A European approach to categorizing medicines for fitness to drive: outcomes of the DRUID project

AIMS

To illustrate (i) the criteria and the development of the DRUID categorization system, (ii) the number of medicines that have currently been categorized, (iii) the added value of the DRUID categorization system and (iv) the next steps in the implementation of the DRUID system.

METHODS

The development of the DRUID categorization system was based on several criteria. The following steps were considered: (i) conditions of use of the medicine, (ii) pharmacodynamic and pharmacokinetic data, (iii) pharmacovigilance data, including prevalence of undesirable effects, (iv) experimental and epidemiological data, (v) additional data derived from the patient information leaflet, existing categorization systems and (vi) final categorization. DRUID proposed four tiered categories for medicines and driving.

RESULTS

In total, 3054 medicines were reviewed and over 1541 medicines were categorized (the rest were no longer on the EU market). Nearly half of the 1541 medicines were categorized 0 (no or negligible influence on fitness to drive), about 26% were placed in category I (minor influence on fitness to drive) and 17% were categorized as II or III (moderate or severe influence on fitness to drive).

CONCLUSIONS

The current DRUID categorization system established and defined standardized and harmonized criteria to categorize commonly used medications, based on their influence on fitness to drive. Further efforts are needed to implement the DRUID categorization system at a European level and further activities should be undertaken in order to reinforce the awareness of health care professionals and patients on the effects of medicines on fitness to drive.     

Clinical, brain electric earth map, endothelin and transcranial ultrasonic Doppler findings after hyperbaric oxygen treatment for severe brain injury

Objective　To analyze the effect and mechanism of hyperbaric oxygen (HBO) treatment for severe brain injury (SBI). Methods　Fifty-five patients were divided into a treatment group of 35 patients and a control group of 20 patients. We observed the alterations of clinical, brain electric earth map (BEAM), endothelin (ET) and transcranial ultrasonic Doppler (TCD) findings before and after HBO treatment as well as outcome. Results　In the treatment group, Glasgow coma scale, BEAM and outcome improved after HBO treatment; compared with that of the control group, it showed a significant difference. After one course of treatment, treatment group ET was reduced from 91.24±12.18?ng/L to 68.88±14.37?ng/L (P<0.01); in control group, ET was reduced from 90.78±15.71?ng/L to 83.12±12.22?ng/L, with a statistically significant difference (P<0.05). TCD records of MCA mean velocity (Vm) was reduced from 64.2±4.8?cm/s to 51.6±4.2?cm/s (P<0.01), and a decrease in MCA systolic velocity (Vs) and pulse index (PI) values was statistically significant (P<0.01). Conclusion　HBO treatment can improve the clinical, BEAM and outcome of severely brain injured patients, by decreasing acute stage ET and improving the blood velocity of MCA and decreasing cerebral vascular resistance. HBO treatment can reduce cerebral vascular spasms, cerebral ischemia and hypoxia. One of the important mechanisms of HBO treatment for severe brain injury is the lowering of intracranial pressure.     

Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.      

Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

The epilepsies are a group of disorders characterised by recurrent seizures caused by episodes of abnormal neuronal hyperexcitability involving the brain. Up to 60 million people are affected worldwide and genetic factors may contribute to the aetiology in up to 40% of patients. The most common human genetic epilepsies display a complex pattern of inheritance. These are categorised as idiopathic in the absence of detectable structural or metabolic abnormalities. Juvenile myoclonic epilepsy (JME) is a distinctive and common variety of familial idiopathic generalised epilepsy (IGE) with a prevalence of 0.5- 1.0 per 1000 and a ratio of sibling risk to population prevalence (lambda(s)) of 42. The molecular genetic basis of these familial idiopathic epilepsies is entirely unknown, but a mutation in the gene CHRNA4, encoding the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (nAChR), was recently identified in a rare Mendelian variety of idiopathic epilepsy. Chromosomal regions harbouring genes for nAChR subunits were therefore tested for linkage to the JME trait in 34 pedigrees. Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005). This major locus contributes to genetic susceptibility to JME in a majority of the families studied.      

New concepts in measles virus replication: getting in and out in vivo and modulating the host cell environment

This review focuses on new concepts important for the understanding of the pathogenesis of measles virus. First the requirement for specific entry receptors restricts the cell types that measles can enter during the initial stages of infection in the human host. Recently, the paradigm for measles has shifted from an epithelial infection similar to that caused in the respiratory tract by other members of the paramyxoviruses to one which displays more similarity to the infection of the immune system by HIV-1, though the route of infection is different. Secondly we review the role of host proteins that support viral replication as well as those that modify the cellular environment in order to promote measles virus replication. The role of specific virus proteins in the anti-antiviral response is also reviewed. Measles virus counteracts all pathways known to induce interferon synthesis as well as signalling by interferons, exemplifying the importance of these in the virulence/attenuation of the virus. We conclude that only studies in relevant animal model systems or humans or in vitro or ex vivo studies of relevant cell types and tissues will bring us closer to an understanding of the pathogenesis of the virus, factors that have often been overlooked in past studies.