MF59-adjuvanted influenza vaccine (FLUAD®) elicits higher immune responses than a non-adjuvanted influenza vaccine (Fluzone®): A randomized, multicenter, Phase III pediatric trial in Mexico.

The poor immune response elicited by trivalent influenza vaccines (TIVs) in children can be enhanced by the addition of adjuvants. This observer-blind, randomized Phase III trial assessed the immunogenicity and safety of the MF59-adjuvanted trivalent influenza vaccine FLUAD® (aTIV) and a non-adjuvanted TIV, in healthy children (aged 6 to <72 months) from 3 centers in Mexico, during the 2014-2015 season. The primary objectives were to assess the non-inferiority of aTIV to TIV, measured by geometric mean titers (GMTs), and the safety of aTIV and TIV. Seroconversion was one of several secondary objectives. In total, 287 children were enrolled. The non-inferiority criteria for GMTs and seroconversion were met for aTIV for all 3 vaccine strains. Lower bounds of the 95% confidence intervals for all 3 aTIV:TIV vaccine ratios were >2, showing that the immunogenicity of aTIV was superior to that of TIV for all 3 strains. Solicited adverse events (AEs) were experienced more frequently with aTIV than TIV by younger children (aged 6 to <36 months), but were more frequent with TIV than aTIV in older children (aged 36 to <72 months) who had been vaccinated previously. More unsolicited AEs were associated with aTIV than the TIV. All AEs were of mild or moderate severity. No deaths, serious AEs, or AEs leading to premature withdrawal were reported. Overall, aTIV was highly immunogenic and was well tolerated in healthy children 6 to <72 months of age. These results indicate that aTIV may be a beneficial addition to national pediatric vaccination programs.

The selective glycine uptake inhibitor org 25935 as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia: results from the GIANT trial.

Using a selective glycine uptake inhibitor as adjunctive to second-generation antipsychotic (SGA) was hypothesized to ameliorate negative and/or cognitive symptoms in subjects with schizophrenia. Subjects with predominant persistent negative symptoms (previously stabilized ≥3 months on an SGA) were enrolled in a randomized, placebo-controlled trial to investigate adjunctive treatment with Org 25935, a selective inhibitor of type 1 glycine transporter, over 12 weeks in a flexible dose design. Org 25935 was tested at 4 to 8 mg twice daily and 12 to 16 mg twice daily versus placebo. Primary efficacy outcome was mean change from baseline in Scale for Assessment of Negative Symptoms composite score. Secondary efficacy end points were Positive and Negative Syndrome Scale total and subscale scores, depressive symptoms (Calgary Depression Scale for Schizophrenia), global functioning (Global Assessment of Functioning scale), and cognitive measures using a computerized battery (Central Nervous System Vital Signs). Responder rates were assessed post hoc. A total of 215 subjects were randomized, of which 187 (87%) completed the trial. Both dose groups of Org 25935 did not differ significantly from placebo on Scale for Assessment of Negative Symptoms, Positive and Negative Syndrome Scale (total or subscale scores), Global Assessment of Functioning, or the majority of tested cognitive domains. Org 25935 was generally well tolerated within the tested dose range, with no meaningful effects on extrapyramidal symptoms and some reports of reversible visual adverse effects. Org 25935 did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning when administered as adjunctive treatment to SGA. In our study population, Org 25935 appeared to be well tolerated in the tested dose ranges.

Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients.

OBJECTIVE: New evidence indicates that treatment response can be predicted with high sensitivity after 2 weeks of treatment. Here, we assess whether early improvement with antidepressant treatment predicts treatment outcome in patients with major depressive disorder (MDD). DATA SOURCES: Forty-one clinical trials comparing mirtazapine with active comparators or placebo in inpatients and outpatients (all-treated population, N = 6907; intent-to-treat population, N = 6562) with MDD (DSM-III-R or DSM-IV Criteria) were examined for early improvement (>or= 20% score reduction from baseline on the 17-item Hamilton Rating Scale for Depression [HAM-D-17] within 2 weeks of treatment) and its relationship to treatment outcome. STUDY SELECTION: Data were obtained from a systematic search of single- or double-blind clinical trials (clinical trials database, Organon, a part of Schering-Plough Corporation, Oss, The Netherlands). All included trials (a total of 41) employed antidepressant treatment for more than 4 weeks and a maximum of 8 weeks. The studies ranged from March 1982 to December 2003. Trials were excluded if there were no HAM-D-17 ratings available, no diagnosis of MDD, or if the study was not blinded. Trials were also excluded if HAM-D-17 assessments were not available at week 2, week 4, and at least once beyond week 4. DATA SYNTHESIS: Early improvement predicted stable response and stable remission with high sensitivity (>or= 81% and >or= 87%, respectively). Studies utilizing rapid titration vs. slow titration of mirtazapine demonstrated improved sensitivity for stable responders (98%, [95% CI = 93% to 100%] vs. 91% [95% CI = 89% to 93%]) and stable remitters (100%, [95% CI = 92% to 100%] vs. 93% [95% CI = 91% to 95%]). Negative predictive values for stable responders and stable remitters were much higher (range = 82%-100%) than positive predictive values (range = 19%-60%). CONCLUSIONS: These results indicate that early improvement with antidepressant medication can predict subsequent treatment outcome with high sensitivity in patients with major depressive disorder. The high negative predictive values indicate little chance of stable response or stable remission in the absence of improvement within 2 weeks. A lack of improvement during the first 2 weeks of therapy may indicate that changes in depression management should be considered earlier than conventionally thought.