AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS: This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.

Vegetarian diets on anthropometric, metabolic and blood pressure outcomes in people with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: It is unknown whether vegetarian diets (VDs) may improve outcomes in people with overweight and obesity. OBJECTIVE: To systematically assess the effects of VDs vs. omnivore diets on anthropometric, metabolic, and blood pressure outcomes in people with overweight and obesity. METHODS: We searched for randomized controlled trials (RCTs) in EMBASE, PubMed, Web of Science, and Scopus until February 2, 2022. Primary outcomes were anthropometric risk factors (weight, body mass index [BMI], waist circumference [WC], hip circumference [HC], and body fat percentage). Secondary outcomes were metabolic risk factors (fasting serum glucose, HbA1c, insulin levels) and blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP]). Random-effects meta-analyses were performed and effects were expressed as mean difference (MD) and their 95% confidence intervals (CI). The quality of evidence was assessed using GRADE methods. RESULTS: Nine RCTs (n = 1628) were included. VDs decreased weight (MD -3.60 kg, 95%CI -4.75 to -2.46) and glucose (MD -10.64 mg/dL, 95%CI -15.77 to -5.51), but did not decrease WC (MD -3.00 cm, 95%CI -6.20 to 0.20), BMI (MD -0.87 kg/m2, 95%CI -1.80 to 0.06), or HC (MD: -0.86 cm, 95%CI -3.46 to 1.74). VDs did not decrease HbA1c (MD -0.40%, 95%CI -0.89 to 0.10), insulin (MD -3.83 mU/L, 95%CI -8.06 to 0.40), SBP (MD -0.25 mmHg, 95%CI -2.58 to 2.07), or DBP (MD -1.57 mmHg, 95%CI -3.93 to 0.78). Subgroup analyses by type of VD (four RCTs evaluated lacto-ovo-vegetarian diets and five RCTs vegan diets) showed similar results to the main analyses. QoE was very low for most of the outcomes. CONCLUSIONS: In comparison to an omnivorous diet, VDs may reduce weight and glucose, but not blood pressure or other metabolic or anthropometric outcomes. However, the QoE was mostly very low. Larger RCTs are still needed to evaluate the effects of VD on anthropometric, metabolic factors, and blood pressure in people with overweight and obesity.

Utility of YouTube online learning for junior gastrointestinal endoscopists: A rewarding or deterring practice?

Endoscopy is a competitive field in clinical practice, in which skilled endoscopists are in high demand. The learning process for Junior Gastrointestinal Endoscopists (JGEs) is difficult, quite long, and technically demanding. This directs JGEs to seek additive learning sources, including online sources. The purpose of this study was to determine the frequency, context, attitudes, perceived benefits, drawbacks, and recommendations for using YouTube videos as an educational platform among JGEs from the uses'prespective. We disseminated a cross-sectional online questionnaire from January 15th to March 17th, 2022, and recruited 166 JGE from 39 different countries. The majority of surveyed JGEs (138, 85.2%) were already using YouTube as a learning tool. The majority of JGEs (97, 59.8%) reported gaining knowledge and applying it in their clinical practice, but 56 (34.6 %) reported gaining knowledge without application in real practice. Most participants (124, 76.5 %) reported missing procedure details in YouTube endoscopy videos. The majority of JGEs (110, 80.9%) reported that YouTube videos are provided by endoscopy specialists. Only one participant, 0.6% out of the 166 JGEs surveyed, disliked video records, including YouTube as a source of learning. Based on their experience, 106 (65.4%) of participants recommended YouTube as an educational tool for the coming generation of JGEs. We consider that YouTube represents a potentially useful tool for JGEs, supplying them with both knowledge and clinical practice tricks. However, many drawbacks could make the experience misleading and time-consuming. Consequently, we encourage educational providers on YouTube and other platforms to upload well-constructed, peerreviewed, interactive educational endoscopy videos.

Effects of Probiotics on Intermediate Cardiovascular Outcomes in Patients with Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Clinical trials evaluating the effect of probiotics on cardiovascular intermediate outcomes have been scarce in recent years. We systematically evaluated the efficacy of probiotics on intermediate cardiovascular outcomes in patients with overweight or obesity. METHODS: We searched for randomized controlled trials (RCTs) in four databases (until August 2021) that evaluated the effects of probiotics versus controls on intermediate cardiovascular outcomes. The outcomes were body mass index (BMI), weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Inverse variance random effects meta-analyses were used. The effects were reported as mean difference (MD), with their 95% confidence intervals (95% CI). The quality of evidence (QoE) was assessed with GRADE (grading of recommendations, assessment, development and evaluations) methodology. RESULTS: A total of 25 RCTs were included (n = 2170), with a range of follow-up from two to six months. Probiotics likely reduced BMI (MD -0.27 kg/m2, 95%CI: -0.35 to -0.19; 17 RCTs; I2 = 26%, QoE: moderate), as well as likely reduced weight (MD -0.61 kg, 95%CI: -0.89 to -0.34; 15 RCTs; I2 = 0%, QoE: moderate), and may have slightly reduce LDL (MD -4.08 mg/dL; 95%CI: -6.99 to -1.17; 9 RCTs; I2 = 87%, QoE: low) in comparison to the controls. However, probiotics had no effect on SBP (MD -0.40 mmHg; 95%CI: -5.04 to 4.25; 7 RCTs; I2 = 100%, QoE: very low), DBP (MD -1.73 mmHg; 95%CI: -5.29 to 1.82; 5 RCTs; I2 = 98%, QoE: very low), glucose (MD -0.07 mg/dL; 95%CI -0.89 to 0.75; I2 = 96%, QoE: very low), HDL (MD -1.83 mg/dL; 95%CI: -4.14 to 2.47; 14 RCTs; I2 = 98%, QoE: very low), or triglycerides (MD -3.29 mg/dL, 95%CI -17.03 to 10.45; 14 RCTs, I2 = 95%, QoE: very low) compared to control arms, and the evidence was very uncertain. CONCLUSIONS: In obese or overweight patients, BMI, weight, and LDL were lower in patients who received probiotics compared to those who received controls. Other lipids, glucose, and blood pressure were not affected by the probiotics.

Short-term outcomes of endoscopic submucosal dissection for the treatment of superficial gastric neoplasms in non-Asian countries: a systematic review and meta-analysis.

Background: Endoscopic submucosal dissection (ESD) is now considered the standard treatment for early gastric cancer (EGC). However, the widespread adoption of ESD in western countries has been slow. We performed a systematic review to evaluate short-term outcomes of ESD for EGC in non-Asian countries. Methods: We searched 3 electronic databases from inception until October 26, 2022. Primary outcomes were en bloc, R0 and curative resections rate by region. Secondary outcomes were overall complications, bleeding, and perforation rate by region. The proportion of each outcome, with the 95% confidence interval (CI), was pooled using a random-effects model with the Freeman-Tukey double arcsine transformation. Results: Twenty-seven studies from Europe (n=14), South America (n=11) and North America (n=2) were included, involving 1875 gastric lesions. Overall, en bloc, R0, and curative resection rates were achieved in 96% (95%CI 94-98%), 85% (95%CI 81-89%), and 77% (95%CI 73-81%) of cases, respectively. Considering only information from lesions with adenocarcinoma, the overall curative resection was 75% (95CI 70-80%). Bleeding and perforation were observed in 5% (95%CI 4-7%) and 2% (95%CI 1-4%) of cases, respectively. Conclusion: Our results suggest that short-term outcomes of ESD for the treatment of EGC are acceptable in non-Asian countries.

Helicobacter pylori World Gastroenterology Organization Global Guideline.

Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.

Utility of YouTube online learning for junior gastrointestinal endoscopists: A rewarding or deterring practice?

Endoscopy is a competitive field in clinical practice, in which skilled endoscopists are in high demand. The learning process for Junior Gastrointestinal Endoscopists (JGEs) is difficult, quite long, and technically demanding. This directs JGEs to seek additive learning sources, including online sources. The purpose of this study was to determine the frequency, context, attitudes, perceived benefits, drawbacks, and recommendations for using YouTube videos as an educational platform among JGEs from the uses'prespective. We disseminated a cross-sectional online questionnaire from January 15th to March 17th, 2022, and recruited 166 JGE from 39 different countries. The majority of surveyed JGEs (138, 85.2%) were already using YouTube as a learning tool. The majority of JGEs (97, 59.8%) reported gaining knowledge and applying it in their clinical practice, but 56 (34.6 %) reported gaining knowledge without application in real practice. Most participants (124, 76.5 %) reported missing procedure details in YouTube endoscopy videos. The majority of JGEs (110, 80.9%) reported that YouTube videos are provided by endoscopy specialists. Only one participant, 0.6% out of the 166 JGEs surveyed, disliked video records, including YouTube as a source of learning. Based on their experience, 106 (65.4%) of participants recommended YouTube as an educational tool for the coming generation of JGEs. We consider that YouTube represents a potentially useful tool for JGEs, supplying them with both knowledge and clinical practice tricks. However, many drawbacks could make the experience misleading and time-consuming. Consequently, we encourage educational providers on YouTube and other platforms to upload well-constructed, peer-reviewed, interactive educational endoscopy videos.

Antecedentes : La endoscopia es un campo competitivo en la práctica clínica en el que los endoscopistas calificados tienen una gran demanda. El proceso de aprendizaje para los endoscopistas gastrointestinales junior (JE) es difícil, bastante largo y técnicamente exigente. Esto dirige a los JE a buscar fuentes de aprendizaje adicionales, incluidas las fuentes en línea. El propósito de este estudio fue determinar la frecuencia, el contexto, las actitudes, los beneficios percibidos, los inconvenientes y las recomendaciones para el uso de videos de YouTube como una plataforma educativa entre los JE desde la perspectiva de los usuarios. Métodos: Se aplicó un cuestionario transversal en línea difundido del 15 de enero al 17 de marzo de 2022 reclutó a 166 endoscopistas gastrointestinales junior de 39 países diferentes. Resultados : La mayoría de los JE encuestados (138, 85,2%) ya utilizaban YouTube como herramienta de aprendizaje. La mayoría de los JE (97, 59,8 %) refirieron adquirir conocimientos y aplicarlos en su práctica clínica, pero 56 (34,6 %) informaron adquirir conocimientos sin aplicación en la práctica real. La mayoría de los participantes (124, 76,5 %) informó que faltaban detalles del procedimiento en los videos de endoscopia de YouTube. La mayoría de los JE (110, 80,9%) informaron que los videos de YouTube son proporcionados por especialistas en endoscopia. Solo a un participante, el 0,6% de los 166 JE encuestados, le disgustaron los registros de video, incluyendo a YouTube como fuente de aprendizaje. Según su experiencia, 106 (65,4 %) de los participantes recomendaron YouTube como una herramienta educativa para la próxima generación de JE. Conclusión: YouTube representa una herramienta potencialmente útil para los EJ, brindándoles tanto conocimientos como trucos para la práctica clínica. Sin embargo, muchos inconvenientes podrían hacer que la experiencia sea engañosa y consuma mucho tiempo. En consecuencia, alentamos a los proveedores de educación en YouTube y otras plataformas a subir videos de endoscopia educativos interactivos, bien construidos y revisados por pares.

Endoscopic submucosal dissection versus surgery for patients with undifferentiated early gastric cancer.

BACKGROUND AND AIMS: endoscopic submucosal dissection (ESD) is the standard treatment for differentiated early gastric cancer (EGC). However, its expanded indication for undifferentiated EGC is controversial. In this study, the efficacy and safety of ESD versus surgery in patients with undifferentiated EGC were compared. METHODS: four databases were searched until February 24, 2022, for studies assessing patients with undifferentiated EGC that met an expanded indication for endoscopic resection and who were treated with ESD or surgery. Primary outcomes were all-cause mortality and any recurrence. Secondary outcomes were complete histological resection, local recurrence, metachronous recurrence, synchronous recurrence, distant metastasis, overall complication, and bleeding. All meta-analyses were performed using a random-effects models. Unadjusted (risk ratio [RR]) and adjusted (aRR and hazard ratio [aHR]) estimates with 95 % confidence interval (CI) were calculated. RESULTS: seven cohort studies were included (n = 2637). The use of ESD was significantly associated with higher all-cause mortality compared to surgery (RR, 2.17; 95 % CI, 1.24-3.81); adjusted all-cause mortality effects were not significant (aRR, 2.28; 95 % CI, 0.95-5.47 and aHR, 1.97; 95 % CI, 0.85-4.53). ESD was associated with a higher risk of any recurrence using unadjusted (RR, 5.24; 95 % CI, 1.49-18.46) and adjusted (aRR, 7.89; 95 % CI, 1.52-40.95 and aHR, 3.73; 95 % CI, 1.17-11.90) estimates. The risk of local recurrence, synchronous recurrence and bleeding were significantly higher for ESD versus surgery. No significant differences were found for other secondary outcomes. CONCLUSIONS: although ESD is associated with a higher risk of any recurrence, adjusted all-cause mortality is similar during follow-up. Overall complications were similar between ESD and surgery.

Endoscopic submucosal dissection versus surgery for patients with undifferentiated early gastric cancer

Background and aims: endoscopic submucosal dissection (ESD) is the standard treatment for differentiated early gastric cancer (EGC). However, its expanded indication for undifferentiated EGC is controversial. In this study, the efficacy and safety of ESD versus surgery in patients with undifferentiated EGC were compared. Methods: four databases were searched until February 24, 2022, for studies assessing patients with undifferentiated EGC that met an expanded indication for endoscopic resection and who were treated with ESD or surgery. Primary outcomes were all-cause mortality and any recurrence. Secondary outcomes were complete histological resection, local recurrence, metachronous recurrence, synchronous recurrence, distant metastasis, overall complication, and bleeding. All meta-analyses were performed using a random-effects models. Unadjusted (risk ratio [RR]) and adjusted (aRR and hazard ratio [aHR]) estimates with 95 % confidence interval (CI) were calculated. Results: seven cohort studies were included (n = 2637). The use of ESD was significantly associated with higher all-cause mortality compared to surgery (RR, 2.17; 95 % CI, 1.24-3.81); adjusted all-cause mortality effects were not significant (aRR, 2.28; 95 % CI, 0.95-5.47 and aHR, 1.97; 95 % CI, 0.85-4.53). ESD was associated with a higher risk of any recurrence using unadjusted (RR, 5.24; 95 % CI, 1.49-18.46) and adjusted (aRR, 7.89; 95 % CI, 1.52-40.95 and aHR, 3.73; 95 % CI, 1.17-11.90) estimates. The risk of local recurrence, synchronous recurrence and bleeding were significantly higher for ESD versus surgery. No significant differences were found for other secondary outcomes. Conclusions: although ESD is associated with a higher risk of any recurrence, adjusted all-cause mortality is similar during follow-up. Overall complications were similar between ESD and surgery (AU)

Effect of COVID-19 on gastrointestinal endoscopy practice: a systematic review.

BACKGROUND: Since the emergence of the novel corona virus (SARS-Cov-2) in the late 2019 and not only the endoscopy practice and training but also the health care systems around the globe suffers. This systematic review focused the impact of Corona Virus Disease (COVID-19) on the endoscopy practice. METHODS: A web search of different databases combining different search terms describing the endoscopy practice and the COVID-19 pandemic was done. Articles were screened for selection of relevant articles in two steps: title and abstract step and full-text screening step, by two independent reviewers and any debate was solved by a third reviewer. RESULTS: Final studies included in qualitative synthesis were 47. The data shown in the relevant articles were evident for marked reduction in the volume of endoscopy, marked affection of colorectal cancer screening, impairments in the workflow, deficiency in personal protective equipment (PPE) and increased likelihood of catching the infection among both the staff and the patients. CONCLUSION: The main outcomes from this review are rescheduling of endoscopy procedures to be suitable with the situation of COVID-19 pandemic in each Country. Also, the endorsement of the importance of PPE use for health care workers and screening of COVID-19 infection pre-procedure.Key messagesThe data focussing Gastrointestinal Endoscopy and COVID-19 emerged from different areas around the globe. The data presented on the published studies were heterogeneous. However, there were remarkable reductions in the volume of GI endoscopy worldwideStaff reallocation added a burden to endoscopy practiceThere was a real risk for COVID-19 spread among both the staff and the patients.

Efficacy of early treatment with hydroxychloroquine in people with mild to moderate COVID-19: a systematic review and meta-analysis.

Introduction: No early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19. Material and methods: Randomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods. Results: Five RCTs (n = 1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow-up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR = 0.80, 95% CI: 0.47-1.36, I 2 = 2%, 5 RCTs, low QoE), all-cause mortality (RR = 0.77, 95% CI: 0.16-3.68, I 2 = 0%, 5 RCTs, very low QoE), symptom resolution (RR = 0.94, 95% CI: 0.77-1.16, I 2 = 71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR = 1.02, 95% CI: 0.82-1.27, I 2 = 65%, 2 RCTs, low QoE). There was a larger non-significant increase of adverse events with hydroxychloroquine vs. controls (RR = 2.17, 95% CI: 0.86-5.45, I 2 = 92%, 5 RCTs, very low QoE). Conclusions: Hydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.

Beneficial and Harmful Effects of Monoclonal Antibodies for the Treatment and Prophylaxis of COVID-19: Systematic Review and Meta-Analysis.

BACKGROUND: We systematically assessed beneficial and harmful effects of monoclonal antibodies for coronavirus disease 2019 (COVID-19) treatment, and prophylaxis in individuals exposed to severe acute respiratory syndrome coronavirus 2. METHODS: We searched 5 engines and 3 registries until November 3, 2021 for randomized controlled trials evaluating monoclonal antibodies vs control in hospitalized or non-hospitalized adults with COVID-19, or as prophylaxis. Primary outcomes were all-cause mortality, COVID-19-related death, and serious adverse events; hospitalization for non-hospitalized; and development of symptomatic COVID-19 for prophylaxis. Inverse variance random effects models were used for meta-analyses. Grading of Recommendations, Assessment, Development, and Evaluations methodology was used to assess certainty of evidence. RESULTS: Twenty-seven randomized controlled trials were included: 20 in hospitalized patients (n = 8253), 5 in non-hospitalized patients (n = 2922), and 2 in prophylaxis (n = 2680). In hospitalized patients, monoclonal antibodies slightly reduced mechanical ventilation (relative risk [RR] 0.74; 95% confidence interval [CI], 0.60-0.9; I2 = 20%, low certainty of evidence) and bacteremia (RR 0.77; 95% CI, 0.64-0.92; I2 = 7%, low certainty of evidence); evidence was very uncertain about the effect on adverse events (RR 1.31; 95% CI, 1.02-1.67; I2 = 77%, very low certainty of evidence). In non-hospitalized patients, monoclonal antibodies reduced hospitalizations (RR 0.30; 95% CI, 0.17-0.53; I2 = 0%, high certainty of evidence) and may slightly reduce serious adverse events (RR 0.47; 95% CI, 0.22-1.01; I2 = 33%, low certainty of evidence). In prophylaxis studies, monoclonal antibodies probably reduced viral load slightly (mean difference -0.8 log10; 95% CI, -1.21 to -0.39, moderate certainty of evidence). There were no effects on other outcomes. CONCLUSIONS: Monoclonal antibodies had limited effects on most of the outcomes in COVID-19 patients, and when used as prophylaxis. Additional data are needed to determine their efficacy and safety.

Efficacy and harms of tocilizumab for the treatment of COVID-19 patients: A systematic review and meta-analysis.

INTRODUCTION: We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. METHODS: Five electronic databases and two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. RESULTS: Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81-0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44-1.02, p = 0.08; very low QoE) vs. control (standard of care [SOC] or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71-0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts. CONCLUSIONS: In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.

Ivermectin for the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: We systematically assessed benefits and harms of the use of ivermectin (IVM) in patients with coronavirus disease 2019 (COVID-19). METHODS: Published and preprint randomized controlled trials (RCTs) assessing the effects of IVM on adult patients with COVID-19 were searched until 22 March 2021 in 5 engines. Primary outcomes were all-cause mortality rate, length of hospital stay (LOS), and adverse events (AEs). Secondary outcomes included viral clearance and severe AEs (SAEs). The risk of bias (RoB) was evaluated using the Cochrane Risk of Bias 2.0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. RESULTS: Ten RCTs (n = 1173) were included. The controls were the standard of care in 5 RCTs and placebo in 5. COVID-19 disease severity was mild in 8 RCTs, moderate in 1, and mild and moderate in 1. IVM did not reduce all-cause mortality rates compared with controls (relative risk [RR], 0.37 [95% confidence interval, .12-1.13]; very low QoE) or LOS compared with controls (mean difference, 0.72 days [95% confidence interval, -.86 to 2.29 days]; very low QoE). AEs, SAEs, and viral clearance were similar between IVM and control groups (low QoE for all outcomes). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality rates in 3 RCTs at high RoB were reduced with IVM. CONCLUSIONS: Compared with the standard of care or placebo, IVM did not reduce all-cause mortality, LOS, or viral clearance in RCTs in patients with mostly mild COVID-19. IVM did not have an effect on AEs or SAEs and is not a viable option to treat patients with COVID-19.