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Biomedical subjects

Xavier Thirion

Publications and source records attributed to Xavier Thirion.

15 recordsLinked to original sources

Anxiolytics, hypnotics, and antidepressants dispensed to adolescents in a French region in 2002.

PURPOSE: This study proposes to complete declarative studies by describing the prescriptions of anxiolytics, hypnotics, and antidepressants dispensed to adolescents in a French region in 2002. METHODS: This cross-sectional study analyzes all the hypnotic, anxiolytic, and antidepressant prescriptions (ATC codes beginning with N05B, N05C, and N06A, respectively) sent by adolescents (aged 13-17 years) to the French Health Insurance system of the study region for reimbursement during one year (2002). It was performed in a southern France area with 120,908 adolescents covered by this insurance scheme. Adverse drug reactions (ADRs) recorded in the Pharmacovigilance database were also studied. RESULTS: Three thousand two hundred and eighty-six adolescents (2.7% of adolescent population) had at least one prescription of the studied drugs. This prevalence increased with age and female sex, leading to a maximum of 6.3% for the 17-year-old girls. Two thousand four hundred and thirty-one of adolescents were dispensed anxiolytics, 935 antidepressants, and 548 hypnotics. The most dispensed drugs were zolpidem, zopiclone, and niaprazine for hypnotics; hydroxyzine, etifoxine, and bromazepam for anxiolytics; and paroxetine, sertraline, and fluoxetine for antidepressants. Zolpidem, hydroxyzine, and paroxetine accounted, respectively, for 82.9%, 57.1%, and 59.8% of the prescriptions. 75.5% of hypnotics users had only one prescription, 77.4% for anxiolytics, and 57.4% for antidepressants. Three ADRs were reported. CONCLUSIONS: This study confirms the large use of psychotropics in French adolescents and the influence of age and sex. Also, the results underline treatment for most adolescents is short, which may be beneficial for hypnotics and anxiolytics but not for antidepressants.

Adolescent↗

Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is the most common hereditary peripheral neuropathy, affecting 1 in 2,500 people. The only treatment currently available is rehabilitation or corrective surgery. The most frequent form of the disease, CMT-1A, involves abnormal myelination of the peripheral nerves. Here we used a mouse model of CMT-1A to test the ability of ascorbic acid, a known promoter of myelination, to correct the CMT-1A phenotype. Ascorbic acid treatment resulted in substantial amelioration of the CMT-1A phenotype, and reduced the expression of PMP22 to a level below what is necessary to induce the disease phenotype. As ascorbic acid has already been approved by the FDA for other clinical indications, it offers an immediate therapeutic possibility for patients with the disease.

Animals↗

Assessment of doctor-shopping for high dosage buprenorphine maintenance treatment in a French region: development of a new method for prescription database.

PURPOSE: To assess the extent of doctor-shopping for buprenorphine maintenance therapy in a French region with a specific indicator. METHODS: Use of a quasi-exhaustive prescription database in a French region (information system of the French General Health Insurance Scheme). Extraction of all buprenorphine prescriptions between September 1999 and December 2000. Definition and calculation of three quantities for each patient: delivered, prescribed and doctor-shopping quantity. The calculation of these three quantities is done by an automated and reproducible method determining the overlaps in prescription periods of different physicians for a given patient. Calculation of the corresponding daily dose was done for each quantity. RESULTS: A total of 64 326 prescriptions of buprenorphine by 1313 physicians to 3259 patients were extracted. Quantities and doses were calculated for 2587 patients. The total doctor-shopping quantity represented 18.6% of the delivered quantity. Doctor-shopping involved a minority of patients and was highly concentrated: 87 patients with doctor-shopping doses superior to 16 mg/day were responsible for 45.4% of the total doctor-shopping quantity. CONCLUSIONS: Doctor-shopping appears to be an important problem for buprenorphine maintenance treatment in France but may be resolved by regulatory interventions. The use of adequate indicators on prescription databases may help to limit the effects of such interventions on legitimate care. The method presented here may be used with slight adaptations for other medications to assess their abuse potential.

Buprenorphine↗

Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the effects of a 48-hr neuromuscular blocking agents (NMBA) infusion on gas exchange over a 120-hr time period in patients with acute respiratory distress syndrome. DESIGN: Multiple center, prospective, controlled, and randomized trial. SETTING: Four adult medical or mixed medical-surgical intensive care units. PATIENTS: A total of 56 patients with acute respiratory distress syndrome with a PaO2/FiO2 ratio of <150 at a positive end-expiratory pressure of > or =5 cm H2O. INTERVENTIONS: After randomization, patients received either conventional therapy without NMBA (control group) or conventional therapy plus NMBA for the next 48 hrs. The initial ventilator mode was volume-assist/control. The ventilator remained on assist-control mode throughout the initial 48-hr period in both groups. Tidal volume was 6-8 mL/kg ideal body weight. MEASUREMENTS AND MAIN RESULTS: When analyzed for the entire 120 hrs, there was a significant effect of the NMBA on the course of PaO2/FiO2 ratio (p =.021). Separate comparisons at each time point indicated that patients randomized to the NMBA group had a higher PaO2/FiO2 at 48, 96, and 120 hrs after randomization. Moreover, a decrease of positive end-expiratory pressure (p =.036) was only found in the NMBA group. Two-way repeated-measures analysis of variance exhibited a decrease in positive end-expiratory pressure over time (p =.036). Concerning short-term effects, there was no modification of PaO2/FiO2 ratio 1 hr after randomization in either group. Only one patient (from the control group) developed pneumothorax. CONCLUSIONS: Use of NMBA during a 48-hr period in patients with acute respiratory distress syndrome is associated with a sustained improvement in oxygenation.

Acute Disease↗

Prone position and positive end-expiratory pressure in acute respiratory distress syndrome.

OBJECTIVE: To determine whether positive end-expiratory pressure (PEEP) and prone position present a synergistic effect on oxygenation and if the effect of PEEP is related to computed tomography scan lung characteristic. DESIGN: Prospective randomized study. SETTING: French medical intensive care unit. PATIENTS: Twenty-five patients with acute respiratory distress syndrome. INTERVENTIONS: After a computed tomography scan was obtained, measurements were performed in all patients at four different PEEP levels (0, 5, 10, and 15 cm H2O) applied in random order in both supine and prone positions. MEASUREMENTS AND MAIN RESULTS: Analysis of variance showed that PEEP (p <.001) and prone position (p <.001) improved oxygenation, whereas the type of infiltrates did not influence oxygenation. PEEP and prone position presented an additive effect on oxygenation. Patients presenting diffuse infiltrates exhibited an increase of Pao2/Fio2 related to PEEP whatever the position, whereas patients presenting localized infiltrates did not have improved oxygenation status when PEEP was increased in both positions. Prone position (p <.001) and PEEP (p <.001) reduced the true pulmonary shunt. Analysis of variance showed that prone position (p <.001) and PEEP (p <.001) reduced the true pulmonary shunt. The decrease of the shunt related to PEEP was more pronounced in patients presenting diffuse infiltrates. A lower inflection point was identified in 22 patients (88%) in both supine and prone positions. There was no difference in mean lower inflection point value between the supine and the prone positions (8.8 +/- 2.7 cm H2O vs. 8.4 +/- 3.4 cm H2O, respectively). CONCLUSIONS: PEEP and prone positioning present additive effects. The prone position, not PEEP, improves oxygenation in patients with acute respiratory distress syndrome with localized infiltrates.

Adult↗

Long-term outcome in intensive care unit survivors after mechanical ventilation for intracerebral hemorrhage.

OBJECTIVE: To evaluate long-term survival and functional outcome in intensive care unit survivors after mechanical ventilation for intracerebral hemorrhage. DESIGN: Retrospective chart review and prospective follow-up study. SETTING: Outpatient follow-up. PATIENTS: Between 1997 and 2000, 120 patients were mechanically ventilated for an intracerebral hemorrhage at our intensive care unit. Sixty-two patients were discharged from hospital (in-hospital mortality = 48%). Sixty patients were evaluated for survival and functional outcome (two were lost to follow-up). Time between discharge and follow-up was > or =1 yr and was a mean of 27 +/- 14 months (range, 12-56). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients' physicians were first asked about survival, and patients or proxies were interviewed by phone. Barthel Index and modified Rankin Scale scores were collected, and demographic information and general data were reviewed. The estimated life-table survival curve after discharge was 64.6% at 1 yr and 57% at 3 yrs. In the 24 patients who died, the mean time between discharge and death was 5 +/- 6 months. Probability of death after discharge significantly increased if age at admission was >65 yrs (p <.01; odds ratio, 3.5; 95% confidence interval, 1.4-9.1) and if Glasgow Coma Scale score at discharge was <15 (p <.01; odds ratio, 3.9; 95% confidence interval, 1.6-9.5). In the 36 long-term survivors, Barthel Index was 67.5 +/- 15 (median +/- median absolute dispersion) and modified Rankin Scale score was 2.6 +/- 0.5. Fifteen patients (42%) had a slight or no disability (Barthel Index > or =90 and modified Rankin Scale score < or =2), whereas 21 patients (58%) had moderate or severe disability (Barthel Index < or =85 and modified Rankin Scale score >2). CONCLUSIONS: Probability of survival at 3 yrs after mechanical ventilation for an intracerebral hemorrhage was >50%. Age was an important determinant of long-term survival. Forty-two percent of long-term survivors were independent for activities of daily living. Only a few long-term survivors had a very high degree of disability.

Adult↗

Cardiopulmonary effects of lipid emulsions in patients with ARDS.

STUDY OBJECTIVES: Lipid emulsions have been suspected of inducing certain modifications in gas exchange and pulmonary hemodynamics. The aim of this prospective study was to evaluate the hemodynamic and pulmonary effects of two lipid emulsions. DESIGN: Prospective, randomized, double-blind, crossover study. SETTING: Medical and surgical ICU in a French university hospital. PATIENTS: Eighteen patients presenting ARDS. INTERVENTIONS: Each patient received a 6-h infusion of a 20% fat emulsion containing 100% long-chain triglycerides (LCTs) and a 6-h infusion of 50% LCTs/50% medium-chain triglycerides (MCTs) 20% lipid emulsion at the rate of 1.0 mL/kg/h. An 18-h period with no lipids separated the two periods. An additional 18-h period after the end of the second lipid emulsion administration was observed prior to the final measurements. MEASUREMENTS AND RESULTS: The MCT/LCT emulsion increased the PaO(2)/fraction of inspired oxygen (FIO(2)) ratio (p = 0.005) compared with LCT emulsion alone. The mean (+/- SD) PaO(2)/FIO(2) ratio increased from 165 +/- 55 to 191 +/- 64 mm Hg after 1 h of LCT/MCT administration (p < 0.03), and to 175 +/- 46 mm Hg after 6 h. Moreover, there was an increase in oxygen delivery after 6 h of LCT/MCT administration (p < 0.001 vs baseline). While a time-related increase in mean pulmonary artery pressure (p = 0.012) during lipid administration was found, no effect of the kind of lipid emulsion was observed. The time-related increase in cardiac index (p = 0.002) was more marked when the patients received the LCT/MCT emulsion (p = 0.002). Pulmonary vascular resistances were not affected by the kind of lipid emulsion. CONCLUSIONS: The present work showed that while the LCT emulsion induced no deleterious effects on oxygenation in ARDS patients, the LCT/MCT emulsion improved the PaO(2)/FIO(2) ratio and had a further beneficial effect on oxygen delivery.

Cross-Over Studies↗

[High-dose buprenorphine prescription in southern France from 1999 to 2001].

Several reports have focused on prescription of high-dose buprenorphine using data electronically transmitted to the French health reimbursement system. This study deals with high-dose buprenorphine prescriptions in the Bouches-du-Rhone region between 1999 and 2001. We determined the number of maintained patients followed by practitioners (either short- or long-term care), the doses administered, and the associated prescription of psychotropic treatments. The number of general practitioners involved in 84% of the prescriptions of high-dose buprenorphine grew with a high turnover (20%). More than 25% of the general practitioners in the region prescribed this drug, but only 38% of them were involved in long-term follow-up of more than one maintained patient. The number of maintained patients and the mean daily treatment dose delivered (13.4 mg/d during 2001) increased. The associated prescriptions of benzodiazepines concerned 47% of the patients during 2001 (on the rise), but the associated prescription of flunitrazepam tended to decrease (29% of the subjects during 2001 versus 32% during 2000). This study shows a tendency for deviant behaviors to increase, constituting a public health concern.

Adult↗

Stage I non-small cell lung cancer: a pragmatic approach to prognosis after complete resection.

BACKGROUND: Long-term results of the surgical treatment of stage I non-small cell lung cancer (NSCLC) are disappointing. METHODS: Univariate and multivariate analyses were conducted on 515 consecutive lung resections for stage I NSCLC performed from 1990 to 1999 and identified by reviewing a database into which data were entered prospectively. Tumors were staged as stages IA (n = 147) and IB (n = 348) according to the 1997 UICC (Union Internationale Contre le Cancer) pTNM classification. RESULTS: Operative mortality rates were 6.2%, 5.3%, 2.3%, and 0% for pneumonectomy, bilobectomy, lobectomy, and lesser resections, respectively. Overall survival rate was 61.1% (55.8% to 66.5%) at 5 years. Univariate analysis identified three significant adverse prognosticators: arteriosclerosis as comorbidity, pathologic T2 status, and blood vessel invasion. Male sex (p = 0.056) and performance of pneumonectomy (p = 0.057) were at the threshold of statistical significance. At multivariate analysis, three independent prognosticators entered the model: arteriosclerosis, blood vessels invasion, and performance of pneumonectomy. CONCLUSIONS: Long-term survival of patients with completely resected stage I NSCLC was adversely influenced in a relatively balanced way by factors related to the clinical status of the patient, to the tumor, and to the treatment.

Adult↗

Upregulation of chemokines in bronchoalveolar lavage fluid as a predictive marker of post-transplant airway obliteration.

BACKGROUND: The early stage of post-transplant obliterative bronchiolitis (OB) is characterized by an influx of inflammatory cells to the lung, among which neutrophils may play a role in key events. The potential for chemokines to induce leukocyte accumulation in the alveolar space was investigated. We assessed whether changes in the chemotactic expression profile could be used as sensitive markers of the onset of OB. METHODS: Serial bronchoalveolar lavage (BAL) fluids from 13 stable healthy recipients and 8 patients who developed bronchiolitis obliterans syndrome (BOS) were analyzed longitudinally for concentrations of interleukin-8 (IL-8), chemokines regulated-upon-activation and normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significantly elevated percentages of BAL neutrophils and IL-8 levels were found at the pre-clinical stage of BOS, on average 151 +/- 164 days and 307 +/- 266 days, respectively, before diagnosis of BOS. There was also early upregulation of RANTES and MCP-1 in the BOS group (mean 253 +/- 323 and 152 +/- 80 days, respectively, before diagnosis of BOS). The level of MCP-1 was consistently higher than that of RANTES until airway obliteration. BAL sICAM-1 and sVCAM-1 levels were not statistically different between the groups. CONCLUSIONS: These data support the belief that RANTES, IL-8 and MCP-1 play a crucial role in the pathogenesis of OB. The results show that relevant increased levels of such chemokines may predict BOS, and suggest that there is potential for some of these markers to be used as early and sensitive markers of the onset of BOS. Longitudinal monitoring of these chemokine signals may contribute to better management of patients at risk for developing OB, at a stage when remodeling can either be reversed or altered.

Biomarkers↗

Can the tomographic aspect characteristics of patients presenting with acute respiratory distress syndrome predict improvement in oxygenation-related response to the prone position?

BACKGROUND: In some patients with acute respiratory distress syndrome, the prone position is able to improve oxygenation, whereas in others it is not. It could be hypothesized that the more opacities that are present in dependent regions of the lung when the patient is in the supine position, the better the improvement in oxygenation is observed when the patients are turned prone. Therefore, we conducted a prospective study to identify computed tomographic scan aspects that could accurately predict who will respond to the prone position. METHODS: We included 46 patients with acute respiratory distress syndrome (31 responders and 15 nonresponders). Computed tomographic scan was performed in the 6-h period preceding prone position. Blood gas analyses were performed before and at the end of the first 6-h period of prone position. RESULTS: Arterial oxygen partial pressure/fraction of inspired oxygen increased from 117 +/- 42 (mean +/- SD) in the supine position to 200 +/- 76 mmHg in the prone position (P < 0.001). There were 31 responders and 15 nonresponders. There was a vertebral predominance of the opacities (P < 0.0001). However, there was no difference between responders and nonresponders. When only the amount of consolidated lung located under the heart was evaluated, there was more consolidated tissue under the heart relative to total lung area in nonresponders than in responders (P = 0.01). CONCLUSIONS: There are no distinctive morphologic features in the pattern of lung disease measured by computed tomographic scanning performed with the patient in the supine position that can predict response to the prone position.

Aged↗

[Misuse of trihexyphenidyl (Artane, Parkinane): recent trends].

Recent observations suggest the existence of trihexyphenidyl abuse linked to its hallucinogenic and euphoric effects. In order to determine the importance of this practice and the characteristics of those involved, a study based on data from the Provence-Alpes-Côte-d'Azur and the Corsica health reimbursement system was carried out. Individuals from these regions affiliated to the French health reimbursement system who had a prescription for trihexyphenidyl (Artane, Parkinane) reimbursed between January 1, 2001, and February 15, 2001, were selected. The delivery of prescriptions was monitored over a 9-month period. In total, 3028 subjects were selected. A subgroup comprising 2.1% of subjects with deviant behaviour was identified by factorial analysis and compared with the subgroup without deviant behaviour. The subjects with deviant behaviour were young and mostly male. The dosage of trihexyphenidyl was higher in these subjects (28 mg/day versus 7 mg/day) and a greater proportion used benzodiazepine and high-dose buprenorphine compared with those without deviant behaviour. The number of prescriptions delivered was higher (23.0 versus 7.7) as well the number of different physicians (4.9 versus 1.5) and pharmacies (5.0 versus 1.3) for those subjects with deviant behaviour. This study confirms the abuse and dependence potential associated with trihexyphenidyl use and the need to increase the supervision of this drug.

Adult↗

[Neocodion misuse: evolution between 1992 and 2002].

Neocodion, a codeine antitussive preparation (codeine camphosulfonate + Grindelia + sulfogaiacol) is known to be misused by opiate addicts. This study aimed to examine the evolution in Neocodion use between 1992 and 2002. Since 1992, three surveys (1992, 1997 and 2002) investigating Neocodion misuse were performed via several community networks of pharmacists. During the same time, data on Neocodion use were extracted from the French drug-dependence monitoring programme (OPPIDUM [Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse]). A marked and continuous decrease in Neocodion consumption was observed. The number of requests for Neocodion per pharmacy and per week largely decreased from 9.9 to 2.1 between 1992 and 2002. OPPIDUM data also showed a reduction in the rate of Neocodion consumption (from 8% in 1992 to 0.4% in 2002). Patients were older (30.4 years in 1992 and 33.7 years in 2002) and their socioeconomic conditions were better. Eighty-six percent of the subjects studied were poly-drug consumers. In fact, Neocodion was less sought after for opiate maintenance than for its psychoactive effects. Despite the reduction in the consumption of Neocodion, the changes observed in the consumption patterns for this medication suggest that vigilance is still required.

Adult↗

[Use of the health insurance database by the centres for evaluation and information on pharmacodependance: examples, interests and future prospects].

In France, the observation and evaluation of drug abuse and dependence associated with pychoactive medications are the responsibility of the National Commission for Narcotics and Psychotropic Drugs. In order to assist this commission, several centres for evaluation and information on pharmacodependence (CEIP) were created throughout in France. Recently, in order to complete their epidemiological tools, several centres have developed another pharmacoepidemiological approach using data for refunded prescriptions obtained from the local and regional French Health Insurance database. This article underlines the potential contribution of the Health Insurance database to improving knowledge of drug use in the real-life conditions based on studies performed by the CEIP. Several examples are given showing the extent of the possibilities (population-based studies, cohort studies, development of misuse indicators). In spite of their limitations (e.g. the difference between consumption and delivery), these examples confirm that these database may be a novel tool for CEIP to assess a potential abuse of a medication.

Anti-Anxiety Agents↗

[Misuse of clonazepam (Rivotril): recent trends].

Recent observations suggest the existence of clonazepam abuse. In order to determine the importance of this practice and the characteristics of these consumers, a study has been carried out, based on data from the Provence-Alpes-Côte-d'Azur and Corsica health reimbursement system. Individuals from these regions affiliated to the French health reimbursement system, who have had a prescription of clonazepam reimbursed between January 1, 2001 and February 15, 2001, have been selected. The deliveries have been monitored over a 9 month-period. 9381 subjects have been selected. A sub-group of 1.5 per cent subjects with a deviant behaviour has been identified by factorial analysis and has been compared to the sub-group without deviant behaviour. The subjects with deviant behaviour are younger and mostly male. The dosage of clonazepam is higher (10.8 mg per day versus 2.1 mg per day) with a significantly higher proportion of benzodiazepine and high-dose buprenorphine. The number of deliveries is higher (19.4 versus 5.9) as well as the number of different physicians (4.5 versus 1.5) and pharmacies (5.9 versus 1.3). This study provides some arguments in favor of the potential of abuse and dependence of clonazepam and the necessity to reinforce its monitoring. This information requires to be relayed to health professionals.

Clonazepam↗