Safety of influenza vaccination during pregnancy: a systematic review.

OBJECTIVE: We conducted a systematic review to evaluate associations between influenza vaccination during pregnancy and adverse birth outcomes and maternal non-obstetric serious adverse events (SAEs), taking into consideration confounding and temporal biases. METHODS: Electronic databases (Ovid MEDLINE ALL, Embase Classic+Embase and the Cochrane Central Register of Controlled Trials) were searched to June 2021 for observational studies assessing associations between influenza vaccination during pregnancy and maternal non-obstetric SAEs and adverse birth outcomes, including preterm birth, spontaneous abortion, stillbirth, small-for-gestational-age birth and congenital anomalies. Studies of live attenuated vaccines, single-arm cohort studies and abstract-only publications were excluded. Records were screened using a liberal accelerated approach initially, followed by a dual independent approach for full-text screening, data extraction and risk of bias assessment. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence certainty. RESULTS: Of 9443 records screened, 63 studies were included. Twenty-nine studies (24 cohort and 5 case-control) evaluated seasonal influenza vaccination (trivalent and/or quadrivalent) versus no vaccination and were the focus of our prioritised syntheses; 34 studies of pandemic vaccines (2009 A/H1N1 and others), combinations of pandemic and seasonal vaccines, and seasonal versus seasonal vaccines were also reviewed. Control for confounding and temporal biases was inconsistent across studies, limiting pooling of data. Meta-analyses for preterm birth, spontaneous abortion and small-for-gestational-age birth demonstrated no significant associations with seasonal influenza vaccination. Immortal time bias was observed in a sensitivity analysis of meta-analysing risk-based preterm birth data. In descriptive summaries for stillbirth, congenital anomalies and maternal non-obstetric SAEs, no significant association with increased risk was found in any studies. All evidence was of very low certainty. CONCLUSIONS: Evidence of very low certainty suggests that seasonal influenza vaccination during pregnancy is not associated with adverse birth outcomes or maternal non-obstetric SAEs. Appropriate control of confounding and temporal biases in future studies would improve the evidence base.

Predictors of Adverse Pregnancy Outcomes in Pregnant Women Living with Obesity: A Systematic Review.

Obesity is a well-recognized risk factor for pregnancy complications. Most studies to date are in large cohorts, with results presented in a way that assumes all women living with obesity are at equal risk. This study investigates which women living with obesity are at higher risk of specific pregnancy complications. A systematic search of MEDLINE and Embase identified 7894 prospective or retrospective cohort studies exploring predictors of adverse outcomes among pregnant women living with obesity. Following screening, 61 studies were deemed eligible. Studies were selected if the effects of exposure to any predictor amongst pregnant women living with obesity could be collected. Maternal characteristics assessed for association with adverse outcomes included maternal age, race/ethnicity, maternal height, mode of conception, complement activation factors, and history of various comorbidities/procedures. Gestational diabetes mellitus was the most studied outcome (n = 32), followed by preterm birth (n = 29), preeclampsia (n = 27), low birthweight infants (n = 20), small for gestational age newborns (n = 12), and stillbirth (n = 7). This review identified important characteristics that should be considered during the screening and follow-up sessions of pregnant women living with obesity, including pre-existing type 1 diabetes, maternal age < 20 years or ≥35 years, non-White ethnicity, abdominal adiposity obesity, and history of bariatric surgery.

Optimising weight-loss interventions in cancer patients-A systematic review and network meta-analysis.

BACKGROUND: Excess weight has been associated with increased morbidity and a worse prognosis in adult patients with early-stage cancer. The optimal lifestyle interventions to optimize anthropometric measures amongst cancer patients and survivors remain inconsistent. OBJECTIVE: To conduct a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) comparing the effects of exercise and dietary interventions alone or in combination on anthropometric measures of adult cancer patients and survivors. METHODS: A systematic search of Medline, Embase and the Cochrane Trials Registry was performed. Outcomes of interest included changes in weight, body mass index (BMI), and waist circumference. Screening and data collection were performed by two reviewers. Bayesian NMAs were performed. RESULTS: Overall, 98 RCTs were included; 75 were incorporated in NMAs (n = 12,199). Groups of intervention strategies included: 3 exercise interventions, 8 dietary interventions, 7 combination interventions of diet and exercise and standard care. Median intervention duration was 26 weeks. NMA suggested that diet alone (mean difference [MD] -2.25kg, 95% CrI -3.43 to -0.91kg) and combination strategies (MD -2.52kg, 95% CrI -3.54 to -1.62kg) were associated with more weight loss compared to standard care. All dietary interventions achieved a similar magnitude of weight loss (MD range from -2.03kg to -2.52kg). Both diet alone and combination strategies demonstrated greater BMI reductions versus standard care, and each of diet alone, exercise alone and combination strategies demonstrated greater reductions in waist circumference than standard care. CONCLUSION: Diet and exercise alone or in combination are effective lifestyle interventions to improve anthropometric measures in cancer patients and survivors. All reputable diets appear to be similarly effective to achieve weight loss.

Pharmacologic and surgical therapies for patients with Meniere's disease: A systematic review and network meta-analysis.

BACKGROUND: Meniere's disease (MD) is a chronic condition of the inner ear consisting of symptoms that include vertigo attacks, fluctuating sensorineural hearing loss, tinnitus and aural fullness. Despite availability of various interventions, there is uncertainty surrounding their relative efficacy, thus making it difficult to select the appropriate treatments for MD. The objective of this systematic review was to assess the relative effects of the available pharmacologic and surgical interventions in patients with MD with regard to vertigo and other key patient outcomes based on data from randomized clinical trials (RCTs). METHODS: Our published protocol registered with PROSPERO (CRD42019119129) provides details on eligibility criteria and methods. We searched various databases including MEDLINE, Embase and the Cochrane Library from inception to December 10th, 2018. Screening at citation and full-text levels and risk of bias assessment were performed by two independent reviewers in duplicate, with discrepancies resolved by consensus or third-party adjudication. Bayesian network meta-analyses (NMA) were performed for hearing change and vertigo control outcomes, along with pairwise meta-analyses for these and additional outcomes. RESULTS: We identified 2,889 unique citations, that yielded 23 relevant publications describing 18 unique RCTs (n = 1,231 patients). Overall, risk-of bias appraisal suggested the evidence base to be at unclear or high risk of bias. Amongst pharmacologics, we constructed treatment networks of five intervention groups that included placebo, intratympanic (IT) gentamicin, oral high-dose betahistine, IT steroid and IT steroid plus high-dose betahistine for NMAs of hearing change (improvement or deterioration) and complete vertigo control. IT steroid plus high-dose betahistine was associated with the largest difference in hearing improvement compared to placebo, followed by high-dose betahistine and IT steroid (though 95% credible intervals failed to rule out the possibility of no difference), while IT gentamicin was worse than IT steroid. The NMA of complete vertigo control suggested IT gentamicin was associated with the highest probability of achieving better complete vertigo control compared to placebo, followed by IT steroid plus high-dose betahistine. Only two studies related to surgical interventions were found, and data suggested no statistically significant difference in hearing changes between endolymphatic duct blockage (EDB) versus endolymphatic sac decompression (ESD), and ESD with or without steroid injection. One trial reported that 96.5% of patients in EDB group compared to 37.5% of the patients in ESD group achieved complete vertigo control 24 months after surgery (p = 0.002). CONCLUSION: To achieve both hearing preservation and vertigo control, the best treatment option among the pharmacologic interventions compared may be IT steroid plus high-dose betahistine, considering that IT gentamicin may have good performance to control vertigo but may be detrimental to hearing preservation with high cumulative dosage and short interval between injections. However, IT steroid plus high-dose betahistine has not been compared in head-to-head trials against other interventions except for IT steroid alone in one trial, thus future trials that compare it with other interventions will help establish comparative effectiveness with direct evidence.

Combination Tests in the Diagnosis of Chronic Periprosthetic Joint Infection: Systematic Review and Development of a Stepwise Clinical Decision-Making Tool.

BACKGROUND: Our objective was to identify combination tests used to diagnose chronic periprosthetic joint infection (PJI) and develop a stepwise decision-making tool to facilitate diagnosis. METHODS: We conducted a systematic review of existing combinations of serum, synovial, and tissue-based tests for diagnosing chronic PJI after hip or knee replacement. This work is an extension of our systematic review of single tests, from which we chose eligible studies that also described the diagnostic performance of combination tests. RESULTS: Thirty-seven eligible articles described the performance of 56 combination tests, of which 8 combinations had at least 2 studies informing both sensitivity and specificity. We also identified 5 types of combination tests: (1) a type-I Boolean combination, which uses Boolean logic (AND, OR) and usually increases specificity at the cost of sensitivity; (2) a type-II Boolean combination, which usually increases sensitivity at the cost of specificity; (3) a triage-conditional rule, in which the value of 1 test serves to triage the use of another test; (4) an arithmetic operation on the values of 2 tests; and (5) a model-based prediction rule based on a fitted model applied to biomarker values. CONCLUSIONS: Clinicians can initiate their diagnostic process with a type-II Boolean combination of serum C-reactive protein (CRP) and interleukin-6 (IL-6). False negatives of the combination can be minimized when the threshold is chosen to reach 90% to 95% sensitivity for each test. Once a joint infection is suspected on the basis of serum testing, joint aspiration should be performed. If joint aspiration yields a wet tap, a leukocyte esterase (LER) strip is highly recommended for point-of-care testing, with a reading of ++ or greater indicating PJI; a reading below ++ should be followed by one of the laboratory-based synovial tests. If joint aspiration yields a dry tap, clinicians should rely on preoperative tissue culture and histological analysis for diagnosis. Combinations based on triage-conditional, arithmetic, and model-based prediction rules require further research. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Comparing Interventions for Management of Hot Flashes in Patients With Breast and Prostate Cancer: A Systematic Review With Meta-Analyses.

PROBLEM IDENTIFICATION: Hot flashes are common and bothersome in patients with breast and prostate cancer and can adversely affect patients' quality of life. LITERATURE SEARCH: Databases were searched for randomized controlled trials (RCTs) evaluating the effects of one or more interventions for hot flashes in patients with a history of breast or prostate cancer. DATA EVALUATION: Outcomes of interest included changes in hot flash severity, hot flash frequency, quality of life, and harms. Pairwise meta-analyses and network meta-analyses were performed where feasible, with narrative synthesis used where required. SYNTHESIS: 40 RCTs were included. Findings from network meta-analysis for hot flash frequency suggested that several therapies may offer benefits compared to no treatment, but little data suggested differences between active therapies. Findings from network meta-analysis for hot flash score were similar. IMPLICATIONS FOR RESEARCH: Although many interventions may offer improvements for hot flashes versus no treatment, minimal data suggest important differences between therapies. SUPPLEMENTARY MATERIALS CAN BE FOUND BY VISITING&NBSP;HTTPS: //bit.ly/2WGzi30.

A scoping review of network meta-analyses assessing the efficacy and safety of complementary and alternative medicine interventions.

BACKGROUND: Network meta-analysis (NMA) has rapidly grown in use during the past decade for the comparison of healthcare interventions. While its general use in the comparison of conventional medicines has been studied previously, to our awareness, its use to assess complementary and alternative medicines (CAM) has not been studied. A scoping review of the literature was performed to identify systematic reviews incorporating NMAs involving one or more CAM interventions. METHODS: An information specialist executed a multi-database search (e.g., MEDLINE, Embase, Cochrane), and two reviewers performed study selection and data collection. Information on publication characteristics, diseases studied, interventions compared, reporting transparency, outcomes assessed, and other parameters were extracted from each review. RESULTS: A total of 89 SR/NMAs were included. The largest number of NMAs was conducted in China (39.3%), followed by the United Kingdom (12.4%) and the United States (9.0%). Reviews were published between 2010 and 2018, with the majority published between 2015 and 2018. More than 90 different CAM therapies appeared at least once, and the median number per NMA was 2 (IQR 1-4); 20.2% of reviews consisted of only CAM therapies. Dietary supplements (51.1%) and vitamins and minerals (42.2%) were the most commonly studied therapies, followed by electrical stimulation (31.1%), herbal medicines (24.4%), and acupuncture and related treatments (22.2%). A diverse set of conditions was identified, the most common being various forms of cancer (11.1%), osteoarthritis of the hip/knee (7.8%), and depression (5.9%). Most reviews adequately addressed a majority of the PRISMA NMA extension items; however, there were limitations in indication of an existing review protocol, exploration of network geometry, and exploration of risk of bias across studies, such as publication bias. CONCLUSION: The use of NMA to assess the effectiveness of CAM interventions is growing rapidly. Efforts to identify priority topics for future CAM-related NMAs and to enhance methods for CAM comparisons with conventional medicine are needed. SYSTEMATIC REVIEW REGISTRATION: https://ruor.uottawa.ca/handle/10393/35658.

Checklists to detect potential predatory biomedical journals: a systematic review.

BACKGROUND: The increase in the number of predatory journals puts scholarly communication at risk. In order to guard against publication in predatory journals, authors may use checklists to help detect predatory journals. We believe there are a large number of such checklists yet it is uncertain whether these checklists contain similar content. We conducted a systematic review to identify checklists that help to detect potential predatory journals and examined and compared their content and measurement properties. METHODS: We searched MEDLINE, Embase, PsycINFO, ERIC, Web of Science and Library, and Information Science & Technology Abstracts (January 2012 to November 2018); university library websites (January 2019); and YouTube (January 2019). We identified sources with original checklists used to detect potential predatory journals published in English, French or Portuguese. Checklists were defined as having instructions in point form, bullet form, tabular format or listed items. We excluded checklists or guidance on recognizing "legitimate" or "trustworthy" journals. To assess risk of bias, we adapted five questions from A Checklist for Checklists tool a priori as no formal assessment tool exists for the type of review conducted. RESULTS: Of 1528 records screened, 93 met our inclusion criteria. The majority of included checklists to identify predatory journals were in English (n = 90, 97%), could be completed in fewer than five minutes (n = 68, 73%), included a mean of 11 items (range = 3 to 64) which were not weighted (n = 91, 98%), did not include qualitative guidance (n = 78, 84%), or quantitative guidance (n = 91, 98%), were not evidence-based (n = 90, 97%) and covered a mean of four of six thematic categories. Only three met our criteria for being evidence-based, i.e. scored three or more "yes" answers (low risk of bias) on the risk of bias tool. CONCLUSION: There is a plethora of published checklists that may overwhelm authors looking to efficiently guard against publishing in predatory journals. The continued development of such checklists may be confusing and of limited benefit. The similarity in checklists could lead to the creation of one evidence-based tool serving authors from all disciplines.

Stress testing journals: a quasi-experimental study of rejection rates of a previously published paper.

BACKGROUND: When a journal receives a duplicate publication, the ability to identify the submitted work as previously published, and reject it, is an assay to publication ethics best practices. The aim of this study was to evaluate how three different types of journals, namely open access (OA) journals, subscription-based journals, and presumed predatory journals, responded to receiving a previously published manuscript for review. METHODS: We performed a quasi-experimental study in which we submitted a previously published article to a random sample of 602 biomedical journals, roughly 200 journals from each journal type sampled: OA journals, subscription-based journals, and presumed predatory journals. Three hundred and three journals received a Word version in manuscript format, while 299 journals received the formatted publisher's PDF version of the published article. We then recorded responses to the submission received after approximately 1 month. Responses were reviewed, extracted, and coded in duplicate. Our primary outcome was the rate of rejection of the two types of submitted articles (PDF vs Word) within our three journal types. RESULTS: We received correspondence back from 308 (51.1%) journals within our study timeline (32 days); (N = 46 predatory journals, N = 127 OA journals, N = 135 subscription-based journals). Of the journals that responded, 153 received the Word version of the paper, while 155 received the PDF version. Four journals (1.3%) accepted our paper, 291 (94.5%) journals rejected the paper, and 13 (4.2%) requested a revision. A chi-square test looking at journal type, and submission type, was significant (χ2 (4) = 23.50, p < 0.001). All four responses to accept our article came from presumed predatory journals, 3 of which received the Word format and 1 that received the PDF format. Less than half of journals that rejected our submissions did so because they identified ethical issues such as plagiarism with the manuscript (133 (45.7%)). CONCLUSION: Few journals accepted our submitted paper. However, our findings suggest that all three types of journals may not have adequate safeguards in place to recognize and act on plagiarism or duplicate submissions.

Screening for esophageal adenocarcinoma and precancerous conditions (dysplasia and Barrett's esophagus) in patients with chronic gastroesophageal reflux disease with or without other risk factors: two systematic reviews and one overview of reviews to inform a guideline of the Canadian Task Force on Preventive Health Care (CTFPHC).

BACKGROUND: Two reviews and an overview were produced for the Canadian Task Force on Preventive Health Care guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease (GERD) without alarm symptoms. The goal was to systematically review three key questions (KQs): (1) The effectiveness of screening for these conditions; (2) How adults with chronic GERD weigh the benefits and harms of screening, and what factors contribute to their preferences and decision to undergo screening; and (3) Treatment options for Barrett's esophagus (BE), dysplasia or stage 1 EAC (overview of reviews). METHODS: Bibliographic databases (e.g. Ovid MEDLINE®) were searched for each review in October 2018. We also searched for unpublished literature (e.g. relevant websites). The liberal accelerated approach was used for title and abstract screening. Two reviewers independently screened full-text articles. Data extraction and risk of bias assessments were completed by one reviewer and verified by another reviewer (KQ1 and 2). Quality assessments were completed by two reviewers independently in duplicate (KQ3). Disagreements were resolved through discussion. We used various risk of bias tools suitable for study design. The GRADE framework was used for rating the certainty of the evidence. RESULTS: Ten studies evaluated the effectiveness of screening. One retrospective study reported no difference in long-term survival (approximately 6 to 12 years) between those who had a prior esophagogastroduodenoscopy and those who had not (adjusted HR 0.93, 95% confidence interval (CI) 0.58-1.50). Though there may be higher odds of a stage 1 diagnosis than a more advanced diagnosis (stage 2-4) if an EGD had been performed in the previous 5 years (OR 2.27, 95% CI 1.00-7.67). Seven studies compared different screening modalities, and showed little difference between modalities. Three studies reported on patients' unwillingness to be screened (e.g. due to anxiety, fear of gagging). Eleven systematic reviews evaluated treatment modalities, providing some evidence of early treatment effect for some outcomes. CONCLUSIONS: Little evidence exists on the effectiveness of screening and values and preferences to screening. Many treatment modalities have been evaluated, but studies are small. Overall, there is uncertainty in understanding the effectiveness of screening and early treatments. SYSTEMATIC REVIEW REGISTRATIONS: PROSPERO (CRD42017049993 [KQ1], CRD42017050014 [KQ2], CRD42018084825 [KQ3]).

A systematic review and network meta-analysis of existing pharmacologic therapies in patients with idiopathic sudden sensorineural hearing loss.

BACKGROUND: Hearing loss is one of the leading causes of disability worldwide. Patients with hearing loss experience impaired quality of life, as well as emotional and financial consequences that affect both themselves and their families. Idiopathic sudden sensorineural hearing loss (ISSNHL) is a common but difficult to treat condition that has a sudden onset of ≤ 72 hour associated with various etiologies, with the majority of cases being idiopathic. There exists a wide range of therapeutic options, however, the uncertainty surrounding their comparative efficacy and safety makes selection of treatment difficult. This systematic review and network meta-analysis (NMA) assessed the relative effects of competing treatments for management of ISSNHL. METHODS: A protocol for this review was registered with PROSPERO (CRD42017073756). A detailed search of MEDLINE, Embase and the Cochrane Library from inception to February 8th, 2018 was carried out by an experienced information specialist. Grey literature was also searched. Screening full-text records, and risk of bias assessment were carried out independently by two reviewers, and disagreements were resolved through consensus or third party adjudication, while data was collected by one reviewer and verified by a second reviewer. Bayesian network meta-analyses (NMA) were performed to inform comparisons between interventions for a priori specified outcomes that included pure tone average (PTA) improvement and hearing recovery. RESULTS: The search identified a total of 1,138 citations, of which 613 remained for review after removal of duplicates. Of these, 23 publications describing 19 unique studies (total sample size of 1,527) met our a priori eligibility criteria, that were assessed to be at unclear or high risk of bias on several domains. We identified data on several interventions for ISSNHL therapy and were able to construct treatment networks consisting of six intervention groups that included placebo; intratympanic (IT) steroid; IT plus systemic steroid; per oral (PO) steroid; intravenous (IV) steroid; and IV plus PO steroid for our NMAs. IT plus systemic steroids demonstrated the largest difference in PTA improvement compared to placebo (25.85 dB, 95% CrI 7.18-40.58), followed by IV plus PO steroids (22.06 dB, 95% CrI 1.24-39.17), IT steroids (18.24 dB, 95% CrI 3.00-29.81). We observed that the difference of PTA improvement between each intervention and placebo diminished over time, attributed to spontaneous recovery. The binary outcomes of hearing recovery demonstrated similar relative ordering of interventions but were less sensitive than PTA improvement to capture the significant differences between interventions and placebo. CONCLUSION: Unclear to high risk of bias trials rated IT plus systemic steroid treatment as the best among the six interventions compared, and all active treatments were better than placebo in improving PTA. However, it should be noted that certain comparisons were based on indirect evidence only or few studies of small sample size, and analyses were unable to control for steroid type and dosage. Given these limitations, further data originating from methodologically sound and rigorous trials with adequate reporting are needed to confirm our findings.

Diagnostic Accuracy of Serum, Synovial, and Tissue Testing for Chronic Periprosthetic Joint Infection After Hip and Knee Replacements: A Systematic Review.

BACKGROUND: Chronic periprosthetic joint infection (PJI) is a devastating complication that can occur following total joint replacement. Patients with chronic PJI report a substantially lower quality of life and face a higher risk of short-term mortality. Establishing a diagnosis of chronic PJI is challenging because of conflicting guidelines, numerous tests, and limited evidence. Delays in diagnosing PJI are associated with poorer outcomes and morbid revision surgery. The purpose of this systematic review was to compare the diagnostic accuracy of serum, synovial, and tissue-based tests for chronic PJI. METHODS: This review adheres to the Cochrane Collaboration's diagnostic test accuracy methods for evidence searching and syntheses. A detailed search of MEDLINE, Embase, the Cochrane Library, and the grey literature was performed to identify studies involving the diagnosis of chronic PJI in patients with hip or knee replacement. Eligible studies were assessed for quality and bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analyses were performed on tests with sufficient data points. Summary estimates and hierarchical summary receiver operating characteristic (HSROC) curves were obtained using a bivariate model. RESULTS: A total of 12,616 citations were identified, and 203 studies met the inclusion criteria. Of these 203 studies, 170 had a high risk of bias. Eighty-three unique PJI diagnostic tests were identified, and 17 underwent meta-analyses. Laboratory-based synovial alpha-defensin tests and leukocyte esterase reagent (LER) strips (2+) had the best performance, followed by white blood-cell (WBC) count, measurement of synovial C-reactive protein (CRP) level, measurement of the polymorphonuclear neutrophil percentage (PMN%), and the alpha-defensin lateral flow test kit (Youden index ranging from 0.78 to 0.94). Tissue-based tests and 3 serum tests (measurement of interleukin-6 [IL-6] level, CRP level, and erythrocyte sedimentation rate [ESR]) had a Youden index between 0.61 to 0.75 but exhibited poorer performance compared with the synovial tests mentioned above. CONCLUSIONS: The quality of the literature pertaining to chronic PJI diagnostic tests is heterogeneous, and the studies are at a high risk for bias. We believe that greater transparency and more complete reporting in studies of diagnostic test results should be mandated by peer-reviewed journals. The available literature suggests that several synovial fluid-based tests perform well for diagnosing chronic PJI and their use is recommended in the work-up of any suspected case of chronic PJI. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Pharmacologic and surgical therapies for patients with Meniere's disease: a protocol for a systematic review and meta-analysis.

BACKGROUND: Hearing loss is one of the leading causes of disability in Canada and worldwide, with more than one million Canadians enduring a hearing-related disability. Meniere's disease (MD) is a chronic condition of the inner ear, manifesting as a triad of disabling symptoms, including attacks of vertigo, fluctuating sensorineural hearing loss (SNHL), and tinnitus. Impacts on quality of life are severe, particularly with respect to restrictions in social participation and physical activity, fatigue, and reduced capacity to work. Anxiety and other psychological disorders may result from the restrictions imposed on life, the constant uncertainty of vertigo attacks, and fluctuating SNHL, with neuroses and depression affecting 40 to 60% of sufferers of intractable MD. There is a need to establish the benefits of previously studied interventions with greater certainty. The planned systematic review and meta-analyses/network meta-analyses (NMAs) will assess the relative effects of competing pharmacologic and surgical interventions for management of MD in adults. METHODS: An experienced medical information specialist in consultation with the review team will develop the electronic search strategies. We will search various databases including MEDLINE, Embase, and the Cochrane Library with no date or language restrictions for published literature, and key clinical trial registries for in-progress and completed trials. Screening of the literature will be performed by two reviewers independently using pre-specified eligibility criteria, and quality of the included studies will be assessed using the Cochrane Risk of Bias tool. We will resolve disagreements through consensus or third-party adjudication. When applicable, meta-analyses and NMAs will be pursued to compare interventions in terms of their effects on outcomes, including frequency and severity of vertigo, occurrence and intensity of tinnitus, changes in hearing and speech recognition, quality of life, and harms. Separate analyses exploring the effects of pharmacologic and surgical approaches will be performed. DISCUSSION: Our planned systematic review will provide informative evaluations of existing treatments for management of Meniere's disease. The findings will inform practitioners as to the relative benefits and harms of the existing competing interventions for MD, offer optimal clinical treatment strategies, identify evidence gaps, and determine promising therapies for evaluation in future trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019119129.

What is a predatory journal? A scoping review.

Background: There is no standardized definition of what a predatory journal is, nor have the characteristics of these journals been delineated or agreed upon. In order to study the phenomenon precisely a definition of predatory journals is needed. The objective of this scoping review is to summarize the literature on predatory journals, describe its epidemiological characteristics, and to extract empirical descriptions of potential characteristics of predatory journals. Methods: We searched five bibliographic databases: Ovid MEDLINE, Embase Classic + Embase, ERIC, and PsycINFO, and Web of Science on January 2 nd, 2018. A related grey literature search was conducted March 27 th, 2018. Eligible studies were those published in English after 2012 that discuss predatory journals. Titles and abstracts of records obtained were screened. We extracted epidemiological characteristics from all search records discussing predatory journals. Subsequently, we extracted statements from the empirical studies describing empirically derived characteristics of predatory journals. These characteristics were then categorized and thematically grouped.   Results: 920 records were obtained from the search. 344 of these records met our inclusion criteria. The majority of these records took the form of commentaries, viewpoints, letters, or editorials (78.44%), and just 38 records were empirical studies that reported empirically derived characteristics of predatory journals. We extracted 109 unique characteristics from these 38 studies, which we subsequently thematically grouped into six categories: journal operations, article, editorial and peer review, communication, article processing charges, and dissemination, indexing and archiving, and five descriptors.    Conclusions: This work identified a corpus of potential characteristics of predatory journals. Limitations of the work include our restriction to English language articles, and the fact that the methodological quality of articles included in our extraction was not assessed. These results will be provided to attendees at a stakeholder meeting seeking to develop a standardized definition for what constitutes a predatory journal.

A protocol for a network meta-analysis of interventions to treat patients with sudden sensorineural hearing loss.

BACKGROUND: Hearing loss is one of the leading causes of disability worldwide, with greater than 20% of Canadian adults having measurable hearing loss in at least one ear. Patients with hearing loss experience impaired quality of life, and emotional and financial consequences that affect themselves and their families. Sudden sensorineural hearing loss (SSNHL) is a common but difficult to treat form of hearing loss that has a sudden onset of ≤ 72 h associated with various etiologies, with the majority of cases being idiopathic. Some patients may partially or completely recover hearing ability, but for 32 to 65% of patients whose hearing does not recover, feelings of social isolation elevate the risk of anxiety and depression. Hearing loss is also associated with poorer functional status, including difficulty with sound localization and hearing in noise. There exists a wide range of therapeutic options; however, treatment of idiopathic SSNHL is controversial because some patients recover spontaneously. The planned systematic review and network meta-analysis (NMA) will assess the relative effects of competing treatments for management of idiopathic SSNHL in adults. METHODS: Electronic search strategies were developed by an experienced medical information specialist in consultation with the review team. We will search MEDLINE, Embase, and the Cochrane Library with no date or language restrictions. Key clinical trial registries will also be searched for in-progress and completed trials. Two reviewers will independently screen the literature using pre-specified eligibility criteria, and assess the quality of included studies using the Cochrane Risk of Bias tool. Disagreements will be resolved through consensus or third party adjudication. Bayesian NMAs will be pursued to compare interventions in terms of their effects on hearing (including audiometric thresholds and speech recognition scores), extent of hearing recovery, quality of life, and incidence of harms (including vestibular dysfunction, incidence of infections, and withdrawals due to adverse events). DISCUSSION: This systematic review and NMA will offer new and informative evaluations of current therapies for SSNHL. The results will inform clinicians as to the relative benefits of the currently available interventions for managing this difficult condition, provide optimal clinical treatment strategies, establish evidence gaps, and identify promising treatments for evaluation in future trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD 42017073756 .

Flaws in the application and interpretation of statistical analyses in systematic reviews of therapeutic interventions were common: a cross-sectional analysis.

OBJECTIVES: The objective of the study was to investigate the application and interpretation of statistical analyses in a cross-section of systematic reviews (SRs) of therapeutic interventions, without restriction by journal, clinical condition, or specialty. STUDY DESIGN AND SETTING: We evaluated a random sample of SRs assembled previously, which were indexed in MEDLINE® during February 2014, focused on a treatment or prevention question, and reported at least one meta-analysis. The reported statistical methods used in each SR were extracted from articles and online appendices by one author, with a 20% random sample extracted in duplicate. RESULTS: We evaluated 110 SRs; 78/110 (71%) were non-Cochrane SRs and 55/110 (50%) investigated a pharmacological intervention. The SRs presented a median of 13 (interquartile range: 5-27) meta-analytic effects. When considering the index (primary or first reported) meta-analysis of each SR, just over half (62/110 [56%]) used the random-effects model, but few (5/62 [8%]) interpreted the meta-analytic effect correctly (as the average of the intervention effects across all studies). A statistical test for funnel plot asymmetry was reported in 17/110 (15%) SRs; however, in only 4/17 (24%) did the test include the recommended number of at least 10 studies of varying size. Subgroup analyses accompanied 42/110 (38%) index meta-analyses, but findings were not interpreted with respect to a test for interaction in 29/42 (69%) cases, and the issue of potential confounding in the subgroup analyses was not raised in any SR. CONCLUSIONS: There is scope for improvement in the application and interpretation of statistical analyses in SRs of therapeutic interventions. The involvement of statisticians on the SR team and establishment of partnerships between researchers with specialist expertise in SR methods and journal editors may help overcome these shortcomings.

Reproducible research practices are underused in systematic reviews of biomedical interventions.

OBJECTIVES: To evaluate how often reproducible research practices, which allow others to recreate the findings of studies, given the original data, are used in systematic reviews (SRs) of biomedical research. STUDY DESIGN AND SETTING: We evaluated a random sample of SRs indexed in MEDLINE during February 2014, which focused on a therapeutic intervention and reported at least one meta-analysis. Data on reproducible research practices in each SR were extracted using a 26-item form by one author, with a 20% random sample extracted in duplicate. We explored whether the use of reproducible research practices was associated with an SR being a Cochrane review, as well as with the reported use of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: We evaluated 110 SRs of therapeutic interventions, 78 (71%) of which were non-Cochrane SRs. Across the SRs, there were 2,139 meta-analytic effects (including subgroup meta-analytic effects and sensitivity analyses), 1,551 (73%) of which were reported in sufficient detail to recreate them. Systematic reviewers reported the data needed to recreate all meta-analytic effects in 72 (65%) SRs only. This percentage was higher in Cochrane than in non-Cochrane SRs (30/32 [94%] vs. 42/78 [54%]; risk ratio 1.74, 95% confidence interval 1.39-2.18). Systematic reviewers who reported imputing, algebraically manipulating, or obtaining some data from the study author/sponsor infrequently stated which specific data were handled in this way. Only 33 (30%) SRs mentioned access to data sets and statistical code used to perform analyses. CONCLUSION: Reproducible research practices are underused in SRs of biomedical interventions. Adoption of such practices facilitates identification of errors and allows the SR data to be reanalyzed.

A protocol for a systematic review of the diagnostic accuracy of blood markers, synovial fluid, and tissue testing in periprosthetic joint infections (PJI).

BACKGROUND: Total joint replacement (TJR) procedures have been one of the most rewarding interventions for treating patients suffering from joint disease. However, developing a periprosthetic joint infection (PJI) is a serious complication that is associated with the highest burden of cost and reduction in patients' quality of life compared to other complications following TJRs. One of the main challenges facing clinicians who are treating PJIs is accurately diagnosing infection in a timely fashion. Multiple orthopedic associations have published clinical guidelines for diagnosing PJI which are based solely on consensus approaches, expert opinions, and narrative reviews. We believe that a higher quality of scientific rigor is necessary to establish a diagnostic guideline that represents current evidence more accurately and that identifies important knowledge gaps in PJI diagnosis. Therefore, we will conduct a systematic review on diagnostic performance of blood markers, synovial fluids, and tissue tests for diagnosing PJI. METHODS/DESIGN: Electronic search strategies will be developed and tested by an experienced medical information specialist in consultation with the review team, and gray literature will be searched using the checklist from CADTH's Grey Matters Light. Two reviewers will independently screen the literature for inclusion using the prespecified eligibility criteria. Non-English language and animal-only studies will be excluded. Quality assessment and data extractions by reviewers will be verified, and disagreements will be resolved through consensus or third party adjudication. We will assess the quality of individual studies using the QUADAS-2 tool and use GRADE to summarize the strength of body of evidence. Analyses of evidence will be conducted in accordance with the Cochrane Handbook for Diagnostic Test Accuracy Reviews. DISCUSSION: We will conduct a systemic review of tests (blood markers, synovial fluids, and tissue testing) for diagnosing PJI in patients' knee, hip, and shoulder joint replacements. This will be the first scientifically rigorous and comprehensive systematic review in the field and may feed into an evidence-based clinical practice guideline. We will compare the findings of this review with the consensus-based guides and discuss the differences, similarities, and knowledge gaps. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023768.