Cardiorespiratory Fitness and Physical Activity in Pediatric Diabetes: A Systemic Review and Meta-Analysis.

Importance: It is unclear whether cardiorespiratory fitness (CRF) and physical activity are lower among youths with type 1 diabetes (T1D) and type 2 diabetes (T2D) compared with youths without diabetes. Objective: To describe the magnitude, precision, and constancy of the differences in CRF and physical activity among youths with and without diabetes. Data Sources: MEDLINE, Embase, CINAHL, and SPORTDiscus were searched from January 1, 2000, to May 1, 2022, for eligible studies. Study Selection: Observational studies with measures of CRF and physical activity in children and adolescents aged 18 years or younger with T1D or T2D and a control group were included. Data Extraction and Synthesis: Data extraction was completed by 2 independent reviewers. A random-effects meta-analysis model was used to estimate differences in main outcomes. The pooled effect estimate was measured as standardized mean differences (SMDs) with 95% CIs. The Preferred Reporting Items for Systematic Review and Meta-Analyses guideline was followed. Main Outcomes and Measures: The main outcomes were objectively measured CRF obtained from a graded maximal exercise test and subjective or objective measures of physical activity. Subgroup analyses were performed for weight status and measurement type for outcome measures. Results: Of 7857 unique citations retrieved, 9 studies (755 participants) with measures of CRF and 9 studies (1233 participants) with measures of physical activity for youths with T2D were included; for youths with T1D, 23 studies with measures of CRF (2082 participants) and 36 studies with measures of PA (12 196 participants) were included. Random-effects models revealed that directly measured CRF was lower in youths with T2D (SMD, -1.06; 95% CI, -1.57 to -0.56; I2 = 84%; 9 studies; 755 participants) and in youths with T1D (SMD, -0.39; 95% CI, -0.70 to -0.09; I2 = 89%; 22 studies; 2082 participants) compared with controls. Random-effects models revealed that daily physical activity was marginally lower in youths with T1D (SMD, -0.29; 95% CI, -0.46 to -0.11; I2 = 89%; 31 studies; 12 196 participants) but not different among youths with T2D (SMD, -0.56; 95% CI, -1.28 to 0.16; I2 = 91%; 9 studies; 1233 participants) compared with controls. When analyses were restricted to studies with objective measures, physical activity was significantly lower in youths with T2D (SMD, -0.71; 95% CI, -1.36 to -0.05; I2 = 23%; 3 studies; 332 participants) and T1D (SMD, -0.67; 95% CI, -1.17 to -0.17; I2 = 93%; 12 studies; 1357 participants) compared with controls. Conclusions and Relevance: These findings suggest that deficits in CRF may be larger and more consistent in youths with T2D compared with youths with T1D, suggesting an increased risk for cardiovascular disease-related morbidity in adolescents with diabetes, particularly among those with T2D. The findings reinforce calls for novel interventions to empower youths living with diabetes to engage in regular physical activity and increase their CRF.

Characterizing research partnerships in child health research: A scoping review.

Research partnerships between researchers and knowledge users (KUs) in child health are understudied. This study examined the scope of KU engagement reported in published child health research, inclusive of health research partnership approaches and KU groups. Search strategies were developed by a health research librarian. Studies had to be in English, published since 2007, and were not excluded based on design. A two-step, multiple-person hybrid screening approach was used for study inclusion. Data on study and engagement characteristics, barriers and facilitators, and effects were extracted by one reviewer, with 10% verified by a second reviewer. Three hundred fifteen articles were included, with 243 (77.1%) published between 2019 and 2021. Community-based participatory research was the most common approach used (n = 122, 38.3%). Most studies (n = 235, 74.6%) engaged multiple KU groups (range 1-11), with children/youth, healthcare professionals, and parents/families being most frequently engaged. Reporting of barriers and facilitators and effects were variable, reported in 170 (53.8%) and 197 (62.5%) studies, respectively. Publications have increased exponentially over time. There is ongoing need to optimize evaluation and reporting consistency to facilitate growth in the field. Additional studies are needed to further our understanding of research partnerships in child health.

A global systematic evidence review with meta-analysis of the epidemiological characteristics of the 2022 Mpox outbreaks.

BACKGROUND: In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarized published full-text epidemiological data from the outbreaks. METHODS: A global evidence review (protocol: osf.io/j3kb7) with systematic literature search up to February 09, 2023. We focused on experimental/observational studies of laboratory confirmed Mpox, excluding case reports and case series of < 5 cases. Epidemiological data were pooled using an inverse variance, random-effects model, and pooled estimates presented with associated 95% confidence intervals. RESULTS: We included 66 studies. Mean incubation period was 7.8 days (6.6-9.0 days, 8 studies: 560 cases), reproductive number 1.8 (1.7-1.9, 6 studies), mean duration from symptom onset to diagnosis 5.8 days (4.8-6.8 days, 4 studies: 982 cases), mean symptom duration 17.5 days (14.7-20.2 days, 3 studies: 292 cases), mean serial interval 8.5 days (7.3-9.9 days, 1 study), hospitalisation 6% (4-9%, 26 studies: 5339 cases), and vaccine effectiveness 78% (65-91%, 3 studies: 953 cases). Highly relevant clinical manifestations were pleomorphic skin lesions 82% (68-94%, 26 studies: 4093 cases), anogenital lesions 64% (51-77%, 9 studies: 10,398 cases), fever 54% (50-57%, 52 studies: 25,992 cases), and lymphadenopathy 51% (46-57%, 42 studies: 17,803 cases), with cases mostly men who have sex with men (MSM). Possibly relevant manifestations were perianal lesions, fatigue, asthenia, myalgia, and headache. CONCLUSIONS: The 2022 Mpox outbreaks presented with sex-related clinical manifestations and were mostly reported among MSM.

Efficacy and Safety of MAO-B Inhibitors Safinamide and Zonisamide in Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ). RESULTS: Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = -  2.18; 95% CI -  2.88 to -  1.49; I 2 =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = -  2.10; 95% CI -  3.09 to -  1.11; I2 = 71%; n = 8 studies) and zonisamide (MD = -  2.31; 95% CI -  3.35 to -  1.27; I2 = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson's Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were reported as a high risk of bias and sensitivity analyses confirmed the primary analysis results. CONCLUSIONS: Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.

Physical Activity for Quiescent and Mildly Active Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: Physical activity (PA) may benefit people with inflammatory bowel diseases (IBD) by improving immunological response, musculoskeletal function, and psychological health. Aims: We distilled available evidence on the efficacy and safety of PA to improve health-related quality of life (HRQoL) and relieve persistent symptoms of fatigue, joint pain, abdominal pain, stress, anxiety, and depression in individuals with quiescent/mild IBD. Methods: We searched for trials in eight databases and trial registries. Trials using PA as an adjunct therapy in the management of adults (≥18 years) with quiescent or mild IBD, published in English between 2011 and 2023 were identified. Summary effect estimates were expressed as standardized mean difference (SMD) or mean difference (MD) with 95% confidence interval (CI) using random-effects model. Results: From the 10,862 citations retrieved, we included seven randomized controlled trials (RCTs) and one non-RCT. There was no evidence of benefit of PA on HRQoL (SMD 0.34, 95%CI -0.08 to 0.77; I2 57%); high heterogeneity was noted among included trials. PA was found to be efficacious in reducing anxiety (SMD -0.35, 95%CI -0.65 to -0.05; I2 0%). There was insufficient evidence to make conclusions regarding changes in fatigue, joint pain, abdominal pain, stress, and depression. All trials deemed physical activity safe. Conclusions: PA contributes to reducing anxiety in quiescent/mild IBD. There is marked heterogeneity in methodology among trials investigating PA in adults with quiescent/mild IBD. This review highlights the need for consistent definitions of PA types and intensities in this field of research.

The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects. RESULTS: There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67). CONCLUSION: Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.

Searching for evidence in public health emergencies: a white paper of best practices.

Objectives: Information professionals have supported medical providers, administrators and decision-makers, and guideline creators in the COVID-19 response. Searching COVID-19 literature presented new challenges, including the volume and heterogeneity of literature and the proliferation of new information sources, and exposed existing issues in metadata and publishing. An expert panel developed best practices, including recommendations, elaborations, and examples, for searching during public health emergencies. Methods: Project directors and advisors developed core elements from experience and literature. Experts, identified by affiliation with evidence synthesis groups, COVID-19 search experience, and nomination, responded to an online survey to reach consensus on core elements. Expert participants provided written responses to guiding questions. A synthesis of responses provided the foundation for focus group discussions. A writing group then drafted the best practices into a statement. Experts reviewed the statement prior to dissemination. Results: Twelve information professionals contributed to best practice recommendations on six elements: core resources, search strategies, publication types, transparency and reproducibility, collaboration, and conducting research. Underlying principles across recommendations include timeliness, openness, balance, preparedness, and responsiveness. Conclusions: The authors and experts anticipate the recommendations for searching for evidence during public health emergencies will help information specialists, librarians, evidence synthesis groups, researchers, and decision-makers respond to future public health emergencies, including but not limited to disease outbreaks. The recommendations complement existing guidance by addressing concerns specific to emergency response. The statement is intended as a living document. Future revisions should solicit input from a broader community and reflect conclusions of meta-research on COVID-19 and health emergencies.

Comparative evaluation of the clinical presentation and epidemiology of the 2022 and previous Mpox outbreaks: a rapid review and meta-analysis.

BACKGROUND: In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarised and compared the findings from published observational studies on the clinical presentation and epidemiology of the 2022 and previous outbreaks of Mpox. METHODS: We registered a review protocol with the Open Science Framework (osf.io/j3kb7). We searched MEDLINE, Embase, CENTRAL, CINAHL and Scopus databases, and relevant websites up to August 30, 2022. Retrieved literature citations were screened for eligibility, and summary clinical presentation and epidemiological data from the included studies were pooled, when possible, using an inverse variance, random-effects model. RESULTS: Seventy-nine studies met the eligibility. Irrespective of outbreak, fever, headache, myalgia, lymphadenopathy, pleomorphic skin lesions, oral lesions, and sore throat were potentially highly relevant Mpox manifestations, while conjunctivitis, cough, and possibly reactivation of varicella zoster virus may be part of the clinical presentation. The mean incubation period for the 2022 outbreaks was 7.4 d (6.4-8.4 d, I2 64.2%; 4 studies: 270 cases) and for previous outbreaks, 12.9 d (10.4-15.5 d; one study: 31 cases), p < .001. None of the male cases from previous outbreaks was reported to have sex with men (MSM) whereas almost all reported male cases from the 2022 outbreak were MSM. Concomitant sexually transmitted infections and perianal lesions were reported only among male cases from the 2022 outbreak, with the cases mostly presenting with genital lesions. CONCLUSIONS: The 2022 Mpox outbreaks appear to be mostly among MSM and have a lower incubation period compared with previous outbreaks.Key messages79 studies met the review's inclusion criteria.The 2022 Mpox outbreaks appear to have shorter incubation period compared with previous outbreaks.Established clinical presentation of Mpox includes fever, headache, myalgia, lymphadenopathy, pleomorphic skin lesions, oral lesions, and sore throat.Almost all reported cases from the 2022 Mpox outbreaks were men who had sex with men (MSM).Concomitant sexually transmitted infections and perianal lesions were only reported among cases from the 2022 Mpox outbreaks.A significantly higher proportion of Mpox cases from the 2022 outbreaks had genital lesions compared with cases from previous outbreaks.The 2022 Mpox outbreaks appear to be mostly among MSM.

Vaccine confidence among those living with allergy during the COVID pandemic (ACCORD): A scoping review.

Background: Reports of allergic reactions to coronavirus disease 2019 (COVID-19) vaccines, coupled with an "infodemic" of misinformation, carry the potential to undermine confidence in the COVID-19 vaccines. However, no attempts have been made to comprehensively synthesize the literature on how allergic disease and fear of allergic reactions to the vaccines contribute to hesitancy. Objectives: Our aim was to review the academic and gray literature on COVID-19 vaccine hesitancy and allergic reactions. Methods: We searched 4 databases (CINAHL, PsycINFO, MEDLINE, and Embase) using a search strategy developed by content and methodologic experts. No restrictions were applied regarding COVID-19 vaccine type, country of study, or patient age. Eligible articles were restricted to 10 languages. Results: Of the 1385 unique records retrieved from our search, 60 articles (4.3%) were included. Allergic reactions to the COVID-19 vaccine were rare but slightly more common in individuals with a history of allergic disease. A fifth of the studies (13 of 60 [22%]) discussed vaccine hesitancy due to possibility of an allergic reaction. Additionally, the present review identified research on details of vaccine-related anaphylaxis (eg, a mean and median [excluding clinical trial data] of 12.4 and 5 cases per million doses, respectively) and allergic reactions (eg, a mean and median [excluding clinical trial data] of 489 and 528 cases per million doses, respectively). Conclusion: COVID-19 vaccine acceptance among individuals living with allergy and among those with no history of allergic disease may be affected by fear of an allergic reaction. Despite the low incidence of allergic reactions to the COVID-19 vaccine, fear of such reactions is one of the most commonly cited concerns reported in the literature.

Preoperative oral fluoroquinolone antibiotics in elective colorectal surgery to prevent surgical site infections: a systematic review and meta-analysis.

BACKGROUND: Preoperative treatment with oral neomycin combined with erythromycin or metronidazole is recommended to decrease the risk of surgical site infections (SSIs) in elective colorectal surgery. However, oral neomycin is not commercially available in Canada, and therefore it is not routinely used. Fluoroquinolones are widely available and have excellent activity against aerobic Gram-negative bacteria. The aim of this systematic review was to identify, critically appraise and summarize the evidence on the efficacy and safety of preoperative use of oral fluoroquinolone antibiotics for the prevention of SSIs in adult patients undergoing elective colorectal resection. METHODS: Following Cochrane guidelines, we included English-language randomized controlled trials (RCTs) comparing oral fluoroquinolones plus routine preoperative intravenous antibiotics against intravenous antibiotics alone from MEDLINE (Ovid), Embase (Ovid), the Cochrane Central Register of Controlled Trials( Ovid) and ClinicalTrials.gov. RESULTS: We included 3 RCTs (1136 patients). Risk of bias was uncertain in 2 trials and high in 1 trial. Preoperative oral fluoroquinolones led to significantly decreased total SSIs (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.32-0.57, I 2 = 0%), superficial incisional (RR 0.38, 95% CI 0.22-0.68, I 2 = 32%), deep incisional (RR 0.19, 95% CI 0.06-0.65, I 2 = 0%) and organ/space SSIs (RR 0.34, 95% CI 0.12-0.90, I 2 = 33%). There was also a significant reduction in anastomotic leaks (RR 0.22, 95% CI 0.06-0.87, I 2 = 0%). No antibiotic-related adverse events were reported. CONCLUSION: This review suggests that preoperative oral fluoroquinolones with intravenous antibiotics are superior to intravenous antibiotics alone for preventing SSIs after colorectal surgery. If neomycin is unavailable, oral fluoroquinolones should be considered as a reasonable alternative. Future trials are required to further compare the relative efficacy of oral antibiotic regimens.

Self-Management Programs for Chronic Non-Cancer Pain: A Rapid Review of Randomized Trials.

BACKGROUND: The body of evidence regarding self-management programs (SMPs) for adult chronic non-cancer pain (CNCP) is steadily growing, and regular updates are needed for effective decision-making. OBJECTIVES: To systematically identify, critically appraise, and summarize the findings from randomized controlled trials (RCTs) of SMPs for CNCP. METHODS: We searched relevant databases from 2009 to August 2021 and included English-language RCT publications of SMPs compared with usual care for CNCP among adults (18+ years old). The primary outcome was health-related quality of life (HR-QoL). We conducted meta-analysis using an inverse variance, random-effects model and calculated the standardized mean difference (SMD) and associated 95% confidence interval (CI) and statistical heterogeneity using the I2 statistic. RESULTS: From 8538 citations, we included 28 RCTs with varying patient populations, standards for SMPs, and usual care. No RCTs were classified as having a low risk of bias. There was no evidence of a significant improvement in overall HR-QoL, irrespective of pain type, immediately post-intervention (SMD 0.01, 95%CI -0.21 to 0.24; I2 57%; 11 RCTs; 979 participants), 1-4 months post-intervention (SMD 0.02, 95%CI -0.16 to 0.20; I2 48.7%; 12 RCTs; 1160 participants), and 6-12 months post-intervention (SMD 0.07, 95%CI -0.06 to 0.21; I2 26.1%; 9 RCTs; 1404 participants). Similar findings were made for physical and mental HR-QoL, and for specific QoL assessment scales (e.g., SF-36). CONCLUSIONS: There is a lack of evidence that SMPs are efficacious for CNCP compared with usual care. Standardization of SMPs for CNCP and better planned/conducted RCTs are needed to confirm these conclusions.

Equity-relevant sociodemographic variable collection in emergency medicine: A systematic review, qualitative evidence synthesis, and recommendations for practice.

OBJECTIVES: The objective was to conduct a systematic review and qualitative evidence synthesis (QES) to identify best practices, benefits, harms, facilitators, and barriers to the routine collection of sociodemographic variables in emergency departments (EDs). METHODS: This work is a systematic review and QES. We conducted a comprehensive search of Medline (Ovid), CINAHL (Ebsco), Cochrane Central (OVID), EMBASE (Ovid), and the multidisciplinary Web of Science Core database using peer-reviewed search strategies, complemented by a gray literature search. We included citations containing perspectives on routine sociodemographic variable collection in EDs and recommendations on definitions or processes of collection or benefits, harms, facilitators, or barriers related to the routine collection of sociodemographic variables in EDs. We conducted this systematic review and QES adhering to the Joanna Briggs Institute guidelines. Two reviewers independently selected included studies and extracted data. We conducted a best-fit framework synthesis and paired inductive thematic analysis of the included studies. We generated recommendations based on the QES. RESULTS: We included 21 unique reports that enrolled 10,454 patients or respondents in our systematic review and QES. Publication dates of included studies ranged from 2011 to 2021. Included citations were published in Australia, Canada, and the United States. We synthesized 11 benefits, 14 potential harms, 15 barriers, and 19 facilitators and identified 14 best practice recommendations from included citations. CONCLUSIONS: Health systems should routinely collect sociodemographic variables in EDs guided by recommendations that minimize harms and maximize benefits and consider relevant barriers and facilitators. Our recommendations can serve as a guide for the equity-focused reformation of emergency medicine health information systems.

Efficacy and safety of perampanel in epilepsy: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures with or without focal to bilateral tonic clonic seizures and primary generalized tonic-clonic seizures. METHODS: This review included RCTs on patients with epilepsy exposed to perampanel compared with placebo, or one or more pre-existing antiseizure medications. Four databases and two clinical trial registries were searched from inception to July 2021. Included outcomes were 50% responder rate, seizure-free rate, discontinuation due to treatment-emergent adverse events (TEAE)s, having any TEAEs, and most reported TEAEs. Cochrane risk of bias tool was used to assess the internal validity of the included RCTs. RESULTS: From 2211 retrieved citations, eight RCTs were included in the meta-analysis. Fifty-percent responder and seizure freedom rates were significantly higher in patients receiving perampanel when compared to placebo (RR 1.57, 95 % CI 1.35 to 1.82, I2 15% and RR 2.79, 95% CI 1.58 to 4.93, I2 7%, respectively). The 50% responder rates for 8mg and 12 mg, when compared to placebo, were similar. The most-reported TEAEs were dizziness and somnolence with <1% reporting serious psychological outcomes. CONCLUSION: This systematic review reports significant reduction in seizures and a potential dose-based increase in discontinuations due to TEAE. The most-reported TEAEs were non-threatening, with the possibility of rare but serious adverse psychological outcomes. Further independent RCTs studying the most efficient dose for efficacy and safety are needed.

Patient Navigators for CKD and Kidney Failure: A Systematic Review.

Rationale & Objective: To what degree and how patient navigators improve clinical outcomes for patients with chronic kidney disease (CKD) and kidney failure is uncertain. We performed a systematic review to summarize patient navigator program design, evidence, and implementation in kidney disease. Study Design: A search strategy was developed for randomized controlled trials and observational studies that evaluated the impact of navigators on outcomes in the setting of CKD and kidney failure. Articles were identified from various databases. Two reviewers independently screened the articles and identified those meeting the inclusion criteria. Setting & Participants: Patients with CKD or kidney failure (in-center hemodialysis, peritoneal dialysis, home hemodialysis, or kidney transplantation). Selection Criteria for Studies: Studies that compared patient navigators with a control, without limits on size, duration, setting, or language. Studies focusing solely on patient education were excluded. Data Extraction: Data were abstracted from full texts and risk of bias was assessed. Analytical Approach: No meta-analysis was performed. Results: Of 3,371 citations, 17 articles met the inclusion criteria including 14 original studies. Navigators came from various healthcare backgrounds including nursing (n=6), social worker (n=2), medical interpreter (n=1), research (n=1), and also included kidney transplant recipients (n=2) and non-medical individuals (n=2). Navigators focused mostly on education (n=9) and support (n = 6). Navigators were used for patients with CKD (n=5), peritoneal dialysis (n=2), in-center hemodialysis (n=4), kidney transplantation (n=2), but not home hemodialysis. Navigators improved transplant workup and listing, peritoneal dialysis utilization, and patient knowledge. Limitations: Many studies did not show benefits across other outcomes, were at a high risk of bias, and none reported cost-effectiveness or patient-reported experience measures. Conclusions: Navigators improve some health outcomes for CKD but there was heterogeneity in their structure and function. High-quality randomized controlled trials are needed to evaluate navigator program efficacy and cost-effectiveness.

vACcine COnfidence amongst those living with alleRgy during the COVID pandemic (ACCORD): a scoping review protocol.

BACKGROUND: Reports of allergic reactions to the COVID-19 vaccines have been documented, which may also contribute to hesitancy. Despite the low likelihood that the COVID-19 vaccine will trigger an allergic reaction, we and others have reported that families with allergy remain vaccine hesitant due to concerns of COVID-19-vaccine-triggered anaphylaxis. OBJECTIVE: To present our scoping review protocol, that will inform a forthcoming living scoping review in which we will investigate the peer-reviewed and grey literature on COVID-19 vaccine hesitancy and allergic disease and/or allergic reactions following a COVID-19 vaccine. METHODS: Informed by Arksey and O'Malley framework for methodological review, we have developed a search strategy with content and methodological experts, and which has undergone Peer Review of Electronic Search Strategies review. A search of four scientific databases, as well as gray literature, will be performed without restriction to articles by type of COVID-19 vaccine, or country of study, and will include publications in the ten languages our team can handle. Bi-monthly search alerts based on the search strategy will be generated. RESULTS: The first search will result in a stand alone peer reviewed scoping review. Bi-monthly updates will be posted on a pre-print server. Depending on the volume of literature, these updates will be synthesized and submitted for peer-review at 6 and/or 12 months. CONCLUSION: COVID-19 vaccine hesitancy amongst individuals with allergy persists, despite very low risk of serious adverse reactions. Our living scoping review, which includes multiple forms of knowledge translation, will be a rigorous way to address hesitancy.

Characteristics and methodological standards across systematic reviews with Meta-analysis of efficacy and/or effectiveness of influenza vaccines: an overview of reviews.

BACKGROUND: While systematic reviews (SR) generally suggest that vaccination is an effective way to prevent influenza infection, it is not clear if these conclusions are based on high quality SR methods. As such, we systematically identified, critically appraised, and summarised the characteristics and adherence to methodological standards in SRs with meta-analysis of efficacy/effectiveness of influenza vaccines. METHODS: We searched MEDLINE, Embase, Scopus, CINAHL, Global Health, and CDSR for English-language SR publications up to July 11, 2022. We summarised the characteristics, adherence to methodological standards and SR quality (AMSTAR 2). RESULTS: From 11,193 retrieved citations, we included 48 publications (47 SRs). Seventy-five percent were of a critically low quality, 19% of a low quality, 2% of a moderate quality, and 4% of a high quality. Thirteen percent were industry-funded, about 13% co-authored by industry employee(s), and 4% commissioned by an organisation or authority. Only 45% percent reported protocol registration, 6% reported collaboration with a knowledge synthesis librarian/information specialist, and 60% utilised a reporting checklist (e.g. PRISMA). CONCLUSIONS AND RELEVANCE: SRs with meta-analysis of efficacy/effectiveness of influenza vaccines are mostly of critically low quality and even the more recent reviews did not follow current best SR practices. These findings are significant in view of the controversies that surround influenza vaccines, and the use of SRs in informed decision-making. However, the findings do not justify curtailment or cessation of influenza vaccine use as vaccines continue to offer substantial net public health benefit.HighlightsWe systematically identified, critically appraised, and summarised the characteristics and adherence to methodological standards in 47 systematic reviews with meta-analysis of efficacy/effectiveness of influenza vaccines.13% of the reviews were industry-funded.About 13% of the reviews were co-authored by industry employee(s).4% of the reviews were commissioned by an organisation/authority.45% of the reviews reported protocol registration.6% of the reviews reported collaborating with a knowledge synthesis librarian/information specialist to prepare the search strategy.60% of the reviews reported using the PRISMA (or similar) checklist.75% of the reviews were judged to be of critically low quality; 19% of low quality; 2% of moderate quality; 4% of high quality.

The Effect of Gender-Affirming Hormone Therapy on Measures of Kidney Function: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Gender-affirming hormone therapy modifies body composition and lean muscle mass in transgender persons. We sought to characterize the change in serum creatinine, other kidney function biomarkers, and GFR in transgender persons initiating masculinizing and feminizing gender-affirming hormone therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to September 16, 2020 for randomized controlled trials, observational studies, and case series that evaluated the change in serum creatinine, other kidney function biomarkers, and GFR before and after the initiation of gender-affirming hormone therapy in adult transgender persons. Two reviewers independently screened and abstracted data, and disagreements were resolved by a third reviewer. A random effects meta-analysis was performed to determine the change in outcomes over follow-up of 3, 6, and 12 months. RESULTS: Of the 4758 eligible studies, 26 met the inclusion criteria, including nine studies that recruited 488 transgender men and 593 women in which data were meta-analyzed. There was heterogeneity in study design, populations, gender-affirming hormone therapy routes, and dosing. At 12 months after initiating gender-affirming hormone therapy, serum creatinine increased by 0.15 mg/dl (95% confidence interval, 0.00 to 0.29) in 370 transgender men and decreased by -0.05 mg/dl (95% confidence interval, -0.16 to 0.05) in 361 transgender women. No study reported the effect of gender-affirming hormone therapy on albuminuria, proteinuria, cystatin C, or measured GFR. CONCLUSIONS: Gender-affirming hormone therapy increases serum creatinine in transgender men and does not affect serum creatinine in transgender women. The effect on gender-affirming hormone therapy on other kidney function biomarkers and measured GFR is unknown. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Change in Kidney Function Biomarkers in Transgender Persons on Gender Affirmation Hormone Therapy-A Systematic Review and Meta-Analysis, CRD42020214248.

The Effects of Resistant Starch Consumption in Adult Patients With Chronic Kidney Disease: A Systematic Review.

Background: Resistant starches (RSs) are not digested by human digestive enzymes and pass through the upper digestive tract to become substrates for colonic bacteria. Resistant starch supplementation has shown promising results in altering the microbiota of animal models of chronic kidney disease (CKD). Resistant starch consumption may influence the production of uremic toxins in CKD. Objective: To conduct a systematic review to determine whether the consumption of RS reduces the progression of kidney disease in adult patients with CKD. Design: We included randomized controlled trials comparing RS supplementation to placebo, no treatment, or standard care. Cochrane Central, Embase, MEDLINE, Web of Science, and CINAHL databases were searched. There was no limitation on publication date, but only English manuscripts were included. The search was conducted in July 2020. Patients: Adult outpatient populations with CKD, using any recognized diagnostic criteria. Measurements: The primary outcome was change in glomerular filtration rate (GFR) from baseline through the end of the trial in patients not on dialysis; secondary outcomes included change in uremic toxin concentrations (p-cresol/p-cresyl sulfate [p-CS], indoxyl sulfate [IS]) and inflammatory markers (tumor necrosis factor alpha [TNF-α], C-reactive protein [CRP], interleukin 6 [IL-6]) from baseline through the end of the trial, and changes in self-reported symptom scores. Methods: The Cochrane Collaboration Risk of Bias tool was used to assess risk of bias in included studies. The systematic review results are reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: We identified 4 unique studies, reported in 9 publications that met our inclusion criteria, including a total of 215 enrolled participants. Results were calculated using data from the longest reported follow-up time. The primary outcome of changes in kidney function markers was only studied in 1 trial; this trial reported an increase in creatinine and a decrease in blood urea nitrogen; no changes in GFR were reported. A review of the secondary outcomes showed an overall decline in IS, TNF-α, and IL-6, in RS groups, but with mixed results in p-CS and CRP/high-sensitivity CRP. Safety data showed that RS was well tolerated with no reports of excessive side effects. Limitations: We determined a meta-analysis was not feasible due to clinical heterogeneity between study populations and differences in reported outcomes in the included studies. Conclusion: There is limited and inconsistent evidence on the impact of RS in adult patients with CKD. Further research is needed to determine the safety and efficacy of RS supplementation in this population.

Contexte: Les amidons résistants ne sont pas dégradés par les enzymes digestives humaines; ils traversent le tube digestif supérieur et deviennent des substrats pour les bactéries du côlon. La supplémentation en amidons résistants a montré des résultats prometteurs dans la modification du microbiote chez les modèles animaux d'insuffisance rénale chronique (IRC). Dans ce contexte, la consommation d'amidons résistants pourrait avoir une incidence sur la production de toxines urémiques. Objectif: Procéder à une revue systématique afin de déterminer si la consommation d'amidons résistants limite la progression de la maladie chez les adultes atteints d'IRC. Conception de l'étude: Ont été inclus les essais contrôlés randomisés qui comparaient la supplémentation en amidons résistants à un placebo, à l'absence de traitement ou aux soins courants. La recherche a été effectuée en juillet 2020 dans les bases de données Cochrane Central, Embase, Medline, Web of Science et CINAHL. La date de publication n'était pas limitée, mais seuls les articles rédigés en anglais ont été inclus. Sujets: Des adultes atteints d'IRC et suivis en ambulatoire, selon tout critère de diagnostic reconnu. Mesures: Le principal critère d'évaluation était un changement dans le taux de filtration glomérulaire entre le début et la fin de l'essai chez les patients non dialysés. Les résultats secondaires comprenaient un changement, entre le début et la fin de l'essai, dans les concentrations de toxines urémiques (sulfate de p-crésol/crésyle, sulfate d'indoxyle) et de marqueurs d'inflammation (TNFα, CRP, IL-6), ainsi que dans les scores de symptômes auto-déclarés. Méthodologie: L'outil de Risque de Biais de la Collaboration Cochrane a été utilisé pour évaluer le risque de biais dans les études incluses. Les résultats de la revue systématique sont présentés conformément aux directives PRISMA. Résultats: Quatre études uniques, présentées dans neuf publications et portant sur un total de 215 patients, répondaient à nos critères d'inclusion. Les résultats ont été calculés à partir des données de la plus longue période de suivi rapportée. Un seul de ces essais avait examiné le critère principal d'évaluation, soit un changement dans les marqueurs de la fonction rénale. On y rapportait une augmentation du taux de créatinine et une diminution du taux de l'urée dans le sang. Aucun changement dans le débit de filtration glomérulaire n'avait été signalé. Un examen des résultats secondaires a révélé une diminution globale du sulfate d'indoxyle, du TNF alpha et d'IL-6 dans les groupes de patients qui prenaient des suppléments d'amidon résistants, mais des résultats mitigés en ce qui concerne les taux de p-CS et de CRP/hsCRP. Les données de sécurité montraient que les amidons résistants étaient bien tolérés, aucun effet secondaire important n'ayant été rapporté. Limites: Une méta-analyse n'était pas réalisable en raison de l'hétérogénéité clinique entre les populations étudiées et des différences dans les résultats rapportés dans les études incluses. Conclusion: Les données sur les effets d'une supplémentation en amidons résistants chez les adultes atteints d'IRC sont limitées et manquent d'uniformité. D'autres recherches examinant la sécurité et l'efficacité d'une supplémentation en amidons résistants dans cette population sont nécessaires.

An overview of the characteristics and methodological standards across systematic reviews with Meta-analysis of efficacy/effectiveness of influenza antiviral drugs.

BACKGROUND: Influenza antiviral drugs remain controversial and it is not clear if conclusions on their efficacy/effectiveness are based on high quality systematic reviews (SRs). We systematically identified, critically appraised, and summarized the characteristics and adherence to methodological standards in SRs with meta-analysis of efficacy/effectiveness of influenza antiviral drugs for prevention and/or treatment of influenza. METHODS: We searched MEDLINE, Embase, Scopus, CINAHL, Global Health, and CDSR for English-language SR publications up to July 2020. We summarized the characteristics, adherence to methodological standards and SR quality (AMSTAR 2). RESULTS: From a total 3,898 citations after removal of duplicates from all identified citations, we included 24 SRs. Seventy-five percent (n = 18) were of a critically low quality, 8% (n = 2) of a low quality, 17% (n = 4) of a moderate quality, and none were of a high quality. Seventeen percent (n = 4) were industry-funded, 4% (n = 1) coauthored by industry employee(s), and 33% (n = 8) commissioned by an organization or authority. Only 33% percent (n = 8) reported protocol registration, 4% (n = 1) reported collaboration with a knowledge synthesis librarian/information specialist, and 17% (n = 4) utilized a systematic review reporting checklist. CONCLUSIONS: The evidence suggests that SRs of efficacy/effectiveness of influenza antiviral drugs are mostly of critically low quality and do not follow current best SR practices. These findings are significant in view of the important role of SRs in decision-making and the controversies that surround the use of the influenza antiviral drugs. However, the findings should not be interpreted to mean curtailment/cessation of use of antiviral drugs for influenza.

Offloading devices for neuropathic foot ulcers in adult persons with type 1 or type 2 diabetes: a rapid review with meta-analysis and trial sequential analysis of randomized controlled trials.

INTRODUCTION: Healing time for neuropathic planter foot ulcers (NPFUs) in persons with diabetes may be reduced through use of non-removable fiberglass total contact casting (F-TCC) compared with removable cast walkers (RCWs), although the evidence base is still growing. RESEARCH DESIGN AND METHODS: We conducted a rapid review and systematically searched for, and critically assessed, randomized controlled trials (RCTs) that compared the efficacy of F-TCC versus RCW, focusing on the time to ulcer healing in adult persons (18+ years) with NPFUs and type 1 or type 2 diabetes. We meta-analysed the mean differences and associated 95% CIs using an inverse variance, random-effects model. We also conducted a trial sequential analysis (TSA) to assess if the available evidence is up to the required information size for a robust conclusion. We assessed and quantified statistical heterogeneity between the included studies using the I2 statistic. RESULTS: Out of 102 retrieved citations, five RCTs met the eligibility criteria. Participants' inclusion in relation to stage of ulcer was highly variable as was peripheral neuropathy complicating comparisons. F-TCC appeared to present a shorter ulcer healing time (-5.42 days, 95% CI -9.66 days to -1.17 days; I2 9.9%; 5 RCTs; 169 participants) compared with RCW. This finding was supported by the TSA. CONCLUSIONS: There is limited evidence from RCTs to suggest that F-TCC has a shorter ulcer healing time compared with RCW among adults with diabetic NPFUs. Properly designed and conducted RCTs are still required for a stronger evidence base.