Comparison of intubating conditions after induction with propofol and remifentanil or sufentanil : Randomized controlled REMIDENT trial for surgical tooth extraction.

PURPOSE: The aim of this study was to compare tracheal intubation conditions after induction of anesthesia with a bolus of propofol-sufentanil or propofol-remifentanil and a rapid induction technique. MATERIAL AND METHODS: A total of 70 patients (American Society of Anesthesiologists (ASA) classification I­II) undergoing outpatient surgery under general anesthesia with intubation for tooth extraction were randomly assigned to two groups in this double-blind study. Patients received either a bolus of remifentanil (3 µg/kg) or sufentanil (0.3 µg/kg) together with 2.5 mg/kg propofol for intubation. The primary outcome was the percentage of excellent intubation conditions and the secondary outcomes were the percentage of patients with a decrease of over 20% in mean arterial pressure (MAP) or heart rate (HR), time to achieve spontaneous respiration, time between the end of surgery and extubation and time to achieve an Aldrete score of 10. VAS pain score was >3 or having laryngeal pain 15 min after arriving in the postanesthesia care unit (PACU) were also analyzed. RESULTS: Intubating conditions (perfect + good conditions) were significantly better with remifentanil than with sufentanil (88.5% vs. 68.6%; p = 0.01). When using remifentanil, the hemodynamic conditions were good. Using remifentanil did not significantly increase the pain score or the laryngeal pain in the recovery room. This was confirmed by no significant differences between the groups for morphine consumption. Remifentanil significantly decreased the time to achieve an Aldrete score of 10. CONCLUSION: When intubation without muscle relaxants is required, intubating conditions are much better when a remifentanil bolus is used compared to a sufentanil bolus. The remifentanil/propofol rapid induction technique is a valuable technique to quickly intubate and achieve good conditions.

Acute ischaemic lesions are associated with cortical superficial siderosis in spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) commonly detects acute ischaemic lesions in patients with acute intracerebral hemorrhage (ICH), especially with cerebral amyloid angiopathy (CAA). We investigated the relationship between cortical superficial siderosis (cSS), a neuroimaging marker of CAA, and DWI lesions in patients with acute ICH. METHODS: We conducted a retrospective analysis of prospectively collected data from consecutive patients with acute supratentorial ICH who underwent brain magnetic resonance imaging within 10 days after symptom onset. Magnetic resonance imaging scans were analyzed for DWI lesions, cSS and other markers for small-vessel disease. Univariate and multivariate analyses were performed to assess the association between cSS and DWI lesions. RESULTS: Among 246 ICH survivors (mean age 71.4 ± 12.6 years) who were enrolled, 126 had lobar ICH and 120 had deep ICH. Overall, DWI lesions were observed in 38 (15.4%) patients and were more common in patients with lobar ICH than deep ICH (22.2% vs. 8.3%; P = 0.003). In multivariate logistic regression analysis, the extent of white matter hyperintensities [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.58; P = 0.02] and cSS severity (focal cSS: OR, 3.54; 95% CI, 1.28-9.84; disseminated cSS: OR, 4.41; 95% CI, 1.78-10.97; P = 0.001) were independently associated with the presence of DWI lesions. CONCLUSIONS: Diffusion-weighted imaging lesions are more frequently observed in patients with acute lobar ICH than in those with deep ICH. cSS severity and white matter hyperintensity extent are independent predictors for the presence of DWI lesions, suggesting that CAA may be involved in the pathogenesis of DWI lesions associated with acute ICH.

Cortical superficial siderosis and acute convexity subarachnoid hemorrhage in cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Acute convexity subarachnoid hemorrhage (cSAH) and cortical superficial siderosis (cSS) are neuroimaging markers of cerebral amyloid angiopathy (CAA) that may arise through similar mechanisms. The prevalence of cSS in patients with CAA presenting with acute cSAH versus lobar intracerebral hemorrhage (ICH) was compared and the physiopathology of cSS was explored by examining neuroimaging associations. METHODS: Data from 116 consecutive patients with probable CAA (mean age, 77.4 ± 7.3 years) presenting with acute cSAH (n = 45) or acute lobar ICH (n = 71) were retrospectively analyzed. Magnetic resonance imaging scans were analyzed for cSS and other imaging markers. The two groups' clinical and imaging data were compared and the associations between cSAH and cSS were explored. RESULTS: Patients with cSAH presented mostly with transient focal neurological episodes. The prevalence of cSS was higher amongst cSAH patients than amongst ICH patients (88.9% vs. 57.7%; P < 0.001). In multivariable logistic regression analysis, focal [odds ratio (OR) 6.73; 95% confidence interval (CI) 1.75-25.81; P = 0.005] and disseminated (OR 11.68; 95% CI 3.55-38.35; P < 0.001) cSS were independently associated with acute cSAH, whereas older age (OR 0.93; 95% CI 0.87-0.99; P = 0.025) and chronic lobar ICH count (OR 0.45; 95% CI 0.25-0.80; P = 0.007) were associated with acute lobar ICH. CONCLUSIONS: Amongst patients with CAA, cSS is independently associated with acute cSAH. These findings suggest that cSAH may be involved in the pathogenesis of the cSS observed in CAA. Longitudinal studies are warranted to assess this potential causal relationship.

Healthcare cost impact of biological drugs compared with traditional systemic treatments in psoriasis: a cohort analysis in the French insurance database.

BACKGROUND: Biological drugs have dramatically improved the management of moderate to severe psoriasis. Little is known about their economic impact in daily clinical practice. OBJECTIVE: The aim of this study was to estimate the costs of biological drugs, in term of health resources consumption, and to compare it with costs induced by traditional systemic treatments. METHODS: This cohort study was built from the French health insurance database in the Midi Pyrénées area (2.8 million inhabitants, South West of France). We compared health care costs between 'exposed' patients treated with biological drugs (adalimumab, etanercept, infliximab or ustekinumab) and 'unexposed' patients defined as patients who received traditional systemic treatments (phototherapy, acitretin, methotrexate or cyclosporin) during a 6-month period. RESULTS: A total of 1924 patients met the inclusion criteria. Sixty-nine patients were 'exposed', whereas 1855 patients were 'unexposed'. 'Exposed' patients had a mean total healthcare cost of 8107€ vs. 1678€ (P < 0.001) for 'unexposed' patients. They had higher costs concerning inpatient admission, medication and consultations including dermatology consultations, laboratory, non-medical care and transportation. Biological drug prescription was associated with an increase in the use of anti-infective drugs and with a reduction in the use of psychoactive drugs. CONCLUSION: The mean total health care expenditure in patients treated with biological drugs was five times higher as compared with patients treated with traditional systemic treatments. The limitation of the study is the short duration of follow-up comprising a loading dose period for some biological drugs. This may have contributed to an overestimation of drug-related costs.

[Generic substitution in primary care in 2011: differences according to pharmacological classes?]. / Différences de taux de substitution des médicaments génériques en Midi-Pyrénées en fonction des classes pharmaco-thérapeutiques.

BACKGROUND: Generic substitution has been permitted for several years in France and is promoted in order to reduce health expenditures. However, reluctance concerning use of generic drugs exists for different reasons: suspicions about their efficacy and/or safety, differences in content (excipients) and discussions about bioequivalency. The aim of our study was to determine whether or not the substitution ratio differs according to pharmacological classes used in primary care. METHODS: We conducted a descriptive study in the French Health Insurance Database using reimbursement data on drugs prescribed and delivered in the Midi-Pyrénées administrative district between March 2010 and March 2011. We selected different pharmacological classes largely used in primary care. For each class, a substitution ratio was calculated (DDD of generics delivered/DDD of brand name plus generics). A Chi(2) test was used in order to detect a difference between these substitution ratios. RESULTS: The global substitution ratio was 72.32%. Values varied from 28.36% for thyroid hormones to 90.39% for antibiotics, with significant statistical difference (P<0.001). The substitution ratio was less than 50% for thyroid hormones (28.36%) and antiepileptics (45.28%). Higher substitution ratios were observed for protein pump inhibitors (88.81%), statins (87.81%), antidepressors (87.37%) and diuretics (86.1%). CONCLUSION: This study highlights major differences in terms of the generic substitution ratio between different pharmacological classes. This difference can be explained in part by published guidelines. Further studies are needed to ascertain the precise point of view of patients, general practitioners and pharmacists concerning this issue.

[Validation of identification criteria for patients having surgery for rhegmatogenous retinal detachment at Toulouse University Hospital]. / Validation des critères d'identification des patients opérés d'un décollement de rétine rhegmatogène au CHU de Toulouse.

INTRODUCTION: Seasonal variations seem to modify the incidence of rhegmatogenous retinal detachment (RRD), with a summer peak, although the meteorological parameters involved have not been studied in France. In order to conduct a national study evaluating the association between the occurrence of RRD and various climatological variables (METEO-POC study), we need to establish a national cohort of patients having undergone surgery for RRD. The data of the National Health Data System (SNDS) allow the realization of epidemiological studies concerning various pathologies. However, as these databases were initially intended for medical administrative use, the identification of the pathologies coded in these databases must be validated before any use for research purposes. In order to carry out a cohort study using SNDS data, the objective of this study is to validate the identification criteria for patients having undergone RRD surgery at Toulouse University Hospital. METHODS: We compared the cohort of RRD surgery patients at Toulouse University Hospital from January to December 2017 assembled from SNDS data with the cohort of patients meeting the same selection criteria assembled from Softalmo software data. RESULTS: With a positive predictive value of 82.0%, a sensitivity of 83.8%, a specificity of 69.9%, and a negative predictive value of 72.5%, we can consider that our eligibility criteria are performing well. CONCLUSION: Since the selection of patients via SNDS data is reliable at Toulouse University Hospital, we can use it at the national level for the METEO-POC study.

Statin-induced lupus: a case/non-case study in a nationwide pharmacovigilance database.

Statin use has been advocated to prevent atheromatous complications in lupus patients and may be widely prescribed for these patients in future. Statin-induced lupus has also been described, though the risk is not confirmed. The goal of this study was to detect a safety signal regarding statin-induced lupus. We conducted a case/non-case study in the French PharmacoVigilance Database from January 2000 until December 2010. Cases were drug-induced lupus reports. Non-cases were all reports of other adverse drug reactions (ADRs). Exposure to statins at the time of ADR was screened in each report. Among 235,147 ADR reports, 232 were drug-induced lupus. Exposure to statins was present in 17 (7.3%) cases and in 10,601 (4.7%) non-cases. Reporting odds ratio (ROR) for statin exposure associated with lupus erythematosus was 1.67 (95% confidence interval 1.02-2.74). The ROR was > 1 for each statin but fluvastatin. This pharmacoepidemiological study suggests a link between statin exposure and lupus induction. The benefit-to-risk ratio of statin therapy in lupus patients should be evaluated through randomized controlled trials.

Peacefull: A French mindfulness-based intervention for adolescents with chronic pain a feasibility study.

INTRODUCTION: Pediatric chronic pain can lead to serious consequences in terms of daily functioning and global quality of life. Mindfulness-based intervention (MBI) approaches that emphasize accepting rather than controlling pain have gained increasing attention in adults with chronic pain. The effectiveness of MBIs for chronic pain in the pediatric population remains unknown. The aim of the Peacefull program was to study the feasibility in France of a mindfulness program for adolescents with chronic pain, based on a program especially developed in Canada and Belgium. METHOD: An MBI for adolescents consisting of eight 90-min sessions was provided. It focused on building skills and incorporated mindfulness meditation, exercises, and activities especially adapted to teenagers with chronic pain. RESULTS: A total of 27 adolescents aged 12-17 years who were diagnosed with a chronic pain condition were enrolled in five cohorts from April 2018 to June 2021. The completion rate of the Peacefull program was 88.89 with no dropouts and good completion of outcome measures. Secondary outcomes were assessed before the program, at the end, and 3 months later. A trend toward an improvement was observed on the mean average score for the Visual Analog Scale (VAS), but it was not statistically significant. Scores increased significantly over time on the Functional Disability Inventory (FDI), and pain catastrophizing also improved. CONCLUSIONS: Although the findings regarding the effectiveness of Peacefull programs were inconsistent and insufficient, they can be indicative of the benefits of mindfulness as an adjuvant treatment for adolescents with chronic pain.

A French survey on the lockdown consequences of COVID-19 pandemic in Parkinson's disease. The ERCOPARK study.

BACKGROUND: In 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March - mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP). METHODS: PwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life. RESULTS: 2653 PwP were included: 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group. CONCLUSIONS: The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .

Influence of fluoroquinolone consumption in inpatients and outpatients on ciprofloxacin-resistant Escherichia coli in a university hospital.

BACKGROUND: The increase in fluoroquinolone-resistant Escherichia coli has raised the issue of treatment failure in common infections. Few studies have investigated the possible relationship between outpatient fluoroquinolone consumption and resistance in hospital. OBJECTIVE: To investigate the relationship between inpatient and outpatient fluoroquinolone use and ciprofloxacin-resistant E. coli in a teaching hospital. METHODS: An ecological study was conducted in Toulouse University Hospital and its surrounding area, the Midi-Pyrénées region (south-western France), in 2004-07. Dynamic regression models were built to study how the hospital resistance rate was linearly related to current and past values of fluoroquinolone consumption. Resistance forecasts for 2008 were then calculated and compared with actual rates for the first 5 months of the year. RESULTS: Mean resistance rate was 13.7% and mean fluoroquinolone use was 89.9 defined daily doses (DDDs)/1000 inpatient days in hospital and 2.6 DDDs/1000 inhabitants/day in the region. Taking into account past values of fluoroquinolone consumption in hospital and in outpatients, only levofloxacin use in the community remained significantly associated with resistance in hospital, with a lag of 12 months. This model explained 50% of the resistance variability. CONCLUSIONS: This ecological analysis, conducted on a teaching hospital scale, suggests that ciprofloxacin resistance in E. coli in hospital is linked to consumption of fluoroquinolones within the hospital and its surrounding community. Among all fluoroquinolones, levofloxacin use was found to be the most important factor. Consumption in outpatients appears to be a relevant determinant to consider in designing interventions to reduce resistance in hospitals.

Clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 infection at Toulouse University hospital (France). Results from the Covid-clinic-Toul cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread worldwide from epicenter of Wuhan, China since December 2019. The aim of our study was to describe the clinical characteristics and outcome of hospitalized patients with SARS-CoV-2 pneumonia at the Toulouse university hospital, France. PATIENTS AND METHODS: We selected the patients included from March 7, 2020 to April 20, 2020 in the retrolective Covid-clinic-Toul cohort that follows all hospitalized patients with SARS-CoV-2 infection at the Toulouse Hospital. Cases were confirmed by real-time reverse transcriptase polymerase chain reaction. We report demographics, clinical, biological and radiological features, as well as unfavorable outcome at Day 14 after admission (admission in an intensive care unit, mechanical ventilation, death). RESULTS: Among 263 hospitalized patients, the median age was 65 years and 155 (58.9%) were males. Two hundred and twenty-seven patients (86.3%) had at least one comorbidity. The median time from first symptom to hospital admission was 7.0 days (interquartile range: 4-10). On day 14 after admission, 111 patients (42.2%) had been transferred to intensive care unit (ICU), including 50 (19.0%) on Day 1; 61 (23.1%) needed mechanical ventilation and 19 patients (7.2%) had died. Patients admitted to ICU at Day 1 of admission (n=50) were more frequently men (66.0% vs 57.3%), smokers (25.0% vs 7.1%), with obesity (42.0% vs 24.7%) and had a higher mean level of C-reactive protein (median: 110.9mg/L vs 46.2mg/L). CONCLUSION: This cohort provides epidemiological data on SARS-CoV-2 in hospitalized patients in a University hospital in the South of France.

Total body composition by DXA of 241 HIV-negative men and 162 HIV-infected men: proposal of reference values for defining lipodystrophy.

The aim of this study was to define standard values for fat mass distribution by dual-energy X-ray absorptiometry in human immunodeficiency virus (HIV)-negative men and to analyze factors associated with lipodystrophy in HIV-infected men. Total-body composition was analyzed in 241 HIV-negative men (controls) and 162 HIV-infected men. We created a fat mass ratio (FMR) as the ratio of the percentage of the trunk fat mass to the percentage of the lower limbs fat mass. We defined the FMR standard values as the mean value+/-standard deviation. We compared body mass index (BMI), fat mass percentage (%FM), lean mass (LM), bone mineral density (BMD), and FMR between the control group and HIV-infected men, by age range, according to prescription of treatment and presence of clinical lipodystrophy. The FMR standard value is equal to 1.3+/-0.2. The FMR was higher in treated HIV-infected men with or without clinical lipodystrophy. The FMR was similar for naïve HIV-infected men and controls. It was positively correlated with age, cumulative time on treatment, zidovudine, stavudine, or indinavir. BMD and fat mass were lower for treated and naïve HIV-infected men than for HIV-negative men. The FMR seems to be a valuable index for measuring fat mass distribution. We defined FMR standard values from the largest group of HIV-negative men to our knowledge. Applying FMR to HIV patients could help physicians to diagnose lipodystrophy earlier.

[Anti-retroviral treatment interruptions in HIV-infected adults: causes, clinical, immunological and virological consequences]. / Etude rétrospective descriptive évaluant les causes et les conséquences cliniques, immunologiques et virologiques des interruptions de traitement antirétroviral chez des adultes infectés par le VIH-1.

INTRODUCTION: This retrospective study analyses causes as well as clinical, immunological and virological consequences of antiretroviral treatment interruptions (Ti) of more than 30 days in HIV-1 infected adults. METHODS: This causes were classified as related to drug toxicity, therapeutic or adherence failure. We studied therapeutic regimens before Ti and after treatment reinitiation (TR), clinical events related to Ti, CD4 cells and viral loads before Ti and at months 3, 6, 9, and 12 after TR. RESULTS: Out of 188 Ti analysed, 42.6% were related to therapeutic failure, 33.5% to drug toxicity, and 23.9% to adherence failure. Eight Aids defining clinical events were reported during Ti, in patients with low CD4 cells and high viral load (P < 0.05). Viral loads evolution after TR was better if Ti was related to treatment failure (P < 0.05), was prolonged (P < 0.05), and if CD4 cells were high before Ti and at TR (P < 0.05). Median CD4 cells was of 296/mm(3) at month 12 after TR vs 382 before Ti. CONCLUSIONS: Ti consequences are strongly related to CD4 cells, which decrease sharply during Ti, increasing Aids defining events probability. Prospective randomised clinical studies are needed to define usefulness of Ti.

[How to read a meta-analysis?]. / Comment lire une méta-analyse?

Meta-analysis is aimed at assessing an exhaustive, unbiased, reproducible, quantified and accurate synthesis of a research problem. It is sustained by a systematic review of the literature and has statistical particularities. Sources of error and bias are numerous. In this paper, we describe them following the methodology steps of a well-conducted meta-analysis. Causes of divergent conclusions of meta-analyses are described and illustrated with the example of cancer risk assessment in TNF inhibitor-treated rheumatoid arthritis patients. Eventually, this article provides key-points to help readers to detect sources of error and bias in meta-analyses.

Confusion, a rather serious adverse drug reaction with valproic acid: a review of the French Pharmacovigilance database.

INTRODUCTION: Confusion is an adverse drug reaction frequently observed with valproic acid. Some case reports are published in the literature but no systematic study from a sample of patients has been published. We performed this study in order to describe the main characteristics of this adverse drug reaction. METHODS: Using the French Pharmacovigilance database, we selected the cases of confusion reported since 1985 with valproic acid. RESULTS: 272 cases of confusion were reported with valproic acid: 153 women and 119 men. Confusion mostly occurred during the two first weeks following valproic acid exposure (39.7%). It was "serious" for almost 2/3 of the patients (62.5%) and its outcome favourable in most of the cases (82%). The occurrence of this ADR was more frequent in patients aged between 61 and 80 years. CONCLUSION: This work shows that confusion with valproic acid is a serious, rather frequent but reversible adverse drug reaction. It occurs especially in older patients and during the first two weeks of treatment.

Was the thrombotic risk of rofecoxib predictable from the French Pharmacovigilance Database before 30 September 2004?

OBJECTIVES: Rofecoxib was withdrawn from the market on 30 September 2004 following the results of a randomized controlled trial. Following this sudden decision, several controversies occurred in the literature to determine whether this adverse drug reaction (ADR) could have been detected earlier. The aim of this study was to investigate whether this kind of signal could have been seen using the French Pharmacovigilance Database before this date of rofecoxib withdrawal. METHODS: Using cases registered in the French Pharmacovigilance Database from May 2000 to December 2006, we applied the case-noncase method to "serious" thrombotic ADRs reported with oral formulations of rofecoxib or celecoxib in patients older than 15 years. Cases were all notifications of thrombotic ADRs [World Health Organization Adverse Reaction Terminology (WHO-ART) codes 1300] occurred under coxib (rofecoxib, celecoxib) and noncases all other reports registered in the database (whatever the drug). We calculated a cumulative odds ratio (OR) from 20 May 2000 to 31 December 2006, with a special interest for the period before the 30 September 2004. RESULTS: Among the 50,087 "serious" ADRs registered in the database during this period, 1,127 were thrombotic ones. Rofecoxib exposure was significantly associated with high values of odds ratio (OR) [4.2 (95% CI 1.97-8.61)] for thrombotic ADRs as early as the end of 2001. The values of ADR reporting ORs remained high (3.0-3.5) until 2006. For celecoxib, a significant trend occurred only from September 2004. CONCLUSION: Despite the compulsory limits of the case/noncase methodology, this study found an association between rofecoxib exposure and the occurrence of "serious" thrombotic ADRs as early as the end of the first year of rofecoxib marketing in France. The association between celecoxib and the occurrence of such ADRs appears less clear. Our work also shows the potential use of careful analysis of pharmacovigilance databases (investigating, for example, cumulative values of risk) in the early identification of new ADRs.

Detection and incidence of drug-induced agranulocytosis in hospital: a prospective analysis from laboratory signals.

AIMS: Our objectives were to assess the detection and incidence of drug-induced agranulocytosis in two university hospitals using hematology laboratory data. METHODS: A prospective study was undertaken at Toulouse University Hospital (France) and Navarra University Hospital (Spain) for 1 year (from 1 May 2004 to 30 April 2005). Using a computerized process and hematology laboratory data, all neutrophil counts with a value less than 500/mm(3) were registered, allowing identification of inpatients suffering from agranulocytosis during the period of the study. Medical records of all selected patients were then consulted. Cytostatic drugs were excluded from this study. RESULTS: During the period of the study, 225,659 neutrophil counts were performed in both hospitals, of which 2,835 (1.26%) had a neutrophil count less than 500/mm(3), corresponding to 739 patients. Seventeen patients were excluded because of lack of data, and 20 cases of infants younger than 3 months were excluded. Among the remaining patients (n = 702), 23 cases of drug-induced agranulocytosis (excluding cytostatic drugs) were suspected. All cases were classified as "serious" since they led to death in 2 cases, hospitalization or prolongation of hospitalization in 19 cases and threatening of vital prognosis in 2 cases. Withdrawal of suspected drugs was done in all cases with regression of neutropenia in 21 cases. According to hospitalization data, the annual incidence of drug-induced agranulocytosis was 1.62 (1.0-2.6) per 10,000 inpatients in Toulouse University hospital (based on 534 cases) and 3.24 (0.9-8.3) per 10,000 inpatients in Navarra University Hospital (based on 168 cases). The involved drugs were mainly antibacterial (30.4%), immunosuppressive (17.4%), antithyroid (13.0%), antiplatelet (8.7%) and nonsteroidal anti-inflammatory (8.7%) ones. Only seven cases from Toulouse University Hospital were spontaneously reported by physicians during the same period. Thus, the underreporting coefficient (U) was 2.71 (63.2%) in France. CONCLUSION: Our survey allowed us to identify the suspected drug-induced agranulocytosis through a prospective study in a large sample of inpatients using only laboratory data analysis. We also note an important underreporting rate of this serious adverse drug reaction (ADR) to the official French pharmacovigilance system. Laboratory data analysis could be used for identifying serious ADRs.

Adverse drug reactions in patients older than 70 years during the heat wave occurred in France in summer 2003: A study from the French PharmacoVigilance Database.

OBJECTIVE: To evaluate adverse drug reactions (ADRs) in patients older than 70 years reported during the 2003 summer heat wave in France to the French Network of Pharmacovigilance Centres and to discuss the interest of such a pharmacovigilance database in the surveillance of such sanitary alerts. METHODS: All 'serious' ADRs occurred in patients older than 70 years between 1st July and 31st August 2003, reported to the French network of Pharmacovigilance Centres and recorded in the French PharmacoVigilance Database, were analysed with respect to age, gender, type of ADR, drug(s) involved as well as imputability of heat wave. RESULTS: The total number of 'serious' ADRs registered in the French PharmacoVigilance Database in patients older than 70 years was similar in 2003 (a year with heat wave) and in 2002 (a year without heat wave). Sixty-eight ADRs [27 'possible' (I1), 27 'plausible' (I2) and 14 'likely' (I3)] related to heat occurred in 2003, with a maximal peak between the 28th July and the 17th August. The most frequently ADRs were metabolic (dehydratation, hydroelectrolytic disturbances) and neuropsychiatric (confusion, falls, coma). Drugs more frequently involved were diuretics, angiotensin converting enzyme inhibitors, antidepressants (mainly serotonin reuptake inhibitors), proton pump inhibitors, digoxin, benzodiazepines, oral hypoglycemics and sartans. CONCLUSION: This study underlines the role of heat wave in the occurrence of 'serious' ADRs in elderly. However, the French PharmacoVigilance Database was not enough sensitive to be used as an efficient surveillance system during such an acute episode, like a heat wave (at least while underreporting remains so important).

"Medicamentation" of society, non-diseases and non-medications: a point of view from social pharmacology.

This review presents the definition and goals of "social pharmacology", a new branch of clinical pharmacology, investigating relationships between drugs and society through the example of "medicamentation", defined as the use of drugs for social problems previously not requiring drug utilisation (ageing, smoking cessation, vigilance troubles, sleep synchronisation, loss of libido, etc.). The involvement of the different "actors" from our society (patients, physicians, pharmaceutical industries, clinical pharmacologists, regulatory agencies, etc.) in this phenomenon is also discussed.

Oral nicorandil-induced lesions are not aphthous ulcers.

OBJECTIVES: (i) To accurately define these lesions determining whether oral nicorandil-induced lesions are aphthous ulcers; (ii) To determine clinical characteristics of oral nicorandil-induced lesions. MATERIALS AND METHODS: Two slide conferences were held. A total of 60 dermatologists assigned diagnosis and clinical criteria to 11 photographs of oral nicorandil-induced lesions. Two slides were randomly selected and duplicated to be used as control. The panel of slides included independent lesions and photographs of different lesions of the same patient. Statistical analysis used chi2-test, estimation of the percentage interobserver agreement, and kappa-values. RESULTS: The diagnosis of non-aphthous ulcer (71.8%) was significantly held in comparison with the diagnosis of oral aphthous ulcer (28.2%; P<0.001). To differentiate aphthous ulcer from non-aphthous ulcer, physicians significantly used three clinical criteria. The diagnosis of non-aphthous ulcer were significantly associated with the absence of yellow-based ulceration (P<0.001), with the linear shape (P=0.006) and the absence of inflammatory halo (P=0.003). CONCLUSION: Oral nicorandil-induced lesions are not aphthous ulcers. We propose that at this stage of our knowledge, oral nicorandil-induced ulcer is the most suitable terminology.