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Elisabeth Frauger,
Jerome Grassi,
Vincent Pradel,
Charleric Bornet,
Frank Rouby,
Jean Delorme,
Sebastien Ousset,
Diane Braguer,
Jean-Philippe Azulay,
Christine Penot-Ragon,
Jean-Robert Harle,
Marie-Claude Bongrand,
Pierre-Jean Weiller,
Jean Pouget,
Gérard Michel,
Joelle Micallef,
Jean-Pierre Reynier, Sophie Tardieu,
Patrice Vanelle,
Olivier Blin
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ABSTRACT: Since several years, the use of intravenous immunoglobulins (IVIg) has increased. This growth has encouraged some countries to publish guidelines. In parallel, some countries have conducted audits to know how IVIg are used in clinical practice in the light of the available guidelines. The objective of this study was to assess IVIg use in three French university hospitals in 2006. All IVIg administrations were evaluated during 6 months (12 September 2005-12 March 2006) in French university hospitals of Marseille. Different data were recorded for each administration: patient characteristics, indication, formulation and quantity. During the study period, 2802 administrations of IVIg (corresponding to a total quantity of 76 780 g) have been recorded. Four hundred and thirty-five patients received at least one of these administrations. The five most reported indications were multifocal motor neuropathy (11.0% of total quantity), chronic inflammatory demyelinating polyradiculoneuropathy (10.2%), corticoresistant dermatomyositis (10.2%), immune thrombocytopaenia (9.9%) and primary immune deficiency (9.1%). According to available French recommendations, 70% of the IVIg use was for 'acknowledged indications', 9% for 'indications to be assessed' and 18% for 'unwarranted indications'. The 10 most reported indications were 'acknowledged indications' according to available recommendations of the French expert group. Nevertheless, the two most reported indications were not approved by the French Health Products Agency (AFSSAPS) at the time of the study and were approved since.
Fundamental and Clinical Pharmacology 01/2011; 25(6):753-61. · 1.80 Impact Factor
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ABSTRACT: To assess the impact of continuous incident reporting and subsequent prevention strategies on the incidence of severe iatrogenic events and targeted priorities in admitted neonates.
We performed preintervention (January 1 to September 1, 2005) and postintervention (January 1, 2008, to January 1, 2009) prospective investigations based on continuous incident reporting. Patient-safety initiatives were implemented for a period of 2 years. The main outcome was a reduction in the incidence of severe iatrogenic events. Secondary outcomes were improvements in 5 targeted priorities: catheter-related infections; invasive procedures; unplanned extubations; 10-fold drug infusion-rate errors; and severe cutaneous injuries.
The first and second study periods included totals of 388 and 645 patients (median gestational ages: 34 and 35 weeks, respectively; P = .015). In the second period the incidence of severe iatrogenic events was significantly reduced from 7.6 to 4.8 per 1000 patient-days (P = .005). Infections related to central catheters decreased significantly from 13.9 to 8.2 per 1000 catheter-days (P < .0001), as did exposure to central catheters, which decreased from 359 to 239 days per 1000 patient-days (P < .0001). Tenfold drug-dosing errors were reduced significantly (P = .022). However, the number of unplanned extubations increased significantly from 5.6 to 15.5 per 1000 ventilation-days (P = .03).
Prospective, continuous incident reporting followed by the implementation of prevention strategies are complementary procedures that constitute an effective system to improve the quality of care and patient safety.
PEDIATRICS 11/2010; 126(6):e1461-8. · 4.47 Impact Factor
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ABSTRACT: To assess the sleepiness induced by pramipexole, a D2/D3-dopamine receptor agonist commonly used in Parkinson's disease and restless legs syndrome, without the problem of the confounding factors related to the disease.
Placebo, bromocriptine (2.5 mg), L-dopa (100 mg) and pramipexole (0.5 mg) were administered in a single oral dose on four separate days, with at least a 2-week wash-out period in a randomized cross-over design. Induced somnolence was assessed using Multiple Sleep Latency Test (MSLT) and subjective scaling of vigilance. Twelve male subjects (26.3 +/- 5.5 years old) without anxiety, mood, sleep or sedation disorders were enrolled.
Pramipexole significantly reduced mean sleep latency compared with placebo 3 h 30 min [-6.1 min (-9.8, -2.4), P = 0.002] and 5 h 30 min [-5.6 min (-7.7, -3.5), P = 0.003] after administration. In addition, the total duration of sleep during the tests was higher with pramipexole than with placebo [+6.0 min (2.3, 9.7), P < 0.001]. These differences were not observed with L-dopa and bromocriptine in comparison with placebo. The induced sleepiness was not associated with an increase in subjective somnolence scaling, indicating that this adverse event may occur without prior warning.
These results show that a single oral dose of pramipexole induces sleepiness as assessed by MSLT in healthy young subjects, independent of disease-related sleep dysfunction.
British Journal of Clinical Pharmacology 02/2009; 67(3):333-40. · 2.96 Impact Factor
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ABSTRACT: Iatrogenic events are increasingly recognised as an important problem in all people admitted to hospital. However, few epidemiological data are available for iatrogenic events in neonatal high-risk units. We aimed to assess the incidence, nature, preventability, and severity of iatrogenic events in a neonatal centre and to establish the association of patient characteristics with the occurrence of iatrogenic events in neonates.
We undertook an observational, prospective study from Jan 1, 2005, to Sept 1, 2005, including all neonates admitted in the Division of Neonatology of an academic, tertiary neonatal centre in southern France. Iatrogenic events were defined as any event that compromised the safety margin for the patient, in the presence or absence of harm. The report of an iatrogenic event was voluntary, anonymous, and non-punitive. The primary outcome was the rate of iatrogenic events per 1000 patient days.
A total of 388 patients were studied during 10 436 patient days. We recorded 267 iatrogenic events in 116 patients. The incidence of iatrogenic events was 25.6 per 1000 patient days. 92 (34%) were preventable and 78 (29%) were severe. Two iatrogenic events (1%) were fatal, but neither was preventable. The most severe iatrogenic events were nosocomial infections (49/62 [79%]) and respiratory events (nine of 26 [35%]). Cutaneous injuries were frequent (n=94) but generally minor (89 [95%]), as were medication errors (15/19 [76%]). Most medication errors occurred during administration stage (12/19 [63%]) and were ten-fold errors (nine of 19 [47%]). The major risk factors were low birthweight and gestational age (both p<0.0001), length of stay (p<0.0001), a central venous line (p<0.0001), mechanical ventilation (p=0.0021), and support with continuous positive airwary pressure (p=0.0076).
Iatrogenic events occur frequently and are often serious in neonates, especially in infants of low birthweight. Improved knowledge of the incidence and characteristics of iatrogenic events, and continuous monitoring could help to improve quality of health care for this vulnerable population.
The Lancet 03/2008; 371(9610):404-10. · 38.28 Impact Factor
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ABSTRACT: Use of albumin (indications and quantities involved) has not been assessed in France since major changes occurred after the publication of Cochrane group meta-analysis. The objectives of this study were to measure the repartition of albumin indications in three French university hospitals in 2004 and to assess the feasibility and usefulness to implement a prescription-monitoring program.
Exhaustive record of albumin prescription during 2 months in three French university hospitals of Marseille. Inclusion of all patients with a first prescription of albumin between 15 March 2004 and 15 May 2004. Indication, formulation and quantity prescribed were recorded for each prescription.
One hundred and eighty-seven patients received a total of 426 prescriptions for a total quantity of 21 094 g of albumin during the study. The first indications were hypoalbuminemia (33% of total quantity), plasmapheresis (30.2%) and ascites or hepatorenal syndrome (13.7%). Fifty per cent of total quantity was used by 14 patients (7.5% of included patients).
Most of albumin consumption in our study is concentrated on recognized indications or indications without alternative to albumin. The different levels of analysis (number of patient treated, number of prescription and quantities used) must be taken into account when analyzing medications such as albumin. Only a marginal proportion of consumption is expected to be saved with close monitoring of indications.
Pharmacoepidemiology and Drug Safety 02/2007; 16(1):79-85. · 2.53 Impact Factor
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ABSTRACT: Little is known about depressed patients' profiles and how they are managed. The aim of the study is to compare GPs and psychiatrists for 1 degrees) sociodemographic and clinical profile of their patients considered as depressed 2 degrees) patterns of care provision.
The study design is an observational cross-sectional study on a random sample of GPs and psychiatrists working in France. Consecutive inclusion of patients seen in consultation considered as depressed by the physician. GPs enrolled 6,104 and psychiatrists 1,433 patients. Data collected: sociodemographics, psychiatric profile, environmental risk factors of depression and treatment. All clinical data were collected by participating physicians; there was no direct independent clinical assessment of patients to check the diagnosis of depressive disorder.
Compared to patients identified as depressed by GPs, those identified by psychiatrists were younger, more often urban (10.5% v 5.4% - OR = 2.4), educated (42.4% v 25.4% - OR = 3.9), met DSM-IV criteria for depression (94.6% v 85.6% - OR = 2.9), had been hospitalized for depression (26.1% v 15.6% - OR = 2.0) and were younger at onset of depressive problems (all adjusted p < .001). No difference was found for psychiatric and somatic comorbidity, suicide attempt and severity of current depression. Compared to GPs, psychiatrists more often prescribed tricyclics and very novel antidepressants (7.8% v 2.3% OR = 5.0 and 6.8% v 3.0% OR = 3.8) with longer duration of antidepressant treatment. GPs' patients received more "non-conventional" treatment (8.8% v 2.4% OR = 0.3) and less psychotherapy (72.2% v 89.1% OR = 3.1) (all adjusted p < .001).
Differences between patients mainly concerned educational level and area of residence with few differences regarding clinical profile. Differences between practices of GPs and psychiatrists appear to reflect more the organization of the French care system than the competence of providers.
BMC Family Practice 02/2006; 7:5. · 1.80 Impact Factor
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ABSTRACT: Little is known about the actual management and treatment of chronic myeloid leukemia (CML) in clinical practice, although there have been many recent changes, such as the introduction of imatinib.
A two-phase cross-sectional observational study with retrospective data collection was conducted in France. In the first phase information regarding health services treating patients with CML was collected. In the second phase, centers caring for 10 or more patients were asked to provide data regarding patients diagnosed with CML that had had a consultation or been hospitalized in the last 3 months.
All French departments of hematology (n=218) were contacted by phone. The median number of patients followed per center is 6 (range 0--200). The median number of new patients seen during the last 12 months was 2 (range 0--60). In the second phase 538 patients were included, the sex ratio being 1.14 and median age 55. At the time of diagnosis, 96.8% (n=519) were in chronic phase, 2.2% (n=12) in accelerated phase and 0.9% (n=5) in blastic phase. Eighty-two percent (n=443) of the patients have been treated by interferon (IFN). Sixteen point 3% (n=87) of the patients received a bone marrow transplantation (BMT). Forty-six percent (n=236) of the patients were treated with imatinib.
This is the first study providing detailed descriptive data concerning the use of medications and procedures in a large population of patients from the medical centers involved in treating CML patients in France. Further observational studies are needed to assess the impact of different treatment strategies and economic impact of CML care in France.
Pharmacoepidemiology and Drug Safety 09/2005; 14(8):545-53. · 2.53 Impact Factor
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ABSTRACT: Announcement of cancer diagnosis and first contact with medical team in charge of treatment is critical for the patient as well as for the quality of care. The French Cancer Plan include a special focus on these announcement which should be performed in adequate conditions and which should include the presentation of a personalised treatment plan, that reflect multidisciplinary discussion and decision performed before. In order to generalized a formal announcement consultation all over the country in 2005, an experimentation has been performed in 58 centers grouped in 37 projects. Neuro-Oncology Unit of the Assistance Publique-Hopitaux de Marseille did participate to that experimentation. Evaluation of these experiment focus on physician, nurse, and patient perception as well as cost impact and exploration of language during that particular time. Implication of a referent nurse in that time was a strong option of our center. We analyzed the result in 80 patients referred in our center for initial diagnosis (78%) or announcement of recurrence (14%) in a 5 months time. Implication of the nurse appear to be critical for patient confidence and accessibility to information for the all medical team. Organization of a particular time devoted to cancer announcement appear to have a favourable impact on quality of care and patient perception, and constitute a first step to a personalized management of patients with cancer.
Bulletin du cancer 05/2005; 92(4):373-80. · 0.67 Impact Factor
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ABSTRACT: Devant l’ampleur des investissements de l’industrie pharmaceutique et les risques financiers encourus par celle-ci, il est important pour les firmes pharmaceutiques de protéger au mieux leurs inventions par de multiples techniques et ce, pendant une longue période. Les brevets appliqués aux molécules sont un moyen de protection temporaire, à ces derniers brevets peuvent s’ajouter des brevets additionnels ou brevets secondaires. Enfin le certificat complémentaire de protection constitue aussi un moyen juridique de protection des brevets de médicaments. Une autre méthode, exclusive cette fois-ci de référence juridique, permet d’étendre la durée de protection des brevets de médicaments, c’est l’inversion chirale.Mots clés : propriété intellectuelle, brevet pharmaceutique, durée de protection, brevet additionnel, certificat complémentaire de protection, inversion chiraleAbstractPharmaceutical research constitutes a significant cost for pharmaceutical companies. Because of the importance of the financial investment in research projects, companies must protect their discoveries. There are multiple ways to do this. First, the legal avenue can be divided into three parts: a pharmaceutical company can protect a new drug by a patent, then an additional patent or a secondary patent; moreover, since 1992 in Europe, the pharmaceutical industry has been able to extend a patent by the “Supplementary Protection Certificate” (le Certificat Complémentaire de Protection [CCP]). The nonjuridical way is to use the chiral “switch”, which can extend patents close to expiring, thus enhancing profitability. Keywords: intellectual property, drug patent, patent’s term, additional patent, supplementary protection certificate, chiral switchTexte reçu le 28 octobre 2003 ; accepté le 9 février 2004
Thérapie 12/2003; 59(2):253-257. · 0.30 Impact Factor
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ABSTRACT: This paper focuses on the methodology and behavioural results of the tryptophan depletion challenge.
A Medline search (1985-2002) using the keywords 'tryptophan depletion' and 'mood' has been performed.
Rapid depletion is obtained by morning intake under fasting condition of a tryptophan-free amino-acid mixture. Subjects with a family history of mood disorders and depressed patients receiving serotoninergic drugs demonstrate a mood-lowering effect. However, these effects are limited or absent in normal volunteers and naive depressed patients.
The tryptophan depletion challenge has largely contributed to the understanding of the physiopathology of depression. However, the mood response to acute tryptophan depletion challenge in healthy volunteers is not as sensitive as a 'depression model'.
Thérapie 58(4):295-303. · 0.30 Impact Factor
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ABSTRACT: Pharmaceutical research constitutes a significant cost for pharmaceutical companies. Because of the importance of the financial investment in research projects, companies must protect their discoveries. There are multiple ways to do this. First, the legal avenue can be divided into three parts: a pharmaceutical company can protect a new drug by a patent, then an additional patent or a secondary patent; moreover, since 1992 in Europe, the pharmaceutical industry has been able to extend a patent by the "Supplementary Protection Certificate" (le Certificat Complémentaire de Protection [CCP]). The nonjuridical way is to use the chiral "switch", which can extend patents close to expiring, thus enhancing profitability.
Thérapie 59(2):253-7. · 0.30 Impact Factor
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ABSTRACT: Ketamine, an antagonist N-Methyl-D-Aspartate receptor, induces a broad range of anomalies in healthy subjects similar to those observed in psychosis. Previous studies have shown that information sensorimotor processing was impaired in patients with schizophrenia. The aim of the study was to assess the effects of subanesthetic doses of ketamine on behavior symptoms and information processing in healthy volunteers. A double-blind, crossover, placebo-controlled study was performed with eight subjects. Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, and Scale for the Assessment of Positive Symptoms assessed behavior changes. Information processing was assessed using a choice reaction time. Three experimental factors (stimulus intensity, stimulus response compatibility, and foreperiod duration) chosen to affect a different stage of information processing were manipulated. Our study has demonstrated that administration of ketamine produced significant effects on Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, and Scale for the Assessment of Positive Symptoms scores. Results on choice reaction time demonstrated a significant longer reaction time under ketamine. Effects of stimulus intensity and compatibility stimulus response were similar under ketamine and under placebo. Moreover, there was a specific interaction between ketamine and foreperiod. This interaction indicated that foreperiod's effect was more prolonged under ketamine (29 ms) than under placebo (17 ms). These results showed that the clinical effects of ketamine were associated with schizophrenic-like impairments on choice reaction time in healthy subjects.
Clinical Neuropharmacology 25(2):101-6. · 2.17 Impact Factor
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ABSTRACT: Hiccup is a sudden contraction of the inspiratory muscles, followed by an abrupt closure of the glottis, thus producing a characteristic sound. In the literature, some drugs have been reported to induce hiccup. We discuss three case reports after administration of benzodiazepine to healthy young subjects during two clinical trials. In the first study (a bioequivalence trial of two forms of lormetazepam, tablets and oral solution), 12 subjects were included in an open controlled crossover study with two periods separated by a washout of 7 days. Two subjects presented with hiccup after administration of lormetazepam (2mg oral solution). The symptom resolved in 10 and 40 minutes, respectively. In one subject, rechallenge with a tablet of lormetazepam was positive. The aim of the second study was to assess the effect of sleep deprivation and lorazepam-induced sedation on saccadic eye movements in 12 healthy subjects. Hiccup occurred in one subject 3h 15 after administration of a single oral dose of lorazepam (2mg) and resolved in 45 minutes. All cases were evaluated according to the French imputation method. These observations are discussed with regard to the drug classes mentioned most frequently in the literature.
Thérapie 60(1):57-60. · 0.30 Impact Factor
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ABSTRACT: Hiccup is a sudden contraction of the inspiratory muscles, followed by an abrupt closure of the glottis, thus producing a characteristic sound. In the literature, some drugs have been reported to induce hiccup. We discuss three case reports after administration of benzodiazepine to healthy young subjects during two clinical trials. In the first study (a bioequivalence trial of two forms of lormetazepam, tablets and oral solution), 12 subjects were included in an open controlled crossover study with two periods separated by a washout of 7 days. Two subjects presented with hiccup after administration of lormetazepam (2 mg oral solution). The symptom resolved in 10 and 40 minutes, respectively. In one subject, rechallenge with a tablet of lormetazepam was positive. The aim of the second study was to assess the effect of sleep deprivation and lorazepam-induced sedation on saccadic eye movements in 12 healthy subjects. Hiccup occurred in one subject 3h 15 after administration of a single oral dose of lorazepam (2 mg) and resolved in 45 minutes. All cases were evaluated according to the French imputation method. These observations are discussed with regard to the drug classes mentioned most frequently in the literature. Le hoquet se définit comme une contraction spasmodique du diaphragme déterminant une brusque secousse de l'abdomen et du thorax. Dans la littérature disponible, quelques médicaments sont retrouvés à l'origine de ce symptôme. Nous rapportons trois observations après administration de benzodiazépine à des sujets sains jeunes, durant deux essais cliniques. Dans la première étude (un essai de bioéquivalence entre deux formes galéniques, comprimés et solution orale), 12 sujets ont été inclus dans un essai en ouvert, contrôlé, randomisé avec deux périodes séparées par un "washout" de 7 jours. Deux sujets ont présenté un hoquet après l'administration de 2 mg de lormétazépam (solution orale). Les symptômes ont régressé en 10 et 40 minutes respectivement. Chez un sujet, la réintroduction avec le comprimé de lormétazépam a été positive. L'objectif de la deuxième étude était d'évaluer les effets d'une privation de sommeil et de la sédation induite par le lorazépam sur les mouvements oculaires saccadiques chez 12 sujets sains. Un hoquet est apparu chez un sujet, 3 h 15 après l'administration de lorazépam (2 mg) et a régressé en 45 minutes. Toutes ces observations ont été évaluées avec la méthode d'imputabilité française et discutées à la lumière des classes de médicaments le plus souvent mentionnés dans la littérature.
http://dx.doi.org/10.2515/therapie:2005007.
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ABSTRACT: Introduction: This paper focuses on the methodology and behavioural results of the tryptophan depletion challenge. Methods: A Medline search (1985–2002) using the keywords "tryptophan depletion" and "mood" has been performed. Results: Rapid depletion is obtained by morning intake under fasting condition of a tryptophan-free amino-acid mixture. Subjects with a family history of mood disorders and depressed patients receiving serotoninergic drugs demonstrate a mood-lowering effect. However, these effects are limited or absent in normal volunteers and naive depressed patients. Conclusion: The tryptophan depletion challenge has largely contributed to the understanding of the physiopathology of depression. However, the mood response to acute tryptophan depletion challenge in healthy volunteers is not as sensitive as a "depression model". Introduction : Le but de cet article est de présenter une synthèse bibliographique sur la méthodologie et les effets sur l'humeur du test de déplétion en tryptophane. Méthode : Nous avons fait une recherche Medline de 1985–2002 autour des mots clés "tryptophan depletion" et "mood". Résultats : La déplétion aiguë est obtenue par l'ingestion le matin à jeun d'un mélange d'acides aminés exempt de tryptophane. Les sujets présentant une prédisposition familiale aux troubles dépressifs ainsi que les patients dépressifs traités par une molécule potentialisant la neurotransmission sérotoninergique présentent une altération plus ou moins importante de l'humeur. En revanche, les effets sont limités, voire inexistants, chez les sujets sains et les patients dépressifs naïfs de tout traitement. Conclusion : Le test de déplétion en tryptophane a largement contribué à la compréhension de la physiopathologie dépressive, mais il ne peut actuellement être utilisé comme modèle de dépression chez le sujet sain.
http://dx.doi.org/10.2515/therapie:2003046.
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ABSTRACT: Pharmaceutical research constitutes a significant cost for pharmaceutical companies. Because of the importance of the financial investment in research projects, companies must protect their discoveries. There are multiple ways to do this. First, the legal avenue can be divided into three parts: a pharmaceutical company can protect a new drug by a patent, then an additional patent or a secondary patent; moreover, since 1992 in Europe, the pharmaceutical industry has been able to extend a patent by the "Supplementary Protection Certificate" (le Certificat Complémentaire de Protection [CCP]). The nonjuridical way is to use the chiral "switch", which can extend patents close to expiring, thus enhancing profitability. Devant l'ampleur des investissements de l'industrie pharmaceutique et les risques financiers encourus par celle-ci, il est important pour les firmes pharmaceutiques de protéger au mieux leurs inventions par de multiples techniques et ce, pendant une longue période. Les brevets appliqués aux molécules sont un moyen de protection temporaire, à ces derniers brevets peuvent s'ajouter des brevets additionnels ou brevets secondaires. Enfin le certificat complémentaire de protection constitue aussi un moyen juridique de protection des brevets de médicaments. Une autre méthode, exclusive cette fois-ci de référence juridique, permet d'étendre la durée de protection des brevets de médicaments, c'est l'inversion chirale.
http://dx.doi.org/10.2515/therapie:2004049.
