Five vs. ten days of antibiotic therapy for acute otitis media in young children.

BACKGROUND: Many publications in recent years have argued in favor of shortened therapy for acute otitis media. However, doubt persists regarding children younger than 2 years, and some authors therefore restrict short course therapy to children older than 2 years. METHODS: In a prospective, comparative, double blind, randomized, multicenter trial we compared cefpodoxime-proxetil, 8 mg/kg/day in two divided doses for 10 days, with an identical 5-day regimen followed by a 5-day placebo period. RESULTS: Between October, 1996, and April, 1997, 450 children (mean age, 14.3 months) were enrolled, 227 in the 5-day group and 223 in the 10-day group. In the per protocol analysis clinical success was obtained on Days 12 to 14 after the beginning of treatment (main analysis) in 175 (84.1%) of the 208 children receiving the 5-day regimen and 194 (92.4%) of the 210 children receiving the 10-day regimen (P = 0.009). The superiority of the standard regimen was more marked among children cared for outside their homes (92.5% vs. 81.5%). Clinical success persisted on Days 28 to 42 among 134 (85.4%) of the 157 assessable patients in the 5-day group and 144 (83.7%) of the 172 assessable patients in the 10-day group (P = 0.68). CONCLUSIONS: The 10-day regimen resulted in a higher success rate at the conclusion of therapy, but there were no differences between the two study groups 4 to 6 weeks after enrollment in the study protocol.

[Toxicology of reproduction: predictive value of experimental models. Round Table No 1 at Giens XIII]. / Toxicologie de la reproduction: valeurs prédictives des modèles expérimentaux. Table Ronde No 1 de Giens XIII.

The carrying out of clinical trials with a view to the marketing of drugs for human use is directly related to results of some animal studies. This workshop was devoted to evaluation of the quality and interest of these experimental models in reproductive toxicology. The predictive ability of preclinical trials to make extrapolations from animals to man decreases from foetotoxic to tetratogenic risks respectively and from the effects on fertility in both sexes to postnatal risks. As a result of this workshop, we propose the following improvements: (1) standardization and generalization of fertility test evaluations, especially the spermogram, in order to improve animal and human correlations; (2) development of knowledge and standardization of the follow up of the oestral cycle; (3) improvement of standardization, harmonization and diffusion of postnatal tests that prove relevant in animals; (4) increase in initiatives aimed at better mutual understanding of all drug partners; (5) creation of registers for new drugs, as soon as possible during clinical trials, to study their effects on the whole reproductive process; (6) recommendations for the creation of guidelines for International Conference on Harmonisation (ICH) to enable classification of observed effects in experimental models. This could lead to specific (potentially for each phase of the reproductive cycle) guidelines, precautions for use and/or contraindications which are listed in the summary of product characteristics.

[Eruption after the 1st dose of standard antitubercular chemotherapy. Thoughts on pyrazinamide]. / Eruption après la première prise d'une chimiothérapie standard antituberculeuse. Penser au pyrazinamide.

UNLABELLED: We report 3 cases of rash after the first dose of antituberculosis polytherapy, thus raising questions concerning the procedures to be followed. CASE REPORT: Three patients developed a pruritic rash 1 hour after the first dose of isoniazide, rifampicine, pyrazinamide and ethambutol given simultaneously. The eruption did not recur after readministration of isoniazide and rifampicine successively. Pyrazinamide, which was readministered last (at the full dose in one case and at progressive doses in the two others), induced a recurrence in two of them. Pyrazinamide was definitively withdrawn in one patient with recurrence and slower pyrazinamide readministration allowed continuation of treatment in the other two patients. CONCLUSION: Since pyrazinamide appeared to be responsible for rash following the first administration of antituberculosis polytherapy, a protocol for readministration of the 4 drugs is suggested. If the responsibility of pyrazinamide is confirmed it should be readministered very slowly.

-Skin eruption after the first dose of antitubercular quadri-therapy: consideration of pyrazinamide-. / Eruption après une première prise d'une quadrithérapie antituberculeuse: penser au pyrazinamide.

UNLABELLED: We report a rash after the first dose of antituberculosis polytherapy which raises questions concerning procedures to be followed. CASE REPORT: An 8-year-old child presented with a pruritic rash 1.5 hours after the first dose of isoniazide, rifampicine, pyrazinamide and ethambutol was simultaneously administered, which did not recur after successive re-administration of isoniazide and rifampicine. Pyrazinamide, which was re-administered last, induced a recurrence. Slower pyrazinamide re-administration allowed continuation of treatment. CONCLUSION: A protocol for re-administration of the four drugs is suggested.

[Syncope with long QT interval in a 39 day-old infant treated with cisapride]. / Malaise avec allongement de l'espace QT chez un nourrisson de 39 jours traité par cisapride.

UNLABELLED: Cardiotoxicity of cisapride may increase when this drug is associated with ranitidine. CASE REPORT: A 37-day old term infant, treated with cisapride (1.2 mg/kg/d) and ranitidine for regurgitations, was hospitalized for malaise. A prolonged QT interval (with isolate ventricular extrasystoles), noted at admission, disappeared rapidly after cisapride withdrawal. Linkage to cisapride was probable, promoted by high dosage and cisapride metabolism inhibition by ranitidine, but its plasma concentration was not measured. CONCLUSION: This case report stresses the problem of cisapride dosage in infants and the question of an interaction between cisapride and ranitidine.

[Does stopping of oral feeding favour the occurrence of auriculoventricular block in premature infants treated with diphemanil?]. / L'arrêt de l'alimentation orale favorise-t-il la survenue d'un bloc auriculoventriculaire chez les prématurés traités par diphémanil?

BACKGROUND: Bradycardia in preterm infants may require anticholinergic therapy (diphemanil methylsulphate). Such treatment may cause prolongation of QT interval and auriculoventricular block. CASE REPORTS: Three premature infants born before 34 weeks of gestational age were given 6-8 mg/kg/d diphemanil because they suffered from bradycardiac episodes. Aggravation and/or persistence of bradycardia required withdrawal of gavage feeding: heart block occurred within a few hours which subsided after cessation of diphemanil and oral refeeding. Diphemanil at progressive dosage was later introduced safely in two of these infants. CONCLUSION: The short interval of time between the oral feeding withdrawal and occurrence of heart block justified therapy be stopped or transiently reduced whenever oral feeding must be interrupted.

Study of the use of vitamin K in neonates in France.

OBJECTIVE: Because of the risk of haemorrhagic disease of the newborn as a result of a deficit in vitamin K, it is generally agreed that newborns should receive vitamin K. However, there is no consensus concerning the route of administration, dose, number of doses, or dose frequency. METHODS: We studied patterns of vitamin K administration in all maternity hospitals in France in order to establish the range of practices and policies. Six hundred and forty questionnaires were analysed. Vitamin K was given systematically to all neonates in 619 maternity hospitals (96.7%), not given to any neonates in 2 (0.3%), and only to certain newborns in 19 (3%). A similar protocol was used for all newborns in 299 (47%) of the maternity hospitals, and the treatment protocol differed according to the neonatal clinical picture in 336 maternity hospitals (53%). RESULTS: The route of administration agreed with the recommendation that healthy newborns receive formula milk. In contrast, infants receiving breast milk were given IM vitamin K in only 19% of the maternity hospitals studied and regular weekly doses were prescribed in only 56%. In premature infants, IM doses were prescribed in only 46% of cases and repeat weekly doses in 34%. The dose generally prescribed (5 mg p.o. or IM) was not the recommended dose.

[Isotretinoin (Roaccutane) in women of childbearing age: failure of following prescription guidelines]. / Isotrétinoïne (Roaccutane) chez la femme en age de procréer: insuffisance de suivi des recommandations de prescription.

BACKGROUND: Despite prominent warnings, pregnancies continue to be reported in women exposed to isotretinoin. PATIENTS AND METHODS: We report results of the analysis of 318 questions asked to pharacovigilance structures in France from 1987 to 1995 because of an exposition to isotretinoin during the risk period and of a prospective inquiry concerning isotretinoin prescription in women conducted among pharmacists. RESULTS: These 318 pregnancies began during the month after Roaccutane withdrawal (n = 104, 33 p. 100), during Roaccutane treatment (n = 163, 51 p. 100) or before Roaccutane treatment (n = 51, 16 p. 100). Of the 267 women with pregnancies conceived during treatment with isotretinoin (n = 104) or during the month after its discontinuation (n = 163), contraception was not prescribed in 28 (15 p. 100) or prescribed but with poor compliance in 109 (60 p. 100). Pregnancy was terminated voluntarily in 199 women (81 p. 100). In the 173 women who were interviewed in pharmacies, 49 (28 p. 100) did not use contraception and among them contraception was prescribed in only 59 p. 100. Only 14 p. 100 had received full information about isotretinoin and pregnancy. The teratogenic effects of isotretinoin were known by 98 p. 100 of the women and the need of contraception during treatment and for one month after discontinuation by 70 p. 100. DISCUSSION: Insufficient compliance with warnings is the main reason for pregnancies in women receiving isotretinoin therapy. A pregnancy prevention program is needed before prescription to ensure comprehension and to obtain informed consent of patients.

Evaluation of ibuprofen versus aspirin and paracetamol on efficacy and comfort in children with fever.

OBJECTIVE: We compared efficacy and impact on the comfort of ibuprofen (7.5 mg/kg per dose), aspirin (10 mg/kg/dose) and paracetamol (10 mg/kg per dose) on children with fever aged 6-24 months in an open, randomised study with three parallel groups. METHODS: The main criterion for efficacy was area under the curve (AUC) of percentage temperature reduction. Comfort was assessed on scores depending on general behaviour and degree of relief. General behaviour was assessed on a verbal scale and on a visual analogue scale (VAS) and the degree of relief was assessed in relation to baseline on a verbal scale. RESULTS: The efficacy of ibuprofen was better than that of aspirin or paracetamol. In spite of more adverse events, the comfort scores were significantly in favour of ibuprofen 6 h after the first dose of treatment.

[Esophageal involvement after tetracycline ingestion]. / Atteines oesophagiennes secondaires à l'ingestion de tétracyclines.

Between 1985 and 1992, 81 spontaneous oesophageal injuries associated with tetracycline were notified to the French Regional Pharmacovigilance Centres. The side effects were oesophageal ulcers (79 per cent), esophagitis (11 per cent) and dysphagia (10 per cent). Esophagitis and dysphagia appeared sooner (4 days) than the ulcers (15 days). The mean age of the patients was 29 +/ 13 years and 73 per cent were women. In 92 per cent of cases, the recommendations for administration were not observed (medication taken at bedtime with not enough or without water). With 96 per cent of patients, doxycycline was the tetracycline in question; this prevalence could be explained by its irritant and cytotoxic properties. The oesophageal injuries were 22 times more frequent with capsules than with tablets, because of their easier adhesion to the oesophageal surface. Oesophageal injuries are potentially serious and must be avoided by clear information to patients and prescribers on tetracycline administration; consumption in the middle of a meal with an adequate quantity of water and never less than one hour before bedtime.

[Methodology of preparing a list of educational objectives: example of application to pharmacology. Groupe Objectifs Pédagogiques de L'Association des Enseignants de Pharmacologie]. / Méthodologie d'élaboration d'une liste d'objectifs éducationnels: exemple d'application à la pharmacologie. Groupe Objectifs Pédagogiques de l'Association des Enseignants de Pharmacologie.

Using a structured approach to categorize pharmacological knowledge and a systemic analysis of prescribing practice, we identified the knowledge needed to optimally prescribe and manage treatments with drugs. The approach consisted in finding the branched chains of knowledge beginning with each operation required to solve each problem which arises in prescribing and managing drugs at the most elementary level. This elementary knowledge is then transformed into educational objectives. The next step is to share the educational objectives between basic medical training, continuing medical education and acquisition of therapeutic knowledge. The method could be applied in other medical teaching domains.

[Aseptic meningitis after mumps vaccination]. / Méningites aseptiques après vaccination anti-ourlienne.

The aim of this retrospective study was to evaluate the incidence and the characteristics of spontaneously reported aseptic meningitis (AM) in France following mumps vaccination with monovalent or multivalent vaccines containing the Urabe strain. Fifty-four cases of AM were reported to the regional drug surveillance centres or to the manufacturer from the time each vaccine was launched up until June 1992. Twenty cases were associated with the time off administration of a monovalent mumps vaccine and 34 with a trivalent measles, mumps and rubella vaccine (MMR). A mumps virus was isolated in four cases in the cerebrospinal fluid and an Urabe-like strain was characterised twice by polymerase chain reaction (PCR). A probable mumps origin was assumed in 17 other cases where the patients presented with other clinical or biological signs of mumps infection. The clinical outcome of AM was always favourable. The global incidence of mumps vaccine-associated AM was 0.82/100,000 doses, which is significantly lower than the incidence in the unvaccinated population. Even considering that the actual incidence of AM is much higher when assessed by active surveillance studies, the risk/benefit ratio of mumps vaccine remains in favour of vaccination. The incidence of mumps vaccines containing Jeryl Lynn (ROR Vax et Imu ORR) associated with AM needs to be evaluated.

[Thrombocytopenic purpura after isolated or combined vaccination against measles, mumps and rubella]. / Purpura thrombopénique après vaccination isolée ou associée contre la rougeole, la rubéole et les oreillons.

A retrospective epidemiological survey was conducted to evaluate the incidence and characteristics of thrombocytopenic purpura (TP) reported in France following measles, mumps or rubella vaccination with monovalent or multivalent vaccines. Sixty cases of TP were reported i.e an incidence/100,000 doses of 0.23 and 0.17 for measles or rubella vaccines respectively given alone, to 0.87 for combined measles-rubella vaccine and 0.95 for MMR vaccine. The mean age was 21 +/- 12 months and the delay of diagnosis was 16 +/- 6 days after vaccination. Thrombopenia was severe (mean platelet count: 8000 +/- 6000/mm3) and always associated with purpura. The immediate outcome was favourable in 89.5 per cent of cases. Vaccine-associated TP appears to be similar to acute childhood idiopathic thrombocytopenic purpura but the clear temporal relationship between MMR vaccination and the occurrence of TP make a causal relationship highly plausible. Acute TP seems a rare complication of measles-rubella and MMR vaccination but clinicians had to be informed of the possibility of their occurrence. Acute TP following vaccination should be reported by physicians to their Regional Drug Surveillance Centre.

[Modality of use of vitamin K in France in newborn infants]. / Modalités d'utilisation de la vitamine K en France chez le nouveau-né.

BACKGROUND: Because of the risk of hemorrhagic disease of the neonate secondary to vitamin K deficiency, it is generally agreed that neonates should be given vitamin K. There is however, no consensus concerning the route of administration, dose, number of doses, or dose frequency. It was therefore necessary to determine patterns of vitamin K administration in France. POPULATION AND METHODS: Routine vitamin K administration was studied in 1993 by questionnaires sent to all maternity units in France. RESULTS: Six hundred and forty of the 1,086 questionnaires could be analysed. Vitamin K was never prescribed in 0.3% of maternity units and was given only to high risk neonates in 3%. In healthy neonates receiving milk formulas, the route of administration (oral or IM) agreed with the recommendations of the French Committee of Pediatric Nutrition. In contrast, breast-fed infants were given IM vitamin K in only 19% of the maternité units whereas regular weekly doses were prescribed in only 56%. In premature infants, IM doses were prescribed in only 46% of cases and repeated weekly doses in 34%. The dose generally prescribed (5 mg orally or IM) was not the recommended dose. Among the available products, oral or parenteral vitamin K Roche was the most frequently prescribed. CONCLUSION: New recommendations for the use of vitamin K in the perinatal period in France are necessary.