[Organising an investigation site: a national training reference document]. / Organiser un site investigateur : un référentiel national de formation pédagogique.

OBJECTIVE: Several surveys have shown a declining performance of French investigators in conducting clinical trials. This is partly due to insufficient and heterogeneous investigator training and site organisation. A multidisciplinary group was set up to propose solutions. We describe the tools developed to improve study site organisation. RESULTS: This working group was made up of clinical research experts from academia, industry, drug regulatory authorities, general practice, and consulting. Methods and tools were developed to improve site organisation. CONCLUSIONS: The proposed tools mainly focus on increasing investigators' awareness of their responsibilities, their research environment, the importance of a thorough feasibility analysis, and the implementation of active patient recruitment strategies. These tools should be able to improve site organisation and performances in conducting clinical trials.

The EULEV cohort study: rates of and factors associated with continuation of levetiracetam after 1 year.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Levetiracetam has shown good safety/tolerability and efficacy in regulatory trials. This was confirmed in observational investigations performed soon after marketing by using continuation or retention rates as a composite measure. When an anti-epileptic drug first becomes available; however, there is evidence of channelling to more severe patients than thereafter. WHAT THIS STUDY ADDS: This study was performed several years after marketing of levetiracetam and found high rates of continuation. It also further explores this measure by determining the continuation in the absence of initiation of additional anti-epileptic drugs. AIMS: To investigate real-life effectiveness of levetiracetam in patients initiating treatment in a stable market situation. METHODS: Epileptic adults who had initiated levetiracetam between 1 January and 31 August in 2005 or 2006 were included and followed for 1 year by hospital or nonhospital neurologists practising in France. One-year continuation rates were estimated using Kaplan-Meier analysis. Among those still treated at end of study, treatment goals were investigated. Factors associated with discontinuation were investigated using Cox proportional hazards regression. RESULTS: A total of 794 subjects were included in the cohort, and 753 subjects were followed up and included in the analysis. Among these, mean (SD) age was 42.6 (±17.0) years, 51.1% were female, 76.6% had partial epilepsy, 93.5% had seizures in the 6 months preceding levetiracetam initiation and 82.9% had at least one concomitant anti-epileptic drug when starting levetiracetam. One-year levetiracetam continuation rate was 83.5% (95% confidence interval, 80.5-86.0%). Of the 579 patients still using levetiracetam at end of study, 46.8% were seizure free during the last 6 months, and 24% were on levetiracetam monotherapy. Reasons for discontinuation (n= 122) were adverse events (45%), lack of efficacy (38%) or both (9%). Levetiracetam discontinuation was most strongly associated with previous exposure to more than four anti-epileptic drugs, whereas continuation was most strongly associated with presence of seizure-related falls in the 6 months preceding levetiracetam initiation. CONCLUSIONS: This population-based cohort study in a stable market situation found a high 1 year levetiracetam continuation rate compared with previous studies done sooner after market introduction.

Effectiveness of antibiotics for acute sinusitis in real-life medical practice.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Determining bacterial aetiology of acute sinusitis is difficult without employing invasive procedures. Most episodes of acute sinusitis resolve spontaneously. Antibiotics have demonstrated efficacy for the treatment of acute bacterial sinusitis in clinical trials yet little is known of their effectiveness in real-life treatment settings. WHAT THIS STUDY ADDS: Most cases of untreated acute sinusitis resolved spontaneously. Antibiotics were more effective when given within the first 10 days of treatment. This had no effect on later recurrence. Patients with poor oro-dental condition or recent antibiotic use may derive the most benefit from an antibiotic prescription and this should be considered by prescribers. The antibiotics used were found to be equally effective. Existing recommendations to identify acute sinusitis with high probability of bacterial origin, such as the French recommendations, fever or duration of symptoms fail to identify patients in whom antibiotics are more effective. AIMS: To assess the effectiveness of antibiotics in acute bacterial sinusitis. METHODS: This was a prospective cohort study with 2 months follow-up of 5640 patients with acute sinusitis included by a random sample from 1174 GPs and 120 ENT specialists. Main outcomes were short-term initial success, defined as the absence of prescription of (another) antibiotic or sinus lavage within 10 days, and lack of recurrence between the 11th and 60th day, after initial success. RESULTS: Initial success was found in 88.7% (95% CI 85.1, 91.4%) of patients without antibiotic prescription at inclusion and 96.2% (95% CI 95.7, 96.7%) of patients prescribed antibiotics. The 10 day adjusted hazard ratio (HR) for treatment failure (new antibiotic prescription or sinus drainage) with initial antibiotics compared with no antibiotics was 0.30 (95% CI 0.21, 0.42) with no difference between antibiotics. Antibiotics were more effective in patients with poor oro-dental condition (HR 0.04, 95% CI 0.01, 0.20) and in patients who had already used antibiotics during the previous 2 months (HR 0.09, 95% CI 0.03, 0.28). For patients without failure at 10 days, recurrence between the 11th and 60th day was similar whether or not they had initially been prescribed an antibiotic, 94.1% (95% CI 93.4, 94.7%) and 93.4% (95%CI 90.3, 95.5%), respectively. CONCLUSION: Most acute sinusitis cases not prescribed antibiotics resolve spontaneously. Antibiotics reduced by 3.3-fold the risk of failure within 10 days, without impact on later recurrence. The greatest benefit of antibiotics was found for patients with poor oro-dental condition or with antibiotic use within the previous 2 months.

The chronic oral administration of arginine aspartate decreases secretion of IGF-1 and IGFBP-3 in healthy volunteers.

To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions.

Patterns and frequency of atypical antipsychotic prescribing in psychiatric medical centers: a cross-sectional national survey.

Studies describing atypical antipsychotics when compared with conventional antipsychotic drugs are few in France. This study aimed to describe the frequency and characteristics of atypical antipsychotic prescribing. A cross-sectional national survey was conducted from February to June 2003 in a random sample of 100 volunteer French psychiatrists practicing in public psychiatric medical centers. Each psychiatrist was asked to complete a questionnaire for patients to whom at least one antipsychotic was prescribed during the period of the survey. The characteristics of the patients treated with atypical antipsychotics were identified with a logistic regression model. A total of 1733 patients were included in the study. The main diagnoses were schizophrenia (46.1%) and other psychoses (40.8%), followed by mood disorders (10%) and other psychiatric disorders (2.5%). Among these patients, 56% had at least one prescription of an atypical antipsychotic, 42.1% at least one conventional antipsychotic with immediate action and 29.9% at least one conventional antipsychotic with delayed action. Seventy percent of patients were treated with single-drug atypical antipsychotics. Compared with conventional antipsychotics with immediate action, atypical antipsychotics were less likely to be prescribed to patients over 35 years of age [odds ratio (OR) 0.4; 95% confidence interval (CI) 0.3-0.6], with duration of illness >10 years (OR 0.5; 95% CI 0.3-0.7), and were less likely to be used with concomitant corrector agents for neurological side effects (OR 0.4; 95% CI 0.3-0.6). This study shows the important use of atypical antipsychotic drugs especially in schizophrenic patients and younger patients.

How is norepinephrine used in intensive care? A field study.

OBJECTIVE: To assess how norepinephrine (NE), an emergency treatment of cardiovascular collapse, is used in intensive care. METHODS: Nurses and physicians of 14 intensive care units of the Bordeaux University Hospital were given questionnaires on the way they say they use NE and on actual NE treatment of patients. RESULTS: The clinical monitoring parameters cited were blood pressure, heart rate and hourly urine flow. Only 25% of the prescribers indicated the systematic use of hemodynamic monitoring. All the prescribers indicated they adapted the treatment to clinical objectives and blood pressure, and 77.5% to hourly urine flow. Initial NE concentrations ranged from 0.5 to 2 mg/ml, diluted in saline or dextrose. Initial prescribed dose ranged from 0.1 to 1 microg/kg/min. Large differences were observed between services and even within units. CONCLUSION: These data clearly show the need for recommendations regarding the use of norepinephrine.

Intravesical glucidic capsaicin versus glucidic solvent in neurogenic detrusor overactivity: a double blind controlled randomized study.

AIMS: Many studies report the use of alcoholic capsaicin instillation to treat neurogenic detrusor overactivity (NDO) in spinal cord injured (SCI) and multiple sclerosis (MS) patients. However, poor tolerability due to the irritative effect of the ethanol solvent limits its use. Our study aimed to evaluate the efficacy and tolerability of a new formulation of capsaicin in a glucidic solution in a multicenter clinical trial. MATERIALS AND METHODS: Thirty-three patients (26MS/7SCI) suffering from urinary incontinence due to refractory NDO were prospectively enrolled in a double-blind placebo controlled study and randomized to capsaicin group (CG, N = 17) or solvent group (SG, N = 16). They respectively received an intravesical instillation of 100 ml capsaicin diluted in glucidic solvent (CG) or glucidic solvent alone (SG). Efficacy (voiding chart, maximum cystometric capacity (MCC)) and tolerability were evaluated on days 0 (D0), 30 and 90. RESULTS: On D0, groups were homogeneous. On D30, significant improvement of overactive bladder syndrome and an increase in MCC were shown in CG, whereas there were no improvement in SG. No significant improvement was shown on D90 in both groups. There were no significant differences between groups regarding prevalence, duration, or intensity of side effects, except for short duration pubic pain during instillation more often reported in CG (58.8%) than in SG (12.5%) (P < 0.01). CONCLUSION: This placebo controlled study using glucidic capsaicin confirms its short-term efficacy in NDO patients. Global tolerance of glucidic capsaicin appeared satisfactory. Long-term efficacy and tolerance of repeated glucidic capsaicin instillations need to be evaluated.