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Cytochrome P450 1A2 (CYP1A2) is involved in the metabolism of antipsychotic drugs such as clozapine and olanzapine. Personalization of these treatments requires an accurate estimation of CYP1A2 activity. In this study, we aimed (1) to evaluate the correlation between activity score (AS), covariate-corrected activity score (CCS) and the phenotype of CYP1A2 using a caffeine test probe and (2) to investigate their relationship with dose-adjusted clozapine concentrations in a subgroup of the cohort.A multicentric, retrospective and observational study was carried out in the French university hospitals of Marseille and Tours. CYP1A2 activity was calculated by the paraxanthine/caffeine (17X/137X) ratio determined 4 h after an oral intake of 100 mg caffeine. AS was calculated according to the CYP1A2*1F alleles. CCS was calculated according to the CYP1A2*1F alleles, smoking status and the presence of concomitant inhibitors.As expected, among the 89 patients included, the 17X/137X ratio was significantly higher in patients who smoked. We found a significant but modest correlation between the 17X/137X ratio and CCS (RCorrelation with clozapine concentrations showed the advantage of the 17X/137X ratio over the CCS in clozapine dose optimization. CYP1A2 activity, especially when determined by the caffeine probe, may be used to personalize clozapine dosing for patients experiencing treatment failure.

Background The use of artificial nutrition, defined as a medical treatment that allows a non‐oral mechanical feeding, for cancer patients with limited life expectancy is deemed nonbeneficial. High‐quality evidence about the use of artificial nutrition near the end of life is lacking. This study aimed (a) to quantify the use of artificial nutrition near the end‐of‐life, and (b) to identify the factors associated with the use of artificial nutrition. Methods This was a retrospective cohort study of decedents based on data from the French national hospital database. The study population included adult cancer patients who died in hospitals in France between 2013 and 2016 and defined to be in a palliative condition. Use of artificial nutrition during the last 7 days before death was the primary endpoint. Results A total of 398 822 patients were included. The median duration of the last hospital stay was 10 (interquartile range, 4‐21) days. The artificial nutrition was used for 11 723 (2.9%) during the last 7 days before death. Being a man, younger, having digestive cancers, metastasis, comorbidities, malnutrition, absence of dementia, and palliative care use were the main factors associated to the use of artificial nutrition. Conclusion This study indicates that the use of artificial nutrition near the end of life is in keeping with current clinical guidelines. The identification of factors associated with the use of artificial nutrition, such as cancer localization, presence of comorbidities or specific symptoms, may help to better manage its use., In France, the artificial nutrition management is rather in accordance with the available clinical guidelines for cancer patients with limited life expectancy.

Objectives It is unknown whether a cytokine signature may help the identification of subgroup of patient who would respond to personalized treatment. As interleukin-1 beta (Il-1β) seems to play a major role in mood disorder, a systematic review and meta-analysis of its potential role in major depressive disorder (MDD) was carried out. Methods A systematic search was performed to identify appropriate MDD vs. control studies pertaining to Il-1β. Methodological quality and possible moderators were also assessed. Results A total of 1922 studies were identified, and 53 articles were selected. Results showed an association between increased blood IL-1β and MDD in high-quality studies only. No association with age was found. No IL-1β gene-related polymorphisms has been associated with MDD. No effect of antidepressant on IL-1β level has been found, although the antidepressants investigated were various. Qualitative analyses indicate that MDD coupled to a history of childhood trauma may be a subgroup for IL-1β -targeted therapies. No difference in studies utilizing a stimulation method has been identified to date. Conclusions The present work has confirmed IL-1β as a biological marker of interest for innovative MDD treatments. However, further studies are needed to clarify the patients with MDD who may benefit from these therapies.

This systematic review summarizes and critically appraises the literature on the effect of erythropoietin (EPO) in schizophrenia patients and the pathophysiological mechanisms that may explain the potential of its use in this disease. EPO is mainly known for its regulatory activity in the synthesis of erythrocytes and is frequently used in treatment of chronic anemia. This cytokine, however, has many other properties, some of which may improve the symptoms of psychiatric illness. The review follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement guidelines. Three databases (Medline, Web of Science, and Cochrane) were searched combining the search terms 'erythropoietin AND (psychotic disorders OR schizophrenia)'. Seventy-eight studies were included in qualitative synthesis, a meta-analytic approach being prohibited. The findings suggest that several EPO cerebral potential properties may be relevant for schizophrenia treatment, such as neurotransmission regulation, neuroprotection, modulation of inflammation, effects on blood-brain barrier permeability, effects on oxidative stress and neurogenesis. Several potentially detrimental side-effects of EPO therapy, such as increased risk of thrombosis, cancer, increased metabolic rate and mean arterial blood pressure leading to cerebral ischemia could severely limit or halt the use of EPO. Overall, because the available data are inconclusive, further efforts in this field are warranted.

The factors predicting smoking abstinence in depressive smokers, and the role of physical activity in precessation, were investigated. One hundred thirty-three smokers with current major depressive disorders (score ≥10 on the Depression subscale of Hospital Anxiety and Depression Scale) were recruited from a large prospective cohort of smokers (n = 1,119). Over a maximum period of 3 years, regression modeling, adjusted for potential confounders, showed that physical activity was associated with relapse (relapse rate = 0.54, 95% confidence interval = 0.34–0.85, p = .008). Also, antidepressants, anxiolytics, level of education, and number of attempts to quit were associated with relapse. The protective role of physical activity on relapse rate could be a modifiable factor in smoking cessation for smokers with depressive disorders. (Am J Addict 2012;00:1–8)