Risk Of Peptic Ulcer Research Articles

Dosage effects of histamine-2 receptor antagonist on the primary prophylaxis of non-steroidal anti-inflammatory drug (NSAID)-associated peptic ulcers: a retrospective cohort study.

A histamine-2 receptor antagonist (H2RA) is one of the common gastroprotective co-therapies used with non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention or treatment of peptic ulcers (PUs). To date, no study has directly compared the prophylactic effectiveness between high-dose and low-dose H2RA. Our objective was to compare the effectiveness of high-dose versus low-dose H2RAs in the primary prophylaxis of PUs among short-term NSAID users. A retrospective cohort study was conducted using the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. Patients aged 18years or above who received a single prescription of oral NSAID with oral H2RA were identified within the study period (1 January 2009-31 December 2012). Patients with a history of or risk factors for PU in the corresponding 2 years prior to the index date (of the first NSAID prescription) were excluded. Log binomial regression analysis was used to calculate the relative risk of PU among NSAID users with high-dose H2RA versus low-dose H2RA exposure. Among the NSAID cohort (n = 102,042), 77,509 (76%) were on low-dose H2RA and 24,533 (24%) were on high-dose H2RA. Of the total 69 PU cases identified during the drug exposure period, 64 (0.08%) received low-dose-H2RA and five (0.02%) received high-dose H2RA. The overall absolute risk of PUs for NSAID users whilst on H2RA was approximately 1 per 1,479 patients. The adjusted relative risk for NSAID users receiving high-dose H2RA versus low-dose H2RA was 0.32 (95% confidence interval [CI] 0.13-0.79). Patients aged ≥65years, receiving a longer duration of treatment, or with concomitant use of antiplatelet agents were found to be at higher risk of PU. High-dose H2RA showed greater effectiveness than low-dose H2RA in the primary prophylaxis of NSAID-associated PUs in short-term new users.

H. pylori eradication lower ulcers in cirrhosis. [Corrected

The study aimed to investigate whether early Helicobacter pylori (H. pylori) eradication therapy in cirrhotic patients caused a dramatic reduction of recurrent peptic ulcers compared with those treated with a late eradication. We identified cirrhotic patients using the International Classifications of Diseases, Revision 9 (ICD-9-CM). Decompensated cirrhotic patients can apply for a catastrophic illness card and were identified via the ICD-9-CM codes 571.2, 571.5 and 571.6. Compensated cirrhotic patients were identified via the ICD-9-CM codes 571.2, 571.5 and 571.6, after excluded decompensated cirrhotic patients. We categorized patients into early (time lag ≤365 days after peptic ulcer diagnosis) and late (time lag >365 days) H. pylori eradication therapy groups. The end-point was the occurrence of recurrent peptic ulcers. Cox proportional hazards model was used to calculate the hazard ratios (HRs). Altogether, 154 cirrhotic patients were included in the early H. pylori eradication group and 103 in the late H. pylori eradication group. Cirrhotic patients had a higher risk of recurrent peptic ulcers in the late H. pylori eradication group (HR 1.58, 95% CI 1.09-2.28, P = 0.015). However, the risk of recurrent peptic ulcers in alcoholic cirrhotic patients in both groups (HR 1.47, 95% CI 0.77-2.83, P = 0.247) was similar. Early H. pylori eradication is associated with a lower risk of recurrent peptic ulcers in cirrhotic patients. H. pylori eradication is the mainstay for treating cirrhotic patients who have contracted peptic ulcers.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: old question new insights.

Previous reports clearly demonstrated that Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAID) or low dose aspirin (ASA) use significantly and independently increased the risk for the development of peptic ulcer disease. Today, the presence of H. pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications. Whether NSAID intake in the presence of H. pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate. Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years. In addition, the interaction between H. pylori infection and low-dose ASA remains even more controversial. In real clinical practice, we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors. These huge variety of possible combinations greatly hinder the decision making process of physicians.

Is combined use of SSRIs and NSAIDs associated with an increased risk of starting peptic ulcer treatment?

De Jong et al. [1] reported that the combined use of nonsteroidal anti-inflammatory drugs (NSAIDs) with selective serotonin reuptake inhibitors (SSRIs) synergistically increased the risk of initiating a treatment course with peptic ulcer drugs as a proxy for gastrointestinal adverse effects. In an attempt to limit confounding by indication, tricyclic antidepressant (TCA) users were used as a control group. As the observed association was not adjusted for potential differences between TCA and SSRI users [1], unmeasured confounding may have affected the estimation of the adverse effects. We therefore addressed the association using another pharmacoepidemiological study design, a so-called prescription sequence symmetry design [2]. The main advantage of this design is that it controls for time-invariant (unmeasured) confounding, because the patient population serves as its own control group. We used data from the same pharmacy prescription database (IADB; http://www.IADB.nl) that de Jong et al. [1] used and applied similar inclusion and exclusion criteria. When assessing the association between initiating treatment A and B, the sequence ratio (SR) is calculated by dividing the number of individuals starting treatment A first and treatment B second by the number of individuals starting treatment B first and treatment A second. For the primary analysis, only patients with a time span between both incident prescriptions between 2 and 28 days were included to limit time-variant confounding. We adjusted for prescription time trends by dividing the crude SR by a null ratio, i.e. the SR obtained assuming no association between both drugs, based on overall prescription rates of both drugs in the total IADB population. We estimated 95% confidence intervals (CIs) of SRs using exact confidence intervals for binomial distributions using STATA 12 software (StataCorp LP, College Station, TX, USA). In total, 50 350 adult patients who initiated SSRI treatment were identified between July 1994 and December 2011. A peptic ulcer drug treatment course was started in 277 of them within a 4 week period of SSRI therapy initiation; 126 (45%) started SSRI therapy prior to peptic ulcer drug treatment, while 151 (55%) patients first started peptic ulcer drug treatment [adjusted (a)SR, 0.83; 95% CI, 0.65–1.06; Table ​Table1].1]. Concurrent use of SSRIs and NSAIDs was associated with a statistically nonsignificant increase in the risk of starting peptic ulcer drug treatment (aSR, 1.48; 95% CI, 0.90–2.49), which did not exceed the risk estimated for NSAID treatment alone (aSR, 2.50; 95% CI, 2.27–2.76). Similar results were obtained for TCA treatment alone and concurrent use of TCAs and NSAIDs (Table ​(Table11). Table 1 Symmetry analysis of selected drug therapy initiation within 4 weeks of peptic ulcer drug therapy initiation using a drug-free run-in period of half a year Given that we used the same database and similar inclusion and exclusion criteria as de Jong et al. [1], the main difference between their study and ours is that we used an alternative design that reduces time-invariant (unmeasured) confounding. In accordance with our results, Dall et al., who applied a case–control design in which they controlled for various potential confounders including alcohol abuse, did not observe an increased risk of uncomplicated peptic ulcers associated with combined use of SSRIs and NSAIDs [3]. As we restricted our analyses to relatively short time spans to reduce the potential influence of time-variant confounding, we could not detect a risk that develops later in the course of treatment. However, de Jong et al. found an increased risk for concomitant use of SSRIs and NSAIDs during an average follow-up of 21 days [1]. In addition, Dall et al. found that the risk of uncomplicated peptic ulcers is greatest during the first 30 days of SSRI treatment [3], indicating that our time span of 4 weeks should be long enough to capture potential drug-related increases in peptic ulcer drug prescribing. We could not capture peptic ulcer drug courses prescribed during hospitalization, measure gastrointestinal adverse effects that required hospitalization or measure over-the-counter NSAID and peptic ulcer drug use. However, de Jong et al. did previously find an increased risk in patients concurrently using SSRIs and NSAIDs, while coping with the same limitations [1]. Therefore, the lack of an increased risk associated with SSRI use, whether used concurrently with NSAIDs or not, is likely not to be related to these potential limitations. In conclusion, our results suggest that the observations reported by de Jong et al. [1] might, at least partly, be attributed to unmeasured confounding. Although comparison with a drug that is used to treat the same indication does limit confounding, it does not eliminate all potential confounders. Therefore, when limited data on potential confounders are available, a self-controlled design can have added value, because it eliminates all time-invariant confounders [4].

Helicobacter pylori Eradication within 120 Days Is Associated with Decreased Complicated Recurrent Peptic Ulcers in Peptic Ulcer Bleeding Patients.

Background/AimsThe connection between Helicobacter pylori and complicated peptic ulcer disease in peptic ulcer bleeding (PUB) patients taking nonsteroidal anti-inflammatory drugs has not been established. In this study, we sought to determine whether delayed H. pylori eradication therapy in PUB patients increases complicated recurrent peptic ulcers.MethodsWe identified inpatient PUB patients using the Taiwan National Health Insurance Research Database. We categorized patients into early (time lag ≤120 days after peptic ulcer diagnosis) and late H. pylori eradication therapy groups. The Cox proportional hazards model was used. The primary outcome was rehospitalization for patients with complicated recurrent peptic ulcers.ResultsOur data indicated that the late H. pylori eradication therapy group had a higher rate of complicated recurrent peptic ulcers (hazard ratio [HR], 1.52; p=0.006), with time lags of more than 120 days. However, our results indicated a similar risk of complicated recurrent peptic ulcers (HR, 1.20; p=0.275) in time lags of more than 1 year and (HR, 1.10; p=0.621) more than 2 years.ConclusionsH. pylori eradication within 120 days was associated with decreased complicated recurrent peptic ulcers in patients with PUB. We recommend that H. pylori eradication should be conducted within 120 days in patients with PUB.

Lack of association of the MDR1 C3435T polymorphism with susceptibility to gastric cancer and peptic ulcer: a systemic review and meta-analysis.

The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU). A literature search was conducted with PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version 5.2), and Stata package (version 12.0) for estimation of publication bias. Six case-control studies were included, of which five were for GC and two for PU. Overall, no evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them. This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings.

Measures of Adiposity Are Associated With Increased Risk of Peptic Ulcer

Obesity is associated with systemic inflammation, alterations in the intestinal microbiome, and decreased epithelial integrity. The association between obesity and peptic ulcer has not been investigated thoroughly. We conducted a prospective cohort study of 47,120 men enrolled in the Health Professionals Follow-Up Study (mean age at baseline, 54 y). Biennially, we updated information on body mass index (BMI), physical activity, smoking, and use of nonsteroidal anti-inflammatory drugs or aspirin. Self-reported waist and hip measurements were validated among a subsample of participants. Self-reported cases of gastric and duodenal ulcers were confirmed by medical record review. Helicobacter pylori status was determined from endoscopic biopsy specimens, serum antibody measurements, and/or stool antigen assays documented in the medical record. We used Cox proportional hazards modeling to calculate hazard ratios and 95% confidence intervals (CIs). We documented 272 gastric and 320 duodenal ulcers over 24 years of follow-up evaluation. The multivariate-adjusted hazard ratio for gastric ulcer was 1.83 (95% CI, 1.20-2.78; P(trend) < .01) for obese men (BMI, ≥30.0 kg/m(2)), compared with men with BMIs of 23.0 to 24.9 kg/m(2), and 1.88 (95% CI, 1.06-3.33; P(trend) = .04) for men with waist-to-hip ratios (WHR) of 1.00 or higher, compared with men with a WHR of 0.85 to 0.89. The risk of duodenal ulcer was not associated with BMI (P(trend) = .24) or WHR (P(trend) = .68). In secondary analyses, increased BMI and WHR each were associated with increased risk of H pylori-negative, but not H pylori-positive, ulcers. The effect of BMI on ulcer risk did not change with use of aspirin or nonsteroidal anti-inflammatory drugs, alcohol consumption, physical activity, or smoking. In a large prospective cohort of male health professionals, central and total obesity were associated with increased risk of peptic ulcer-particularly gastric and H pylori-negative ulcers.

Helicobacter pylori vacA d1 Genotype Predicts Risk of Gastric Adenocarcinoma and Peptic Ulcers in Northwestern Iran

There is a close relationship between Helicobacter pylori (H pylori)-specific factors and different gastroduodenal diseases. The present study aimed to investigate the prevalence of vacA d1, d2 genotypes in the H pylori isolates from patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and gastritis in East Azerbaijan region, where the incidence of gastric cancer (GC) is high. Strains isolated from this area are likely to be of European ancestry. In this study, genotyping of the vacA d region of 115 isolates obtained from patients with different gastrodoudenal diseases was accomplished by PCR methods. In addition to PCR amplification of H pylori 16S rDNA, rapid urease tests or histological examination were used to confirm the presence of H pylori in biopsy specimens. Data were collected and analyzed using SPSS version 19. Of the total of 83 H pylori isolates, 36 (43.4%) contained the d1 allele and 47 (56.6%) were subtype d2. The results of the multiple linear/logistic regression analysis showed high correlation between allele d1 and gastric adenocarcinoma or PUD. This study suggests that the H pylori vacA d1 genotype helps predict risk for gastric adenocarcinoma and PUD in East Azerbaijan, Iran.

Haplotype Analysis of TNFA Gene in Peptic Ulcer Patients

The TNFA gene product TNF- is a cytokine promoting an immune response after bacterial infections. An excessive production of the cytokine is thought to be connected with Helicobacter pylori-induced disorders like gastritis, peptic ulcer disease (PUD), intestinal metaplasia, or even gastric cancer. The synthesis of TNF-a is controlled at transcriptional level and dependent on single nucleotide polymorphisms (SNPs) of TNFA promoter region. SNPs assembled in haplotype have been implicated as potential risk factors for various autoimmune and infectious diseases. The aim of this study was to determine the frequencies of TNFA haplotypes composed of the four common single-nucleotide polymorphisms of the gene (-1031C>T: rs1799964, -863C>A: rs1800630, 857C>T: rs1799724, -308G>A: rs1800629) in peptic ulcer patients and to assess the significance of the haplotypes as the risk factors of H. pylori infection development. 203 peptic ulcer patients were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Haplotypes and degree of linkage disequilibrium (LD) were inferred with PHASE 2.1 and EMLD software. There was no statistically significant difference in haplotype frequencies between the H. pylori-infected and -uninfected peptic ulcer cases (p=0.62). Analogous association was also absent in the subgroups: peptic ulcer woman (p=0.69), peptic ulcer men (p=0.17). The locus pairs -308_-857, -863_-1031, and -857_-1031 was found to be in very strong LD , -308_-1031 and -857 and -863 in strong LD, and -308_-863 in modest LD. TNFA haplotype structure is not connected with individual differences in susceptibility to development of H. pylori infection in peptic ulcer patients. Address for correspondence: Dr. Aleksandra Salagacka Medical University of Lodz Musuynskiego 1, 90-151, Lodz, Poland Telephone/Fax: +48 42 677 91 30 E-mail: aleksandra.salagacka@umed.lodz.pl INTRODUCTION Tumour necrosis factor-alpha (TNF-) is a cytokine known for having the multitude of functions. One of the most prominent is to promote of immune response after bacterial infections. In gastric mucosa infected by Helicobacter pylori TNF- prompts recruitment of mononuclear cells and neutrophils into the gastric lamina propria (Crabtree 1991; Huseyinov 1999). An excessive production of the cytokine could also exert some pathogenic effects (Beutler 1993) and is thought to be connected with H. pylori-induced disorders like gastritis, peptic ulcer disease (PUD), intestinal metaplasia, or even gastric cancer (Goto 2003; Shanks 2009). The synthesis of TNF- is controlled at transcriptional level in a cell typeand stimulus-specific manner involving different transcription factors to a promoter region of the TNFA encoding TNF- (Falvo 2010). An important role in the regulation of TNFA expression is attributed to single nucleotide polymorphisms (SNPs) of promoter region of the gene. Accordingly, these genetic variations are implicated as potential risk factors for various autoimmune and infectious diseases. To date, SNPs at positions -238, -308, -857, 863, -1031 of TNFA have been investigated in various populations afflicted by PUD or other H. pylori-induced disorders (Lee 2005; Lu 2005; Lee 2004; Wilschanski 2007; Kim 2006; Machado 2003). Unfortunately, studies focused on determining the importance of individual TNFA loci have produced non-significant or conflicting results. However, some evidence has supported the hypothesis that effects exerts by these SNPs could be observed or are more pronounced when the polymorphisms are researched and analysed concomitantly. Studies by Lu et al. (2005) conducted in Taiwanese revealed that risk of ulceration after H. pylori infection was higher for carriers of both -1031C or -863A allele of TNFA than for individuals having only one of the mentioned alleles. Similarly, the risk of gastric ulcers among Japanese was found to be greatest in simultaneous carriers of so called ‘high-producer’ alleles of TNFA -857/-863/-1031 than when the presence of these particular alleles was stated individually (Sugimoto 2007). 10 ALEKSANDRA SALAGACKA, MARTA ZEBROWSKA, AGNIESZKA JELEN ET AL Some research results could imply the best approach to investigate the relevancy of TNFA variations, in the development of gastroduodenal diseases, is to explore haplotype structure of TNFA gene. Although Chakravorty et al. (2008) did not stated any connection between single TNFA loci (-308, -857, -863, -1031) and H. pylorimediated duodenal ulcer, the researchers found the TNFA haplotype -308G_-857C_-863A_-1031T in H. pylori-infected duodenal ulcer individuals was significantly more frequent than in the infected but ulcer-free cases. Thus far, haplotype analysis of the gene has been applied in the studies on type 1 diabetes (Stayoussef 2010), gastric cancer (Canedo 2008), iron deficiency anemia (Atkinson 2008), Behcet’s disease (Park 2006), schizophrenia (Saviouk 2005), juvenile oligoarthritis (Zeggini 2002), hepatitis C virus infection (Thio 2004), and some others. Recently, the researchers investigated association between individual -308G>A or -1031T>C SNPs of TNFA and peptic ulcer risk in Poles (Salagacka 2014). In this study the researchers conducted haplotype analysis of TNFA combining mentioned genotyping data and newly obtained for -308 locus and two further -857 and -863 loci of TNFA. The aim of presented research was to estimate the TNFA haplotype structure and its significance in development peptic ulcer disease in Polish population.

Peptic Ulcer Disease Risk in Chronic Kidney Disease: Ten-Year Incidence, Ulcer Location, and Ulcerogenic Effect of Medications

ObjectivesWe aimed at determining peptic ulcer disease (PUD) incidence among chronic kidney disease (CKD) patients during 1998–2008, compared to patients without CKD, and at examining associations between CKD and PUD.MethodsData for 1998–2008 were extracted from the National Health Insurance Research Database in Taiwan. The annual PUD incidence (cases per thousand persons per year) was calculated separately for patients with and without CKD. Characteristics of patients with newly diagnosed PUD (n = 16322) were compared to those of a control group without PUD (n = 32644). The 2 groups were matched for age, sex, and index year. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression.ResultsOver the 10-year period, the PUD incidence was ∼10–12 times higher in CKD patients than in those without CKD. Its incidence in elderly CKD patients increased rapidly over time. For CKD patients, most PUD events (>95%) were managed during hospitalization. Peptic ulcer risk, adjusted for all potential confounders, was much higher in CKD patients undergoing hemodialysis (adjusted OR, 9.74; 95% CI, 7.11–13.31). Maintenance hemodialysis patients were 2 times more likely to have gastric ulcers than duodenal ulcers, while CKD patients not on dialysis had similar risks for both. There were no significant interactions between medications and CKD status on the peptic ulcer risk. Unlike CKD patients on nonsteroidal anti-inflammatory drugs and clopidogrel, those on aspirin did not have a higher peptic ulcer risk (adjusted OR, 0.88; 95% CI, 0.44–1.77).ConclusionsCKD patients have a substantially increased PUD risk, and the majority of CKD patients with PUD require hospital management. Further, peptic ulcer risk is affected by hemodialysis therapy, patient status (inpatient vs. outpatient), and ulcerogenic medications.

Anatlysis of HSPA1B A1267G gene polymorphism in peptic ulcer

Peptic ulcer disease is a common illness, affecting a considerable number of people worldwide, and its occurrence can be influenced by environmental and genetic factors. Heat shock proteins (HSPs) function mostly as molecular chaperones, and are induced by various stresses. The A to G transition at position 1267 of the HSPA1B gene was shown to correlate with changes in the level of HSPA mRNA expression. Here, the relation between A1267G polymorphism of the HSPAIB gene and risk of peptic ulcer in the Iranian population was evaluated. One hundred subjects, who underwent gastroscopy, took part in the study. DNA samples extracted from the biopsy tissues were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). After gastroscopy, peptic ulcer was diagnosed for 50 patients; among them the distribution of AA/AB/BB genotypes was 10, 88 and 2%, respectively. As for the other 50 subjects (without peptic ulcer) included in the control group, the AA/AB/BB genotypes were identified as 40, 52 and 8%, respectively. A significant association was found between the HSPA1B genotype and peptic ulcer (6.76 OR; 95% CI, 2.26-20.2; p = 0.0006). Thus, the HSPA1B A1267G polymorphism may be a marker of susceptibility to peptic ulcer.

Predictive Factors for Endoscopic Hemostasis in Patients with Upper Gastrointestinal Bleeding

Predictive Factors for Endoscopic Hemostasis in Patients with Upper Gastrointestinal Bleeding

Haplotype Analysis of ABCB1 in Patients with Peptic Ulcer–Predisposition to Diseases Development

The aim of this study was to determine the significance of ABCB1 haplotypes composed of the three most common single-nucleotide polymorphisms (c.1236C>T: rs1128503, c.2677G>T/A: rs2032582, c.3435C>T: rs1045642) in the context of peptic ulcer risk and Helicobacter pylori infection development in this condition. The ABCB1 gene product P-glycoprotein is a membrane protein that functions as an ATP-dependent exporter of xenobiotics from cells. The function of the transporter is determined by the assembles of ABCB1 polymorphism called haplotypes. Particular haplotypes have been reported as determining individual susceptibility to conditions such as inflammatory bowel diseases, colorectal cancer.202 peptic ulcer patients and 96 healthy subjects were genotyped. Genotyping was performed for c.1236C>T and c.2677G>T/A by automated sequencing and for c.3435C>T by polymerase chain reaction-restriction fragment length polymorphism method. Haplotypes and degree of linkage disequilibrium (LD) were inferred using PHASE 2.1 and EMLD software. The groups of peptic ulcer and healthy subjects differed significantly in haplotype frequencies (p=0.04). Moreover, there was a statistically significant difference in haplotype frequencies between the H. pylori-infected and-uninfected peptic ulcer cases (p=0.01), and between H. pylori-infected and-uninfected peptic ulcer men (p=0.03). In the peptic ulcer group 1236-2677 locus pair was observed to be in modest LD (D’=0.187), 1236-3435 and 2677-3435 pairs were almost in linkage equilibrium (D’=0.036 and 0.051, respectively). Haplotype structure could be responsible for individual differences in peptic ulcer predisposition and in development of H. pylori infection in peptic ulcer patients.

Low-dose aspirin-associated upper gastric and duodenal ulcers in Japanese patients with no previous history of peptic ulcers

BackgroundLong-term administration of low-dose aspirin (LDA) is associated with a greater risk of adverse events, including gastroduodenal ulcers. The purpose of this study was to identify the risk factors for and assess the role of medication use in the development of peptic ulcer disease in Japanese patients with no history of peptic ulcers.MethodsConsecutive outpatients receiving LDA (75 mg/day) who underwent esophagogastroduodenoscopy between January and December 2010 were enrolled. Clinical parameters, peptic ulcer history, concomitant drugs, the presence of Helicobacter pylori infection, reason for endoscopy, and endoscopic findings were analysed.ResultsOf 226 total patients, 14 (6.2%) were endoscopically diagnosed with peptic ulcer. Age, sex, current smoking status, current alcohol consumption, endoscopic gastric mucosal atrophy, and abdominal symptoms were not significantly associated with peptic ulcers. Diabetes mellitus was more frequent (42.9% vs. 16.5%; P = 0.024) in patients with peptic ulcers than in those without peptic ulcers. Using multiple logistic regression analysis, co-treatment with anticoagulants or proton pump inhibitors (PPIs) was significantly associated with increased and decreased risk for peptic ulcer, respectively (odds ratio [OR], 5.88; 95% confidence interval [CI], 1.19 − 28.99; P = 0.03 and OR, 0.13; 95% CI, 0.02 − 0.73; P = 0.02, respectively). Co-treatment with additional antiplatelet agents, H2-receptor antagonists, angiotensin II Type 1 receptor blockers, angiotensin-converting enzyme inhibitor, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, or nonsteroidal anti-inflammatory drugs was not associated with peptic ulcer development.ConclusionThe use of PPIs reduces the risk of developing gastric or duodenal ulcers in Japanese patients taking LDA without pre-existing gastroduodenal ulcers. However, this risk is significantly increased in both patients ingesting anticoagulants and patients with diabetes. These results may help identify patients who require intensive prophylaxis against aspirin-induced peptic ulcers.

NSAID is inversely associated with asymptomatic gastric ulcer: Local health examination data from the Korean National Health Insurance Corporation

Background. Silent peptic ulcer has been considered to be associated with nonsteroidal anti-inflammatory drug (NSAID). The recent studies have reported no relationship between them. Aim. We attempted to investigate an association between asymptomatic peptic ulcer and NSAID in Korean adults. Methods. The subjects were enrolled from participants visiting Myongji Hospital for health examination program of the Korean National Health Insurance Corporation. The questionnaires were designed to investigate individual medical information and gastroduodenal symptoms. Results. From May 2005 to March 2009, 5459 participants were enrolled and 299 participants were excluded. Of 5160 participants, 3144 (60.9%) participants were asymptomatic and 424 (8.2%) participants had peptic ulcer. Among 3144 asymptomatic participants, NSAID-taking participants had the odds ratio of 1.4 [95% confidence interval (CI): 0.7–2.6, p = 0.339] for the risk of peptic ulcer. Among 424 peptic ulcer patients, 247 (58.3%) were asymptomatic. They had lower prevalence of NSAID use (4.9% vs. 14.7%). The asymptomatic gastric ulcer patients had smaller size and more frequent healing stage than the symptomatic gastric ulcer patients. In multivariable analysis of 424 peptic ulcer patients, NSAID patients had the odds ratio of 0.249 (95%CI: 0.115–0.536, p < 0.05) for asymptomatic peptic ulcer. In subgroup analysis of 284 gastric ulcer patients, NSAID-taking patients had the odds ratio of 0.263 (95% CI: 0.105–0.657, p = 0.004) for asymptomatic peptic ulcer. Conclusion. NSAID has an inverse association with asymptomatic patients with gastric peptic ulcer, but has no association with gastroduodenal symptoms in duodenal ulcer patients. These suggest that NSAID may be associated with gastroduodenal symptoms rather than masking symptoms, at least in gastric ulcer patients.

Assessment of Dietary Pattern for Patients with Peptic Ulcer

Objective: To assess dietary pattern that may contribute to the occurrence of peptic ulcer as risk factors and find out the relationships between dietary pattern indicators and some demographic characteristics (age groups&amp; gender) of the patients with peptic ulcer. Methodology: A descriptive study was carried out in liver and digestive disease hospital and Al-Kadhmiya Teaching Hospital in Baghdad city during the period of March/13/2012 to June/10/2012. A purposive (non- probability) sample was selected that consisted of (100) patients with peptic ulcer their age between (20-60) years old. A questionnaire format and observational checklist were used which consist of three parts the first part includes demographic information of the sample, the second part includes risk factors information and the third part includes dietary pattern indicators distributed to (18) items. The data were collected through the utilization of questionnaire and the structure interview technique with peptic ulcer patients, the interview with each patient took approximately (12-15) minutes. The data were analyzed by using descriptive statistical measures which included frequencies &amp; percentage, as well as the use of inferential statistical measures which include Chi- Square (X2) and p-value. Results: The results of the study sample have revealed that more than one third of patients with peptic ulcer were with the age group(20-29) years, mostly females, college graduate, married and government employee (officer). However, the greater number of these patients were non smoker and not drinking alcohol. Most patients with peptic ulcer were (63%) always eat hot foods. Conclusions; The study concluded that there was a significant differences between dietary pattern indicators with age and gender. Recommendations: The study recommended that: 1- Educational program should be designed to increase people information toward the disease and to reduce the risk of peptic ulcer. 2- A booklet should be prepared and presented to patients with peptic ulcer as guide for the management of the disease.

Multisystem Morbidity and Mortality in Cushing's Syndrome: A Cohort Study

Cushing's syndrome (CS) is associated with hypercoagulability, insulin resistance, hypertension, bone loss, and immunosuppression. To date, no adequately large cohort study has been performed to assess the multisystem effects of CS. We aimed to examine the risks for mortality, cardiovascular disease, fractures, peptic ulcers, and infections in CS patients before and after treatment. Population-based cohort study. Source population was the entire population of Denmark (1980 to 2010). Data were obtained from the Danish National Registry of Patients and the Danish Civil Registration System. Benign CS of adrenal or pituitary origin and a matched population comparison cohort were included. We used Cox regression, and computed hazard ratios (HR) with 95% confidence intervals (95% CI). Morbidity was investigated in the 3 years before diagnosis; morbidity and mortality were assessed during complete follow-up after diagnosis and treatment. Included were 343 CS patients and 34 300 controls. Mortality was twice as high in CS patients (HR 2.3, 95%CI 1.8-2.9) compared with controls. Patients with CS were at increased risk for venous thromboembolism (HR 2.6, 95%CI 1.5-4.7), myocardial infarction (HR 3.7, 95%CI 2.4-5.5), stroke (HR 2.0, 95%CI 1.3-3.2), peptic ulcers (HR 2.0, 95%CI 1.1-3.6), fractures (HR 1.4, 95%CI 1.0-1.9), and infections (HR 4.9, 95%CI 3.7-6.4). This increased multimorbidity risk was present before diagnosis. Mortality and risk of myocardial infarction remained elevated during long-term follow-up. Mortality and risks for acute myocardial infarction, venous thromboembolism, stroke, and infections were similarly increased in adrenal and pituitary CS. Despite the apparently benign character of the disease, CS is associated with clearly increased mortality and multisystem morbidity, even before diagnosis and treatment.

Association between adherence to concomitant proton pump inhibitor therapy in current NSAID users and upper gastrointestinal complications

Proton pump inhibitors (PPIs) play a well-documented role as a gastroprotective agent among NSAID users at an increased risk of peptic ulcer and bleeding. Observational studies have, however, suggested that the clinical efficacy of PPI therapy may be reduced because of poor adherence. To study the association between adherence to concomitant PPI in current NSAID users and the risk of peptic ulcer and bleeding. Case-control study linking nationwide data from the Swedish Patient Registry with the Swedish Drug Prescription Database. The study population included patients admitted for a first-time peptic ulcer or bleeding and who were incident users of NSAID. Each case was matched on age, sex, NSAID duration, and calendar month with five controls. PPI adherence was calculated as the proportion of NSAID days being covered by PPI therapy. Matched and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using conditional logistic regression. A total of 3649 cases were identified. Patients with poor adherence (<20% PPI coverage) had a significantly increased risk of upper gastrointestinal complications (OR=1.88, 95% CI 1.22-2.88) compared with fully adherent patients (≥80% PPI coverage). As a continuous variable, the risk of an event increased with 6% points for every 10% decrease in PPI adherence (OR=1.06, 95% CI 1.03-1.10). The gastroprotective effect of PPI in NSAID users is highly dependent on adherence, with about twice the risk in patients with poor adherence. Efforts to increase adherence should be an integrated part of clinical practice.

Reply to the letter regarding “Comparison of gastrointestinal adverse effects between cyclooxygenase-2 inhibitors and non-selective, non-steroidal anti-inflammatory drugs plus proton pump inhibitors: a systematic review and meta-analysis”

To the Editor:We thank Dr. Lai and his colleagues for their commentsrelated to our article ‘‘Comparison of gastrointestinaladverse effects between cyclooxygenase-2(COX-2) inhib-itors and non-selective, non-steroidal anti-inflammatorydrugs (ns-NSAID) plus proton pump inhibitors (PPI)’’ [1].According to our analyses, the risk of major gastrointesti-nal (GI) complications was lower in COX-2 inhibitors, ascompared to ns-NSAIDs plus PPI. We agree that patientswho take COX-2 inhibitors are still at risk for GI adverseevents, when compared to patients who do not take thesemedications. As shown in a metaanalysis by Rostrom et al.[2], high-dose COX-2 inhibitors insignificantly increasedthe risk of gastric (relative risk or RR 1.22; 95% CI0.83–1.80) and duodenal (RR, 1.29; 95% CI 0.63–2.66)ulcers, as compared to placebo. However, when comparedto ns-NSAIDs, the risk of major GI complications includ-ing perforation, ulceration, bleeding, and obstruction werelower in COX-2 inhibitors.The increased risk of peptic ulcer in a cohort studyneeds to be cautiously interpreted because this study designis susceptible to selection bias resulting in imbalancedprognostic characteristics at baseline. In daily practice,physicians usually prescribe COX-2 inhibitors for patientswho are at high risk of developing GI complications, e.g.,old age, prior GI ulcer or bleeding, aspirin or anti-coagu-lant user, and steroid use, whereas patients with low riskare usually treated with ns-NSAIDs. Therefore, the risk ofGI complications between COX-2 inhibitors vs. ns-NSA-IDs may be comparable or even higher in COX-2inhibitors.We totally agree that COX-2 inhibitors are associatedwith increased risk of GI complication. Patients requiringNSAID therapy who are at high risk should receive COX-2inhibitor and GI protective therapy (e.g., misoprostol orPPI) or alternative therapy for pain control.Reference

Esomeprazole for Prevention and Resolution of Upper Gastrointestinal Symptoms in Patients Treated With Low-dose Acetylsalicylic Acid for Cardiovascular Protection

Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.