Janet Mifsud

The administration of rescue medication to children with prolonged acute convulsive seizures in the community: What happens in practice?

This paper presents the findings of a review of existing clinical and non-clinical guidance on the management of children with prolonged acute convulsive seizures (PCS) and the administration of rescue medication in community settings. Findings are based on desk- and web-based research in 6 countries. Published clinical guidelines are mostly limited to the hospital setting and offer few explicit recommendations for community settings. Non-clinical guidance on the management of medicines at school exists at the national or regional level in all 6 countries, however rescue epilepsy medication is often not mentioned specifically. Existing legal frameworks are vague and open to interpretation. As a result, whether a child receives rescue medication at school depends primarily on the availability of a willing teacher who accepts responsibility for administering it to that child during school hours. Comprehensive guidelines are clearly needed that provide practical guidance to ensure that children with PCS are treated as quickly as possible in all community settings. Recommendations for future action include: providing clearer information on PCS and rescue medication to parents and schools; putting in place an individual healthcare plan for every child with a history of PCS at his or her school; collecting more empirical data to gain a better understanding of the experience of children with PCS at school, their parents and teachers; and finally, implementing systematic training for all carers of children with PCS. The epilepsy specialist may play an important role in ensuring that these recommendations are put into place for their patients.

Epilepsy priorities in Europe: A report of the ILAE‐IBE Epilepsy Advocacy Europe Task Force

The European Forum on Epilepsy Research (ERF2013), which took place in Dublin, Ireland, on May 26–29, 2013, was designed to appraise epilepsy research priorities in Europe through consultation with clinical and basic scientists as well as representatives of lay organizations and health care providers. The ultimate goal was to provide a platform to improve the lives of persons with epilepsy by influencing the political agenda of the EU. The Forum highlighted the epidemiologic, medical, and social importance of epilepsy in Europe, and addressed three separate but closely related concepts. First, possibilities were explored as to how the stigma and social burden associated with epilepsy could be reduced through targeted initiatives at EU national and regional levels. Second, ways to ensure optimal standards of care throughout Europe were specifically discussed. Finally, a need for further funding in epilepsy research within the European Horizon 2020 funding programme was communicated to politicians and policymakers participating to the forum. Research topics discussed specifically included (1) epilepsy in the developing brain; (2) novel targets for innovative diagnostics and treatment of epilepsy; (3) what is required for prevention and cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on aging and mental health. This report provides a summary of recommendations that emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the treatment gap, and (3) reduce the burden and stigma associated with epilepsy.

The effect of turmeric (Curcumin) supplementation on cytokine and inflammatory marker responses following 2 hours of endurance cycling

BackgroundEndurance exercise induces IL-6 production from myocytes that is thought to impair intracellular defence mechanisms. Curcumin inhibits NF-κB and activator protein 1, responsible for cytokine transcription, in cell lines. The aim of this study was to investigate the effect of curcumin supplementation on the cytokine and stress responses following 2 h of cycling.MethodsEleven male recreational athletes (35.5 ± 5.7 years; Wmax 275 ± 6 W; 87.2 ± 10.3 kg) consuming a low carbohydrate diet of 2.3 ± 0.2 g/kg/day underwent three double blind trials with curcumin supplementation, placebo supplementation, and no supplementation (control) to observe the response of serum interleukins (IL-6, IL1-RA, IL-10), cortisol, c-reactive protein (CRP), and subjective assessment of training stress. Exercise was set at 95% lactate threshold (54 ± 7% Wmax) to ensure that all athletes completed the trial protocol.ResultsThe trial protocol elicted a rise in IL-6 and IL1-RA, but not IL-10. The supplementation regimen failed to produce statistically significant results when compared to placebo and control. IL-6 serum concentrations one hour following exercise were (Median (IQR): 2.0 (1.8-3.6) Curcumin; 4.8 (2.1-7.3) Placebo; 3.5 (1.9-7.7) Control). Differences between supplementation and placebo failed to reach statistical significance (p = 0.18) with the median test. Repeated measures ANOVA time-trial interaction was at p = 0.06 between curcumin supplementation and placebo. A positive correlation (p = 0.02) between absolute exercise intensity and 1 h post-exercise for IL-6 concentration was observed. Participants reported “better than usual” scores in the subjective assessment of psychological stress when supplementing with curcumin, indicating that they felt less stressed during training days (p = 0.04) compared to placebo even though there was no difference in RPE during any of the training days or trials.ConclusionThe limitations of the current regimen and trial involved a number of factors including sample size, mode of exercise, intensity of exercise, and dose of curcumin. Nevertheless these results provide insight for future studies with larger samples, and multiple curcumin dosages to investigate if different curcumin regimens can lead to statistically different interleukin levels when compared to a control and placebo.

A sensitive gas chromatographic/mass spectrometric method for the resolution and quantification of ethosuximide enantiomers in biological fluids.

A modified specific, sensitive and reproducible chiral gas chromatographic (GC) method for the resolution and quantification of ethosuximide enantiomers in urine and plasma was developed. The samples were extracted by liquid-liquid extraction, using diethylether and the enantiomers were separated and quantified on a chiral gas chromatographic column (25QC2 / CYDEX- beta 0.25). The method involved the use of GC/MS instrumentation for the acquisition of data in the electron impact selective-ion monitoring mode, collecting ions characteristic of both ethosuximide and alpha, alpha - dimethyl - beta - methylsuccinimide, the internal standard and of mass-to-charge ratio (m/z) exactly equal to 55 and 70 units. The limit of quantitation of the method was 2.5 microg/ml for both urine and plasma with both enantiomers. The method proved to be linear, precise and reproducible in the 5-300 microg/ml concentration range for urine samples and in the 10-250 microg/ml concentration range for plasma samples. Future research work envisaged the application of this method in pharmacokinetic and pharmacodynamic studies.

A novel chiral GC/MS method for the analysis of fluoxetine and norfluoxetine enantiomers in biological fluids.

Aims: A novel robust chiral gas chromatographic/mass spectrometric (GC/MS) method for the separation and measurement of fluoxetine and norfluoxetine enantiomers in urine and plasma was developed. Materials and Methods: The drug was extracted from the samples by a liquid–liquid technique, using chloroform, and the enantiomers were separated and measured on a chiral gas chromatographic column (HYDRODEX β-6TBDM®, 0.25 μm × 0.25 mm × 50 m). GC/MS instrumentation was used for the acquisition of data in the electron impact selective-ion monitoring mode. Results: The ions chosen were of a mass-to-charge ratio (m/z) exactly equal to 44 units, in order to measure fluoxetine enantiomers, 134 units in order to measure norfluoxetine enantiomers, and 58 units in order to measure diphenhydramine, the internal standard. The method was found to be linear and reproducible in the 50–500 ng/mL concentration range for both urine samples and plasma samples and for both fluoxetine and norfluoxetine, with correlation coefficients ranging between 0.994 and 0.997. Conclusions: This methodology has an enormous potential for application in pharmacokinetic studies of the enantiomers of fluoxetine

Knowledge and sources of information about medicines among adolescents in Malta

Objective To investigate knowledge of medicines and sources of information about medicines among adolescents in Malta. Methods A self-administered questionnaire was used to survey knowledge of medicines and information sources among adolescents attending secondary schools in Malta. A random stratified sample design generated a sample size of 514 students. Knowledge of medicines was investigated by questions that included topics about the efficacy of medicines, proper communication during a medical consultation, the safety of medicines, antibiotic use and pictograms. Results The analytical sample, of which 53.8% were girls, was made up of 474 students, aged 1416 years. The students obtained a mean score of 22.92 points (SD = 4.31) out of a maximum of 32 points for medicine knowledge. More than 30.0% of the respondents did not mark the correct answer for 40.6% of the questions that investigated knowledge of medicines. The family physician, community pharmacist and parents were the sources of information that were mostly cited. A proportion of 4.4% had obtained information from the teacher. A quarter of the respondents (24.7%) had obtained information from friends/schoolmates, young relatives or the media, generally television (17.3%). Conclusion Although the level of knowledge about medicines among this study sample of Maltese students was good, there appeared to be particular misconceptions with regard to important aspects associated with the proper use of medicines. These findings highlight the need to educate adolescents about the proper use of medicines. The most important information providers about medicines appeared to be the physician, pharmacist and parents. It is being suggested that education campaigns should be organized in order to help parents guide adolescents on how to use medicines appropriately. In addition, adolescents would benefit if more information about the proper use of medicines would be disseminated by means of television programs and school-based health education curricula.

The metabolism of ethosuximide

SummaryThe metabolism of the antiepileptic drug ethosuximide (3-ethyl-3-methylpyrollidine-2,5-dione) (I) in animals and humans is reviewed. Chiral aspects of the metabolism of ethosuximide are discussed. Clarification of the precise nature of the hydroxymetabolites of ethosuximide is presented.

Are we failing to provide adequate rescue medication to children at risk of prolonged convulsive seizures in schools

Objective This paper explores the issues that arise from the discussion of administering rescue medication to children who experience prolonged convulsive seizures in mainstream schools in the UK. Situation analysis Current guidelines recommend immediate treatment of children with such seizures (defined as seizures lasting more than 5 min) to prevent progression to status epilepticus and neurological morbidity. As children are unconscious during prolonged convulsive seizures, whether or not they receive their treatment in time depends on the presence of a teacher or other member of staff trained and able to administer rescue medication. However, it is thought that the situation varies between schools and depends mainly on the goodwill and resources available locally. Recommendations A more systematic response is needed to ensure that children receive rescue medication regardless of where their seizure occurs. Possible ways forward include: greater use of training resources for schools available from epilepsy voluntary sector organisations; consistent, practical information to schools; transparent guidance outlining a clear care pathway from the hospital to the school; and implementation and adherence to each childs individual healthcare plan. Implications Children requiring emergency treatment for prolonged convulsive seizures during school hours test the goals of integrated, person-centred care as well as joined-up working to which the National Health Service (NHS) aspires. As changes to the NHS come into play and local services become reconfigured, every effort should be made to take account of the particular needs of this vulnerable group of children within broader efforts to improve the quality of paediatric epilepsy services overall.

Health complaints and use of medicines among adolescents in Malta

Objective To investigate self-reported health complaints and the use of medicines among adolescents in Malta. Methods A self-administered questionnaire was used to survey self-reported health complaints, the use and the sources of medicines that had been accessed, during the preceding 3 months among adolescents attending secondary schools in Malta. A stratified random sample design generated a sample size of 514 students. The health complaints and use of medicines that were investigated included ear problems/hay fever/cold/cough, headache, skin problems, sport injuries, indigestion/diarrhoea/constipation, eye problems and menstrual pain (for girls). The use of vitamins and antibiotics was also investigated. Results A total of 477 students participated in the final data collection. Correct information was submitted by 474 students, (aged 14-16 years), who formed the analytical sample, of which 53.8% were girls. The students reported a mean number of 2.70 (SD = 1.39) out of a total of 7 health complaints and 90.3% reported using at least 1 medicine during the preceding 3 months. The community pharmacy was cited as the most commonly accessed source for most of the medicines that were investigated. A proportion of 24.3% of the students had taken at least 1 medicine without adult guidance during the preceding 3 months. Almost 10% of those who had taken antibiotics, had accessed them from the home medicine cabinet. Conclusion A high proportion of adolescents in Malta reported the use of medicines to alleviate the symptoms of common health complaints. This result is concordant with previous research carried out in the United Kingdom, Germany, Slovakia and Kuwait. A considerable proportion of students in this study had obtained medicines without adult guidance and accessed antibiotics from the home medicine cabinet. This highlights the importance of carefully designed education programs for adolescents that will integrate information about the proper use of medicines.

Interactions between valproic acid and quetiapine/olanzapine in the treatment of bipolar disorder and the role of therapeutic drug monitoring.

The anticonvulsant valproic acid and the atypical antipsychotics olanzapine and quetiapine provide synergistic mood‐stabilising, antidepressant and antipsychotic activities in the treatment of bipolar and schizoaffective disorders. Existing literature shows that pharmacokinetic and pharmacodynamics drug–drug interactions (DDIs) possibly occur with the use of such a combination. Clinical reports of a possible interaction between the drugs leading to an increased risk of adverse drug reactions have also emerged. The main objective of this paper is to review the incidence of DDIs between the anticonvulsant and the antipsychotics, to postulate the possible mechanisms of the interaction and to establish whether certain target populations are at an increased susceptibility to such interactions. The usefulness of therapeutic drug monitoring (TDM) of the antipsychotics to monitor for an interaction was also assessed. A systematic database search was carried out using the search engine provided by PubMed using the following key words: olanzapine, quetiapine, valproic acid, pharmacokinetic drug–drug interaction, bipolar disorder, therapeutic drug monitoring.