• Analgesics
• anti-epileptic drugs
• antidepressants
• defined daily doses
• persistent use

• NSAIDs
• anticoagulants
• aspirin
• checkpoint inhibitors
• drug-induced gastric damage
• gastritis
• glucocorticoids
• iron therapy
• mycophenolate

• 5-alkoxypyrazoles
• alkylation
• analgesia
• molecular docking
• partial agonists
• the transient receptor potential vanilloid 1 (TRPV1)

• Cricetinae
• Rats
• Mice
• Animals
• Analgesics/pharmacology
• Analgesics/therapeutic use
• CHO Cells
• Rats, Sprague-Dawley
• Cricetulus
• TRPV Cation Channels

• 21-13-00390 Russian Science Foundation

Dyspepsia is a common complaint in upper gastrointestinal disorders. It is described as predominant epigastric pain lasting for at least one month. Globally, peptic ulcer disease occurs in 3.5–32% of patients with dyspepsia. Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drugs/aspirin use are the widely known risk factors for peptic ulcer disease. There was no recent document on H. pylori infection rate among patients with peptic ulcer disease in Ethiopia. This study aimed to determine magnitude and associated factors of peptic ulcer disease among dyspeptic patients in Northwest Ethiopia.

An institutional-based cross sectional study was conducted at the University of Gondar hospital, Northwest Ethiopia. A convenience sampling method was used to recruit 218 study subjects. A pre-designed semi-structured questionnaire was used to extract clinical information. Olympus flexible fiber-optic endoscope (Olympus, GIF-E 600, Olympus Corp., Hamburg, Germany) was used to confirm the presence of peptic ulcer disease. Diagnosis of active H. pylori infection was made using the fecal H. pylori Antigen 25 T Card Test (Anamol Lab., Pvt. Ltd., Palghar, India). The Data were entered into EPI Info version 4.6.0.2, and then exported to SPSS version 20 for analysis. Explanatory variables associated with peptic ulcer disease were analyzed by applying logistic regression model. P value < 0.05 was used to declare significant association.

A total of 218 dyspeptic patients who underwent upper gastrointestinal endoscopic evaluations were included in the study. The mean (+ SD) age of patients was 42 ± 16.4 years. Forty nine percent (95% CI 42.4–56.2) of dyspeptic patients had active H. pylori infection. Peptic ulcer disease was diagnosed in 35% (95% CI 31.4–39.2) of patients with dyspepsia. H. pylori infection (AOR = 6.298, 95% CI 2.965–13.378, P value <  0.001) and NSAIDs/ASA use (AOR = 6.252, 95% CI 2.925–13.362, P value <  0.001) were identified as risk factors for peptic ulcer disease.

Medical treatment of peptic ulcer disease should target treatment of H. pylori infection and cautious use of non-steroidal anti-inflammatory drugs/aspirin.

• Dyspepsia
• H. pylori
• NSAIDs
• Northwest Ethiopia
• Peptic ulcer disease

• Gastric ulcer
• HO-1
• Inflammatory factors
• NF-κB
• Nrf2
• Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils

• Animals
• Body Weight/drug effects
• Cell Survival/drug effects
• Cytokines/genetics
• Cytokines/metabolism
• Ethanol/toxicity
• Fruit/chemistry
• Gastric Mucosa/drug effects
• Gastric Mucosa/pathology
• Gene Expression Regulation/drug effects
• Mice
• NF-E2-Related Factor 2/genetics
• NF-E2-Related Factor 2/metabolism
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Phytotherapy
• Plant Extracts/chemistry
• Plant Extracts/therapeutic use
• RAW 264.7 Cells
• Rats
• Rats, Wistar
• Rosa
• Signal Transduction
• Stomach Ulcer/chemically induced
• Stomach Ulcer/drug therapy

Low-dose aspirin can cause gastric and duodenal ulceration, hereafter called peptic ulcer disease (PUD). Predisposition is thought to be related to clinical and genetic factors; our aim was to identify genetic risk factors associated with aspirin-induced PUD.

Patients (n=1478) were recruited from 15 UK hospitals. Cases (n=505) were defined as patients with endoscopically confirmed PUD within 2 weeks of using aspirin and non-aspirin Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). They were compared to two control groups: patients with endoscopically confirmed PUD without any history of NSAID use within 3 months of diagnosis (n=495), and patients with no PUD on endoscopy (n=478). A genome-wide association study (GWAS) of aspirin-induced cases (n=247) was compared to 476 controls. The results were validated by replication in another 84 cases and 162 controls.

The GWAS identified one variant, rs12678747 (p=1·65×10⁻⁷) located in the last intron of EYA1 on chromosome 8. The association was replicated in another sample of 84 PUD patients receiving aspirin (p=0·002). Meta-analysis of discovery and replication cohort data for rs12678747, yielded a genome-wide significant association (p=3·12×10⁻¹¹; OR=2·03; 95% CI 1·65-2·50). Expression of EYA1 was lower at the gastric ulcer edge when compared with the antrum.

Genetic variation in an intron of the EYA1 gene increases the risk of endoscopically confirmed aspirin-induced PUD. Reduced EYA1 expression in the upper gastrointestinal epithelium may modulate risk, but the functional basis of this association will need mechanistic evaluation.

Department of Health Chair in Pharmacogenetics, MRC Centre for Drug Safety Science and the Barts Cardiovascular NIHR Biomedical Research Centre, British Heart Foundation (BHF)

• Aspirin
• GWAS
• NSAID
• ulcer

• Cancer
• Chemoprevention
• Colorectal
• Neoplasia

• Aspirin/therapeutic use
• Chemoprevention
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/prevention & control
• Diabetes Mellitus, Type 2
• Humans
• Neoplasm Recurrence, Local

Glycyrrhizae Radix et Rhizoma (GRR) is one of the commonly used traditional Chinese medicines in clinical practice, which has been applied to treat digestive system diseases for hundreds of years. GRR is preferred for anti-gastric ulcer, however, the main active compounds are still unknown. In this study, GRR was used as precursor to synthesize carbon dots (CDs) by a environment-friendly one-step pyrolysis process. GRR-CDs were characterized by using transmission electron microscopy, high-resolution TEM, fourier transform infrared, ultraviolet-visible and fluorescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. In addition, cellular toxicity of GRR-CDs was studied by using CCK-8 in RAW264.7 cells, and the anti-gastric ulcer activity was evaluated and confirmed using mice model of acute alcoholic gastric ulcer. The experiment confirmed that GRR-CDs were the spherical structure with a large number of active groups on the surface and their particle size ranged from 2 to 10 nm. GRR-CDs had no toxicity to RAW264.7 cells at concentration of 19.5 to 5000 μg/mL and could reduce the oxidative damage of gastric mucosa and tissues caused by alcohol, as demonstrated by restoring expression of malondialdehyde, superoxide dismutase and nitric oxide in serum and tissue of mice. The results indicated the explicit anti-ulcer activity of GRR-CDs, which provided a new insights for the research on effective material basis of GRR.

• Glycyrrhizae Radix et Rhizoma
• acute alcoholic gastric ulcer
• carbon dots
• protective effect

• Animals
• Carbon/chemistry
• China
• Chromatography, High Pressure Liquid/methods
• Drugs, Chinese Herbal/chemistry
• Drugs, Chinese Herbal/pharmacology
• Glycyrrhiza/chemistry
• Male
• Medicine, Chinese Traditional/methods
• Mice
• Photoelectron Spectroscopy/methods
• Pyrolysis
• Quantum Dots/chemistry
• RAW 264.7 Cells
• Spectrometry, Fluorescence/methods

• Drug
• Heart Disease Prevention
• Stomach
• Thrombosis

• Helicobacter pylori
• Peptic ulcer disease

To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA).

PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies.

43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=−0.30, 95% CI −0.40 to –0.20) and improving function (SMD=−0.35, 95% CI −0.45 to –0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=−0.81, 95% CI −1.12 to –0.52) and piroxicam was most effective for functional improvement (SMD=−1.04, 95% CI −1.60 to –0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs.

Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study.

• meta-analysis
• osteoarthritis

The purpose of this study is to investigate the recurrence rate of peptic ulcer disease (PUD) over a long follow-up period with PUD patients without Helicobacter pylori.

We retrospectively reviewed patients diagnosed with PUD on endoscopy and divided them into two groups: a H. pylori-negative group (HP-negative group), and a group of patients with untreated H. pylori (HP noneradicated group). We compared the recurrence rates of PUD in these two groups and analyzed the factors that affected ulcer recurrence.

Total of nine hospitals in Korea participated, and a total of 1,761 patients were retrospectively reviewed. The HP-negative group included 553 patients, and the HP noneradicated group included 372 patients. The 5-year cumulative probabilities of PUD recurrence were 36.4% in the HP-negative group and 43.8% in the HP noneradicated group (p=0.113). The factors that were found to affect recurrence in the HP-negative group were elder, male, and comorbid chronic kidney disease.

The 5-year cumulative probability of PUD recurrence without H. pylori infection after a long-term follow-up was 36.4% and the factors that affected recurrence were elder, male, and comorbid chronic kidney disease.

• Helicobacter negative
• Natural course
• Peptic ulcer disease

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of the most commonly used medicines and proven to be effective for certain disorders. Some people use NSAIDs on daily basis for preventive purpose. But a variety of severe side effects can be induced by NSAIDs. Studies have shown that edible natural ingredients exhibit preventive benefit of gastric ulcer. This paper reviews the efficacy and safety of edible natural ingredients in preventing the development of gastric ulcer induced by NSAIDs in animal models.

A systematic literature search was conducted on PubMed, using the terms “herbal medicines” and “gastric ulcer”, “herbal medicines” and “peptic ulcer”, “food” and “peptic ulcer”, “food” and “gastric ulcer”, “natural ingredient” and “peptic ulcer”, “natural ingredient” and “gastric ulcer”, “alternative medicine” and “peptic ulcer”, “alternative medicine” and “gastric ulcer”, “complementary medicine” and “peptic ulcer”, “complementary medicine” and “gastric ulcer” in papers published in English between January 1, 1960 and January 31, 2016, resulting in a total of 6146 articles containing these terms. After exclusion of studies not related prevention, not in NSAID model or using non-edible natural ingredients, 54 articles were included in this review.

Numerous studies have demonstrated that edible natural ingredients exhibit antiulcerogenic benefit in NSAID-induced animal models. The mechanisms by which edible, ingredient-induced anti-ulcerogenic effects include stimulation of mucous cell proliferation, antioxidation, inhibition of gastric acid secretion, as well as inhibition of H (+), K (+)- ATPase activities. Utilization of edible, natural ingredients could be a safe, valuable alternative to prevent the development of NSAID-induced gastric ulcer, particularly for the subjects who are long-term users of NSAIDs.

• Animal models
• Food
• Gastric ulcer
• Nonsteroidal anti-inflammatory drugs
• Prevention

• ASP6537 (PubChem CID: 9922739), Aspirin (PubChem CID: 2244)
• Aspirin
• Clopidogrel
• Clopidogrel (PubChem CID: 60606)
• Cyclooxygenase-1
• P2Y(12) receptor
• Platelet
• Thrombosis

• Epidemiology
• Helicobacter pylori
• Peptic ulcer
• Prevalence
• Therapy

• antioxidant activity
• arctigenin
• gastroprotective
• inflammation

At December 2014, this review has been withdrawn from the Cochrane Library. This review is out of date, although it is correct at the date of publication. The review may be misleading as new studies could alter the original conclusions. All previous versions of the review can be found in the ‘Other versions’ tab. We are seeking additional authors to support the updating of this review. For further information, please contact PaPaS Managing Editor, Anna Hobson [Contact Person].

The editorial group responsible for this previously published document have withdrawn it from publication.

• Acute Disease
• Adolescent
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Child
• Diclofenac/adverse effects
• Diclofenac/therapeutic use
• Humans
• Pain/drug therapy
• Pain Measurement
• Pain, Postoperative/drug therapy
• Randomized Controlled Trials as Topic

• Adult
• Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Aspirin/administration & dosage
• Aspirin/adverse effects
• Female
• Gastrointestinal Diseases/chemically induced
• Gastrointestinal Diseases/prevention & control
• Gastrointestinal Hemorrhage/chemically induced
• Gastrointestinal Hemorrhage/epidemiology
• Humans
• Male
• Middle Aged
• Preventive Health Services

• 16891 Cancer Research UK
• British Heart Foundation

• acetylsalicylic acid
• nested case–control study
• uncomplicated peptic ulcer disease

• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Aspirin/administration & dosage
• Aspirin/adverse effects
• Cardiovascular Diseases/prevention & control
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Odds Ratio
• Peptic Ulcer/chemically induced
• Peptic Ulcer/epidemiology
• Proportional Hazards Models
• Retrospective Studies
• Risk Factors
• Secondary Prevention

Gastric ulcer is a common disorder of the digestive system. Current therapeutic regimens largely rely on Western medicine. However, numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and various animal models via divergent mechanisms. This review updates the efficacy and safety of herbal medicines in treating gastric ulcer, and the mechanisms of their action in humans and animal models. Studies have demonstrated that the efficacy of herbal medicines is comparable or superior to that of drugs such as omeprazole or cimetidine in humans and animal models, and herbal medicines display fewer adverse effects. The mechanisms by which herbal medicines benefit gastric ulcer include stimulation of mucous cell proliferation, anti-oxidation, and inhibition of gastric acid secretion and H(+)/K(+)-ATPase activity. Some herbal medicines also exhibit antimicrobial properties. Utilization of herbal medicines could be a valuable alternative to treat gastric ulcer in humans effectively, with few adverse effects.

• Herbal medicines
• Gastric ulcer
• Mechanism of action

• Animals
• Anti-Ulcer Agents/adverse effects
• Anti-Ulcer Agents/therapeutic use
• Antioxidants/therapeutic use
• Gastric Acid/metabolism
• Gastric Mucosa/drug effects
• Gastric Mucosa/metabolism
• Gastric Mucosa/pathology
• Humans
• Phytotherapy
• Plant Preparations/adverse effects
• Plant Preparations/therapeutic use
• Plants, Medicinal
• Proton Pump Inhibitors/therapeutic use
• Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors
• Sodium-Potassium-Exchanging ATPase/metabolism
• Stomach Ulcer/drug therapy
• Stomach Ulcer/metabolism
• Stomach Ulcer/pathology
• Treatment Outcome
• Wound Healing/drug effects

Few epidemiologic studies have investigated predictors of uncomplicated peptic ulcer disease (PUD) separately from predictors of complicated PUD.

To analyze risk factors associated with uncomplicated PUD and medication use after diagnosis.

Patients diagnosed with uncomplicated PUD (n = 3,914) were identified from The Health Improvement Network database among individuals aged 40–84 years during 1997–2005, with no previous history of PUD. Prescription records for the year after the date of diagnosis were reviewed and a nested case–control analysis was performed to calculate the odds ratios for the association of potential risk factors with PUD.

Medications associated with developing uncomplicated PUD included current use of acetylsalicylic acid (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, selective serotonin reuptake inhibitors, antidepressants, antihypertensives or acid suppressants. Uncomplicated PUD was significantly associated with being a current or former smoker and having had a score of at least 3 on the Townsend deprivation index. Approximately 50% of patients who were users of ASA (19% of patients) or chronic users of NSAIDs (7% of patients) at diagnosis did not receive another prescription of the medication in the 60 days after diagnosis, and 30% were not represcribed therapy within a year. Among patients who were current users of ASA or chronic NSAIDs at the time of the PUD diagnosis and received a subsequent prescription for their ASA or NSAID during the following year, the vast majority (80–90%) also received a proton pump inhibitor coprescription.

Our results indicate that several risk factors for upper gastrointestinal bleeding are also predictors of uncomplicated PUD, and that some patients do not restart therapy with ASA or NSAIDs after a diagnosis of uncomplicated PUD. Further investigation is needed regarding the consequences for these patients in terms of increased cardiovascular burden due to discontinuation of antiplatelet therapy.

• Adult
• Aged
• Aged, 80 and over
• Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Aspirin/administration & dosage
• Aspirin/adverse effects
• Case-Control Studies
• Comorbidity
• Female
• Helicobacter Infections/complications
• Humans
• Male
• Middle Aged
• Peptic Ulcer/diagnosis
• Peptic Ulcer/epidemiology
• Peptic Ulcer/etiology
• Proton Pump Inhibitors/administration & dosage
• Proton Pump Inhibitors/adverse effects
• Risk Factors
• United Kingdom/epidemiology

Background: The risk of upper gastrointestinal (GI) complications associated with the use of NSAIDs is a serious public health concern. The risk varies between individual NSAIDs; however, there is little information on the risk associated with some NSAIDs and on the impact of risk factors. These data are necessary to evaluate the benefit-risk of individual NSAIDs for clinical and health policy decision making. Within the European Community’s Seventh Framework Programme, the Safety Of non-Steroidal anti-inflammatory drugs (NSAIDs) [SOS] project aims to develop decision models for regulatory and clinical use of individual NSAIDs according to their GI and cardiovascular safety.

Objective: The aim of this study was to conduct a systematic review and meta-analysis of observational studies to provide summary relative risks (RR) of upper GI complications (UGIC) associated with the use of individual NSAIDs, including selective cyclooxygenase-2 inhibitors.

Methods: We used the MEDLINE database to identify cohort and case-control studies published between 1 January 1980 and 31 May 2011, providing adjusted effect estimates for UGIC comparing individual NSAIDs with non-use of NSAIDs. We estimated pooled RR and 95% CIs of UGIC for individual NSAIDs overall and by dose using fixed- and random-effects methods. Subgroup analyses were conducted to evaluate methodological and clinical heterogeneity between studies.

Results: A total of 2984 articles were identified and 59 were selected for data abstraction. After review of the abstracted information, 28 studies met the meta-analysis inclusion criteria. Pooled RR ranged from 1.43 (95% CI 0.65, 3.15) for aceclofenac to 18.45 (95% CI 10.99, 30.97) for azapropazone. RR was less than 2 for aceclofenac, celecoxib (RR 1.45; 95% CI 1.17, 1.81) and ibuprofen (RR 1.84; 95% CI 1.54, 2.20); 2 to less than 4 for rofecoxib (RR 2.32; 95% CI 1.89, 2.86), sulindac (RR 2.89; 95% CI 1.90, 4.42), diclofenac (RR 3.34; 95% CI 2.79, 3.99), meloxicam (RR 3.47; 95% CI 2.19, 5.50), nimesulide (RR 3.83; 95% CI 3.20, 4.60) and ketoprofen (RR 3.92; 95% CI 2.70, 5.69); 4–5 for tenoxicam (RR 4.10; 95% CI 2.16, 7.79), naproxen (RR 4.10; 95% CI 3.22, 5.23), indometacin (RR 4.14; 95% CI 2.91, 5.90) and diflunisal (RR 4.37; 95% CI 1.07, 17.81); and greater than 5 for piroxicam (RR 7.43; 95% CI 5.19, 10.63), ketorolac (RR 11.50; 95% CI 5.56, 23.78) and azapropazone. RRs for the use of high daily doses of NSAIDs versus non-use were 2-3 times higher than those associated with low daily doses.

Conclusions: We confirmed variability in the risk of UGIC among individual NSAIDs as used in clinical practice. Factors influencing findings across studies (e.g. definition and validation of UGIC, exposure assessment, analysis of new vs prevalent users) and the scarce data on the effect of dose and duration of use of NSAIDs and on concurrent use of other medications need to be addressed in future studies, including SOS.

• AA
• ACS
• Arachidonic acid
• Aspirin
• COX
• Cyclooxygenase
• DMSO
• GI
• MC
• MED
• MI
• NSAIDs
• PGI(2)
• PRP
• Platelet
• Prostaglandin I(2)
• TTO
• TXA(2)
• Thrombosis
• Thromboxane A(2)
• acute coronary syndrome
• cyclooxygenase
• dimethylsulfoxide
• gastrointestinal
• methylcellulose
• minimum effective dose
• myocardial infarction
• non-steroidal anti-inflammatory drugs
• platelet-rich plasma
• prostaglandin I(2)
• thromboxane A(2)
• time to occlusion

Low-dose aspirin (LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society. On the other hand, a very low dose of aspirin (10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage. The incidence of LDA-induced gastrointestinal mucosal injury and bleeding has increased. It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug (NSAID)-induced lesions. The pathogenesis related to inhibition of cyclooxygenase (COX)-1 includes reduced mucosal flow, reduced mucus and bicarbonate secretion, and impaired platelet aggregation. The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence. The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation. The factors associated with an increased risk of upper gastrointestinal (GI) complications in subjects taking LDA are aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs, and Helicobacter pylori (H. pylori) infection. Moreover, no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea, acid regurgitation, heartburn, and bloating. It has been shown that the ratios of ulcers located in the body, fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA. Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers. In contrast to NSAID-induced gastrointestinal ulcers, a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers. The eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Continuous aspirin therapy for patients with gastrointestinal bleeding may increase the risk of recurrent bleeding but potentially reduces the mortality rates, as stopping aspirin therapy is associated with higher mortality rates. It is very important to prevent LDA-induced gastroduodenal ulcer complications including bleeding, and every effort should be exercised to prevent the bleeding complications.

• Gastroduodenal ulcer
• Upper gastrointestinal bleeding
• Low-dose aspirin
• Non-steroidal anti-inflammatory drugs

• Animals
• Anti-Bacterial Agents/therapeutic use
• Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Aspirin/administration & dosage
• Aspirin/adverse effects
• Cyclooxygenase 1/metabolism
• Cyclooxygenase 2/metabolism
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Gastric Mucosa/drug effects
• Gastric Mucosa/enzymology
• Gastric Mucosa/microbiology
• Gastric Mucosa/pathology
• Gastrointestinal Hemorrhage/etiology
• Helicobacter Infections/complications
• Helicobacter Infections/microbiology
• Helicobacter pylori/pathogenicity
• Histamine H2 Antagonists/therapeutic use
• Humans
• Peptic Ulcer/chemically induced
• Peptic Ulcer/enzymology
• Peptic Ulcer/microbiology
• Peptic Ulcer/pathology
• Peptic Ulcer/prevention & control
• Prognosis
• Proton Pump Inhibitors/therapeutic use
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Outcome

• Adult
• Aged
• Anastomosis, Surgical/adverse effects
• Duodenal Ulcer/surgery
• Duodenum/surgery
• Female
• Humans
• Jejunum/surgery
• Male
• Middle Aged
• Peptic Ulcer Perforation/surgery
• Postoperative Complications
• Reoperation
• Wound Closure Techniques/adverse effects

• confounding
• databases
• pharmacoepidemiology
• propensity score analysis
• thin

• Adult
• Aged
• Aged, 80 and over
• Algorithms
• Anti-Inflammatory Agents, Non-Steroidal/adverse effects
• Confounding Factors, Epidemiologic
• Cyclooxygenase 2 Inhibitors/adverse effects
• Databases, Factual/statistics & numerical data
• Electronic Health Records/statistics & numerical data
• Female
• Gastrointestinal Hemorrhage/chemically induced
• Gastrointestinal Hemorrhage/epidemiology
• Gastrointestinal Hemorrhage/etiology
• Humans
• Male
• Middle Aged
• Pharmacoepidemiology/methods
• Propensity Score
• Risk Factors
• United Kingdom

• R01 HL080644 NHLBI NIH HHS
• R01 HL080644-07 NHLBI NIH HHS