Although healthcare administrative data are commonly used for traumatic brain injury research, there is currently no consensus or consistency on using the International Classification of Diseases version 10 codes to define traumatic brain injury among children and youth. This protocol is for a systematic review of the literature to explore the range of International Classification of Diseases version 10 codes that are used to define traumatic brain injury in this population.
The databases MEDLINE, MEDLINE In-Process, Embase, PsychINFO, CINAHL, SPORTDiscus, and Cochrane Database of Systematic Reviews will be systematically searched. Grey literature will be searched using Grey Matters and Google. Reference lists of included articles will also be searched. Articles will be screened using predefined inclusion and exclusion criteria and all full-text articles that meet the predefined inclusion criteria will be included for analysis. The study selection process and reasons for exclusion at the full-text level will be presented using a PRISMA study flow diagram. Information on the data source of included studies, year and location of study, age of study population, range of incidence, and study purpose will be abstracted into a separate table and synthesized for analysis. All International Classification of Diseases version 10 codes will be listed in tables and the codes that are used to define concussion, acquired traumatic brain injury, head injury, or head trauma will be identified.
The identification of the optimal International Classification of Diseases version 10 codes to define this population in administrative data is crucial, as it has implications for policy, resource allocation, planning of healthcare services, and prevention strategies. It also allows for comparisons across countries and studies. This protocol is for a review that identifies the range and most common diagnoses used to conduct surveillance for traumatic brain injury in children and youth. This is an important first step in reaching an appropriate definition using International Classification of Diseases version 10 codes and can inform future work on reaching consensus on the codes to define traumatic brain injury for this vulnerable population.
Children and youth; Definition; ICD-10; Prevention; Protocol; Systematic review; Traumatic brain injury
Dapagliflozin is a first-in-class oral sodium glucose co-transporter 2 (SGLT2) inhibitor. It is often used in combination with conventional anti-diabetic drugs such as metformin, glimepiride, and insulin in treating type 2 diabetes (T2D). It not only reduces glucose reabsorption in the kidney but also increases renal glucose excretion. Some studies found the actions of dapagliflozin independent of insulin and free from risk of weight gain. This meta-analysis aims to evaluate whether dapagliflozin is synergistic with other anti-diabetic drugs without risk of weight gain.
This meta-analysis will include the randomized controlled trials (RCT) evaluating the efficacy of dapagliflozin as an add-on drug in treating T2D for >8 weeks with the outcome measures glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight. Information of relevant RCTs will be retrieved from major databases including PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and Google Scholar according to a pre-specified search strategy. Google and manual search will find other unpublished reports and supplementary data. Eligible RCTs will be selected according to pre-specified inclusion and exclusion criteria. Data will be extracted and input into a pre-formatted spreadsheet. The Cochrane risk of bias tool will be used to assess the quality of the eligible RCTs. Meta-analysis based on the random-effects model will be conducted to compare the changes of HbA1c (%), FPG (mmol/L), and body weight (kg) between dapagliflozin arm and placebo arm. Publication bias will be evaluated with a funnel plot and the Egger’s test. Heterogeneity will be assessed with the I2 statistics. Sensitivity analysis will be conducted on follow-up periods. The evidential quality of the findings will be assessed with the GRADE profiler.
The findings of this meta-analysis will be important to clinicians, patients, and health policy-makers regarding the use of dapagliflozin in T2D treatment.
PROSPERO registration number: CRD42013005034
Systematic review; Dapagliflozin; Type 2 diabetes; Meta-analysis
The essential clinical diagnostic components of brain death must include evidence for an established etiology capable of causing brain death, two independent clinical confirmations of the absence of all brainstem reflexes and an apnea test, and exclude confounders that can mimic brain death. Numerous confounders can render the clinical neurological determination of death (NDD) virtually impossible. As such, clinicians must rely on additional ancillary testing.
We will conduct a systematic review and a meta-analysis of ancillary testing for the neurological determination of death. The primary objective of this systematic review is to evaluate the accuracy of these ancillary tests compared to the three accepted reference standards: (1) clinical diagnosis, (2) four-vessel angiography and (3) radionuclide imaging. This objective will be investigated using two different populations with different baseline risks of brain death: comatose patients and patients with a neurological determination of death. We will search MEDLINE, EMBASE and the Cochrane Central databases for retrospective and prospective diagnostic test studies and interventional studies. We will report study characteristics and assess methodological quality using QUADAS-2, which is used to assess the quality of diagnostic tests. If pooling is appropriate, we will compute parameter estimates using a bivariate model to produce summary receiver operating curves, summary operating points (pooled sensitivity and specificity), and 95% confidence regions around the summary operating point. Clinical and methodological subgroup and sensitivity analyses will be performed to explore heterogeneity.
The results of this project will provide a critical evidence base for the neurological determination of death. The results will help clinicians to select ancillary tests based on the best available evidence. Our systematic review will also identify the strengths and weaknesses in the current evidence for the use of ancillary tests in diagnosing brain death. It will serve as a foundation for further research and the development of prospective studies on currently used or novel techniques for NDD.
PROSPERO Registration Number: CRD42013005907
Somatoform-type disorders and functional medically unexplained symptoms are extremely common in primary care settings. These disorders, however, are consistently underdiagnosed and under-recognised which precludes effective treatment. Given that somatoform symptoms are associated with high impairment, healthcare costs and both physician and patient frustration, it is critical to improve early detection. The first step in improving patient care is to identify the current barriers which obstruct successful diagnosis to enable the design of targeted interventions. We aim to conduct a systematic review to identify the possible physician-, patient- and society-related factors and other practical constraints which may impede successful diagnosis. In the process, we will also be able to recognise the differences in methodological techniques, recommend potential avenues for future research and comment on the literature in this field as a whole.
We aim to conduct a systematic review of the relevant peer-reviewed literature published in English or German in the past 10 years in MEDLINE, EMBASE, PsycINFO and the Cochrane Database of Systematic Reviews. Additional studies may be identified from the reference lists of included studies. Title and abstract screening and data extraction from full text manuscripts will be conducted by two independent reviewers. Because we are including a combination of qualitative and quantitative studies, the review will provide a broad understanding of the current situation. Wherever possible, the method and reporting of the review will adhere to the guidelines outlined in the PRISMA statement and bias will be assessed using the Cochrane collaboration’s recommendations. We envisage that data will be synthesised using a multilevel (qualitative and quantitative) approach which combines textual narrative and thematic analysis. Barriers will be categorised as modifiable or non-modifiable according to a conceptual framework. The review has been registered in an international registry of systematic reviews PROSPERO (CRD42013002540).
We hope that this study will provide an insight into the barriers to diagnosis of somatoform-type disorders and the results can be used to target appropriate interventions to improve care for these patients.
Somatoform; Somatization; Somatisation; Primary care; Diagnosis; Recognition; Problems with diagnosis; Medically unexplained symptoms; Systematic review; Functional symptom
Non-cognitive behavioural and psychological symptoms of dementia affect up to 90% of people with dementia during the disease course and result in distress, increased carer burden, high service utilization and unwanted moves to care homes. Research has focused on long-term settings and has not considered people with dementia living at home and at different stages of the disease trajectory. Our aim is to review systematically the evidence concerning non-pharmacological strategies to minimise behavioural and psychological symptoms in community-dwelling older people with dementia.
Our approach is a two-stage co-design: a systematic mapping of the broad evidence around behavioural and psychological symptoms followed by an in-depth systematic review of studies of non-pharmacological interventions for behavioural and psychological symptoms from the perspective of their impact on community-dwelling older people with dementia and their carers. The review will include published literature involving a wide range of electronic databases using sensitive and comprehensive searches and lateral searching including checking citations.
We will produce a descriptive map of the studies by design and by the focus of interventions and apply further inclusion criteria, developed in conjunction with lay experts, to select studies for an in-depth systematic review that will include independent quality assessment and detailed data extraction by two reviewers.
The review process will be integrated with stakeholder meetings and a multidisciplinary expert advisory group to guide the review parameters and shape the research questions on the management of behavioural and psychological symptoms in people with dementia. Because studies are likely to be diverse in methodology and interventions, we will conduct a narrative synthesis of the in-depth systematic review. If appropriate, we will pool studies in a meta-analysis. We will explore review findings at both stages through focus groups and interviews with service providers, practitioners, people with dementia and carers.
This integrated review in collaboration with key stakeholders will synthesise research evidence to identify appropriate interventions for effective management of behavioural and psychological symptoms that supports people with dementia living at home and their carers, and which reflects their priorities. It will make recommendations for research and practice.
PROSPERO registration number: CRD42013004344
Behavioural and psychological symptoms; Community dwelling; Dementia; Synthesis; Systematic review
In 2011, The Institute of Medicine (IOM) identified a set of methodological standards to improve the validity, trustworthiness, and usefulness of systematic reviews. These standards, based on a mix of theoretical principles, empiric evidence, and commonly considered best practices, set a high bar for authors of systematic reviews.
Based on over 15 years of experience conducting systematic reviews, the Agency for Healthcare Research and Quality Evidence-based Practice Center (EPC) program has examined the EPC’s adherence and agreement with the IOM standards. Even such a large program, with infrastructure and resource support, found challenges in implementing all of the IOM standards. We summarize some of the challenges in implementing the IOM standards as a whole and suggest some considerations for individual or smaller research groups needing to prioritize which standards to adhere to, yet still achieve the highest quality and utility possible for their systematic reviews.
Systematic review methods; Institute of Medicine Standards; Evidence-based practice centers
Infection occurs commonly among patients hospitalized after traumatic brain injury (TBI) and has been associated with increased intensive care unit and hospital lengths of stay and an elevated risk of poor neurological outcome and mortality. However, as many relevant published studies to date have varied in the type and severity of TBI among included patients as well as in their design (randomized versus non-randomized), risk of bias, and setting (hospital ward versus intensive care unit), their reported estimates of infection occurrence vary considerably. Thus, the purpose of this systematic review and meta-analysis is to estimate the incidence, prevalence, and occurrence rate of infection among patients hospitalized after TBI.
We will search electronic bibliographic databases (MEDLINE, EMBASE, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews) from their first available date as well as personal files, reference lists of included articles, and conference proceedings. Two investigators will independently screen titles and abstracts and select cohort studies, cross-sectional studies, and randomized controlled trials involving adults hospitalized after TBI that reported estimates of cumulative incidence, incidence rate, prevalence, or occurrence rate of infection for inclusion in the systematic review. These investigators will also independently extract data and assess risk of bias. We will exclude studies with fewer than ten patients; experimental groups allocated to treatment with antibiotics, glucocorticoids, immunosuppressants, barbiturates, or hypothermia; and studies focused on military/combat-related TBI. Pooled estimates of cumulative incidence, incidence rate, prevalence, and occurrence rate will be calculated using random effects models. We will also calculate I2 and Cochran Q statistics to assess for inter-study heterogeneity and conduct stratified analyses and univariate meta-regression to determine the influence of pre-defined study-level covariates on our pooled estimates.
This study will compile the world literature regarding the epidemiology of infection among adults hospitalized after TBI. A better understanding of the role of infection will be helpful in the development of guidelines for patient management. This protocol has been registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42013005146).
Craniocerebral trauma; Infection; Incidence; Prevalence; Systematic review; Meta-analysis
Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.
A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.
Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.
Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality.
Child; Food; Fortification; Nutrition; Supplementation; Women
Opioids are prescribed frequently and increasingly for the management of chronic non-cancer pain (CNCP). Current systematic reviews have a number of limitations, leaving uncertainty with regard to the benefits and harms associated with opioid therapy for CNCP. We propose to conduct a systematic review and meta-analysis to summarize the evidence for using opioids in the treatment of CNCP and the risk of associated adverse events.
Methods and design
Eligible trials will include those that randomly allocate patients with CNCP to treatment with any opioid or any non-opioid control group. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to evaluate confidence in the evidence on an outcome-by-outcome basis. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. To ensure interpretability of our results, we will present risk differences and measures of relative effect for all outcomes reported and these will be based on anchor-based minimally important clinical differences, when available. We will conduct a priori defined subgroup analyses consistent with current best practices.
Our review will evaluate both the effectiveness and the adverse events associated with opioid use for CNCP, evaluate confidence in the evidence using the GRADE approach, and prioritize patient-important outcomes with a focus on functional gains guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with CNCP and identify key areas for future research.
Our protocol is registered on PROSPERO (CRD42012003023), http://www.crd.york.ac.uk/PROSPERO.
Chronic pain; Opioid analgesics; Systematic review; Meta-analysis; Randomized controlled trials; Quality of life; Adverse effects
Literature documents that immigrant women in Canada have a higher prevalence of postpartum depression symptomatology than Canadian-born women. There exists a need to synthesize information on the contextual factors and social determinants of health that influence immigrant women’s reception of and behavior in accessing existing mental health services. Our research question is: what are the ethnoculturally defined patterns of help-seeking behaviors and decision-making and other predictive factors for therapeutic mental health care access and outcomes with respect to postpartum depression for immigrant women in Canada?
Our synthesis incorporates a systematic review using narrative synthesis of reports (peer- and non-peer reviewed) of empirical research and aims to provide stakeholders with perspectives on postpartum mental health care services as experienced by immigrant women. To reach this goal we are using integrated knowledge translation, thus partnering with key stakeholders throughout the planning, implementation and dissemination stages to ensure topic relevancy and impact on future practice and policy. The search and selection strategies draw upon established systematic review methodologies as outlined by the Centre for Reviews and Dissemination and also incorporate guidelines for selection and appraisal of gray literature. Two search phases (a database and a gray literature phase) will identify literature for screening and final selection based on an inclusion/exclusion checklist. Quality appraisal will be performed using the tools produced by the Centre for Evidence Based Management. The narrative synthesis will be informed by Popay et al. (2006) framework using identified tools for each of its four elements. The integrated knowledge translation plan will ensure key messages are delivered in an audience-specific manner to optimize their impact on policy and practice change throughout health service, public health, immigration and community sectors.
The narrative synthesis methodology will facilitate understandings and acknowledgement of the broader influences of theoretical and contextual variables, such as race, gender, socio-economic status, pre-migration history and geographical location. Our review aims to have a substantive and sustainable impact on health outcomes, practice, programs and/or policy in the context of postpartum mental health of immigrant women. PROSPERO registration number CRD42012003020.
Narrative synthesis; Immigrant women; Postpartum depression; Maternity care experiences; Canada; Systematic review protocol
The role of vitamin D in management of depression is unclear. Results from observational and emerging randomized controlled trials (RCTs) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association.
The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors’ original definition. Secondary aims include assessing the change in quality of life, adverse events and treatment discontinuation. We will conduct the systematic review and meta-analysis according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), PsychINFO (1967 to present) and ClinicalTrials.gov. Unpublished work will be identified by searching two major conferences: the International Vitamin Conference, the Anxiety Disorders and Depression Conference, while grey literature will be acquired by contacting authors of included studies. We will use the random-effects meta-analysis to synthesize the data by pooling the results of included studies.
The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant settings.
Unique identifier: CRD42013003849.
Vitamin D; Depression; Randomized controlled trial; Adults; Efficacy; Systematic review protocol
Most patients who sustain mild traumatic brain injury (mTBI) have persistent symptoms at 1 week and 1 month after injury. This systematic review investigated the effectiveness of interventions initiated in acute settings for patients who experience mTBI.
We performed a systematic review of all randomized clinical trials evaluating any intervention initiated in an acute setting for patients experiencing acute mTBI. All possible outcomes were included. The primary sources of identification were MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central register of Controlled Trials, from 1980 to August 2012. Hand searching of proceedings from five meetings related to mTBI was also performed. Study selection was conducted by two co-authors, and data abstraction was completed by a research assistant specialized in conducting systematic reviews. Study quality was evaluated using Cochrane’s Risk of Bias assessment tool.
From a potential 15,156 studies, 1,268 abstracts were evaluated and 120 articles were read completely. Of these, 15 studies fulfilled the inclusion/exclusion criteria. One study evaluated a pharmacological intervention, two evaluated activity restriction, one evaluated head computed tomography scan versus admission, four evaluated information interventions, and seven evaluated different follow-up interventions. Use of different outcome measures limited the possibilities for analysis. However, a meta-analysis of three studies evaluating various follow-up strategies versus routine follow-up or no follow-up failed to show any effect on three outcomes at 6 to 12 months post-trauma. In addition, a meta-analysis of two studies found no effect of an information intervention on headache at 3 months post-injury.
There is a paucity of well-designed clinical studies for patients who sustain mTBI. The large variability in outcomes measured in studies limits comparison between them.
mTBI; Traumatic brain injury; Head concussion; Systematic review; Treatment
The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP.
This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy.
We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study.
PROSPERO registration number: CRD42012003072
Meta-analysis; Diagnostic accuracy; Optic nerve sheath diameter; Individual patient data
Health professionals and policymakers aspire to make healthcare decisions based on the entire relevant research evidence. This, however, can rarely be achieved because a considerable amount of research findings are not published, especially in case of ‘negative’ results - a phenomenon widely recognized as publication bias. Different methods of detecting, quantifying and adjusting for publication bias in meta-analyses have been described in the literature, such as graphical approaches and formal statistical tests to detect publication bias, and statistical approaches to modify effect sizes to adjust a pooled estimate when the presence of publication bias is suspected. An up-to-date systematic review of the existing methods is lacking.
The objectives of this systematic review are as follows:
• To systematically review methodological articles which focus on non-publication of studies and to describe methods of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses.
• To appraise strengths and weaknesses of methods, the resources they require, and the conditions under which the method could be used, based on findings of included studies.
We will systematically search Web of Science, Medline, and the Cochrane Library for methodological articles that describe at least one method of detecting and/or quantifying and/or adjusting for publication bias in meta-analyses. A dedicated data extraction form is developed and pilot-tested. Working in teams of two, we will independently extract relevant information from each eligible article. As this will be a qualitative systematic review, data reporting will involve a descriptive summary.
Results are expected to be publicly available in mid 2013. This systematic review together with the results of other systematic reviews of the OPEN project (To Overcome Failure to Publish Negative Findings) will serve as a basis for the development of future policies and guidelines regarding the assessment and handling of publication bias in meta-analyses.
Publication bias; Full publication; Underreporting; Detecting; Quantifying; The OPEN project
Rehabilitation interventions are a key component of the services required by individuals with neurotrauma to recover or compensate for altered abilities and achieve optimal social participation. Primary studies have produced evidence of the effect of rehabilitation length of stay on individuals with neurotrauma. However, to date no systematic review of this evidence has been performed. This makes it difficult for managers and clinicians to base their rehabilitation practices upon evidence.
Supported by a committee of stakeholders, we will search electronic databases for research articles examining the association between length of stay or intensity of inpatient rehabilitation services and outcomes or the determinants of inpatient rehabilitation length of stay in adults with neurotrauma published after January 1990. Two researchers will independently screen the article titles and abstracts for inclusion. Two reviewers will independently extract the data. Primary outcomes of interest will be level of function, participation and return to work. If the data allow it, a meta-analysis of the studies will be performed.
The results of this systematic review will clarify the factors that influence length of stay and intensity of rehabilitation services for individuals with TBI and SCI. They will give clinicians indications for optimal length of stay in these patient populations, contributing to better quality of care and better functional results.
This review protocol has been registered on the PROSPERO database (CRD42012003120) and is available at http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42012003120.
Brain injury; Spinal cord injury; Length of stay; Rehabilitation; Systematic review
There is a significant global health burden associated with acute rheumatic fever (ARF) and rheumatic heart disease (RHD), especially in developing countries. ARF and RHD most often strike children and young adults living in impoverished settings, where unhygienic conditions and lack of awareness and knowledge of streptococcal infection progression are common. Secondary prophylactic measures have been recommended in the past, but primary prevention measures have been gaining more attention from researchers frustrated by the perpetual prevalence of ARF and RHD in developing countries. Health education aims to empower people to take responsibility for their own well-being by gaining control over the underlying factors that influence health. We therefore conducted a review of the current best evidence for the use of health education interventions to increase awareness and knowledge of streptococcal pharyngitis and ARF.
Methods and design
This article describes the protocol for a systematic review of the effectiveness of health education interventions aimed at increasing awareness and knowledge of the symptoms, causes and consequences of streptococcal pharyngitis, rheumatic fever and/or rheumatic heart disease. Studies will be selected in which the effect of an intervention is compared with either a pre-intervention or a control, targeting all possible audience types. Primary and secondary outcomes of interest are pre-specified. Randomized controlled trials, quasi-randomized trials, controlled before–after studies and controlled clinical trials will be considered. We will search several bibliographic databases (for example, PubMed, EMBASE, World Health Organization Library databases, Google Scholar) and search sources for gray literature. We will meta-analyze included studies. We will conduct subgroup analyses according to intervention subtypes: printed versus audiovisual and mass media versus training workshops.
This review will provide evidence for the effectiveness of educational components in health promotion interventions in raising public awareness in regard to the symptoms, causes and consequences of streptococcal pharyngitis, ARF and/or RHD. Our results may provide guidance in the development of future intervention studies and programs.
Acute rheumatic fever; Awareness; Health education; Pharyngitis; Rheumatic heart disease
Despite strong indications that fatigue is the most common and debilitating symptom after traumatic brain injury, little is known about its frequency, natural history, or relation to other factors. The current protocol outlines a strategy for a systematic review that will identify, assess, and critically appraise studies that assessed predictors for fatigue and the consequences of fatigue on at least two separate time points following traumatic brain injury.
MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CINAHL, and PsycINFO will be systematically searched for relevant peer-reviewed studies. Reference lists of eligible papers will also be searched. All English language studies with a longitudinal design that focus on fatigue in adults with primary-impact traumatic brain injury will be included. Studies on fatigue following brain injury due to secondary pathological processes (intracranial complications, edema, ischemia/infarction, and systemic intracranial conditions) will be excluded. Excluded studies, along with the reasons for exclusion will be reported. Two independent reviewers will conduct all levels of screening, data abstraction, and quality appraisal. Randomized control trial data will be treated as a cohort. The quality will be assessed using the criteria defined by Hayden and colleagues. The review will be conducted and reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
The review will summarize the current knowledge in the field with the aim of increasing understanding and guiding future research on the associations between fatigue and clinically important factors, as well as the consequences of fatigue in traumatic brain injury. PROSPERO registry number: CRD42013004262.
Post-traumatic fatigue; Traumatic brain injury; Rehabilitation; Protocol; Systematic review
The evidence that higher levels of physical activity and/or lower levels of physical inactivity are associated with beneficial health-related outcomes stems mainly from observational studies. Findings from these studies often differ from randomised controlled trials and systematic reviews currently demonstrate mixed results, due partly to heterogeneity in physical activity interventions, methodologies used and populations studied. As a result, translation into clinical practice has been difficult. It is therefore essential that an overview is carried out to compare and contrast systematic reviews, and to identify those physical activity interventions that are the most effective in preventing and/or treating major chronic disease. This protocol has been registered on PROSPERO 2013: CRD42013003523.
We will carry out an overview of Cochrane systematic reviews. We will search the Cochrane Database of Systematic Reviews for systematic reviews of randomised controlled trials that have a primary focus on disease-related outcomes. We will restrict reviews to those in selected major chronic diseases. Two authors will independently screen search outputs, select studies, extract data and assess the quality of included reviews using the assessment of multiple systematic reviews tool; all discrepancies will be resolved by discussing and reaching a consensus, or by arbitration with a third author. The data extraction form will summarise key information from each review, including details of the population(s) (for example, disease condition), the context (for example, prevention, treatment or management), the participants, the intervention(s), the comparison(s) and the outcomes. The primary outcomes of interest are the prevention of chronic disease and/or improved outcomes, in the treatment or management of chronic disease. These outcomes will be summarised and presented for individual chronic diseases (for example, any change in blood pressure in hypertension or glucose control in diabetes). Secondary outcomes of interest are to describe the structure and delivery of physical activity interventions across chronic disease conditions and adverse events associated with physical activity.
We anticipate that our results could inform researchers, guideline groups and policymakers of the most efficacious physical activity interventions in preventing and/or managing major chronic disease.
Physical activity; Inactivity; Exercise; Adherence; Non-communicable disease; Management; Systematic overview
Each year, 287,000 women die from complications related to pregnancy or childbirth, and 3.8 million newborns die before reaching 28 days of life. The near totality (99%) of maternal and neonatal deaths occurs in low- and middle-income countries (LMICs). Utilization of essential obstetric care services including postnatal care (PNC) largely contributes to the reduction of maternal and neonatal mortality and morbidity. There is a strong need to evaluate the evidence on the unmet needs in utilization of PNC services to inform health policy planning. Our objective is to assess systematically the socioeconomic, geographic and demographic inequalities in the use of PNC interventions in low- and middle-income countries.
The current protocol adopts a strategy informed by the guidelines of The Cochrane Handbook for Systematic Reviews. Our systematic review will identify studies in English, French, Spanish, Portuguese and Chinese – provided inclusion of an English abstract - from 1960 onwards, by searching MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and the gray literature. Study selection criteria include research setting, study design, reported outcomes and determinants of interest. Our primary outcome is the utilization of PNC services, and determinants of concern are: 1) socioeconomic status (for example, income, education); 2) geographic determinants (for example, distance to a health center, rural versus urban residence); and 3) demographic determinants (for example, ethnicity, immigration status). Screening, data abstraction, and scientific quality assessment will be conducted independently by two reviewers using standardized forms. Where feasible, study results will be combined through meta-analyses to obtain a pooled measure of association between utilization of PNC services and key determinants. Results will be stratified by countries’ income levels (World Bank classification).
Our review will inform policy-making with the aim of decreasing inequalities in utilization of PNC services. This research will provide evidence on unmet needs for PNC services in LMICs, knowledge gaps and recommendations to health policy planners. Our research will help promote universal coverage of quality PNC services as an integral part of the continuum of maternal and child health care. This protocol was registered with the Prospero database (registration number: CRD42013004661).
Postnatal care; Health services utilization; Maternal health; Low- and middle-income countries; Inequalities; Systematic review; Protocol
Compared to subgroup analyses in a single study or in a traditional meta-analysis, an individual patient data meta-analysis (IPDMA) offers important potential advantages. We studied how many IPDMAs report on surgical interventions, how many of those surgical IPDMAs perform subgroup analyses, and whether these subgroup analyses have changed decision-making in clinical practice.
Surgical IPDMAs were identified using a comprehensive literature search. The last search was conducted on 24 April 2012. For each IPDMA included, we obtained information using a standardized data extraction form, and the quality of reporting was assessed. We also checked whether results were implemented in clinical guidelines.
Of all 583 identified IPDMAs, 22 (4%) reported on a surgical intervention. Eighteen (82%) of these IPDMAs presented subgroup analyses. Subgroups were mainly based on patient and disease characteristics. The median number of reported subgroup analyses was 3.5 (IQR 1.25-6.5). Statistical methods for subgroup analyses were mentioned in 11 (61%) surgical IPDMAs.
Eleven (61%) of the 18 IPDMAs performing subgroup analyses reported a significant overall effect estimate, whereas six (33%) reported a non-significant one. Of the IPDMAs that reported non-significant overall results, three IPDMAs (50%) reported significant results in one or more subgroup analyses. Results remained significant in one or more subgroups in eight of the IPDMAs (73%) that reported a significant overall result.
Eight (44%) of the 18 significant subgroups appeared to be implemented in clinical guidelines. The quality of reporting among surgical IPDMAs varied from low to high quality.
Many of the surgical IPDMAs performed subgroup analyses, but overall treatment effects were more often emphasized than subgroup effects. Although, most surgical IPDMAs included in the present study have only recently been published, about half of the significant subgroups were already implemented in treatment guidelines.
Based on small to moderate effect sizes for the wide range of symptomatic treatments in osteoarthritis (OA), and on the heterogeneity of OA patients, treatment guidelines for OA have stressed the need for research on clinical predictors of response to different treatments. A meta-analysis to quantify the effect modified by the predictors using individual patient data (IPD) is suggested. The initiative to collect and analyze IPD in OA research is commenced by the OA Trial Bank. The study aims are therefore: to evaluate the efficacy of intra-articular glucocorticoids for knee or hip OA in specific subgroups of patients with severe pain and (mild) inflammatory signs, over both short-term and long-term follow-up, using IPD from existing studies; to reach consensus on the rules for cooperation in a consortium; and to develop and explore the methodological issues of meta-analysis with individual OA patient data.
For the current IPD analysis we will collect and synthesize IPD from randomized trials studying the effect of intra-articular glucocorticoid injections in patients with hip or knee OA. Subgroup analyses will be performed for the primary outcome of pain at both short-term and long-term follow-up, in the subgroups of patients with and without severe pain and with and without inflammatory signs.
This study protocol includes the first study of the OA Trial Bank, an international collaboration that initiates meta-analyses on predefined subgroups of OA patients from existing literature. This approach ensures a widely supported initiative and is therefore likely to be successful in data collection of existing trials. The collaboration developed (that is, the OA Trial Bank) may also lead to future IPD analyses on subgroups of patients with several intervention strategies applied in OA patients.
Osteoarthritis; Individual patient data; Corticosteroid injection
To identify demographic and clinical characteristics associated with cases of hepatosplenic T-cell lymphoma (HSTCL) in patients with Crohn’s disease, and to assess strength of evidence for a causal relationship between medications and HSTCL in Crohn’s disease.
We identified cases of HSTCL in Crohn’s disease in studies included in a comparative effectiveness review of Crohn’s disease medications, through a separate search of PubMed and Embase for published case reports, and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). We used three causality assessment tools to evaluate the relationship between medication exposure and HSTCL.
We found 37 unique cases of HSTCL in patients with Crohn’s disease. Six cases were unique to the published literature and nine were unique to AERS. Cases were typically young (<40 years of age) and male (86%). The most commonly reported medications were anti-metabolites (97%) and anti-tumor necrosis factor alpha (anti-TNFa) medications (76%). Dose and duration of therapy were not consistently reported. Use of aminosalicylates and corticosteroids were rarely reported, despite the high prevalence of these medications in routine treatment. Using the causality assessment tools, it could only be determined that anti-metabolite and anti-TNFa therapies were possible causes of HSTCL in Crohn’s disease based on the data contained in the case reports.
Systematic reviews that incorporate case reports of rare lethal events should search both published literature and AERS, but consideration should be given to the limitations of case reports. In this study, establishing a causative effect other than ‘possible’ between anti-metabolite or anti-TNFa therapies and HSTCL was not feasible because case reports lacked data required by the causality assessments, and because of the limited applicability of causality assessment tools for rare irreversible events. We recommend minimum reporting requirements for case reports to improve causality assessment and routine reporting of rare life-threatening events, including their absence, in clinical trials to help clinicians determine whether rare adverse events are causally related to a medication.
Crohn’s disease; Hepatosplenic T-cell lymphoma; Causality assessment; Adverse event reporting; Case reports; Systematic reviews
Hysterosalpingosonography has been suggested as a less invasive alternative to hysterosalpingography for detecting tubal occlusion among subfertile women. We aim to determine the diagnostic accuracy of hysterosalpingosonography and to compare it to hysterosalpingography.
We will conduct a systematic review of diagnostic test accuracy. We will search Medline, Embase, Cochrane Library, Web of Science and Biosis, as well as reference lists of included studies and previous related review articles. Diagnostic studies that compared hysterosalpingosonography ± hysterosalpingography to laparoscopy with chromotubation in women suffering from subfertility will be eligible. Two authors will independently screen for inclusion, data extraction, and quality assessment. Methodological quality will be assessed using the Quality Assessment of Diagnostic Accuracy Study 2 tool (QUADAS-2). We will use SAS 9.3 (SAS Institute Inc., Cary, NC, USA, 2011) to program bivariate random-effects models, estimate pooled sensitivity and specificity with 95% confidence intervals and to generate summary receiver operating characteristics curves. We will perform sensitivity analyses to examine the effect of differences in techniques used for hysterosalpingosonography and in methodological quality of studies.
This systematic review will help to determine if hysterosalpingosonography is an adequate alternative screening test for diagnosing tubal occlusion. Accuracy of specific sono-HSG techniques may also be identified.
This review has been registered at PROSPERO. The registration number is CRD42013003829
Hysterosalpingosonography; HyCoSy; Hysterosalpingography; Tubal patency; Subfertility; Diagnostic test accuracy; Systematic review; Meta-analysis
The identification of eligible controlled trials for systematic reviews of complementary and alternative medicine (CAM) interventions can be difficult. To increase access to these difficult to locate trials, the Cochrane Collaboration Complementary Medicine Field (CAM Field) has established a specialized register of citations of CAM controlled trials. The objective of this study is to describe the sources and characteristics of citations included in the CAM Field specialized register.
Between 2006 and 2011, regular searches for citations of CAM trials in MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) were supplemented with contributions of controlled trial citations from international collaborators. The specialized register was ‘frozen’ for analysis in 2011, and frequencies were calculated for publication date, language, journal, presence in MEDLINE, type of intervention, and type of medical condition.
The CAM Field specialized register increased in size from under 5,000 controlled trial citations in 2006 to 44,840 citations in 2011. Most citations (60%) were from 2000 or later, and the majority (71%) were reported in English; the next most common language was Chinese (23%). The journals with the greatest number of citations were CAM journals published in Chinese and non-CAM nutrition journals published in English. More than one-third of register citations (36%) were not indexed in MEDLINE. The most common CAM intervention type in the register was non-vitamin, non-mineral dietary supplements (e.g., glucosamine, fish oil) (34%), followed by Chinese herbal medicines (e.g., Astragalus membranaceus, Schisandra chinensis) (27%).
The availability of the CAM Field specialized register presents both opportunities and challenges for CAM systematic reviewers. While the register provides access to thousands of difficult to locate trial citations, many of these trials are of low quality and may overestimate treatment effects. When including these trials in systematic reviews, adequate analysis of their risk of bias is of utmost importance.
Complementary medicine; Randomized controlled trials; Data collection; Registries