Biomedical subjects

Pierre-Michel Llorca

Publications and source records attributed to Pierre-Michel Llorca.

15 recordsLinked to original sources

PubMed2006

Alcohol consumption during pregnancy: a urge to increase prevention and screening.

Alcohol consumption was evaluated in 1,027 pregnant women in the Auvergne region of central France. Only 53% declared total abstinence during pregnancy. 33% had 1-4 units on monthly occasion, while 13% drunk more frequently. One percent had 5 or more units per occasion. Despite the consensus recommending total abstinence during pregnancy, prenatal alcohol exposure remains a major public health issue.

Alcohol Drinking↗

PubMed2006

Impact of practitioner's training in the management of alcohol dependence: a quasi-experimental 18-month follow-up study.

BACKGROUND: In many European countries, medical education on alcohol remains inadequate in terms of both quantity and quality. The expansion of GP training and care protocols would improve the management and outcome of alcoholic patients. Our purpose was to assess the impact of a multifaceted intervention by trained GPs in the management of alcohol-dependent patients. RESULTS AND DISCUSSION: Trained GPs proved better i) in the attempt at abstinence, with 67% patients becoming sober vs. 47% in a comparison sample and ii) in repeat attempt at abstinence in the event of relapse, with an average 2.99 vs. 1.31 attempts per patient. There were no differences in terms of i) relapses, which involved about three in four patients, and ii) prolonged abstinence, which averaged two months. Overall, patients managed by trained GPs remained abstinent 103 days during the 18-month follow-up period vs 68 days for the comparison sample (p = 0.016). METHODS: This 18-month follow-up study had a quasi-experimental design with 24 volunteer trained GPs and a comparison sample of a representative sample of 24 GPs. All GPs included their own already existing DSM-IV alcohol-dependent patients. Patients with depression or anxiety comorbidities were included. Participants were 126 patients in the trained sample and 122 in the comparison sample. The two patient samples were evenly-balanced, averaging 47 years old and 80% males. In the trained sample, consultations were scheduled and management (medication, biological workup) was protocolized, whereas the comparison sample representing standard practice had no obligations. CONCLUSION: Medical education can sharply improve the management of alcohol-dependent patients and short-term outcome. Trained GPs lead more patients to attempt abstinence and more often than in standard practice. However, a strict medical approach remains limited in the maintenance of medium-term abstinence (over two months), providing a strong argument for multidisciplinary management of alcohol-dependent patients.

Alcoholism↗

PubMed2006

Effects of cyamemazine on hERG, INa, ICa, Ito, Isus and IK1 channel currents, and on the QTc interval in guinea pigs.

The antipsychotic and anxiolytic phenothiazine, cyamemazine, was investigated for its effects on the hERG (human ether-à-go-go related gene) channel expressed in HEK 293 cells and on native INa, ICa, Ito, Isus, or IK1 of human atrial myocytes. Moreover, cyamemazine and terfenadine were compared for their effects on the QT interval in anesthetized guinea pigs. Cyamemazine reduced hERG current amplitude with an IC50 value of 470 nM. Cyamemazine 1 microM failed to significantly affect INa, Ito, Isus, or IK1 amplitudes and slightly decreased ICa (18%). For comparison, haloperidol (30 nM) and olanzapine (300 nM) reduced hERG current amplitude by 44.2+/-3.9% and 49.7+/-4.2%, respectively. The cardiac safety ratio of cyamemazine, calculated from the IC50/receptor affinity ratios, is 81 and 313 against dopamine D2 receptors and 5-HT2A receptors, respectively. In guinea pigs, QT and QTcBazett were not significantly modified by intravenous cyamemazine when compared to the effects produced by the vehicle. Conversely, terfenadine (5 mg/kg iv) increased significantly QTcBazett (+58 ms), QTcFrediricia (+83 ms) and QTcVan de Water (+78 ms). In conclusion, cyamemazine concentrations required to inhibit hERG current exceed substantially those necessary to achieve therapeutic activity in humans. Moreover, cyamemazine, in contrast to terfenadine, does not delay cardiac repolarization in the anesthetized guinea pig. These non-clinical findings confirm the excellent cardiac safety records of cyamemazine during its 30 years of extensive therapeutic use.

Animals↗

PubMed2006

AlQoL 9 for measuring quality of life in alcohol dependence.

AIMS: Quality of life (QoL) is an important factor of outcome tracking and treatment in alcohol misuse. A 9-item QoL scale, AlQoL 9, obtained from the generic SF 36, is proposed as a measure that characterizes the QoL of alcohol-dependent patients. Our objective was to study the psychometric properties of this subscale. METHODS: AlQoL 9 was evaluated in two study groups of patients with DSM-IV diagnosis of dependence: 104 inpatients, and 114 outpatients. Severity of dependence, alcohol consumption, psychiatric, and somatic comorbidities were assessed. We studied the global properties of AlQoL 9 and its structure. RESULTS: Cronbach alpha-coefficients in both populations indicated good internal consistency (0.71 and 0.85). Test-retest intraclass coefficients for a 2-day interval in hospital were in the range 0.57-0.78. Principal component analysis found a unidimensional scale. This subscale has properties that are consistent with the concept of QoL in alcohol dependence, i.e. lowered QoL compared with the general population, influenced by gender, and depression. CONCLUSIONS: AlQoL 9 epitomizes QoL in alcohol-dependence. It gives a global measurement with good psychometric properties. It could be used in clinical practice as a diagnosis and management support instrument and may also be useful in research for evaluating treatment efficacy.

Adolescent↗

PubMed2005

[Systematic use in hospitals of a alcohol problems detecting questionnaire. The CAGE (cut down, annoyed, guilty, eye opener) questionnaire].

OBJECTIVES: The CAGE questionnaire is considered a useful tool for detecting alcohol problems, especially in clinical populations. Its sensitivity exceeds 75% and its specificity 90%. Our objective was to assess performance of the French version of the CAGE (DETA) in identifying patients who meet the DSM-IV criteria and to discuss its usefulness in hospitals. METHODS: Data come from study of hospital morbidity in the Auvergne district of central France in 1998. Alcohol problems were diagnosed by physicians using the DSM-IV alcohol abuse or dependency criteria. For each diagnostic category, we calculated the performance of the CAGE questionnaire at a cut-off of 2 (CAGE 2+) and of 1 (CAGE 1+). RESULTS: The study included 5,452 patients--48.5% of them men--in acute- and intermediate-care facilities. CAGE 2+ had a sensitivity of 77% and a specificity of 94% among the diagnosed patients. It was more sensitive for patients diagnosed as alcohol-dependent than for alcohol abusers (61% vs 84%), but specificity was identical for both groups (94%). These results are similar to the properties of the English version. For a cut-off of 1 the CAGE had a sensitivity of 88% and a specificity of 87%. CONCLUSION: The French version of CAGE is a useful screening tool for alcohol abuse and dependance. Its systematic use in hospitals is desirable: a positive response to any item should attract the physician's attention and lead to further investigation.

Adult↗

PubMed2005

Validity of the CAGE questionnaire in hospital.

OBJECTIVE: The CAGE questionnaire is considered a useful screening and case-finding tool for alcohol use disorders in clinical populations. Our objectives were to validate the French version of the CAGE against DSM-IV criteria and to assess performance of each item of the scale. METHOD: Data were extracted from a hospital morbidity study conducted in central France. It concerned 5452 patients-48.5% men-in short and medium-stay units. Patients answered the CAGE questionnaire as a past-year assessment. The alcohol use disorders were diagnosed by the physicians using DSM-IV alcohol abuse or dependency criteria. RESULTS: The CAGE questionnaire for a cut-off of 2 had a sensitivity of 77% and a specificity of 94%. The CAGE test was more sensitive for patients diagnosed as alcohol-dependent than for alcohol abusers (61% vs. 84%) with the same specificity (94%). These values are close to those for the English-language CAGE. The first three items (CAG) were very similar, with sensitivity 70% and specificity 94%. The eye-opening question (E) differentiated sharply between abuse and dependency, with sensitivities of 18% and 46%, respectively. A questionnaire comprising only the CAG questions of the CAGE had properties similar to the full questionnaire. CONCLUSION: CAGE is a good screening tool for alcohol abuse or alcohol dependency. Given the frequent-and insufficiently diagnosed-alcohol problems among inpatients, CAGE is indicated as a first-line tool for screening for the most severe alcohol use disorders in hospital. It should ideally be used systematically. A positive reply to any of the first three items should alert the clinician and prompt further investigation.

Adult↗

PubMed2005

Efficacy and safety of direct transition to risperidone long-acting injectable in patients treated with various antipsychotic therapies.

The maintained antipsychotic efficacy of risperidone long-acting injectable (RLAI) was investigated in patients with schizophrenia or other psychoses who were transitioned directly from their previous antipsychotic medication. Patients symptomatically stable, but considered to require a treatment change, received 25 mg of RLAI (increased to 37.5 or 50 mg, if necessary) every 2 weeks for 6 months. Assessments included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), Global Assessment of Functioning (GAF), SF-36 Health-Related Quality of Life Questionnaire and Extrapyramidal Symptoms Rating Scale (ESRS). Of 1876 patients enrolled, 74% completed the 6-month study. The most frequent reasons for treatment change were non-compliance (38%), insufficient efficacy (33%) and side-effects (26%). There was a significant reduction from baseline to endpoint in mean total PANSS score and in the scores on all PANSS subscales and symptom factors (P<0.001). CGI-S improved significantly, as did mean GAF score, all factors on the SF-36 and patient satisfaction with treatment. Scores on ESRS showed significant, sustained improvements throughout the study period. Direct initiation of RLAI was effective and well tolerated. RLAI provides an advancement in the treatment options available for a wide range of patients requiring long-term antipsychotic therapy.

Adolescent↗

PubMed2005

Performance of asialotransferrin in detecting alcohol abuse.

BACKGROUND: The spectrum of alcohol use disorders covers hazardous use, alcohol abuse, and alcohol dependence. The present study evaluated the performance of asialotransferrin, a newly proposed biomarker for alcohol use disorders, in detecting alcohol abuse and alcohol dependence. METHOD: A 4-month trial was conducted in three groups of participants: alcohol abusers and alcohol-dependent patients, as defined in DSM-IV, and a control group. Asialotransferrin was assayed by capillary zone electrophoresis. RESULTS: Asialotransferrin demonstrated a sensitivity of 0.34 and a specificity of 1.00 for alcohol abuse. The sensitivity of asialotransferrin increased to 0.57 in alcohol-dependent patients. CONCLUSION: Despite the high specificity of asialotransferrin in alcohol use disorders, its sensitivity is too low to make it a useful marker of alcohol abuse.

Adult↗

PubMed2004

The use of biological laboratory markers in the diagnosis of alcohol misuse: an evidence-based approach.

BACKGROUND: A large number of patients seen in clinical practice have an underlying alcohol problem. There is a pressing need for accurate methods to diagnose alcohol over-consumption objectively. Our aim was to determine how best to use biological markers to objectify alcohol problems in patients with clinical suspicion of alcohol misuse. METHODS: A 6-month longitudinal multicenter trial was conducted, using four study groups (alcohol abusers, alcohol-dependents, healthy controls and consulting controls). CDT, GGT and MCV were measured. Statistical analyses used a computer learning system that created classification systems displayed in decision trees. RESULTS: In 379 subjects the marker that best discriminated those with alcohol problems from controls was CDT. GGT then helped to differentiate between alcohol abuse and alcohol dependence in cases of high CDT. MCV, age and gender provided no extra information. DISCUSSION: We recommend CDT as a first-line biological marker to confirm or disprove suspected alcohol misuse. High CDT plus GGT above normal points to alcohol dependence, while high CDT plus GGT below normal is evidence of alcohol abuse.

Adolescent↗

PubMed2004

Multicenter validation study of the %CDT TIA kit in alcohol abuse and alcohol dependence.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl transferase (GGT) are used as biomarkers of alcohol misuse. The aim of this study was to evaluate, in terms of sensitivity and specificity, the performance of the new Bio-Rad %CDT TIA kit and GGT assay for identifying alcohol abuse and alcohol dependence (according to the DSM-IV criteria). METHODS: An open multicenter study (30 centers) over 3 months, including patient groups of "abusers," "dependents," and controls, was conducted in France. RESULTS: In alcohol abuse, the sensitivity of GGT was 0.56, and that of CDT was 0.80; in alcohol dependence, the sensitivity of GGT was 0.86, and that of CDT was 0.91. The specificity of GGT was 0.77, and that of CDT was 0.83. The association of GGT with CDT increased sensitivity for alcohol abuse to 0.90 and for alcohol dependence to 0.99, but it appreciably decreased specificity (0.63). CONCLUSIONS: %CDT is the better screening marker for alcohol abuse and dependence, but GGT is still a useful marker for the detection of alcohol dependence. As an assay method, the second-generation Bio-Rad %CDT immunoassay can be recommended for routine CDT measurement.

Adult↗

PubMed2003

General practitioners and alcohol use disorders: quantity without quality.

BACKGROUND: General medical practitioners are essential for the prevention, diagnosis, and management of alcohol use disorders. Studies to examine medical practice in this field, however, are very rare. METHOD: A cross-sectional study involving 2010 patients seen by a sample of 145 general practitioners in the Auvergne region of central France was conducted on a given day in May 1998. The purpose of the study was to evaluate the prevalence of alcohol use disorders (using the DSM-IV diagnostic criteria for alcohol abuse or dependence and the CAGE questionnaire) and so to estimate the proportion of nonsomatic alcohol-related care dispensed. RESULTS: Sixteen percent of patients consulting their general practitioner had an alcohol problem, 27% of men and 5% of women. On average, a quarter of these patients had not been previously identified by the physician. Diagnosis seemed particularly difficult in women: 11% of women aged between 36 and 45 had an alcohol-related problem that went unidentified in 60% of cases. Care for alcohol-related health problems was therefore seriously inadequate. In one third of cases, patients with a diagnosed alcohol-related problem were not followed up by the physician for that problem. Two thirds received no medication, and in more than 80% of cases the physician did not refer to a specialist or prescribe admission to a specialized hospital ward. CONCLUSIONS: These results underline the diagnostic and therapeutic difficulties experienced by general practitioners. This study has led to the establishment of a pilot health care network for patients suffering from alcohol use disorders. This network involves voluntary doctors who have been trained and are better paid for their services. Care protocols have been established to which these practitioners have to adhere.

Adolescent↗

PubMed2003

Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic.

BACKGROUND: The long-term safety and efficacy of long-acting injectable risperidone, the first long-acting second-generation antipsychotic, were evaluated in stable patients with schizophrenia. METHOD: After a 2-week run-in period during which patients with DSM-IV schizophrenia received flexible doses of 1 to 6 mg of oral risperidone, patients received injections of 25 mg, 50 mg, or 75 mg of long-acting risperidone every 2 weeks for 12 months. Severity of extrapyramidal symptoms was assessed with the Extrapyramidal Symptom Rating Scale (ESRS), and efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS). This study was conducted from March 29, 1999 to July 19, 2000. RESULTS: The subjects were 615 patients with schizophrenia who received at least 1 injection of long-acting risperidone. The 12-month trial was completed by 65% of patients. Treatment was discontinued because of adverse events in 5% of patients. Extrapyramidal symptoms as adverse events were reported by 25% of the patients. Severity of extrapyramidal symptoms (according to ESRS scores) was low at baseline and decreased in each of the groups during the 12 months. The other most common adverse events were anxiety in 24%, insomnia in 21%, psychosis in 17%, and depression in 14% of the patients. Little pain was associated with the injections. Severity of symptoms of schizophrenia was improved in each group, with significant reductions in PANSS total scores (p <.01) and positive (p <.01) and negative (p <.001) factor scores. CONCLUSION: In terms of both safety and efficacy, symptomatically stable patients with schizophrenia benefit from being switched to long-acting injectable risperidone.

Administration, Oral↗

PubMed2002

Tardive dyskinesias and antipsychotics: a review.

Currently, tardive dyskinesia (TD) remains an important clinical problem. The average prevalence is estimated at 30%. The appearance of antipsychotics has opened new paths. The extrapyramidal profile of these molecules is more favorable than that of conventional neuroleptics. In order to assess their prophylactic as well as curative potential, we reviewed the literature concerning four of these atypical antipsychotics: clozapine, risperidone olanzapine and amisulpride. Clozapine seems to induce fewer cases of TD than the conventional neuroleptics, and has a specific therapeutic effect. However, the risk of agranulocytosis reduces the possibility of utilisation. Risperidone appears to be an effective therapy, but several authors report cases of TD during treatment. Furthermore, larger studies and longer follow-ups are necessary to confirm the efficiency of olanzapine and amisulpride. Further studies and observations are still necessary before drawing any conclusion for these new atypical antipsychotic actions. They are doubtlessly promising, but we cannot ignore the notion of risk-benefit; regular monitoring and listening to the subjective experience of the patients must remain uppermost in the choice of therapy.

Amisulpride↗

PubMed2002

Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study.

BACKGROUND: The prevalence of generalized anxiety disorder (GAD) represents an important public health issue. Hydroxyzine, an antagonist of histamine receptors, showed both efficacy and safety in previous short-term double-blind studies over placebo in this pathology. The aim of the current study was to confirm those positive results over a 3-month period in adult outpatients. METHOD: This multicenter, parallel (hydroxyzine [50 mg/day]; bromazepam [6 mg/day]), randomized, double-blind, placebo-controlled trial included 2 weeks of single-blind run-in placebo, 12 weeks of double-blind randomized treatment, and 4 weeks of single-blind run-out placebo. Three hundred thirty-four of 369 selected outpatients with a diagnosis of GAD according to DSM-IV criteria and a Hamilton Rating Scale for Anxiety (HAM-A) total score >/= 20 were randomized before entering the double-blind period. The primary outcome criterion was the change in the HAM-A score from baseline to 12 weeks of double-blind treatment with hydroxyzine compared with placebo. RESULTS: In the intent-to-treat analysis, the mean +/- SD change in HAM-A scores from baseline to endpoint was -12.16 +/- 7.74 for hydroxyzine and -9.64 +/- 7.74 for placebo (p =.019). Results at endpoint for percentage of responders (p =.003) and remission rates (p =.028), Clinical Global Impressions-Severity scale score (p =.001), maintenance of efficacy (p =.022), and Hospital Anxiety and Depression scale score on day 84 (p =.008) also confirmed the efficacy of hydroxyzine over placebo. The study showed no statistically significant difference between hydroxyzine and bromazepam. Except for drowsiness, which was more frequent with bromazepam, safety results were comparable in the 3 groups. CONCLUSION: Hydroxyzine showed both efficacy and safety in the treatment of GAD and appears to be an effective alternative treatment to benzodiazepine prescription.

Adult↗

PubMed2002

Effectiveness of clozapine in neuroleptic-resistant schizophrenia: clinical response and plasma concentrations.

OBJECTIVE: To assess the relation between plasma concentrations of clozapine and its 2 main metabolites desmethyl clozapine and clozapine N-oxide, and clinical change in a sample of inpatients with schizophrenia who were resistant to conventional neuroleptics. METHOD: Thirty-seven patients (27 men and 10 women, mean age 34.8 yr) with treatment-resistant schizophrenia were treated with clozapine for 18 weeks; dosage was adjusted according to clinical response, and plasma concentrations of clozapine and of its metabolites were measured weekly by high-performance liquid chromatography. Clinical status was also assessed weekly with the Positive and Negative Syndrome Scale (PANSS). Patients were considered "responsive" if they showed at least a 20% improvement over their baseline PANSS ratings. RESULTS: The mean endpoint clozapine dosage was 486.5 mg/day. There was a significant correlation between the daily dosage of clozapine and the plasma levels of clozapine and of its metabolites (p < 0.05). There was no correlation between the clozapine plasma level and the percent improvement on the PANSS. Clozapine plasma levels were not significantly different between those who responded to clozapine (n = 19) and those who did not (n = 18) and were not significantly different between patients who smoked (n = 28) and those who did not (n = 9). Receiver operating characteristic (ROC) curve analysis determined the plasma level threshold (above which a better clinical response was obtained) to be 550 ng/mL. Using the total of plasma levels of clozapine and its metabolites did not lead to a better sensitivity and specificity. CONCLUSIONS: Our calculated plasma clozapine threshold was higher than that reported by others, but this may be related to the severity of symptoms of our patient sample. Monitoring plasma rates remains a useful tool, together with clinical evaluation, to establish the clozapine dosage for an optimum benefit-risk ratio.

Adult↗