[Show abstract][Hide abstract] ABSTRACT: Background
In this post-hoc analysis of a randomized, double blind, placebo controlled trial, we measured the sensitivity and specificity of Helicobacter pylori IgG-antibody titer changes, hematoxylin and eosin (H&E) stains, immunohistochemical (IHC) stains and culture results in NSAID using patients, following H. pylori eradication therapy or placebo.
347 NSAID using patients who were H. pylori positive on serological testing for H. pylori IgG-antibodies were randomized for H. pylori eradication therapy or placebo. Three months after randomization, gastric mucosal biopsies were taken for H. pylori culture and histological examination. At 3 and 12 months, blood samples were taken for repeated serological testing. The gold standard for H. pylori infection was based on a positive culture or both a positive histological examination and a positive serological test. Sensitivity, specificity and receiver operating curves (ROC) were calculated.
H. pylori eradication therapy was successful in 91% of patients. Culture provided an overall sensitivity of 82%, and 73% after eradication, with a specificity of 100%. Histological examination with either H&E or IHC stains provided sensitivities and specificities between 93% and 100%. Adding IHC to H&E stains did not improve these results. The ROC curve for percent change in H. pylori IgG-antibody titers had good diagnostic power in identifying H. pylori negative patients, with an area under the ROC curve of 0.70 (95 % CI 0.59 to 0.79, P = 0.085) at 3 months and 0.83 (95% CI 0.76 to 0.89, P < 0.0001) at 12 months. A cut-off point of at least 21% decrease in H. pylori IgG-antibody titers at 3 months and 58% at 12 months provided a sensitivity of 64% and 87% and a specificity of 81% and 74% respectively, for successful eradication of H. pylori.
In NSAID using patients, following H. pylori eradication therapy or placebo, histological examination of gastric mucosal tissue biopsies provided good sensitivity and specificity ratios for evaluating success of H. pylori eradication therapy. A percentual H. pylori IgG-antibody titer change has better sensitivity and specificity than an absolute titer change or a predefined H. pylori IgG-antibody titer cut-off point for evaluating success of H. pylori eradication therapy.
[Show abstract][Hide abstract] ABSTRACT: The treatment of choice of H. pylori infections is a 7-day triple-therapy with a proton pump inhibitor (PPI) plus amoxicillin and either clarithromycin or metronidazole, depending on local antibiotic resistance rates. The data on efficacy of eradication therapy in a group of rheumatology patients on long-term NSAID therapy are reported here. This study was part of a nationwide, multicenter RCT that took place in 2000-2002 in the Netherlands. Patients who tested positive for H. pylori IgG antibodies were included and randomly assigned to either eradication PPI-triple therapy or placebo. After completion, follow-up at 3 months was done by endoscopy and biopsies were sent for culture and histology. In the eradication group 13% (20/152, 95% CI 9-20%) and in the placebo group 79% (123/155, 95% CI 72-85%) of the patients were H. pylori positive by histology or culture. H. pylori was successfully eradicated in 91% of the patients who were fully compliant to therapy, compared to 50% of those who were not (difference of 41%; 95% CI 18-63%). Resistance percentages found in isolates of the placebo group were: 4% to clarithromycin, 19% to metronidazole, 1% to amoxicillin and 2% to tetracycline.
European Journal of Clinical Microbiology 02/2011; 30(7):903-8. DOI:10.1007/s10096-011-1174-5 · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Maintenance use of nonsteroidal anti-inflammatory drugs (NSAIDs) is often complicated by gastropathy. In non-NSAID users, eradication of Helicobacter pylori is associated with decreased mucosal inflammation, and may halt the progression to atrophy and intestinal metaplasia, but the continuous use of NSAIDs may interfere with these processes.
To investigate the effect of H. pylori eradication on gastric mucosal histology during long-term NSAID use, with and without gastroprotective therapy.
Patients were eligible for inclusion if they were on long-term NSAIDs and were H. pylori-positive on serologic testing. Patients were randomly assigned to either eradication or placebo. Gastritis was assessed according to the updated Sydney classification for activity, chronic inflammation, gastric glandular atrophy, intestinal metaplasia, and H. pylori density.
Biopsy specimens were available for histology of 305 patients. Of these, 48% were on chronic gastroprotective medication. Significant less active gastritis, inflammation, and H. pylori density was found in the eradication group compared with the placebo group in both corpus and antrum (P<0.001). In the corpus, less atrophy was found in the eradication group compared with the placebo group.
H. pylori eradication in patients on long-term NSAID therapy leads to healing of gastritis despite ongoing NSAID therapy.
[Show abstract][Hide abstract] ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause gastrointestinal (GI) ulcers and complications of ulcers. In 1997 in Amsterdam, the incidence of symptomatic GI events was 2.1% (95% CI 1.0-3.1) in patients with rheumatoid arthritis (RA). We conducted a new prospective, observational study on the symptomatic GI events in our outpatient clinics, and compared the data to a previous study conducted by our group. Over the same time period, a decline of GI events over the last decade was reported for US patients.
In 2003, three questionnaires were sent to all RA patients in Amsterdam at 4-month intervals, addressing medication use, dyspepsia, and symptomatic GI events in the previous 4 months.
The incidence of GI events in high-risk patients, defined as age >or=60 and/or history of GI event) using NSAIDs or cyclo-oxygenase 2 specific inhibitors (COXIBs) was 1.2% (95% CI 0.2-2.3), which appears to be substantially lower than the 2.1% observed in 1997; however this difference did not reach statistical significance (p = 0.3). In 64% (95% CI 61-68) of the high-risk patients, acid-suppressive drugs (ie, proton pump inhibitors, prostaglandin analogues or high dose H2 antagonists) were used. In 1997 this percentage was significantly lower at 49% (45-52; p<0.001). The compliance to the Dutch guidelines for prevention of NSAID-related gastropathy was almost 75%, with 64% of the patients using acid-suppressive drugs and 11% using COXIBs.
The present study reveals a decline of NSAID-induced gastrointestinal events, which is similar to the results observed in the US. This is most likely due to a more strict adherence to guidelines for prevention of NSAID gastropathy, and better treatment of rheumatoid arthritis.
Annals of the rheumatic diseases 02/2008; 67(2):256-9. DOI:10.1136/ard.2006.068015 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major causes of gastroduodenal ulcers. Studies on the benefit of eradication of H. pylori in NSAID users yielded conflicting results.
To investigate whether H. pylori eradication in patients on long-term NSAIDs reduces the incidence of gastroduodenal ulcers.
Patients on long-term NSAID treatment and who are H. pylori positive on serologic testing, were randomly assigned to either H. pylori eradication (omeprazole, amoxicillin, and clarithromycin) or placebo. Primary endpoint was the presence of endoscopic gastric or duodenal ulcers 3 months after randomization.
One hundred sixty-five (48%) of a total of 347 patients were on gastroprotective medication. At endoscopy, gastroduodenal ulcers were diagnosed in 6 (4%) and 8 (5%) patients in the eradication and placebo group, respectively (p = .65). During follow-up of 12 months, no symptomatic ulcers or ulcer complications developed. No significant differences were found in the development of gastroduodenal erosions, dyspepsia, or in quality of life.
H. pylori eradication therapy in patients on long-term NSAID treatment had no beneficial effect on the occurrence of ulcers, erosions, or dyspepsia. Ulcer rates in both study arms are remarkably low, in both patients with and without gastroprotective therapy.
[Show abstract][Hide abstract] ABSTRACT: Relapsing splenic vein thrombosis, a very rare complication of Wegener granulomatosis (WG), is described in a female patient. Positive antiphospholipid antibodies found in this case are a rare occurrence in primary vasculitis, especially in WG. This probably caused or accentuated an effect of the WG on the splenic vein. Treatment of such patients with antiphospholipid syndrome and WG must include anticoagulation and immunosuppression and, as noted in this patient, the splenic vein thrombosis and other antiphospholipid syndrome and WG can resolve quickly.
[Show abstract][Hide abstract] ABSTRACT: The separate contribution of NSAIDs and H. pylori in the pathogenesis of peptic ulcer disease has not been fully elucidated. The aim of this study was to investigate the seroprevalence of H. pylori in patients with rheumatic diseases and chronic NSAID treatment. Patients with a rheumatic disease, age 40-80 years, and regular use of NSAIDs (at least 3 times a week) were included (n= 1214). IgG-antibodies to H. pylori were found in 39% and increased gradually with age: from 25% in patients in the 40-50 years age group to 48% in patients aged 70-80 years (p<0.0001). No difference was observed between men and women, or between the three centres. In our population of rheumatic patients treated with NSAIDs the seroprevalence of H. pylori is substantial (39%), but seems to be lower than in previous reports, which may be due to a cohort effect.
[Show abstract][Hide abstract] ABSTRACT: Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed in patients with rheumatoid arthritis (RA). Because of its frequency and severity, NSAID gastropathy is the most important side effect. The clinical spectrum of NSAID gastropathy includes gastrointestinal complaints, ulcers and their complications. To reduce NSAID gastropathy, rheumatologists in greater Amsterdam decided in January 1997 that prophylactic agents should be prescribed for patients with RA at high risk for NSAID gastropathy, defined as age 60 or older or a history of gastrointestinal (GI) ulcers, or both.
To determine the incidence of clinically manifest ulcers and their complications in patients with RA at high risk for NSAID gastropathy during a period in which prophylaxis was recommended. Published reports show that the incidence of clinically manifest ulcers and their complications varies from 1.3% to 5%.
Within one year, three questionnaires were sent to all outpatients with RA of our clinic (n=2680). The patients were asked if they had had a gastroscopy and/or complication of an ulcer in the preceding months. When a GI event (ulcer or complication) had occurred an analysis was carried out to determine whether the event was possibly related to a compliance failure or a policy failure-for example, no prophylaxis prescribed when it was recommended.
The response rate for the three questionnaires was 88%, 76%, and 77%, respectively. All three questionnaires were returned by 1856 patients; NSAIDs were used in 1246 (67%) of them. Of the NSAID users 731 (59%) were in the high risk group. Clinically manifest ulcers occurred in seven high risk NSAID users (four gastric ulcers, two duodenal ulcers, and in one patient both types of ulcer). Complications of ulcers were diagnosed in eight (other) patients: seven (upper) GI bleedings and one perforation. Thus the incidence during one year of clinically manifest ulcers in the high risk group was 1.0% and of complications of ulcers 1.1%, together 2.1%. In the group of 15 patients with GI events, only one patient had not taken the adequately prescribed gastroprotective drugs (compliance failure). Misguidedly, gastroprotective drugs were not prescribed in seven patients (policy failure), but in the remaining seven patients gastroprotective drugs were adequately prescribed and used.
The incidence of clinically manifest ulcers and of complications of ulcers in patients with RA at high risk for NSAID gastropathy is relatively low, and might be related to our strategy to prescribe prophylactic agents in these patients.
Annals of the Rheumatic Diseases 06/2001; 60(5):443-7. DOI:10.1136/ard.60.5.443 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dutch rheumatologists were given a questionnaire on NSAID gastropathy, in which older age (>60 years) and previous ulcers were mentioned by them as being the most important risk factors. Dutch rheumatologists follow different strategies for the prevention of NSAID gastropathy, with a slight preference for proton pump inhibitors and the use of COX-2 selective NSAIDs.
[Show abstract][Hide abstract] ABSTRACT: NSAID gastropathy, because of its severity and prevalence, is the most important side effect of nonsteroidal anti-inflammatory drugs. Protective strategies are advocated in patients with high risk for NSAID gastropathy (age over 60 years and/or previous ulcer). Different strategies for the prevention of NSAID gastropathy are: using a cyclo-oxygenase (COX)-2 inhibitor, adding a prostaglandin analogue, an H2-receptor antagonist or a proton pump inhibitor or eradicating Helicobacter pylori. On the basis of efficacy, safety and costs prescription of a proton pump inhibitor as a prophylactic agent appears to be the best option; prescription of a prostaglandin analogue is a good alternative. The preliminary data on the COX-2 inhibitors are promising. The role of H. pylori in NSAID gastropathy is not yet elucidated.
Nederlands tijdschrift voor geneeskunde 09/1999; 143(32):1649-52.