Risk Factors For Ulcer Development Research Articles

Diabetic Pedal Osteomyelitis and Its Treatment.

Diabetes is a fast-growing chronic metabolic disorder that is widely associated with foot ulcers. The major challenge among these ulcers is wound infections, altered inflammatory responses, and a lack of angiogenesis that can complicate limb amputation. The foot, because of its architecture, becomes the part most prone to complications and the infection rate is higher mainly between the toes due to the humid nature. Therefore, the infection rate is significantly higher. Wound healing in diabetes is a dynamic process usually delayed due to poor immune function. Diabetes-related pedal neuropathy and perfusion disturbances can lead to a loss of sensation in the foot. This neuropathy can further be a risk factor for ulcer development due to repetitive mechanical stress that later might get infected by the invasion of microorganisms extending to the bone and causing an infection called pedal osteomyelitis. This review details the pathophysiology, the biomaterials aiding in the infection cure and regeneration of bone along with their limitations, as well as their future prospects.

Methamphetamine-related peptic ulcer perforation: a growing medical concern.

Many studies have been done in the literature on perforations due to substance abuse, and there are limited publications on perforations related to inhaled methamphetamine. Recently, in our clinic, we observed an increase in the number of patients with perforated peptic ulcer, which we think is secondary to a significant increase in the consumption of this drug. The main purpose of this study is to determine whether the use of inhaled methamphetamine known as 'fire and ice' is a factor directly related to peptic perforation and its complications and also to determine the demographic variables of patients with peptic ulcer perforation due to this substance use, in the context of the literature. A retrospective study was conducted by examining the medical records of 29 gastric perforation patients who underwent surgical treatment in our clinic in 2021. Data were transferred to SPSS.23 (IBM Inc., Chicago, IL, USA) program and evaluated with statistical analysis. Normality assumptions of continuous variables were examined with Kolmogorov-Smirnov test, and variance homogeneity was examined with Levene's test. Bi-level comparisons, t-test if the data are normally distributed and Mann-Whitney U-test for bi-level comparisons where the data are not normally distributed were used. Relationships between categorical variables were examined by Chi-square test analysis. P<0.05 was accepted as the level of significance in all analyzes. Twenty-nine patients were divided into two groups as methamphetamine users (n=13) and non-users (n=16). There was a statistically significant difference according to the lower age in the group using methamphetamine (31.69-48.8-P=0.025). The pres-ence of PU history differed significantly between the groups (P=0.009). Interestingly, aspartate transaminase alanine aminotransferase values were lower in substance dependents (P=0.020). Furthermore, there was a significant difference in localization between groups (P<0.001). There was no statistically significant difference between the two groups in terms of gender, clinical presentation, and other laboratory values. Methamphetamine consumption, known as fire and ice, is an important risk factor for ulcer development and subsequent perforation, especially in young patients and long-term consumption of this narcotic substance. It has been determined that this risk factor, which is currently considered rare, has been seen in a very large number in a short time in our clinic. The use of this substance, which is considered a major social threat, is becoming more and more widespread, and this study is only a small part of the iceberg reflected in the general surgery clinic of a hospital.

Prediction of callus and ulcer development in patients with diabetic peripheral neuropathy by isosceles triangle-forming tuning fork.

Objectives:Tuning fork vibration sensation testing is widely used as a diagnostic test to detect diabetic neuropathy. However, evidence-based literature indicates that reliability between examiners is low. Attaching isosceles triangle diagrams on tuning forks lowers the discrepancy between examiners. This study aimed to analyze the relationship between vibration sensation measurement using an improved tuning fork and the presence of callus and wound development in patients with diabetic peripheral neuropathy.Methods:Participants included 56 general older adults and 52 patients with diabetic peripheral neuropathy. The methods included confirmation of the presence or absence of callus, range of motion of the ankle and the first metatarsophalangeal joint, vibratory sensitivity of the medial malleolus and the dorsal aspect of the first distal phalanx using an improved tuning fork, and touch-pressure sensitivity of the plantar aspect of the hallux. Patients with diabetic peripheral neuropathy were followed up for 3 years to check for the presence or absence of wounds.Results:When compared with the general older adults, the patients with diabetic peripheral neuropathy had significantly lower touch-pressure sensitivity (p < 0.01), vibratory sensitivity at the distal phalanx (p < 0.01) and medial malleolus (p < 0.01), ankle dorsiflexion range of motion (p < 0.01), and metatarsophalangeal joint extension range of motion (p < 0.01). The area under the receiver operating characteristic curve with callus formation was 0.93 for the medial malleolus and 0.96 for the distal phalanx, indicating that the accuracy of the distal phalanx was higher (p < 0.01) than the medial malleolus. According to the Cox proportional hazard analysis, the vibratory sensitivity of the distal phalanx was a significant risk factor for ulcer development (p < 0.05).Conclusion:These findings suggest that the vibration sensation test, which we improved via the technique described in this study, is useful for predicting the occurrence of callus and ulcer.

Marginal ulceration following Roux-en-Y gastric bypass: risk factors for ulcer development, recurrence and need for revisional surgery.

Marginal ulcer formation is a known complication following RYGB. While most respond to medical therapy, many patients have recurrent or chronic MU. Although non-steroidal anti-inflammatory drug (NSAID) use, smoking and Helicobacter pylori infection are known risk factors of MU, little is known about what increases the likelihood of developing recalcitrant ulcers. The objective of this study is to identify risk factors for marginal ulcer (MU) formation, including recalcitrant ulcers requiring surgical revision, and to define the incidence and outcomes of revisional surgery. All patients who underwent RYGB between 2011 and 2017 at a high-volume academic center were included. Patients with a postoperative diagnosis of MU were identified from the institution's bariatric database. Patient characteristics, operative data and surgical outcomes were analyzed using data collected in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program and the Ontario Bariatric Registry. A total of 2830 RYGB were performed during the study period. The incidence of MU was 6.9% with 1% of patients requiring revisional surgery for a recalcitrant ulcer. Patients with a history of smoking (HR 5.03), immunosuppression (HR 4.60) and preoperative NSAID use (HR 3.11) were significantly more likely to develop a MU requiring surgical revision. Patients undergoing revision reported resolution of their symptoms in only 36% of cases with 57% developing a recurrent ulcer. Patients with a history of smoking and use of immunosuppressive medication were at significantly higher risk of developing MU that failed medical therapy. Additional evidence is needed to inform perioperative management of bariatric patients.

An Integrative Review of Depression in Patients Receiving Hemodialysis for End-stage Renal Disease and the Relevance to Patients With Wounds

An integrative review was conducted to examine studies regarding depression in adults receiving hemodialysis for ESRD. PubMed and the Cumulative Index for Nursing and Allied Health Literature were searched for English-language publications from 2012 to 2017 regarding ESRD using the search terms epidemiology, hemodialysis, and depression and hemodialysis, depression, nocturnal, and wounds, respectively. Eight (8) of 152 articles found met the inclusion criteria and were categorized thematically. Depression was noted to affect 9.3% to 83% of persons receiving hemodialysis for ESRD. The occurrence of depression does not change across the course of ESRD. Although no publications on patients that included all search terms were found, ESRD and hemodialysis were noted to be independent risk factors for ulcer development, poor healing, and amputation. Wounds can be another source for risk of depression. Although the literature does not include studies that contain all components, ESRD, depression, and wounds are linked. Depression is a common occurrence in patients with ESRD and dialysis. Examining the effect of wounds on depression for these patients is critical. As such, additional research is warranted to explore the interconnections of ESRD, depression, and wounds to improve clinician awareness and patient outcomes.

Vitamin K Antagonist Therapy Is a Risk Factor for Ulcer Development and Death Among Dialyzed Patients.

Peripheral artery disease is a common complication among dialyzed patients. Since Vitamin K antagonists promote metastatic calcifications and these are the main determinants of vascular damage, we investigated their role in the development of lower limb ulcers in dialyzed patients. We retrospectively enrolled 316 dialyzed patients, aged 68±15years, 65% male, 32% diabetic, 43% with ischemic heart disease and followed them for 36±25months. 60 patients assumed Vitamin K antagonists: they were older, with a higher prevalence of heart disease, at greater risk of death and they developed more ulcers and underwent more lower limb amputations compared to the rest of our cohort. Peripheral artery disease, Vitamin K antagonists and diabetes were independent risk factors for foot lesions. In addition, Vitamin K antagonists were also an independent risk factor for death. Vitamin K antagonists are a potent independent risk factor for the development of the uremic foot syndrome and death.

Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons

Objectives: A combination tablet of ibuprofen 800 mg and famotidine 26.6 mg given three times daily is effective for the treatment of rheumatoid arthritis and osteoarthritis and decreases the risk of developing upper gastrointestinal (GI) ulcers. This analysis evaluated the gastroprotective efficacy and safety of the single-tablet combination of ibuprofen/famotidine compared with ibuprofen alone on the basis of age and the presence of one or more risk factors for development of upper GI ulcer. Methods: Pooled data from the 24-week, randomized, double-blind, parallel-group REDUCE-1 and REDUCE-2 trials were used. Endoscopies were performed in patients aged 40–80 years. The proportion of patients who developed ≥1 upper GI ulcer during treatment with ibuprofen/famotidine versus ibuprofen alone stratified on the basis of age (<60 or ≥60 years) was evaluated. Further, analyses were performed on additional risk factors for ulcer development. Results: Gastroprotective efficacy of the combination was not affected by age. Pooled results demonstrated statistically significantly fewer upper GI (10.0 vs 19.5%, p < 0.0001), gastric (8.9 vs 16.8%, p = 0.0004), and duodenal ulcers (1.1 vs 5.4%, p < 0.0001) in patients <60 years treated with ibuprofen/famotidine versus ibuprofen alone compared with 12.9 vs 26.6% (p = 0.0002), 11.9 vs 23.4% (p = 0.0011), and 1.0 vs 4.5% (p = 0.0096), respectively, in patients ≥60 years. The ibuprofen/famotidine combination provided nearly 51 and 59% reduction in the risk of developing a GI ulcer in patients <60 years and ≥60 of age, respectively. Efficacy was maintained in the presence of additional risk factors, as well. Conclusions: These results indicate that the fixed-combination of ibuprofen/famotidine provides gastroprotection in those of older age, with or without additional risk factors for the development of upper GI ulcers, as compared with ibuprofen alone. US National Institutes of Health registry, http://www.clinicaltrials.gov, NCT00450658 and NCT00450216.

Helicobacter pylori management in non-steroidal anti-inflammatory drug therapy patients in primary care

Non-steroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal ulcers and its complications. Helicobacter pylori infection is recognized as an additional risk factor for ulcer development, its eradication in NSAIDs users being recommended. In this cross-sectional study, during a 1-week period, consecutive patients who were routinely visiting in 58 primary care clinics were enrolled. A questionnaire was used to collect clinical data on the patients who were chronically taking NSAIDs. Patients with age >65 years, a personal history of peptic ulcer, concomitant therapy with steroids, anti-coagulants, multiple NSAIDs, or relevant co-morbidities were considered at high risk for NSAIDs gastroduodenal complications. Data on H. pylori infection management were collected. Overall, H. pylori was searched for in 140 (16.1%) out of 869 patients receiving chronic NSAID therapy, and it was eventually cured in 43 (72.9%) of the infected cases. In detail, H. pylori status was not investigated in 670 (77.1%) of those patients at high risk of NSAID-related gastroduodenal lesions, including 516 patients ≥65 years old, and 154 younger, but with at least 1 adjunctive risk factor. In addition, 234 (35%) of these high-risk patients were not receiving any gastric mucosa protection. Our data find that H. pylori infection is investigated in fewer than one of every five NSAID-user patients in primary care. The low alertness towards such an infection in these patients suggests a need for prompt implementation of current guidelines.

Independent Predictors for the Development of Upper Gastrointestinal Ulcers: Results from Two 24-Week Double-Blind Trials of a Single-Tablet Combination of Ibuprofen-Famotidine vs. Ibuprofen Alone

Purpose: Although a number of observational studies provide data on risk factors for the development of upper gastrointestinal (GI) complications in NSAID users, there are scant data identifying independent risk factors for the development of ulcers at endoscopy among NSAID users. We determined predictors for the development of upper GI ulcers among NSAID users in two large 24-week double-blind prospective trials of identical design (REDUCE-1 and REDUCE-2). Methods: Patients 40-80 yrs expected to require daily NSAID therapy ≥ 6 months with no history of ulcer complications, a negative H. pylori stool antigen test and baseline EGD showing no ulcers and <5 erosions in the upper GI tract were randomly assigned in a 2:1 ratio to HZT-501 [a single tablet combination of ibuprofen (800 mg) and famotidine (26.6 mg)] or identical-appearing ibuprofen (800 mg) tablets thrice daily. Concomitant low-dose aspirin (< or = 325 mg daily) and anticoagulant therapies were permitted. Randomization was stratified based on aspirin/anticoagulant therapy and prior ulcer history. Study EGDs were done at 8, 16 and 24 weeks of therapy. The predefined population for primary analyses of ulcers was all patients with at least one on-study EGD. A multivariable proportional hazard regression analysis was done to assess potential risk factors for ulcer development in the combined studies. Results: The REDUCE-1 and REDUCE-2 studies included a combined 1382 patients (HZT-501 N=930, ibuprofen N=452) in the primary analysis population. The life table estimate of the proportion of patients developing ulcers over 24 weeks was significantly lower with HZT-501 than ibuprofen (14.1% vs. 26.5%, p<0.0001). Multivariable risk factors are shown in the Table. Significant risk factors associated with development of ulcers were use of ibuprofen without concomitant famotidine therapy, prior ulcer and older age.Table: Multivariable analysis: risk of upper GI ulcersConclusion: Independent risk factors for the development of ulcers in NSAID users included use of NSAID without histamine-2 receptor antagonist therapy, history of ulcer disease and older age. Disclosure: L. Laine Consultant: Company 1, GlaxoSmithKline, 2, Takeda Pharmaceutical, 3, Horizon Therapeutics, 4, AstraZeneca, 5, Eisai, 6, Pozen, 7, Merck, 8, Pfizer Inc.; M.Schiff, Horizon Therapeutics, Consultant; M. Genovese, Horizon Therapeutics, Consultant; A. Kivitz, site investigator REDUCE-1; A.Bello, Horizon Therapeutics, Consultant; A. Grahn, Horizon Therapeutics, Employee; T. Walbert, Horizon Therapeutics, Employee; M. Weinblatt, Horizon Therapeutics, Consultant. This research was supported by an industry grant from Horizon Therapeutics, Inc.

Skin ulcers in systemic sclerosis: Determinants of presence and predictive factors of healing

Skin ulcers are common vascular complications of systemic sclerosis (SSc). The aim of the study was to identify clinical, biologic, and imaging parameters that constitute risk factors for the occurrence and persistence of skin ulcers. One hundred thirty Italian SSc patients were examined at entry and after 20 months of follow-up. The diffuse SSc phenotype with avascular areas on capillaroscopy, thrombophilia, and systemic inflammation as defined by interleukin 6 plasma levels, represented the major risk factors for ulcer development. Infection was associated with a risk of poor or no healing, and cardiopulmonary involvement was a major comorbid factor in patients with ulcers. The presence of infection and avascular areas represented the main determinants for ulcer healing. Our data should be confirmed with a longer follow-up period since skin ulcers represent a frequent vascular complication in scleroderma patients. Aggressive therapies aiming at improving angiogenesis and controlling infection and the course of the disease appear to be crucial to obtain ulcer healing.

Bisphosphonate increases risk of gastroduodenal ulcer in rheumatoid arthritis patients on long-term nonsteroidal antiinflammatory drug therapy

Rheumatoid arthritis (RA) patients are at increased risk of peptic ulcers (PU) induced by nonsteroidal antiinflammatory drugs (NSAIDs). However, the impact of potential drug interactions on the development of PU has yet to be determined in a daily clinical setting. The aim was to estimate the clinical important interactions for PU presented by comedication in Japanese RA outpatients on long-term NSAID treatment. This retrospective cohort study enrolled 196 consecutive RA outpatients on NSAID medication for at least 3 months. Potential risk factors for endoscopic PU were analyzed in RA outpatients on longterm NSAID treatment. PU incidence was 31% with bisphosphonate co-therapy and 17% without the co-therapy. PU incidence was only 5% in subjects with proton pump inhibitors (PPI) or prostaglandin E1 analogues (PG) co-therapy, 14% with histamine-H(2) receptor antagonists(H2RA) co-therapy, and 27% without anti-ulcer agents. In multivariate logistic regression analysis, bisphosphonate co-therapy remained a significant risk factor for PU (OR, 2.29; 95% CI, 1.09-4.81). Other risk factors for ulcer development were advanced age (greater than 60 years) and smoking (OR, 2.58; 95% CI, 1.03-6.49 and OR, 2.71; 95% CI, 1.13-5.53, respectively.) Factors that significantly reduced the incidence of PU were H2RA or PPI/PG cotherapies (OR, 0.29; 95% CI, 0.12-0.68.). Bisphosphonate co-therapy as well as advanced age and smoking was found to be a significant risk factor in PU, while co-therapies of standard-dose H2RA or PPI/PG proved effective in preventing PU in Japanese RA patients on long-term NSAID treatment.

Effect of paddock vs. stall housing on 24 hour gastric pH within the proximal and ventral equine stomach

Stall housing has been suggested as a risk factor for ulcer development in the equine stomach; however, the exact pathogenesis for this has not been established. To investigate the effect of 3 environmental situations (grass paddock, stall alone or stall with adjacent companion) on pH in the proximal and the ventral stomach. Six horses with permanently implanted gastric cannulae were used in a randomised, cross-over, block design. Each horse rotated through each of three 24 h environmental situations. Horses remained on their normal diet (grass hay ad libitum and grain b.i.d.) throughout the study. Intragastric pH was measured continuously for 72 h just inside the lower oesophageal sphincter (proximal stomach) and via a pH probe in the gastric cannula (ventral stomach). Neither proximal nor ventral 24 h gastric pH changed significantly between the 3 environmental situations. Mean hourly proximal gastric pH decreased significantly in the interval from 01.00-09.00 h compared to the interval from 13.00-20.00 h, regardless of environmental situation. Median hourly proximal pH only differed in the interval from 06.00-07.00 h compared to the interval 14.00-19.00 h. Neither mean nor median hourly ventral gastric pH varied significantly with the time of day. The change in housing status used in the current study did not affect acid exposure within either region of the equine stomach. The pH in the ventral stomach was uniformly stable throughout the study, while the proximal pH demonstrated a 24 h circadian pattern.

Bisphosphonate Increases Risk of Peptic Ulcer in Rheumatoid Arthritis Patients On Long-Term Non-Steroidal Anti-Inflammatory Drug Therapy

Objective: Rheumatoid arthritis (RA) patients are at increased risk of developing peptic ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). However, despite the recent introduction of a variety of new drugs for the treatment of RA patients, the impact of potential drug interactions on the development of ulceration has yet to be determined in a daily clinical setting. The aim of the present study was to estimate the potential risks for peptic ulcer presented by co-medication in Japanese RA outpatients on long-term NSAID treatment. Methods: Our hospital-based cohort study enrolled 196 consecutive RA outpatients on NSAID medication for at least three months. The incidence of peptic ulcer was determined by esophagogastroduodenoscopy (EGD) from February 2003 to June 2006. Potential risk factors for developing peptic ulcer were evaluated by univariate and multivariate analysis. Results: Peptic ulcer was found in 43 (21.9%) out of 196 RA outpatients on long-term NSAID treatment. Peptic ulcer incidence was 31% with bisphosphonate co-therapy and 17% without co-therapy. peptic ulcer incidence was only 5% in subjects with proton pump inhibitors (PPI) or prostaglandin E1 analogs (PG) co-therapy, 14% with histamine-H2 receptor antagonists (H2RA) co-therapy, and 28% without anti-ulcer agents. In multivariate logistic regression analysis, bisphosphonate co-therapy remained a significant risk factor for peptic ulcer (OR, 2.36 versus non-users; 95% CI, 1.12-4.97; P = 0.024). Other risk factors for ulcer development were advanced age greater than 60 years and smoking (OR, 2.58; 95% CI, 1.03-6.48; P = 0.043 and OR, 2.72; 95% CI, 1.13-5.54; P = 0.026, respectively.) Factors that significantly reduced the incidence of ulceration were H2RA and PPI/PG co-therapies (OR, 0.33; 95% CI, 0.12-0.88; P = 0.027 and 0.09; 95% CI, 0.01-0.86; P = 0.037, respectively.) Conclusions: Bisphosphonate co-therapy was found to be a significant risk factor in peptic ulcer, while standard-dose H2RA as well as PPI/PG co-therapies proved effective in preventing gastroduodenal injuries in Japanese RA patients on long-term NSAID treatment.

Nonsteroidal Anti-Inflammatory Drug-Associated Upper Gastrointestinal Lesions in Rheumatoid Arthritis Patients: Relationships to Gastric Histology, Helicobacter pylori Infection, and Other Risk Factors for Peptic Ulcer

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are risk factors for peptic ulcer in rheumatoid arthritis (RA) patients, but the contribution of reactive gastritis, concomitant Helicobacter pylori infection, or RA activity to NSAID ulcer pathogenesis is unknown. Methods: Ninety-six RA patients taking NSAIDs and dyspeptic sex- and age-matched control patients without NSAID use or an RA diagnosis were enrolled in the study. Results: Gastric ulcer (GU) was detected in 29 (30%) RA patients and 3 control patients (P < 0.001). Sixteen RA patients and no control patient had an H. pylori-negative GU. The GUs of the RA patients were mainly located in the prepyloric region (28%) and antrum (62%). Nine of the 29 RA patients (31%) with GU had more than 1 ulcer. Erosive gastropathy was detected in 34 (71% H. pylori-negative) RA patients and in 13 (62% H. pylori-negative) control subjects (P < 0.001). Chronic gastritis was observed in 65 RA patients (48% H. pylori-negative) and in 58 control subjects (43% H. pylori-negative) (NS), whereas reactive gastritis was found in only 2 RA patients and in none of the controls. Corticosteroid use was the only independent risk factor for GU: odds ratio was 6.8 (95% confidence interval, 1.3-36.0). The prevalences of duodenal ulcer or esophagitis were not increased in RA patients. Conclusions: RA patients using NSAIDs continuously are at a greatly increased risk of developing both H. pylori-negative and -positive GUs, and corticosteroid use is an independent risk factor for ulcer development. Most RA patients have chronic gastritis, whereas reactive gastritis is rarely associated with continuous NSAID use in RA patients.

Ulcerative Keratitis in Bullous Keratopathy

Purpose: The authors review a large series of patients with bullous keratopathy (BK) to analyze the frequency of ulcerative keratitis, and determine the contributory roles of bullae, bandage soft contact lenses, steroids, and prophylactic antibiotics.Methods: A retrospective review of all cases of pseudophakic or aphakic bullous keratopathy presenting to the cornea service between January 1, 1986 and September 1, 1995 was performed. The influence of time, bullae, bandage contact lenses, steroids, and prophylactic antibiotics was evaluated by actuarial methods and multivariate analysis.Results: Nine hundred eighteen patients were included in this study, 44 (4.7%) of whom had infectious or inflammatory complications; 813 cases were available for statistical analysis. Steroids (P < 0.0001), bandage soft contact lens use (P = 0.004), and bullae (P = 0.01) had statistically significant independent effects on the risk of developing ulcerative keratitis, and the combination of steroids and bandage lenses yielded the highest risk (P < 0.001). Prophylactic antibiotic use paradoxically had a statistically significant association with ulcerative keratitis in these patients (P = 0.01). Increasing BK time was also associated with ulcer development, and the risk remained relatively constant over the 60 months of the study. Streptococcus was the most frequent organism cultured.Conclusions: Ulcerative keratitis developed in 4.7% of patients with bullous keratopathy. Prolonged BK time alone was a risk factor for infection. The strongest single additional risk factor for ulcer development was steroid use, followed by bandage soft contact lens use, and their simultaneous use had the greatest effect. The presence of bullae was also a risk factor for infection, and prophylactic antibiotic use did not prevent ulcer development.

NSAID-induced peptic ulcer disease: a critical review of pathogenesis and management.

Nonsteroidal anti-inflammatory drugs (NSAIDs) initiate gastroduodenal ulceration and promote complications such as bleeding and perforation. Age greater than 60 years, a prior history of ulcer disease, and concomitant corticosteroid use are important risk factors for ulcer development. NSAIDs interfere with mucosal defense via direct toxic effects in addition to cyclooxygenase inhibition and subsequent depletion of endogenous prostaglandins. While all NSAIDs are ulcerogenic, drugs which avoid topical injury and do not inhibit mucosal prostaglandins appear to have lesser risk of toxicity. Although NSAID injury requires luminal acid, prophylactic use of H2 receptor antagonists has been disappointing, preventing duodenal injury only. Greater acid suppression with proton pump inhibition appears promising. Prostaglandins are effective for prevention of NSAID-induced gastroduodenal injury, but are not well tolerated. Recent evidence suggests NSAID ulcers heal rapidly with proton pump inhibitors compared to H2 receptor antagonists in those patients who require continued NSAID therapy.