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.

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.

SAGES/AHPBA guidelines for the use of microwave and radiofrequency liver ablation for the surgical treatment of hepatocellular carcinoma or colorectal liver metastases less than 5 cm.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the liver's two most common malignant neoplasms. Liver-directed therapies such as ablation have become part of multidisciplinary therapies despite a paucity of data. Therefore, an expert panel was convened to develop evidence-based recommendations regarding the use of microwave ablation (MWA) and radiofrequency ablation (RFA) for HCC or CRLM less than 5 cm in diameter in patients ineligible for other therapies. METHODS: A systematic review was conducted for six key questions (KQ) regarding MWA or RFA for solitary liver tumors in patients deemed poor candidates for first-line therapy. Subject experts used the GRADE methodology to formulate evidence-based recommendations and future research recommendations. RESULTS: The panel addressed six KQs pertaining to MWA vs. RFA outcomes and laparoscopic vs. percutaneous MWA. The available evidence was poor quality and individual studies included both HCC and CRLM. Therefore, the six KQs were condensed into two, recognizing that these were two disparate tumor groups and this grouping was somewhat arbitrary. With this significant limitation, the panel suggested that in appropriately selected patients, either MWA or RFA can be safe and feasible. However, this recommendation must be implemented cautiously when simultaneously considering patients with two disparate tumor biologies. The limited data suggested that laparoscopic MWA of anatomically more difficult tumors has a compensatory higher morbidity profile compared to percutaneous MWA, while achieving similar overall 1-year survival. Thus, either approach can be appropriate depending on patient-specific factors (very low certainty of evidence). CONCLUSION: Given the weak evidence, these guidelines provide modest guidance regarding liver ablative therapies for HCC and CRLM. Liver ablation is just one component of a multimodal approach and its use is currently limited to a highly selected population. The quality of the existing data is very low and therefore limits the strength of the guidelines.

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.

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.

SAGES/AHPBA guidelines for the use of minimally invasive surgery for the surgical treatment of colorectal liver metastases (CRLM).

BACKGROUND: Colorectal liver metastases (CRLM) occur in roughly half of patients with colorectal cancer. Minimally invasive surgery (MIS) has become an increasingly acceptable and utilized technique for resection in these patients, but there is a lack of specific guidelines on the use of MIS hepatectomy in this setting. A multidisciplinary expert panel was convened to develop evidence-based recommendations regarding the decision between MIS and open techniques for the resection of CRLM. METHODS: Systematic review was conducted for two key questions (KQ) regarding the use of MIS versus open surgery for the resection of isolated liver metastases from colon and rectal cancer. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Additionally, the panel developed recommendations for future research. RESULTS: The panel addressed two KQs, which pertained to staged or simultaneous resection of resectable colon or rectal metastases. The panel made conditional recommendations for the use of MIS hepatectomy for both staged and simultaneous resection when deemed safe, feasible, and oncologically effective by the surgeon based on the individual patient characteristics. These recommendations were based on low and very low certainty of evidence. CONCLUSIONS: These evidence-based recommendations should provide guidance regarding surgical decision-making in the treatment of CRLM and highlight the importance of individual considerations of each case. Pursuing the identified research needs may help further refine the evidence and improve future versions of guidelines for the use of MIS techniques in the treatment of CRLM.

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.

Multi-society consensus conference and guideline on the treatment of gastroesophageal reflux disease (GERD).

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD. METHODS: Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/m2) and concomitant GERD. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI > 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss. CONCLUSION: Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.

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.

International air travel-related control measures to contain the Covid-19 pandemic: A companion review to a Cochrane rapid review.

Background: COVID-19 has proven to be challenging to manage for many reasons, including its high infection rate. One of the potential ways to limit its spread is by limiting international travel. The objective of this systematic review was to identify, critically appraise and summarise evidence on international air travel-related control measures for COVID-19. Methods: This review is based on the Cochrane review: International travel-related control measures to contain the COVID-19 pandemic and followed the same methods. In brief, we searched for clinical and modelling studies in general health and COVID-19-specific bibliographic databases. The primary outcome categories were (i) cases avoided, (ii) a shift in epidemic development and, (iii) cases detected. Results: From 6,202 citations identified by the search strategy, we included 22 new studies (modelling = 9, observational = 13) in addition to the 62 studies identified in the Cochrane review. Studies suggest that quarantine or microbial detection or a combination may avoid further cases. Similarly, these interventions may produce a positive shift in epidemic development and case detection may improve. Most studies were evaluated as having a moderate to critical risk of bias. The studies did not change the main conclusions of the Cochrane review nor the quality of the evidence (very low certainty); however, they added to the evidence base for most outcomes. Conclusions: Weak evidence supports the use of international air travel-related control measures to limit the spread of COVID-19 via air travel. More real-world studies are required to support these conclusions.

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.

Minimally invasive versus open hepatectomy for the resection of colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: While surgical resection has a demonstrated utility for patients with colorectal liver metastases (CRLM), it is unclear whether minimally invasive surgery (MIS) or an open approach should be used. This review sought to assess the efficacy and safety of MIS versus open hepatectomy for isolated, resectable CRLM when performed separately from (Key Question (KQ) 1) or simultaneously with (KQ2) the resection of the primary tumor. METHODS: PubMed, Embase, Google Scholar, Cochrane CENTRAL, International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov databases were searched to identify both randomized controlled trials (RCTs) and non-randomized comparative studies published during January 2000-September 2020. Two independent reviewers screened literature for eligibility, extracted data from included studies, and assessed internal validity using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed using risk ratios (RR) and mean differences (MD). RESULTS: From 2304 publications, 35 studies were included for meta-analysis. For staged resections, three RCTs and 20 observational studies were included. Data from RCTs indicated MIS having similar disease-free survival (DFS) at 1-year (RR 1.03, 95%CI 0.70-1.50), overall survival (OS) at 5-years (RR 1.04, 95%CI 0.84-1.28), fewer complications of Clavien-Dindo Grade III (RR 0.62, 95%CI 0.38-1.00), and shorter hospital length of stay (LOS) (MD -6.6 days, 95%CI -10.2, -3.0). For simultaneous resections, 12 observational studies were included. There was no evidence of a difference between MIS and the open group for DFS-1-year, OS-5-year, complications, R0 resections, blood transfusions, along with lower blood loss (MD -177.35 mL, 95%CI -273.17, -81.53) and shorter LOS (MD -3.0 days, 95%CI -3.82, -2.17). CONCLUSIONS: Current evidence regarding the optimal approach for CRLM resection demonstrates similar oncologic outcomes between MIS and open techniques, however MIS hepatectomy had a shorter LOS, lower blood loss and complication rate, for both staged and simultaneous resections.

Correlation between country-level numbers of COVID-19 cases and mortalities, and country-level characteristics: A global study.

Background: Not much is known about correlations between country-level characteristics and country-level numbers of COVID-19 cases and mortalities. Methods: Using data from the World Health Organization and other international organisations, we summarised country-level COVID-19 case and mortality counts per 100,000 population, and COVID-19 case fatality rate from January 2020 to August 2021. We conducted adjusted linear regression analysis to assess relationships between these counts/rate and certain country-level characteristics. We reported adjusted regression coefficients, ß and associated 95% confidence intervals. Results: There was a positive correlation between the number of cases and country-level male/female ratio, and positive correlations between the numbers of cases and mortalities and country-level proportion of 60+-year-olds, universal health coverage index of service coverage (UHC) and tourism. Country economic status correlated negatively with the numbers of cases and mortalities. COVID-19 case fatality rate was highest in Peru, South American region (9.2%), and lowest in Singapore, Western Pacific region (0.1%). A negative correlation was observed between case fatality rate and country-level male/female ratio, population density and economic status. These observations remained mostly among mid-/low-income countries, particularly a positive correlation between the number of cases and male/female ratio and proportion of 60+-year-olds. Conclusions: Various country-level characteristics such as male/female ratio, proportion of older adults, country economic status, UHC and tourism appear to be correlated with the country-level number of COVID-19 cases and/or mortalities. Consideration of these characteristics may be necessary when designing country-level COVID-19 epidemiological studies and in comparing COVID-19 data between countries.

Comparison of Power Training vs Traditional Strength Training on Physical Function in Older Adults: A Systematic Review and Meta-analysis.

Importance: Strength training exercise is recommended for improving physical function in older adults. However, whether strength training (lifting and lowering weights under control) and power training (PT) (lifting weights fast and lowering under control) are associated with improved physical function in older adults is not clear. Objective: To evaluate whether PT vs traditional strength training is associated with physical function improvement in older adults. Data Sources: Systematic searches of MEDLINE, Embase, Cochrane Central, CINAHL, PsycInfo, PEDro, and SPORTDiscus were conducted from database inception to October 20, 2021. Study Selection: Randomized clinical trials (RCTs) that compared strength training with instructions to move the weight as fast as possible in the lifting phase with traditional strength training in healthy, community-living older adults (age ≥60 years). Data Extraction and Synthesis: Two authors independently selected trials, extracted data, assessed the risk of bias using the Cochrane risk-of-bias tool 2, and assessed the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach. Summary effect size measures were calculated using a multilevel random-effects model with cluster robust variance estimation and are reported as standardized mean differences (SMDs). Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Main Outcomes and Measures: Primary outcomes included physical function and self-reported physical function. Secondary outcomes included power, strength, muscle mass, walk speed, balance, and adverse effects. Results: A total of 20 RCTs enrolling 566 community-living older adults (mean [SD] age, 70.1 [4.8] years; 368 [65%] women) were included. For the primary outcomes, PT was associated with an improvement in physical function with low-certainty evidence in 13 RCTs (n = 383) (SMD, 0.30; 95% CI, 0.05-0.54) and self-reported function with low-certainty evidence in 3 RCTs (n = 85) (SMD, 0.38; 95% CI, -0.62 to 1.37). The evidence was downgraded by 2 levels for high risk of bias and imprecision for physical function and very serious imprecision for self-reported physical function. Conclusions and Relevance: In this systematic review and meta-analysis, PT was associated with a modest improvement in physical function compared with traditional strength training in healthy, community-living older adults. However, high-quality, larger RCTs are required to draw more definitive conclusions.

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.

Impact of employing primary healthcare professionals in emergency department triage on patient flow outcomes: a systematic review and meta-analysis.

OBJECTIVES: To identify, critically appraise and summarise evidence on the impact of employing primary healthcare professionals (PHCPs: family physicians/general practitioners (GPs), nurse practitioners (NP) and nurses with increased authority) in the emergency department (ED) triage, on patient flow outcomes. METHODS: We searched Medline (Ovid), EMBASE (Ovid), Cochrane Library (Wiley) and CINAHL (EBSCO) (inception to January 2020). Our primary outcome was the time to provider initial assessment (PIA). Secondary outcomes included time to triage, proportion of patients leaving without being seen (LWBS), length of stay (ED LOS), proportion of patients leaving against medical advice (LAMA), number of repeat ED visits and patient satisfaction. Two independent reviewers selected studies, extracted data and assessed study quality using the National Institute for Health and Care Excellence quality assessment tool. RESULTS: From 23 973 records, 40 comparative studies including 10 randomised controlled trials (RCTs) and 13 pre-post studies were included. PHCP interventions were led by NP (n=14), GP (n=3) or nurses with increased authority (n=23) at triage. In all studies, PHCP-led intervention effectiveness was compared with the traditional nurse-led triage model. Median duration of the interventions was 6 months. Study quality was generally low (confounding bias); 7 RCTs were classified as moderate quality. Most studies reported that PHCP-led triage interventions decreased the PIA (13/14), ED LOS (29/30), proportion of patients LWBS (8/10), time to triage (3/3) and repeat ED visits (5/6), and increased the patient satisfaction (8/10). The proportion of patients LAMA did not differ between groups (3/3). Evidence from RCTs (n=8) as well as other study designs showed a significant decrease in ED LOS favouring the PHCP-led interventions. CONCLUSIONS: Overall, PHCP-led triage interventions improved ED patient flow metrics. There was a significant decrease in ED LOS irrespective of the study design, favouring the PHCP-led interventions. Evidence from well-designed high-quality RCTs is required prior to widespread implementation. PROSPERO REGISTRATION NUMBER: CRD42020148053.

Antiviral drugs for coronavirus disease 2019 (COVID-19): a systematic review with network meta-analysis.

BACKGROUND: To better inform clinical practice, we summarized the findings from randomized controlled trials (RCTs) of antivirals for COVID-19. METHODS: We systematically searched for literature up to September 2020, and included English-language publications of RCTs among hospitalized COVID-19 patients. We conducted network meta-analysis combining results of both the direct and indirect comparisons of interventions. The efficacy outcomes were clinical progression, all-cause mortality, and viral clearance, and safety outcomes were diarrhea, nausea, and vomiting. We generated treatment rankings (best to worst) and summarized rank probabilities using rankogram. RESULTS: We included 15 RCTs (14,418 patients) from 7,237 retrieved citations. There was no evidence for efficacy of the assessed antivirals compared with placebo/no treatment or with another antiviral for all efficacy outcomes. Lopinavir (400 mg)/ritonavir (100 mg) significantly increased diarrhea, nausea, and vomiting compared with placebo/no treatment and other antivirals, and was ranked worst for these outcomes, while triazavirin (250 mg), baloxavir marboxil (80 mg), and remdesivir (100 mg - 10 days) ranked best, respectively. CONCLUSIONS AND RELEVANCE: The available evidence does not support the use of any antiviral drugs for COVID-19. Cautious interpretations of the findings are, however, advised considering the paucity of the evidence. More RCTs are needed for a stronger evidence base.

The Number Needed to Vaccinate (NNV) against herpes zoster: a systematic review with meta-analysis.

OBJECTIVES: The number needed to vaccinate (NNV) quantifies the effectiveness of vaccination programs. We summarised the published data on NNV against herpes zoster to inform vaccination policies. METHODS: We systematically identified studies based on a priori established and registered methods. The main outcomes were the NNV against herpes zoster infection, hospitalisation and mortality. Where appropriate, we conducted meta-analyses using inverse variance, random-effects models, pooling estimated NNV with associated 95% confidence interval (CI). Statistical heterogeneity between pooled estimates was calculated using the I2 statistic. RESULTS: Out of 229 unique citations, we included eight nonrandomized studies. Among 50+ year-olds, the NNV against herpes zoster infection using the recombinant subunit vaccine was 11 (95%CI 8-14; I2 = 0%; 3 studies) and variable (I2 = 94.4%; 7 studies) using live attenuated vaccine, ranging from 10 (95%CI 1-19) to 58 (95%CI 49-67). Among 65+ year-olds, the NNV against herpes zoster infection using the recombinant subunit vaccine was 12 (95%CI: 9-15; I2 = 0%; 2 studies) and variable (I2 = 98.5%; 4 studies) using live attenuated vaccine, ranging from 14 (95%CI 5-23) to 75 (95%CI 66-84). The NNV against herpes zoster hospitalisation among 65+ year-olds using the live attenuated vaccine was 280 (95%CI 209-352; I2 = 0%; 2 studies). There was a paucity of data to inform other meta-analyses. CONCLUSION: Evidence on the NNV against herpes zoster is scarce. Vaccination with the recombinant subunit herpes zoster vaccine may be more effective than with the live attenuated vaccine in preventing infection among 50+ year-olds. More studies are needed for a stronger evidence base for decision-making.

Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis.

The effectiveness of T cell-mediated rejection (TCMR) therapy for achieving histological remission remains undefined in patients on modern immunosuppression. We systematically identified, critically appraised, and summarized the incidence and histological outcomes after TCMR treatment in patients on tacrolimus (Tac) and mycophenolic acid (MPA). English-language publications were searched in MEDLINE (Ovid), Embase (Ovid), Cochrane Central (Ovid), CINAHL (EBSCO), and Clinicaltrials.gov (NLM) up to January 2021. Study quality was assessed with the National Institutes of Health Study Quality Tool. We pooled results using an inverse variance, random-effects model and report the binomial proportions with associated 95% confidence intervals (95% CI). Statistical heterogeneity was explored using the I2  statistic. From 2875 screened citations, we included 12 studies (1255 participants). Fifty-eight percent were good/high quality while the rest were moderate quality. Thirty-nine percent of patients (95% CI 0.26-0.53, I2 77%) had persistent ≥Banff Borderline TCMR 2-9 months after anti-rejection therapy. Pulse steroids and augmented maintenance immunosuppression were mainstays of therapy, but considerable practice heterogeneity was present. A high proportion of biopsy-proven rejection exists after treatment emphasizing the importance of histology to characterize remission. Anti-rejection therapy is foundational to transplant management but well-designed clinical trials in patients on Tac/MPA immunosuppression are lacking to define the optimal therapeutic approach.

Interventions to improve early cancer diagnosis of symptomatic individuals: a scoping review.

OBJECTIVES: To summarise the current evidence regarding interventions for accurate and timely cancer diagnosis among symptomatic individuals. DESIGN: A scoping review following the Joanna Briggs Institute's methodological framework for the conduct of scoping reviews and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. DATA SOURCES: MEDLINE (Ovid), CINAHL (EBSCOhost) and PsycINFO (Ovid) bibliographic databases, and websites of relevant organisations. Published and unpublished literature (grey literature) of any study type in the English language were searched for from January 2017 to January 2021. ELIGIBILITY AND CRITERIA: Study participants were individuals of any age presenting at clinics with symptoms indicative of cancer. Interventions included practice guidelines, care pathways or other initiatives focused on achieving predefined benchmarks or targets for wait times, streamlined or rapid cancer diagnostic services, multidisciplinary teams and patient navigation strategies. Outcomes included accuracy and timeliness of cancer diagnosis. DATA EXTRACTION AND SYNTHESIS: We summarised findings graphically and descriptively. RESULTS: From 21 298 retrieved citations, 88 unique published articles and 16 unique unpublished documents (on 18 study reports), met the eligibility for inclusion. About half of the published literature and 83% of the unpublished literature were from the UK. Most of the studies were on interventions in patients with lung cancer. Rapid referral pathways and technology for supporting and streamlining the cancer diagnosis process were the most studied interventions. Interventions were mostly complex and organisation-specific. Common themes among the studies that concluded intervention was effective were multidisciplinary collaboration and the use of a nurse navigator. CONCLUSIONS: Multidisciplinary cooperation and involvement of a nurse navigator may be unique features to consider when designing, delivering and evaluating interventions focused on improving accurate and timely cancer diagnosis among symptomatic individuals. Future research should examine the effectiveness of the interventions identified through this review.