Randomised clinical trial: once- vs. twice-daily prolonged-release mesalazine for active ulcerative colitis.

BACKGROUND: Aminosalicylates are first-choice treatment for mild-to-moderately active ulcerative colitis (UC); however, multi-dosing regimens are inconvenient. AIM: To compare the efficacy and safety of once- (OD) vs. twice- (BD) daily prolonged-release mesalazine (Pentasa, Ferring, Saint-Prex, Switzerland) for active mild-to-moderate UC in a non-inferiority study. METHODS: Eligible patients (n = 206) were randomised to 8 weeks of mesalazine (4 g/day), either OD with two sachets of 2 g mesalazine granules in the morning (n = 102) or BD with one 2 g sachet in the morning and one in the evening (n = 104). Patients also received 4 weeks of mesalazine enema 1 g/day. Disease activity was assessed at randomisation, weeks 4, 8 and 12 using the UC Disease Activity Index (UC-DAI). Clinical and endoscopic remission (primary endpoint) was assessed after 8 weeks. Patients recorded stool frequency and rectal bleeding in a daily diary. RESULTS: The primary endpoint, non-inferiority in clinical and endoscopic remission with OD vs. BD mesalazine at 8 weeks, was met (intent-to-treat population: 52.1% vs. 41.8%, respectively, 95% confidence interval -3.4, 24.1; P = 0.14). Improvement of UC-DAI score (92% vs. 79%; P = 0.01) and mucosal healing (87.5% vs. 71.1%; P = 0.007) were significantly better, time to remission significantly shorter (26 vs. 28 days; P = 0.04) and safety similar with OD vs. BD dosing. CONCLUSIONS: When combined with mesalazine enema, prolonged-release mesalazine once-daily 4 g is as effective and well tolerated as 2 g twice-daily for inducing remission in patients with mild-to-moderately active ulcerative colitis (Clinicaltrials.gov: NCT00737789).

Peptic ulcer bleeding: interaction between non-steroidal anti-inflammatory drugs, Helicobacter pylori infection, and the ABO blood group system.

BACKGROUND: Helicobacter pylori infection is found in almost all patients with an uncomplicated ulcer. Non-steroidal anti-inflammatory drug (NSAID) use is the main risk factor for bleeding peptic ulcer. In the older literature ABO blood groups were mentioned as a risk factor. There is continuing uncertainty about the interaction between these risk factors and the development of peptic ulcer bleeding. We therefore determined the separate and combined effect of NSAIDs, H. pylori infection, and the ABO blood group system in patients with a bleeding peptic ulcer. METHODS: The prevalence of NSAID use, H. pylori infection, and blood group O was determined in 227 patients who were admitted with a bleeding gastric or duodenal ulcer between 1990 and 1997. These results were compared with the expected frequency of these risk factors in the Dutch population. RESULTS: NSAID use was reported in 48.2% of the patients with a bleeding peptic ulcer. The H. pylori prevalence was 62.0%, whereas blood group O was present in 49.3% of the patients. NSAID use was the strongest risk factor for hemorrhage caused by a peptic ulcer (relative risk, 8.4), whereas the relative risk associated with H. pylori infection and blood group O was 1.5 and 1.2, respectively. With univariate analysis NSAID use and H. pylori infection seemed to be separate risk factors and did not really potentiate each other's effect. Moreover, blood group O did not potentiate the strong effect of NSAIDs. CONCLUSION: H. pylori infection may add only a little to the important risk of NSAID use in the development of bleeding peptic ulcers.

Graves' dermopathy: does octreotide scintigraphy predict the response to octreotide treatment?

We report on three patients with severe Graves' dermopathy who were treated with octreotide despite a negative octreotide scintigraphy. One patient showed a complete recovery while two others had a partial response. In contrast to active Graves' ophthalmopathy, an octreotide scintigraphy appears not to be useful for pretreatment identification of patients with Graves' dermopathy who are likely to respond to octreotide treatment.

Prosthetic valve endocarditis: analysis of risk factors for mortality.

Between 1975 and 1990, 70 episodes of prosthetic valve endocarditis (PVE) were diagnosed in 65 patients at Leiden University Hospital. The overall mortality rate was 27%. Antecedent endocarditis attributable to the same micro-organism (mortality 63%, P = 0.02) and Staphylococcus aureus as the causative micro-organism (mortality 100%, P = 0.001) were significant predictors for mortality. Sex, type and position of the valve and therapy had no significant influence on the mortality. All patients infected with S. aureus died, irrespective of whether they received medical treatment alone or in combination with surgery. None of the patients with streption, endocarditis had abscesses at reoperation; the mortality rate for this group was 14%. Abscess formation, especially in aortic valves, was the most important finding at reoperation and corresponded with a mortality rate of 55%. Ring abscesses occurred equally in patients with mechanical and bioprosthetic valves. Seven of the 15 patients (47%) with significant prosthetic valve dehiscence died. In patients with mitral valve endocarditis, localized dehiscence of the valve was observed. In conclusion a previous endocarditis attributable to the same micro-organism and the causative micro-organism (S. aureus) were important risk factors for mortality due to PVE.