PubMed Health⌕ Search

Biomedical subjects

Abdelilah Abouelfath

Publications and source records attributed to Abdelilah Abouelfath.

7 recordsLinked to original sources

Myocardium distribution of sertindole and its metabolite dehydrosertindole in guinea-pigs.

Sertindole, like other atypical antipsychotics, has been shown to increase the action potential duration and QT interval in a concentration dependent manner, in in vitro electrophysiological studies. However, this does not always translate into increased duration of the QT interval, increased risk of torsade de pointes or sudden death in clinical practice. The reasons for these apparent discrepancies are unclear and many studies have underscored the importance of the interpretation of in vitro electrophysiological data in the context of other pharmacodynamic (e.g. cardiac ion channels target, receptor affinity) and pharmacokinetic parameters (total plasma drug concentration and drug distribution). To address the possible relevance of the concentrations used in experimental studies, the myocardium distribution of sertindole and its metabolite was determined after single and repeated intraperitoneal administration to guinea-pigs. The data suggest that the plasma concentration appears to predict the concentration in the myocardium and that the myocardium concentrations of sertindole are 3.1 times higher than plasma concentrations. Using these data, the relevance of in vitro electrophysiological studies to clinical plasma concentrations has been appraised.

Animals↗

Surveillance of adverse effects during a vaccination campaign against meningitis C.

OBJECTIVE: To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. METHODS: A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrénées atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. RESULTS: The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. CONCLUSIONS: This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.

Adolescent↗

Psychiatric disorders and their comorbidity in subjects with parasuicide by intentional drug overdose: prevalence and gender differences.

The aims of the present study were to assess the prevalence and comorbidity of psychiatric disorders in subjects with intentional drug overdose and to explore whether there were gender differences in prevalence and comorbidity. A standardized psychiatric evaluation was performed in 100 randomly selected subjects, 18 years old and older, with intentional drug overdose referred to an emergency department. The prevalences of psychiatric morbidity and comorbidity were very high in both genders: 88% presented with at least one psychiatric diagnosis, and three-quarters presented with comorbid psychiatric disorders. Affective and anxiety disorders were the most prevalent diagnoses. One patient out of three presented with alcohol or substance misuse. Compared to females, males suffered five times more often from substance misuse and three times more often from psychotic syndrome and were three times less likely to present with anxiety disorder. When subjects are referred to hospital for intentional drug overdose, medical management should systematically involve a psychiatric assessment in order to identify not only affective and anxiety disorders, but also alcohol and substance misuse, due to the high prevalence of these disorders, especially in male subjects.

Adolescent↗

An easy to use method to approximate Poisson confidence limits.

Despite the ever larger choice of softwares and statistical packages allowing fast and accurate computation of binomial and Poisson confidence limits, there is always a need for a simple and reliable formula allowing non-computerized computations. The method proposed in this paper is derived from the Freeman and Tukey's variance stabilizing transformation for a random Poisson variable and adjusted for giving the best fit with the exact Poisson values. Despite its simplicity, allowing its use in any circumstances, this method provides very satisfactory results and a much better fit than classical formula based on the normal approximation, even if a continuity correction is used. It allows computation of Poisson confidence limits both for count or rates and proportions.

Biometry↗

Determination of myocardium to plasma concentration ratios of five antipsychotic drugs: comparison with their ability to induce arrhythmia and sudden death in clinical practice.

Reviewing available data shows that most of antipsychotic drugs are associated with arrhythmia and sudden death. Experimental studies have shown a HERG channel blockade, a dose-dependent increase in duration of action potential or of QT interval, with various degrees of indicators of serious arrhythmogenicity. However, it seems difficult to relate these in vitro and in vivo preclinical models to clinical findings, in part, because the relationship between concentrations used and in vivo tissue concentrations during treatment in man is not known. Consequently, we established the myocardium to plasma concentration ratios for a series of antipsychotic drugs by intraperitoneal administration of different level doses to the guinea pig. Then, we compared these values to their ability to induce arrhythmia or torsade de pointes in clinical practice. The myocardium to plasma concentration ratios were 2.2 for clozapine, 2.7 for olanzapine, 3.1 for sertindole, 4.5 for risperidone, and 6.4 for haloperidol. These data suggest that when the ratio is higher than 4, arrhythmia and sudden death may be expected. On the contrary, when the ratio is less than 3, little effect may be predicted. These results underscore the importance of interpreting HERG channel data and electrophysiological data in the context of other pharmacokinetic parameters such as myocardium to plasma distribution.

Animals↗

A multicenter cluster randomized controlled trial of strategies to improve thyroid function testing.

OBJECTIVES: This project aimed to compare the independent and combined effectiveness of two implementation interventions of guidelines for ordering thyroid function tests: a Memorandum Pocket Card (MPC) and a Test Request Form (TRF). RESEARCH DESIGN: Intervention groups were wards. The study used an experimental 2*2 factorial design with matching hospitals according to size and activity and wards according to preintervention appropriateness for test ordering. Four ward groups were established: the dual intervention group, the order form group, the pocket card group and the control group. Physicians in all groups received guidelines and were invited to a local information meeting. MEASURES: The main outcome measure of effectiveness was the Guideline Conformity Rate (GCR). RESULTS: Six hospitals participated in the study (two middle-sized hospitals, two small-sized hospitals and two psychiatric hospitals). A total of 1412 orders for thyroid function tests were collected. GCR was 78% in the dual intervention group, 83% in the order form group, 73% in the pocket card group and 62% in the control group. The interaction between TRF and MPC was not significant (beta = -0.70; P = 0.21). Compared with simple information, TRF was effective in increasing GCR (OR, 2.65; 95% CI, 1.52-4.62), unlike MPC (OR, 1.28; CI, 0.75-2.19). CONCLUSIONS: Using a robust design, our study shows the greater effectiveness of TRF than MPC and their association in implementing thyroid function test guidelines.

Adult↗

[Real-life use of inhaler devices for chronic obstructive pulmonary disease in primary care].

The correct use of inhalation devices is an inclusion criterion in many comparative studies. However, patients can make errors, thus compromising the effectiveness of their own inhaler. The aim of the study is to evaluate inhaler use by patients with chronic obstructive pulmonary disease (COPD) [n = 984]. General practitioners assessed inhalation technique, using a specific checklist previously established for each inhaler model (Aerolizer, Autohaler, Diskus, a pressurised metered-dose inhaler (pMDI) or a Turbuhaler). A total of 24% of the patients using a pMDI did not make an error compared with 34-40% of those using breath-actuated devices. The frequency of critical errors varied according to the device: 11.5-14.9% of the subjects using an Aerolizer, Autohaler or Diskus versus 37.4% and 38.1% of the patients using a pMDI and a Turbuhaler, respectively. The proper use of the Turbuhaler is often overestimated (24.7%) compared with the pMDI (2.1%). The development of educational programmes for patients and prescribers is needed to improve the management of COPD.

Aged↗