Is reporting rate a good predictor of risks associated with drugs?

AIMS: Uncertainty as to relative under-reporting plagues the comparisons of spontaneous reporting rates as a tool for decision-making in pharmacovigilance. However, it is generally accepted that under-reporting should be reasonably similar for similar drugs sharing the same indication, country and period of marketing. To test this, we compared the adverse drug reaction reporting rates to the French regional pharmacovigilance centres for six pairs of identical drug marketed at the same time by different companies under different brand names (co-marketing). METHODS: All reaction reports were related to sales, to compute reporting rate; within each pair, the reporting rate ratio and its confidence interval were calculated. RESULTS: The rate ratios were all between 0.76 and 1.33. Two of them were significantly different from 1 (1.28; 95% C.I. [1.01; 1.60] and 1.33; 95% C.I. [1.06; 1.74]). CONCLUSIONS: These small differences in reporting rates would not warrant regulatory action and support the usual assumption of similar reporting for similar drugs.     

Mandatory reporting of domestic violence: the law, friend or foe?

Should physicians be mandated to report domestic violence involving a competent adult patient regardless of whether or not he or she consents to the report? This is a complex ethical and moral issue; in some states such as California, Colorado, Kentucky, New Hampshire, Rhode Island and New Mexico it has become a legal one as well. The Federal health privacy regulation instituted in the Health Insurance Portability and Accountability Act of 1996 (HIPAA) addresses issues of privacy protection for survivors of domestic violence, but it does not preempt those state laws that are less (or more) protective of patient privacy. In the above states, physicians and/or health care providers are mandated to report acts of domestic violence to an agency, under their own circumstances, regardless of whether the physician or health care worker believes that reporting the violence is in the patient's best interest or not. But is mandatory reporting truly "good" or "bad" for the patient, the physician or society as a whole? This article explores the laws and the evidence (including evidence-based research) surrounding the issue of mandatory reporting of domestic violence when it pertains to a competent adult.     

Lipoic acid - the drug of the future?

Numerous experimental and clinical studies proved efficiency of treatment with lipoic acid-containing drugs in diseases, in which pro- and antioxidant balance is disrupted (diabetes, neurodegenerative diseases, acquired immune deficiency syndrome (AIDS), tumors, etc.). Efficiency of lipoate has been attributed to unique antioxidant properties of lipoate/dihydrolipoate system, its reactive oxygen species (ROS) scavenging ability and significant effect on the tissue concentrations of reduced forms of other antioxidants, including one of the most powerful, glutathione (thus lipoate is called an antioxidant of antioxidants). Moreover, analysis of literature data suggests participation of lipoic acid in processes of cell growth and differentiation. This fact can be crucial to clinical practice, however, this problem requires further studies.     

Are cytochrome b gene mutations the only cause of atovaquone resistance in Pneumocystis ?

There is evidence that exposure of the opportunistic pathogen Pneumocystis to atovaquone enhances the development of resistance to the drug. Atovaquone is a structural analog of ubiquinone, which binds to the mitochondrial cytochrome bc(1) complex and inhibits electron transport. Like the parasites Plasmodium and Toxoplasma, atovaquone resistance can result from mutations in the cytochrome b gene of Pneumocystis. However, atovaquone resistance cannot be explained by cytochrome b gene mutations in all cases. The discovery that atovaquone also inhibits biosynthesis of ubiquinone in P. carinii may unfold other mechanisms by which drug resistance develops.     

Squalamine: a polyvalent drug of the future?

The purpose of this mini-review is to summarize and highlight the different advances in our understanding of the antimicrobial and antiangiogenic activity of squalamine, a cationic steroid isolated in 1993 from the dogfish shark Squalus Acanthias. Indeed, squalamine has shown to be useful for the treatment of important diseases such as cancers (lung, ovarian, brain and others), age-related macular degeneration (AMD) and the control of body weight in man. All these results led to a question: could we consider squalamine as a polyvalent drug of the future?     

Oleamide: a member of the endocannabinoid family?

The fatty acid amide class of compounds, which include the endocannabinoid anandamide and the sleep-inducing compound oleamide, have been shown in vitro to have a multiplicity of actions upon different neurochemical systems. In the present issue of this journal, Leggett et al present data indicating that oleamide functionally activates CB(1) cannabinoid receptors in vitro. The significance of their finding is discussed in this commentary.     

Is aripiprazole the only choice of treatment of the patients who developed anti-psychotic agents-induced leucopenia and neutropenia? A case report

Leucopenia and neutropenia could be side effects of anti-psychotic drugs, especially clozapine. However, there is evidence that other anti-psychotics can cause leucopenia and neutropenia. We present the clinical follow-up and treatment process of a patient, who had initially developed quetiapine and amisulpride related neutropenia, but not with aripiprazole.     

Psychoneurendocrinology: a science of the past or a new pathway for the future?

Psychoneuroendocrinology is a branch of neuroscience that developed in the beginning of the last century, which investigates the possibility of a cause-effect link between endocrinopathies and mental disorders - with these studies ending in negative results. Psychoneuroendocrinology was then used as a methodological approach for the investigation of neurotransmitter function, on the basis of the observation that neurotransmitters regulate neurohormone and peripheral hormone secretions. Data were obtained for hypothalamic noradrenergic, serotoninergic, dopaminergic, gabaergic and acetylcholinergic functions, which could not be automatically extended to higher brain centers whose impairments might be etiopathogenetically involved in the development of mental disorders. Future studies should focus on new methodological approaches to brain biochemistry, on investigation of genetic, molecular biology, brain imaging, psychoneuroimmunoendocrinology, neuropeptide and neurosteroid secretion in relation to brain endocrine function in mental diseases.     

How useful is linear regression analysis in detecting the existence of dose-response relationships in large-scale epidemiologic studies when only a fraction of the population is sensitive? The case of methylmercury

The existence of a dose response in epidemiologic studies is generally determined from the linear regression slope after controlling for covariates. This approach assumes the entire population is equally sensitive to the toxicant and that response is a function only of dose and a random error function. However, sensitive subpopulations have been identified for a variety of toxicants possibly including methylmercury (MeHg). The study of MeHg exposure in the Seychelles Islands has failed to find significant effects (dose-response slope not significantly different from zero) while other studies have found such effects. Using data on the error function in developmental test scores and MeHg exposure distributions from that study, and assuming plausible dose-response relationships for sensitive subpopulations, we conducted Monte-Carlo simulations of the power of linear regression analysis to detect a dose-response relationship from the total sample (n=700), and to compare dose-response slopes in the total and sensitive populations. Linear regression did not reliably detect a dose-response relationship for most scenarios when sensitives were 5% of the total and for some scenarios when sensitives were 10% of the total. We also found that the dose-response slope for the total population underestimated the sensitive dose-response slope in all cases by about an order of magnitude. These findings may have important implications for detection and quantification of dose-response relationships from epidemiologic studies.