Cathy Bennett

Consensus Statements for Management of Barrett's Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barretts esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

Performance measures for lower gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have identified quality of endoscopy as a major priority and we described our rationale for this in a first manuscript that also addressed the methodology of the quality initiative process.1 The identification of upper gastrointestinal (UGI) performance measures presents a considerable challenge, in contrast to the situation with colonoscopy for instance, where several performance measures (inspection time, adenoma detection rate, and interval cancers, among others) have been identified over the last decade.2,3 Following the Quality in UGI Endoscopy meeting held in Lisbon in 2013, it was clear that there was a need to identify performance measures for the UGI tract, and that quality standards could be identified although there is a paucity of evidence. This lack of evidence helps however to identify research priorities for the development of clinical trials that will further validate and substantiate the implementation of performance measures. The aim therefore of the UGI working group was twofold: (a) to identify performance measures for UGI endoscopy; (b) to identify the evidence or absence of evidence that would develop the research priorities in this field. We used an innovative methodology to facilitate the quality initiative process, which combined a thorough search and standardized evaluation of the available evidence for each clinical question, followed by a Delphi process (http://is.njit.edu/pubs/delphibook/delphibook.pdf) using an online platform.4,5 This online platform permitted iterative rounds of modification and comment by all members of the UGI working group until agreement was reached on the performance measure. We now report these newly identified performance measures.

BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia

OBJECTIVES:Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD).METHODS:We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations.RESULTS:In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients.CONCLUSIONS:In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.

Use of the capture-recapture technique to evaluate the completeness of systematic literature searches

Capture-recapture methods were pioneered in ecology and derive their name from censuses of wildlife in which several animals are captured, marked, released, and subject to recapture. In epidemiology the technique examines the degree of overlap between two (or more) methods of ascertainment and uses a simple formula to estimate the total size of the population. When the number already identified is subtracted from this estimate the number of cases not ascertained by either (or any) of the methods can then be calculated. It has been suggested that studies which attempt to ascertain all cases of a given disease in a population should use this method to estimate the number of missing cases.1 2 There are direct parallels between epidemiological studies which attempt to ascertain all available cases and systematic literature …

Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Objective Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes. Design Systematic review and meta-analysis. Data Sources and Study Selection We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks. Comparison groups could receive placebo or oral antidiabetic drugs (OAD) including metformin, sulphonylureas (SU), or dipeptidyl peptidase 4 inhibitors (DPP-4-i). Trials were identified through electronic databases and extensive manual searches. Primary outcomes were glycated haemoglobin A1c (HbA1c) levels, serious adverse events, death, severe hypoglycaemia, ketoacidosis and CVD. Secondary outcomes were fasting plasma glucose, body weight, blood pressure, heart rate, lipids, liver function tests, creatinine and adverse events including infections. The quality of the evidence was assessed using GRADE. Results Meta-analysis of 34 RCTs with 9,154 patients showed that SGLT2-i reduced HbA1c compared with placebo (mean difference -0.69%, 95% confidence interval -0.75 to -0.62%). We downgraded the evidence to ‘low quality’ due to variability and evidence of publication bias (P = 0.015). Canagliflozin was associated with the largest reduction in HbA1c (-0.85%, -0.99% to -0.71%). There were no differences between SGLT2-i and placebo for serious adverse events. SGLT2-i increased the risk of urinary and genital tract infections and increased serum creatinine, and exerted beneficial effects on bodyweight, blood pressure, lipids and alanine aminotransferase (moderate to low quality evidence). Analysis of 12 RCTs found a beneficial effect of SGLT2-i on HbA1c compared with OAD (-0.20%, -0.28 to -0.13%; moderate quality evidence). Conclusion This review includes a large number of patients with type 2 diabetes and found that SGLT2-i reduces HbA1c with a notable increased risk in non-serious adverse events. The analyses may overestimate the intervention benefit due bias.

The European Society of Gastrointestinal Endoscopy Quality Improvement Initiative: developing performance measures

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have a vision to create a thriving community of endoscopy services across Europe, collaborating with each other to provide high quality, safe, accurate, patient-centered and accessible endoscopic care. Whilst the boundaries of what can be achieved by advanced endoscopy are continually expanding, we believe that one of the most fundamental steps to achieving our goal is to raise the quality of everyday endoscopy. The development of robust, consensus- and evidence-based key performance measures is the first step in this vision. ESGE and UEG have identified quality of endoscopy as a major priority. This paper explains the rationale behind the ESGE Quality Improvement Initiative and describes the processes that were followed. We recommend that all units develop mechanisms for audit and feedback of endoscopist and service performance using the ESGE performance measures that will be published in future issues of this journal over the next year. We urge all endoscopists and endoscopy services to prioritize quality and to ensure that these performance measures are implemented and monitored at a local level, so that we can provide the highest possible care for our patients.

Systemic antifungal therapy for tinea capitis in children: An abridged Cochrane Review

Background: The comparative efficacy and safety profiles of systemic antifungal drugs for tinea capitis in children remain unclear. Objective: We sought to assess the effects of systemic antifungal drugs for tinea capitis in children. Methods: We used standard Cochrane methodological procedures. Results: We included 25 randomized controlled trials with 4449 participants. Terbinafine and griseofulvin had similar effects for children with mixed Trichophyton and Microsporum infections (risk ratio 1.08, 95% confidence interval 0.94‐1.24). Terbinafine was better than griseofulvin for complete cure of T tonsurans infections (risk ratio 1.47, 95% confidence interval 1.22‐1.77); griseofulvin was better than terbinafine for complete cure of infections caused solely by Microsporum species (risk ratio 0.68, 95% confidence interval 0.53‐0.86). Compared with griseofulvin or terbinafine, itraconazole and fluconazole had similar effects against Trichophyton infections. Limitations: All included studies were at unclear or high risk of bias. Lower quality evidence resulted in a lower confidence in the estimate of effect. Significant clinical heterogeneity existed across studies. Conclusions: Griseofulvin or terbinafine are both effective; terbinafine is more effective for T tonsurans and griseofulvin for M canis infections. Itraconazole and fluconazole are alternative but not optimal choices for Trichophyton infections. Optimal regimens of antifungal agents need further studies.

Group-Based Parenting Programs for Improving Parenting and Psychosocial Functioning: A Systematic Review

Parental psychosocial health can have a significant effect on the later psychological health of the child. Parenting programs have been shown to have an effect on the emotional and behavioral adjustment of children, and this review examined such programs’ effect on parental psychosocial well-being. We searched a range of electronic databases and included randomized controlled trials that compared a group-based parenting program with a control condition and used at least 1 standardized measure of parental psychosocial health. We used a random effects meta-analysis, and we report standardized mean differences (SMD) and 95% confidence intervals (CI) for all outcomes. We included 48 studies with 4,937 participants and evaluated 3 types of programs: behavioral, cognitive-behavioral, and multimodal. Overall, we find parents’ participation in group-based parenting programs is associated with statistically significant short-term improvements in depression (SMD -0.17, 95% CI -0.28 to -0.07), anxiety (SMD -0.22, 95% CI -0.43 to -0.01), stress (SMD -0.29, 95% CI -0.42 to -0.15), anger (SMD -0.60, 95% CI -1.00 to -0.20), guilt (SMD -0.79, 95% CI -1.18 to -0.41), confidence (SMD -0.34, 95% CI -0.51 to -0.17) and satisfaction with the partner relationship (SMD -0.28, 95% CI -0.47 to -0.09). However, only stress and confidence continued to be significant at the 6-month follow-up, and none were significant at 1year. The findings of this review support the use of parenting programs to improve the short-term psychosocial wellbeing of parents. Further training might be required to ensure that these benefits are maintained.

Endoscopic therapies for the prevention and treatment of early esophageal neoplasia

Esophageal cancers have traditionally been diagnosed late and prognosis has been dire. For many years the only real treatment option was esophagectomy with substantial morbidity and mortality. This situation has now changed dramatically. Improvements have been achieved in surgical outcomes and there is an array of new effective treatment options now available, particularly for the increasing proportion diagnosed with early-stage disease. Minimally invasive endoscopic therapies can now prevent, cure or palliate esophageal cancers. This article aims to investigate the role and evidence base for these new therapeutic options.

Management of Barrett esophagus: a practical guide for clinicians based on the BADCAT and BoB CAT recommendations.

We undertook two of the largest evidence-based reviews in clinical medicine to assess the rationale for the management of gastroesophageal reflux disease, Barrett esophagus (BE), dysplasia, and early invasive esophageal adenocarcinoma. These reviews involved over 150 world experts in 4 continents, and over 20 000 papers were assessed. Quality assessment of the publications was made using Grading of Recommendations Assessment, Development and Evaluation, and of over 240 questions formulated, we were able to answer 30% with an agreement of at least 80%. We agreed on a unique global definition of BE meaning that the presence both of hiatus hernia endoscopically and of intestinal metaplasia histologically should be noted. In addition, we devised an escalation and deescalation pathway for the management of esophagitis, metaplasia, dysplasia, and adenocarcinoma sequence. Endoscopic resection (ER) is recommended for visible mucosal lesions. Moreover, we endorsed the early use of ablation therapy for persistent dysplasia of any degree. In this regard, ER may be both diagnostic and therapeutic and may be sufficient even in early mucosal lesions (T1m). In conclusion, fewer people should be surveyed but those that do will require more detailed mapping and endoscopic interventions than currently. In addition, patients accumulating other potentially life-threaten-ing comorbidities should be offered cessation of surveillance. In the future, chemoprevention may be the game-changing solution but results from large randomized trials, including AspECT and BOSS, are awaited.