Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study.

PURPOSE: To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs. METHODS: A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibitors users identified from the Dutch PHARMO Record Linkage System in the period 1998-2012. Cases were patients aged ≥18 years with a first hospital admission for PUB. For each case, up to four controls were matched for age and sex at the date a case was hospitalized (index date). Logistic regression analysis was used to calculate odds ratios (ORs). RESULTS: At the index date, 2634 cases and 5074 controls were current users of conventional NSAIDs or selective COX-2 inhibitors. Compared with conventional NSAIDs, selective COX-2 inhibitors with PPIs had the lowest risk of PUB (adjusted OR 0.51, 95% confidence interval [CI]: 0.35-0.73) followed by selective COX-2 inhibitors (adjusted OR 0.66, 95%CI: 0.48-0.89) and conventional NSAIDs with PPIs (adjusted OR 0.79, 95%CI: 0.68-0.92). Compared with conventional NSAIDs, the risk of PUB was lower for those aged ≥75 years taking conventional NSAIDs with PPIs compared with younger patients (adjusted interaction OR 0.79, 95%CI: 0.64-0.99). However, those aged ≥75 years taking selective COX-2 inhibitors, the risk was higher compared with younger patients (adjusted interaction OR 1.22, 95%CI: 1.01-1.47). CONCLUSIONS: Selective COX-2 inhibitors with PPIs, selective COX-2 inhibitors, and conventional NSAIDs with PPIs were associated with lower risks of PUB compared with conventional NSAIDs. These effects were modified by age. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

[Prophylaxis for stress ulcer bleeding in the intensive care unit]. / Profilaxis para sangrado por ulceras de estrés en la unidad de cuidados intensivos.

BACKGROUND: The critically ill patient can develop gastric erosions and, on occasion, stress ulcers with severe gastrointestinal bleeding that can be fatal. AIMS: The purpose of this review was to provide current information on the pathophysiology, risk factors, and prophylaxis of digestive tract bleeding from stress ulcers in the intensive care unit. METHODS: We identified articles through a PubMed search, covering the years 1970 to 2013. The most relevant articles were selected using the search phrases "stress ulcer", "stress ulcer bleeding prophylaxis", and "stress-related mucosal bleeding" in combination with "intensive care unit". RESULTS: The incidence of clinically significant bleeding has decreased dramatically since 1980. The most important risk factors are respiratory failure and coagulopathy. Proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) are used in stress ulcer bleeding prophylaxis. Both drugs have been shown to be superior to placebo in reducing the risk for gastrointestinal bleeding and PPIs are at least as effective as H2RAs. Early enteral feeding has been shown to reduce the risk for stress ulcer bleeding, albeit in retrospective studies. CONCLUSIONS: Admittance to the intensive care unit in itself does not justify prophylaxis. PPIs are at least as effective as H2RAs. We should individualize the treatment of each patient in the intensive care unit, determining risk and evaluating the need to begin prophylaxis.

Risk of complications after a peptic ulcer diagnosis: effectiveness of proton pump inhibitors.

BACKGROUND: Few studies have evaluated the prevention of upper gastrointestinal complications (UGIC; bleeding or perforation) in patients with uncomplicated peptic ulcer (PU). We assessed the effect of proton pump inhibitors (PPI) in a non-randomized setting. To maximize exchangeability of exposed and unexposed groups we restricted the study to patients with a new diagnosis of PU, i.e., a clear indication. To minimize selection bias we mimicked an intention to treat approach by assessing the effect of PPI prescription after PU diagnosis. METHODS: Within a population of subjects aged 40-84 years from The Health Improvement Network database, 1997-2006, we identified 3,850 patients with incident PU. Among them, we confirmed 74 first UGIC episodes during a mean follow-up of 4 years. Exposure was prescription coverage during the month following PU diagnosis. We performed a nested case-control analysis and compared UGIC cases with 400 controls matched for age, sex, year and duration of follow-up. Relative risks (RR) and 95 % confidence intervals (CI) were estimated. RESULTS: The overall incidence of UGIC was 4.6 cases/1,000 person-years; it was highest during the months after PU diagnosis, increased with age, and it was higher in men and subjects with Helicobacter pylori infection, anemia, and alcohol use at PU diagnosis. The RR for UGIC associated with PPI prescriptions during the month after PU diagnosis was 0.56 (95 % CI 0.31-1.0). The RR for NSAIDs with and without a PPI was 1.72 (0.68-4.45) and 3.27 (0.85-12.67), respectively. CONCLUSIONS: Findings suggest that prescription of PPIs after a PU diagnosis is associated with a reduced risk of UGIC.

[Surgical treatment of gastroduodenal ulcers according to principles of a modern antirecurrence therapy with postoperative complications prophylaxis].

Modern approaches to surgical treatment of gastroduodenal ulcers in accordance with principles of antirecurrence therapy, directed on prophylaxis of postoperative complications occurrence, are enlighted.

Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study.

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 +/- 16.7 years (mean +/- SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications.

Helicobacter pylori eradication prevents recurrence after simple closure of perforated duodenal ulcer.

BACKGROUND AND AIM: Evidence remains inconclusive as to whether eradication of Helicobacter pylori prevents ulcer relapse after simple closure of a perforated duodenal ulcer. This study was conducted to determine the effect of H. pylori eradication using a quadruple drug regimen along with a probiotic on ulcer recurrence after perforation closure. METHODS: A total of 93 patients who had presented with perforated duodenal ulcer and had a simple closure of a duodenal perforation comprised the study group. Three months postoperatively, patients who were found to be positive for H. pylori infection (n = 60) were administered quadruple therapy consisting of omeprazole, clarithromycin, amoxicillin and colloidal bismuth subcitrate for 10 days along with the probiotic Lactobacillus sporogenes for 14 days. Diagnosis of H. pylori was carried out by urease test and histology. Patients were followed for 18 months. Recurrence of ulcer was analyzed for correlation with H. pylori status. RESULTS: Of 60 patients who received H. pylori eradication therapy, 53 were available for subsequent follow up. H. pylori eradication was achieved in 43/53 (81.1%) patients. The ulcer recurrence in the eradicated group was 18.6% (8/43) compared to 70% (7/10) in the noneradicated group (P = 0.003). CONCLUSION: Eradication of H. pylori significantly reduces the relapse of duodenal ulcer after simple closure of perforation. Anti H. pylori therapy must be recommended for all H. pylori positive patients after simple closure of a perforated duodenal ulcer.

Gastrointestinal injury from NSAID therapy. How to reduce the risk of complications.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin is accompanied by risk of upper and lower gastrointestinal (GI) complications, some of which can be serious or even fatal. Management strategies to reduce this risk include gastroprotective pharmacotherapy, use of safer NSAIDs, and eradication of Helicobacter pylori infection. In this article, Dr Lanas summarizes the GI risks associated with NSAID and low-dose aspirin therapy and weighs the efficacy of current risk management strategies.

[Importance of morphofunctional condition of endocrine cells of gastric mucosa in prognosis of ulcer disease complications]. / Znachenie morfofunktsional'nogo sostoianiia éndokrinnykh kletok slizistoi zheludka v prognoze oslozhneniia iazvennoi bolezni.

Problems of morphofunctional condition of endocrine cells of gastric mucosa and their importance in prognosis of ulcer disease complications are discussed. Sixty patients with various complications of ulcer disease were examined. Investigation of quantity and functional activity of 4 most frequent types of gastric mucosa endocrine cells in different zones of affected area permitted to reveal strong correlation between quantity and functional activity of these cells. Changes of endocrine cells are reliable and have high prognostic significance in development of ulcer disease complications and must be taken into account by physicians to select right policy for prevention of these complications.

[Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria]. / Unerwünschte Wirkungen unter nichtsteroidalen Antiphlogistika. Eine Prävalenzstudie aus Osterreich.

OBJECTIVE: Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. METHODS: A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. RESULTS: Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. CONCLUSION: The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.

[Clinical investigation of perforated duodenal ulcer--with special reference to the presence of Helicobacter pylori infection and rate of recurrence].

Perforated duodenal ulcer was clinically evaluated with respect to Helicobacter pylori infection and rate of recurrence in 38 ulcer patients perforated and 154 patients with non-perforated duodenal ulcer who visited our hospital in past 5 years and 6 months. The frequency of occurrence of H. pylori-positivity was 42.1% in patients with perforated duodenal ulcer, significantly lower than that of 92.9% in patients with non-perforated lesions. This result suggests that H. pylori is hardly involved in the development of perforated duodenal ulcer. The rate of recurrence was significantly lower for perforated duodenal ulcer than for non-perforated ulcer. In particular, perforated duodenal ulcer did not recur in the group on maintenance therapy with H2-recepter antagonists. Maintenance therapy using inhibitors of gastric acid secretion seems effective for the prevention of recurrence of perforated duodenal ulcer.

Prevention of complicated ulcer disease among chronic users of nonsteroidal anti-inflammatory drugs: the use of a nomogram in cost-effectiveness analysis.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of clinical upper gastrointestinal tract (UGI) events, namely, symptomatic ulcer, perforation, bleeding, and obstruction. Our objective in this study was to compare the cost-effectiveness of several strategies aimed at reducing the risk of clinical UGI events in NSAID users. METHODS: A decision tree model was used for patients requiring long-term treatment with NSAIDs to compare conventional NSAID therapy alone with 7 other treatment strategies to reduce the risk of NSAID-related clinical UGI events (cotherapy with proton-pump inhibitor, cotherapy with misoprostol, cyclooxygenase [COX]-2-selective NSAID therapy, or Helicobacter pylori treatment followed by each of the previous strategies, including conventional NSAID treatment, respectively). The outcome measure is the incremental cost per clinical UGI event prevented compared with conventional NSAID treatment over 1 year. RESULTS: The use of a COX-2-selective NSAID and cotherapy with proton-pump inhibitors were the 2 most cost-effective strategies. However, the incremental cost associated with these strategies was high (>$35 000) in persons with a low risk of clinical UGI event with conventional NSAIDs (eg, 2.5% per year). If the baseline risk of clinical UGI events is moderately high (eg, 6.5%), using a COX-2-selective NSAID becomes the most effective and least costly (dominant) treatment strategy, followed closely by cotherapy with a daily proton-pump inhibitor. Because small changes in costs or assumed efficacy of these drugs could change the conclusions, the incremental cost-effectiveness ratios between any 2 strategies were presented in a nomogram that allows the flexible use of a wide range of values for costs and rates of clinical UGI events. CONCLUSIONS: The risk of clinical UGI events in NSAID users depends on their baseline risk, the added risk associated with the individual NSAID, and the protection conferred by cotherapy. A nomogram can be used to incorporate these factors and derive estimates regarding cost-effectiveness of competing strategies aimed at reducing the risk of clinical UGI events.

[Perforated peptic ulcers]. / Peptik ülser perforasyonlari.

Two hundred forty-eight patients were operated for perforated peptic ulcer between 1983 and 1998. Of the patients 112 (45.1%) had chronic, 34 (13.7%) had acute ulcer history and 102 (41.2%) had no ulcer history. Of the patients 228 (92.0%) had duodenal, 9 (3.6%) had juxtapyloric, 6 (2.4%) had marginal, and 5 (2.0%) had antral ulcer. Forty two patients (16.9%) admitted within 12 hours and 206 patients (83.1%) between 12 hours and six days after perforation. Simple closure and omental patch was performed in 32 patients (12.9%) who had severe concomitant illness and 126 (50.8%) intraabdominal sepsis, truncal vagotomy + pyloroplasty in 32 (12.9%), simple closure + omental patch + truncal vagotomy + gastroenterostomy in 34 (13.7%), simple closure + omental patch + parietal cell vagotomy in 21 (8.5%), truncal vagotomy + antrectomy in 3 (1.2%). Patients who didn't have definitive procedure received H2 receptor blockers or proton pomp inhibitors. One hundred ninety-three patients (77.8%) underwent endoscopic control. Two of 53 patients with definitive procedure (3.8%) and 34 of 140 patients (24.3%) with simple closure had recurrence. Two patients in simple closure group underwent parietal cell vagotomy, the others received medical treatment. The recurrence rate was significantly higher in simple closure group (p < 0.01).

Some studies on the rodenticidal action of indomethacin.

The oral LD50 of indomethacin for a seven-day observation was found to be 12.58 +/- 1.15 mg/kg. At LD10 of 6.61 mg/kg, a dose to weight ratio of 28 was obtained for a 240 g rat, while at a maximum single dose of 3 mg/kg in man it is only 0.04. Neither diazepam nor phenobarbital influenced death at the doses of both drugs used. However, cholestyramine 2 g/kg/day was found to protect by 50% from the LD100 of indomethacin. Gross pathological studies showed dose-dependent ulceration and perforation (P < 0.001, 12 vs 24 mg/kg) and such lesions occurred in starved rats, were low in bile duct-ligated compared to sham-operated rats (P < 0.001) and were also low in cholestyramine-treated rats. Indomethacin-induced lethality in rats was found to be dose-dependent.

Duodenal ulcer perforation: have H2 receptor blockers reduced mortality?

Elective surgery for peptic ulcer is becoming rare with the use of more effective medical therapy. However, life threatening complications have not reduced in number. A retrospective study was carried out to compare perforation rates per 10,000 admissions, mortality rates from perforated duodenal ulcers per 10,000 admission and the proportion of patients with perforated duodenal ulcer who died, before and after the introduction of H2 receptor blockers in a large teaching hospital in South India. Perforation rates were not significantly different between the two periods under study. There was a small, but statistically significant (p = 0.047) drop in mortality per 10,000 admissions and a significant drop in proportion of patients with perforated ulcer who died (p = 0.028). Inspite of effective medical therapy, there is a subset of patients with duodenal ulcer who continue to perforate. Efforts should be directed towards identifying this subset and offering them early surgery. Mortality rates have not changed significantly.

[The prognosis and prevention of the occurrence of acute ulcers and erosions of the stomach and duodenum in surgical patients]. / Prognozirovanie i profilaktika vozniknoveniia ostrykh iazv i érozii zheludka i dvenadtsatiperstnoi kishki u khirurgicheskikh bol'nykh.

Acute ulceration of the gastric and duodenal mucosa was found in 20.3% among 404 patients who died at the surgical department of the hospital. In 89.7% of the patients acute erosive-ulcerous lesions were localized in the gastric mucosa. In 39 patients (9.7%) acute ulcers of the stomach and duodenum complicated by bleedings or perforations were the direct cause of death. Based on results of an analysis of severity of the main and concomitant diseases as well as their complications the authors have determined the factors responsible for the appearance of the ulcers. A complex of prophylactic measures aimed at the main links of the pathogenesis of acute ulcers is proposed.