The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Effectiveness and safety of stag beetle knife (SB knife) in management of Zenker's diverticulum: a systematic review and meta-analysis

: Stag Beetle Knife (SB Knife) is increasingly being utilized for Zenker's Diverticulectomy (ZD). Our study assessed the effectiveness and safety of the SB Knife for the management of ZD. Ovid EBM reviews, Ovid Embase, Ovid Medline, ClinicalTrials.gov, Scopus, and Web of Science were searched to identify studies that utilized SB knife for ZD. Pooled proportions (PP) were calculated using the random-effects model. Heterogeneity was evaluated using I2 statistics. A total of 7 studies with 268 patients were included in the final analysis. Dysphagia and regurgitation were the most common clinical symptoms. The mean size of the ZD was 2.8 ± 0.7 cm and 28 (of 148) patients had undergone previous treatments. The PP of technical success was 98% (95% CI: 92.3-99.5; I20) with a mean procedure duration of 26.2 ± 8.3 minutes. The PP of clinical response at first follow-up and relapse after index procedure was 87.9% (95% CI: 81.6-92.3; I219) and 13.5% (95% CI: 9.6-18.6; I22), respectively. At final follow-up, the PP of clinical remission was 96.2% (95% CI: 91-98.4; I230.6) while the PP of procedure failure was 3.6% (95% CI: 1.6-8.1; I20). No severe adverse events (AEs) were noted while using the SB Knife. However, the PP of intraprocedural and postprocedural AEs was 13.2% (95% CI: 9.6-17.8; I20) and 9.3% (95% CI: 5.7-14.9; I2 < 20.9), respectively. SB Knife is highly safe and effective for Zenker's Diverticulectomy with a failure rate of only 3.6%

Endoscopic Balloon Dilatation of Ileal Pouch-Anal Anastomosis Strictures in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Background: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for medically refractory inflammatory bowel disease (IBD). In this systematic review and meta-analysis, we assess outcomes and safety of endoscopic balloon dilatation (EBD) for IPAA strictures. Methods: A systematic search of numerous databases was performed through June 2023 to identify studies reporting on the outcomes of EBD in pouch-related strictures. Outcomes included technical success, clinical success at index dilation and in pouch retention, recurrence of symptoms post-EBD, and adverse events of EBD. Meta-analysis was performed using a random-effects model, and results were expressed in terms of pooled rates along with relevant 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran Q statistical test with I2 statistics. Results: Seven studies with 504 patients were included. The pooled rate of technical success and clinical success of index dilatation was 98.9% (95% CI, 94.8-99.8%; I20%) and 30.2% (95% CI, 7.1-71%; I20%), respectively. The pooled rate of clinical success in pouch retention without the need for additional surgery was 81.4% (95% CI, 69.6-89.3%; I272%). The pooled failure rate of EBD was 18.6% (95% CI, 10.7-30.4%, I272%). The pooled rate of recurrence of symptoms after index dilatation was 58.9% (95% CI, 33.3-80.5%; I213%). The pooled rate of serious adverse events was 1.8% (95% CI, 1-3.5%, I20%). No deaths related to EBD were reported. Conclusions: Endoscopic balloon dilatation is safe and highly effective for management of IPAA strictures. Additional studies are needed to compare its efficacy with surgical interventions

Colonoscopy related adverse events in patients with abnormal stool-based tests - A systematic review of literature and meta-analysis of outcomes

Introduction: Colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) and guaiac-based fecal occult blood (gFOBT) are associated with a substantial reduction in CRC incidence and mortality. We conducted a systematic review and comprehensive meta-analysis to evaluate colonoscopy related adverse events in individuals with a positive FIT or gFOBT. Methods: A systematic and detailed search was run in January 2021 with the assistance of a medical librarian for studies reporting on colonoscopy related adverse events as part of organized colorectal cancer screening programs. Meta-analysis was performed using random-effects model and results were expressed in terms of pooled proportions along with relevant 95% confidence intervals (CI). Results: A total of 771,730 colonoscopies were performed in patients undergoing CRC screening using either gFOBT or FIT across 31 studies. Overall pooled incidence of severe adverse events in the entire patient cohort was 0.42% (CI 0.20-0.64); I2=38.76%. In patients with abnormal gFOBT, the incidence was 0.2% (CI 0.1-0.3); I2=24.6% and in patients with a positive FIT, it was 0.4% (CI 0.2-0.7); I2=48.89%. The overall pooled incidence of perforation, bleeding and death was 0.13% (CI 0.09-0.21); I2=22.84%, 0.3% (CI 0.2-0.4); I2=35.58% and 0.01% (CI 0.00-0.01); I2=33.21%, respectively. Discussion: Our analysis shows that in colonoscopies performed following abnormal stool-based testing, the overall risk of severe adverse events, perforation, bleeding, and death is minimal

Pooled Rates of Adenoma Detection by Colonoscopy in Asymptomatic Average Risk Individuals with Positive Fecal Immunochemical Test: A Systematic Review and Meta-Analysis

Background & aims: Current adenoma detection rate (ADR) benchmarks for colonoscopy in individuals positive for a fecal immunochemical test (FIT), are ≥45% in males and ≥35% in females. These are based on weak, low-quality evidence. We performed a meta-analysis to ascertain the pooled ADR in FIT-positive colonoscopy. Methods: Major databases like PubMed, EMBASE and Web-of-Science were searched in Oct-2021 for studies reporting on ADR of colonoscopy in FIT-positive population. Meta-analysis was performed by standard methodology using the random-effects model. Heterogeneity was assessed by I2% and 95% prediction-interval statistics. Results: 34 high-quality studies that included more than 6-million asymptomatic average risk individuals were analyzed. 2,655,345 individuals completed a screening FIT test. The pooled FIT screening rate was 69.8% (95% CI [62.8-76.1]), the pooled FIT positivity rate was 5.4%[4.3-6.9], and the colonoscopy completion rate was 85%[82.8-86.9]. The pooled ADR was 47.8%[44.1-51.6], pooled aADR was 25.3%[22-29], and the pooled CRCDR was 5.1%[4.4-5.9]. The pooled ADR in males was 58.3%[52.8-63.6] and in females was 41.9%[36.4-47.6]. The pooled ADR with qualitative FIT assessment was 67.7%[50.7-81], with 1-stool sample FIT was 52.8%[48.8-56.8] and at a cut-off threshold of 100ngHb/ml was 52.1%[47-57.1]. Based on time-period cumulative analysis, the ADR improved over time from 30.5%[24.6-37.2] to 47.8%[44.1-51.6]. Conclusion: This meta-analysis supports the current ADR benchmarks for colonoscopy in FIT-positive individuals. Excellent pooled ADR parameters were demonstrated with qualitative assessment of one stool sample at a test cut-off value of 100ng Hb/ml, and ADR per endoscopist improved over time

Snare tip soft coagulation (STSC) after endoscopic mucosal resection (EMR) of large (> 20 mm) non pedunculated colorectal polyps: a systematic review and meta-analysis

Background and study aims Endoscopic mucosal resection (EMR) of laterally spreading tumors (LSTs) > 20 mm in size can be challenging. Piecemeal EMR of these lesions results in high rates of adenoma recurrence at first surveillance colonoscopy (SC1). Snare tip soft coagulation (STSC) of post resection margins is a safe and effective technique to prevent adenoma recurrence. We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of this technique.Patients and methods Multiple databases were searched through April 2021 for studies that reported on outcomes of post EMR STSC for LSTs > 20 mm in size. Meta-analysis was performed to determine pooled odds of adenoma recurrence as well as pooled proportion of adverse events including intraprocedural and delayed bleeding as well as intraprocedural perforation events.Results Six studies including two randomized controlled trials (RCT) and four cohort studies with 2122 patients were included in the final analysis. Overall pooled odds of adenoma recurrence at SC1 with post EMR STSC compared to no STSC was 0.27 (95 % 0.18-0.42; I-2 = 0 %), P < 0.001. Pooled rate of adenoma recurrence at SC1 in post EMR STSC cohort was 6 %. Rates of intraprocedural bleeding, delayed bleeding and intraprocedural perforation were 10.3 %, 6.5 % and 2 % respectively.Conclusions Our results show that thermal ablation of resection margins with STSC in LSTs > 20 mm is a safe and effective technique in reducing the incidence of adenoma recurrence

Safety and Effectiveness of Vedolizumab in Elderly Patients with Inflammatory Bowel Disease: A Systematic Review & Meta-Analysis

BACKGROUND: There is limited data on Vedolizumab utilization in elderly patients. Our study aims to assess the effectiveness and safety of Vedolizumab in this subset population. MATERIALS AND METHODS: Databases including Cochrane Central, Embase, Medline (via Ovid), Scopus, and Web of Science were searched in August 2022 to identify studies that assessed Vedolizumab therapy in elderly patients. Pooled proportion and risk ratios (RR) were calculated. RESULTS: Total 11 studies with 3546 IBD patients (1314 elderly and 2232 young) were included in the final analysis. Pooled rate of overall and serious infections in the elderly cohort was 8.45% (95% CI=6.27-11.29; I 2 23%) and 2.59% (95% CI=0.78-8.29; I 2 76%), respectively. However, there was no difference in overall infection rates between elderly and young patients. Pooled rate of endoscopic, clinical, and steroid-free remission for elderly IBD patients was 38.45% (95% CI=20.74-59.56; I 2 93%), 37.95% (95% CI=33.08-43.06; I 2 13%), and 38.8% (95% CI=31.6-46.4; I 2 77%), respectively. Elderly patients had lower steroid-free remission rates [RR 0.85, 95% CI=0.74-0.99; I 2 0%, P =0.03]; however, there was no difference in rates of clinical (RR 0.86, 95% CI=0.72-1.03; I 2 0%, P =0.10) or endoscopic remission (RR 1.06, 95% CI=0.83-1.35; I 2 0%, P =0.63) compared with younger patients. Pooled rate of IBD-related surgery and IBD-related hospitalizations was 9.76% (95% CI=5.81-15.92; I 2 78%) and 10.54% (95% CI=8.37-13.2; I 2 0%), respectively for the elderly cohort. There was no statistical difference in IBD-related surgeries between elderly and young IBD patients, RR 1.20 (95% CI=0.79-1.84; I 2 16%), P =0.4. CONCLUSIONS: Vedolizumab is equally safe and effective for clinical and endoscopic remission in elderly and younger populations

Hydrogen Peroxide Assisted Endoscopic Necrosectomy of Pancreatic Walled-Off Necrosis: A Systematic Review and Meta-Analysis

Background: Use of hydrogen peroxide (H2O2) has been reported in the direct endoscopic necrosectomy (DEN) of pancreatic walled-off necrosis (WON). The aim of this meta-analysis was to study the pooled clinical outcomes of H2O2-assisted DEN of pancreatic WON. Methods: We conducted a comprehensive search of several databases (inception to July 2021) to identify studies reporting on the use of H2O2 in DEN of WON. Random effects model was used to calculate the pooled rates and I2% values, 95% prediction intervals were used to assess the heterogeneity. The outcomes studied were technical success, clinical success, and adverse events in H2O2-assisted DEN of pancreatic WON. Results: 7-studies were analyzed, in which a total of 186 patients underwent H2O2-assisted DEN of WON. The pooled rate of technical success was 95.8% (95% CI 88.5-98.5), the clinical success was 91.6% (95% CI 86.1-95), and the cumulative rate of overall adverse events was 19.3% (95% CI 7.6-41). The pooled rate of bleeding was 7.9% (95% CI 2.4-22.7), stent migration was 11.3% (95% CI 4.9-23.9), perforation was 5.4% (95% CI 1.7-15.7), infection was 5.7% (95% CI 2-15.1), and pulmonary complication was 2.9% (95% CI 1.3-6.1). Mean treatment sessions ranged from 2 to 5. Conclusion: H2O2-assisted DEN of WON demonstrated excellent clinical outcomes, with minimal heterogeneity. No adverse events attributable to H2O2 were reported. Future controlled studies are warranted comparing the clinical outcomes with and without H2O2 before H2O2 use can be established in the DEN of pancreatic WON

Vonoprazan versus lansoprazole in erosive esophagitis - A systematic review and meta-analysis of randomized controlled trials

Background: Proton-pump inhibitors (PPIs) are the mainstay of treatment in erosive esophagitis (EE). An alternative to PPIs in EE is Vonoprazan, a potassium competitive acid blocker. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing vonoprazan to lansoprazole. Methods: Multiple databases searched through November 2022. Meta-analysis was performed to assess endoscopic healing at two, four and eight weeks, including for patients with severe EE (Los Angeles C/D). Serious adverse events (SAE) leading to drug discontinuation were assessed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Four RCTs with 2208 patients were included in the final analysis. Vonoprazan 20 mg once-daily was compared to lansoprazole 30 mg once-daily dosing. Among all patients, at two and eight weeks post-treatment, vonoprazan resulted in significantly higher rates of endoscopic healing as compared to lansoprazole, risk ratios (RR) 1.1, p\u3c 0.001 and RR 1.04, p=0.03. The same effect was not observed at four weeks, RR 1.03 (CI 0.99-1.06, I2=0%) following therapy. Among patients with severe EE, vonoprazan resulted in higher rates of endoscopic healing at two weeks, RR 1.3 (1.2-1.4, I2=47%), p=\u3c 0.001, at four weeks, RR 1.2 (1.1-1.3, I2=36%), p=\u3c 0.001 and at eight weeks post-treatment, RR 1.1 (CI 1.03-1.3, I2=79%), p=0.009. We found no significant difference in the overall pooled rate of SAE and pooled rate of adverse events leading to drug discontinuation. Finally, the overall certainty of evidence for our main summary estimates was rated as high (grade A). Conclusion: Based on limited number of published non-inferiority RCTs, our analysis demonstrates that among patients with EE, vonoprazan 20 mg once-daily dosing achieves comparable and in those with severe EE, higher endoscopic healing rates as compared to lansoprazole 30 mg once-daily dosing. Both drugs have a comparable safety profile