Prevention Of Upper Gastrointestinal Bleeding Research Articles

Prescribing of Proton Pump Inhibitors for Prevention of Upper Gastrointestinal Bleeding in US Outpatient Visits

Antisecretory medications, primarily proton pump inhibitors (PPIs), have proven effective in reducing upper gastrointestinal toxicities, including upper gastrointestinal bleeding (UGIB), associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are among the most commonly used medications in the United States.1 Accordingly, professional guidance recommends PPIs for patients at high risk for UGIB.2-4 However, little is known about trends in use of antisecretory medications for gastrointestinal prophylaxis ("gastroprotection"). Herein, we examined contemporary use and prescribing of antisecretory medications in visits by patients at high risk for UGIB, relative to visits by patients diagnosed with acid-related disorders.

Do Proton Pump Inhibitors Reduce Upper Gastrointestinal Bleeding in Older Patients with Atrial Fibrillation Treated with Oral Anticoagulants? A Nationwide Cohort Study in France.

Proton pump inhibitors (PPIs) are largely used in older adults and data are needed in off-label indications, such as the prevention of upper gastrointestinal bleeding (UGIB) in patients receiving oral anticoagulants (OACs). This study aimed to assess whether PPIs reduce the risk of UGIB in patients initiating oral anticoagulation. We conducted a longitudinal study based on the French national health database. The study population included 109,693 patients aged 75-110 years with a diagnosis of atrial fibrillation who initiated OACs [vitamin K antagonist (VKA) or direct OAC(DOAC)] between 2012 and 2016. We used multivariable Cox models weighted by inverse of probability of treatment to estimate the adjusted hazard ratio (aHR) of UGIB between PPI users and nonusers over a 6- and 12-month follow-up. PPI users represented 23% of the study population (28% among VKA initiators and 17% among DOAC initiators). The mean age (83 ± 5.3 years) and proportion of women (near 60%) were similar between groups. The risk of UGIB in the first 6 months after initiation of OAC decreased by 20% in PPI users compared with PPI nonusers [aHR6 months = 0.80, 95% confidence interval (CI) 0.65-0.98], but was not significantly modified when the follow-up was extended to 12 months (aHR12 months = 0.90, 95% CI 0.76-1.07), with a stronger effect among patients treated with vitamin K antagonists (aHR6 months = 0.73, 95% CI 0.58-0.93; aHR12 months = 0.81, 95% CI 0.67-0.99). This study suggests that PPIs were associated with reduced risk of gastrointestinal bleeding after initiation of oral anticoagulation in older patients with atrial fibrillation, particularly within 6 months after initiation of an antivitamin K antagonist.

The use of endoscopic band ligation in the primary prevention of bleeding in patients with ascites listed in the liver transplantation waiting list

Background. Saving lives and preventing patients from dropping out of the waiting list for liver transplantation due to the progression of portal hypertension and the development of complications is an urgent task of transplantology in conditions of a donor organ shortage, which causes long waiting times for this operation. Aim. To study the efficacy of endoscopic band ligation versus no intervention in the primary prevention of upper gastrointestinal bleeding and assess the impact on survival of patients with ascites listed in the liver transplantation waiting list. Material and methods. A retrospective comparative study was conducted in patients with decompensated liver diseases with severe ascites and varicose veins, without a history of bleeding, when included in the waiting list for liver transplantation. Primary prevention of bleeding from varices was carried out in patients by means of endoscopic ligation of varicose veins (n=92, group 1); this intervention was not performed in other patients (n=89, group 2). Results. The compared groups were comparable in demographics, clinical parameters, MELD and Child-TurcottePugh scores, or the incidence of severe ascites. The study groups of patients did not have significant differences in the numbers of medium-size and large varices. The incidence of bleeding was significantly lower in the group of patients with endoscopic band ligation as a method of primary prevention than in the group of patients without this intervention (23.9% and 78.7%, respectively, p=0.0001). Patient survival was significantly higher in the group of patients who underwent endoscopic band ligation than in the group of patients without interventions, which was established using the Kaplan-Meier method (Log Rank=0.0001). Conclusion. Primary prevention of bleeding from the upper digestive tract through endoscopic band ligation is an effective method of saving lives and preventing patients with ascites from dropping out of the liver transplantation waiting list in conditions of a donor organ shortageб which causes a long waiting period for surgery.

Characteristics, Outcomes, and Risk Factors for Upper Gastrointestinal Bleeding in Inpatients - A Comparison with Outpatients.

Objective The study objectives were to clarify the clinical findings and the causes of intractability and mortality of upper gastrointestinal (UGI) bleeding in inpatients. Methods The patients were divided into Inpatient (Ip) and Outpatient (Op) onset groups, and their characteristics, clinical and bleeding data, and outcomes were compared. Patients or Materials Our study included 375 patients who developed UGI bleeding during hospitalization or were admitted after being diagnosed with UGI bleeding in an outpatient setting from January 1, 2015, to June 30, 2020. Results The Ip group had worse general condition; increased percentages of comorbidities; and more common use of proton pump inhibitor, anti-coagulant, and steroid than the Op group. Compared with the Op group, the Ip group had lower serum albumin levels and platelet counts at the onset of bleeding, whereas rebleeding, mortality, and bleeding-related death rates were higher. Multivariate analysis of the Ip group revealed that the risks of rebleeding included endoscopic high-risk stigmata, maintenance dialysis, and duodenal bleeding, whereas the risks of mortality were gastric ulcer and a Charlson Comorbidity Index update score of ≥3. Conclusion UGI bleeding in the Ip group was associated with higher rebleeding and mortality rates. Because of their poor general health condition, the pathology of UGI bleeding in these patients may differ from that of patients with common UGI bleeding. A different approach for the care and prevention of UGI bleeding in inpatients is required.

Prevention of upper gastrointestinal bleeding in critical illness.

Prevention of upper gastrointestinal bleeding in critical illness.

Association of Antisecretory Drugs with Upper Gastrointestinal Bleeding in Patients Using Oral Anticoagulants: A Systematic Review and Meta-Analysis

BackgroundThe role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis. MethodsWe searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models. ResultsSix observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I2 = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02). ConclusionsEvidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.

Association of direct oral anticoagulant-proton pump inhibitor cotherapy with adverse outcomes: protocol for a population-based cohort study

IntroductionProton pump inhibitors (PPIs) are widely used for primary and secondary prevention of upper gastrointestinal bleeding. However, there remains controversy about the overall net clinical benefit of PPIs (omeprazole, rabeprazole,...

Risk factors and outcomes of gastrointestinal bleeding in patients with stable coronary artery disease: data from the observational registry of long-term antithrombotic therapy REGATTA-1

Aim. To optimize the upper gastrointestinal bleeding (UGIB) risk scale in patients Material and methods. The UGIB risk scale was developed based on the with chronic coronary artery disease (CAD) receiving long-term antiplatelet therapy. prospective REGistry of long-term AnTithrombotic TherApy-1 REGATTA-1(ClinicalTrials.gov Identifier: NCT04347200). The registry includes 934 patients with stable CAD (men, 78,6%; median age, 61±10,7 years), 76% of whom were included after elective percutaneous coronary interventions and received dual antiplatelet therapy for 6-12 months. After a UGIB episode, patients were prescribed proton pump inhibitors. The 2015 European Society of Cardiology (ESC) scale was used for assessing the UGIB risk. In addition, we evaluated the ultrasound data on atherosclerotic burden (abdominal aorta and peripheral arteries).Results. The median follow-up was 2,5 years [1,1-14,7 years]. The incidence of UGIB was 1,9 cases per 100 patient/years. Recurrent UGIB episodes and thrombosis was recorded in 13,7% and 31,4%, respectively. Based on the results of a multivariate logistic regression, a novel scale for assessing the UGIB risk (REGATTA) has been developed. In accordance with the odds ratio, points were assigned for each independent risk factor (RF): age ≥80 years — 3 points, prior gastric erosion, peptic ulcer disease or UGIB — 3 points for each RF, anticoagulation therapy — 4 points, non-steroidal antiinflammatory drug therapy — 2 points. The atherosclerotic burden (peripheral atherosclerosis and/or abdominal aortic aneurysm; 2 points) and heart failure (in most cases after a myocardial infarction; 2 points) were marked as a new independent predictor. The cutoff value (≥4 points) was determined, reflecting the high UGIB risk (sensitivity, 80,4%; specificity, 84,5%). The REGATTA scale was more powerful than the traditional 2015 ESC scale: AUC of 0,88, (95% confidence interval, 0,86-0,9) vs AUC of 0,79, (95% confidence interval, 0,760,82) (p=0,04).Conclusion. The identified UGIB predictors (atherosclerotic burden and heart failure) and the developed REGATTA scale made it possible to improve the prognosis and prevention of UGIB in patients with stable CAD receiving long-term antiplatelet therapy.

Prevention of recurrent bleeding from varicose veins of the esophagus and stomach among patients with decompensated liver cirrhosis

Aim. To evaluate the efficiency of laparoscopic devascularization of the esophagus and stomach with endoscopic ligation of varicose esophageal veins in the prevention of esophageal-gastric bleeding among patients with decompensated liver cirrhosis. Methods. The results of treatment of 73 patients with decompensated liver cirrhosis and high risk of bleeding were analyzed. To prevent recurrent bleeding from esophageal and gastric veins, all patients underwent endoscopic ligation at the first step of treatment. In case of inefficiency of ligation and recurrence of varicose veins of esophagus, laparoscopic devascularization of esophagus and stomach was performed. The efficiency of laparoscopic devascularization with intraoperative endoscopic ligation of varicose esophageal veins and ligation as an independent method of treatment for the prevention of upper gastrointestinal bleeding was estimated by comparison of the frequency of recurrence of esophageal and gastric bleeding and recurrence of esophageal varices according to upper endoscopy in comparison groups. Results. In 6 months, 1 and 2 years after laparoscopic devascularization of the esophagus and stomach in combination with endoscopic ligation, the risk of bleeding is less compared to endoscopic ligation as an isolated treatment method (p=0.05; p=0.052; p=0.06). Laparoscopic devascularization with ligation reduces the risk of recurrence of esophageal varices during the first year after surgery by 20% (χ2=2.61; p=0.106), in 2 years by 23% (χ2=1.75; p=0.091) compared to endoscopic ligation only. Conclusion. Patients with liver cirrhosis with decompensated hepatic failure satisfactorily postpone endovideosurgical interventions; laparoscopic gastric devascularization with the intersection of the main inflows to the esophageal varicose veins is an effective method to prevent esophageal-gastric hemorrhage among patients with decompensated liver cirrhosis after ineffective endoscopic ligation.

Proton-pump inhibitors for the prevention of upper gastrointestinal bleeding in adults receiving antithrombotic therapy

Proton-pump inhibitors for the prevention of upper gastrointestinal bleeding in adults receiving antithrombotic therapy

Pharmacological interventions for prevention and treatment of upper gastrointestinal bleeding in newborn infants.

Upper gastrointestinal bleeding is typically a mild, self-limiting condition that can affect both preterm and term neonates, although it can be severe particularly when associated with co-morbidities. Pharmacological interventions with a proton pump inhibitor (PPI), H2 receptor antagonist (H2RA), antacid, bismuth and sucralfate may have effects on both the prevention and treatment of upper gastrointestinal bleeding in infants. To assess how different pharmacological interventions (PPIs, H2RAs, antacids, sucralfate or bismuth salts) administered to preterm and term neonates for the prevention or treatment of upper gastrointestinal bleeding to reduce morbidity and mortality compare with placebo or no treatment, supportive care, or each other. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 6), MEDLINE via PubMed (1966 to 12 July 2018), Embase (1980 to 12 July 2018), and CINAHL (1982 to 12 July 2018). We also searched clinical trial databases, conference proceedings, the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials, and online for Chinese literature articles. We selected randomised, quasi-randomised and cluster-randomised trials involving preterm and term neonates. Trials were included if they used a proton pump inhibitor, H2 receptor antagonist, antacid, sucralfate or bismuth either for the prevention or treatment of upper gastrointestinal bleeding. Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. We conducted meta-analysis using a fixed-effect model. We used the GRADE approach to assess quality of evidence. Eleven studies with 818 infants met the criteria for inclusion in this review.Four trials with 329 infants assessed the use of an H2 receptor antagonist for prevention of upper gastrointestinal bleeding in high-risk newborn infants. Meta-analysis of these four trials identified a reduction in any upper gastrointestinal bleeding when using an H2 receptor antagonist (typical risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.58; typical risk difference (RD) -0.20, 95% CI -0.28 to -0.11; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 9). The quality of evidence was moderate. A single trial with 53 infants assessing prevention of upper gastrointestinal bleeding reported no difference in mortality in infants assigned H2 receptor antagonist versus no treatment; however the quality of evidence was very low.Seven trials with 489 infants assessed an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) for treatment of gastrointestinal bleeding in newborn infants. Meta-analysis of two trials (131 infants) showed no difference in mortality from use of a H2 receptor antagonist compared to no treatment. The quality of evidence was low. Meta-analysis of two trials (104 infants) showed a reduction in duration of upper gastrointestinal bleeding from use of an inhibitor of gastric acid compared to no treatment (mean difference -1.06 days, 95% CI -1.28 to -0.84). The quality of evidence was very low. Meta-analysis of six trials (451 infants) showed a reduction in continued upper gastrointestinal bleeding from use of any inhibitor of gastric acid compared to no treatment (typical RR 0.36, 95% CI 0.26 to 0.49; typical RD -0.26, 95% CI -0.33, -0.19; NNTB 4, 95% CI 3 to 5). The quality of evidence was low. There were no significant subgroup differences in duration of upper gastrointestinal bleeding or of continued upper gastrointestinal bleeding according to type of inhibitor of gastric acid. A single trial (38 infants) reported no difference in anaemia requiring blood transfusion from use of a H2 receptor antagonist compared to no treatment.Although no serious adverse events were reported from the use of a H2 receptor antagonist or proton pump inhibitor, some neonatal morbidities - including necrotising enterocolitis, ventilator-associated pneumonia, duration of ventilation and respiratory support, and duration of hospital stay - were not reported. Long-term outcome was not reported. There is moderate-quality evidence that use of an H2 receptor antagonist reduces the risk of gastrointestinal bleeding in newborn infants at high risk of gastrointestinal bleeding. There is low-quality evidence that use of an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) reduces the duration of upper gastrointestinal bleeding and the incidence of continued gastric bleeding in newborn infants with gastrointestinal bleeding. However, there is no evidence that use of an inhibitor of gastric acid in newborn infants affects mortality or the need for blood transfusion. As no study reported the incidence of necrotising enterocolitis, ventilator- or hospital-associated pneumonia, sepsis, or long-term outcome, the safety of inhibitors of gastric acid secretion is unclear.

Band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in adults with cirrhosis and oesophageal varices.

The presence of oesophageal varices is associated with the risk of upper gastrointestinal bleeding. Endoscopic variceal ligation is used to prevent this occurrence but the ligation procedure may be associated with complications. To assess the beneficial and harmful effects of band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in adults with cirrhosis and oesophageal varices. We combined searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 9 February 2019. We included randomised clinical trials comparing band ligation verus no intervention regardless of publication status, blinding, or language in the analyses of benefits and harms, and observational studies in the assessment of harms. Included participants had cirrhosis and oesophageal varices with no previous history of variceal bleeding. Three review authors extracted data independently. The primary outcome measures were all-cause mortality, upper gastrointestinal bleeding, and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RRs) with 95% confidence intervals (CIs) and I2 values as a marker of heterogeneity. In addition, we calculated the number needed to treat to benefit (NNTTB) for the primary outcomes . We assessed bias control using the Cochrane Hepato-Biliary domains; determined the certainty of the evidence using GRADE; and conducted sensitivity analyses including Trial Sequential Analysis. Six randomised clinical trials involving 637 participants fulfilled our inclusion criteria. One of the trials included an additional small number of participants (< 10% of the total) with non-cirrhotic portal hypertension/portal vein block. We classified one trial as at low risk of bias for the outcome, mortality and high risk of bias for the remaining outcomes; the five remaining trials were at high risk of bias for all outcomes. We downgraded the evidence to moderate certainty due to the bias risk. We gathered data on all primary outcomes from all trials. Seventy-one of 320 participants allocated to band ligation compared to 129 of 317 participants allocated to no intervention died (RR 0.55, 95% CI 0.43 to 0.70; I2 = 0%; NNTTB = 6 persons). In addition, band ligation was associated with reduced risks of upper gastrointestinal bleeding (RR 0.44, 95% CI 0.28 to 0.72; 6 trials, 637 participants; I2 = 61%; NNTTB = 5 persons), serious adverse events (RR 0.55, 95% CI 0.43 to 0.70; 6 trials, 637 participants; I2 = 44%; NNTTB = 4 persons), and variceal bleeding (RR 0.43, 95% CI 0.27 to 0.69; 6 trials, 637 participants; I² = 56%; NNTTB = 5 persons). The non-serious adverse events reported in association with band ligation included oesophageal ulceration, dysphagia, odynophagia, retrosternal and throat pain, heartburn, and fever, and in the one trial involving participants with either small or large varices, the incidence of non-serious side effects in the banding group was much higher in those with small varices, namely ulcers: small versus large varices 30.5% versus 8.7%; heartburn 39.2% versus 17.4%. No trials reported on health-related quality of life.Two trials did not receive support from pharmaceutical companies; the remaining four trials did not provide information on this issue. This review found moderate-certainty evidence that, in patients with cirrhosis, band ligation of oesophageal varices reduces mortality, upper gastrointestinal bleeding, variceal bleeding, and serious adverse events compared to no intervention. It is unlikely that further trials of band ligation versus no intervention would be considered ethical.

Carvedilol versus traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices.

Non-selective beta-blockers are recommended for the prevention of bleeding in people with cirrhosis, portal hypertension and gastroesophageal varices. Carvedilol is a non-selective beta-blocker with additional intrinsic alpha1-blocking effects, which may be superior to traditional, non-selective beta-blockers in reducing portal pressure and, therefore, in reducing the risk of upper gastrointestinal bleeding. To assess the beneficial and harmful effects of carvedilol compared with traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices. We combined searches in the Cochrane Hepato-Biliary's Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 08 May 2018. We included randomised clinical trials comparing carvedilol versus traditional, non-selective beta-blockers, irrespective of publication status, blinding, or language. We included trials evaluating both primary and secondary prevention of upper gastrointestinal bleeding in adults with cirrhosis and verified gastroesophageal varices. Three review authors (AZ, RJ and LH), independently extracted data. The primary outcome measures were mortality, upper gastrointestinal bleeding and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RR) or mean differences (MD), both with 95% confidence intervals (CIs), and I2 values as a marker of heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary domains and the quality of the evidence with GRADE. Eleven trials fulfilled our inclusion criteria. One trial did not report clinical outcomes. We included the remaining 10 randomised clinical trials, involving 810 participants with cirrhosis and oesophageal varices, in our analyses. The intervention comparisons were carvedilol versus propranolol (nine trials), or nadolol (one trial). Six trials were of short duration (mean 6 (range 1 to 12) weeks), while four were of longer duration (13.5 (6 to 30) months). Three trials evaluated primary prevention; three evaluated secondary prevention; while four evaluated both primary and secondary prevention. We classified all trials as at 'high risk of bias'. We gathered mortality data from seven trials involving 507 participants; no events occurred in four of these. Sixteen of 254 participants receiving carvedilol and 19 of 253 participants receiving propranolol or nadolol died (RR 0.86, 95% CI 0.48 to 1.53; I2 = 0%, low-quality evidence). There appeared to be no differences between carvedilol versus traditional, non-selective beta-blockers and the risks of upper gastrointestinal bleeding (RR 0.77, 95% CI 0.43 to 1.37; 810 participants; 10 trials; I2 = 45%, very low-quality evidence) and serious adverse events (RR 0.97, 95% CI 0.67 to 1.42; 810 participants; 10 trials; I2 = 14%, low-quality evidence). Significantly more deaths, episodes of upper gastrointestinal bleeding and serious adverse events occurred in the long-term trials but there was not enough information to determine whether there were differences between carvedilol and traditional, non-selective beta-blockers, by trial duration. There was also insufficient information to detect differences in the effects of these interventions in trials evaluating primary or secondary prevention. There appeared to be no differences in the risk of non-serious adverse events between carvedilol versus its comparators (RR 0.55, 95% CI 0.23 to 1.29; 596 participants; 6 trials; I2 = 88%; very low-quality evidence). Use of carvedilol was associated with a greater reduction in hepatic venous pressure gradient than traditional, non-selective beta-blockers both in absolute (MD -1.75 mmHg, 95% CI -2.60 to -0.89; 368 participants; 6 trials; I2 = 0%; low-quality evidence) and percentage terms (MD -8.02%, 95% CI -11.49% to -4.55%; 368 participants; 6 trials; I2 = 0%; low-quality evidence). However, we did not observe a concomitant reduction in the number of participants who failed to achieve a sufficient haemodynamic response (RR 0.76, 95% CI 0.57 to 1.02; 368 participants; 6 trials; I2 = 42%; very low-quality evidence) or in clinical outcomes. We found no clear beneficial or harmful effects of carvedilol versus traditional, non-selective beta-blockers on mortality, upper gastrointestinal bleeding, serious or non-serious adverse events despite the fact that carvedilol was more effective at reducing the hepatic venous pressure gradient. However, the evidence was of low or very low quality, and hence the findings are uncertain. Additional evidence is required from adequately powered, long-term, double-blind, randomised clinical trials, which evaluate both clinical and haemodynamic outcomes.

Only full adherence to proton pump inhibitors protects against drug-induced upper gastrointestinal bleeding.

The use of gastroprotective agents has allowed significant progress in the prevention of upper gastrointestinal bleeding (UGIB) associated with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents. Nevertheless, some concerns remain regarding the gastroprotective dosage and treatment duration. Our aim was to study the effect of gastroprotective agents in UGIB induced by NSAIDs and single- or dual-antiplatelet therapy. A multicenter case-control study was conducted including 577 cases diagnosed with UGIB and 1343 sex-, age-, and hospital-matched controls. To estimate exposure to NSAIDs and gastroprotective agents, consumption was calculated for the 4weeks prior to hospital admission in terms of defined daily doses (DDDs). Risk groups for UGIB induced by NSAIDs and single- or dual-antiplatelet therapy were defined as a function of each drug dose, use of gastrointestine-damaging drugs, and risk factors for UGIB. Odds ratios (ORs) with 95% confidence intervals (CIs) were adjusted for single- (model 1) and dual- (model 2) antiplatelet therapy. Full adherence (> 0.80DDD) to proton pump inhibitors (PPIs) was the only gastroprotective therapy that significantly reduced the risk of UGIB, considering NSAID risk (OR: 0.53; 95% CI: 0.30-0.95) and dose (OR: 0.48; 95% CI: 0.27-0.87) with ORs adjusted for single-antiplatelet therapy (model 1) and NSAID risk (OR: 0.55; 95% CI: 0.31-0.98) and dose (OR: 0.49; 95% CI: 0.28-0.89) with ORs adjusted for dual-antiplatelet therapy (model 2). These results reinforce the recommendation of adding a PPI at effective doses (full adherence) to prevent UGIB induced by NSAIDs, or single- or dual-antiplatelet therapy.

Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine

Objective: To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator.Methods: A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique.Results: Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive “coffee grounds” material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients.Conclusions: Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control.Trial registration: ClinicalTrials.gov identifier NCT02157376.

Tu1315 - The Prevention of Upper Gastrointestinal Bleeding in Seriously Ill Chinese Patients: A Randomised, Double-Blind Study Evaluating Esomeprazole vs Cimetidine

Tu1315 - The Prevention of Upper Gastrointestinal Bleeding in Seriously Ill Chinese Patients: A Randomised, Double-Blind Study Evaluating Esomeprazole vs Cimetidine

Evaluation of endoscopic secondary prophylaxis in children and adolescents with esophageal varices.

- Bleeding of esophageal varices is the main cause of morbidity and mortality in children and adults with portal hypertension and there are few studies involving secondary prophylaxis in children and adolescents. - To evaluate the efficacy of endoscopic secondary prophylaxis in prevention of upper gastrointestinal bleeding in children and adolescents with esophageal varices. - This is a prospective analysis of 85 patients less than 18 years of age with or without cirrhosis, with portal hypertension. Participants underwent endoscopic secondary prophylaxis with sclerotherapy or band ligation. Eradication of varices, incidence of rebleeding, number of endoscopic sessions required for eradication, incidence of developing gastric fundus varices and portal hypertensive gastropathy were evaluated. - Band ligation was performed in 34 (40%) patients and sclerotherapy in 51 (60%) patients. Esophageal varices were eradicated in 81.2%, after a median of four endoscopic sessions. Varices relapsed in 38 (55.1%) patients. Thirty-six (42.3%) patients experienced rebleeding, and it was more prevalent in the group that received sclerotherapy. Gastric varices and portal hypertensive gastropathy developed in 38.7% and 57.9% of patients, respectively. Patients undergoing band ligation showed lower rebleeding rates (26.5% vs 52.9%) and fewer sessions required for eradication of esophageal varices (3.5 vs 5). - Secondary prophylaxis was effective in eradicating esophageal varices and controlling new upper gastrointestinal bleeding episodes due to the rupture of esophageal varices. Band ligation seems that resulted in lower rebleeding rates and fewer sessions required to eradicate varices than did sclerotherapy.

Naloxone combined with pantoprazole for prevention of upper gastrointestinal bleeding in patients with respiratory failure

Naloxone combined with pantoprazole for prevention of upper gastrointestinal bleeding in patients with respiratory failure

Pharmacological interventions for prevention and treatment of upper gastrointestinal bleeding in newborn infants

Background Upper gastrointestinal bleeding is typically a mild, self-limiting condition that can affect both preterm and term neonates, although it can be severe particularly when associated with co-morbidities. Pharmacological interventions with a proton pump inhibitor (PPI), H2 receptor antagonist (H2RA), antacid, bismuth and sucralfate may have effects on both the prevention and treatment of upper gastrointestinal bleeding in infants. Objectives To assess how different pharmacological interventions (PPIs, H2RAs, antacids, sucralfate or bismuth salts) administered to preterm and term neonates for the prevention or treatment of upper gastrointestinal bleeding to reduce morbidity and mortality compare with placebo or no treatment, supportive care, or each other. Search methods We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 6), MEDLINE via PubMed (1966 to 12 July 2018), Embase (1980 to 12 July 2018), and CINAHL (1982 to 12 July 2018). We also searched clinical trial databases, conference proceedings, the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials, and online for Chinese literature articles. Selection criteria We selected randomised, quasi-randomised and cluster-randomised trials involving preterm and term neonates. Trials were included if they used a proton pump inhibitor, H2 receptor antagonist, antacid, sucralfate or bismuth either for the prevention or treatment of upper gastrointestinal bleeding. Data collection and analysis Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. We conducted meta-analysis using a fixed-effect model. We used the GRADE approach to assess quality of evidence. Main results Eleven studies with 818 infants met the criteria for inclusion in this review.Four trials with 329 infants assessed the use of an H2 receptor antagonist for prevention of upper gastrointestinal bleeding in high-risk newborn infants. Meta-analysis of these four trials identified a reduction in any upper gastrointestinal bleeding when using an H2 receptor antagonist (typical risk ratio (RR) 0.36, 95% confidence interval (CI) 0.22 to 0.58; typical risk difference (RD) -0.20, 95% CI -0.28 to -0.11; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 9). The quality of evidence was moderate. A single trial with 53 infants assessing prevention of upper gastrointestinal bleeding reported no difference in mortality in infants assigned H2 receptor antagonist versus no treatment; however the quality of evidence was very low.Seven trials with 489 infants assessed an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) for treatment of gastrointestinal bleeding in newborn infants. Meta-analysis of two trials (131 infants) showed no difference in mortality from use of a H2 receptor antagonist compared to no treatment. The quality of evidence was low. Meta-analysis of two trials (104 infants) showed a reduction in duration of upper gastrointestinal bleeding from use of an inhibitor of gastric acid compared to no treatment (mean difference -1.06 days, 95% CI -1.28 to -0.84). The quality of evidence was very low. Meta-analysis of six trials (451 infants) showed a reduction in continued upper gastrointestinal bleeding from use of any inhibitor of gastric acid compared to no treatment (typical RR 0.36, 95% CI 0.26 to 0.49; typical RD -0.26, 95% CI -0.33, -0.19; NNTB 4, 95% CI 3 to 5). The quality of evidence was low. There were no significant subgroup differences in duration of upper gastrointestinal bleeding or of continued upper gastrointestinal bleeding according to type of inhibitor of gastric acid. A single trial (38 infants) reported no difference in anaemia requiring blood transfusion from use of a H2 receptor antagonist compared to no treatment.Although no serious adverse events were reported from the use of a H2 receptor antagonist or proton pump inhibitor, some neonatal morbidities - including necrotising enterocolitis, ventilator-associated pneumonia, duration of ventilation and respiratory support, and duration of hospital stay - were not reported. Long-term outcome was not reported. Authors' conclusions There is moderate-quality evidence that use of an H2 receptor antagonist reduces the risk of gastrointestinal bleeding in newborn infants at high risk of gastrointestinal bleeding. There is low-quality evidence that use of an inhibitor of gastric acid (H2 receptor antagonist or proton pump inhibitor) reduces the duration of upper gastrointestinal bleeding and the incidence of continued gastric bleeding in newborn infants with gastrointestinal bleeding. However, there is no evidence that use of an inhibitor of gastric acid in newborn infants affects mortality or the need for blood transfusion. As no study reported the incidence of necrotising enterocolitis, ventilator- or hospital-associated pneumonia, sepsis, or long-term outcome, the safety of inhibitors of gastric acid secretion is unclear.

Self-Medication With Analgesics and Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) is a Gram-negative bacillus responsible for one of the most commonly diagnosed infections in humans worldwide. It is recognized to be associated closely with gastric and duodenal ulcers in adults and children (1, 2). Helicobacter pylori persistently colonizes the human stomach, induces inflammatory cytokines, and causes gastric inflammation and then increases gastric acid production (1, 3). Sometimes, H. pylori can cause pan gastritis with decreased gastric acid production and gastric atrophy. The prevalence rate is different from 10 to 60% according to developed or under developing countries. Crowding and poor personal hygiene play an important role in person-to-person transmission of H. pylori infection and also socio-economic level is strongly related to the prevalence of H. pylori infection, an important finding that may also reflect the same factors as those noted in developing countries. In these situations, infection clusters are reported, particularly in families with infected children. The possible routes are fecal-oral and oral-oral (1, 2). Nonsteroidal anti-inflammatory drugs (NSAIDs) are also well-established risk factors for the development of uncomplicated and complicated gastric ulcers. Evidence suggests the use of NSAIDs, especially in patients with H. pylori infection can cause the chance of gastric and duodenal ulcers. On the other hand, coprescription of NSAIDs with proton-pump inhibitors (PPIs) reduces gastroduodenal lesions. NSAID-naive users benefit from testing for H. pylori infection and, if positive, H. pylori eradication therapy is recommended prior to the initiation of NSAID (1, 4). There are studies showing that the interaction between H. pylori and NSAIDs in ulcer development maybe synergistic. Chan (3) showed that H. pylori eradication is essential to prevent peptic ulcers caused by the use of nonsteroidal anti-inflammatory drugs, whose risk is reduced by almost four-fold after the disappearance of the H. pylori infection. Some researchers reported that PPI therapy is superior to the eradication of H. pylori for the secondary prevention of upper gastrointestinal bleeding in patients with H. pylori who continue to take NSAIDs (1, 3-6). It is clear that, ulcer risk reduction after H. pylori eradication therapy is more marked in patients starting to use NSAIDs than in patients who receive NSAIDs without eradication therapy. In some countries, like our region, self-medication is common and some patients, who suffer from any pain, use the NSAIDs even with high dose. Moreover, some pharmacies offer these drugs without any prescription to patients. Hence, the rate of infection is high in this area and also using NSAIDs and aspirin in this situation can cause peptic ulcer and hemorrhage. Therefore, we must acknowledge patients about this issue.