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Background Critically ill patients in the intensive care unit (ICU) are at risk of clinically important gastrointestinal bleeding, and acid suppressants are frequently used prophylactically. However, stress ulcer prophylaxis may increase the risk of serious adverse events and, additionally, the quantity and quality of evidence supporting the use of stress ulcer prophylaxis is low. The aim of the SUP-ICU trial is to assess the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in adult patients in the ICU. We hypothesise that stress ulcer prophylaxis reduces the rate of gastrointestinal bleeding, but increases rates of nosocomial infections and myocardial ischaemia. The overall effect on mortality is unpredictable. Methods/design The SUP-ICU trial is an investigator-initiated, pragmatic, international, multicentre, randomised, blinded, parallel-group trial of stress ulcer prophylaxis with a proton pump inhibitor versus placebo (saline) in 3350 acutely ill ICU patients at risk of gastrointestinal bleeding. The primary outcome measure is 90-day mortality. Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischaemia, days alive without life support in the 90-day period, serious adverse reactions, 1-year mortality, and health economic analyses. The sample size will enable us to detect a 20 % relative risk difference (5 % absolute risk difference) in 90-day mortality assuming a 25 % event rate with a risk of type I error of 5 % and power of 90 %. The trial will be externally monitored according to Good Clinical Practice standards. Interim analyses will be performed after 1650 and 2500 patients. Conclusion The SUP-ICU trial will provide high-quality data on the benefits and harms of stress ulcer prophylaxis with a proton pump inhibitor in critically ill adult patients admitted in the ICU. Trial registration ClinicalTrials.gov Identifier: NCT02467621 .

ObjectiveThe objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy.DesignA randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment.ResultsOf the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated.ConclusionVonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer.Trial registration numberNCT01505127.

Peptic ulcer disease usually occurs in the stomach and proximal duodenum. The predominant causes in the United States are infection with Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs. Symptoms of peptic ulcer disease include epigastric discomfort (specifically, pain relieved by food intake or antacids and pain that causes awakening at night or that occurs between meals), loss of appetite, and weight loss. Older patients and patients with alarm symptoms indicating a complication or malignancy should have prompt endoscopy. Patients taking nonsteroidal anti-inflammatory drugs should discontinue their use. For younger patients with no alarm symptoms, a test-and-treat strategy based on the results of H. pylori testing is recommended. If H. pylori infection is diagnosed, the infection should be eradicated and antisecretory therapy (preferably with a proton pump inhibitor) given for four weeks. Patients with persistent symptoms should be referred for endoscopy. Surgery is indicated if complications develop or if the ulcer is unresponsive to medications. Bleeding is the most common indication for surgery. Administration of proton pump inhibitors and endoscopic therapy control most bleeds. Perforation and gastric outlet obstruction are rare but serious complications. Peritonitis is a surgical emergency requiring patient resuscitation; laparotomy and peritoneal toilet; omental patch placement; and, in selected patients, surgery for ulcer control.

Clinicians routinely administer stress ulcer prophylaxis to mechanically ventilated patients in the intensive care unit (ICU), most commonly prescribing proton pump inhibitors (PPIs). However, the incidence of gastrointestinal (GI) bleeding from stress ulceration is low and recent observational studies suggest these agents may increase infections. Therefore, a large randomized clinical trial (RCT) is needed to inform modern practice. The aim of this multicenter pilot trial is to determine the feasibility of performing a large RCT to investigate the efficacy and safety of withholding intravenous pantoprazole. We will include adult critically ill patients who have an anticipated duration of ventilation of >=48 hours. We will exclude patients with acute or recent GI bleeding, pregnancy, dual antiplatelet therapy, poor prognosis or intent to withdraw life support, or previous enrolment in this or a confounding trial. Following informed consent, patients will be randomized to receive the intervention of placebo (0.9% NaCl) or intravenous pantoprazole 40 mg daily. Patients, families, clinicians, data collectors, adjudicators of outcome and statisticians will be blind to allocation. The three primary feasibility outcomes are the informed consent rate, recruitment rate, and protocol adherence. Clinical outcomes include clinically important upper GI bleeding, ventilator-associated pneumonia (VAP), Clostridium difficile infection, length of stay and mortality in ICU and hospital. This study has been approved by Health Canada, and research ethics board (REB) at each of the participating centers. This trial was registered on 31 October 2014. The trial registration number is NCT02290327. REVISE Pilot Trial is funded by Research Grant awarded by Physicians Services Incorporated, Dammam University Research Funds, Capital Health Authority Research Award Halifax, and Royal Adelaide Hospital Project Committee Grant.

Objective To evaluate the efficacy of intravenous pantoprazole as a stress ulcer prophylaxis in sick children to prevent gastrointestinal (GI) bleeding. Methods A randomized controlled trial included children aged one-month to 18 years requiring intensive care. Participants were randomly assigned to receive intravenous pantoprazole or a placebo (normal saline) daily. The primary outcome was the incidence of GI bleeding (clinically significant or overt). Secondary outcomes were the median time of onset of GI bleeding, incidence of ventilator-associated pneumonia (VAP), duration of hospitalization, organ dysfunction scores, and all-cause mortality. Results A total of 151 and 150 children were allocated to group A (pantoprazole) and group B (placebo), respectively. No significant difference was observed in the incidence of GI bleeding between the groups (group A: 21/151 vs group B: 19/150 [RR (95% CI) 1.03 (0.18, 5.82), P  = 0.985]. Comparable results were observed for clinically significant GI bleeding (1.3% vs 0.6%; RR (95% CI) 0.54 (0.21, 1.28); P  = 0.653 and overt GI bleeding [12.6% vs 12%; RR (95% CI) 0.98 (0.39, 2.23); P value = 0.313]. On multivariate analysis, there was a reduced incidence of GI bleeding in children with coagulopathy in pantoprazole group ( n  = 29) as compared to placebo ( n  = 25) [RR (95%CI) 0.52 (0.32, 0.87); P  = 0.022]. Conclusion Among critically ill children, pantoprazole prophylaxis did not reduce the incidence of gastrointestinal bleeding, although, a notable decrease in gastrointestinal bleeding was observed in children with coagulopathy. Trials Registry Clinical Trials Registry of India, Ref no: CTRI/2021/08/035785, Date of registration:18th August 2021.

Background Critically ill infants with congenital heart disease (CHD) are often prescribed stress ulcer prophylaxis (SUP) to prevent upper gastrointestinal bleeding, despite the low incidence of stress ulcers and limited data on the safety and efficacy of SUP in infants. Recently, SUP has been associated with an increased incidence of hospital-acquired infections, community-acquired pneumonia, and necrotizing enterocolitis. The objective of this pilot study is to investigate the feasibility of performing a randomized controlled trial to assess the safety and efficacy of withholding SUP in infants with congenital heart disease admitted to the cardiac intensive care unit. Methods A single center, prospective, double-blinded, randomized placebo-controlled pilot feasibility trial will be performed in infants with CHD admitted to the cardiac intensive care unit and anticipated to require respiratory support for > 24 h. Patients will be randomized to receive a histamine-2 receptor antagonist (H2RA) or placebo until they are discontinued from respiratory support. Randomization will be performed within 2 strata defined by admission type (medical or surgical) and age (neonate, age < 30 days, or infant, 1 month to 1 year). Allocation will be a 1:1 ratio using permuted blocks to ensure balanced allocations across the two treatment groups within each stratum. The primary outcomes include feasibility of screening, consent, timely allocation of study drug, and protocol adherence. The primary safety outcome is the rate of clinically significant upper gastrointestinal bleeding. The secondary outcomes are the difference in the relative and absolute abundance of the gut microbiota and functional microbial profiles between the two study groups. We plan to enroll 100 patients in this pilot study. Discussion Routine use of SUP to prevent upper gastrointestinal bleeding in infants is controversial due to a low incidence of bleeding events and concern for adverse effects. The role of SUP in infants with CHD has not been examined, and there is equipoise on the risks and benefits of withholding this therapy. In addition, this therapy has been discontinued in other neonatal populations due to the concern for hospital-acquired infections and necrotizing enterocolitis. Furthermore, exploring changes to the microbiome after exposure to SUP may highlight the mechanisms by which SUP impacts potential microbial dysbiosis of the gut and its association with hospital-acquired infections. Assessment of the feasibility of a trial of withholding SUP in critically ill infants with CHD will facilitate planning of a larger multicenter trial of safety and efficacy of SUP in this vulnerable population. Trial registration ClinicalTrials.gov , NCT03667703. Registered 12 September 2018, https://clinicaltrials.gov/ct2/show/NCT03667703?term=SUPPRESS+CHD&draw=2&rank=1 . All WHO Trial Registration Data Set Criteria are met in this manuscript.

Our aims were to assess risks of early rebleeding after successful endoscopic hemostasis for Forrest oozing (FIB) peptic ulcer bleeding (PUBs) compared with other stigmata of recent hemorrhage (SRH). These were post hoc multivariable analyses of a large, international, double-blind study (NCT00251979) of patients randomized to high-dose intravenous (IV) esomeprazole (PPI) or placebo for 72 h. Rebleeding rates of patients with PUB SRH treated with either PPI or placebo after successful endoscopic hemostasis were also compared. For patients treated with placebo for 72 h after successful endoscopic hemostasis, rebleed rates by SRH were spurting arterial bleeding (FIA) 22.5%, adherent clot (FIIB) 17.6%, non-bleeding visible vessel (FIIA) 11.3%, and oozing bleeding (FIB) 4.9%. Compared with FIB patients, FIA, FIIB, and FIIA had significantly greater risks of rebleeding with odds ratios (95% CI's) from 2.61 (1.05, 6.52) for FIIA to 6.66 (2.19, 20.26) for FIA. After hemostasis, PUB rebleeding rates for FIB patients at 72 h were similar with esomeprazole (5.4%) and placebo (4.9%), whereas rebleed rates for all other major SRH (FIA, FIIA, FIIB) were lower for PPI than placebo, but the treatment by SRH interaction test was not statistically significant. After successful endoscopic hemostasis, FIB patients had very low PUB rebleeding rates irrespective of PPI or placebo treatment. This implies that after successful endoscopic hemostasis the prognostic classification of FIB ulcers as a high-risk SRH and the recommendation to treat these with high-dose IV PPI's should be re-evaluated.

Background Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. Objective To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. Design We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores <6 served as controls (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding. Results Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th–28th day in the oral double-dose group remained lower than that of the group with Rockall scores <6 (p=0.03, log-rank test). Among patients with Rockall scores ≥6, the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group (4th–28th day: 10.8% vs 28.7%, p=0.002). Conclusions Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6. Trial registration number NCT01591083.

Objectives The objective of this study was to evaluate the feasibility and efficacy of ERAS pathways in patients undergoing emergency simple closure of perforated duodenal ulcer (PDU). Methods This single-center, prospective, open-labeled, superiority, RCT was carried out from August 2014 to July 2016. Patients of PDU undergoing open simple closure were randomized preoperatively in 1:1 ratio into standard care and adapted ERAS group. Patients with refractory shock, ASA class ≥3, and perforation size ≥1 cm were excluded. Primary outcome was the length of hospitalization (LOH). Secondary outcomes were functional recovery parameters and morbidity. Results Forty-nine and 50 patients were included in standard care and ERAS group, respectively. Patients in ERAS group had a significantly early functional recovery (days) for the time to first flatus (1.47 ± 0.18; p  < 0.001), first stool (2.25 ± 0.20; p  < 0.001), first fluid diet (2.72 ± 0.38; p  < 0.001), and solid diet (3.70 ± 0.44; p  < 0.001). LOH in ERAS group was significantly shorter (mean difference of 4.41 ± 0.64 days; p  < 0.001). There was a significant reduction in postoperative morbidity such as superficial SSI (RR 0.35, p  = 0.02), postoperative nausea and vomiting (RR 0.28, p  < 0.0001), and pulmonary complications (RR 0.24, p  = 0.04) in the ERAS vs. standard care group with similar leak rates (1/50 vs.2/49). Conclusion ERAS pathways are safe and feasible in select patients undergoing emergency simple closure of PDU.

Whether Helicobacter pylori increases the risk of ulcers in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) is controversial. We hypothesised that eradication of H pylori infection would reduce the risk of ulcers for patients starting long-term NSAID treatment. Patients were enrolled if they were NSAID naïve, had a positive urea breath test, had dyspepsia or an ulcer history, and required long-term NSAID treatment. They were randomly assigned omeprazole triple therapy (eradication group) or omeprazole with placebo antibiotics (placebo group) for 1 week. All patients were given diclofenac slow release 100 mg daily for 6 months from randomisation. Endoscopy was done at 6 months or if severe dyspepsia or gastrointestinal bleeding occurred. The primary endpoint was the probability of ulcers within 6 months. Analyses were by intention to treat. Of 210 arthritis patients screened, 128 (61%) were positive for H pylori. 102 patients were enrolled, and 100 were included in the intention-to-treat analysis. H pylori was eradicated in 90% of the eradication group and 6% of the placebo group. Five of 51 eradication-group patients and 15 of 49 placebo-group patients had ulcers. The 6-month probability of ulcers was 12·1% (95% CI 3·1–21·1) in the eradication group and 34·4% (21·1–47·7) in the placebo group (p=0·0085). The corresponding 6-month probabilities of complicated ulcers were 4·2% (1·3–9·7) and 27·1% (14·7–39·5; p=0·0026). Screening and treatment for H pylori infection significantly reduces the risk of ulcers for patients starting long-term NSAID treatment.