Publications by authors named "Colin W Howden"

138 Publications

Efficacy of empiric esophageal dilation in patients with non-obstructive dysphagia: systematic review and meta-analysis.

Scand J Gastroenterol 2021 Sep 3:1-6. Epub 2021 Sep 3.

Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, TN, USA.

Background And Aims: Empiric esophageal dilation is frequently performed for non-obstructive dysphagia. Studies evaluating its efficacy have reported conflicting results. In this meta-analysis, we have evaluated the efficacy of esophageal dilation in the management of non-obstructive dysphagia.

Methods: We reviewed several databases from inception to 26 May 2021 to identify randomized controlled trials (RCTs) and observational studies that evaluated the role of empiric esophageal dilation for non-obstructive dysphagia. Our outcomes of interest were clinical success (improvement in dysphagia after dilation) and difference in post-operative dysphagia score between groups. For categorical variables, we calculated pooled odds ratios (OR) with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effects model. We used GRADE framework to ascertain the quality of evidence.

Results: We included 4 studies (3 RCTs and one observational) with 243 patients; there were 133 treated with empiric dilation and 110 controls. We found no significant difference in clinical success (OR (95% CI) 1.91 (0.89, 4.08)) or post-procedure dysphagia score between groups (SMD (95% CI) 0.38 (-0.37, 1.14)). Our findings remained consistent on subgroup analysis including RCTs only. Quality of evidence ranged from low to very low based on GRADE framework.

Conclusions: Our meta-analysis does not support the use of empiric esophageal dilation in patients with non-obstructive dysphagia. More studies are required to confirm these findings.
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http://dx.doi.org/10.1080/00365521.2021.1971288DOI Listing
September 2021

The Effect of Food on the Pharmacokinetics of the Potassium-Competitive Acid Blocker Vonoprazan.

Clin Pharmacol Drug Dev 2021 Aug 24. Epub 2021 Aug 24.

Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

Herein, we report a food-effect study of vonoprazan, an oral potassium-competitive acid blocker. In a phase 1, randomized, open-label, crossover study, healthy subjects received a single 20-mg dose of vonoprazan either following an overnight fast or 30 minutes after a high-fat breakfast. Plasma vonoprazan levels were determined at 0 hour and at 17 subsequent assessment points up to 48 hours after dosing. After a 5-day washout, subjects received a second 20-mg vonoprazan dose in the alternative fed/fasted state (identical process repeated). Twenty-four subjects completed the study. Vonoprazan exposure was not meaningfully affected by food. Geometric mean ratios for maximum concentration, area under the concentration-time curve from time 0 to 24 hours, and area under the plasma concentration-time curve extrapolated to infinity obtained under fed and fasting conditions were 1.05 (90% confidence interval, 0.98-1.12), 1.13 (1.09-1.18), and 1.15 (1.11-1.19), respectively. Four subjects experienced 6 adverse events that were all mild and considered unrelated to the study drug. Vonoprazan can be administered without regard to food intake.
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http://dx.doi.org/10.1002/cpdd.1009DOI Listing
August 2021

Alarming Trends in Opioid Use Among Patients With GERD.

Am J Gastroenterol 2021 Jun 16. Epub 2021 Jun 16.

IBM Watson Health, Cambridge, Massachusetts, USA.

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http://dx.doi.org/10.14309/ajg.0000000000001329DOI Listing
June 2021

A Patient with Eosinophilic Esophagitis and Herpes Simplex Esophagitis: A Case Report and Literature Review.

Case Rep Gastrointest Med 2021 25;2021:5519635. Epub 2021 May 25.

Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN 38104, USA.

Acute herpes simplex esophagitis (HSE) is common in immunocompromised patients. Eosinophilic esophagitis (EoE) is characterized by immune-mediated eosinophil-predominant esophageal inflammation. We report a patient with human immunodeficiency virus infection who presented with dysphagia and odynophagia and was found to have HSE and EoE. The combination of these two relatively rare conditions suggests possible predisposition.
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http://dx.doi.org/10.1155/2021/5519635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169267PMC
May 2021

A change at the top.

Authors:
Colin W Howden

Aliment Pharmacol Ther 2021 07;54(1)

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http://dx.doi.org/10.1111/apt.16442DOI Listing
July 2021

Insights on the Potential Use of Potassium-Competitive Acid Blockers in Erosive Esophagitis.

Authors:
Colin W Howden

Gastroenterol Hepatol (N Y) 2021 Apr;17(4):178-180

Hyman Professor of Medicine Chief, Division of Gastroenterology University of Tennessee Health Science Center Memphis, Tennessee.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132630PMC
April 2021

Estimate of Refractory Reflux Disease in the United States: Economic Burden and Associated Clinical Characteristics.

J Clin Gastroenterol 2021 Mar 12. Epub 2021 Mar 12.

*College of Medicine, University of Tennessee, Memphis, TN †Ironwood Pharmaceuticals ‡IBM Watson Health, Cambridge, MA.

Goals: To update the estimate of the prevalence of refractory gastroesophageal reflux disease (GERD) in the United States, and to assess the clinical and economic differences between patients with and without refractory GERD.

Background: GERD affects 18% to 28% of the US population, with nearly 40% of GERD patients presenting with refractory symptoms despite ongoing therapy.

Study: Retrospective analysis of the IBM MarketScan databases between January 2011 and June 2018. Inclusion criteria were prescription fill and subsequent refill of a proton pump inhibitor or H2-receptor antagonist (earliest claim=index date), diagnosis of GERD 60 days preceding and/or following index, continuous insurance enrolment for 12 months preceding/following index, and absence of prior GERD diagnosis or GERD medication. We derived refractory GERD symptom scores for all patients on the basis of a previously published algorithm. Health care costs and comorbidities were assessed for all patients and compared between those with and without refractory GERD.

Results: In total, 399,017 GERD patients qualified for the study; 103,654 (26%) met our definition of having indications of refractory GERD symptoms. Patients with refractory GERD symptoms reported significantly higher rates of hiatal hernia (25.1% vs. 5.9%), esophagitis (37.3% vs. 11.8%), esophageal stricture (11.3% vs. 1.5%), and dysphagia (26.8% vs. 7.1%; P<0.01 for each). The refractory GERD symptoms cohort incurred ~$10,000 greater health care costs per patient per year compared with patients without refractory GERD symptoms ($26,057±$58,948 vs. $15,285±$39,307; P<0.01).

Conclusions: Refractory GERD symptoms were associated with a substantial increase in health care costs. Treatments aimed at improving refractory GERD symptoms may mitigate symptom burden, potentially reducing health care expenditure.
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http://dx.doi.org/10.1097/MCG.0000000000001518DOI Listing
March 2021

Efficacy and safety of peroral endoscopic myotomy in the management of recurrent achalasia after failed Heller myotomy: a systematic review and meta-analysis.

Ann Gastroenterol 2021 7;34(2):155-163. Epub 2020 Dec 7.

Division of Gastroenterology, University of Utah, Salt Lake City, UT (Stephanie McDonough, Douglas G. Adler).

Background: Heller myotomy (HM) is an established treatment for achalasia but can fail in up to 10-20% of patients. Peroral endoscopic myotomy (POEM) may be an appropriate treatment for patients with failed HM.

Methods: We searched several databases to identify non-comparative studies evaluating the efficacy and/or safety of POEM after failed HM and comparative studies comparing the efficacy and/or safety of POEM in patients with and without prior HM. Outcomes assessed included clinical success, technical success, adverse events, post-treatment gastroesophageal reflux disease (GERD), and presence of esophagitis on endoscopy. We calculated weighted pooled rates with 95% confidence intervals (CI) for all outcomes in patients undergoing POEM with prior HM. We calculated pooled odds ratios with 95%CI to compare the outcomes between patients with and without previous HM who underwent POEM.

Results: We included 11 observational studies with 1205 patients. Weighted pooled rates (95%CI) for overall clinical success and technical success in patients with failed HM were 87% (81-91%) and 97% (94-99%), respectively. Weighted pooled rates (95%CI) for major adverse events, new-onset GERD and presence of esophagitis on endoscopy were 5% (2-10%), 33% (26-41%), and 38% (22-58%), respectively. There were no differences in clinical success, adverse events, post-treatment GERD and esophagitis between patients with and without previous HM.

Conclusions: POEM is safe and effective in patients with failed HM and should be considered in patients with recurrent achalasia after HM. Outcomes of POEM are comparable in patients with and without prior HM.
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http://dx.doi.org/10.20524/aog.2020.0563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903572PMC
December 2020

Review article: potassium-competitive acid blockers for the treatment of acid-related disorders.

Aliment Pharmacol Ther 2021 04 16;53(7):794-809. Epub 2021 Feb 16.

Division of Gastroenterology, University of Tennessee College of Medicine, Memphis, TN, USA.

Background: Potassium-competitive acid blockers (P-CABs) are a novel group of acid-suppressing medicines for the management of acid-related disorders.

Aims: To review published clinical pharmacology studies and clinical trials of P-CABs.

Methods: We conducted a comprehensive literature search including Medline (PubMed), EMBASE, Web of Science and the Cochrane Library from inception until November 2020, for studies of the clinical pharmacology of P-CABs and relevant clinical trials of those that are currently licensed or in development.

Results: Most publications concerned vonoprazan, which forms the bulk of this review. It is currently licensed in some Asian and South American countries and is being developed for North America. In clinically relevant doses, P-CABs have produced more rapid and profound suppression of intragastric acidity than proton pump inhibitors (PPIs). Vonoprazan was non-inferior to lansoprazole in healing erosive oesophagitis (2 randomised controlled trials [RCTs] in 1137 subjects) and superior in maintaining remission (1 RCT; 607 subjects). In 2 RCTs (1120 total subjects), both vonoprazan and tegoprazan were non-inferior to lansoprazole for healing peptic ulcers. Three RCTs and numerous non-randomised studies have compared vonoprazan-based and PPI-based regimens for Helicobacter pylori infection; vonoprazan-based triple or dual regimens have been highly effective.

Conclusions: P-CABs have some potential advantages over PPIs. To date, most research has been conducted in Asia; results of clinical trials that are underway in the United States and Europe are anticipated in 2021.
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http://dx.doi.org/10.1111/apt.16295DOI Listing
April 2021

Efficacy and safety of supplemental intravenous lidocaine for sedation in gastrointestinal endoscopic procedures: systematic review and meta-analysis of randomized controlled trials.

Gastrointest Endosc 2021 06 21;93(6):1241-1249.e6. Epub 2021 Jan 21.

Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

Background And Aims: Some studies have shown that intravenous (IV) lidocaine reduces the dose requirement of propofol in GI endoscopic procedures. We conducted this study to evaluate the efficacy and safety of the combination of IV lidocaine and propofol compared with propofol alone in GI endoscopic procedures.

Methods: We reviewed several databases from inception to October 13, 2020, to identify randomized controlled trials (RCTs) that compared the role of IV propofol and lidocaine with IV propofol plus placebo for sedation in endoscopic procedures. Our outcomes of interest were the differences in total dose of propofol administered, procedure time, and intraoperative adverse events. For categorical variables, we calculated pooled risk ratios with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effect model. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework to ascertain the quality of evidence.

Results: We included 5 randomized controlled trials with 318 patients. We found that the total dose of propofol administered was significantly lower in the lidocaine group than the control group (SMD, -0.76; 95% CI, -1.09 to -0.42). We found no significant difference in procedure time (SMD, 0.16; 95% CI, -0.26 to 0.57) or adverse events (risk ratio, 0.60; 95% CI, 0.35-1.03) between the groups. There was moderate to substantial heterogeneity in the data. Quality of evidence based on the GRADE framework ranged from low to moderate.

Conclusions: Moderate quality of evidence suggests that IV lidocaine decreases the dose of propofol administered for GI endoscopic procedures.
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http://dx.doi.org/10.1016/j.gie.2021.01.008DOI Listing
June 2021

Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials.

Gastrointest Endosc 2021 06 5;93(6):1228-1237.e5. Epub 2021 Jan 5.

Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee, USA.

Background And Aims: Studies evaluating the role of routine second-look endoscopy in patients with acute upper GI bleed because of peptic ulcer disease (PUD) have reported conflicting results. This meta-analysis evaluates the usefulness of routine second-look endoscopy in these patients.

Methods: We reviewed several databases from inception to September 15, 2020 to identify randomized controlled trials (RCTs) that compared routine second-look endoscopy with no planned second-look endoscopy in patients with acute upper GI bleed because of PUD. Our outcomes of interest were recurrent bleeding, mortality, need for surgery, and mean number of units of blood transfused. For categorical variables, we calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs); for continuous variables, we calculated standardized mean difference with 95% CIs. Data were analyzed using a random effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to ascertain the quality of evidence.

Results: We included 9 RTCs comprising 1452 patients; 726 patients underwent planned/routine second-look endoscopy and 726 did not. We found no significant difference in recurrent bleeding (RR, .79; 95% CI, .51-1.23), need for surgery (RR, .58; 95% CI, .29-1.15), mortality (RR, .69; 95% CI, .33-1.45), or mean number of units of blood transfused (standardized mean difference, -.06; 95% CI, -.19 to .07). Quality of evidence ranged from low to moderate based on the GRADE framework.

Conclusions: Single endoscopy with complete endoscopic hemostasis is not inferior to routine second-look endoscopy in reducing the risk of recurrent bleeding, mortality, or need for surgery in patients with acute upper GI bleed because of PUD.
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http://dx.doi.org/10.1016/j.gie.2020.12.039DOI Listing
June 2021

Recent Developments Pertaining to H. pylori Infection.

Am J Gastroenterol 2021 01;116(1):1-3

Baylor College of Medicine, Houston, Texas.

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http://dx.doi.org/10.14309/ajg.0000000000001031DOI Listing
January 2021

A Message from the Editors.

Aliment Pharmacol Ther 2021 01;53(1):4-5

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http://dx.doi.org/10.1111/apt.16188DOI Listing
January 2021

Editorial: pharmacodynamics of potassium-competitive acid blockers: comparing apples with apples-and with oranges.

Authors:
Colin W Howden

Aliment Pharmacol Ther 2021 01;53(1):190-191

Division of Gastroenterology, University of Tennessee College of Medicine, Memphis, TN, USA.

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http://dx.doi.org/10.1111/apt.16140DOI Listing
January 2021

Efficacy and safety of tranexamic acid in acute upper gastrointestinal bleeding: meta-analysis of randomised controlled trials.

Scand J Gastroenterol 2020 Dec 28;55(12):1390-1397. Epub 2020 Oct 28.

Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, TN, USA.

Background: Studies evaluating the role of tranexamic acid in acute upper GI bleeding (UGIB) have reported conflicting results. In this systematic review, we have evaluated the efficacy and safety of tranexamic acid in UGIB.

Methods: We searched several databases from inception to June 6, 2020 to identify randomised controlled trials (RCTs) that compared tranexamic acid and placebo in UGIB. Our outcomes of interest were mortality, rebleeding, all thromboembolic events, venous thromboembolic events, need for transfusion, endoscopic intervention and surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using fixed effect model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess the certainty of evidence.

Results: We included 12 RCTs comprising 14,100 patients. We found no significant difference in mortality, pooled RR (95% CI) 0.87 (0.74-1.01), rebleeding, pooled RR (95% CI) 0.90 (0.79-1.02), need for surgery, pooled RR (95% CI) 0.86 (0.73-1.02), need for transfusion, pooled RR (95% CI) 1.00 (0.99-1.01) or thromboembolic events, RR (95% CI) 1.16 (0.87-1.56) between treatments. We found an increased risk of venous thromboembolic events with tranexamic acid, pooled RR (95% CI) 1.94 (1.23-3.05). Certainty of evidence based on the GRADE framework for the different outcomes ranged from low to very low.

Conclusions: Tranexamic acid does not improve outcomes in UGIB and may increase the risk of venous thromboembolic events.
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http://dx.doi.org/10.1080/00365521.2020.1839963DOI Listing
December 2020

Underwater vs conventional endoscopic mucosal resection in the management of colorectal polyps: a systematic review and meta-analysis.

Endosc Int Open 2020 Oct 22;8(10):E1264-E1272. Epub 2020 Sep 22.

Division of Gastroenterology, California Pacific Medical Center, San Francisco, California, United States.

Recently, underwater endoscopic mucosal resection (UEMR) has shown promising results in the management of colorectal polyps. Some studies have shown better outcomes compared to conventional endoscopic mucosal resection (EMR). We conducted this systematic review and meta-analysis to compare UEMR and EMR in the management of colorectal polyps. We searched several databases from inception to November 2019 to identify studies comparing UEMR and EMR. Outcomes assessed included rates of en bloc resection, complete macroscopic resection, recurrent/residual polyps on follow-up colonoscopy, complete resection confirmed by histology and adverse events. Pooled risk ratios (RR) with 95 % confidence interval were calculated using a fixed effect model. Heterogeneity was assessed by I statistic. Funnel plots and Egger's test were used to assess publication bias. We used the Newcastle-Ottawa scale (NOS) for assessment of quality of observational studies, and the Cochrane tool for assessing risk of bias for RCTs Seven studies with 1291 patients were included; two were randomized controlled trials and five were observational. UEMR demonstrated statistically significantly better efficacy in rates of en bloc resection, pooled RR 1.16 (1.08, 1.26), complete macroscopic resection, pooled RR 1.28 (1.18, 1.39), recurrent/residual polyps; pooled RR 0.26 (0.12, 0.56) and complete resection confirmed by histology; pooled RR 0.75 (0.57, 0.98). There was no significant difference in adverse events (AEs); pooled RR 0.68 (0.44, 1.05). This meta-analysis found statistically significantly better rates of en bloc resection, complete macroscopic resection, and lower risk of recurrent/residual polyps with UEMR compared to EMR. We found no significant difference in AEs between the two techniques.
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http://dx.doi.org/10.1055/a-1214-5692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508646PMC
October 2020

Prophylactic hemoclips in prevention of delayed post-polypectomy bleeding for ≥ 1 cm colorectal polyps: meta-analysis of randomized controlled trials.

Endosc Int Open 2020 Sep 31;8(9):E1102-E1110. Epub 2020 Aug 31.

Division of Gastroenterology, University of Tennessee Health Science Center, Memphis, Tennessee, United States.

Studies evaluating the role of prophylactic hemoclips (HC) in prevention of delayed post-polypectomy bleeding (DPPB) have reported conflicting results. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the role of prophylactic HC placement in prevention of DPPB for polyps ≥ 1 cm in size. We reviewed several databases to identify RCTs evaluating the role of HC in prevention of DPPB. The outcomes assessed included prevention of DPPB with polyps 1 to 1.9 cm, ≥ 2 cm, any polyp ≥ 1 cm, proximal colon polyps, distal colon polyps, and perforation. We analyzed data using a fixed effect model and reported summary pooled risk ratios (RR) with 95 % confidence intervals (CI). We assessed heterogeneity with the I statistic. We included nine RCTs with 4550 patients. For polyps ≥ 2 cm, there was a statistically significantly lower risk of DPPB with use of HC; RR 0.55, 95 % CI 0.36, 0.86. There was also a statistically significantly lower risk for proximal colon polyps ≥ 2 cm; RR 0.41 (0.24, 0.70) but no significant difference for distal polyps; RR 1.23 (0.45, 3.32). There was also no significant difference in risk for polyps 1 to 1.9 cm; RR 1.07 (0.59, 1.97). There was no significant reduction in risk of perforation with HC use for any polyp size. Prophylactic HC placement is effective in prevention of DPPB from proximal colon polyps ≥ 2 cm, but of no significant benefit for polyps 1 to 1.9 cm in size or for distal colon polyps ≥ 2 cm.
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http://dx.doi.org/10.1055/a-1164-6315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458729PMC
September 2020

Update on the Management of Infection.

Curr Treat Options Gastroenterol 2020 Jul 17:1-12. Epub 2020 Jul 17.

Division of Gastroenterology, University of Tennessee College of Medicine, 956 Court Avenue, Suite H210, Memphis, TN 38163 USA.

Purpose Of Review: Our purpose was to provide an update on methods and indications for testing and treatment selection focusing on novel modalities.

Recent Findings: Increasing antibiotic resistance has reduced treatment effectiveness. Antibiotic resistance testing is not widely available in North America where there are insufficient resistance and susceptibility data. Quadruple regimens (bismuth-based or concomitant/non-bismuth-based) have been recommended first-line. A rifabutin-based combination product recently approved by the US Food and Drug Administration is highly effective and should simplify treatment. The potassium-competitive acid blocker vonoprazan is being evaluated as part of dual or triple combination regimens. Molecular-based genotypic testing for antibiotic resistance and an effective vaccine remain under development.

Summary: Inability to test for antibiotic resistance renders treatment selection empiric. However, resistance to rifabutin and amoxicillin remains rare. Effective management continues to comprise appropriate diagnostic testing for active infection, utilization of an effective regimen, and post-treatment testing.
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http://dx.doi.org/10.1007/s11938-020-00300-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365691PMC
July 2020

Endoscopy and central reading in inflammatory bowel disease clinical trials: achievements, challenges and future developments.

Gut 2021 02 22;70(2):418-426. Epub 2020 Jul 22.

Department of Medicine IV, Medical University Vienna, Vienna, Austria.

Central reading, that is, independent, off-site, blinded review or reading of imaging endpoints, has been identified as a crucial component in the conduct and analysis of inflammatory bowel disease clinical trials. Central reading is the final step in a workflow that has many parts, all of which can be improved. Furthermore, the best reading algorithm and the most intensive central reader training cannot make up for deficiencies in the acquisition stage (clinical trial endoscopy) or improve on the limitations of the underlying score (outcome instrument). In this review, academic and industry experts review scoring systems, and propose a theoretical framework for central reading that predicts when improvements in statistical power, affecting trial size and chances of success, can be expected: Multireader models can be conceptualised as statistical or non-statistical (social). Important organisational and operational factors, such as training and retraining of readers, optimal bowel preparation for colonoscopy, video quality, optimal or at least acceptable read duration times and other quality control matters, are addressed as well. The theory and practice of central reading and the conduct of endoscopy in clinical trials are interdisciplinary topics that should be of interest to many, regulators, clinical trial experts, gastroenterology societies and those in the academic community who endeavour to develop new scoring systems using traditional and machine learning approaches.
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http://dx.doi.org/10.1136/gutjnl-2020-320690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815632PMC
February 2021

Systematic review and meta-analysis: monopolar hemostatic forceps with soft coagulation in the treatment of peptic ulcer bleeding.

Eur J Gastroenterol Hepatol 2020 06;32(6):678-685

Division of Gastroenterology, University of Tennessee College of Medicine, Memphis, Tennessee, USA.

Monopolar hemostatic forceps with soft coagulation (MHFSC) have been compared with hemoclips, heater probe, and argon plasma coagulation (APC) for the treatment of peptic ulcer bleeding. In this systematic review and meta-analysis, we compared MHFSC with other modalities in the treatment of peptic ulcer bleeding. We reviewed MEDLINE, Embase, Scopus, Cochrane, Web of Science, and Scopus from inception to 7 January 2019 to identify studies comparing MHFSC with other modalities for peptic ulcer bleeding. The primary outcome of interest was achievement of initial hemostasis. Secondary outcomes were rebleeding, adverse events, procedure time, and length of hospital stay. Data were analyzed using a random effects model and summarized as pooled odds ratio (OR) with 95% confidence interval (CI). Heterogeneity was assessed by I statistic. We included five randomized controlled trials and one observational study comprising 693 patients with endoscopically confirmed actively bleeding ulcers (spurting or oozing) or nonbleeding visible vessel. MHFSC was superior to other modalities in achieving initial hemostasis (OR 0.25; 95% CI 0.08-0.81; I = 67%) and prevention of rebleeding (OR 0.28; 95% CI 0.09-0.86; I = 46%). Rates of adverse events were similar between MHFSC and other modalities. Procedure times were shorter with MHFSC (mean difference -4.15 min; 95% CI -4.83 to -3.47; I= 59%). Length of hospital stay was also shorter with MHFSC. MHFSC appears to be more effective than other modalities for achievement of initial hemostasis and reduction of rebleeding among patients with peptic ulcer bleeding.
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http://dx.doi.org/10.1097/MEG.0000000000001738DOI Listing
June 2020

PPIs and GI Cancers: Impeached But Likely to Be Acquitted.

Authors:
Colin W Howden

Am J Gastroenterol 2020 05;115(5):683-684

Division of Gastroenterology, University of Tennessee College of Medicine, Memphis, Tennessee, USA.

In this edition of the journal, there is an important nested case-control study from investigators at Kaiser Permanente, Northern California. Proton pump inhibitor exposure for 10 or more years was not associated with any increased risk of gastric cancer. Small observed increased risks of colorectal, hepatocellular, and pancreatic cancers with 10 or more years of exposure are likely to have been spurious. If proton pump inhibitors were to be impeached on the basis of gastrointestinal cancer risk, they are likely to be subsequently acquitted.
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http://dx.doi.org/10.14309/ajg.0000000000000590DOI Listing
May 2020

No Association Linking Short-Term Proton Pump Inhibitor Use to Dementia: Systematic Review and Meta-analysis of Observational Studies.

Am J Gastroenterol 2020 05;115(5):671-678

Division of Gastroenterology and Hepatology, University of Tennessee College of Medicine, Memphis, Tennessee, USA.

Introduction: Long-term use of proton pump inhibitors (PPIs) has been associated with a wide variety of potentially serious adverse effects including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions. We aimed to evaluate this proposed association further and to assess the quality of the evidence in its support.

Methods: We searched MEDLINE, EMBASE, ISI Web of Science, and Cochrane databases for studies examining a link between PPI use and dementia, up to February 2019. Studies reporting summary results as hazard ratio (HR) or odds ratio (OR) were pooled using the DerSimonian and Laird random-effects model for meta-analyses. Methodological quality of individual observational studies was assessed using the Newcastle-Ottawa scale and the overall quality of evidence rated as per the GRADE approach.

Results: We identified and included 11 observational studies comprising 642,949 subjects; 64% were women. Most studies were short-term ranging from 5 to 10 years. There were 158,954 PPI users and 483,995 nonusers. For studies summarizing data as adjusted HR, pooled HR for all causes of dementia was 1.10 (0.88-1.37); for Alzheimer dementia only, it was 1.06 (0.72-1.55). For studies summarizing data as adjusted OR, pooled OR for all causes of dementia was 1.03 (0.84-1.25) and for Alzheimer dementia only 0.96 (0.82-1.11). Per Newcastle-Ottawa scale assessment, 10 studies were of high quality and 1 was of moderate quality. By applying GRADE methodology, quality of evidence for both outcomes was very low.

Discussion: We found no evidence to support the proposed association between PPI use and an increased risk of dementia. PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.
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http://dx.doi.org/10.14309/ajg.0000000000000500DOI Listing
May 2020

Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis.

BMJ 2019 Dec 11;367:l6483. Epub 2019 Dec 11.

Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK

Objective: To determine the effectiveness of management strategies for uninvestigated dyspepsia.

Design: Systematic review and network meta-analysis.

Data Sources: Medline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to September 2019, with no language restrictions. Conference proceedings between 2001 and 2019.

Eligibility Criteria For Selecting Studies: Randomised controlled trials that assessed the effectiveness of management strategies for uninvestigated dyspepsia in adult participants (age ≥18 years). Strategies of interest were prompt endoscopy; test for and perform endoscopy in participants who test positive; test for and eradication treatment in those who test positive ("test and treat"); empirical acid suppression; or symptom based management. Trials reported dichotomous assessment of symptom status at final follow-up (≥12 months).

Results: The review identified 15 eligible randomised controlled trials that comprised 6162 adult participants. Data were pooled using a random effects model. Strategies were ranked according to P score, which is the mean extent of certainty that one management strategy is better than another, averaged over all competing strategies. "Test and treat" ranked first (relative risk of remaining symptomatic 0.89, 95% confidence interval 0.78 to 1.02, P score 0.79) and prompt endoscopy ranked second, but performed similarly (0.90, 0.80 to 1.02, P score 0.71). However, no strategy was significantly less effective than "test and treat." Participants assigned to "test and treat" were significantly less likely to receive endoscopy (relative risk prompt endoscopy 0.23, 95% confidence interval 0.17 to 0.31, P score 0.98) than all other strategies, except symptom based management (relative risk symptom based management 0.60, 0.30 to 1.18). Dissatisfaction with management was significantly lower with prompt endoscopy (P score 0.95) than with "test and treat" (relative risk "test and treat" 0.67, 0.46 to 0.98), and empirical acid suppression (relative risk empirical acid suppression 0.58, 0.37 to 0.91). Upper gastrointestinal cancer rates were low in all trials. Results remained stable in sensitivity analyses, with minimal inconsistencies between direct and indirect results. Risk of bias of individual trials was high; blinding was not possible because of the pragmatic trial design.

Conclusions: "Test and treat" was ranked first, although it performed similarly to prompt endoscopy and was not superior to any of the other strategies. "Test and treat" led to fewer endoscopies than all other approaches, except symptom based management. However, participants showed a preference for prompt endoscopy as a management strategy for their symptoms.

Systematic Review Registration: PROSPERO registration number CRD42019132528.
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