[Second wave of the French drug harmonisation programme to prevent medication errors: overall appreciation of healthcare professionals]. / Évaluation de l'impact auprès des professionnels de la mise en œuvre de la seconde vague du plan d'harmonisation de l'étiquetage des injectables.

BACKGROUND: Medication errors are a significant cause of severe healthcare-associated complications. In December 2006, the French Health Products Agency (Afssaps) has issued a protocol to harmonise labeling of injectable drugs vials. In 2007, a first change was launched for four drugs and was followed in 2008-2009 by a second wave concerning 42 active drugs. METHODS: The present study describes how healthcare professionals have perceived this change and their overall appreciation of the drug harmonisation programme. A survey using an electronic questionnaire was distributed to medical and non-medical professionals in anaesthesia and intensive care and pharmacists in a representative sample of 200 French hospitals. RESULTS: The harmonisation procedure was felt as being overall satisfactory by 53% of professionals who had responded but it was recognised that the new procedure is associated with improved readability and understanding of drug dosage. The use of colour coding was also well accepted by the personnel of clinical units. Respondents expressed significant criticisms regarding both the communication plan and the way the plan was implemented locally in hospitals. Old and new labeling coexisted in 66% of responding hospitals and many respondents described being aware of errors or near-misses that were considered related to the transition. For many important topics, pharmacists had views that were significantly different from clinicians. CONCLUSION: This national survey describing the perception of healthcare professionals regarding the new harmonisation procedure for injectable drugs highlighted some progress but also a number of deficiencies, notably regarding communication and implementation of the change in clinical units. This survey will be used by the French Health Products Agency to improve future steps of the long-lasting campaign against medication errors.

[The use of postnatal corticosteroid therapy in premature infants to prevent or treat bronchopulmonary dysplasia: current situation and recommendations]. / Utilisation de la corticothérapie postnatale chez le nouveau-né prématuré dans la prévention et le traitement de la dysplasie bronchopulmonaire : état des lieux et conduite à tenir.

In the last few years, several studies related to the benefit/risk balance of postnatal corticosteroids administered to premature neonates for prevention or treatment of bronchopulmonary dysplasia (BPD) have been published. These data encourage caution, given the risk of long-term adverse neurodevelopmental outcomes. In the meantime, the clinical profile of BPD has been altered based on the progress made in the pre- and postnatal care of premature infants. In 2006, a survey conducted in France in neonatal centers showed that corticosteroids were still frequently used (57% of the centers) following various protocols in very preterm-born infants for respiratory impairment. To promote safer practices and rational use of corticosteroids in the prevention and treatment of BPD in preterm-born neonates, we reviewed the available data in order to establish recommendations. Systemic administration of corticosteroids for prevention or treatment of BPD: (i) should not be used during the first 4 days of life; (ii) is not indicated in the first 3 weeks of life nor (iii) in extubated infants (nasal ventilation or oxygen therapy). The systemic administration of steroids can only be considered after the first 3 weeks of life in very preterm-born ventilator-dependent infants to facilitate extubation (or prevent reintubation related to the severity of BPD). Postnatal dexamethasone administration studied in several randomized clinical trials was shown to have an unfavorable benefit/risk profile, mainly because of the long-term adverse neurocognitive outcomes. Very few studies have been conducted with betamethasone in the postnatal period. According to sparse data, this drug might be as efficacious as dexamethasone, but its long-term risk profile is unknown. It should be noted that following prenatal administration, the benefit/risk profile of betamethasone is better than that of dexamethasone, especially with regard to neurocognitive development. Intravenous hydrocortisone administered at an early stage for the prevention of BPD is being evaluated and should not be administered in this indication, except within clinical trials approved by the ethics committee. No other corticosteroids have been evaluated in the postnatal period in respiratory indications. In conclusion, in the situations described above for which systemic corticosteroids could be justified, the use of betamethasone (or hydrocortisone) appears to be better. As usual, the lowest possible dose of corticosteroids should be administered for the shortest possible duration. The betamethasone-equivalent dose of 0.125 mg/kg/day for 3 days is deemed adequate. If inhaled, corticosteroid therapy may facilitate extubation. Neither its efficacy in respiratory diseases nor its long-term risk profile has been so far established.

Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H.

OBJECTIVE: To report a case of eosinophilic pleuropericarditis resulting from concomitant use of vitamins B5 and H. CASE SUMMARY: A 76-year-old white woman was admitted to the hospital because of chest pain and dyspnea related to pleurisy and a pericardial tamponade. This patient had no history of allergy and had been taking vitamins B5 and H for two months. Blood tests performed showed an inflammatory syndrome and a high eosinophil concentration (1200-1500 cells/mm3). Pleurocentesis and pericardiotomy yielded a sterile exudative fluid with an eosinophilic infiltrate. There were no nuclear antibodies and no rheumatic factor; screenings for viruses, parasites, bacteria, and malignant tumor were negative. A myelogram, biopsy of the iliac crest bone, and concentration of immunoglobulin E were also normal. After withdrawal of the vitamins, the patient recovered and the eosinophilia disappeared. DISCUSSION: Prolonged hypereosinophilia has marked predilection to damage specific organs, including the heart, but pleuropericardial effusion is uncommon. Drug-related pleuropericarditis usually occurs without an increased eosinophil count. Other drugs responsible for eosinophilic pleuropericarditis are cephalosporins, dantrolene, propylthiouracil, and nitrofurantoin. To our knowledge, this is the first case report of pleuropericarditis related to vitamins B5 and H. CONCLUSIONS: This case suggests that vitamins B5 and H may cause symptomatic, life-threatening, eosinophilic pleuropericarditis. Physicians prescribing these commonly used vitamins should be aware of this potential adverse reaction.

[Acute methotrexate poisoning: apropos of 16 cases reported to the Paris Poison Control Center and review of the literature]. / L'intoxication aiguë au méthotrexate: a propos de 16 cas rapportés au Centre Anti-Poisons de Paris et revue de la littérature.

16 cases of acute methotrexate (MTX) poisoning were reported to the Paris Poison Control Centre and 62 others were published between 1974 and 1995. Until 1992, MTX was mainly prescribed for neoplastic diseases. Clinical features involve acute renal failure, pancytopenia, and cutaneous or mucous injury. These cases emphasise major risk factors responsible for misuse and overdosage. Since 1992, MTX has been increasingly used in rheumatological or pulmonary diseases (rheumatoid arthritis, steroid-dependent asthma). Most of the overdosages were due to a medical misuse (in the dosage regimen or a misunderstanding of the prescription by nurse, pharmacist or patient). All patients had a bone marrow suppression. The treatment is based especially on early administration of folinic acid rescue.

[Evaluation of unexpected and toxic effects of omeprazole (Mopral) reported to the regional centers of pharmacovigilance during the first 22 postmarketing months]. / Bilan des effets inattendus et toxiques de l'oméprazole (Mopral) rapportés aux centres régionaux de pharmacovigilance, au cours des 22 premiers mois de commercialisation.

Omeprazole has been marketed in France since 1989, for the healing of peptic ulcers, erosive reflux esophagitis and the Zollinger Ellison syndrome. It is a proton pump inhibitor which inhibits the acid secretion in the stomach. In the majority of the clinical trials, omeprazole has been found to be well tolerated: headache, dizziness, skin rash, constipation have just been noted. Since September 1989, 143 adverse reactions have been reported to pharmacovigilance centres and Astra France: 37 neurological and psychiatric side effects, especially confusion in patients with hepatic diseases and/or advanced age; 35 cutaneous reactions, generally rash and urticaria; 22 hematological effects: leucopenia and agranulocytosis have been reported but the relation with omeprazole is very uncertain; 10 gastrointestinal effects, generally diarrhoea, nausea, vomiting and abdominal pain; 8 hepatic disorders, especially moderate elevation of aminotransferases. This study confirms the safety of this drug, during short treatment; the frequency of notified adverse effects is about 1/12 200 treatments of 4 weeks. The ministry of health, has decided, in november 1991, to inform the prescribers of this potential toxicity of omeprazole, particularly, of the risk of confusion, hepatotoxicity and leucopenia.

[Acute toxicity of zidovudine. Analysis of the literature and number of cases at the Paris Poison Control Center]. / Toxicité aiguë de la zidovudine. Analyse de la littérature et des cas notifiés au centre Anti-Poisons de Paris.

13 cases of zidovudine overdosage have been previously published; 30 have been notified to Paris Control Poison Centre up to January 1991. This analysis shows that acute toxicity appears infrequent and mild when ingested dose is lower than 25 gr. However it appears from this series that an haematologic monitoring is needed because of the risk of myelosuppression.

Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity.

OBJECTIVE: To show that germander (Teucrium chamaedrys), an herbal medicine used to facilitate weight loss, may be hepatotoxic and to delineate the nature of the injury. DESIGN: Retrospective study. SETTING: Liver units of several centers in the French Network of Pharmacovigilance. PATIENTS: Seven patients who developed hepatitis after germander administration and who had no other cause of liver injury. MEASUREMENTS: Clinical examination, liver function tests, various serologic tests, ultrasonography, and histologic study. RESULTS: Hepatitis characterized by jaundice and a marked increase in serum aminotransferase levels occurred 3 to 18 weeks after germander administration. Liver biopsy specimens in three patients showed hepatocyte necrosis. After discontinuing treatment with germander, jaundice disappeared within 8 weeks and recovery was complete in 1.5 to 6 months. In three cases, germander readministration was followed by the prompt recurrence of hepatitis. CONCLUSION: Germander may be hepatotoxic, which supports the view that herbal medicines are not always as safe as generally assumed.

["Eosinophilia-myalgia" syndrome due to L-tryptophan containing products. Cooperative evaluation of French Regional Centers of Pharmacovigilance. Analysis of 24 cases]. / Syndrome "éosinophilie-myalgies" dû à des produits contenant du L-tryptophane. Bilan coopératif de l'Association Française des Centres Régionaux Français de Pharmacovigilance. Analyse de 24 cas.

By November 17, 1989, the MMWR published the 154 first reports of a syndrome consisting of myalgia and eosinophilia (EMS), occurring with the consumption of L-tryptophan containing products (L-TrpCp) and which might represent a new clinical entity. To standardize reporting over the country, the CDC of Atlanta developed the following case definition: 1) a peripheral blood total eosinophil count of more than 1 x 10(9) cells per liter 2) generalized myalgia sufficiently severe to affect a patient's ability to pursue daily activities 3) the exclusion of infections or neoplastic conditions. The FDA then, announced its intention to seek a nationwide recall of all tryptophan containing products, followed by other european countries (UK, Germany, France). In France, a first decree (January 4th 1990) completed by a decree on May 11th confirms this decision for one year. This measure did not concern the medicinal products or some dietary supplements for newborn or young children. Since December 11th, 1989, 24 cases have been reported to the Regional Adverse Drug Reaction Monitoring Centres in France. These cases share the same features as the cases notified previously in the USA: overrepresentation of females, no relationship with the time and the daily intake, clinical similarities to the Shulman syndrome, and unknown prognosis. Now, more than one year after the onset of this illness, it seems that discontinuation of the ingestion of L-TrpCp can resolve or improve the symptoms in most cases, but sometimes the syndrome can persist. The causal relationship between the ingestion of L-TrpCp and this syndrome has been established. Whatever the mechanism for the development of EMS among tryptophan users remains unclear, as well as the role of eosinophilia and the factors for fibroblast proliferation. The epidemic emergence of this syndrome in July 89 raises the possibility of the contamination of tryptophan during the manufacturing process. To confirm this hypothesis, the same unusual peak in HPLC analysis was found both in case-associated L-Trp lots and in implicated-japanese manufacturer L-Trp lots in USA. But this would not explain the previous EMS reports before this contamination. Other hypotheses consist an inabnormality of tryptophan metabolism and/or an autoimmune process.

[Cancers from tobacco smoke]. / Cancers du tabagisme.

The proximity of smokers exposes non-smokers to the inhalation of tobacco smoke. The existence of this absorption has been established by assays of blood nicotine concentrations or urinary thiocyanate concentrations, in volunteers: proximity with an individual who smokers approximately ten cigarettes is equivalent to smoking one cigarette. Consequences of this passive smoking are not negligible. Two studies, one Japanese and one Greek, have shown that the risk of lung cancer in wives of smokers is twice that in non-smoking women married to non-smokers, even though various American studies seem more reassuring. Another risk of cancer exists in the offspring of mothers who smoked during their pregnancy, with a rate of 14.9 x 10(5) if the mother smoked, versus 11. 4 x 10(5) if she didn't. Experimental rates of cancer in hamster fetuses confirm this risk.

[Lung injury after use of respiratory revival materials sterilized with ethylene oxide]. / Accident pulmonaire lors de l'utilisation de matériels de réanimation respiratoire stérilisés a l'oxyde d'éthylène.

One of the most used method of medical appliances sterilization uses ethylene oxide. At high concentration, this very reactive product, causes caustic burns of skin and mucous membranes. In one case of acute pulmonary oedema, levels of ethylene oxide in the endotracheal catheter were discovered. This led us to review the toxicological data on this substance. It should be emphasized that the sterilization and the desorption according to simple and precise rules should prevent such acute accidents.

[Human allergic hypersensitivity and chemical residues in food]. / Hypersensibilité allergique humaine et résidus alimentaires.

Chemical and immunological basis of hypersensitivity reactions to low molecular weight substances are recalled. Then the authors give examples of directly reactive chemicals as penicillins and some antineoplastic drugs. The possible role of reactive impurities as penicillins and aspirin is also reminded. It is emphazised that some substances induce allergic reactions through their metabolites: such reactions are mostly unforeseeable. The second part of the paper recalls the main clinical manifestations of these allergic hypersensitivity reactions to chemical residues in food. It is finally emphazised that the datas from animal experiments and epidemiological studies could allow a classification of chemical substances according to their potential risk. This would be of great importance to determine which substances may be authorized in food stuffs and/or to specify the maximum allowable concentrations.