Insight significantly predicted the general clinical course, treatment adherence and functional outcome in our FEP sample after 1 year. Only education additionally accounted for the longitudinal course. Since our results suggest that better insight improves treatment adherence and consequently clinical course and functional outcome, insight could be a specific target of treatment in early intervention programs.

The cardiac safety of ebastine, a long-acting, non-sedating antihistamine, has been thoroughly assessed in phase I-III clinical studies. Ebastine alone at the recommended doses of 10 mg and 20 mg has no clinically relevant effect on QTc interval in adults and in special patient populations (elderly, children or subjects with hepatic or renal impairment). Ebastine administered at 60 and 100 mg/day (3-5 times the maximum recommended dose) for 1 week had statistically significantly smaller effects (3.7 and 10.3 msec, respectively) on the QTc interval than terfenadine (18 msec) at three times the recommended dose (360 mg/day). The mean QTc interval prolongation observed with ebastine 100 mg/day was small and not clinically meaningful, although the results were statistically significant vs. placebo. The effect of ebastine 60 mg/day was not statistically different from placebo. Steady-state drug interaction studies demonstrated that the co-administration of ebastine 20 mg with ketoconazole or erythromycin produced significant increases in systemic exposure for ebastine, which were accompanied by small increases in QTc (approximately 10 msec above ketoconazole or erythromycin alone). Results from individual studies suggest that, when coadministered with ketoconazole, ebastine produces similar changes in QTc interval measurements compared to loratadine and cetirizine. Pooled data from clinical efficacy trials of ebastine 1-30 mg/day administered for 2-3 weeks showed no clinically relevant cardiac effects as assessed by serial electrocardiographs and Holter monitoring. The overall cardiac safety profile based on currently available information suggests that ebastine, like loratadine and cetirizine, has a lower potential for causing adverse cardiovascular effects than terfenadine.

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The aims of this study were to analyze the presence of gender differences in the phenotypic expression of schizophrenia at the onset of illness and to explore whether these differences determine clinical and functional outcome 2 years after the initiation of treatment. Data from 231 first-episode-psychosis non-substance-dependent patients (156 men and 75 women) participating in a large-scale naturalistic open-label trial with risperidone were recorded at inclusion and months 1, 6, 12, and 24. Men presented a significant earlier age of onset (24.89 years vs. 29.01 years in women), poorer premorbid functioning, and a higher presence of prodromal and baseline negative symptoms. Women were more frequently married or lived with their partner and children and more frequently presented acute stress during the year previous to onset than men. No other significant clinical or functional differences were detected at baseline. The mean dose of antipsychotic treatment was similar for both genders during the study, and no significant differences in UKU scores were found. The number of hospitalizations was similar between groups, and adherence was more frequent among women. At the 2-year follow-up, both groups obtained significant improvements in outcome measures: PANSS, CGI severity, and GAF scores. Significant gender * time interactions were detected for negative and general PANSS subscales, with the improvement being more pronounced for men. However, no differences were detected for the mean scores obtained during the study in any outcome measure, and the final profile was similar for men and women. Our results suggest that although the initial presentation of schizophrenia can differ according to gender, these differences are not sufficient enough to determine differentiated outcome 2 years after the initiation of treatment in non-substance-dependent patients. The influence of gender on the early course of schizophrenia does not seem to be clinically or functionally decisive in this population.

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Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

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