of about 93%. Students reported that in 40% of cases they observed a suspected serious ADR, in almost 60% a suspected non-serious. ADR and 66% a side ...
Clinical Therapeutics Background: Disseminated intravascular coagulation (DIC) is a serious syndrome occurring in a variety of clinical conditions, including drug therapy. We aimed to investigate the association between several drug classes use and the onset of DIC using the reports of suspected adverse drug reactions (ADRs) collected in the WHO database. Methods: Data were obtained from VigiBase, the WHO Global Individual Case Safety Report (ICSR) database, at the Uppsala Monitoring Centre. We collected all suspected reports of drug-related DIC between 1968 to September 2015 and classified in VigiBase according to MedDRA (Medical Dictionary for Regulatory Activities) term “disseminated intravascular coagulation”. A disproportionality analysis using reporting odds ratio (ROR) with 95% confidence interval and p value ≤ 0.05 was performed. Results: After exclusion of duplicates, 4653 reports of drug-associated DIC collected in the VigiBase, corresponding to 1111 drugreaction pairs, were selected. Among these, DIC was significantly (ROR > 1) associated with 88 drugs. According to ATC classification system, drugs more frequently associated to DIC were antineoplastic agents, antithrombotic agents and antibacterials for systemic use. Furthermore, drugs that were most frequently reported and, at the same time, were statistically significant were paracetamol (n= 117) ROR= 1.21 (CI 95% 1.00 – 1.48), dabigatran (94) ROR= 1.34 (1.08 – 1.67), oxaliplatin and bevacizumab both with 75 reports and ROR= 1.77 (1.38 – 2.27) and 2.02 (1.57 – 2.61), respectively. For all these drugs, DIC was an unknown ADR. Conclusions: The high number of drugs involved and the great number of fatal outcomes (more than 50%) underline the importance to evaluate this condition such as an ADR that might occur during therapy. Clinicians should be aware of the importance to report every case of suspected drug-related DIC and regulatory authorities should update the SPCs (Summary of Product Characteristics) of several drugs accordingly.
The Determinants of Reporting of Adverse Drug Reactions by Nursing And Medicine Students In Italy: A CrossSectional, Observational, Web-Based Questionnaire Study A. Nappo1; L. Gasperoni2*; S. Grandi2; G. Bonaldo2; S. Scalorbi3; D. Di Lorenzo3; A. Vaccheri2; and D. Motola2 1 Aviano National Cancer Institute, Aviano, Italy; 2University of Bologna, Bologna, Italy; and 3University Hospital S. OrsolaMalpighi, Bologna, Italy Background: Adverse drug reactions (ADRs) are a major health problem in terms of mortality, morbidity and costs. Under-reporting of ADRs is an emerging problem that reduces the potential of pharmacovigilance. The Inman model identifies the determinants of the ADR reports and literature provides the elements of the attitudes of health professionals related to the same reports. The aim of this research was to identify the determinants of the ADR reports in the nursing and medicine students in Italy. Methods: The research was conducted through an observational cross-sectional, questionnaire-based study. The sample was represented by nursing (third year of course) and medicine (sixth year of course) students on a voluntary basis. The self-produced and prevalidated questionnaire, relating to pharmacovigilance knowledge and determinants of the ADR reports, was anonymous and administered via web. Results: 118 students completed the questionnaire. The first determinant hindering the reports was lethargy (reporting complex method and lack of knowledge of the use of information) with a frequency of about 93%. Students reported that in 40% of cases they observed a suspected serious ADR, in almost 60% a suspected non-serious ADR and 66% a side effect, but only 6 students reported an ADR
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(5%). Less than 50% of students reported the presence of a course on pharmacovigilance in their own course of study. 47,5% of the sample reported to know the objectives of pharmacovigilance. Conclusions: Among the Italian nursing and medicine students the problem of under-reporting is visible through the data from this study. Lethargy is the main determinant leading students to underreport suspected ADRs. Training on pharmacovigilance should be included in all basic training of health professionals and it is crucial to give practical examples to students to enhance their knowledge and their confidence in reporting ADR.
CYP4F2 Genotype Affects Circulating Plasma Vitamin K Concentration In Children on Chronic Warfarin Therapy E. Kampouraki1; P. Avery2; T. Biss3; and F. Kamali1 1 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; 2School of Mathematics & Statistics, Newcastle University, Newcastle upon Tyne, United Kingdom; and 3Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom Background: Vitamin K is essential for not only the activation of clotting proteins, but also the biosynthesis of osteocalcin in bones and the bioactivation of Matrix-Gla protein (MGP) in the vasculature. Recent studies suggest that cytochrome p450 CYP4F2 enzyme is involved in the ω -hydroxylation of vitamin K. Genetic polymorphism in CYP4F2 is thus likely to affect vitamin K systemic availability, which may in turn affect bone development and vascular health in children on long-term anticoagulation therapy with warfarin. Methods: Plasma vitamin K level was determined according to an established high performance liquid chromatography (HPLC) method. Plasma samples belonging to 110 children on warfarin therapy, recruited as part of a previous warfarin pharmacogenetics study, were available for HPLC analysis. Demographic and clinical data as well as CYP2C9, VKORC1 and CYP4F2 genotypes for the children were available. Results: Plasma vitamin K was detectable (> 10 pg/ml) in only 19.6% of the study population (range 10.1 - 765.0 pg/ml). 76.2% of the children with plasma vitamin K levels above 10 pg/ml had at least one variant CYP4F2 allele. There was a statistically significant difference (p= 0.012; chi squared test) in the frequency of CYP4F2 variant allele carriers between the group of children with plasma vitamin K> 10 pg/ml and the group with plasma vitamin K
