND: Chronic myeloid leukaemia (CML) is a form of cancer affecting the blood, characterised by excessive proliferation of white blood cells in the bone marrow and circulating blood. In the UK, an estimated 560 new cases of CML are diagnosed each year. OBJECTIVES: the purpose of this study was to assess the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in the treatment of people with imatinib-resistant (ImR) and imatinib-intolerant (ImI) CML. A systematic review of the clinical effectiveness literature, a review of manufacturer submissions and a critique and exploration of manufacturer submissions for accelerated phase and blast crisis CML were carried out and a decision-analytic model was developed to estimate the cost-effectiveness of dasatinib and nilotinib in chronic phase CML. SYSTEMATIC REVIEW METHODS: Key databases were searched for relevant studies from their inception to June 2009 [MEDLINE (including MEDLINE In-Process & Other Non-Indexed Citations), EMBASE, (ISI Web of Science) Conference Proceedings Citation Index and four others]. One reviewer assessed titles and abstracts of studies identified by the search strategy, with a sample checked by a second reviewer. The full text of relevant papers was obtained and screened against the full inclusion criteria independently by two reviewers. Data from included studies were extracted by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through narrative review. ECONOMIC EVALUATION METHODS: Cost-effectiveness analyses reported in manufacturer submissions to the National Institute of Health and Clinical Excellence were critically appraised and summarised narratively. In addition, the models for accelerated phase and blast crisis underwent a more detailed critique and exploration. Two separate decision-analytic models were developed for chronic phase CML, one simulating a cohort of individuals who have shown or developed resistance to normal dose imatinib and one representing individuals who have been unable to continue imatinib treatment owing to adverse events. One-way, multiway and probabilistic sensitivity analyses were performed to explore structural and parameter uncertainty. RESULTS: Fifteen studies were included in the systematic review. Chronic phase: effectiveness data were limited but dasatinib and nilotinib appeared efficacious in terms of obtaining cytogenetic response and haematological response in both ImR and ImI populations. In terms of cost-effectiveness, it was extremely difficult to reach any conclusions regarding either agent in the ImR population. All three models (Novartis, PenTAG and Bristol-Myers Squibb) were seriously flawed in one way or another, as a consequence of the paucity of data appropriate to construct robust decision-analytic models. Accelerated and blast crisis: all available data originated from observational single-arm studies and there were considerable and potentially important differences in baseline characteristics which seriously undermined any process for making meaningful comparisons between treatments. Owing to a lack of available clinical data, de novo models of accelerated phase and blast crisis have not been developed. The economic evaluations carried out by the manufacturers of nilotinib and dasatinib were seriously undermined by the absence of evidence on high-dose imatinib in these populations. LIMITATIONS: the study has been necessarily constrained by the paucity of available clinical data, the differences in definitions used in the studies and the subsequent impossibility of undertaking a meaningful cost-effectiveness analyses to inform all policy questions. CONCLUSIONS: Dasatinib and nilotinib appeared efficacious in terms of obtaining cytogenetic and haematological responses in both ImR and ImI populations. It was difficult to reach any cost-effectiveness conclusions as a consequence of the paucity of the data. Future research should include a three-way, double-blind, randomised clinical trial of dasatinib, nilotinib and high-dose imatinib.

Objective: to compare the effectiveness of interventions aimed at reducing the rate of acute paediatric hospital admissions. Design: Systematic review. Data sources: Medline, Embase, PsychINFO, the Cochrane Library, Science Citation Index Expanded from inception to September 2010; hand searches of the reference lists of included papers and other review papers identified in the search. Review methods: Controlled trials were included. Articles were screened for inclusion independently by two reviewers. Data extraction and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. Results: Seven papers were included. There is some evidence to suggest that short stay units may reduce admission rates. However, there is a general lack of detail in the reporting of interventions and the methods used in their evaluation which precludes detailed interpretation and extrapolation of the results. The authors found no evidence that the use of algorithms and guidelines to manage the admission decision was effective in reducing acute admission rates. Furthermore, the authors were unable to locate any eligible papers reporting the effects on admission rates of admission decision by paediatric consultant, telephone triage by paediatric consultant or the establishment of next day emergency paediatric clinics. Conclusion: There is little published evidence upon which to base an optimal strategy for reducing paediatric admission rates. The evidence that does exist is subject to substantial bias. There is a pressing need for high quality, well conducted research to enable informed service change.

OBJECTIVE: to compare the effectiveness of interventions aimed at reducing the rate of acute paediatric hospital admissions. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, PsychINFO, the Cochrane Library, Science Citation Index Expanded from inception to September 2010; hand searches of the reference lists of included papers and other review papers identified in the search. REVIEW METHODS: Controlled trials were included. Articles were screened for inclusion independently by two reviewers. Data extraction and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. RESULTS: Seven papers were included. There is some evidence to suggest that short stay units may reduce admission rates. However, there is a general lack of detail in the reporting of interventions and the methods used in their evaluation which precludes detailed interpretation and extrapolation of the results. The authors found no evidence that the use of algorithms and guidelines to manage the admission decision was effective in reducing acute admission rates. Furthermore, the authors were unable to locate any eligible papers reporting the effects on admission rates of admission decision by paediatric consultant, telephone triage by paediatric consultant or the establishment of next day emergency paediatric clinics. CONCLUSION: There is little published evidence upon which to base an optimal strategy for reducing paediatric admission rates. The evidence that does exist is subject to substantial bias. There is a pressing need for high quality, well conducted research to enable informed service change.

Our objective was to compare the effects on mental and physical wellbeing, health related quality of life and long-term adherence to physical activity, of participation in physical activity in natural environments compared with physical activity indoors. We conducted a systematic review using the following data sources: Medline, Embase, Psychinfo, GreenFILE, SportDISCUS, the Cochrane Library, Science Citation Index Expanded, Social Sciences Citation Index, Arts and Humanities Citation Index, Conference Proceedings Citation Index--Science and BIOSIS from inception to June 2010. Internet searches of relevant Web sites, hand searches of relevant journals, and the reference lists of included papers and other review papers identified in the search were also searched for relevant information. Controlled trials (randomized and nonrandomized) were included. To be eligible trials had to compare the effects of outdoor exercise initiatives with those conducted indoors and report on at least one physical or mental wellbeing outcome in adults or children. Screening of articles for inclusion, data extraction, and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. Due to the heterogeneity of identified studies a narrative synthesis was performed. Eleven trials (833 adults) were included. Most participants (6 trials; 523 adults) were young students. Study entry criteria and methods were sparsely reported. All interventions consisted of a single episode of walking or running indoors with the same activity at a similar level conducted outdoors on a separate occasion. A total of 13 different outcome measures were used to evaluate the effects of exercise on mental wellbeing, and 4 outcome measures were used to assess attitude to exercise. Most trials (n = 9) showed some improvement in mental wellbeing on one or other of the outcome measures. Compared with exercising indoors, exercising in natural environments was associated with greater feelings of revitalization and positive engagement, decreases in tension, confusion, anger, and depression, and increased energy. However, the results suggested that feelings of calmness may be decreased following outdoor exercise. Participants reported greater enjoyment and satisfaction with outdoor activity and declared a greater intent to repeat the activity at a later date. None of the identified studies measured the effects of physical activity on physical wellbeing or the effect of natural environments on exercise adherence. The hypothesis that there are added beneficial effects to be gained from performing physical activity outdoors in natural environments is very appealing and has generated considerable interest. This review has shown some promising effects on self-reported mental wellbeing immediately following exercise in nature which are not seen following the same exercise indoors. However, the interpretation and extrapolation of these findings is hampered by the poor methodological quality of the available evidence and the heterogeneity of outcome measures employed. The review demonstrates the paucity of high quality evidence on which to base recommendations and reveals an undoubted need for further research in this area. Large, well designed, longer term trials in populations who might benefit most from the potential advantages of outdoor exercise are needed to fully elucidate the effects on mental and physical wellbeing. The influence of these effects on the sustainability of physical activity initiatives also awaits investigation.

OBJECTIVES: to assess the clinical effectiveness and cost-effectiveness of bevacizumab, combined with interferon (IFN), sorafenib tosylate, sunitinib and temsirolimus in the treatment of people with advanced and/or metastatic renal cell carcinoma (RCC). DATA SOURCES: Electronic databases, including MEDLINE, EMBASE and the Cochrane Library, were searched up to September/October 2007 (and again in February 2008). REVIEW METHODS: Systematic reviews and randomised clinical trials comparing any of the interventions with any of the comparators in participants with advanced and/or metastatic RCC were included, also phase II studies and conference abstracts if there was sufficient detail to adequately assess quality. Results were synthesised narratively and a decision-analytic Markov-type model was developed to simulate disease progression and estimate the cost-effectiveness of the interventions under consideration. RESULTS: a total of 888 titles and abstracts were retrieved in the clinical effectiveness review, including reports of eight clinical trials. Treatment with bevacizumab plus IFN or sunitinib had clinically relevant and statistically significant advantages over treatment with IFN alone, in terms of progression-free survival and tumour response, doubling median progression-free survival from approximately 5 months to 10 months. Temsirolimus had similar advantages over treatment with IFN in terms of progression-free and overall survival, increasing median overall survival from 7.3 to 10.9 months [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.58 to 0.92)], as did sorafenib in comparison with best supportive care in terms of overall survival, progression-free survival and tumour response, with a doubling of progression-free survival (HR 0.51; 95% CI 0.43 to 0.60). However, the last was associated with an increased frequency of hypertension and hand-foot skin reaction compared with placebo. No fully published economic evaluations of any of the interventions could be located. However, estimates from the PenTAG model suggested that none of the interventions would be considered cost-effective at a willingness-to-pay threshold of 30,000 pounds per quality-adjusted life-year (QALY). Estimates of cost per QALY ranged from 71,462 pounds for sunitinib to 171,301 pounds for bevacizumab plus IFN. Although there are many similarities in the methodology and structural assumptions employed by PenTAG and the manufacturers of the interventions, in all cases the cost-effectiveness estimates from the PenTAG model were higher than those presented in the manufacturers' submissions. Cost-effectiveness estimates were particularly sensitive to variations in the estimates of treatment effectiveness, drug pricing (including dose intensity data), and health-state utility input parameters. CONCLUSIONS: Treatment with bevacizumab plus IFN and sunitinib has clinically relevant and statistically significant advantages over treatment with IFN alone in patients with metastatic RCC. In people with three of six risk factors for poor prognosis, temsirolimus had clinically relevant advantages over treatment with IFN, and sorafenib tosylate was superior to best supportive care as second-line therapy. The frequency of adverse events associated with bevacizumab plus IFN, sunitinib and temsirolimus was comparable with that seen with IFN, although the adverse event profile is different. Treatment with sorafenib was associated with a significantly increased frequency of hypertension and hand-foot syndrome. Estimates from the PenTAG model suggested that none of the interventions would be considered cost-effective at a willingness-to-pay threshold of 30,000 pounds per QALY.

OBJECTIVES: to estimate the cost-effectiveness of sorafenib (Nexavar, Bayer, Leverkusen, Germany) versus best supportive care (BSC) for second-line treatment of advanced renal cell carcinoma from the perspective of the UK National Health Service. METHODS: a decision analytic model was developed to estimate the cost-effectiveness of sorafenib. The clinical effectiveness of sorafenib versus BSC was taken from a recent randomized phase III trial. Utility values were taken from a phase II trial of sunitinib, using EQ-5D tariffs. Cost data were obtained from published literature and were based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses. RESULTS: Compared to BSC, sorafenib treatment resulted in an incremental cost per quality-adjusted life year (QALY) gained of pound75,398, based on an estimated mean gain of 0.27 QALYs per patient, at a mean additional cost of pound20,063 (inflated to 2007/2008). The probability that sorafenib is cost-effective compared to BSC at a willingness to pay threshold of pound30,000 per QALY is 0.0%. In sensitivity analysis, estimates of cost per QALY were sensitive to changes in the clinical effectiveness parameters, and to health state utilities and drug costs. CONCLUSIONS: Sorafenib has been shown to be clinically effective compared to BSC, offering additional health benefits; however, with a cost per QALY in excess of pound70,000, it may not be regarded as a cost-effective use of resources in some health-care settings.

OBJECTIVES: to estimate the cost-effectiveness of temsirolimus compared to interferon-alpha for first line treatment of patients with advanced, poor prognosis renal cell carcinoma, from the perspective of the UK National Health Service. METHODS: a decision-analytic model was developed to estimate the cost-effectiveness of temsirolimus. The clinical effectiveness of temsirolimus compared with interferon-alpha and the utility values (using EQ-5D tariffs) were taken from a recent phase III randomized clinical trial. Cost data were obtained from published literature and based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses. RESULTS: Compared to interferon-alpha, temsirolimus treatment resulted in an incremental cost per QALY gained of pound94,632; based on an estimated mean gain of 0.24 quality-adjusted life years (QALYs) per patient, at a mean additional cost of pound22,331 (inflated to 2007/8). The cost per QALY for patient subgroups ranged from pound74,369 to pound154,752. The probability that temsirolimus is cost-effective compared to interferon-alpha at a willingness to pay threshold of pound30,000 per QALY for all patient groups is expected to be close to zero. The cost per QALY was sensitive to the clinical effectiveness parameters, health state utilities, drug costs and the cost of administration of temsirolimus. CONCLUSIONS: Temsirolimus has been shown to be clinically effective compared to interferon-alpha offering additional health benefits, however, with a cost per QALY in excess of pound90,000, it may not be regarded as a cost-effective use of resources in some health care settings.

BACKGROUND: Hypercholesterolaemia is directly associated with an increased risk for coronary heart disease and other sequelae of atherosclerosis. Artichoke leaf extract (ALE) has been implicated in lowering cholesterol levels. Whether ALE is truly effective for this indication, however, is still a matter of debate. OBJECTIVES: to assess the evidence of ALE versus placebo or reference medication for treating hypercholesterolaemia defined as mean total cholesterol levels of at least 5.17 mmol/L (200 mg/dL). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials 2008 Issue 2, MEDLINE, EMBASE, AMED and CINAHL from their respective inception until June 2008; CISCOM until June 2001. Reference lists of articles were checked. Manufacturers of preparations containing artichoke extract and experts on the subject were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) of ALE mono-preparations compared with placebo or reference medication for patients with hypercholesterolaemia were included. Trials assessing ALE as one of several active components in a combination preparation or as a part of a combination treatment were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted systematically and methodological quality was evaluated using a standard scoring system and the Cochrane risk of bias assessment. The screening of studies, selection, data extraction and assessment of methodological quality were performed independently by two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: Three RCTs (262 participants) met all inclusion criteria. In one trial the total cholesterol level in participants receiving ALE decreased by 4.2% from 7.16 (0.62) mmol/L to 6.86 (0.68) mmol/L after 12 weeks and increased from 6.90 (0.49) mmol/L to 7.04 (0.61) mmol/L in patients receiving placebo, the total difference being statistically significant (P = 0.025). In a further trial ALE reduced total cholesterol levels by 18.5% from 7.74 mmol/L to 6.31 mmol/L after 42 +/- 3 days of treatment whereas the placebo reduced cholesterol by 8.6% from 7.69 mmol/L to 7.03 mmol/L (P = 0.00001). Another trial did state that ALE significantly reduced blood cholesterol compared with placebo in a sub-group of patients with baseline total cholesterol levels of more than 230 mg/dL (P. <. 0.05). Trial reports indicate mild, transient and infrequent adverse events. AUTHORS' CONCLUSIONS: Some data from clinical trials assessing ALE for treating hypercholesterolaemia exist. There is an indication that ALE has potential in lowering cholesterol levels, the evidence is, however, as yet not convincing. The limited data on safety suggest only mild, transient and infrequent adverse events with the short term use of ALE.

BACKGROUND: Two new agents have recently been licensed for use in the treatment of metastatic renal cell carcinoma (RCC) in Europe. This paper aims to systematically review the evidence from all available randomised clinical trials of sunitinib and bevacizumab (in combination with interferon-alpha (IFN-alpha)) in the treatment of advanced metastatic RCC. METHODS: Systematic literature searches were performed in six electronic databases. Bibliographies of included studies were searched for further relevant studies. Individual conference proceedings were searched using their online interfaces. Studies were selected according to the predefined criteria. All randomised clinical trials of sunitinib or bevacizumab in combination with IFN for treating advanced metastatic RCC in accordance with the European licensed indication were included. Study selection, data extraction, validation and quality assessment were performed by two reviewers with disagreements being settled by discussion. The effects of sunitinib and bevacizumab (in combination with IFN-alpha) on progression-free survival were compared indirectly using Bayesian Markov Chain Monte-Carlo (MCMC) sampling in Win BUGS, with IFN as a common comparator. RESULTS: Three studies were included. Median progression-free survival was significantly prolonged with both interventions (from approximately 5 months to between 8 and 11 months) compared with IFN. Overall survival was also prolonged, compared with IFN, although the published data are not fully mature. Indirect comparison suggests that sunitinib is superior to bevacizumab plus IFN in terms of progression-free survival (hazard ratios 0.796; 95% CI 0.63-1.0; P=0.0272). CONCLUSION: There is evidence to suggest that treatment with sunitinib and treatment with bevacizumab plus IFN has clinically relevant and statistically significant advantages over treatment with IFN alone in patients with metastatic RCC.

Using a decision-analytic model, we evaluated the effectiveness and cost-effectiveness of surveillance for hepatocellular carcinoma (HCC) in individuals with cirrhosis. Separate cohorts with cirrhosis due to alcoholic liver disease, hepatitis B and hepatitis C were simulated. Results were also combined to approximate a mixed aetiology population. Comparisons were made between a variety of surveillance algorithms using alpha-foetoprotein (AFP) assay and/or ultrasound at 6- and 12-monthly intervals. Parameter estimates were obtained from comprehensive literature reviews. Uncertainty was explored using one-way and probabilistic sensitivity analyses. In the mixed aetiology cohort, 6-monthly AFP+ultrasound was predicted to be the most effective strategy. The model estimates that, compared with no surveillance, this strategy may triple the number of people with operable tumours at diagnosis and almost halve the number of people who die from HCC. The cheapest strategy employed triage with annual AFP (incremental cost-effectiveness ratio (ICER): 20,700 pounds per quality-adjusted life-year (QALY) gained). At a willingness-to-pay threshold of 30,000 pounds per QALY the most cost-effective strategy used triage with 6-monthly AFP (ICER: 27,600 pounds per QALY gained). The addition of ultrasound to this strategy increased the ICER to 60,100 pounds per QALY gained. Surveillance appears most cost-effective in individuals with hepatitis B-related cirrhosis, potentially due to younger age at diagnosis of cirrhosis. Our results suggest that, in a UK NHS context, surveillance of individuals with cirrhosis for HCC should be considered effective and cost-effective. The economic efficiency of different surveillance strategies is predicted to vary markedly according to cirrhosis aetiology.

To evaluate the effectiveness, cost-effectiveness and cost-utility of surveillance of patients with cirrhosis [alcoholic liver disease (ALD)-, hepatitis B (HBV)- and C virus (HCV)-related], using periodic serum alpha-fetoprotein (AFP) testing and/or liver ultrasound examination, to detect hepatocellular carcinoma (HCC), followed by treatment with liver transplantation or resection, where appropriate. Electronic databases were searched up to March 2006. A systematic review was carried out using standard methodological guidelines. A computerised decision-analytic model was then developed to compare various surveillance strategies. No studies were identified that met the criteria of the systematic review. Based on the assumptions used in the model, the most effective surveillance strategy uses a combination of AFP testing and ultrasound at 6-monthly intervals. Compared with no surveillance, this strategy is estimated to more than triple the number of people with operable HCC tumours at time of diagnosis, and almost halves the number of deaths from HCC. On all effectiveness measures and at both testing frequencies, AFP- and ultrasound-led surveillance strategies are very similar. This may be because test sensitivity was varied according to tumour size, which means that AFP testing is capable of identifying many more small tumours than ultrasound. The best available evidence suggests that AFP tests will detect approximately six times as many small tumours as ultrasound. Increasing the frequency of either test to 6-monthly intervals is more effective than performing combined testing on an annual basis. The undiscounted lifetime cost of the surveillance strategies, including all care and treatment costs, ranges from 40,300 pounds (annual AFP triage) to 42,900 pounds (6-monthly AFP and ultrasound). The equivalent discounted costs are 28,400 pounds and 30,400 pounds. Only a small proportion of these total costs results from the cost of the screening tests. However, screening test costs, and the cost of liver transplants and caring for people post-transplant, accounted for most of the incremental cost differences between alternative surveillance strategies. The results suggest that different surveillance strategies may provide the best value for money in patient groups of different cirrhosis aetiologies. The surveillance of people with HBV-related cirrhosis for HCC provides the best value for money, while surveillance in people with ALD-related cirrhosis provides the poorest value for money. In people with HBV-related cirrhosis, at an assumed maximum willingness to pay (WTP) for a quality-adjusted life-year (QALY) of 30,000 pounds, both the deterministic and probabilistic cost-utility analyses suggest the optimal surveillance strategy would be 6-monthly surveillance with the combination of AFP testing and ultrasound. In contrast, for those with ALD-related cirrhosis, annual screening with AFP as a triage test is the only surveillance strategy that is likely to be considered cost-effective at this WTP. The probabilistic analysis implies that the estimated benefits of a 6-monthly AFP triage strategy will only be worth the cost in those with ALD when society's WTP for a QALY exceeds around 40,000 pounds. For people with HCV-related cirrhosis, the model suggests that the most cost-effective surveillance strategy at a WTP threshold of 30,000 pounds/QALY would be surveillance with a 6-monthly AFP triage strategy. In a mixed-aetiology cohort, the most effective surveillance strategy is to screen each patient with AFP assay and ultrasound imaging on a 6-monthly basis. However, when costs are taken into account it is doubtful whether ultrasound should be routinely offered to those with blood AFP of less than 20 ng/ml, unless policy-makers are prepared to pay over 60,000 pounds per QALY for the benefits achieved. Furthermore, the cost-effectiveness of surveillance for HCC varies considerably depending on the aetiology of cirrhosis; it is much more likely to be cost-effective in those with HBV-related cirrhosis, and much less likely to be cost-effective in those with ALD-related cirrhosis. Further development of the model would help to enable refinement of an optimal screening strategy. Research into the use of contrast-enhanced ultrasound technology for HCC detection would also be valuable, as would research into the epidemiology and natural history of ALD-related cirrhosis. Studies are also needed to investigate the influence of cirrhosis aetiology on tumour AFP expression.

OBJECTIVE: to critically assess the evidence of supplements containing Trifolium pratense (red clover) isoflavones in the reduction of hot flush frequency in menopausal women. DATA SOURCES: Systematic literature searches were performed in (Medline (1951 - April 2006), Embase (1974 - April 2006), CINAHL (1982 - April 2006), Amed (1985 - April 2006) and the Cochrane Library (Issue 2, 2006). Reference lists located were checked for further relevant publications. Experts in the field and manufacturers of identified products were contacted for unpublished material. No language restrictions were imposed. REVIEW METHODS: Studies were selected according to predefined inclusion and exclusion criteria. All randomized clinical trials of monopreparations containing T. pratense isoflavones for treating hot flushes were included. Study selection, data extraction and validation were performed by at least two reviewers with disagreements being settled by discussion. Weighted means and 95% confidence intervals were calculated and sensitivity analyses were performed. RESULTS: Seventeen potentially relevant articles were retrieved for further evaluation. Five were suitable for inclusion in the meta-analysis. The meta-analysis indicates a reduction in hot flush frequency in the active treatment group (40-82 mg daily) compared with the placebo group (weighted mean difference -1.5 hot flushes daily; 95% CI -2.94 to 0.03; p=0.05). CONCLUSION: There is evidence of a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women. Whether the size of this effect can be considered clinically relevant is unclear. Whereas there is no apparent evidence of adverse events during short-term use, there are no available data on the safety of long-term administration.

BACKGROUND: Hepatitis C is an important public health problem. The need for more intensified action to identify those infected with the virus has been recognized. Primary care is an important setting for case finding. OBJECTIVES: to estimate the cost utility of case finding for hepatitis C in primary care, specifically amongst former injecting drug users (IDUs). METHODS: a Markov model was developed to investigate the impact of case finding and treatment on progression of hepatitis C (HCV) in a hypothetical cohort of 1000 former IDUs. Comparison was made with a similar cohort in which no systematic case finding was implemented but spontaneous presentation for testing was allowed. Two scenarios were explored. The testing protocol utilized ELISA and PCR tests. Those eligible for treatment received combination therapy with pegylated interferon and ribavirin. Parameter estimates were obtained from literature searches and experts in the field. RESULTS: Few estimates of the uptake of HCV testing in primary care are available. Cost utility was estimated at around 16,000 pounds sterling/QALY for both scenarios. At a willingness to pay of 30,000 pounds sterling/QALY, there is approximately a 75% probability that the initiatives would be cost-effective. Choices regarding the utility data, discounting and the rates of spontaneous/re-presentation outside of a case-finding programme appear to be important areas of uncertainty in this model. CONCLUSION: Case finding for HCV in primary care is likely to be considered cost-effective but substantial uncertainties remain. Further research is needed on different approaches to case finding in primary care.

OBJECTIVES: the aim of this review is to systematically summarize and assess all prospective, controlled, cost-effectiveness studies of complementary therapies carried out in the UK. DATA SOURCES: Medline (via PubMed), Embase, CINAHL, Amed (Alternative and Allied Medicine Database, British Library Medical Information Centre), the Cochrane Library, National Health Service Economic Evaluation Database (via Cochrane) and Health Technology Assessments up to October 2005. REVIEW METHODS: Articles describing prospective, controlled, cost-effectiveness studies of any type of complementary therapy for any medical condition carried out in the UK were included. Data extracted included the main outcomes for health benefit and cost. These data were extracted independently by two authors, described narratively and also presented as a table. RESULTS: Six cost-effectiveness studies of complementary medicine in the UK were identified: four different types of spinal manipulation for back pain, one type of acupuncture for chronic headache and one type of acupuncture for chronic back pain. Four of the six studies compared the complementary therapy with usual conventional treatment in pragmatic, randomized clinical trials without sham or placebo arms. Main outcome measures of effectiveness favored the complementary therapies but in the case of spinal manipulation (four studies) and acupuncture (one study) for back pain, effect sizes were small and of uncertain clinical relevance. The same four studies included a cost-utility analyses in which the incremental cost per quality adjusted life year (QALY) was less than pound10 000. The complementary therapy represented an additional health care cost in five of the six studies. CONCLUSIONS: Prospective, controlled, cost-effectiveness studies of complementary therapies have been carried out in the UK only for spinal manipulation (four studies) and acupuncture (two studies). The limited data available indicate that the use of these therapies usually represents an additional cost to conventional treatment. Estimates of the incremental cost of achieving improvements in quality of life compare favorably with other treatments approved for use in the National Health Service. Because the specific efficacy of the complementary therapies for these indications remains uncertain, and the studies did not include sham controls, the estimates obtained may represent the cost-effectiveness non-specific effects associated with the complementary therapies.

Objectives: to evaluate the effectiveness and cost-effectiveness of testing for hepatitis C (HCV) among former injecting drug users (IDUs). Data sources: Electronic databases 1996-October 2004. Trent Regional Database Study. Routine UK mortality data. Review methods: a decision analytic model was developed to investigate the impact of case-finding and treatment on progression of HCV disease in a hypothetical cohort of 1000 people. This was compared with a cohort in whom no systematic case-finding is implemented but spontaneous presentation for testing is allowed to occur. A group of epidemiological and clinical experts informed the structure of the model, which has three main components: (1) testing and diagnosis, (2) treatment, and (3) long-term consequences of infection. A fourth component, case-finding strategies, examines the potential impact of case-finding in three settings: prisons, general practice and drug services. Results: Case-finding for HCV is likely to prevent, for 1000 people approached, three cases of decompensated cirrhosis, three deaths due to HCV and one case of hepatocellular cancer (at 30 years). Twenty-five additional people are likely to undergo combination therapy as a result of initial case-finding. One liver transplant is likely to be prevented for 10,000 people included in case-finding. Case-finding is likely to cost, in the general case, around £760,000 more than a policy of not case-finding. The total cost of either strategy is high and driven predominantly by the cost of treatment with combination therapy (the costs of long-term consequences are heavily discounted owing to the duration of the model). Systematically offering testing to 1000 people would cost around £70,000. In terms of life-years gained, case-finding is likely to result in an additional life-year gained for an investment of £20,084. Taking impacts on quality of life into account gives an estimate for the cost-utility of case-finding as £16,514 per QALY the probabilistic sensitivity analysis shows that, if NHS policy makers view £30,000 per QALY as an acceptable return on investment, there is a 74% probability that case-finding for HCV would be considered cost-effective. At £30,000 per QALY, the probability that case-finding would be considered cost-effective is 64%. In all analyses, the probability of case-finding being considered cost-effective at a level of £30,000 per QALY was high. Case-finding in drug services is likely to be the most expensive, owing to the high prevalence of cases in the tested population. Correspondingly, benefits are highest for this strategy and cost-effectiveness is similar, in average terms, to the general case. Case-finding in general practice by offering testing to the whole population aged 30-54 years is, paradoxically, estimated to be the least expensive option as only a small number of people accept the offer of testing and HCV prevalence in this group is much higher than would be expected from the general population. Two approaches to case-finding in prison were considered, based on the results of studies in Dartmoor and the Isle of Wight prisons. These differed substantially in the prevalence of cases identified in the tested populations. The analysis based on data from Dartmoor prison had the least favourable average cost-effectiveness of the strategies considered (£20,000 per QALY). Subgroup analyses based on duration of infection show that case-finding is likely to be most cost-effective in people whose infection is more long-standing and who are consequently at greater risk of progression. In people who were infected more than 20 years previously, case-finding yields benefits at around £15,000 per QALY Treatment effectiveness was modelled using estimates from randomised controlled trials and lower rates of viral response may be seen in practice. However, estimates of cost-effectiveness remained below £30,000 for all levels of treatment effectiveness above 58% of those shown in the relevant trials. The value of information analysis, based on assumptions that 10,000 people might be eligible for case-finding and that programmes would run for 15 years, suggests that the maximum value of further research into case-finding is in excess of £19 million. Partial expected value of perfect information (EVPI) analysis shows that the utility estimates used in the model eclipse all other factors in terms of importance to parameter uncertainty. This is not surprising, since the point estimates for differences in utility between states and across the arms of the model are small. Conclusions: Case-finding for hepatitis C is likely to be considered cost-effective by NHS commissioners. Although there remains considerable uncertainty, it appears unlikely that cost-effectiveness would exceed the levels considered acceptable. Further improvements in the effectiveness of treatments to slow or halt disease progression are likely to improve the cost-effectiveness of case-finding. Case-finding is likely to be most cost-effective if targeted at people whose HCV disease is probably more advanced. Further empirical work is required to specify, in practice, different approaches to case-finding in appropriate settings and to evaluate their effectiveness and cost-effectiveness directly. © Queen's Printer and Controller of HMSO 2006. All rights reserved.

To evaluate the effectiveness and cost-effectiveness of testing for hepatitis C (HCV) among former injecting drug users (IDUs). Electronic databases 1996-October 2004. Trent Regional Database Study. Routine UK mortality data. A decision analytic model was developed to investigate the impact of case-finding and treatment on progression of HCV disease in a hypothetical cohort of 1000 people. This was compared with a cohort in whom no systematic case-finding is implemented but spontaneous presentation for testing is allowed to occur. A group of epidemiological and clinical experts informed the structure of the model, which has three main components: (1) testing and diagnosis, (2) treatment, and (3) long-term consequences of infection. A fourth component, case-finding strategies, examines the potential impact of case-finding in three settings: prisons, general practice and drug services. Case-finding for HCV is likely to prevent, for 1000 people approached, three cases of decompensated cirrhosis, three deaths due to HCV and one case of hepatocellular cancer (at 30 years). Twenty-five additional people are likely to undergo combination therapy as a result of initial case-finding. One liver transplant is likely to be prevented for 10,000 people included in case-finding. Case-finding is likely to cost, in the general case, around pounds sterling 760,000 more than a policy of not case-finding. The total cost of either strategy is high and driven predominantly by the cost of treatment with combination therapy (the costs of long-term consequences are heavily discounted owing to the duration of the model). Systematically offering testing to 1000 people would cost around pounds sterling 70,000. In terms of life-years gained, case-finding is likely to result in an additional life-year gained for an investment of pounds sterling 20,084. Taking impacts on quality of life into account gives an estimate for the cost-utility of case-finding as pounds sterling 16,514 per QALY. The probabilistic sensitivity analysis shows that, if NHS policy makers view pounds sterling 30,000 per QALY as an acceptable return on investment, there is a 74% probability that case-finding for HCV would be considered cost-effective. At pounds sterling 20,000 per QALY, the probability that case-finding would be considered cost-effective is 64%. In all analyses, the probability of case-finding being considered cost-effective at a level of pounds sterling 30,000 per QALY was high. Case-finding in drug services is likely to be the most expensive, owing to the high prevalence of cases in the tested population. Correspondingly, benefits are highest for this strategy and cost-effectiveness is similar, in average terms, to the general case. Case-finding in general practice by offering testing to the whole population aged 30-54 years is, paradoxically, estimated to be the least expensive option as only a small number of people accept the offer of testing and HCV prevalence in this group is much higher than would be expected from the general population. Two approaches to case-finding in prison were considered, based on the results of studies in Dartmoor and the Isle of Wight prisons. These differed substantially in the prevalence of cases identified in the tested populations. The analysis based on data from Dartmoor prison had the least favourable average cost-effectiveness of the strategies considered (pounds sterling 20,000 per QALY). Subgroup analyses based on duration of infection show that case-finding is likely to be most cost-effective in people whose infection is more long-standing and who are consequently at greater risk of progression. In people who were infected more than 20 years previously, case-finding yields benefits at around pounds sterling 15,000 per QALY. Treatment effectiveness was modelled using estimates from randomised controlled trials and lower rates of viral response may be seen in practice. However, estimates of cost-effectiveness remained below pounds sterling 30,000 for all levels of treatment effectiveness above 58% of those shown in the relevant trials. The value of information analysis, based on assumptions that 10,000 people might be eligible for case-finding and that programmes would run for 15 years, suggests that the maximum value of further research into case-finding is in excess of pounds sterling 19 million. Partial expected value of perfect information (EVPI) analysis shows that the utility estimates used in the model eclipse all other factors in terms of importance to parameter uncertainty. This is not surprising, since the point estimates for differences in utility between states and across the arms of the model are small. Case-finding for hepatitis C is likely to be considered cost-effective by NHS commissioners. Although there remains considerable uncertainty, it appears unlikely that cost-effectiveness would exceed the levels considered acceptable. Further improvements in the effectiveness of treatments to slow or halt disease progression are likely to improve the cost-effectiveness of case-finding. Case-finding is likely to be most cost-effective if targeted at people whose HCV disease is probably more advanced. Further empirical work is required to specify, in practice, different approaches to case-finding in appropriate settings and to evaluate their effectiveness and cost-effectiveness directly.

Ginkgo biloba, currently one of the most popular herbal remedies for self-medication, has repeatedly been associated with bleeding. This systematic review of case reports is aimed at determining whether the risk is real. Five electronic literature searches were carried out to locate all reports of bleeding associated with Ginkgo biloba mono-preparations. Twelve articles met the inclusion criteria and these were assessed by two independent reviewers according to pre-defined criteria. The likelihood of causality was also assessed. The results show that the clinical evidence for Ginkgo biloba causing bleeding is far from compelling. Pre-clinical studies yield inconsistent effects on platelet aggregation and the majority of rigorous trials refute a risk of bleeding. It is concluded that the causality between Ginkgo biloba intake and bleeding is unlikely. However, continuous vigilance seems well advised. © Verlag Perfusion GmbH.

Echinacea spp. are native to North America and were traditionally used by the Indian tribes for a variety of ailments, including mouth sores, colds and snake-bites. The three most commonly used Echinacea spp. are E. angustifolia, E. pallida and E. purpurea. Systematic literature searches were conducted in six electronic databases and the reference lists of all of the papers located were checked for further relevant publications. Information was also sought from the spontaneous reporting programmes of the WHO and national drug safety bodies. Twenty-three manufacturers of echinacea were contacted and asked for data held on file. Finally our own departmental files were searched. No language restrictions were imposed. Combination products and homeopathic preparations were excluded. Data from clinical studies and spontaneous reporting programmes suggest that adverse events with echinacea are not commonly reported. Gastrointestinal upsets and rashes occur most frequently. However, in rare cases, echinacea can be associated with allergic reactions that may be severe. Although there is a large amount of data that investigates the efficacy of echinacea, safety issues and the monitoring of adverse events have not been focused on. Short-term use of echinacea is associated with a relatively good safety profile, with a slight risk of transient, reversible, adverse events. The association of echinacea with allergic reactions is supported by the present evaluation. While these reactions are likely to be rare, patients with allergy or asthma should carefully consider their use of echinacea. The use of echinacea products during pregnancy and lactation would appear to be ill-advised in light of the paucity of data in this area.

Vitex agnus castus L. (VAC) [Verbenaceae] is a deciduous shrub that is native to Mediterranean Europe and Central Asia. Traditionally, VAC fruit extract has been used in the treatment of many female conditions, including menstrual disorders (amenorrhoea, dysmenorrhoea), premenstrual syndrome (PMS), corpus luteum insufficiency, hyperprolactinaemia, infertility, acne, menopause and disrupted lactation. The German Commission E has approved the use of VAC for irregularities of the menstrual cycle, premenstrual disturbances and mastodynia. Clinical reviews are available for the efficacy of VAC in PMS, cycle disorders, hyperprolactinaemia and mastalgia, but so far no systematic review has been published on adverse events or drug interactions associated with VAC. Therefore, this review was conducted to evaluate all the available human safety data of VAC monopreparations. Literature searches were conducted in six electronic databases, in references lists of all identified papers and in departmental files. Data from spontaneous reporting schemes of the WHO and national drug safety bodies were also included. Twelve manufacturers of VAC-containing preparations and five herbalist organisations were contacted for additional information. No language restrictions were imposed. Combination preparations including VAC or homeopathic preparations of VAC were excluded. Data extraction of key data from all articles reporting adverse events or interactions was performed independently by at least two reviewers, regardless of study design. Data from clinical trials, postmarketing surveillance studies, surveys, spontaneous reporting schemes, manufacturers and herbalist organisations indicate that the adverse events following VAC treatment are mild and reversible. The most frequent adverse events are nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus and erythematous rash. No drug interactions were reported. Use of VAC should be avoided during pregnancy or lactation. Theoretically, VAC might also interfere with dopaminergic antagonists. Although further rigorous studies are needed to assess the safety of VAC, the data available seem to indicate that VAC is a safe herbal medicine.

OBJECTIVES: the purpose of this study was to systematically review the literature for, and critically appraise, randomized controlled trials of any type of complementary and alternative therapies for labor pain. STUDY DESIGN: Six electronic databases were searched from their inception until July 2003. The inclusion criteria were that they were prospective, randomized controlled trials, involved healthy pregnant women at term, and contained outcome measures of labor pain. RESULTS: Our search strategy found 18 trials. Six of these did not meet our inclusion criteria. The remaining 12 trials involved acupuncture (2), biofeedback (1), hypnosis (2), intracutaneous sterile water injections (4), massage (2), and respiratory autogenic training (1). CONCLUSION: There is insufficient evidence for the efficacy of any of the complementary and alternative therapies for labor pain, with the exception of intracutaneous sterile water injections. For all the other treatments described it is impossible to make any definitive conclusions regarding effectiveness in labor pain control.

BACKGROUND/AIMS: Hepatitis C is an escalating global health problem. The recommended treatment regimen is associated with considerable expense, adverse effects and poor efficacy in some patients. Complementary therapies are widely promoted for and used by patients with hepatitis C. The aim is to systematically assess the efficacy of complementary therapies in treating chronic hepatitis C. METHODS: Systematic searches were conducted in six databases, reference lists of all papers were checked for further relevant publications and information was requested from experts. No language restrictions were imposed. RESULTS: Twenty-seven eligible randomised clinical trials were located involving herbal products and supplements. No randomised clinical trials were identified for any other complementary therapy. In 14 of the trials, patients received interferon-alpha in combination with the complementary therapy. Less than half the trials (11/27) were of good methodological quality. Compared with the control group, significant improvements in virological and/or biochemical response were seen in trials of vitamin E, thymic extract, zinc, traditional Chinese medicine, Glycyrrhiza glabra and oxymatrine. CONCLUSIONS: We identified several promising complementary therapies, although extrapolation of the results is difficult due to methodological limitations. More research is warranted to establish the role of these and other therapies in the treatment of hepatitis C.

BACKGROUND: Patients with asthma are interested in the use of breathing exercises but their role is uncertain. The effects of the Buteyko breathing technique, a device which mimics pranayama (a yoga breathing technique), and a dummy pranayama device on bronchial responsiveness and symptoms were compared over 6 months in a parallel group study. METHODS: Ninety patients with asthma taking an inhaled corticosteroid were randomised after a 2 week run in period to Eucapnic Buteyko breathing, use of a Pink City Lung Exerciser (PCLE) to mimic pranayama, or a PCLE placebo device. Subjects practised the techniques at home twice daily for 6 months followed by an optional steroid reduction phase. Primary outcome measures were symptom scores and change in the dose of methacholine provoking a 20% fall in FEV(1) (PD(20)) during the first 6 months. RESULTS: Sixty nine patients (78%) completed the study. There was no significant difference in PD(20) between the three groups at 3 or 6 months. Symptoms remained relatively stable in the PCLE and placebo groups but were reduced in the Buteyko group. Median change in symptom scores at 6 months was 0 (interquartile range -1 to 1) in the placebo group, -1 (-2 to 0.75) in the PCLE group, and -3 (-4 to 0) in the Buteyko group (p=0.003 for difference between groups). Bronchodilator use was reduced in the Buteyko group by two puffs/day at 6 months; there was no change in the other two groups (p=0.005). No difference was seen between the groups in FEV(1), exacerbations, or ability to reduce inhaled corticosteroids. CONCLUSION: the Buteyko breathing technique can improve symptoms and reduce bronchodilator use but does not appear to change bronchial responsiveness or lung function in patients with asthma. No benefit was shown for the Pink City Lung Exerciser.

OBJECTIVES: to systematically review the clinical evidence for herbal medicinal products in the treatment of hypercholesterolemia. STUDY DESIGN: a systematic review of randomized clinical trials of herbal medicinal products used to lower serum cholesterol. Systematic literature searches were conducted in 6 electronic data-bases. The reference lists of all papers and our files were searched for more relevant publications. Experts in the field and manufacturers of identified herbal medicinal products were contacted for published and unpublished data. No language restrictions were imposed. OUTCOMES MEASURED: all randomized clinical trials of serum cholesterol reduction, in which mono-preparations of herbal medicinal products were administered as supplements to human subjects, were included. RESULTS: Twenty-five randomized clinical trials involving 11 herbal medicinal products were identified. Guggul (Commiphora mukul), fenugreek (Trigonella foenum-graecum), red yeast rice, and artichoke (Cynara scolymus) have been most extensively studied and have demonstrated reductions in total serum cholesterol levels of between10% and 33%. The methodological quality as assessed by the Jadad score was less than 3 (maximum, 5) for 13 of the 25 trials. CONCLUSIONS: Many herbal medicinal products have potential hypocholesterolemic activity and encouraging safety profiles. However, only a limited amount of clinical research exists to support their efficacy. Further research is warranted to establish the value of these extracts in the treatment of hypercholesterolemia.

BACKGROUND: Hypercholesterolaemia is directly associated with an increased risk for coronary heart disease and other sequelae of atherosclerosis. Artichoke leaf extract (ALE), which is available as an over-the-counter remedy, has been implicated in lowering cholesterol levels. Whether ALE is truly efficacious for this indication, however, is still a matter of debate. OBJECTIVES: to assess the evidence of ALE versus placebo or reference medication for treating hypercholesterolaemia defined as mean total cholesterol levels of at least 5.17 mmol/L (200 mg /dL). SEARCH STRATEGY: We searched MEDLINE, Embase, Amed, Cinahl, CISCOM and the Cochrane Controlled Trial Register. All databases were searched from their respective inception until June 2001. Reference lists of articles were also searched for relevant material. Manufacturers of preparations containing artichoke extract and experts on the subject were contacted and asked to contribute published and unpublished material. SELECTION CRITERIA: Randomized controlled trials of ALE mono-preparations compared with placebo or reference medication for patients with hypercholesterolaemia were included. Trials assessing ALE as one of several active components in a combination preparation or as a part of a combination treatment were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted systematically and methodological quality was evaluated using a standard scoring system. The screening of studies, selection, data extraction and the assessment of methodological quality were performed independently by two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: Two randomised trials including 167 participants met all inclusion criteria. In one trial ALE reduced total cholesterol levels from 7.74 mmol/l to 6.31 mmol/l after 42 +/- 3 days of treatment whereas the placebo reduced cholesterol from 7.69 mmol/l to 7.03 mmol/l (p=0.00001). Another trial did state that ALE significantly (p

BACKGROUND: Hypercholesterolaemia is directly associated with an increased risk for coronary heart disease and other sequelae of atherosclerosis. Artichoke leaf extract (ALE), which is available as an over-the-counter remedy, has been implicated in lowering cholesterol levels. Whether ALE is truly efficacious for this indication, however, is still a matter of debate. OBJECTIVES: to assess the evidence of ALE versus placebo or reference medication for treating hypercholesterolaemia defined as mean total cholesterol levels of at least 5.17 mmol/L (200 mg /dL). SEARCH STRATEGY: We searched MEDLINE, Embase, Amed, Cinahl, CISCOM and the Cochrane Controlled Trial Register. All databases were searched from their respective inception until June 2001. Reference lists of articles were also searched for relevant material. Manufacturers of preparations containing artichoke extract and experts on the subject were contacted and asked to contribute published and unpublished material. SELECTION CRITERIA: Randomized controlled trials of ALE mono-preparations compared with placebo or reference medication for patients with hypercholesterolaemia were included. Trials assessing ALE as one of several active components in a combination preparation or as a part of a combination treatment were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted systematically and methodological quality was evaluated using a standard scoring system. The screening of studies, selection, data extraction and the assessment of methodological quality were performed independently by two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion. MAIN RESULTS: Two randomised trials including 167 participants met all inclusion criteria. In one trial ALE reduced total cholesterol levels from 7.74 mmol/l to 6.31 mmol/l after 42 +/- 3 days of treatment whereas the placebo reduced cholesterol from 7.69 mmol/l to 7.03 mmol/l (p=0.00001). Another trial did state that ALE significantly (p

Panax ginseng C. A. Meyer is a perennial herb native to Korea and China and has been used as an herbal remedy in eastern Asia for thousands of years. Modern therapeutic claims refer to vitality, immune function, cancer, cardiovascular diseases, improvement of cognitive and physical performance and sexual function. A recent systematic review of randomised controlled trials found that the efficacy of ginseng root extract could not be established beyond doubt for any of these indications. In order to obtain a balanced assessment of the therapeutic value of P. ginseng it is also necessary to consider the safety profile. In view of the extremely widespread use of P. ginseng it seems important to ask whether this herbal medicine involves health risks for the consumer. This review was conducted as a systematic attempt to document and evaluate all the available safety data on P. ginseng root extracts. Systematic searches were performed in five electronic databases and the reference lists of all papers located were checked for further relevant publications. All articles containing original data on adverse events and drug interactions with P. ginseng were included. Information was also requested from 12 manufacturers of ginseng preparations, the spontaneous reporting schemes of the WHO and national drug safety bodies. No language restrictions were imposed. Data from clinical trials suggest that the incidence of adverse events with ginseng monopreparations is similar to that with placebo. The most commonly experienced adverse events are headache, sleep and gastrointestinal disorders. The possibility of more serious adverse events is indicated in isolated case reports and data from spontaneous reporting schemes; however, causality is often difficult to determine from the evidence provided. Combination products containing ginseng as one of several constituents have been associated with serious adverse events and even fatalities. Interpretation of these cases is difficult as ingredients other than P. ginseng may have caused the problems. Possible drug interactions have been reported between P. ginseng and warfarin, phenelzine and alcohol. Collectively, these data suggest that P. ginseng monopreparations are rarely associated with adverse events or drug interactions. The ones that are documented are usually mild and transient. Combined preparations are more often associated with such events but causal attribution is usually not possible.

BACKGROUND: Between 4% and 25% of school age children complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with daily activities. For the majority of such children no organic cause for their pain can be found on physical examination or investigation. Although most children are likely managed by reassurance and simple measures, a large range of interventions has been recommended. OBJECTIVES: to determine the effectiveness of medication for recurrent abdominal pain in school-age children. SEARCH STRATEGY: the Cochrane Library (CENTRAL), MEDLINE, EMBASE, CINAHL, ERIC, PsycLIT, LILACS and JICST were searched using a strategy combining (Recurrent OR synonyms) AND (Abdomen OR synonyms) AND (Pain OR synonyms). Where appropriate search filters were employed. In addition, researchers working in this area were asked to identify relevant studies. SELECTION CRITERIA: Any study in which the majority of participants were school age children fulfilling standard criteria for RAP, and who were allocated by random or quasi-random methods to any drug treatment compared with a placebo or no treatment. DATA COLLECTION AND ANALYSIS: References identified by the searches were screened against the inclusion criteria by two independent reviewers. MAIN RESULTS: Only one trial met the inclusion criteria. This cross-over trial in 14 children who met suggested criteria for "abdominal migraine" compared pizotifen and placebo, each given for one month with no washout period. Participants reported a mean of 8.21 (95% CI 2.93, 13.48) fewer days of pain while taking the active drug. They also reported that the mean difference on an "Index of Severity" was -16.21 (95% CI -26.51, -5.90) and on an "Index of Misery" was -56.07 (95% CI -94.07, -18.07). REVIEWER'S CONCLUSIONS: There is little evidence to suggest that recommended drugs are effective in the management of RAP. At present there seems little justification for the use of these drugs other than in clinical trials. There is an urgent need for trials of all suggested pharmacologic interventions in children with RAP.

BACKGROUND: Non-ulcer dyspepsia is predominantly a self-managed condition, although it accounts for a significant number of general practitioner consultations and hospital referrals. Herbal medicinal products are often used for the relief of dyspeptic symptoms. AIMS: : to critically assess the evidence for and against herbal medicinal products for the treatment of non-ulcer dyspepsia. METHODS: Systematic searches were performed in six electronic databases and the reference lists located were checked for further relevant publications. No language restrictions were imposed. Experts in the field and manufacturers of identified herbal extracts were also contacted. All randomized clinical trials of herbal medicinal products administered as supplements to human subjects were included. RESULTS: Seventeen randomized clinical trials were identified, nine of which involved peppermint and caraway as constituents of combination preparations. Symptoms were reduced by all treatments (60-95% of patients reported improvements in symptoms). The mechanism of any anti-dyspeptic action is difficult to define, as the causes of non-ulcer dyspepsia are unclear. There appear to be few adverse effects associated with these remedies, although, in many cases, comprehensive safety data were not available. CONCLUSIONS: There are several herbal medicinal products with anti-dyspeptic activity and encouraging safety profiles. Further research is warranted to establish their therapeutic value in the treatment of non-ulcer dyspepsia.

Aims: We investigated whether the deterioration in asthma control reported following cessation of theophylline was due to tolerance to theophylline. Methods: Eighteen subjects with mild stable asthma were given oral theophylline 10 mg kg -1 day -1 or placebo for 2 weeks in a double- blind crossover study, FEV1 and PD20 histamine were measured before and 8 h after the first dose of treatment and 8, 32 and 56 h after the final dose, PD20 AMP was measured before treatment and 9 h after the final dose. Results: Six patients did not tolerate theophylline. In the other 12 subjects there were no differences between treatments in daily PEF, symptom scores, rescue bronchodilator use, PD20 histamine or FEV1 up to 8 h post treatment. Following withdrawal of theophylline there were significantly lower values for mean FEV1 (mean difference 0.15 l. 95% CI 0.03, 026) and PD20 AMP compared to placebo but no difference in other end points. Conclusions: the small rebound deterioration in lung function following regular treatment with therapeutic doses of oral theophylline is consistent with the development of tolerance.

AIMS: We investigated whether the deterioration in asthma control reported following cessation of theophylline was due to tolerance to theophylline. METHODS: Eighteen subjects with mild stable asthma were given oral theophylline 10 mg kg(-1) day(-1) or placebo for 2 weeks in a double-blind crossover study. FEV1 and PD20 histamine were measured before and 8 h after the first dose of treatment and 8, 32 and 56 h after the final dose. PD20 AMP was measured before treatment and 9 h after the final dose. RESULTS: Six patients did not tolerate theophylline. In the other 12 subjects there were no differences between treatments in daily PEF, symptom scores, rescue bronchodilator use, PD20 histamine or FEV1 up to 8 h post treatment. Following withdrawal of theophylline there were significantly lower values for mean FEV1 (mean difference 0.151, 95% CI 0.03, 026) and PD20 AMP compared to placebo but no difference in other end points. CONCLUSIONS: the small rebound deterioration in lung function following regular treatment with therapeutic doses of oral theophylline is consistent with the development of tolerance.

BACKGROUND: Inhaled adenosine monophosphate (AMP) is thought to cause bronchoconstriction in asthmatic patients indirectly through mast cell mediator release. It may therefore be a more sensitive marker of airway inflammation in asthma and hence more specific for epidemiological surveys of asthma than challenges that act directly on airway smooth muscle such as histamine. There is some uncertainty as to how repeatable the measurement is and this is important if it is to be used for epidemiological studies. METHODS: the response to histamine and AMP challenges and the protection afforded by terbutaline (500 micrograms) against these two challenges was measured on two occasions two weeks apart in 20 subjects with asthma (19 completed the study). The response to histamine and AMP was measured as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20) and the protection afforded by terbutaline in doubling doses (DD). Repeatability was assessed as the limits of agreement. RESULTS: Although terbutaline had a slightly greater protective effect against AMP than histamine on both the first (delta PD20 = 2.66 versus 2.11 DD) and second occasion (2.56 and 2.15 DD), the differences were not statistically significant. The limits of agreement for the two histamine and two AMP challenges after placebo were from 3.06 to -3.5 and from 3.78 to -4.54 DD respectively, and these values did not differ significantly. The agreement limits between the first PD20 histamine and PD20 AMP values after placebo were similar, being from 3.73 to -3.72 DD after allowing for the 17.8-fold higher PD20 values for AMP compared with histamine. CONCLUSIONS: Terbutaline caused a slightly greater inhibition of the bronchoconstrictor response to AMP than histamine but the differences were small and non-significant. Any differences in repeatability between AMP and histamine challenges are small and in this study were not significant. The fact that the agreement between histamine and AMP PD20 values was similar to the agreement between repeat histamine or repeat AMP PD20 values suggests that, within an asthmatic population, PD20 AMP may not be providing different information from that provided by PD20 histamine.

OBJECTIVES: to determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: a double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: in subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.