Placebo rates in Crohn's disease randomized clinical trials: An individual patient data meta-analysis.

BACKGROUND & AIMS: Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data (IPD) from Crohn's disease (CD) trials. METHODS: We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate-to-severe CD (2010-2021). Deidentified IPD were obtained through Vivli Inc. and Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using one- and two-stage meta-analytical approaches. Regression analyses identified patient-level factors associated with placebo rates. RESULTS: Using IPD from eight induction (n=1147) and four maintenance (n=524) trials, overall placebo clinical response and remission rates for induction were 27% (95%CI=23-32%) and 10% (95%CI=8-14%) respectively, and 32% (95%CI=23-42%) and 22% (95%CI=14-33%) for maintenance, respectively. Among bio-naïve patients, placebo response and remission rates during induction were 29% (95%CI=24-35%) and 11% (95%CI=8-15%) respectively, and 26% (95% CI=20-33%) and 10% (95% CI=8-14%) for bio-exposed, respectively. During maintenance, bio-naïve response and remission rates were 41% (95%CI=34-48%) and 32% (95%CI=24-40%), respectively, and 29% (95%CI=24-34%) and 16% (95%CI=13-21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, while higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn's Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance. CONCLUSION: Patient- and trial-level characteristics influence placebo rates in CD trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates.

Relative Efficacies of Interventions to Improve the Quality of Screening-Related Colonoscopy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND & AIMS: Significant variability exists in colonoscopy quality indicators, including adenoma detection rate (ADR). We synthesized evidence from randomized trials in a network meta-analysis on interventions to improve colonoscopy quality. METHODS: We included trials from database inceptions to September 25, 2023, of patients undergoing screening-related colonoscopy and presented efficacies of interventions within domains (periprocedural parameters, endoscopist-directed interventions, intraprocedural techniques, endoscopic technologies, distal attachment devices, and additive substances) compared to standard colonoscopy. The primary outcome was ADR. We used a Bayesian random-effects model using Markov-chain Monte Carlo simulation, with 10,000 burn-ins and 100,000 iterations. We calculated odds ratios with 95% credible intervals and present surface under the cumulative ranking (SUCRA) curves. RESULTS: We included 124 trials evaluating 37 interventions for the primary outcome. Nine interventions resulted in statistically significant improvements in ADR compared to standard colonoscopy (9-minute withdrawal time, dual observation, water exchange, i-SCAN [Pentax Ltd], linked color imaging, computer-aided detection, Endocuff [Olympus Corp], Endocuff Vision [Olympus Corp], and oral methylene blue). Dual observation (SUCRA, 0.84) and water exchange (SUCRA, 0.78) ranked highest among intraprocedural techniques; i-SCAN (SUCRA, 0.95), linked color imaging (SUCRA, 0.85), and computer-aided detection (SUCRA, 0.78) among endoscopic technologies; WingCap (A&A Medical Supply LLC) (SUCRA, 0.87) and Endocuff (SUCRA, 0.85) among distal attachment devices and oral methylene blue (SUCRA, 0.94) among additive substances. No interventions improved detection of advanced adenomas, and only narrow-band imaging improved detection of serrated lesions (odds ratio, 2.94; 95% credible interval, 1.46-6.25). CONCLUSIONS: Several interventions are effective in improving adenoma detection and overall colonoscopy quality, many of which are cost-free. These results can inform endoscopists, unit managers, and endoscopy societies on relative efficacies.

Comparison of endoscopic mucosal resection versus endoscopic submucosal dissection for Barrett's neoplasia and esophageal adenocarcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are both accepted resection strategies for Barrett's esophagus-related neoplasia and esophageal adenocarcinoma (EAC). However, a lack of consensus exists regarding which technique offers superior outcomes. This study aims to systematically review the evidence comparing EMR versus ESD in treating Barrett's neoplasia and EAC. METHODS: We searched 3 databases (Embase, MEDLINE, Cochrane Central) through October 2023. We included studies comparing the efficacy of EMR and ESD for Barrett's neoplasia and EAC. Primary outcomes include en bloc, R0, and curative resection; complete remission of dysplasia (CRD), and local recurrence. Secondary outcomes encompass adverse events. RESULTS: Our search identified 905 records. Eleven studies were included in the final analyses. Data showed significantly higher en bloc resection rates with ESD (odds ratio [OR], 31.53; 95% confidence interval [CI], 10.02-99.19; P < .01; 7 studies). R0 resection rates were significantly higher with ESD (OR, 5.92; 95% CI, 2.75-12.77; P < .01; 8 studies). Curative resection rates tended to be higher with ESD (OR, 3.49; 95% CI, 0.86-14.14; P = .080; 4 studies). There was no significant difference in CRD rates (OR, 0.92; 95% CI, 0.37-2.26; P = .86; 3 studies). Local recurrence rates tended to be lower with ESD (OR, 0.35; 95% CI, 0.11-1.04; P = .058; 10 studies). As for adverse events, there was no significant difference in bleeding, perforation, and postoperative stricture rates. CONCLUSIONS: This systematic review and meta-analysis demonstrates that ESD achieves higher en bloc, R0, and curative resection rates, with a tendency toward lower recurrence rates. These results suggest that ESD may be a more effective option for managing Barrett's neoplasia and EAC. (International Prospective Register of Systematic Reviews [PROSPERO] registration number: CRD42023426486.).

Management of complications in patients with an ileostomy: an umbrella review of systematic reviews for the EndOTrial Consortium.

BACKGROUND: Standardized clinical care processes for patients with Crohn's disease (CD) and a permanent ileostomy (PI) are lacking. The EndOTrial consortium aims to address this gap by developing pathways for care. METHODS: In this umbrella review, we searched major databases for relevant systematic reviews (SRs) or scoping reviews (ScR) published until January 5, 2024. Screening, data extraction, and quality appraisal (AMSTAR 2) were performed by two independent reviewers. RESULTS: Of 1349 screened papers, 22 reviews met our inclusion criteria, including 20 SRs (eight with meta-analysis) and 2 ScRs. None exclusively focused on PI. Furthermore, nine reviews did not mention patients with inflammatory bowel disease (IBD), and only two reviews included patients with high-output ileostomy, highlighting a large evidence gap. The identified reviews covered six categories with nine types of interventions, including ostomy care pathways, peristomal skin care, patient education, clinical management of high-output stoma, management and prevention of postoperative ileus, dietary and nutritional support, nursing and supporting care, telemedicine, and self-management interventions. Most SRs including nursing interventions for stoma care highlighted nurses' role in a variety of standard and specialized treatments. Notably, none of the reviews exclusively examined disease recurrence, stoma pouching systems or adhesives, behavioral interventions, or mental health in patients living with ileostomy. CONCLUSIONS: Evidence for best practice interventions to treat complications and improve quality of life in patients living with an ileostomy for CD is limited and heterogeneous. These results outline the need for standardized clinical care processes and pathways tailored to the unique needs of this patient population.

Efficacy of endoscopic interventions versus surgery for pain management in patients with chronic calcific pancreatitis: a systematic review and meta-analysis.

INTRODUCTION: Chronic calcific pancreatitis (CCP) is a debilitating inflammatory condition characterized by the accumulation of calcific deposits in the pancreatic tissue, leading to chronic abdominal pain and functional insufficiencies. This study aims to systematically review and meta-analyse comparative studies assessing the efficacy of endotherapy versus surgery in managing CCP-related pain. METHODS: MEDLINE, EMBASE, and Cochrane library (CENTRAL and CDSR), from inception to October 2023, were searched. The inclusion criteria encompassed randomized controlled trials (RCTs) and non-randomized controlled trials (NRS), and cohort studies comparing endoscopic interventions to surgery for pain management in patients with CCP. Pain relief, procedural technical success, and procedural-related complications were the outcomes of interest. Two review authors (CN, KK) independently assessed study eligibility criteria and performed data extraction. Using a random-effects model, pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. The level of certainty of the evidence was assessed using the GRADE approach. RESULTS: Five studies were included. For the outcome of pain relief, a meta-analysis of five studies (3 RCTs and 2 cohort studies) demonstrated a significant therapeutic effect in favour of surgery with an OR of 2.36 (95% CI: 1.12 to 5.00, I2 = 41.70), with moderate level of certainty of evidence. In the analysis of five studies (3 RCTs, 1 NRS and 2 cohort studies), procedural technical success was comparable between the two groups (OR of 3.02, 95% CI: 0.47 to 19.59, I2 = 79.27%) as were adverse events (OR 1.31, 95% CI: 0.47 to 3.70, I2 = 50.93%). CONCLUSION: In conclusion, this systematic review and meta-analysis suggest that surgery may be more effective in relieving pain in patients with CCP compared to endoscopic interventions. Disease stage may be important to determine the appropriateness of each procedure. PROSPERO (CRD42023476153).

Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate-Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society.

BACKGROUND: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI). METHODS: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. RESULTS: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. CONCLUSIONS: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).

What is the Prevalence of Clinically Significant Endoscopic Findings in Subjects With Dyspepsia? Updated Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The prevalence of clinically significant endoscopic findings in people with dyspepsia and understanding how symptoms can predict endoscopic pathology can help inform dyspepsia guidelines. We evaluated this in an updated systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, Cochrane CENTRAL, and the Cochrane Database of Systematic Reviews from 2010 through to January 2022 to identify relevant articles. Eligible studies enrolled adults from the community, workplace, blood donation or screening clinics, family physician offices, or internal medicine clinics. Studies were required to report prevalence of dyspepsia and perform esophagogastroduodenoscopy (EGD). Prevalence of clinically significant endoscopic findings in subjects with and without dyspepsia was pooled for all studies and compared using odds ratios and 95% confidence intervals (CIs). The data were pooled with those of the 9 studies included in the prior review. RESULTS: Of 511 papers evaluated, 184 reported prevalence of dyspepsia. Fifteen reported prevalence of endoscopic findings among 41,763 participants (40.4% with dyspepsia). Erosive esophagitis was the most common abnormality (pooled prevalence, 11.0%; 95% CI, 8.9%-13.2%) followed by peptic ulcer (pooled prevalence, 4.4%; 95% CI, 2.5%-6.7%). The only finding encountered more frequently in individuals with dyspepsia, compared with those without, was peptic ulcer (odds ratio, 1.61; 95% CI, 1.08-2.39). More than 85% of EGDs were completely normal. Gastroesophageal cancer was rare (<0.4%) and equally prevalent among those with and without dyspepsia. CONCLUSIONS: Erosive esophagitis was the most common clinically significant finding at EGD, whereas gastroesophageal cancers were rare. Most pathology, including esophagitis and cancer, were found in similar proportions in both groups. These findings support noninvasive approaches to managing dyspepsia in the community, with EGD reserved for those at high risk of malignancy.

Peri- and post-operative outcomes, complications, and functional results amongst different modifications of endoscopic enucleation of the prostate (EEP): a systematic review and meta-analysis.

PURPOSE: To investigate and assess outcomes, complications, and functional results amongst different modifications of endoscopic enucleation of the prostate (EEP). METHODS: We conducted a systematic review and meta-analysis according to the PRISMA checklist. We searched the Medline, Cochrane, and Embase databases. We included only randomised-controlled trials (RCT) comparing modifications of EEPs and assessed the risk of bias (RoB). RESULTS: Seven RCTs were included in the study. Overall, 1266 patients were treated with Holmium laser enucleation of the prostate (HoLEP) and 80 patients with thulium laser vapo-enucleation of the prostate (ThuVEP). The operative time during pulse shape-modified HoLEP was shorter when compared to standard pulse HoLEP (MD 18.08 min, 95% CI 8.11-28.05 min, p = 0.0004). The decrease in haemoglobin was significantly lower for two-lobe HoLEP when compared to three-lobe HoLEP (MD 0.16 g/dl, 95% CI 0.22-0.1 g/dl, p < 0.00001). Virtual Basket (VB) HoLEP showed a smaller haemoglobin decrease when compared to standard pulse HoLEP (1.12 ± 1.78 vs. 2.54 ± 1.23 g/dl, p = 0.03). When directly comparing one- vs. two- vs. three-lobe HoLEP, surgical time (p < 0.001) and enucleation efficiency (p = 0.006) were significantly different and favouring one- and two-lobe HoLEP in the study with the largest patient population included. No significant differences for complications were observed; however, Clavien-Dindo IVa events were reported for two patients. CONCLUSION: All variations of EEP improve symptoms and functional parameters with a low incidence of high-grade complications. One- and two-lobe approaches and pulse shape-modified HoLEP seem to be beneficial in terms of operative time and blood loss.

Obesity as an independent risk factor for COVID-19 severity and mortality.

BACKGROUND: Since December 2019, the world has struggled with the COVID-19 pandemic. Even after the introduction of various vaccines, this disease still takes a considerable toll. In order to improve the optimal allocation of resources and communication of prognosis, healthcare providers and patients need an accurate understanding of factors (such as obesity) that are associated with a higher risk of adverse outcomes from the COVID-19 infection. OBJECTIVES: To evaluate obesity as an independent prognostic factor for COVID-19 severity and mortality among adult patients in whom infection with the COVID-19 virus is confirmed. SEARCH METHODS: MEDLINE, Embase, two COVID-19 reference collections, and four Chinese biomedical databases were searched up to April 2021. SELECTION CRITERIA: We included case-control, case-series, prospective and retrospective cohort studies, and secondary analyses of randomised controlled trials if they evaluated associations between obesity and COVID-19 adverse outcomes including mortality, mechanical ventilation, intensive care unit (ICU) admission, hospitalisation, severe COVID, and COVID pneumonia. Given our interest in ascertaining the independent association between obesity and these outcomes, we selected studies that adjusted for at least one factor other than obesity. Studies were evaluated for inclusion by two independent reviewers working in duplicate.  DATA COLLECTION AND ANALYSIS: Using standardised data extraction forms, we extracted relevant information from the included studies. When appropriate, we pooled the estimates of association across studies with the use of random-effects meta-analyses. The Quality in Prognostic Studies (QUIPS) tool provided the platform for assessing the risk of bias across each included study. In our main comparison, we conducted meta-analyses for each obesity class separately. We also meta-analysed unclassified obesity and obesity as a continuous variable (5 kg/m2 increase in BMI (body mass index)). We used the GRADE framework to rate our certainty in the importance of the association observed between obesity and each outcome. As obesity is closely associated with other comorbidities, we decided to prespecify the minimum adjustment set of variables including age, sex, diabetes, hypertension, and cardiovascular disease for subgroup analysis.  MAIN RESULTS: We identified 171 studies, 149 of which were included in meta-analyses.  As compared to 'normal' BMI (18.5 to 24.9 kg/m2) or patients without obesity, those with obesity classes I (BMI 30 to 35 kg/m2), and II (BMI 35 to 40 kg/m2) were not at increased odds for mortality (Class I: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.94 to 1.16, high certainty (15 studies, 335,209 participants); Class II: OR 1.16, 95% CI 0.99 to 1.36, high certainty (11 studies, 317,925 participants)). However, those with class III obesity (BMI 40 kg/m2 and above) may be at increased odds for mortality (Class III: OR 1.67, 95% CI 1.39 to 2.00, low certainty, (19 studies, 354,967 participants)) compared to normal BMI or patients without obesity. For mechanical ventilation, we observed increasing odds with higher classes of obesity in comparison to normal BMI or patients without obesity (class I: OR 1.38, 95% CI 1.20 to 1.59, 10 studies, 187,895 participants, moderate certainty; class II: OR 1.67, 95% CI 1.42 to 1.96, 6 studies, 171,149 participants, high certainty; class III: OR 2.17, 95% CI 1.59 to 2.97, 12 studies, 174,520 participants, high certainty). However, we did not observe a dose-response relationship across increasing obesity classifications for ICU admission and hospitalisation. AUTHORS' CONCLUSIONS: Our findings suggest that obesity is an important independent prognostic factor in the setting of COVID-19. Consideration of obesity may inform the optimal management and allocation of limited resources in the care of COVID-19 patients.

Prediction model for labour dystocia occurring in the active phase.

To establish and verify a model for labour dystocia occurring in the active phase, this study retrospectively analysed the clinical data of primiparas with singleton cephalic full-term foetuses, who had delivered after a trial of labour. The Chi-square test, t-test, Mann-Whitney U test and multivariate logistic regression analysis were used for statistical analysis. Based on the model a nomogram was established using the R programming language. Multivariate logistic regression analysis showed that the foetal abdominal circumference, premature rupture of membranes (PROM), prolonged latent phase, foetal station and foetal position at the early stage of the active phase were independent factors influencing labour dystocia occurring in the active phase. The established model could effectively and accurately support clinicians in the early identification of labour dystocia to improve maternal and infant outcomes.Impact statementWhat is already known on this subject? Labour dystocia occurring during the active phase of the first stage, is the most commonly diagnosed as labour aberration. Previous studies have suggested that maternal age, body mass index, macrosomia and abnormal foetal position are the independent risk factors for labour dystocia. However, only the risk factors were reported, and few prediction models were established.What do the results of this study add? This study uses data in the real world to establish a prediction model of full-term singleton primipara with labour dystocia occurring in the active phase by logistic regression analysis. Foetal abdomen circumference, PROM, prolonged latent phase, the foetal station and foetal position at the early stage of the active phase are independent factors influencing labour dystocia that occurs in the active phase. In addition, a nomogram is established as a visual graph to predict the probability of it.What are the implications of these findings for clinical practice and/or further research? The nomogram based on the predictive model discarded complicated calculations and presented an easy visual graph-based method to predict the probability of labour dystocia occurring in the active phase. It helps to introduce interventions that could reduce the CS rate and occurrence of adverse maternal and foetal outcomes to ensure the safety of mothers and infants.

Efficacy of Helicobacter pylori eradication therapy for functional dyspepsia: updated systematic review and meta-analysis.

OBJECTIVE: Functional dyspepsia (FD) is a chronic disorder that is difficult to treat. Helicobacter pylori may contribute to its pathophysiology. A Cochrane review from 2006 suggested that eradication therapy was beneficial, but there have been numerous randomised controlled trials (RCTs) published since. We evaluated impact of eradication therapy on both cure and improvement of FD, as well as whether any benefit was likely to arise from eradication of H. pylori. DESIGN: We searched the medical literature through October 2021 to identify RCTs examining efficacy of eradication therapy in H. pylori-positive adults with FD. The control arm received antisecretory therapy or prokinetics, with or without placebo antibiotics, or placebo alone. Follow-up was for ≥3 months. We pooled dichotomous data to obtain a relative risk (RR) of symptoms not being cured or symptoms not improving with a 95% CI. We estimated the number needed to treat (NNT). RESULTS: Twenty-nine RCTs recruited 6781 H. pylori-positive patients with FD. Eradication therapy was superior to control for symptom cure (RR of symptoms not being cured=0.91; 95% CI 0.88 to 0.94, NNT=14; 95% CI 11 to 21) and improvement (RR of symptoms not improving=0.84; 95% CI 0.78 to 0.91, NNT=9; 95% CI 7 to 17). There was no significant correlation between eradication rate and RR of FD improving or being cured (Pearson correlation coefficient=-0.23, p=0.907), but the effect was larger in patients with successful eradication of H. pylori than with unsuccessful eradication (RR=0.65; 95% CI 0.52 to 0.82, NNT=4.5, 95% CI 3 to 9). Adverse events (RR=2.19; 95% 1.10 to 4.37) and adverse events leading to withdrawal (RR=2.60; 95% CI 1.47 to 4.58) were more common with eradication therapy. CONCLUSION: There is high quality evidence to suggest that H. pylori eradication therapy leads to both cure and improvement in FD symptoms, although the benefit is modest.

Bidirectional brain-gut axis effects influence mood and prognosis in IBD: a systematic review and meta-analysis.

OBJECTIVE: The role of the brain-gut axis is of increasing interest in IBD, as the link between common mental disorders and GI inflammation may be bidirectional. We performed a systematic review examining these issues. DESIGN: We searched EMBASE Classic and EMBASE, Medline, and APA PsychInfo (to 11 July 2021) for longitudinal follow-up studies examining effect of symptoms of anxiety or depression on subsequent adverse outcomes in IBD, or effect of active IBD on subsequent development of symptoms of anxiety or depression. We pooled relative risks (RRs) and HRs with 95% CIs for adverse outcomes (flare, escalation of therapy, hospitalisation, emergency department attendance, surgery or a composite of any of these) according to presence of symptoms of anxiety or depression at baseline, or RRs and HRs with 95% CIs for new onset of symptoms of anxiety or depression according to presence of active IBD at baseline. RESULTS: We included 12 separate studies, recruiting 9192 patients. All 12 studies examined brain-to-gut effects. Anxiety at baseline was associated with significantly higher risks of escalation of therapy (RR=1.68; 95% CI 1.18 to 2.40), hospitalisation (RR=1.72; 95% CI 1.01 to 2.95), emergency department attendance (RR=1.30; 95% CI 1.21 to 1.39), or a composite of any adverse outcome. Depression at baseline was associated with higher risks of flare (RR=1.60; 95% CI 1.21 to 2.12), escalation of therapy (RR=1.41; 95% CI 1.08 to 1.84), hospitalisation (RR=1.35; 95% CI 1.17 to 1.57), emergency department attendance (RR=1.38; 95% CI 1.22 to 1.56), surgery (RR=1.63; 95% CI 1.19 to 2.22) or a composite of any of these. Three studies examined gut-to-brain effects. Active disease at baseline was associated with future development of anxiety or depression (RR=2.24; 95% CI 1.25 to 4.01 and RR=1.49; 95% CI 1.11 to 1.98, respectively). CONCLUSION: Bidirectional effects of the brain-gut axis are present in IBD and may influence both the natural history of the disease and psychological health.

What is the role of single-stage oral mucosa graft urethroplasty in the surgical management of lichen sclerosus-related stricture disease in men? A systematic review.

PURPOSE: The benefits and harms of the available types of surgical management for lichen sclerosus-related (LS) strictures remain unclear and, thus, clear and robust clinical practice recommendations cannot be given. MATERIALS AND METHODS: To assess the role of single-stage OMGU in the management of LS strictures and explore how its benefits and harms compare with the alternative management options. Medline, Embase and Cochrane controlled trial databases (CENTRAL, CDSR) were systematically searched. Randomized (RCTs) and nonrandomized studies (NRCSs) comparing single-stage OMGU with other surgical management options for LS strictures and single-arm studies on single-stage OMGU were included. Risk of bias (RoB) was assessed. RESULTS: Of the 1912 abstracts identified, 15 studies (1 NRCS and 14 single-arm studies) were included, recruiting in total 649 patients. All studies were at high RoB. In the only NRCS available, stricture-free rate (SFR) for single-stage and staged OMGU was 88% vs 60%, respectively (p = 0.05), at a mean follow-up of 66.5 months. SFR range for single-stage OMGU in single-arm studies was 65-100% (mean/median follow-up, 12-59 months). Single-stage OMGU had low complication rates and beneficial impact on LUTS and QoL. CONCLUSIONS: The present SR highlights the methodological limitations of the available literature. In the absence of adverse local tissue conditions, and taking into consideration benefit-harm balance and surgeon's skills and expertise, single-stage OMGU can be justified in patients with LS strictures.

Guidewire-assisted cannulation of the common bile duct for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis.

BACKGROUND: Cannulation techniques have been recognized as being important in causing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy exists about the usefulness of the guidewire-assisted cannulation technique for the prevention of PEP. OBJECTIVES: To assess the effectiveness and safety of the guidewire-assisted cannulation technique compared to the conventional contrast-assisted cannulation technique for the prevention of PEP in people undergoing diagnostic or therapeutic ERCP for biliary or pancreatic diseases. SEARCH METHODS: For the previous version of this review, we searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL and major conference proceedings, up to February 2012, with no language restrictions. An updated search was performed on 26 February 2021 for the current version of this review. Two clinical trial registries, clinicaltrials.gov and WHO ICTRP, were also searched in this update. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing the guidewire-assisted cannulation technique versus the contrast-assisted cannulation technique in people undergoing ERCP. DATA COLLECTION AND ANALYSIS: Two review authors conducted study selection, data extraction, and methodological quality assessment independently. Using intention-to-treat analysis with random-effects models, we combined dichotomous data to obtain risk ratios (RR) with 95% confidence intervals (CI). We assessed heterogeneity using the Chi² test (P < 0.10) and I² statistic (> 50%). To explore sources of heterogeneity, we conducted a priori subgroup analyses according to trial design, publication type, risk of bias, use of precut sphincterotomy, inadvertent guidewire insertion or contrast injection of the pancreatic duct (PD), use of a PD stent, cannulation device, and trainee involvement in cannulation. To assess the robustness of our results, we carried out sensitivity analyses using different summary statistics (RR versus odds ratio (OR)) and meta-analytic models (fixed-effect versus random-effects) and per-protocol analysis. MAIN RESULTS: 15 RCTs comprising 4426 participants were included. There was moderate heterogeneity among trials for the outcome of PEP (P = 0.08, I² = 36%). Meta-analyses suggest that the guidewire-assisted cannulation technique probably reduces the risk of PEP compared to the contrast-assisted cannulation technique (RR 0.51, 95% CI 0.36 to 0.72, 15 studies, moderate-certainty evidence). In addition, the guidewire-assisted cannulation technique may result in an increase in primary cannulation success (RR 1.06, 95% CI 1.01 to 1.12, 13 studies, low-certainty evidence), and probably reduces the need for precut sphincterotomy (RR 0.79, 95% CI 0.64 to 0.96, 10 studies, moderate-certainty evidence). Compared to the contrast-assisted cannulation technique, the guidewire-assisted cannulation technique may result in little to no difference in the risk of post-sphincterotomy bleeding (RR 0.87, 95% CI 0.49 to 1.54, 7 studies, low-certainty evidence) and perforation (RR 0.93, 95% CI 0.11 to 8.23, 8 studies, very low-certainty evidence). Procedure-related mortality was reported by eight studies, and there were no cases of deaths in both arms (moderate-certainty evidence). Subgroup analyses suggest that the heterogeneity for the outcome of PEP could be explained by differences in trial design. The results were robust in sensitivity analyses. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that the guidewire-assisted cannulation technique probably reduces the risk of PEP compared to the contrast-assisted cannulation technique. There is low-certainty evidence that the guidewire-assisted cannulation technique may result in an increase in primary cannulation success. There is low- and very low-certainty evidence that the guidewire-assisted cannulation technique may result in little to no difference in the risk of bleeding and perforation. No procedure-related deaths were reported. Therefore, the guidewire-assisted cannulation technique appears to be superior to the contrast-assisted cannulation technique considering the certainty of evidence and the balance of benefits and harms. However, the routine use of guidewires in biliary cannulation will be dependent on local expertise, availability, and cost. Future research should assess the effectiveness and safety of the guidewire-assisted cannulation technique in the context of other pharmacologic or non-pharmacologic interventions for the prevention of PEP.

Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding. OBJECTIVES: To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding. SEARCH METHODS: We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (H2RA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.

Differences in Gut Microbiota in Patients With vs Without Inflammatory Bowel Diseases: A Systematic Review.

BACKGROUND & AIMS: Altering the intestinal microbiota has been proposed as a treatment for inflammatory bowel diseases (IBDs), but there are no established associations between specific microbes and IBD. We performed a systematic review to identify frequent associations. METHODS: We searched the MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases, through April 2, 2018 for studies that compared intestinal microbiota (from fecal or colonic or ileal tissue samples) among patients (adult or pediatric) with IBD vs healthy individuals (controls). The primary outcome was difference in specific taxa in fecal or intestinal tissue samples from patients with IBD vs controls. We used the Newcastle-Ottawa scale to assess the quality of studies included in the review. RESULTS: We identified 2631 citations; 48 studies from 45 articles were included in the analysis. Most studies evaluated adults with Crohn's disease or ulcerative colitis. All 3 studies of Christensenellaceae and Coriobacteriaceae and 6 of 11 studies of Faecalibacterium prausnitzii reported a decreased amount of those organisms compared with controls, whereas 2 studies each of Actinomyces, Veillonella, and Escherichia coli revealed an increased amount in patients with Crohn's disease. For patients with ulcerative colitis, Eubacterium rectale and Akkermansia were decreased in all 3 studies, whereas E coli was increased in 4 of 9 studies. The microbiota diversity was either decreased or not different in patients with IBD vs controls. Fewer than 50% of the studies stated comparable sexes and ages of cases and controls. CONCLUSIONS: In a systematic review, we found evidence for differences in abundances of some bacteria in patients with IBD vs controls, but we cannot make conclusions due to inconsistent results and methods among studies. Further large-scale studies, with better methods of assessing microbe populations, are needed.

Transmission of Severe Acute Respiratory Syndrome Coronavirus 1 and Severe Acute Respiratory Syndrome Coronavirus 2 During Aerosol-Generating Procedures in Critical Care: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVES: To assess the risk of coronavirus transmission to healthcare workers performing aerosol-generating procedures and the potential benefits of personal protective equipment during these procedures. DATA SOURCES: MEDLINE, EMBASE, and Cochrane CENTRAL were searched using a combination of related MeSH terms and keywords. STUDY SELECTION: Cohort studies and case controls investigating common anesthetic and critical care aerosol-generating procedures and transmission of severe acute respiratory syndrome coronavirus 1, Middle East respiratory syndrome coronavirus, and severe acute respiratory syndrome coronavirus 2 to healthcare workers were included for quantitative analysis. DATA EXTRACTION: Qualitative and quantitative data on the transmission of severe acute respiratory syndrome coronavirus 1, severe acute respiratory syndrome coronavirus 2, and Middle East respiratory syndrome coronavirus to healthcare workers via aerosol-generating procedures in anesthesia and critical care were collected independently. The Risk Of Bias In Non-randomized Studies - of Interventions tool was used to assess the risk of bias of included studies. DATA SYNTHESIS: Seventeen studies out of 2,676 yielded records were included for meta-analyses. Endotracheal intubation (odds ratio, 6.69, 95% CI, 3.81-11.72; p < 0.001), noninvasive ventilation (odds ratio, 3.65; 95% CI, 1.86-7.19; p < 0.001), and administration of nebulized medications (odds ratio, 10.03; 95% CI, 1.98-50.69; p = 0.005) were found to increase the odds of healthcare workers contracting severe acute respiratory syndrome coronavirus 1 or severe acute respiratory syndrome coronavirus 2. The use of N95 masks (odds ratio, 0.11; 95% CI, 0.03-0.39; p < 0.001), gowns (odds ratio, 0.59; 95% CI, 0.48-0.73; p < 0.001), and gloves (odds ratio, 0.39; 95% CI, 0.29-0.53; p < 0.001) were found to be significantly protective of healthcare workers from contracting severe acute respiratory syndrome coronavirus 1 or severe acute respiratory syndrome coronavirus 2. CONCLUSIONS: Specific aerosol-generating procedures are high risk for the transmission of severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2 from patients to healthcare workers. Personal protective equipment reduce the odds of contracting severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2.

Nonantibiotic Strategies for the Prevention of Infectious Complications following Prostate Biopsy: A Systematic Review and Meta-Analysis.

PURPOSE: We identify which nonantibiotic strategies could reduce the risk of infectious complications following prostate biopsy. MATERIALS AND METHODS: We performed a literature search on MEDLINE®, Embase® and the Cochrane Database for randomized controlled trials (inception to May 2020) assessing nonantibiotic interventions in prostate biopsy. Primary outcome was pooled infectious complications (fever, sepsis and symptomatic urinary tract infection) and secondary outcome was hospitalization. Cochrane risk of bias tool and GRADE approach were used to assess the bias and the certainty of evidence. The study protocol was registered with PROSPERO (CRD42015026354). RESULTS: A total of 90 randomized controlled trials (16,941 participants) were included in the analysis, with 83 trials being categorized into one of 10 different interventions. Transperineal biopsy was associated with significantly reduced infectious complications as compared to transrectal biopsy (RR 0.55, 95% CI 0.33-0.92, p=0.02, I2=0%, 1,330 participants, 7 studies). Rectal preparation with povidone-iodine was also shown to reduce infectious complications (RR 0.50, 95% CI 0.38-0.65, p <0.000001, I2=27%, 1,686 participants, 8 studies) as well as hospitalization (RR 0.38, 95% CI 0.21-0.69, p=0.002, I2=0%, 620 participants, 4 studies). We found no difference in infectious complications/hospitalization for 6 other interventions, ie number of biopsy cores, periprostatic nerve block, number of injections for periprostatic nerve block, needle guide type, needle type and rectal preparation with enema. In 2 interventions (needle diameter, rectal preparation with chlorhexidine) meta-analysis was not possible. Finally, 7 studies had unique interventions. The certainty of evidence was rated as low/very low for all interventions. CONCLUSIONS: Transperineal biopsy significantly reduces infectious complications compared to transrectal biopsy and should therefore be preferred. If transrectal biopsy is performed, rectal preparation with povidone-iodine is highly recommended. The other investigated nonantibiotic strategies did not significantly influence infection and hospitalization after prostate biopsy.

A systematic review on COVID-19: urological manifestations, viral RNA detection and special considerations in urological conditions.

PURPOSE AND OBJECTIVE: We performed a systematic review on COVID-19 and its potential urological manifestations. METHODS: A literature search was performed using combination of keywords (MeSH terms and free text words) relating to COVID-19, urology, faeces and stool on multiple databases. Primary outcomes were the urological manifestations of COVID-19, and SARS-CoV-2 viral RNA detection in urine and stool samples. Meta-analyses were performed when there were two or more studies reporting on the same outcome. Special considerations in urological conditions that were relevant in the pandemic of COVID-19 were reported in a narrative manner. RESULTS: There were a total of 21 studies with 3714 COVID-19 patients, and urinary symptoms were absent in all of them. In patients with COVID-19, 7.58% (95% CI 3.30-13.54%) developed acute kidney injury with a mortality rate of 93.27% (95% CI 81.46-100%) amongst them. 5.74% (95% CI 2.88-9.44%) of COVID-19 patients had positive viral RNA in urine samples, but the duration of viral shedding in urine was unknown. 65.82% (95% CI 45.71-83.51%) of COVID-19 patients had positive viral RNA in stool samples, which were detected from 2 to 47 days from symptom onset. 31.6% of renal transplant recipients with COVID-19 required non-invasive ventilation, and the overall mortality rate was 15.4%. CONCLUSIONS: Acute kidney injury leading to mortality is common amongst COVID-19 patients, likely as a result of direct viral toxicity. Viral RNA positivity was detected in both urine and stool samples, so precautions are needed when we perform transurethral or transrectal procedures.

Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis.

OBJECTIVES: Gastric cancer is strongly associated with Helicobacter pylori (H. pylori). We conducted a previous systematic review and meta-analysis that suggested eradication therapy reduced future incidence of gastric cancer, but effect size was uncertain, and there was no reduction in gastric cancer-related mortality. We updated this meta-analysis, as more data has accumulated. We also evaluated impact of eradication therapy on future risk of gastric cancer in patients having endoscopic mucosal resection for gastric neoplasia. DESIGN: We searched the medical literature through February 2020 to identify randomised controlled trials (RCTs) examining effect of eradication therapy on subsequent occurrence of gastric cancer in healthy H. pylori-positive adults, and in H. pylori-positive patients with gastric neoplasia undergoing endoscopic mucosal resection. The control arm received placebo or no treatment. Follow-up was for ≥2 years. We estimated the relative risk (RR) number needed to treat (NNT), and evaluated the disability-adjusted life-years (DALYs) gained from screening from the meta-analysis. RESULTS: We identified 10 RCTs, seven recruited 8323 healthy individuals, and three randomised 1841 patients with gastric neoplasia. In healthy individuals, eradication therapy reduced incidence of gastric cancer (RR=0.54; 95% CI 0.40 to 0.72, NNT=72), and reduced mortality from gastric cancer (RR=0.61; 95% CI 0.40 to 0.92, NNT=135), but did not affect all-cause mortality. These data suggest that 8 743 815 DALYs (95% CI 5 646 173 to 11 847 456) would be gained if population screening and treatment was implemented globally. In patients with gastric neoplasia, eradication therapy also reduced incidence of future gastric cancer (RR=0.49; 95% CI 0.34 to 0.70, NNT=21). Adverse events were incompletely reported. CONCLUSION: There is moderate evidence to suggest that H. pylori eradication therapy reduces the incidence of gastric cancer in healthy individuals and patients with gastric neoplasia in East Asian countries. There also appears to be a reduction in gastric cancer-related mortality.