Violence among schizophrenia out-patients compliant with medication: prevalence and associated factors.

OBJECTIVE: Aggressive behaviour has been related to schizophrenia both in in-patient and out-patient samples. In this study, we aimed to assess the prevalence and factors associated with aggressive behaviour in out-patient compliant with their prescribed medication. METHOD: Eight hundred and ninety-five patients were interviewed at Community-Based Mental Health Services about aggressive-violent behaviour within the week prior to the study visit. Adult patients diagnosed with schizophrenia and receiving stable pharmacological treatment were enrolled. Presence of aggressive episodes, including type of aggression, severity and frequency, was assessed with the Modified Overt Aggression Scale (MOAS). Violence was defined as a score of 3 or more in any of the MOAS subscores. RESULTS: Prevalence of recent aggressive behaviour was 5.07%, (95% CI 5.04-5.10), where 47% (43 behaviours 91) reached the violent threshold. Among the 91 violent episodes rated, most episodes were verbal (44%), followed by physical violence towards objects (29%), violence towards others (19%) and self-directed violence (8%). Recent episodes of any severity were more likely among patients with a history of violence and also with relapses within the previous year and with low treatment satisfaction. CONCLUSION: Five per cent of the studied cases showed aggressive behaviour in the week prior to assessment, despite having been compliant with their medication. Most aggressive behaviour was verbal rather than physical.

Criteria used by general practitioners in prescribing prokinetic or antisecretory drugs in patients with functional dyspepsia.

OBJECTIVE: To analyze the clinical factors considered by general practitioners for the prescription of prokinetic or antisecretory drugs in patients with functional dyspepsia (FD), and to assess therapeutic outcomes and factors predicting effectiveness. DESIGN: Multicentric, prospective and observational study. PATIENTS: 1,021 patients with FD were included. One hundred and thirty-two (132) were excluded from the analysis because they were taking ASA or NSAID. Patients were classified according to their predominant symptoms as reflux, ulcer, dysmotility or non-specific. At the physician discretion, treatment with alkali drugs was prescribed to 38 patients, prokinetic drugs to 574, antisecretory drugs to 123 and a combined therapy to 154. One month later, patient self-perception of symptomatic improvement was evaluated in patients treated with prokinetic drugs and antisecretory drugs. RESULTS: 85% of the patients reported symptomatic improvement after one month of treatment. Patients with non-specific FD had lower improvement rates regardless of the drug used (prokinetic or antisecretory) (77%) compared to all the other types (p = 0.03). Prescription of prokinetics was associated to female gender (OR: 0.43; 95% CI: 0.28-0.66) and early satiety (OR: 2.5; 95% CI: 1.6-4.1). A longer symptomatic evolution (OR 0.92: 95% CI: 0.88-0.97) was the only independent predictive factor of a poor response to prokinetic drugs. CONCLUSIONS: Among patients with FD attended by general practitioners, female gender and early satiety symptom were associated to the prescription of prokinetic drugs. Early symptomatic effectiveness rates for prokinetic or antisecretory drugs alike were high (85%). Patients with non-specific dyspepsia or long symptomatic evolution showed less favorable symptomatic response to prokinetic drugs.

Criterios de los médicos de atención primaria para la indicación de tratamiento con procinéticos o antisecretores en pacientes con dispepsia funcional / Criteria used by ge neral practitioners in prescribing prokinetic or antisecretory drugs in patients with functional dyspepsia

Objetivo: analizar los factores clínicos que valoran los médicos de atención primaria para la prescripción de procinéticos o antisecretores en pacientes con dispepsia funcional (DF) y evaluar los resultados terapéuticos y factores predictivos de efectividad. Diseño: estudio multicéntrico, prospectivo y observacional. Pacientes: se incluyeron 1.021 pacientes con DF, se excluyeron 132 porque tomaban AAS o AINE. Se clasificaron según sintomatología predominante en tipo reflujo, ulceroso, dismotilidad e inespecífica. A criterio del facultativo se prescribió tratamiento con alcalinos en 38 pacientes, procinéticos en 574, antisecretores en 123 o mixto en 154. Al mes se evaluó la percepción de mejoría sintomática de los pacientes tratados con procinéticos y antisecretores. Resultados: se produjo mejoría sintomática en un 85 por ciento de pacientes al mes de tratamiento. Los pacientes con DF tipo inespecífico, tanto con procinéticos como con antisecretores, tuvieron menores tasas de mejoría (77 por ciento) que el resto de subtipos (p = 0,03). La prescripción de procinéticos se relacionó con el sexo femenino (OR: 0,43; IC 95 por ciento: 0,28-0,66) y el síntoma saciedad precoz (OR: 2,5; IC 95 por ciento: 1,6-4,1). Una evolución sintomática más larga (OR 0,92: IC 95 por ciento: 0,88-0,97) fue el único predictor independiente de peor respuesta a procinéticos. Conclusiones: en los pacientes con DF atendidos por médicos de Atención Primaria, el sexo femenino y el síntoma de saciedad precoz se relacionaron con la prescripción de procinéticos. Las tasas de eficacia sintomática precoz con procinéticos o antisecretores fueron altas (85 por ciento). Los pacientes con dispepsia del tipo inespecífico o sintomatología de larga evolución presentaron respuesta terapéutica menos favorable a procinéticos (AU)

Continuous intragastric pH monitoring in the evaluation of ebrotidine, cimetidine and placebo on gastric acidity in healthy volunteers.

This study was conducted to determine the efficacy and tolerance of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl) methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43.9, FI-3542), a new H2-receptor antagonist, on reducing gastric acidity after a single 800 mg dose, compared with cimetidine 800 mg once daily and placebo by means of a continuous intragastric pH monitoring. A total of 30 healthy volunteers were allocated to receive in a double blind, parallel design the study medication. Clinical observations, physical examinations and visual analogue scales (VAS) were performed during the study to assess the tolerability of the three treatments. Ebrotidine and cimetidine caused a greater and longer-lasting gastric acid inhibition than placebo. With ebrotidine, significantly (p < 0.05) higher median pH values (and interquartile range, IQR) were reached in the post-administration (2.61, IQR 2.02-3.93), postprandial (3.38, IQR 2.82-3.91) and nocturnal (2.83, IQR 1.69-3.77) periods than with placebo: 1.82 (IQR, 1.66-2.09), 2.81 (IQR, 2.02-3.28), and 1.89 (IQR, 1.44-2.13), respectively. Cimetidine showed significant differences compared to placebo in the post-administration (2.36, IQR 1.89-3.46) and nocturnal (2.46, IQR 1.88-4.33) periods. No statistical differences were observed between the active treatments. Ebrotidine caused a significantly higher percentage of time above pH 2.0 in the post-administration and nocturnal periods compared to placebo (p < 0.05), and above pH 3.0 in the post-administration, postprandial and nocturnal periods. No serious adverse effects, or disturbances in the VAS or in the vital signs were reported, and all medications were well tolerated. It is concluded that a single dose of ebrotidine 800 mg is as effective as cimetidine 800 mg in reducing total and nocturnal intragastric acidity. The study also confirms the excellent safety profile of the new drug.

Ebrotidine versus ranitidine in the treatment of acute duodenal ulcer. A multicentre, randomized, double-blind, controlled clinical trial.

A total of 478 patients with endoscopically confirmed duodenal ulcer entered this randomized, parallel, double-blind trial. Patients were randomly assigned to receive ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]- 4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfona mid e, CAS 100981-43-9, FI-3542) 400 mg or ranitidine 300 mg tablets (4:1) respectively, administered in single evening doses. Endoscopy, clinical examination and symptom assessment were performed at baseline and at weeks 4 and 8. Safety evaluations including laboratory tests, treatment compliance and antacid consumption checks were conducted at the beginning and/or at the 4 and 8 week visits. Patients whose ulcer showed endoscopic healing at the 4-week control left the study. Both groups were matched in all parameters studied. The healing rates at 4 weeks were 76.4% and 75.3% for ebrotidine and ranitidine respectively, while at 8 weeks the final rates were 95% and 91.8% respectively. Accompanying symptoms disappeared rapidly and the patients returned to normal. Smoking proved to be a highly significant negative risk factor, since healing rates were 83.4% and 71.2% at 4 weeks and 97.4% and 92.3% at 8 weeks in non-smokers and smokers respectively (p = 0.0046). Smokers treated with ranitidine showed significantly lower final healing rates than non-smokers (86% vs 100%; p = 0.0358), while the healing rates among patients treated with ebrotidine were similar regardless of whether they were smokers or not (93.9% and 96.7% N.S.). Ebrotidine (94%) proved to be more effective than ranitidine (86%) in smokers with higher healing rates (p < 0.05). Alcohol intake showed no significant relationship with the healing rates. Both drugs demonstrated an excellent safety. There were no changes in blood parameters, and no significant adverse events were reported.

Efficacy of ebrotidine and ranitidine in the treatment of benign gastric ulcer.

This is a phase III, randomized, double-blind, clinical trial with two parallel groups of 50 patients to assess the efficacy of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]ethyl ] amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) 800 mg and ranitidine 300 mg as a single evening dose in the treatment of benign gastric peptic ulcer. Prior to treatment, an endoscopy was performed to detect ulcer lesions and to discard malignancies. Clinical and endoscopic examinations were performed at 6, 9 and 12 weeks. Healing rates were significant for both treatments at week 6, while at week 12 there was statistical significance for ebrotidine as compared to ranitidine (96% vs 88% in the intention-to-treat analysis and 98% vs 87.5% in the per protocol analysis). Decrease in ulcer diameter was significant for both treatments at week 6, and for ebrotidine versus ranitidine at weeks 9 and 12. The overall improvement of symptoms was higher with ebrotidine, which was already significant at week 6. Safety was considered to be excellent, since no significant adverse events were reported for the patients included in the study.

Studies on the protective effect of ebrotidine on experimental ulcers induced by non-steroidal anti-inflammatory drugs in healthy volunteers.

Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]- 4-thiazolyl]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamid e, CAS 100981-43-9, FI-3542) is a new H2-receptor antagonist providing a new therapy for the prevention and healing of non-steroidal anti-inflammatory drugs-induced gastroduodenal lesions. Carbonic anhydrase is a zinc enzyme, and its isozyme (carbonic anhydrase II) in parietal cells plays a central role in HCl secretion. The effects of ebrotidine on carbonic anhydrase in human subjects are reported. Eighteen healthy volunteers were distributed in 3 equal subgroups and treated for 10 days as follows: ebrotidine 800 mg/d p.o. (Group A); indometacin 4 mg/kg/d p.o. in 3 divided doses (Group B); ebrotidine 800 mg/d p.o. plus indometacin 4 mg/kg/d p.o. (Group C). Assessment of the enzymatic activity of carbonic anhydrase was based on the colorimetric method of changing pH with the stopped-flow technique. In group A, ebrotidine reduced total gastric mucosal carbonic anhydrase activity by 62%; in group B, indometacin increased carbonic anhydrase activity in gastric mucosa by 138%; in group C, the combined treatment with ebrotidine plus indometacin decreased gastric mucosal carbonic anhydrase activity by 38%. The present study shows that, unlike ranitidine, ebrotidine, a competitive H2-receptor antagonist, is also a non-competitive inhibitor of carbonic anhydrase I and II. By antagonizing the activating effects of indometacin on gastric mucosal carbonic anhydrase, ebrotidine prevents mucosal lesions caused by anti-inflammatory drugs.

Comparative study of the safety and efficacy of ebrotidine versus ranitidine and placebo in the prevention of piroxicam-induced gastroduodenal lesions.

This study assessed the efficacy of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) versus ranitidine and placebo in preventing gastroduodenal lesions induced by piroxicam. Thirty patients with rheumatic disease, who were divided into 5 groups, received an oral treatment of piroxicam 20 mg once daily for 6 days plus ebrotidine 400 mg/day (Group I); ebrotidine 800 mg/day (Group II); ranitidine 150 mg/day (Group III); ranitidine 300 mg/day (Group IV); or placebo (Group V). Patients were endoscopically examined before and after treatment. Lanza's score was also determined, and laboratory tests were performed. The results of this study showed that the most powerful protective effect against mucosal gastric lesions induced by piroxicam was achieved with 800 mg/day of ebrotidine. Ranitidine at doses of 150 mg/day did not protect gastric mucosa, and the 300 mg/day dose exerted a poor gastroprotective effect.

Efficacy of ebrotidine and ranitidine combined with amoxicillin and metronidazole in the eradication of Helicobacter pylori in patients with duodenal ulcer.

This double-blind, randomized, phase III clinical trial was carried out in two parallel groups to assess the efficacy of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl]methyl]thio]ethyl]amino] methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) 400 mg and ranitidine 300 mg given in single evening dose, combined with amoxicillin 750 mg and metronidazole 500 mg three times daily for 14 days, in the eradication of Helicobacter pylori in patients with duodenal ulcer. Thirty patients were included, divided into two groups of 15, to whom one of the study therapies was administered based on a randomization code. Clinical and endoscopic controls were performed 4, 6 and 8 weeks after the onset of the treatment. No differences were seen between the two treatment groups with regard to demographic parameters and clinical histories. They were both perfectly homogeneous. There were no differences between the eradication of both therapies in both the antrum and gastric body samples (over 80% eradication), allowing the results to be classified as satisfactory. Moreover, perfect control was achieved through the study of clinical symptoms, which even disappeared in some cases. There were no differences in the healing rate of the duodenal ulcer after four weeks, 86.7% being achieved for both groups.