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Background and aim: Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most frequently prescribed drugs. Gastrointestinal damage, the most common side effect of NSAIDs, can be limited by the prescription of cytoprotective agents. In order to assess determinants of NSAID-associated cytoprotective agent prescriptions in primary care practice, we performed a general practitioner (GP)-based study. Methods: After a 2-month intensive information campaign, the participation of all GPs of the Cote d'Or (France) administrative area was requested. During a 2-month period, GPs had to return a mailed questionnaire on NSAID prescription for up to ten consecutive patients aged over 18 years who required NSAIDs. This 30-item questionnaire included questions about the patient, the type of NSAID and the GP. Results: GP participation rate was 24%, and 791 prescriptions were provided. GPs who participated in the study were representative of GPs of the area in terms of sex, time elapsed since graduation and GP practice area. Around 80% of the patients included in the study were under the age of 65 years. The proportion of prescriptions combining NSAIDs and gastroprotective agents was 29.5%. Omeprazole accounted for 58% of the co-prescriptions and misoprostol for 29%. Independent determinants associated with the co-prescription of a cytoprotective agent were age [odds ratio (OR) 4.1; confidence interval (CI) 95% 2.3–7.4], previous history of poor NSAID tolerance (OR 10.4; CI 95% 5.8–18.6), previous history of moderate to severe digestive disorders (OR 13.4; CI 95% 5.1–35.4) and indication for chronic illness (OR 1.8, CI 95% 1.1–3.1). Prescriptions of cytoprotective drugs were in conformity with official guidelines for 78.3% of the patients. Although around 60% of the patients with risk factors for poor tolerance received a gastroprotective drug, 50% of the patients over 65 years did not receive it. Conversely, nearly 12% of the patients with no risk factors were prescribed cytoprotective agents. Patient history was the main reason put forward by GPs for prescribing cytoprotective drugs. Conclusion: Although a large majority of GP prescriptions were in accordance with official recommendations, inadequate NSAID prescription practices remain relatively frequent especially with regard to the elderly.

PURPOSE: To quantify the risk of acute leukemia after adjuvant therapy, especially chemotherapy with topoisomerase II inhibitors. PATIENTS AND METHODS: We performed a population-based study in a cohort of 3,093 women younger than 85 years who resided in the French administrative area of the Côte d’Or, who were given a first diagnosis of primary breast cancer between 1982 and 1996, and who received a curative treatment. Information about therapy and follow-up events was obtained from records of cancer registries that covered this area. RESULTS: Until December 1998, 10 cases of acute leukemia, including nonlymphoid acute leukemia and refractory anemia with excess of blasts, occurred in patients before any local or distant recurrence. All cases developed in the first 4 years of follow-up. Compared with the general female population, the incidence rate of leukemia was significantly increased in women who received radiotherapy and chemotherapy (standardized incidence ratio, 28.5; P < .0001). A dose-dependent increase in the risk of leukemia was observed in women treated with mitoxantrone. Cox regression analysis showed that the risk of leukemia was significantly lower in patients treated with anthracyclines than in those treated with mitoxantrone at cumulative doses ≥ 13 mg/m2. CONCLUSION: The combination of adjuvant radiotherapy and chemotherapy with mitoxantrone induces a high risk of acute leukemia in patients with breast cancer. A leukemogenic effect of chemotherapy with anthracyclines cannot be ruled out with certainty. However, there are some suggestions that these topoisomerase II inhibitors might be less leukemogenic than mitoxantrone and could be preferred in an adjuvant setting.

on si de re d ne ga tiv e or in tr av en ou s ad m in is tr at io n w ith no re ac tio n. TO THE EDITOR: Although immediate hypersensitivity reactions to iodinated contrast media (ICM) are well recognized, delayed cutaneous reactions (1 hour to 7 days) are much less easily diagnosed. The clinical manifestation usually is moderate, but sometimes serious reactions may occur. To our knowledge, we report the largest series of cutaneous delayed reaction that presented as acute generalized exanthematous pustulosis (AGEP) after ICM administration confirmed by skin testing. Skin tests performed 6 weeks after AGEP included patch tests followed by intradermal tests (IDT). ICMs tested were the same for all patients (ioxaglate, iomeprol, iopamidol, iodixanol, iohexol, iobitridol). Patch tests were conducted with undiluted ICM. Readings were conducted on days 2 and 4. Positive results were considered in accordance with the recommendations of the European Society of Contact Dermatitis. IDTs were performed with 10-fold diluted and undiluted ICM, and readings were conducted after 20 minutes and on day 2. Intravenous administration was performed 1 month later by using an alternative ICM that had negative skin tests and was also selected in consultation with the radiologist based on the ICM needed. The first dose injected was 0.5 mL. Two hours later, if no reaction occurred, then 2 mL was injected. The entire dose was administered only for the radiologic examination. All skin tests and intravenous administrations were conducted in a dermatology hospital unit.

Objective. – To describe joint symptoms related to bupropion therapy. Methods. – We retrospectively reviewed adverse events in bupropion-treated patients reported to the Bourgogne Drug Surveillance Center, France, between October 2001 and December 2002. Joint symptoms classified by the causality assessment as related to bupropion were identified and examined. Results. – Four cases were found. Three patients had semi-delayed hypersensitivity reactions resembling serum sickness, manifesting as urticaria and arthralgia with or without a fever. The remaining patient had an unusual presentation consisting in acute monoarthritis of the wrist that started a few days after bupropion initiation. Conclusion. – Hypersensitivity reactions to bupropion are fairly common and include rare cases of serum sickness-like reaction. Urticaria and incapacitating arthralgia are at the forefront of the clinical picture and may require a brief period of inpatient care. Antihistamines are the treatment of choice. Other manifestations such as acute monoarthritis might occur, although this awaits confirmation as we identified a single case.

Objectives: To compare characteristics of patients exhibiting cetuximab infusion reactions or another adverse drug reaction related to cetuximab and to identify factors associated with the severity of cetuximab infusion reactions. Methods: All cases of adverse drug reaction reported with cetuximab from 1985 to 2010 were extracted from the French Pharmacovigilance database. The severity of infusion reactions was assessed according to the NCI-CTCAE criteria (v4.0). Multiple logistic regression analysis was performed to identify factors associated with the severity of infusion reactions. Results: Among the 602 adverse drug reaction reported with cetuximab during the study period, 374 infusion reactions were identified. Indication is more likely to be head and neck than colorectal cancer among patients experiencing an infusion reaction ( p Conclusion: Our study found that reports of infusion reactions more often concerned patients treated for head and neck cancer, that in these patients the adverse drug reaction was more often fatal and severe infusion reactions were more likely during the first administration. In daily practice, the close monitoring of patients during the first infusion, especially patients with head and neck cancer, is recommended. Considering the possible immunoglobulin E–mediated mechanism, reliable tests for their detection need to be readily available.

To report the first case of severe hypoglycaemia episodes related to voriconazole, involving neither over dosage nor any identified interaction with hypoglycaemic drugs. A 51-year-old man developed faints without loss of consciousness, with sweating in the morning for 3-4 days and low blood glucose, about 1 month after initiating voriconazole therapy. Hypoglycaemia was diagnosed and the patient required permanent intravenous glucose solutions for 8 days after voriconazole was stopped, after which glycaemia remained normal. A hyperinsulinaemia peak was observed, which disappeared when glycaemia normalized. Hypoglycaemia is known as a less common adverse event resulting from high voriconazole concentration and hepatic dysfunction. The mechanism of hypoglycaemia may be linked to insulinemia as its serum values are similar to glycaemia. Voriconazole may induce hypoglycaemia in patients without over dosage nor drug interaction.

Results: On-treatment platelet reactivity with clopidogrel 75mg, 150mg or prasugrel 10mg was always higher in elderly patients (n=197) than in younger patients (n=1074) whatever the test used. The difference in PRU in response to ADP-PGE1 agonist between the two populations was +45; p

This study investigated the effects of two K+ channel openers, aprikalim and pinacidil, on hypoxic pulmonary vasoconstriction induced in isolated rat lung perfused at constant flow. In order to evaluate the mechanism of the hypoxic vasoconstriction we also studied the effects of an inhibitor of the endothelium-derived relaxing factor (EDRF), NG-nitro-L-arginine methyl ester (100 microM), an inhibitor of the guanylate cyclase, methylene blue (30 microM), two K+ channel blockers, glibenclamide (1 microM) and tetraethylammonium (20 mM). In normoxia, NG-nitro-L-arginine methyl ester, methylene blue, glibenclamide or tetraethylammonium did not enhance significantly the baseline perfusion pressure, suggesting that neither EDRF nor K+ channels are involved in the modulation of the low basal pulmonary vascular tone. In hypoxia, aprikalim and pinacidil (0.03-3 microM) induced a concentration-dependent decrease of pulmonary pressure, exhibiting their spasmolytic effects in acute hypoxia. The hypoxic pressure response was significantly increased by NG-nitro-L-arginine methyl ester, methylene blue and tetraethylammonium, but not by glibenclamide suggesting that EDRF and K+ channels other than ATP-sensitive K+ channels are involved in the modulation of the hypoxic pressure response. The spasmolytic effects of aprikalim and pinacidil (1 microM) were not modified by NG-nitro-L-arginine methyl ester, but were partially reduced by tetraethylammonium and completely abolished by glibenclamide, suggesting that these effects are mainly but not exclusively mediated through ATP-sensitive K+ channel opening.