Huoi C, Casalegno JS, Bénet T, Neuraz A, Billaud G, Eibach D, Mekki Y, Rudigoz R, Massardier J, Huissoud C, Massoud M, Gaucherand P, Claris O, Gillet Y, Floret D, Lina B, Vanhems P.
A report on the large measles outbreak in Lyon, France, 2010 to 2011. Euro Surveill 2012;17(36):20264.
AbstractIn 2010 and 2011, the city of Lyon, located in the Rhône-Alpes region (France), has experienced one of the highest incidences of measles in Europe. We describe a measles outbreak in the Lyon area, where cases were diagnosed at Lyon University hospitals (LUH) between 2010 and mid-2011. Data were collected from the mandatory notification system of the regional public health agency, and from the virology department of the LUH. All patients and healthcare workers who had contracted measles were included. Overall, 407 cases were diagnosed, with children of less than one year of age accounting for the highest proportion (n=129, 32%), followed by individuals between 17 and 29 years-old (n=126, 31%). Of the total cases, 72 (18%) had complications. The proportions of patients and healthcare workers who were not immune to measles were higher among those aged up to 30 years. Consequently, women of childbearing age constituted a specific population at high risk to contract measles and during this outbreak, 13 cases of measles, seven under 30 years-old, were identified among pregnant women. This study highlights the importance of being vaccinated with two doses of measles vaccine, the only measure which could prevent and allow elimination of the disease.
Bauer-Mehren A, van Mullingen EM, Avillach P, Carrascosa MDC, Garcia-Serna R, Piñero J, Singh B, Lopes P, Oliveira JL, Diallo G, Helgee EA, Boyer S, Mestres J, Sanz F, Kors JA, Furlong LI.
Automatic filtering and substantiation of drug safety signals. PLoS Comput Biol 2012;8(4):e1002457.
AbstractDrug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions.
Pariente A, Avillach P, Salvo F, Thiessard F, Miremont-Salamé G, Fourrier-Reglat A, Haramburu F, Bégaud B, Moore N.
Effect of competition bias in safety signal generation: analysis of a research database of spontaneous reports in France. Drug Saf 2012;35(10):855-64.
AbstractBACKGROUND: Automated disproportionality analysis of spontaneous reporting is increasingly used routinely. It can theoretically be influenced by a competition bias for signal detection owing to the presence of reports related to well-established drug-event associations.
OBJECTIVE: The aim of the study was to explore the effects of competition bias on safety signals generated from a large spontaneous reporting research database.
METHODS: Using the case/non-case approach in the French spontaneous reporting research database, which includes data of reporting in France from January 1986 to December 2001, the effects of the competition bias were explored by generating safety signals associated with six events of interest (gastric and oesophageal haemorrhages, central nervous system haemorrhage and cerebrovascular accidents, ischaemic coronary disorders, migraine headaches, muscle pains, and hepatic enzymes and function abnormalities) before and after removing from the database reports relating to drugs known to be strongly associated with these events, whether they constituted cases or non-cases. As this study was performed on a closed database (last data entered 31 December 2001), potential signals unmasked by removal were considered as real signals if no or only incomplete knowledge about the association was available from the literature before 1 January 2002.
RESULTS: For gastric and oesophageal haemorrhages, after removing reports involving antithrombotic agents or NSAIDs, three potential signals were unmasked (prednisone, rivastigmine and isotretinoin). For central nervous system haemorrhage and cerebrovascular accidents, after removing reports involving antithrombotic agents, three potential signals were unmasked (ethinylestradiol, interferon-α-2B and methylprednisolone). For ischaemic coronary disorders, after removing reports involving anthracyclines, bleomycine, anti-HIV drugs or triptans, one potential signal was unmasked (ondansetron). For migraine headaches, after removing reports involving nitrates, calcium channel blockers, opioid analgesics or intravenous immunoglobulins, six potential signals were unmasked (ammonium chloride, leflunomide, milnacipran, montelukast, proguanil and pyridostigmine). For muscle pains, after removing reports involving statins or fibrates, seven potential signals were unmasked (hydroxychloroquine, lactulose, levodopa in combination with dopadecarboxylase inhibitor, nevirapine, nomegestrol, ritonavir and stavudine). Finally, for hepatic enzymes and function abnormalities, after removing reports involving NSAIDs, anilides, antituberculosis drugs, antiepileptics, ketoconazole, tacrine, or amineptine, two potential signals were unmasked (caffeine, metformin). Of all these unmasked potential signals, ten appeared non/incompletely documented as at 1 January 2002 and were considered as real signals, with three of these later being confirmed by the literature and finally considered as true positives (isotretinoin, methylprednisolone and milnacipran).
CONCLUSION: This study confirms that a competition bias can occur when performing safety signal generation in spontaneous reporting databases. The minimization of this bias could lead to previously masked signals being revealed.
Sahut D'Izarn M, Caumont Prim A, Planquette B, Revel MP, Avillach P, Chatellier G, Sanchez O, Meyer G.
Risk factors and clinical outcome of unsuspected pulmonary embolism in cancer patients: a case-control study. J Thromb Haemost 2012;10(10):2032-8.
AbstractBACKGROUND: Little is known about the risk factors and outcome of unsuspected pulmonary embolism (UPE) in cancer patients.
OBJECTIVES: To assess the risk factors and outcome of UPE in cancer patients.
METHODS: The charts of 66 patients diagnosed with UPE were reviewed. Two control groups were selected: 132 cancer patients without pulmonary embolism (PE) and 65 cancer patients with clinically suspected PE. Variables associated with UPE were identified by multivariable analysis. Six-month survival and recurrent venous thromboembolism were compared by use of Cox proportional analysis.
RESULTS: Twenty-seven (40.9%) patients with UPE had symptoms suggesting PE. Adenocarcinoma (odds ratio [OR] 4.45; 95% confidence interval [CI] 1.98-9.97), advanced age (OR 1.18; 95% CI 1.02-1.38), recent chemotherapy (OR 4.62; 95% CI 2.26-9.44), performance status > 2 (OR 7.31; 95% CI 1.90-28.15) and previous venous thromboembolism (OR 4.47; 95% CI 1.16-17.13) were associated with UPE. When adjusted for tumor stage and performance status, 6-month mortality did not differ between patients with UPE and patients without PE (hazard ratio 1.40; 95% CI 0.53-3.66; P = 0.50). Patients with UPE were more likely to have central venous catheters and chemotherapy and less likely to have proximal clots than patients with clinically suspected PE. Recurrent venous thromboembolism occurred in 6.1% and 7.7% of patients with UPE and symptomatic PE, respectively.
CONCLUSION: UPE is not associated with an increased risk of death. Patients with clinically suspected PE and those with UPE have similar risks of recurrent venous thromboembolism.