ObjectiveTo assess whether corticosteroids are associated with increased risk of gastrointestinal bleeding or perforation.DesignSystematic review and meta-analysis of randomised, double-blind, controlled trials comparing a corticosteroid to placebo for any medical condition or in healthy participants. Studies with steroids given either locally, as a single dose, or in crossover studies were excluded.Data sourcesLiterature search using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews between 1983 and 22 May 2013.Outcome measureOutcome measures were the occurrence of gastrointestinal bleeding or perforation. Predefined subgroup analyses were carried out for disease severity, use of non-steroidal anti-inflammatory drugs (NSAIDs) or gastroprotective drugs, and history of peptic ulcer.Results159 studies (N=33 253) were included. In total, 804 (2.4%) patients had a gastrointestinal bleeding or perforation (2.9% and 2.0% for corticosteroids and placebo). Corticosteroids increased the risk of gastrointestinal bleeding or perforation by 40% (OR 1.43, 95% CI 1.22 to 1.66). The risk was increased for hospitalised patients (OR 1.42, 95% CI 1.22 to 1.66). For patients in ambulatory care, the increased risk was not statistically significant (OR 1.63, 95% CI 0.42 to 6.34). Only 11 gastrointestinal bleeds or perforations occurred among 8651 patients in ambulatory care (0.13%). Increased risk was still present in subgroup analyses (studies with NSAID use excluded; OR 1.44, 95% CI 1.20 to 1.71, peptic ulcer as an exclusion criterion excluded; OR 1.47, 95% CI 1.21 to 1.78, and use of gastroprotective drugs excluded; OR 1.42, 95% CI 1.21 to 1.67).ConclusionsCorticosteroid use was associated with increased risk of gastrointestinal bleeding and perforation. The increased risk was statistically significant for hospitalised patients only. For patients in ambulatory care, the total occurrence of bleeding or perforation was very low, and the increased risk was not statistically significant.

ObjectiveTo assess a question–answer pair (QAP) database integrated with websites developed for drug information centres to answer complex questions effectively.DesignDescriptive study with comparison of two subsequent 6-year periods (1995–2000 and 2001–2006).SettingThe Regional Medicines Information and Pharmacovigilance Centres in Norway (RELIS).ParticipantsA randomised sample of QAPs from the RELIS database.Primary outcome measureAnswer time in days compared with Mann–Whitney U test.Secondary outcome measureNumber of drugs involved (one, two, three or more), complexity (judgemental and/or patient-related or not) and literature search (none, simple or advanced) compared with χ2 tests.Results842 QAPs (312 from 1995 to 2000 and 530 from 2001 to 2006) were compared. The fraction of judgemental and patient-related questions increased (66%–75% and 54%–72%, respectively, p<0.01). Number of drugs and literature search (>50% advanced) was similar in the two periods, but the fraction of answers referring to the RELIS database increased (13%–31%, p<0.01). Median answer time was reduced from 2 days to 1 (p<0.01), although the fraction of complex questions increased from the first to the second period. Furthermore, the mean number of questions per employee per year increased from 66 to 89 from the first to the second period.ConclusionsThe authors conclude that RELIS has a potential to efficiently answer complex questions. The model is of relevance for organisation of drug information centres.

Atorvastatin and simvastatin appear to differ in their potential to interact with warfarin. Clinicians should be aware of the interaction risk when starting simvastatin treatment in patients on warfarin therapy.

PurposeOral vitamin E is used in several childhood diseases, but dosage recommendations differ. Few oral products have a marketing authorization for therapeutic use in children. Preliminary data indicate differences in bioavailability among the various vitamin E compounds. Our objective was to review published data on oral vitamin E therapy in neonates and children in order to establish dosage recommendations at a local level.MethodsA literature search was conducted, including Medline Ovid, EMBASE (1980-Feb 2008), Cochrane databases, product monographs, handbooks, and textbooks.ResultsThe main vitamin E compounds being used in children are α-tocopherol, α-tocopheryl acetate, and tocofersolan. The most data are available on tocopheryl acetate, both in neonates and older children. In children with malabsorption disorders, tocofersolan appears to have an increased bioavailability compared to tocopherol or tocopheryl acetate. Published data on pharmacokinetics and dosages for clinical use are few and heterogeneous. No pharmacokinetic studies were found for tocofersolan in neonates and infants. There are few comparative studies on pharmacokinetics, therapeutic use, and adverse drug reactions (ADRs) in children. Dosages used in clinical studies and dosage recommendations in handbooks differ considerably.ConclusionsThe differences in dosing recommendations in children may be due to lack of systematic studies. Existing published data on oral vitamin E do not provide a basis for evaluation of dosage recommendations in children. Comparative clinical studies are required for scientific evaluation of pharmacokinetics, dosage regimens, and efficacy/ADR assessments in children.

ObjectiveTo identify all publications from the ‘Treatment for Adolescents With Depression Study (TADS)’ and assess the findings regarding occurrence of any adverse effects in the treatment groups both for the short-term and long-term study stages.DesignDescriptive analysis of TADS publications with any information on adverse effects.ResultsWe identified 48 publications describing various aspects of the TADS, in which 439 adolescent patients received treatment with fluoxetine, cognitive–behavioural therapy, cognitive–behavioural therapy plus fluoxetine or placebo. Eight publications were assessed as providing some data on adverse effects. Risk of suicidal behaviour was the only adverse effect that was addressed in all publications. Several psychiatric and physical adverse effects were reported during the first 12 weeks, but not mentioned in reports from later study stages. Common adverse effects of fluoxetine, such as weight changes or sexual problems, were not identified or mentioned in the publications.ConclusionsThe TADS publications do not present a comprehensive assessment of treatment risk with fluoxetine in adolescents, especially for more than 12 weeks of treatment. Risk of suicidality was the only adverse effect that was reported over time. Reporting of adverse effects was incomplete with regard to the long-term safety profile of fluoxetine.