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1.  Thanks to all those who reviewed for Systematic Reviews in 2014 
Systematic Reviews  2015;4:14.
Contributing reviewers
A peer-reviewed journal would not survive without the generous time and insightful comments of the reviewers, whose efforts often go unrecognized. Although final decisions are always editorial, they are greatly facilitated by the deeper technical knowledge, scientific insights, understanding of social consequences, and passion that reviewers bring to our deliberations. For these reasons, the Editors-in-Chief and staff of the journal warmly thank the 219 reviewers whose comments helped to shape Systematic Reviews, for their invaluable assistance with review of manuscripts for the journal in Volume 3 (2014).
doi:10.1186/s13643-015-0003-9
PMCID: PMC4335375
2.  A systematic review protocol for measuring comorbidity in inpatient rehabilitation for non-traumatic brain injury 
Systematic Reviews  2015;4(1):14.
Background
Comorbidity can affect health-care utilization and outcomes, and the results and interpretation of risk adjustment studies that attempt to predict rehabilitation utilization and outcomes are influenced by the choice of comorbidity measurement. Although the identification of an appropriate measurement has been conducted in some populations and outcomes, this information is currently lacking for the non-traumatic brain injury (nTBI) population in inpatient rehabilitation settings. As such, this is a systematic review protocol to survey the methods used to measure comorbidities in the rehabilitation setting for patients with nTBI.
Methods/design
MEDLINE, MEDLINE In-Process, Embase, The Cochrane Database of Systematic Reviews, PsycINFO, and Health and Psychosocial Instruments will be systematically searched using the concepts ‘nTBI,’ ‘comorbidity,’ and ‘rehabilitation.’ Grey matters and the reference list of eligible articles will also be searched. Study selection will be performed independently by two reviewers based on predetermined eligibility criteria through two rounds of screening using, first, the title and abstract, followed by full-text. Extracted information will include study purpose, design, and setting; data source and type; outcomes variables; statistical methods; comorbidity measurement method, rationale, justification, or validation; and results involving comorbidity. The data will be tabulated and narratively synthesized. Meta-analyses will be performed if appropriate.
Systematic review registration
This protocol has not been registered with PROSPERO.
Discussion
This protocol provides a systematic method for surveying current practice as well as monitoring the progress on comorbidity measurement methodology and effects of comorbidity on rehabilitation outcomes for patients with nTBI. The selection of an appropriate comorbidity measurement method has implications for the interpretation of both descriptive and risk adjustment studies, and thus, the validity of evidence used to inform planning and delivery of services.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-4-14) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-4-14
PMCID: PMC4328947  PMID: 25634135
Brain injury; Rehabilitation; Health services; Comorbidity; Risk adjustment; Epidemiology; Systematic review
3.  User-centered design and the development of patient decision aids: protocol for a systematic review 
Systematic Reviews  2015;4(1):11.
Background
Providing patient-centered care requires that patients partner in their personal health-care decisions to the full extent desired. Patient decision aids facilitate processes of shared decision-making between patients and their clinicians by presenting relevant scientific information in balanced, understandable ways, helping clarify patients’ goals, and guiding decision-making processes. Although international standards stipulate that patients and clinicians should be involved in decision aid development, little is known about how such involvement currently occurs, let alone best practices. This systematic review consisting of three interlinked subreviews seeks to describe current practices of user involvement in the development of patient decision aids, compare these to practices of user-centered design, and identify promising strategies.
Methods/design
A research team that includes patient and clinician representatives, decision aid developers, and systematic review method experts will guide this review according to the Cochrane Handbook and PRISMA reporting guidelines. A medical librarian will hand search key references and use a peer-reviewed search strategy to search MEDLINE, EMBASE, PubMed, Web of Science, the Cochrane Library, the ACM library, IEEE Xplore, and Google Scholar. We will identify articles across all languages and years describing the development or evaluation of a patient decision aid, or the application of user-centered design or human-centered design to tools intended for patient use. Two independent reviewers will assess article eligibility and extract data into a matrix using a structured pilot-tested form based on a conceptual framework of user-centered design. We will synthesize evidence to describe how research teams have included users in their development process and compare these practices to user-centered design methods. If data permit, we will develop a measure of the user-centeredness of development processes and identify practices that are likely to be optimal.
Discussion
This systematic review will provide evidence of current practices to inform approaches for involving patients and other stakeholders in the development of patient decision aids. We anticipate that the results will help move towards the establishment of best practices for the development of patient-centered tools and, in turn, help improve the experiences of people who face difficult health decisions.
Systematic review registration
PROSPERO CRD42014013241
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-4-11) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-4-11
PMCID: PMC4328638  PMID: 25623074
Patient decision aids; Decision support; Shared decision-making; Patient education; Counseling; User-centered design; Human-centered design; Patient partnership; Stakeholder engagement; Implementation; Knowledge translation; Patient-centered care
4.  PCR-based specific techniques used for detecting the most important pathogens on strawberry: a systematic review 
Systematic Reviews  2015;4(1):9.
Background
Strawberry diseases are a major limiting factor that severely impact plant agronomic performance. Regarding limitations of traditional techniques for detection of pathogens, researchers have developed specific DNA-based tests as sensitive and specific techniques. The aim of this review is to provide an overview of polymerase chain reaction (PCR)-based methods used for detection or quantification of the most widespread strawberry pathogens, such as Fusarium oxysporum f.sp. fragariae, Phytophthora fragariae, Colletotrichum acutatum, Verticillium dahliae, Botrytis cinerea, Macrophomina phaseolina, and Xanthomonas fragariae. An updated and detailed list of published PCR protocols is presented and discussed, aimed at facilitating access to information that could be particularly useful for diagnostic laboratories in order to develop a rapid, cost-effective, and reliable monitoring technique.
Methods
The study design was a systematic review of PCR-based techniques used for detection and quantification of strawberry pathogens. Using appropriate subject headings, AGRICOLA, AGRIS, BASE, Biological Abstracts, CAB Abstracts, Google Scholar, Scopus, Web of Knowledge, and SpringerLink databases were searched from their inception up to April 2014. Two assessors independently reviewed the titles, abstracts, and full articles of all identified citations. Selected articles were included if one of the mentioned strawberry pathogens was investigated based on PCR methods, and a summary of pre-analytical requirements for PCR was provided.
Results
A total of 259 titles and abstracts were reviewed, of which 22 full texts met all the inclusion criteria. Our systematic review identified ten different protocols for X. fragariae, eight for P. fragariae, four for B. cinerea, six for C. acutatum, three for V. dahlia, and only one for F. oxysporum. The accuracy and sensitivity of PCR diagnostic methods is the focus of most studies included in this review. However, a large proportion of errors in laboratories occur in the pre-analytical phase of the testing process. Due to heterogeneity, results could not be meta-analyzed.
Conclusions
From a systematic review of the currently available published literature, effective detection assays to detect the major strawberry pathogens have been developed. These assays can function as a basis for clinical labs, regulatory personnel, and other diagnosticians to adapt or implement for detection of these six important strawberry pathogens.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-4-9) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-4-9
PMCID: PMC4320524  PMID: 25588564
Molecular diagnostic methods; PCR-based techniques; Strawberry pathogen detection; Systematic review
5.  Reviews: Rapid! Rapid! Rapid! …and systematic 
Systematic Reviews  2015;4(1):4.
doi:10.1186/2046-4053-4-4
PMCID: PMC4320433  PMID: 25589399
6.  An evaluation of methods used to teach quality improvement to undergraduate healthcare students to inform curriculum development within preregistration nurse education: a protocol for systematic review and narrative synthesis 
Systematic Reviews  2015;4(1):8.
Background
Despite criticism, quality improvement (QI) continues to drive political and educational priorities within health care. Until recently, QI educational interventions have varied, targeting mainly postgraduates, middle management and the medical profession. However, there is now consensus within the UK, USA and beyond to integrate QI explicitly into nurse education, and faculties may require redesign of their QI curriculum to achieve this. Whilst growth in QI preregistration nurse education is emerging, little empirical evidence exists to determine such effects. Furthermore, previous healthcare studies evaluating QI educational interventions lend little in the way of support and have instead been subject to criticism. They reveal methodological weakness such as no reporting of theoretical underpinnings, insufficient intervention description, poor evaluation methods, little clinical or patient impact and lack of sustainability. This study aims therefore to identify, evaluate and synthesise teaching methods used within the undergraduate population to aid development of QI curriculum within preregistration nurse education.
Methods/design
A systematic review of the literature will be conducted. Electronic databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Psychological Information (PsychINFO), Education Resources Information Centre (ERIC), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Applied Social Sciences Index and Abstracts (ASSIA), will be searched alongside reference list scanning and a grey literature search. Peer-reviewed studies from 2000–2014 will be identified using key terms quality improvement, education, curriculum, training, undergraduate, teaching methods, students and evaluation. Studies describing a QI themed educational intervention aimed at undergraduate healthcare students will be included and data extracted using a modified version of the Reporting of Primary Studies in Education (REPOSE) Guidelines. Studies will be judged for quality and relevance using the Evidence for Policy and Practice Information and Co-ordinating Centre’s (EPPI) Weight of Evidence framework and a narrative synthesis of the findings provided.
Discussion
This study aims to identify, evaluate and synthesise the teaching methods used in quality improvement education for undergraduate healthcare students where currently this is lacking. This will enable nursing faculty to adopt the most effective methods when developing QI education within their curriculum.
Systematic review registration
Prospero CRD42014013847
doi:10.1186/2046-4053-4-8
PMCID: PMC4320447  PMID: 25588516
Systematic review protocol; Quality improvement; Curriculum; Education; Preregistration nursing; Teaching methods; Evaluation; Narrative synthesis
7.  Using text mining for study identification in systematic reviews: a systematic review of current approaches 
Systematic Reviews  2015;4(1):5.
Background
The large and growing number of published studies, and their increasing rate of publication, makes the task of identifying relevant studies in an unbiased way for inclusion in systematic reviews both complex and time consuming. Text mining has been offered as a potential solution: through automating some of the screening process, reviewer time can be saved. The evidence base around the use of text mining for screening has not yet been pulled together systematically; this systematic review fills that research gap. Focusing mainly on non-technical issues, the review aims to increase awareness of the potential of these technologies and promote further collaborative research between the computer science and systematic review communities.
Methods
Five research questions led our review: what is the state of the evidence base; how has workload reduction been evaluated; what are the purposes of semi-automation and how effective are they; how have key contextual problems of applying text mining to the systematic review field been addressed; and what challenges to implementation have emerged?
We answered these questions using standard systematic review methods: systematic and exhaustive searching, quality-assured data extraction and a narrative synthesis to synthesise findings.
Results
The evidence base is active and diverse; there is almost no replication between studies or collaboration between research teams and, whilst it is difficult to establish any overall conclusions about best approaches, it is clear that efficiencies and reductions in workload are potentially achievable.
On the whole, most suggested that a saving in workload of between 30% and 70% might be possible, though sometimes the saving in workload is accompanied by the loss of 5% of relevant studies (i.e. a 95% recall).
Conclusions
Using text mining to prioritise the order in which items are screened should be considered safe and ready for use in ‘live’ reviews. The use of text mining as a ‘second screener’ may also be used cautiously. The use of text mining to eliminate studies automatically should be considered promising, but not yet fully proven. In highly technical/clinical areas, it may be used with a high degree of confidence; but more developmental and evaluative work is needed in other disciplines.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-4-5) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-4-5
PMCID: PMC4320539  PMID: 25588314
Text mining; Automation; Screening; Study selection; Review efficiency
8.  Methods of a multi-faceted rapid knowledge synthesis project to inform the implementation of a new health service model: Collaborative Emergency Centres 
Systematic Reviews  2015;4(1):7.
Background
The aim of this rapid knowledge synthesis was to provide relevant research evidence to inform the implementation of a new health service in Nova Scotia, Canada: Collaborative Emergency Centres (CECs). CECs propose to deliver both primary and urgent care to rural populations where traditional delivery is a challenge. This paper reports on the methods used in a rapid knowledge synthesis project to provide timely evidence to policy makers about this novel healthcare delivery model.
Methods
We used a variety of methods, including a jurisdictional/scoping review, modified systematic review methodologies, and integrated knowledge translation. We scanned publicly available information about similar centres across our country to identify important components of CECs and CEC-type models to operationalize the definition of a CEC. We conducted literature searches in PubMed, CINAHL, and EMBASE, and in the grey literature, to identify evidence on the key structures and processes and effectiveness of CEC-type models of care delivery. Our searches were limited to published systematic reviews. The research team facilitated two integrated knowledge translation workshops during the project to engage stakeholders, to refine the research goals and objectives, and to share interim and final results. Citations and included articles were categorized by whether they addressed the CEC model or component structures and processes. Data and key messages were extracted from these reviews to inform implementation.
Results
CEC-type models have limited peer-reviewed evidence available; no peer-reviewed studies on CECs as a standalone healthcare model were found. As a result, our evidence search and synthesis was revised to focus on core CEC-type structures and processes, prioritized through consensus methods with the stakeholder group, and resulted in provision of a meaningful evidence synthesis to help inform the development and implementation of CECs in Nova Scotia.
Conclusions
A variety of methods and partnership with decision-makers and stakeholders enabled the project to address the limitations in the evidence regarding CECs and meet the challenge of identifying the best available evidence in a transparent way to meet the needs of decision-makers in a short timeframe.
doi:10.1186/2046-4053-4-7
PMCID: PMC4320554  PMID: 25588468
Rapid review; Jurisdictional review; Integrated knowledge translation; Evidence synthesis; Collaborative Emergency Centres; Rural health care
9.  Better duplicate detection for systematic reviewers: evaluation of Systematic Review Assistant-Deduplication Module 
Systematic Reviews  2015;4(1):6.
Background
A major problem arising from searching across bibliographic databases is the retrieval of duplicate citations. Removing such duplicates is an essential task to ensure systematic reviewers do not waste time screening the same citation multiple times. Although reference management software use algorithms to remove duplicate records, this is only partially successful and necessitates removing the remaining duplicates manually. This time-consuming task leads to wasted resources. We sought to evaluate the effectiveness of a newly developed deduplication program against EndNote.
Methods
A literature search of 1,988 citations was manually inspected and duplicate citations identified and coded to create a benchmark dataset. The Systematic Review Assistant-Deduplication Module (SRA-DM) was iteratively developed and tested using the benchmark dataset and compared with EndNote’s default one step auto-deduplication process matching on (‘author’, ‘year’, ‘title’). The accuracy of deduplication was reported by calculating the sensitivity and specificity. Further validation tests, with three additional benchmarked literature searches comprising a total of 4,563 citations were performed to determine the reliability of the SRA-DM algorithm.
Results
The sensitivity (84%) and specificity (100%) of the SRA-DM was superior to EndNote (sensitivity 51%, specificity 99.83%). Validation testing on three additional biomedical literature searches demonstrated that SRA-DM consistently achieved higher sensitivity than EndNote (90% vs 63%), (84% vs 73%) and (84% vs 64%). Furthermore, the specificity of SRA-DM was 100%, whereas the specificity of EndNote was imperfect (average 99.75%) with some unique records wrongly assigned as duplicates. Overall, there was a 42.86% increase in the number of duplicates records detected with SRA-DM compared with EndNote auto-deduplication.
Conclusions
The Systematic Review Assistant-Deduplication Module offers users a reliable program to remove duplicate records with greater sensitivity and specificity than EndNote. This application will save researchers and information specialists time and avoid research waste. The deduplication program is freely available online.
doi:10.1186/2046-4053-4-6
PMCID: PMC4320616  PMID: 25588387
Systematic Review Assistant-Deduplication Module; SRA-DM; Deduplication; EndNote; Reference-manager; Citation-screening; Systematic review; Bibliographic database
10.  Weight gain, overweight and obesity in solid organ transplantation—a study protocol for a systematic literature review 
Systematic Reviews  2015;4(1):2.
Background
Overweight and obesity, which have a substantial impact on health in the general population, have similar prevalence in solid organ transplant recipients but carry even more serious ramifications. As this group’s use of immunosuppressive medication increases the risk for comorbidities, e.g. metabolic syndrome and cardiovascular disease, the prevention of additional risk factors is vital. This systematic review will be the first to summarize the issue of weight gain, overweight and obesity concurrently within and across solid organ transplantation. The three research questions relating to solid organ transplantation are the following: (1) What are the prevalence and evolution of overweight and obesity from pre- to post-transplant?; (2) Which pre- and post-transplant risk factors are associated with post-transplant weight gain, overweight or obesity? and (3) Which post-transplant patient outcomes and comorbidities are associated with pre- and post-transplant weight gain, overweight and obesity?
Methods/Design
MEDLINE via PubMed, The Cochrane Library, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO and Excerpta Medica DataBase (EMBASE) will be searched for original quantitative studies in adult liver, heart, lung or kidney transplant patients. Topics of interest will be the prevalence and evolution of overweight and obesity over time, risk factors associated with changes in weight or body mass index (BMI), overweight and obesity, and the relationship of weight or BMI with post-transplant outcomes and comorbidities. Screening of titles and abstracts, full-text reading and data extraction will be divided between three researchers. Researchers will cross-check one another’s screening decisions for random samples of studies to adhere as closely as possible to the recommendations of The Cochrane Collaboration. For quality assessment, a purpose-adapted 19-item instrument will be used. Effect sizes will be calculated for relationships investigated in a minimum of five studies. Random effects meta-analysis with moderator analyses will be conducted if applicable.
Discussion
This systematic review will comprehensively synthesize the existing evidence concerning weight gain, overweight and obesity in solid organ transplantation in view of magnitude, influencing factors and associations with patient outcomes and comorbidities. The results can fuel the development of interventions to prevent weight gain in the solid organ transplant population.
Systematic review registration
PROSPERO CRD42014009151
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-4-2) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-4-2
PMCID: PMC4320543  PMID: 25563983
Weight gain; Overweight; Obesity; Survival; Risk factors; Outcomes; Adult; Transplantation; Systematic review
11.  Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement 
Systematic Reviews  2015;4(1):1.
Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
doi:10.1186/2046-4053-4-1
PMCID: PMC4320440  PMID: 25554246
12.  Systematic reviews of observational studies of risk of thrombosis and bleeding in urological surgery (ROTBUS): introduction and methodology 
Systematic Reviews  2014;3(1):150.
Background
Pharmacological thromboprophylaxis in the peri-operative period involves a trade-off between reduction in venous thromboembolism (VTE) and an increase in bleeding. Baseline risks, in the absence of prophylaxis, for VTE and bleeding are known to vary widely between urological procedures, but their magnitude is highly uncertain. Systematic reviews and meta-analyses addressing baseline risks are uncommon, needed, and require methodological innovation. In this article, we describe the rationale and methods for a series of systematic reviews of the risks of symptomatic VTE and bleeding requiring reoperation in urological surgery.
Methods/design
We searched MEDLINE from January 1, 2000 until April 10, 2014 for observational studies reporting on symptomatic VTE or bleeding after urological procedures. Additional studies known to experts and studies cited in relevant review articles were added. Teams of two reviewers, independently assessed articles for eligibility, evaluated risk of bias, and abstracted data. We derived best estimates of risk from the median estimates among studies rated at the lowest risk of bias. The primary endpoints were 30-day post-operative risk estimates of symptomatic VTE and bleeding requiring reoperation, stratified by procedure and patient risk factors.
Discussion
This series of systematic reviews will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding. Our work advances standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at best estimates of risk (including modeling of timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate certainty in estimates of risk. The results will be incorporated in the upcoming European Association Urology Guideline on Thromboprophylaxis.
Systematic review registration
PROSPERO CRD42014010342.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-150) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-150
PMCID: PMC4307154  PMID: 25540016
Baseline risk; Bleeding; Hemorrhage; Modeling; Risk of bias; Surgical complications; Thromboprophylaxis; Thrombosis; Urology
13.  A protocol for a systematic review of the use of process evaluations in knowledge translation research 
Systematic Reviews  2014;3(1):149.
Background
Experimental designs for evaluating knowledge translation (KT) interventions for professional behavior change can provide strong estimates of intervention effectiveness but offer limited insight how the intervention worked or not. Furthermore, trials provide little insight into the ways through which interventions lead to behavior change and how they are moderated by different facilitators and barriers. As a result, the ability to generalize the findings from one study to a different context, organization, or clinical problem is severely compromised. Consequently, researchers have started to explore the causal mechanisms in complementary studies (process evaluations) alongside experimental designs for evaluating KT interventions. This study focuses on improving process evaluations by synthesizing current evidence on process evaluations conducted alongside experimental designs for evaluating KT interventions.
Methods/Design
A medical research librarian will develop and implement search strategies designed to identify evidence that is relevant to process evaluations in health research. Studies will not be excluded based on design. Included studies must contain a process evaluation component aimed at understanding or evaluating a KT intervention targeting professional behavior change. Two reviewers will perform study selection, quality assessment, and data extraction using standard forms. Disagreements will be resolved through discussion or third party adjudication. Data to be collected include study design, details about data collection approaches and types, theoretical influences, approaches to evaluate intervention dose delivered, intervention dose received, intervention fidelity, intervention reach, data analysis, and study outcomes. This study is not registered with PROSPERO.
Discussion
There is widespread acceptance that the generalizability of quantitative trials of KT interventions would be significantly enhanced to other contexts, health professional groups, and clinical conditions through complementary process evaluations alongside trials. This systematic review will serve as a ‘state of the science’ on methodological approaches to process evaluations and will allow us to: 1) take stock of current research approaches and 2) develop concrete recommendations for knowledge users (e.g., quality consultants and health services researchers) designing future KT process evaluations.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-149) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-149
PMCID: PMC4307977  PMID: 25534345
Process evaluation; Knowledge translation; Research use; Health interventions; Systematic review
14.  Protocol for a systematic review and meta-analysis of hepatitis C virus (HCV) prevalence and incidence in the Horn of Africa sub-region of the Middle East and North Africa 
Systematic Reviews  2014;3(1):146.
Background
In the Middle East and North Africa (MENA), hepatitis C virus (HCV) distribution appears to present a wide range of prevalence. The scale and nature of HCV disease burden is poorly known in the Horn of Africa sub-region of MENA including Djibouti, Somalia, and Sudan in addition to Yemen at the southwest corner of the Arabian Peninsula. The aim of this review is to provide a systematic review and synthesis of all epidemiological data on HCV prevalence and incidence among the different population groups in this sub-region of MENA. A second aim of the study is to estimate the national population-level HCV prevalence for each of these four countries.
Methods/design
The systematic review will be conducted based on the items outlined in the PRISMA statement. PubMed, Embase, and the World Health organization (WHO) regional databases will be searched for eligible studies without language or date restrictions. Observational and intervention studies reporting data on the prevalence or incidence of HCV in any population group in Djibouti, Somalia, Sudan, or Yemen will be included. Additional sources will be obtained through the database of the MENA HIV/AIDS Epidemiology Synthesis Project, including international organizations’ reports and country-level reports, and abstracts of international conferences. Study and population characteristics will be extracted from eligible publications, with previously agreed pro formas; and entered into a computerized database. We will pool prevalence using DerSimonian and Laird random-effects models after a Freeman-Tukey transformation to stabilize variances. We will conduct meta-regression analysis to explore the effect of study-level characteristics as potential sources of heterogeneity.
Discussion
This proposed systematic review and meta-analysis aims to better describe HCV infection distribution across countries in the Horn of Africa sub-region of MENA; and between sub-population groups within each country. The study will provide empirical evidence necessary for researchers, policy-makers, and public health stakeholders to set research, policy, and programming priorities for HCV prevention, control, and treatment.
Systematic review registration
PROSPERO CRD42014010318
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-146) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-146
PMCID: PMC4274704  PMID: 25516265
Hepatitis C; Incidence; Prevalence; Epidemiology; Middle East and North Africa; Djibouti; Somalia; Sudan; Yemen
15.  Educational interventions for general practitioners to identify and manage depression as a suicide risk factor in young people: a systematic review and meta-analysis protocol 
Systematic Reviews  2014;3(1):145.
Background
Suicide is a major public health problem and globally is the second leading cause of death in young adults. Globally, there are 164,000 suicides per year in young people under 25 years. Depression is a strong risk factor for suicide. Evidence shows that 45% of those completing suicide, including young adults, contact their general practitioner rather than a mental health professional in the month before their death. Further evidence indicates that risk factors or early warning signs of suicide in young people go undetected and untreated by general practitioners. Healthcare-based suicide prevention interventions targeted at general practitioners are designed to increase identification of at-risk young people. The rationale of this type of intervention is that early identification and improved clinical management of at-risk individuals will reduce morbidity and mortality. This systematic review will synthesise evidence on the effectiveness of education interventions for general practitioners in identifying and managing depression as a suicide risk factor in young people.
Methods/design
We shall conduct a systematic review and meta-analysis following the Cochrane Handbook for Systematic Reviews of Interventions guidelines and conform to the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. Electronic databases will be systematically searched for randomised controlled trials and quasi-experimental studies investigating the effectiveness of interventions for general practitioners in identifying and managing depression as a suicide risk factor in young people in comparison to any other intervention, no intervention, usual care or waiting list. Grey literature will be searched by screening trial registers. Only studies published in English will be included. No date restrictions will be applied. Two authors will independently screen titles and abstracts of potential studies. The primary outcome is identification and management of depression. Secondary outcomes are suicidal ideation, suicide attempts, deliberate self-harm, knowledge of suicide risk factors and suicide-related behaviours, attitudes towards suicide risk and suicide-related behaviours, confidence in dealing with suicide risk factors and suicide-related behaviour.
Discussion
Our study will inform the development of future education interventions and provide feasibility and acceptability evidence, to help general practitioners identify and manage suicidal behaviour in young people.
Systematic review registration
PROSPERO registration number: CRD42014009110.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-145) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-145
PMCID: PMC4276044  PMID: 25510820
Systematic review; Meta-analysis; Suicide; Prevention; Adolescents; Young adult; General practice
16.  Effect of standardized training on the reliability of the Cochrane risk of bias assessment tool: a study protocol 
Systematic Reviews  2014;3(1):144.
Background
The Cochrane risk of bias (RoB) tool has been widely embraced by the systematic review community, but several studies have reported that its reliability is low. We aim to investigate whether training of raters, including objective and standardized instructions on how to assess risk of bias, can improve the reliability of this tool. We describe the methods that will be used in this investigation and present an intensive standardized training package for risk of bias assessment that could be used by contributors to the Cochrane Collaboration and other reviewers.
Methods/Design
This is a pilot study. We will first perform a systematic literature review to identify randomized clinical trials (RCTs) that will be used for risk of bias assessment. Using the identified RCTs, we will then do a randomized experiment, where raters will be allocated to two different training schemes: minimal training and intensive standardized training. We will calculate the chance-corrected weighted Kappa with 95% confidence intervals to quantify within- and between-group Kappa agreement for each of the domains of the risk of bias tool. To calculate between-group Kappa agreement, we will use risk of bias assessments from pairs of raters after resolution of disagreements. Between-group Kappa agreement will quantify the agreement between the risk of bias assessment of raters in the training groups and the risk of bias assessment of experienced raters. To compare agreement of raters under different training conditions, we will calculate differences between Kappa values with 95% confidence intervals.
Discussion
This study will investigate whether the reliability of the risk of bias tool can be improved by training raters using standardized instructions for risk of bias assessment. One group of inexperienced raters will receive intensive training on risk of bias assessment and the other will receive minimal training. By including a control group with minimal training, we will attempt to mimic what many review authors commonly have to do, that is—conduct risk of bias assessment in RCTs without much formal training or standardized instructions. If our results indicate that an intense standardized training does improve the reliability of the RoB tool, our study is likely to help improve the quality of risk of bias assessments, which is a central component of evidence synthesis.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-144) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-144
PMCID: PMC4273317  PMID: 25495124
Systematic review; Meta-analysis; Risk of bias; RCT; Cochrane
17.  Processes, contexts, and rationale for disinvestment: a protocol for a critical interpretive synthesis 
Systematic Reviews  2014;3(1):143.
Background
Practical solutions are needed to support the appropriate use of available health system resources as countries are continually pressured to ‘do more with less’ in health care. Increasingly, health systems and organizations are exploring the reassessment of possibly obsolete, inefficient, or ineffective health system resources and potentially redirecting funds to those that are more effective and efficient. Such processes are often referred to as ‘disinvestment’. Our objective is to gain further understanding about: 1) whether how and under what conditions health systems decide to pursue disinvestment; 2) how health systems have chosen to undertake disinvestment; and 3) how health systems have implemented their disinvestment approach.
Methods/Design
We will use a critical interpretive synthesis (CIS) approach, to develop a theoretical framework based on insights drawn from a range of relevant sources. We will conduct systematic searches of databases as well as purposive searches to identify literature to fill conceptual gaps that may emerge during our inductive process of synthesis and analysis. Two independent reviewers will assess search results for relevance and conceptually map included references. We will include all empirical and non-empirical articles that focus on disinvestment at a system level. We will then extract key findings from a purposive sample of articles using frameworks related to government agendas, policy development and implementation, and health system contextual factors and then synthesize and integrate the findings to develop a framework about our core areas of interest. Lastly, we will convene a stakeholder dialogue with Canadian and international policymakers and other stakeholders to solicit targeted feedback about the framework (e.g., by identifying any gaps in the literature that we may want to revisit before finalizing it) and deliberating about barriers for developing and implementing approaches to disinvestment, strategies to address these barriers and about next steps that could be taken by different constituencies.
Discussion
Disinvestment is an emerging field and there is a need for evidence to inform the prioritization, development, and implementation of strategies in different contexts. Our CIS and the framework developed through it will support the actions of those involved in the prioritization, development, and implementation of disinvestment initiatives.
Systematic review registration
PROSPERO CRD42014013204
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-143) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-143
PMCID: PMC4273322  PMID: 25495034
Disinvestment; Critical interpretive synthesis; Health technologies; Health system context; Policy development; Policy implementation; Reassessment; Appropriateness
18.  Randomised placebo-controlled trials of individualised homeopathic treatment: systematic review and meta-analysis 
Systematic Reviews  2014;3(1):142.
Background
A rigorous and focused systematic review and meta-analysis of randomised controlled trials (RCTs) of individualised homeopathic treatment has not previously been undertaken. We tested the hypothesis that the outcome of an individualised homeopathic treatment approach using homeopathic medicines is distinguishable from that of placebos.
Methods
The review’s methods, including literature search strategy, data extraction, assessment of risk of bias and statistical analysis, were strictly protocol-based. Judgment in seven assessment domains enabled a trial’s risk of bias to be designated as low, unclear or high. A trial was judged to comprise ‘reliable evidence’ if its risk of bias was low or was unclear in one specified domain. ‘Effect size’ was reported as odds ratio (OR), with arithmetic transformation for continuous data carried out as required; OR > 1 signified an effect favouring homeopathy.
Results
Thirty-two eligible RCTs studied 24 different medical conditions in total. Twelve trials were classed ‘uncertain risk of bias’, three of which displayed relatively minor uncertainty and were designated reliable evidence; 20 trials were classed ‘high risk of bias’. Twenty-two trials had extractable data and were subjected to meta-analysis; OR = 1.53 (95% confidence interval (CI) 1.22 to 1.91). For the three trials with reliable evidence, sensitivity analysis revealed OR = 1.98 (95% CI 1.16 to 3.38).
Conclusions
Medicines prescribed in individualised homeopathy may have small, specific treatment effects. Findings are consistent with sub-group data available in a previous ‘global’ systematic review. The low or unclear overall quality of the evidence prompts caution in interpreting the findings. New high-quality RCT research is necessary to enable more decisive interpretation.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-142) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-142
PMCID: PMC4326322  PMID: 25480654
Individualised homeopathy; Meta-analysis; Randomised controlled trials; Systematic review
19.  Childhood socioeconomic position and adult leisure-time physical activity: a systematic review protocol 
Systematic Reviews  2014;3(1):141.
Background
Participation in leisure-time physical activity benefits health and is thought to be more prevalent in higher socioeconomic groups. Evidence indicates that childhood socioeconomic circumstances may have long-term influences on adult health and behaviour; however, it is unclear if this extends to an influence on adult physical activity. The aim of this review is to examine whether a lower childhood socioeconomic position is associated with lower levels of leisure-time physical activity during adulthood.
Methods/design
Keywords will be used to systematically search five online databases and additional studies will be located through a search of reference lists. At least two researchers working independently will screen search results assess the quality of included studies and extract all relevant data. Studies will be included if they are English language publications that test the association between at least one indicator of childhood socioeconomic position and a leisure-time physical activity outcome measured during adulthood. Any disagreements and discrepancies arising during the conduct of the study will be resolved through discussion.
Discussion
This study will address the gap in evidence by systematically reviewing the published literature to establish whether childhood socioeconomic position is related to adult participation in leisure-time physical activity. The findings may be used to inform future research and policy.
Systematic review registration
PROSPERO CRD42014007063.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-141) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-141
PMCID: PMC4265411  PMID: 25480487
Socioeconomic inequalities; Occupation; Education; Socioeconomic position; Physical activity; Exercise; Life course
20.  Methodological issues and recommendations for systematic reviews of prognostic studies: an example from cardiovascular disease 
Systematic Reviews  2014;3(1):140.
Background
Prognostic factors are associated with the risk of future health outcomes in individuals with a particular health condition. The prognostic ability of such factors is increasingly being assessed in both primary research and systematic reviews. Systematic review methodology in this area is continuing to evolve, reflected in variable approaches to key methodological aspects. The aim of this article was to (i) explore and compare the methodology of systematic reviews of prognostic factors undertaken for the same clinical question, (ii) to discuss implications for review findings, and (iii) to present recommendations on what might be considered to be ‘good practice’ approaches.
Methods
The sample was comprised of eight systematic reviews addressing the same clinical question, namely whether ‘aspirin resistance’ (a potential prognostic factor) has prognostic utility relative to future vascular events in patients on aspirin therapy for secondary prevention. A detailed comparison of methods around study identification, study selection, quality assessment, approaches to analysis, and reporting of findings was undertaken and the implications discussed. These were summarised into key considerations that may be transferable to future systematic reviews of prognostic factors.
Results
Across systematic reviews addressing the same clinical question, there were considerable differences in the numbers of studies identified and overlap between included studies, which could only partially be explained by different study eligibility criteria. Incomplete reporting and differences in terminology within primary studies hampered study identification and selection process across reviews. Quality assessment was highly variable and only one systematic review considered a checklist for studies of prognostic questions. There was inconsistency between reviews in approaches towards analysis, synthesis, addressing heterogeneity and reporting of results.
Conclusions
Different methodological approaches may ultimately affect the findings and interpretation of systematic reviews of prognostic research, with implications for clinical decision-making.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-140) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-140
PMCID: PMC4265412  PMID: 25466903
Systematic review methodology; Prognostic utility; Prognostic factor; Aspirin resistance; Cardiovascular disease; Search strategy; Study selection; Quality assessment; Reporting bias
21.  Health status of and health-care provision to asylum seekers in Germany: protocol for a systematic review and evidence mapping of empirical studies 
Systematic Reviews  2014;3(1):139.
Background
There are more than 100,000 asylum seekers registered in Germany, who are granted limited access to health services. This study aims to provide a systematic overview of the empirical literature on the health status of and health-care provision to asylum seekers in Germany in order to consolidate knowledge, avoid scientific redundance, and identify research gaps.
Methods/design
A systematic review and evidence mapping of empirical literature on the health status of and health-care provision to asylum seekers in Germany will be performed. We will apply a three-tiered search strategy: 1. search in databases (PubMed/MEDLINE, Web of Science, IBSS, Sociological Abstracts, Worldwide Political Science Abstracts, CINAHL, Sowiport, Social Sciences Citation Index, ASSIA, MedPilot, DNB), dissertation and theses databases, and the internet (Google); 2. screening references of included studies; 3. contacting authors and civil society organizations for grey literature. Included will be studies which report quantitative and/or qualitative data or review articles on asylum seekers in Germany, published in German or English language. Outcome measures will include physical, mental, or social well-being, and all aspects of health-care provision (access, availability, affordability, and quality). Search results will be screened for eligibility by screening titles, abstracts and full texts. Data extraction comprises information on study characteristics, research aims, and domains of health or health-care services analyzed. The quality of studies will be appraised and documented by appropriate assessment tools. A descriptive evidence map will be drawn by categorizing all included articles by research design and the health conditions and/or domains of health-care provision analyzed. The body of evidence will be evaluated, and a narrative evidence synthesis will be performed by means of a multi-level approach, whereby quantitative and qualitative evidence are analyzed as separate streams and the product of each stream is configured in a final summary.
Discussion
This systematic review will provide an evidence map and synthesis of available research findings on the health status of and health-care provision to asylum seekers in Germany. In anticipation of identifying areas which are amenable to health-care interventions, deserve immediate action, or further exploration, this review will be of major importance for policy-makers, health-care providers, as well as researchers.
Systematic review registration
PROSPERO 2014: CRD42014013043
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-139) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-139
PMCID: PMC4259011  PMID: 25433520
Asylum seekers; Refugees; Germany; Health status; Health-care provision; Access; Health services; Systematic review; Evidence mapping
22.  Association of industry sponsorship and positive outcome in randomised controlled trials in general and abdominal surgery: protocol for a systematic review and empirical study 
Systematic Reviews  2014;3(1):138.
Background
Industry sponsorship has been identified as a factor correlating with positive research findings in several fields of medical science. To date, the influence of industry sponsorship in general and abdominal surgery has not been fully studied. This protocol describes the rationale and planned conduct of a systematic review to determine the association between industry sponsorship and positive outcome in randomised controlled trials in general and abdominal surgery.
Methods/design
A literature search in the Cochrane Library, MEDLINE and EMBASE and additional hand searches in relevant citations will be conducted. In order to cover all relevant areas of general and abdominal surgery, a new literature search strategy called multi-PICO search strategy (MPSS) has been developed. No language restriction will be applied. The search will be limited to publications between January 1985 and July 2014. Information on funding source, outcome, study characteristics and methodological quality will be extracted.
The association between industry sponsorship and positive outcome will be tested by a chi-squared test. A multivariate logistic regression analysis will be performed to control for possible confounders, such as number of study centres, multinational trials, methodological quality, journal impact factor and sample size.
Discussion
This study was designed to clarify whether industry-sponsored trials report more positive outcomes than non-industry trials. It will be the first study to evaluate this topic in general and abdominal surgery. The findings of this study will enable surgical societies, in particular, to give advice about cooperation with the industry and disclosure of funding source based on empirical evidence.
Systematic review registration
PROSPERO CRD42014010802
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-138) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-138
PMCID: PMC4280764  PMID: 25431307
Industry bias; Industry sponsorship; General and abdominal surgery; Randomised controlled trial; Medical devices; Systematic review; Science study; Health care research
23.  Impact of missing participant data for dichotomous outcomes on pooled effect estimates in systematic reviews: a protocol for a methodological study 
Systematic Reviews  2014;3(1):137.
Background
There is no consensus on how authors conducting meta-analysis should deal with trial participants with missing outcome data. The objectives of this study are to assess in Cochrane and non-Cochrane systematic reviews: (1) which categories of trial participants the systematic review authors consider as having missing participant data (MPD), (2) how trialists reported on participants with missing outcome data in trials, (3) whether systematic reviewer authors actually dealt with MPD in their meta-analyses of dichotomous outcomes consistently with their reported methods, and (4) the impact of different methods of dealing with MPD on pooled effect estimates in meta-analyses of dichotomous outcomes.
Methods/Design
We will conduct a methodological study of Cochrane and non-Cochrane systematic reviews. Eligible systematic reviews will include a group-level meta-analysis of a patient-important dichotomous efficacy outcome, with a statistically significant effect estimate. Teams of two reviewers will determine eligibility and subsequently extract information from each eligible systematic review in duplicate and independently, using standardized, pre-piloted forms. The teams will then use a similar process to extract information from the trials included in the meta-analyses of interest. We will assess first which categories of trial participants the systematic reviewers consider as having MPD. Second, we will assess how trialists reported on participants with missing outcome data in trials. Third, we will compare what systematic reviewers report having done, and what they actually did, in dealing with MPD in their meta-analysis. Fourth, we will conduct imputation studies to assess the effects of different methods of dealing with MPD on the pooled effect estimates of meta-analyses. We will specifically calculate for each method (1) the percentage of systematic reviews that lose statistical significance and (2) the mean change of effect estimates across systematic reviews.
Discussion
The impact of different methods of dealing with MPD on pooled effect estimates will help judge the associated risk of bias in systematic reviews. Our findings will inform recommendations regarding what assumptions for MPD should be used to test the robustness of meta-analytical results.
Electronic supplementary material
The online version of this article (doi:10.1186/2046-4053-3-137) contains supplementary material, which is available to authorized users.
doi:10.1186/2046-4053-3-137
PMCID: PMC4285551  PMID: 25423894
Missing participant data; Imputation; Risk of bias; Trials; Systematic reviews; Meta-analysis
24.  Efficacy and safety of damage control in experimental animal models of injury: protocol for a systematic review and meta-analysis 
Systematic Reviews  2014;3:136.
Background
Although abbreviated surgery with planned reoperation (damage control surgery) is now widely used to manage major trauma patients, the procedure and its component interventions have not been evaluated in randomized controlled trials (RCTs). While some have suggested the need for such trials, they are unlikely to be conducted because of patient safety concerns. As animal studies may overcome several of the limitations of existing observational damage control studies, the primary objective of this study is to evaluate the efficacy and safety of damage control versus definitive surgery in experimental animal models of injury.
Methods/design
We will search electronic databases (Medline, Embase, PubMed, Web of Science, Scopus, and the Cochrane Library), conference abstracts, personal files, and bibliographies of included articles. We will include RCTs and prospective cohort studies that utilized an animal model of injury and compared damage control surgery (or specific damage control interventions or adjuncts) to definitive surgery (or specific definitive surgical interventions). Two investigators will independently evaluate the internal and external/construct validity of individual studies. The primary outcome will be all-cause mortality. Secondary outcomes will include blood loss amounts; blood pressures and heart rates; urinary outputs; core body temperatures; arterial lactate, pH, and base deficit/excess values; prothrombin and partial thromboplastin times; international normalized ratios; and thromboelastography (TEG) results/activated clotting times. We will calculate summary relative risks (RRs) of mortality and mean differences (for continuous outcomes) using DerSimonian and Laird random effects models. Heterogeneity will be explored using subgroup meta-analysis and meta-regression. We will assess for publication bias using funnel plots and Begg’s and Egger’s tests. When evidence of publication bias exists, we will use the Duval and Tweedie trim and fill method to estimate the potential influence of this bias on pooled summary estimates.
Discussion
This study will evaluate the efficacy and safety of damage control in experimental animal models of injury. Study results will be used to guide future clinical evaluations of damage control surgery, determine which animal study outcomes may potentially be generalizable to the clinical setting, and to provide guidelines to strengthen the conduct and relevance of future pre-clinical studies.
doi:10.1186/2046-4053-3-136
PMCID: PMC4285082  PMID: 25416175
Animal experiments; Damage control surgery; Damage control interventions; Meta-analysis; Systematic review; Wounds and injuries
25.  Conflicts of interest and critiques of the use of systematic reviews in policymaking: an analysis of opinion articles 
Systematic Reviews  2014;3:122.
Background
Strong opinions for or against the use of systematic reviews to inform policymaking have been published in the medical literature. The purpose of this paper was to examine whether funding sources and author financial conflicts of interest were associated with whether an opinion article was supportive or critical of the use of systematic reviews for policymaking. We examined the nature of the arguments within each article, the types of disclosures present, and whether these articles are being cited in the academic literature.
Methods
We searched for articles that expressed opinions about the use of systematic reviews for policymaking. We included articles that presented opinions about the use of systematic reviews for policymaking and categorized each article as supportive or critical of such use. We extracted all arguments regarding the use of systematic reviews from each article and inductively coded each as internal or external validity argument, categorized disclosed funding sources, conflicts of interest, and article types, and systematically searched for undisclosed financial ties. We counted the number of times each article has been cited in the “Web of Science.” We report descriptive statistics.
Results
Articles that were critical of the use of systematic reviews (n = 25) for policymaking had disclosed or undisclosed industry ties 2.3 times more often than articles that were supportive of the use (n = 34). We found that editorials, comments, letters, and perspectives lacked published disclosures nearly twice as often (60% v. 33%) as other types of articles. We also found that editorials, comments, letters, and perspectives were less frequently cited in the academic literature than other article types (median number of citations = 5 v. 19).
Conclusions
It is important to consider whether an article has industry ties when evaluating the strength of the argument for or against the use of systematic reviews for policymaking. We found that journal conflict of interest disclosures are often inadequate, particularly for editorials, comments, letters, and perspectives and that these articles are being cited as evidence in the academic literature. Our results further suggest the need for more consistent and complete disclosure for all article types.
doi:10.1186/2046-4053-3-122
PMCID: PMC4241194  PMID: 25417178
Systematic reviews; Health policy; Conflicts of interest; Bias

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