Family-based Helicobacter pylori infection control and management strategy and screen-and-treat strategy are highly cost-effective in preventing multiple upper gastrointestinal diseases in Chinese population at national level.

BACKGROUND: The overall benefits of the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management (FBCM) and screen-and-treat strategies in preventing multiple upper gastrointestinal diseases at national level in China have not been explored. We investigate the cost-effectiveness of these strategies in the whole Chinese population. MATERIALS AND METHODS: Decision trees and Markov models of H. pylori infection-related non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were developed to simulate the cost-effectiveness of these strategies in the whole 494 million households in China. The main outcomes include cost-effectiveness, life years (LY), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS: When compared with no-screen strategy, both FBCM and screen-and-treat strategies reduced the number of new cases of NUD, PUD, PUD-related deaths, and the prevalence of GC, and cancer-related deaths. The costs saved by these two strategies were $1467 million and $879 million, quality-adjusted life years gained were 227 million and 267 million, and life years gained were 59 million and 69 million, respectively. Cost-effectiveness analysis showed that FBCM strategy costs -$6.46/QALY and -$24.75/LY, and screen-and-treat strategy costs -$3.3/QALY and -$12.71/LY when compared with no-screen strategy. Compared to the FBCM strategy, the screen-and-treat strategy reduced the incidence of H. pylori-related diseases, added 40 million QALYs, and saved 10 million LYs, but at the increased cost of $588 million. Cost-effectiveness analysis showed that screen-and-treat strategy costs $14.88/QALY and $59.5/LY when compared with FBCM strategy. The robustness of the results was also verified. CONCLUSIONS: Both FBCM and screen-and-treat strategies are highly cost-effective in preventing NUD, PUD, and GC than the no-screen strategy in Chinese families at national level. As FBCM strategy is more practical and efficient, it is expected to play a more important role in preventing familial H. pylori infection and also serves as an excellent reference for other highly infected societies.

Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation.

BACKGROUND: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear. METHODS: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding. RESULTS: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups. CONCLUSIONS: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).

Peptic ulcer disease.

Annual prevalence estimates of peptic ulcer disease range between 0·12% and 1·5%. Peptic ulcer disease is usually attributable to Helicobacter pylori infection, intake of some medications (such as aspirin and non-steroidal anti-inflammatory medications), or being critically ill (stress-related), or it can be idiopathic. The clinical presentation is usually uncomplicated, with peptic ulcer disease management based on eradicating H pylori if present, the use of acid-suppressing medications-most often proton pump inhibitors (PPIs)-or addressing complications, such as with early endoscopy and high-dose PPIs for peptic ulcer bleeding. Special considerations apply to patients on antiplatelet and antithrombotic agents. H pylori treatment has evolved, with the choice of regimen dictated by local antibiotic resistance patterns. Indications for primary and secondary prophylaxis vary across societies; most suggest PPIs for patients at highest risk of developing a peptic ulcer, its complications, or its recurrence. Additional research areas include the use of potassium-competitive acid blockers and H pylori vaccination; the optimal approach for patients at risk of stress ulcer bleeding requires more robust determinations of optimal patient selection and treatment selection, if any. Appropriate continuation of PPI use outweighs most possible side-effects if given for approved indications, while de-prescribing should be trialled when a definitive indication is no longer present.

Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs. METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers. RESULTS: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy. CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.

Prevalence and factors associated with inappropriate continuation of stress ulcer prophylaxis at discharge.

Stress ulcer prophylaxis is started in the critical care unit to decrease the risk of upper gastrointestinal ulcers in critically ill persons and to decrease mortality caused by stress ulcer complications. Unfortunately, the drugs are often continued after recovery through discharge, paving the way for unnecessary polypharmacy. STUDY DESIGN: We conducted a retrospective cross-sectional study including patients admitted to the adult critical care unit and started on the stress ulcer prophylaxis with a proton pump inhibitor (PPI) or histamine receptor 2 blocker (H2 blocker) with an aim to determine the prevalence of inappropriate continuation at discharge and associated factors. RESULT: 3200 people were initiated on stress ulcer prophylaxis, and the medication was continued in 1666 patients upon discharge. Indication for long-term use was not found in 744 of 1666, with a 44% prevalence of inappropriate continuation. A statistically significant association was found with the following risk factors: discharge disposition (home vs other medical facilities, p=0.002), overall length of stay (more than 10 days vs less than or equal to 10 days, p<0.0001), mechanical ventilator use (p<0.001), number of days on a mechanical ventilator (more than 2 days vs less than or equal to 2 days, p<0.001) and class of stress ulcer prophylaxis drug used (H2 blocker vs PPI, p<0.001). CONCLUSION: The prevalence of inappropriate continuation was found to be higher than prior studies. Given the risk of unnecessary medication intake and the associated healthcare cost, a web-based quality improvement initiative is being considered.

Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease.

OBJECTIVES: The routine use of stress ulcer prophylaxis (SUP) in infants with congenital heart disease (CHD) in the cardiac ICU (CICU) is controversial. We aimed to conduct a pilot study to explore the feasibility of performing a subsequent larger trial to assess the safety and efficacy of withholding SUP in this population (NCT03667703). DESIGN, SETTING, PATIENTS: Single-center, prospective, double-blinded, parallel group (SUP vs. placebo), pilot randomized controlled pilot trial (RCT) in infants with CHD admitted to the CICU and anticipated to require respiratory support for greater than 24 hours. INTERVENTIONS: Patients were randomized 1:1 (stratified by age and admission type) to receive a histamine-2 receptor antagonist or placebo until respiratory support was discontinued, up to 14 days, or transfer from the CICU, if earlier. MEASUREMENTS AND MAIN RESULTS: Feasibility was defined a priori by thresholds of screening rate, consent rate, timely drug allocation, and protocol adherence. The safety outcome was the rate of clinically significant upper gastrointestinal (UGI) bleeding. We screened 1,426 patients from February 2019 to March 2022; of 132 eligible patients, we gained informed consent in 70 (53%). Two patients did not require CICU admission after obtaining consent, and the remaining 68 patients were randomized to SUP (n = 34) or placebo (n = 34). Ten patients were withdrawn early, because of a change in eligibility (n = 3) or open-label SUP use (n = 7, 10%). Study procedures were completed in 58 patients (89% protocol adherence). All feasibility criteria were met. There were no clinically significant episodes of UGI bleeding during the pilot RCT. The percentage of patients with other nonserious adverse events did not differ between groups. CONCLUSIONS: Withholding of SUP in infants with CHD admitted to the CICU was feasible. A larger multicenter RCT designed to confirm the safety of this intervention and its impact on incidence of UGI bleeding, gastrointestinal microbiome, and other clinical outcomes is warranted.

Stress Ulcer Prophylaxis in Cardiac Surgery: A Retrospective Cohort Study to Analyze the Effects of SUP Cessation.

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is an important complication among critically ill adults, especially those having cardiac surgery as management is complicated by the requirement for antiplatelet/anticoagulant therapy. As a result, stress ulcer prophylaxis (SUP) has become routine practice in many centers, utilizing either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). Recent evidence from the PEPTIC trial indicated an increase in mortality risk among cardiac surgery patients receiving PPIs compared to H2RBs. Considering these findings, alongside practical difficulties surrounding the transition to H2RBs as a prophylactic agent in New Zealand, Wellington Hospital intensive care unit elected to discontinue routine PPI use for SUP in cardiac surgery patients. A retrospective study was conducted to assess patient outcomes following the discontinuation of routine SUP. METHOD: A retrospective cohort study was conducted of all adult patients who underwent cardiac surgery at Wellington Hospital between February/2018 and January/2022, and divided patients into cohorts before and after the discontinuation of routine use of SUP on the 31st of January 2020. The primary outcomes were the rate of UGIB, oesophagogastroduodenoscopy (OGD) and 180-day postoperative mortality. Secondary outcomes included rates of postoperative Clostridium difficile enteritis, pneumonia, deep sternal wound infection, and length of stay of the index admission. RESULTS: The rate of UGIB statistically significantly increased since the cessation of routine SUP in January 2020 (2.4% vs 5.4%, P-value = .004). This finding was mirrored with the increased rates of OGD (1.9% vs 4.0%, P-value = .005). There were no significant changes in 180-day mortality, hospital length of stay, or any of the postoperative infective complications analyzed, pneumonia, deep sternal wound infection, or C difficile enteritis. CONCLUSION: This study suggests an association between routine use of SUP and reduced rates of clinically significant UGIB and OGD requirements in cardiac surgery patients without increasing risk of infective complications or postoperative mortality.

In older patients receiving aspirin, H pylori eradication reduced hospitalization or death due to peptic ulcer bleeding at 2.5 y.

SOURCE CITATION: Hawkey C, Avery A, Coupland CAC, et al; HEAT trialists. Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial. Lancet. 2022;400:1597-1606. 36335970.

Prophylactic acid suppression and enteral nutrition.

PURPOSE OF REVIEW: Stress ulcer prophylaxis (SUP) is routinely administered to critically ill patients who are at high-risk for clinically important gastrointestinal bleeding. Recent evidence however has highlighted adverse effects with acid suppressive therapy, particularly proton pump inhibitors where associations with higher mortality have been reported. Enteral nutrition may provide benefits in reducing the incidence of stress ulceration and may mitigate the need for acid suppressive therapy. This manuscript will describe the most recent evidence evaluating enteral nutrition for the provision of SUP. RECENT FINDINGS: There are limited data evaluating enteral nutrition for SUP. The available studies compare enteral nutrition with or without acid suppressive therapy rather than enteral nutrition vs. placebo. Although data exist demonstrating similar clinically important bleeding rates in patients on enteral nutrition who receive SUP vs. no SUP, these studies are underpowered for this endpoint. In the largest placebo-controlled trial conducted to date, lower bleeding rates were observed with SUP and most patients were receiving enteral nutrition. Pooled analyses had also described benefit with SUP vs. placebo and enteral nutrition did not change the impact of these therapies. SUMMARY: Although enteral nutrition may provide some benefit as SUP, existing data are not strong enough to validate their use in place of acid suppressive therapy. Clinicians should continue to prescribe acid suppressive therapy for SUP in critically ill patients who are at high risk for clinically important bleeding even when enteral nutrition is being provided.

Perioperative Interventions to Prevent Gastroesophageal Reflux Disease and Marginal Ulcers After Bariatric Surgery - an International Experts' Survey.

OBJECTIVE: This study aimed to survey international experts in metabolic and bariatric surgery (MBS) to improve and consolidate perioperative interventions to prevent gastroesophageal reflux disease (GERD) and marginal ulcers (MU) after MBS. BACKGROUND: Very important long-term complications after MBS include GERD, Barrett's esophagus, and MU. Prevention might be fundamental to reduce the incidence, severe complications, and the increasing number of revisional bariatric surgeries. METHODS: An international scientific team designed an online confidential questionnaire with 45 multiple-choice questions. The survey was sent to 110 invited experts and 96 of them (from 41 different countries) participated from 21 July 2022 to 4 September 2022. RESULTS: Most experts (≥ 90%) prescribe postoperative acid suppression agents after MBS. Life-long proton pump inhibitors prophylaxis in smokers with avoidance of non-steroidal anti-inflammatory drugs are recommended by most of the experts (66%, 73%) after any type of gastric bypass. Two-thirds of experts (69%) perform Helicobacter pylori eradication prior to MBS. Two-thirds of experts (68%) routinely perform EGD and biopsy before MBS. Follow-up esophagogastroduodenoscopy (EGD) and timing threshold for revisional and conversional MBS were variable among experts. CONCLUSION: This expert survey underlines important perioperative interventions that reached a two-thirds consensus among MBS international experts. Variability in follow-up EGD, approach to complication management, and thresholds for revisional and conversional MBS emphasize the need for further researches and consensus guidelines.

Associations between enteral nutrition and outcomes in the SUP-ICU trial: Protocol for exploratory post hoc analyses.

Critically ill patients are at risk of gastrointestinal (GI) bleeding. Counter measures to minimise this risk include the use of pharmacological stress ulcer prophylaxis (SUP). The effect of enteral nutrition as SUP on GI bleeding event rates is unknown. There are conflicting data describing the effect of co-administration of enteral nutrition with pharmacological SUP, and there is substantial variation in practice. We aim to conduct an exploratory post hoc analysis to evaluate the association of enteral nutrition with clinically important GI bleed rates in ICU patients included in the SUP-ICU trial, and to explore any interactions between enteral nutrition and pharmacologic SUP on patient outcomes. The SUP-ICU trial dataset will be used to assess if enteral nutrition is associated with the outcomes of interest. Extended Cox models will be used considering relevant competing events, including treatment allocation (SUP or placebo) and enteral nutrition as a daily time-varying covariate, with additional adjustment for severity of illness (SAPS II). Results will be presented as adjusted hazard ratios for treatment allocation and enteral nutrition, and for treatment allocation and enteral nutrition considering potential interactions with the other variable, all with 95% confidence intervals and p-values for the tests of interaction. All results will be considered as exploratory only. This post hoc analysis may yield important insights to guide practice and inform the design of future randomised clinical trial investigating the effect of enteral nutrition on GI bleeding.

Stress ulcer prophylaxis in critically ill adult patients with sepsis at risk of gastrointestinal bleeding: a retrospective cohort study.

BACKGROUND: The Surviving Sepsis Campaign Guidelines recommend stress ulcer prophylaxis (SUP) for patients with sepsis who have gastrointestinal (GI) bleeding risks; however, the effect of SUP has not been specially studied in these patients. AIMS: To determine the effects of SUP versus no prophylaxis on patient-important outcomes in critically ill adult patients with sepsis who have risk factors for GI bleeding. METHODS: This retrospective cohort study utilised data from the Medical Information Mart for Intensive Care III database. We compared those who received SUP with proton-pump inhibitors or histamine-2 receptor antagonists for ≥3 days with those who received no prophylaxis. Propensity score matching (PSM) was conducted to make comparisons between groups with similar distributions of study variables. The primary outcome was inhospital mortality. RESULTS: A total of 7744 patients were included in the analysis, with 1088 (14.0%) in the non-SUP group and 6656 (86.0%) in the SUP group. A 1:1 PSM created 866 patients in each cohort. No significant differences were noted between the two groups with regard to inhospital mortality (22.3% vs 20.4%; P = 0.379), GI bleeding (4.7% vs 6.4%; P = 0.172), pneumonia (38.9% vs 36.6%; P = 0.346), Clostridium difficile infection (CDI) (6.4% vs 8.9%; P = 0.0.057) or intensive care unit (ICU) length of stay (LOS) (4.2 days vs 4.6 days; P = 0.394). CONCLUSIONS: Among critically ill, septic, adult patients at risk for GI bleeding, SUP showed no effect on hospital mortality, the rate of GI bleeding, pneumonia, CDI and ICU LOS.

Associated Mortality Risk of Proton Pump Inhibitor Therapy for the Prevention of Stress Ulceration in Intensive Care Unit Patients: A Systematic Review and Meta-analysis.

GOALS: The aim was to systematically evaluate risks and benefits of proton pump inhibitor (PPI) use for stress ulcer prophylaxis in the critically ill patient. BACKGROUND: Whether PPIs increase mortality in the critically ill patient remains controversial. STUDY: Systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies with trial sequential analysis, Bayesian sensitivity analysis, and fragility index analysis. RESULTS: A total of 31 studies in 78,009 critically ill adults receiving PPIs versus any comparator were included. PPI use was associated with an increased mortality risk in all studies [19.6% PPI vs. 17.5% comparator; RR: 1.10; 95% confidence interval (CI): 1.02-1.20; P =0.01], in the subgroup of RCTs (19.4% vs. 18.7%; RR: 1.05; 95% CI: 1.0-1.09, P =0.04), but not cohort studies (19.9% vs. 16.7%; RR: 1.12; 95% CI: 0.98-1.28, P =0.09). Results were maintained with a Bayesian sensitivity analysis (RR: 1.13; 95% credible interval: 1.035-1.227) and a fragility index analysis, but not sequential analysis ( P =0.16). RCTs with a higher baseline severity of illness revealed the greatest mortality risk with PPI use (32.1% PPI vs. 29.4% comparator; RR: 1.09; 95% CI: 1.04-1.14; P <0.001). PPI use reduced clinically important bleeding in RCTs (1.4% PPI vs. 2.1% comparator; RR: 0.67; 95% CI: 0.5-0.9; P =0.009) but increased bleeding in cohort studies (2.7% PPI vs. 1.2% comparator; RR: 2.05; 95% CI: 1.2-3.52; P =0.009). PPI use was not associated with a lower incidence of clinically important bleeding when compared with histamine-2 receptor antagonists (1.3% vs. 1.9%; RR: 0.59; 95% CI: 0.28-1.25, P =0.09). CONCLUSIONS: This meta-analysis demonstrated an association between PPI use and an increased risk of mortality.

Pharmacist-Initiated De-Prescribing Efforts Reduce Inappropriate Continuation of Acid-Suppression Therapy Initiated in the ICU.

OBJECTIVES: Stress ulcer prophylaxis initiated for intensive care unit (ICU)-specific indications is often continued upon transfer or discharge despite lack of indication. This quality improvement initiative aimed to achieve a 25% reduction from baseline in ICU-initiated acid suppression therapy prescriptions by May 2021. METHODS: This initiative was conducted in adult ICU patients at Boston Medical Center from July 2020 through May 2021. A multidisciplinary approach to de-prescribing was utilized, including the implementation of formalized stress ulcer prophylaxis criteria and an electronic handoff tool used to identify patients appropriate for assessment of acid suppression therapy continuation post-ICU stay. The primary outcome measure was the number of discharge prescriptions for ICU-initiated acid suppression therapy. Secondary endpoints included incidence of de-prescribing workflow failures, percentage of acid suppression therapy discharge prescriptions with inappropriate indications, and incidence of stress ulcer-related gastrointestinal bleeding. RESULTS: A 55% decrease in ICU-initiated acid suppression therapy discharge prescriptions occurred after implementing the multidisciplinary workflow. The decrease was sustained for 28 weeks through the completion of the study. CONCLUSIONS: Implementation of a pharmacist-initiated electronic handoff tool along with provider education and creation of formalized stress ulcer prophylaxis criteria may reduce the number of ICU-initiated acid suppression therapy prescriptions inadvertently or inappropriately continued at discharge.

Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against aspirin-associated ulcer bleeding. METHODS: We conducted a randomised, double-blind, placebo-controlled trial (Helicobacter Eradication Aspirin Trial [HEAT]) at 1208 primary care centres in the UK, using routinely collected clinical data. Eligible patients were aged 60 years or older who were receiving aspirin at a daily dose of 325 mg or less (with four or more 28-day prescriptions in the past year) and had a positive C13 urea breath test for H pylori at screening. Patients receiving ulcerogenic or gastroprotective medication were excluded. Participants were randomly assigned (1:1) to receive either a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (active eradication), or oral placebo (control), twice daily for 1 week. Participants, their general practitioners and health-care providers, and the research nurses, trial team, adjudication committee, and analysis team were all masked to group allocation throughout the trial. Follow-up was by scrutiny of electronic data in primary and secondary care. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding, and was analysed by Cox proportional hazards methods in the intention-to-treat population. This trial is registered with EudraCT, 2011-003425-96. FINDINGS: Between Sept 14, 2012, and Nov 22, 2017, 30 166 patients had breath testing for H pylori, 5367 had a positive result, and 5352 were randomly assigned to receive active eradication (n=2677) or placebo (n=2675) and were followed up for a median of 5·0 years (IQR 3·9-6·4). Analysis of the primary outcome showed a significant departure from proportional hazards assumptions (p=0·0068), requiring analysis over separate time periods. There was a significant reduction in incidence of the primary outcome in the active eradication group in the first 2·5 years of follow-up compared with the control group (six episodes adjudicated as definite or probable peptic ulcer bleeds, rate 0·92 [95% CI 0·41-2·04] per 1000 person-years vs 17 episodes, rate 2·61 [1·62-4·19] per 1000 person-years; hazard ratio [HR] 0·35 [95% CI 0·14-0·89]; p=0·028). This advantage remained significant after adjusting for the competing risk of death (p=0·028) but was lost with longer follow-up (HR 1·31 [95% CI 0·55-3·11] in the period after the first 2·5 years; p=0·54). Reports of adverse events were actively solicited; taste disturbance was the most common event (787 patients). INTERPRETATION: H pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this might not be sustained in the long term. FUNDING: National Institute for Health and Care Research Health Technology Assessment.

Which ICU patients need stress ulcer prophylaxis?

Critically ill patients are at an increased risk for developing stress ulcers of the mucosa of the upper gastrointestinal (GI) tract. Bleeding from stress ulcers was previously associated with a longer stay in the intensive care unit and an increased risk of death. Thus, most patients admitted to the intensive care unit receive stress ulcer prophylaxis. However, there is a growing concern that acid-suppression drugs may be associated with increased frequency of nosocomial pneumonia and Clostridioides difficile infection. In this article, the authors address controversies regarding stress ulcer prophylaxis in critically ill patients and provide guidance for its appropriate use in this setting.

Prophylactic acid suppressants in patients with primary neurologic injury: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Neurocritical care patients are at risk of stress-induced gastrointestinal ulceration. We performed a systematic review and meta-analysis of stress ulcer prophylaxis (SUP) in critically ill adults admitted with a primary neurologic injury. MATERIALS AND METHODS: We included randomized controlled trials (RCTs) comparing SUP with histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to placebo/no prophylaxis, as well as to each other. The primary outcome was in-ICU gastrointestinal bleeding (GIB). Predefined secondary outcomes were all-cause 30-day mortality, ICU length of stay (LOS), nosocomial pneumonia, and other complications. RESULTS: We identified 14 relevant trials enrolling 1036 neurocritical care patients; 11 trials enrolling 930 patients were included in the meta-analysis. H2RAs resulted in a lower incidence of GIB as compared to placebo or no prophylaxis (Risk ratio [RR] 0.42, 95% CI 0.30-0.58; p < 0.001); PPIs with a lower risk of GIB compared to placebo/no prophylaxis (RR 0.37, 95% CI 0.23-0.59; p < 0.001). No significant difference was observed in GIB comparing PPIs with H2RAs (RR 0.53, 95% CI 0.26-1.06; p = 0.07; I2 = 0%). CONCLUSIONS: In neurocritical care patients, the overall high or unclear risk of bias of individual trials, the low event rates, and modest sample sizes preclude strong clinical inferences about the utility of SUP.

Stress ulcer prophylaxis for critically ill children: routine use needs to be re-examined.

INTRODUCTION: Stress ulcer prophylaxis (SUP) is commonly used in Paediatric Intensive Care Units (PICUs). However, strong evidence for this practice is lacking and there is a dire need for paediatric randomized controlled trials (RCTs). Our aim was to assess the usefulness of SUP with omeprazole in critically ill children. PATIENTS AND METHODS: We conducted a randomized, controlled open-label trial, including 144 children admitted into a PICU with a paediatric Sequential Organ Failure Assessment (pSOFA) score of less than 16. We randomly allocated patients to SUP with omeprazole or no SUP. The primary outcome was development of upper gastrointestinal bleeding or nosocomial infection. RESULTS: The incidence of gastrointestinal bleeding was 27.1%, but clinically significant bleeding developed in only 5.6% of patients. We did not find a significant difference in the incidence of bleeding between the prophylaxis and control groups (27.8% vs 26.4%; P = .85). We also did not find a significant difference between the groups in the incidence of ventilator-associated pneumonia (VAP) (9.6% vs 8.3%; P = .77). The incidence of central line-associated bloodstream infection (CLABSI) was higher in the prophylaxis group compared to the control group (30.6% vs 12.5%; P = .014). None of the patients developed Clostridium difficile-associated diarrhoea. We did not find significant differences in mortality, length of PICU stay or duration of mechanical ventilation. Mechanical ventilation was an independent predictor of bleeding (OR, 6.4; 95%CI, 2.73-14.9). CONCLUSION: In PICU patients with mild to moderate organ dysfunction, omeprazole does not seem to be useful for prevention of gastrointestinal bleeding while at the same time increasing the risk of CLABSI. Thus, we recommend restricting SUP to mechanically ventilated children.