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Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD). Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8) or failed to tolerate the dose. Results Forty-two patients (70%) completed the study. Twenty-one patients (35%) achieved remission with 8 of the 21 patients (38%) needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20%) patients had adverse events leading to discontinuation. The most common adverse events were headache (35%), nausea, diarrhoea and nasopharyngitis (all 25%). Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

Background: It has been suggested that probiotics may improve gastrointestinal discomfort. Not all probiotics exhibit the same effects and consequently meta-analyses on probiotics should be confined to well-defined strains or strain combinations. The aim of this study was to evaluate the effectiveness of a probiotic fermented milk (PFM) that includes Bifidobacterium lactis (B. lactis) CNCM I-2494 and lactic acid bacteria on gastrointestinal discomfort in the general adult population. Methods: Double-blind randomized controlled trials in the general adult population comparing PFM with a control dairy product for at least 4 weeks were searched from multiple literature databases (up to February 2015). Meta-analyses using random-effects models, with individual participant data were undertaken to calculate an odds ratio (OR) or standard mean difference (SMD), with a 95% confidence interval (CI). Results: The search strategy identified 12,439 documents. Overall, three trials with a total of 598 adults (female = 96.5%) met the inclusion criteria. Consumption of the PFM product was associated with a significant improvement in overall gastrointestinal discomfort compared with the control product (OR = 1.48; 95% CI 1.07–2.05), with a number needed to treat (NNT) of 10.24 (95% CI 5.64–55.93). PFM was also superior to the control in reducing digestive symptoms, as measured using a composite score (SMD = −0.21; 95% CI −0.37 to −0.05). Sensitivity analyses produced similar results, and the heterogeneity between studies was minimal. Conclusions: This meta-analysis shows that the consumption of PFM with B. lactis CNCM I-2494 and lactic acid bacteria is associated with a modest but consistent and significant improvement of outcomes related to gastrointestinal discomfort in healthy adults. [ABSTRACT FROM AUTHOR]

Unlabelled: Relative potency bioassays are used to estimate the potency of a test biological product relative to a standard or reference product. It is established practice to assess the parallelism of the dose-response curves of the products prior to calculating relative potency. This paper provides a review of parallelism testing for bioassays. In particular three common methods for parallelism testing are reviewed: two significance tests (the F-test, the χ(2)-test) and an equivalence test. Simulation is used to compare these methods. We compare the sensitivity and specificity and receiver operating characteristic curves, and find that both the χ(2)-test and the equivalence test outperform the F-test on average, unless the assay-to-assay variation is considerable. No single method is optimal in all situations. We describe how bioassay scientists and statisticians can work together to determine the best approach for each bioassay, taking into account its properties and the context in which it is applied., Lay Abstract: Bioassays are experiments that use living organisms, tissues, or cells to measure the concentration of a pharmaceutical. Typically the response of the living matter to a test sample with an unknown concentration of a pharmaceutical is compared to the response to a standard reference sample with a known concentration. An important step in the analysis of bioassays is checking that the test sample is responding like a diluted copy of the reference sample; this is known as testing for parallelism. There are three statistical methods commonly used to test for parallelism: the F-test, the χ(2)-test, and the equivalence test. This paper compares the three methods using computer simulations. We conclude that different methods are best in different situations, and we provide guidelines to help bioassay scientists and statisticians decide which method to use., (© PDA, Inc. 2015.)