Infection and Inflammation Leading to Clozapine Toxicity and Intensive Care: A Case Series

Objective: To describe 3 cases of clozapine toxicity associated with infectious and/or inflammatory processes. Case Summaries: 3 patients stable on clozapine therapy prior to a medical hospital admission developed clozapine toxicity. It was suspected that an acute infectious and/or inflammatory process in each patient was related to abrupt mental status changes, onset of sialorrhea, myoclonus, and/or need for ventilatory support. Investigations of altered mental status did not reveal alterative causes and presentations were not consistent with neuroleptic malignant syndrome, other acute neurologic complications, or psychiatric decompensation. All patients improved after clozapine dose reductions allowing for transfer from intensive care units. Using the Naranjo ADR Probability Scale for each case, a probable relation between clozapine toxicity and the infectious and/or inflammatory process was determined. Discussion: Clozapine toxicity may manifest with multiple symptoms including sedation, sialorrhea, and hypotension. In addition to overdose and drug interactions; infection and/or inflammation may precipitate clozapine toxicity. This may be related to cytokine-mediated inhibition of cytochrome P450 1A2. The likelihood of toxicity via this mechanism has not been well-characterized, thus careful monitoring is required for medically ill patient receiving clozapine. Clozapine is extensively bound to the acute phase reactant, alpha-1 acid glycoprotein, which may unpredictably protect against clinical toxicity. C-reactive protein has also been investigated to relate clozapine toxicity to infection and/or inflammation. Conclusion: Clozapine toxicity developed in 3 patients admitted to a medical setting suspected to be related to infection and/or inflammation. Clinicians should be aware of this potential adverse drug event with clozapine

Implementation of the Integrated Approach in Different Types of Exposure Scenarios

The ICRP recognises three types of exposure situations (planned, existing and emergency). In all three situations, the release of radionuclides into the natural environment leads to exposures of non-human biota, as well as the potential for exposures of the public. This paper describes how the key principles of the ICRP system of radiological protection apply to non-human biota and members of the public in each of these exposure situations. Current work in this area within ICRP Task Group (TG) 105 is highlighted. For example, how simplified numeric criteria may be used in planned exposure situations that are protective of both the public and non-human biota. In emergency exposure situations, the initial response will always be focused on human protection however, understanding the potential impacts of radionuclide releases on non-human biota will likely become important in terms of communication as governments and the public seek to understand the exposures that are occurring. For existing exposure situations, we need to better understand the potential impacts of radionuclides on animals and plants especially when deciding on protective actions. Understanding the comparative impacts from radiological, non-radiological and physical aspects is often important in managing remediating legacy sites. The TG is making use of case studies of how exposure situations have been managed in the past to provide additional guidance and advice for the protection of non-human biota

Photographic measurement of leaf angles in field crops

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Effects of early, combined endurance and resistance training in mechanically ventilated, critically ill patients: a study protocol for a randomised controlled trial.

BACKGROUND Prolonged need for intensive care is associated with neuromuscular weakness, termed Intensive Care Unit Acquired Weakness. Those affected suffer from severe functional impairment that can persist for years. First studies suggest a positive effect of physiotherapy and early mobilisation. However, the ideal intervention for a preferential functional outcome is not known. So far no randomised controlled trial has been conducted to specifically evaluate an early endurance and resistance training in the mechanically ventilated, critically ill patient. METHODS/DESIGN A randomised controlled trial with blinded assessors and 6-month follow-up will be conducted in a tertiary, interdisciplinary intensive care unit in Switzerland. Participants (n = 115; expected dropouts: n = 15) will be randomised to a control group receiving standard physiotherapy and to an experimental group that undergoes early mobilisation combined with endurance and resistance training. The inclusion criteria are being aged 18 years or older, expected mechanical ventilation for more than 72 h and qualitative independence before the illness. Primary endpoints are functional capacity (6-Minute Walk Test) and the ability to perform activities of daily living (Functional Independence Measure) measured at hospital discharge. Secondary endpoints include muscle strength (Medical Research Council sum score, handgrip strength and handheld dynamometry for quadriceps muscle), joint contractures (range of motion), exercise capacity (Timed 'Up & Go' Test) and health-related quality of life (Short Form 36). Safety will be monitored during interventions by indirect calorimetry and continuous intensive care standard monitoring. All previously defined adverse events will be noted. The statistical analysis will be by intention-to-treat with the level of significance set at p < 0.05. DISCUSSION This prospective, single-centre, allocation-concealed and assessor-blinded randomised controlled trial will evaluate participant's function after an early endurance and resistance training compared to standard care. Limitations of this study are the heterogeneity of the critically ill and the discontinuity of the protocol after relocation to the ward. The strengths lie in the pragmatic design and the clinical significance of the chosen outcome measures. TRIAL REGISTRATION German Clinical Trials Register (DRKS): DRKS00004347 , registered on 10 September 2012

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity

Teacher Training for Children with Autism Spectrum Disorders in Finland

This chapter first provides a short description of the historical background and development of special education teacher training in Finland. The relationship between special education and teaching pupils with autism spectrum disorder (ASD) is covered by chronologically presenting the main events, turning points, publications, and people that have had a significant effect on the education of pupils with ASD in Finland. This is followed by a description of the organization of teacher training, in general, and the particular characteristics of teaching pupils with ASD. In the context of ASD, it is essential to examine questions concerning the link between learning as social practice and the challenges of interaction manifested in learning difficulties. The chapter ends with a description of the continuing teacher education for special education teachers in Finland.Peer reviewe

Reduced postprandial energy expenditure and increased exogenous fat oxidation in young woman after ingestion of test meals with a low protein content

<p>Abstract</p> <p>Background</p> <p>Macronutrient composition of diets can influence energy balance in humans. We tested the hypothesis whether low protein content in single meals may induce lower values of energy expenditure (EE) and fat oxidation (FO) as compared to adequate protein content.</p> <p>Methods</p> <p>Indirect calorimetry was combined with a breath test using naturally ¹³C-enriched corn oil to differentiate between postprandial exogenous and endogenous FO. Young women ingested single meals containing either 3.9% (low protein, LP) or 11.4% (adequate protein, AP) of total energy (~3100 kJ) as protein.</p> <p>Results</p> <p>Postprandial EE was 160 kJ/6 h lower (p < 0.01) after LP meals and diet induced thermogenesis (DIT) increased less (p < 0.001) as compared to AP meals. Total postprandial FO was not significantly different between meals (~17 g/6 h). However, exogenous postprandial FO was significantly (p < 0.01) higher (4.28 ± 1.57 g/6 h) after exposure to LP meals as compared to AP meals (1.87 ± 1.00 g/6 h). Less than 10% of ingested fat (50 g) was oxidized in the postprandial phase. The overall postprandial fat balance was approximately + 33 g.</p> <p>Conclusion</p> <p>Breath tests using naturally ¹³C-labeled corn oil mirror exogenous FO. Low protein meals resulted in reduced postprandial EE and increased exogenous FO as compared to adequate protein meals without differences in total FO.</p