Where next for partial randomisation of research funding? The feasibility of RCTs and alternatives.

We outline essential considerations for any study of partial randomisation of research funding, and consider scenarios in which randomised controlled trials (RCTs) would be feasible and appropriate. We highlight the interdependence of target outcomes, sample availability and statistical power for determining the cost and feasibility of a trial. For many choices of target outcome, RCTs may be less practical and more expensive than they at first appear (in large part due to issues pertaining to sample size and statistical power). As such, we briefly discuss alternatives to RCTs. It is worth noting that many of the considerations relevant to experiments on partial randomisation may also apply to other potential experiments on funding processes (as described in The Experimental Research Funder's Handbook. RoRI, June 2022).

How to improve scientific peer review: Four schools of thought.

Peer review plays an essential role as one of the cornerstones of the scholarly publishing system. There are many initiatives that aim to improve the way in which peer review is organized, resulting in a highly complex landscape of innovation in peer review. Different initiatives are based on different views on the most urgent challenges faced by the peer review system, leading to a diversity of perspectives on how the system can be improved. To provide a more systematic understanding of the landscape of innovation in peer review, we suggest that the landscape is shaped by four schools of thought: The Quality & Reproducibility school, the Democracy & Transparency school, the Equity & Inclusion school, and the Efficiency & Incentives school. Each school has a different view on the key problems of the peer review system and the innovations necessary to address these problems. The schools partly complement each other, but we argue that there are also important tensions between them. We hope that the four schools of thought offer a useful framework to facilitate conversations about the future development of the peer review system.

Governance of Intersectoral Collaborations for Population Health and to Reduce Health Inequalities in High-Income Countries: A Complexity-Informed Systematic Review.

BACKGROUND: A 'Health in All Policies' (HiAP) approach has been widely advocated as a way to involve multiple government sectors in addressing health inequalities, but implementation attempts have not always produced the expected results. Explaining how HiAP-style collaborations have been governed may offer insights into how to improve population health and reduce health inequalities. METHODS: Theoretically focused systematic review. Synthesis of evidence from evaluative studies into a causal logic model. RESULTS: Thirty-one publications based on 40 case studies from nine high-income countries were included. Intersectoral collaborations for population health and equity were multi-component and multi-dimensional with collaborative activity spanning policy, strategy, service design and service delivery. Governance of intersectoral collaboration included structural and relational components. Both internal and external legitimacy and credibility delivered collaborative power, which in turn enabled intersectoral collaboration. Internal legitimacy was driven by multiple structural elements and processes. Many of these were instrumental in developing (often-fragile) relational trust. Internal credibility was supported by multi-level collaborations that were adequately resourced and shared power. External legitimacy and credibility was created through meaningful community engagement, leadership that championed collaborations and the identification of 'win-win' strategies. External factors such as economic shocks and short political cycles reduced collaborative power. CONCLUSION: This novel review, using systems thinking and causal loop representations, offers insights into how collaborations can generate internal and external legitimacy and credibility. This offers promise for future collaborative activity for population health and equity; it presents a clearer picture of what structural and relational components and dynamics collaborative partners can focus on when planning and implementing HiAP initiatives. The limits of the literature base, however, does not make it possible to identify if or how this might deliver improved population health or health equity.

An overview of innovations in the external peer review of journal manuscripts.

Background: There are currently numerous innovations in peer review and quality assurance in scholarly publishing. The Research on Research Institute conducted a programme of co-produced projects investigating these innovations. This literature review was part of one such project 'Experiments in peer review' which created an inventory and framework of peer review innovations. The aim of this literature review was to aid the development of the inventory by identifying innovations in peer review reported in the scholarly literature and by providing a summary of the different approaches. Methods: This meta-summary is based on data identified from Web of Science and Scopus limited from 2010 to 2021. A total of 247 papers were screened, with 6 review articles chosen for the focus of the literature review. Items were selected that described approaches to innovating peer review or illustrated examples.   Results: The summary of innovations are drawn from 6 review articles. The innovations are divided into three high-level categories: approaches to peer review, reviewer focussed initiatives and technology to support peer review with sub-categories of results presented in tabular form and summarised. A summary of all innovations found is also presented. Conclusions: From a simple synthesis of the review authors' conclusions, three key messages are presented: observations on current practice; authors' views on the implications of innovations in peer review; and calls for action in peer review research and practice.

Should screening for risk of gambling-related harm be undertaken in health, care and support settings? A systematic review of the international evidence.

BACKGROUND: Gambling-related harm is an increasing recognised problem internationally. Recent years have seen an explosion in opportunities to gamble, both in person and online. Health and other care settings have the potential to act as screening sites to identify and support gamblers who may be at high risk of experiencing gambling-related harm. This study aimed to identify interventions to screen for risk of gambling-related harm in the general population which may be delivered in health, care and support settings. METHODS: Systematic review. Searches of key databases and grey sources since 2012 were undertaken in October 2019. Electronic database searches generated a total of 5826 unique hits. Nine studies published 2013-2019, along with thirteen grey literature documents met our eligibility criteria. The criteria were setting (health, care and support settings), participants (any attendee in help, care and support settings), interventions (screening to identify risk of harm from gambling behaviours) and outcome measures (gambling behaviours, service use). RESULTS: Three papers evaluating screening interventions delivered in general practice (repeat visits and written advice), mental health service (the use of screening tools to identify risk of harm), and substance abuse treatment (intensive outpatient treatment for substance use disorders or methadone maintenance) indicated evidence of potential effectiveness. Six papers supported the feasibility and acceptability of delivering interventions in various settings. Grey literature reports described the implementation of interventions such as training materials, and transfer of interventions developed for substance abuse populations by practitioners. CONCLUSIONS: Health, care and support services offer potentially important contexts in which to identify and offer support to people who are at risk of gambling related harm. Screening interventions appear feasible and acceptable in a range of community and healthcare settings for those at risk of gambling harm. Evaluation of effectiveness and cost-effectiveness of screening in these populations should therefore be prioritised.

Interventions to reduce the public health burden of gambling-related harms: a mapping review.

Recognition is growing that gambling, although highly profitable for corporations and governments, is a source of serious and unevenly distributed harm. This recognition has led to demands for public health strategies at the local, national, and international levels. We aimed to identify review-level evidence for interventions to address or prevent gambling-related harms and explore policy implications, using stakeholder consultation to assess the evidence base, identify gaps, and suggest key research questions. We opted for a systematic mapping review and narrative synthesis for all forms of gambling in any setting. We included participants from the whole population, identified gamblers including self-defined, and specific populations at risk (eg, children and young people). We included all outcome measures relating to prevention or treatment of gambling-related harms that were reported by review authors. After duplication, the searches generated 1080 records. Of 43 potential papers, 13 were excluded at the full paper stage and 30 papers were included in the Review. We identified whole-population preventive interventions, such as demand reduction (n=3) and supply reduction (n=4) interventions, and targeted treatment interventions for individuals addicted to gambling, such as therapeutic (n=12), pharmacological (n=5), and self-help or mutual support (n=4) interventions. We also reviewed studies (n=2) comparing these approaches. Interventions to screen, identify, and support individuals at risk of gambling-related harms and interventions to support ongoing recovery and prevent relapse for individuals with a gambling addiction were not represented in the review-level evidence. A public health approach suggests that there are opportunities to reduce gambling-related harms by intervening across the whole gambling pathway, from regulation of access to gambling to screening for individuals at risk and services for individuals with an identified gambling problem. The dearth of evidence for some interventions means that implementation must be accompanied by robust evaluation.

Incentivising research data sharing: a scoping review.

Background: Numerous mechanisms exist to incentivise researchers to share their data. This scoping review aims to identify and summarise evidence of the efficacy of different interventions to promote open data practices and provide an overview of current research. Methods: This scoping review is based on data identified from Web of Science and LISTA, limited from 2016 to 2021. A total of 1128 papers were screened, with 38 items being included. Items were selected if they focused on designing or evaluating an intervention or presenting an initiative to incentivise sharing. Items comprised a mixture of research papers, opinion pieces and descriptive articles. Results: Seven major themes in the literature were identified: publisher/journal data sharing policies, metrics, software solutions, research data sharing agreements in general, open science 'badges', funder mandates, and initiatives. Conclusions: A number of key messages for data sharing include: the need to build on existing cultures and practices, meeting people where they are and tailoring interventions to support them; the importance of publicising and explaining the policy/service widely; the need to have disciplinary data champions to model good practice and drive cultural change; the requirement to resource interventions properly; and the imperative to provide robust technical infrastructure and protocols, such as labelling of data sets, use of DOIs, data standards and use of data repositories.

Measuring quality of life in Duchenne muscular dystrophy: a systematic review of the content and structural validity of commonly used instruments.

Duchenne muscular dystrophy (DMD) is an inherited X-linked neuromuscular disorder. A number of questionnaires are available to assess quality of life in DMD, but there are concerns about their validity. This systematic review aimed to appraise critically the content and structural validity of quality of life instruments for DMD. Five databases (EMBASE, MEDLINE, CINAHL, PsycINFO, and Cochrane Library) were searched, with supplementary searches in Google Scholar. We included articles with evidence on the content and/or structural validity of quality of life instruments in DMD, and/or instrument development. Evidence was evaluated against the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. Fifty five articles featured a questionnaire assessing quality of life in DMD. Forty instruments were extracted and 26 underwent assessment. Forty-one articles contained evidence on content or structural validity (including 37 development papers). Most instruments demonstrated low quality evidence and unsatisfactory or inconsistent validity in DMD, with the majority not featuring direct validation studies in this population. Only KIDSCREEN received an adequate rating for instrument design and a satisfactory result for content validity based on its development, yet, like the majority of PROMs, the measure has not been directly validated for use in DMD. Further research is needed on the validity of quality of life instruments in DMD, including content and structural validity studies in this population.

Are Current Reporting Standards Used to Describe Health State Utilities in Cost-Effectiveness Models Satisfactory?

OBJECTIVE: The aims of this study were to examine current reporting standards of health state utilities (HSU) using a review of published cost-effectiveness analyses in cardiovascular disease and to explore the impact of variation in model inputs used in these on estimated quality-adjusted life-years (QALYs) and cost-effectiveness. METHODS: Key health/economics bibliographic databases were searched to identify relevant articles published after 2014. Any narrative or values relating to the HSU used in the model were extracted and reviewed. The HSUs were systematically applied to an existing model to explore the influence of different values on QALYs and the incremental cost-effectiveness ratio. RESULTS: Twenty-four peer-reviewed articles were identified. Only 2 studies referred to a literature review for the HSUs. Most (18 of 24) referenced previously published economic studies (as opposed to the original source) for at least 1 of the HSUs. Only 4 studies referenced the original sources and reported all of the HSUs accurately, and several did not provide all the HSUs. Little information was provided on the methods used to calculate QALYs, for example, the duration of time for acute HSUs, what the baseline HSU was, the method that was used to assign HSUs for subsequent different events, or how constant HSUs for clinical events were combined with age-adjusted baseline values. The huge differences in HSUs used in the studies produced substantial variations in the QALYs and incremental cost-effectiveness ratios generated from the cost-effectiveness model. CONCLUSION: Current standards are poor, and there is a need for greater transparency in reporting the HSUs used in cost-effectiveness models.

Expediting learning through peer teaching: experiences with the Jigsaw technique.

When designing a teaching session, lack of time and the weight of custom and practice can lead to methods being repeated routinely (Woods, 2013a). The institutional context and student demographic are also fundamental in determining teaching design (Fry, Ketteridge & Marshall, 2015). In this feature, a versatile teaching method (Jigsaw) is described with reference to theories of learning. Examples of its application in professional learning contexts are presented and discussed. D.I.

Impact of Carotid Artery Stenosis on Quality of Life: A Systematic Review.

OBJECTIVES: The aim of this study was to identify themes that determine health-related quality of life (HRQoL) in patients with carotid artery stenosis and identify the patient-reported outcome measures (PROMs) that best cover the identified themes. METHODS: A systematic review of the main six databases from inception to September 2018 was undertaken to identify primary qualitative studies reporting on the HRQoL of patients with carotid artery stenosis. The quality of studies was assessed using the Critical Appraisal Skills Programme (CASP) criteria. Findings from the included studies were analysed using framework analysis methodology. The identified themes were mapped against the items/domains from the PROMs used previously in patients with carotid artery stenosis. RESULTS: The systematic review identified four papers that fulfilled the inclusion criteria. The included papers reported the views of 62 patients with symptomatic carotid artery stenosis; 24 of the patients were awaiting assessment for intervention, 26 had carotid endarterectomy, and 12 were turned down for intervention and received best medical therapy. The overall quality of the included studies was good based on CASP criteria. Framework analysis identified 16 themes that were divided into five main domains: anxiety, impact on personal roles and activities, effect on independence, psychological impact, and symptoms. The best-fit generic and disease-specific PROMs were the Medical Outcomes Study 36-Item Short Form (SF-36®) and the Carotid Stenosis Specific Outcome Measure (CSSOM), respectively. None of the PROMs covered all the themes identified in the qualitative systematic review. CONCLUSION: The findings from the review identified the important themes that affect patients with carotid stenosis disease. The current generic and disease-specific PROMs do not cover all themes that impact the HRQoL of patients suffering with this disease. The proposed themes can be used to develop a new disease-specific PROM to measure HRQoL.

A review of quality of life themes in Duchenne muscular dystrophy for patients and carers.

Duchenne Muscular Dystrophy (DMD) is a severe, life-limiting and incurable condition. However, studies estimating quality of life and those measuring actual quality of life in people living with DMD vary considerably. This discrepancy indicates potential difficulties with assessing quality of life using common generic quality of life instruments in this rare and unique population. This study sought to document the range of themes relevant to quality of life for people with DMD by examining the published literature and additionally to investigate the themes that are relevant to quality of life for carers and the wider family. Eligible studies for the review were primary studies of any study design that reported outcomes or themes relevant to quality of life for either people with DMD, their families, or both. A review of studies identified from searching medical bibliographic sources between 2010 and 2016 found 45 relevant published studies. A thematic framework is proposed to categorise the themes identified into: i. physical; ii. psychological; iii. Social; iv. well-being domains. A final "other" domain was included to encompass themes identified from the literature that are not covered by commonly used quality of life instruments. The rich variety of themes identified from the review highlights that DMD has a complex quality of life profile which is not currently captured by standard quality of life tools that are commonly employed in the healthcare setting. The findings also highlight that the resulting impact on the quality of life of carers and wider family of people with DMD requires consideration.

Themes that Determine Quality of Life in Patients with Peripheral Arterial Disease: A Systematic Review.

OBJECTIVES: The aim of this study was to identify domains that determine quality of life in patients with peripheral arterial disease and find the patient-reported outcome measures that can examine the identified themes. METHODS: A systematic review of all the main six databases was undertaken to identify primary qualitative studies reporting on the health and/or quality of life of patients with peripheral arterial disease. The quality of studies was assessed using the Critical Appraisal Skills Program criteria. Findings from the included studies were analysed using framework analysis methodology. The identified themes were mapped against the items/domains of validated patient-reported outcome measures used in patients with peripheral arterial disease. RESULTS: The systematic review identified eight papers that fulfilled the inclusion criteria. The included papers reported the views of 186 patients with peripheral arterial disease including patients with intermittent claudication, critical ischaemia and amputation secondary to peripheral arterial disease. The overall quality of the included studies was good based on Critical Appraisal Skills Program criteria. Framework analysis identified 35 themes that were divided into six main groups: symptoms, impact on physical functioning, impact on social functioning, psychological impact, financial impact and process of care. The best-fit generic and disease-specific patient-reported outcome measures were the Nottingham Health Profile and the Vascular Quality of Life Questionnaire, respectively. None of the patient-reported outcome measures covered all the themes important to patients with peripheral arterial disease. DISCUSSION: The findings from the review identified the important domains that affect patients living with peripheral arterial disease. None of the current generic and disease-specific patient-reported outcome measures provide a comprehensive measure for all themes that impact the daily living of patients with peripheral arterial disease.

The association between long-term conditions and uptake of population-based screening for colorectal cancer: results from two English cohort studies.

INTRODUCTION: Uptake of screening for colorectal cancer (CRC) can reduce mortality, and population-based screening is offered in England. To date, there is little evidence on the association between having a long-term condition (LTC) and CRC screening uptake. The objective of this study was to examine the association between having an LTC and uptake of CRC screening in England with the guaiac fecal occult blood test, with a particular focus on common mental disorders. METHODS: The study was a preregistered secondary analysis of two cohorts: first, a linked data set between the regional Yorkshire Health Study (YHS) and the National Health Service National Bowel Cancer Screening Program (BCSP, years 2006-2014); second, the national English Longitudinal Study of Ageing (ELSA, years 2014-2015). Individuals eligible for BCSP screening who participated in either the YHS (7,142) or ELSA Wave 7 (4,099) were included. Study registration: ClinicalTrials.gov, number NCT02503969. RESULTS: In both the cohorts, diabetes was associated with lower uptake (YHS odds ratio [OR] for non-uptake 1.35, 95% CI 1.03-1.78; ELSA 1.33, 1.03-1.72) and osteoarthritis was associated with increased uptake (YHS 0.75, 0.57-0.99; ELSA 0.76, 0.62-0.93). After controlling for broader determinants of health, there was no evidence of significantly different uptake for individuals with common mental disorders. CONCLUSION: Two large independent cohorts provided evidence that uptake of CRC screening is lower among individuals with diabetes and higher among individuals with osteoarthritis. Further work should compare barriers and facilitators to screening among individuals with either of these conditions. This study also demonstrates the benefits of data linkage for improving clinical decision-making.

Patient-Reported Outcome Measures in Carotid Artery Revascularization: Systematic Review and Psychometric Analysis.

BACKGROUND: Patient-reported outcome measures (PROMs) provide a way to measure the impact of a disease and its associated treatments on the quality of life (QoL) from the patients' perspective. The aim of this review was to identify PROMs that have been developed and/or validated in patients with carotid artery stenosis (CAS) undergoing revascularization and to assess their psychometric properties and examine suitability for research and clinical use. METHODS: Eight electronic databases including MEDLINE and CINAHL were searched using a 2-stage search approach to identify studies reporting the development and/or validation of relevant PROMs in patients with CAS undergoing revascularization. Supplementary citation searching and hand-searching reference lists of included studies were also undertaken. The COnsensus-based Standards for the selection of health Measurement INstruments and Oxford criteria were used to assess the methodological quality of the included studies, and the psychometric properties of the PROMs were evaluated using established assessment criteria. RESULTS: Five studies reporting on 6 PROMs were included: 36-Item Short Form Health Survey (SF-36), Euro-QoL-5-Dimension Scale (EQ-5D), Hospital Anxiety and Depression Scale, Dizziness Handicap Inventory, QoL for carotid artery disease scale, and a disease-specific PROM for CAS. The rigor of the psychometric assessment of the PROMs was variable with most only attempting to assess a single psychometric criterion. No study reported evidence on construct validity and test-retest reliability. Evidence for acceptability for the use of SF-36, EQ-5D, and the disease-specific PROM was rated good in most studies. Only one study reported a Cronbach alpha score >0.70 as evidence of internal consistency. Overall, the psychometric evaluation of all included PROMs was rated as poor within the CAS population undergoing revascularization. CONCLUSIONS: This review highlighted a lack of evidence in validated PROMs used for patients undergoing carotid artery revascularization. As a result, the development and validation of a new PROM for this patient population is warranted to provide data which can supplement traditional clinical outcomes (stroke<30 days post-procedural, myocardial infarction, and death) and capture changes in health status and QoL to help inform treatment decisions.

A systematic review of qualitative research into people's experiences of living with venous leg ulcers.

AIM: To systematically identify, evaluate and synthesize qualitative research that examined the symptoms and health-related quality of life themes that are important from the perspective of patients with venous leg ulceration. BACKGROUND: Venous leg ulceration is a common chronic condition; the symptoms and associated treatments have a negative effect on health-related quality of life. Qualitative research methods can provide insight into the personal experiences of patients with venous leg ulceration. DESIGN: Qualitative evidence synthesis (using framework synthesis). DATA SOURCES: Multiple electronic databases including MEDLINE, EMBASE, PsycINFO and CINAHL were comprehensively searched from inception to November 2015. REVIEW METHODS: Systematic identification, quality assessment and synthesis of existing qualitative research were performed; framework synthesis was conducted on included studies. An inductive approach was used and emergent themes were identified. The final stage in the synthesis involved the development of new interpretations. RESULTS: Thirteen studies met the inclusion criteria; the overall quality of the included studies was good. Four overarching themes were identified; physical impact, psychological impact, social impact and treatment and, in these, further subthemes were identified. Ulcer and treatment-related pain, as well as odour and exudate appeared to have significant and direct negative effects on quality of life, with additional and cumulative effects on sleep, mobility and mood. CONCLUSION: The themes identified in this review should be considered by professionals providing services, care and treatment for venous leg ulcer patients and in the selection, or development, of patient-reported outcome measures for use with this population.

GENE EXPRESSION PROFILING AND EXPANDED IMMUNOHISTOCHEMISTRY TESTS TO GUIDE SELECTION OF CHEMOTHERAPY REGIMENS IN BREAST CANCER MANAGEMENT: A SYSTEMATIC REVIEW.

OBJECTIVES: The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer. METHODS: A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint, and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016. RESULTS: Searches identified 7,064 citations, of which forty-one citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat, and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests. CONCLUSIONS: The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomized controlled trial data.

Patient-reported outcome measures in patients with peripheral arterial disease: a systematic review of psychometric properties.

BACKGROUND: Peripheral arterial disease (PAD) is generally associated with considerable morbidity and reduced quality of life. Patient-reported outcome measures (PROMs) provide important information about the burden of disease and impact of treatment in affected patients. OBJECTIVES: The objective of the review was to identify and appraise studies reporting the psychometric evaluation of PROMs administered to a specified population of patients with PAD with a view to recommending suitable PROMs. METHODS: A systematic review of peer-reviewed English language articles was undertaken to identify primary studies reporting psychometric properties of PROMs in English-speaking patients with various stages of PAD. Comprehensive searches were completed up until January 2015. Study selection, data extraction and quality assessment were undertaken independently by at least two researchers. Findings were presented as tabular and narrative summaries based on accepted guidance. RESULTS: Psychometric evaluation of 6 generic and 7 condition-specific PROMs reported in 14 studies contributed data to the review. The frequently reported measure was the SF-36 (n = 11 studies); others included the Walking Impairment Questionnaire (n = 8 studies), EQ-5D (n = 5 studies) and the Vascular Quality of Life Questionnaire (n = 3 studies). Studies included a diverse PAD population and varied in methodology, including approach to validation of PROMs. CONCLUSIONS: Various PROMs have been validated in patients with PAD but no study provided evidence of a full psychometric evaluation in the patient population. Careful selection is required to identify reliable and valid PROMs to use in clinical and research settings.

Building the Evidence Base of Blood-Based Biomarkers for Early Detection of Cancer: A Rapid Systematic Mapping Review.

BACKGROUND: The Early Cancer Detection Consortium is developing a blood-test to screen the general population for early identification of cancer, and has therefore conducted a systematic mapping review to identify blood-based biomarkers that could be used for early identification of cancer. METHODS: A mapping review with a systematic approach was performed to identify biomarkers and establish their state of development. Comprehensive searches of electronic databases Medline, Embase, CINAHL, the Cochrane library and Biosis were conducted in May 2014 to obtain relevant literature on blood-based biomarkers for cancer detection in humans. Screening of retrieved titles and abstracts was performed using an iterative sifting process known as "data mining". All blood based biomarkers, their relevant properties and characteristics, and their corresponding references were entered into an inclusive database for further scrutiny by the Consortium, and subsequent selection of biomarkers for rapid review. This systematic review is registered with PROSPERO (no. CRD42014010827). FINDINGS: The searches retrieved 19,724 records after duplicate removal. The data mining approach retrieved 3990 records (i.e. 20% of the original 19,724), which were considered for inclusion. A list of 814 potential blood-based biomarkers was generated from included studies. Clinical experts scrutinised the list to identify miss-classified and duplicate markers, also volunteering the names of biomarkers that may have been missed: no new markers were identified as a result. This resulted in a final list of 788 biomarkers. INTERPRETATION: This study is the first to systematically and comprehensively map blood biomarkers for early detection of cancer. Use of this rapid systematic mapping approach found a broad range of relevant biomarkers allowing an evidence-based approach to identification of promising biomarkers for development of a blood-based cancer screening test in the general population.

Preventing the progression to type 2 diabetes mellitus in adults at high risk: a systematic review and network meta-analysis of lifestyle, pharmacological and surgical interventions.

AIMS: Individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) have an increased risk of progression to Type 2 diabetes mellitus. The objective of this review was to quantify the effectiveness of lifestyle, pharmacological and surgical interventions in reducing the progression to Type 2 diabetes mellitus in people with IFG or IGT. METHODS: A systematic review was carried out. A network meta-analysis (NMA) of log-hazard ratios was performed. Results are presented as hazard ratios and the probabilities of treatment rankings. RESULTS: 30 studies were included in the NMA. There was a reduced hazard of progression to Type 2 diabetes mellitus associated with all interventions versus standard lifestyle advice; glipizide, diet plus pioglitazone, diet plus exercise plus metformin plus rosiglitazone, diet plus exercise plus orlistat, diet plus exercise plus pedometer, rosiglitazone, orlistat and diet plus exercise plus voglibose produced the greatest effects. CONCLUSIONS: Lifestyle and some pharmacological interventions are beneficial in reducing the risk of progression to Type 2 diabetes mellitus. Lifestyle interventions require significant behaviour changes that may be achieved through incentives such as the use of pedometers. Adverse events and cost of pharmacological interventions should be taken into account when considering potential risks and benefits.