Impact of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions in individuals living with epilepsy: a case-control study.

Epilepsy is characterized by repeated seizure activity. Valproate, a commonly used antiepileptic drug, shows large inter-individual variation in plasma valproic levels and causes many adverse drug reactions. Aim: To find the influence of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions and plasma valproic acid levels in people with epilepsy. Methods: We recruited 158 people with epilepsy (79 cases and 79 controls) from an epilepsy clinic. Steady-state plasma valproic acid levels were measured using liquid chromatography-mass spectrometry and genotyping of CYP2C9 variants was carried out with helps of RT-PCR. Results: The presence of a mutant heterozygous genotype showed an odds ratio (OR) of 2.82 (95% CI: 1.10-7.24) and the adjusted OR was 5.39 (95% CI: 1.69-17.16). There was no significant difference in steady-state plasma valproate concentration between genotypes. Conclusion: The presence of a mutant heterozygous CYP2C9 genotype possesses five-times the risk of developing adverse drug reactions to valproate in people with epilepsy.

Atomoxetine Does Not Improve Complex Attention in Idiopathic Parkinson's Disease Patients with Cognitive Deficits: A Meta-Analysis.

OBJECTIVES: To evaluate the effects of atomoxetine on complex attention and other neurocognitive domains in idiopathic Parkinson's disease (PD). METHODS: Interventional trials reporting changes in complex attention and other neurocognitive functions (Diagnostic and Statistical Manual of Mental Disorders-5) following administration of atomoxetine for at least 8 weeks in adults with idiopathic PD were included. Effect sizes (Cohen's d), the standardized mean difference in the scores of each cognitive domain, were compared using a random-effects model (MetaXL version 5.3). RESULTS: Three studies were included in the final analysis. For a change in complex attention in PD with mild cognitive impairment (MCI), the estimated effect size was small and nonsignificant (0.16 (95% CI: -0.09, 0.42), n = 42). For changes in executive function, perceptual-motor function, language, social cognition, and learning and memory, the estimated effect sizes were small and medium, but nonsignificant. A deteriorative trend in executive function was observed after atomoxetine treatment in PD with MCI. For a change in global cognitive function in PD without MCI, the estimated effect size was large and significant. CONCLUSION: In idiopathic PD with MCI, atomoxetine does not improve complex attention. Also, a deteriorative trend in the executive function was noted.

Hepatitis B Vaccine and Immunoglobulin: Key Concepts.

Hepatitis B virus (HBV) immunization is safe and has been accepted worldwide as a routine practice. The target of such vaccination is to induce the immune response in the host, resulting in the prevention of replication of HBV. There are several immunological and clinical factors which determine the clinical efficacy and safety of the HBV vaccine. In this article we have highlighted the response of the host immune system to HBV vaccination (immunogenicity), efficacy, and safety of the vaccine, issues with booster dosing, paths of development (preclinical and clinical) of the HBV vaccine, novel and upcoming strategies for improvement of HBV vaccination, and the concept of therapeutic HBV vaccination. The different aspects and regulatory recommendations pertaining to HBV vaccine development are also discussed. The new strategies for improvement of HBV vaccination include pre-S1 and pre-S2 portions of the HBV surface antigen, increasing the antigen dose, accelerated vaccination schedules, alternative vaccination route, use of adjuvants like immunostimulatory DNA sequences, etc. Therapeutic vaccination is being explored for initiation of a multifunctional and multispecific T cell response against the major HBV antigens and also effective activation of humoral immunity for viral control.