This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

Objectives: This study sought to determine the risk factors for short term mortality in the victims of the heat wave of August 2003 in France from among patients evaluated in our emergency department (ED). It was hypothesised that age, temperature, and some long term therapies and pre-existing pathologies were factors associated with short term mortality. Methods: A retrospective analysis of a seven day period. Four experts decided blindly, in pairs, whether a patient had presented with a heat related problem. Inclusion criteria were: core temperature >38˚C and/ or clinical signs of dehydration. Comparisons were made between the survivors and one month nonsurvivors for 57 different items. Short term mortality was defined as death in the ED or within the first month of the ED visit. Results: Of 841 patients attending the ED in the study period, 165 were included in the study, of which most were elderly women. Thirty one (18.8%) died within one month. Factors associated with short term mortality were: a greater degree of dependent living; more severe clinical condition on admission (higher temperature and heart rate, lower blood pressure, hypoxia, and altered mental status); higher values of blood glucose, troponin, and white blood cell count; lower values of serum protein and prothrombin levels; pre-existing ischaemic cardiomyopathy; pneumonia as associated infection; and previous psychotropic treatment. The total number of survivors at one year was 91. Conclusions: Although this study is limited because of the small sample size, the results have helped determine factors useful for future identification of patients at greatest risk of death in order to implement a more efficient patient care protocol. In August 2003, France experienced an unusual and severe heat wave, responsible for an estimated 14 802 excess deaths during a period of 20 days. In Île-de-France, between 4 August and 12 August 2003, maximum temperatures were higher than 35˚C, and the minimum were never lower than 20˚C. In this region (which includes Paris) mortality increased to over 130%; 33% of all deaths registered in France during this period.1 Normally Île-de-France has a temperate climate, and it is rare to have air conditioning in homes and hospitals. The heat wave caused an influx of patients to French emergency services.Our emergency department (ED) is an adult urban teaching emergency service which is part of the university hospital system of the Public Assistance Hospitals of Paris (AP-HP). Our yearly attendance is 43 000 patients. Between 8 August and 14 August 2003, the number of patients attending our ED increased by about 10% compared with the previous year.Until now, studies performed in the setting of heat wave have essentially concerned heat stroke.2 3 This condition requires a fever of >40˚C and altered mental status, and is the best defined of all heat related illnesses. Studies concerning all other clinical presentations, whether heat stress or heat exhaustion, in which signs and symptoms are related to water or salt depletion...

International audienceIn this paper, we study the centralized spectrum access and power management for several opportunistic users, secondary users (SUs), without hurting the primary users (PUs). The radio resource manager's objective is to minimize the overall power consumption of the opportunistic system over several orthogonal frequency bands under constraints on the minimum quality of service (QoS) and maximum peak and average interference to the PUs. Given the opposing nature of these constraints, we first study the problem of feasibility, and we provide sufficient conditions and necessary conditions for the existence of a solution. The main challenge lies in the non-convexity of this problem because of the discrete spectrum scheduling: one band can be allocated to at most one SU to avoid interference impairments. To overcome this issue, we use a Lagrangian relaxation technique, and we prove that the discrete solutions of the relaxed problem are the solutions to the initial problem. We propose a projected sub-gradient algorithm to compute the solution, when it exists. Assuming that the channels are drawn randomly from a continuous distribution, this algorithm converges to the optimal solution. We also study a specific symmetric system for which we provide the analytical solution. Our numerical results compare the energy-efficiency of the proposed algorithm with other spectrum allocation solutions and show the optimality of our approach