Detection of signals of abuse and dependence applying disproportionality analysis.

INTRODUCTION: Prescription drug abuse and dependence is a widespread phenomenon in many countries. The use of disproportionality measures in drug abuse surveillance is rarely performed. PURPOSE: The aim of this study is to determine the occurrence of signals of abuse and dependence for different psychoactive drugs in real-life settings. METHODS: Disproportionality analysis was realised from a database specifically constructed for the monitoring of drug abuse and dependence. This database provides information on approximately 5000 patients and 8000 consumption modalities for more than 100 distinct psychoactive medications for 2010 and 2011. Proportional reporting ratio (PRR) was computed in two population groups: subjects under an opiate maintenance treatment (OMT) versus those not under OMT, and focused on four types of behaviours: abuse and dependence, illegal acquisition, diverted route of administration and concomitant alcohol use. RESULTS: Among the 100 psychoactive drugs for which a signal could be detected, those presenting the highest signals were the following: flunitrazepam, clonazepam, methylphenidate, ketamine, morphine sulfate, codeine and buprenorphine. CONCLUSIONS: The present study shows an innovative application of disproportionality measures for drug abuse monitoring based on two cross-national, annual studies. The disproportionality analysis provided the opportunity to reveal and compare the magnitude of signals between 100 psychoactive drugs. This approach helps to compare the magnitude of abuse and dependence behaviours for a large number of drugs, and allows prioritizing actions in a context where such events are usually underreported.

[Analysis of addictive behaviours among new prisoners in France using the OPPIDUM program]. / Evaluation des conduites addictives chez les personnes entrant en milieu pénitentiaire à partir du programme OPPIDUM du réseau des centres d'évaluation et d'information sur la pharmacodépendance (CEIP).

INTRODUCTION: The data on consumption of psychoactive substances among new prisoners are documented but not detailed with precision. Nevertheless, analyzing the consumption's characteristics of psychoactive products would led to a better caring of subjects at the entry in the prison. The consumption of psychoactive drugs the week before the imprisonments of subjects seen in prison were studied from the Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) program's between 2003 and 2006. These were compared to those of others subjects with an history of abuse/dependence or under an opiate maintenance therapy presented in other structures of care. METHODS: OPPIDUM is an annual cross-sectional national study, repeated each year in October since several years. It is based on the Network of the Centres for Evaluation and Information on Pharmacodependence (CEIP) which recruits, via the medical system (drug users outpatient care centers, psychiatric units, drug-addict units...), subjects presenting a drug dependency or benefiting of an opiate maintenance treatment. RESULTS: During the four years between (2003 to 2006), 13,008 subjects were included. Seven percent (n=893) of them were in prison. They are younger and present worse social-economical indicators compared to the others subjects seen in other structures of care. In comparison to other subjects, the prisoners consume more products, more illicit ones and more benzodiazepines like flunitrazepam and clonazepam before their imprisonment. The medicines are consumed with higher doses and are more often obtained illegally (35% vs 14%). These subjects are less often under an opiate maintenance therapy (51% vs 74%). Between 2003 and 2006 the consumption of cocaine, increased from 18% to 28% for the patients before their confinement and from 11% to 21% for the heroine. Nevertheless, the consumption of benzodiazepines have decreased passing from 41% to 25%; and the consumption and of opiate maintenance treatment taken out of a protocol have decreased from 11% to 4%. DISCUSSION: This study underlines the specificity of the characteristics of consumption of psychotropic drugs before the imprisonment of the subjects with history of abuse/dependence or under an opiate maintenance therapy by report to consumers presented in other structures of care. It outlines the need to optimize the care by a better knowledge of the consumption of psychoactive products.

[Adverse drug events in hospitalized elderly patients in a geriatric medicine unit: study of prevalence and risk factors]. / Accidents iatrogènes médicamenteux chez le sujet âgé hospitalisé en court séjour gériatrique : étude de prévalence et des facteurs de risques.

INTRODUCTION: In the elderly, both the presence of a multiple pathology and multiple medication have been shown to be frequent risk factors for adverse drug events. However, a few studies only have included parameters of standardized geriatric assessment for the purpose of identifying other risk factors. Our study compared the parameters of standard geriatric assessment, in the presence or absence of adverse drug events and evaluated the prevalence of adverse drug events in elderly inpatients, the symptoms, and the drugs involved. METHODS: A total of 823 patients were studied during a two-year period. Two groups of patients were identified, according to the presence or absence of an adverse drug event. Eight fields of geriatric assessment were compared: comorbidities, number of drugs, functional status, nutritional status, mobility, mood, neurosensory disorders, and cognition. For patients who experienced an adverse drug event, we also analyzed the drugs involved and the symptoms of the adverse drug events. RESULTS: One hundred and twelve patients (13.6%) aged 82 years+/-7.5 experienced 144 adverse drug events. Significant differences between the two groups were observed in the following: symptoms of depression, problems of mobility, risk of malnutrition (respectively p=0.001, p=0.002, p=0.007), the female sex, number of drugs, number of comorbidities, and the administration of diuretics. Cardiovascular (23.2%), psychotropic (17.9%) and anti-infectious (17%) medicines were the most frequently involved. The symptoms that occurred most frequently were orthostatic hypotension (14.6%), gastrointestinal disorders (12.5%), and neuropsychological (10.4%) disorders. CONCLUSION: Elderly patients with multiple pathology and multiple medication are at high risk for adverse drug events. Other lesser known factors, such as depression, problems of mobility, and malnutrition must be researched, as they are evidence of the underlying the frailty of the elderly population.

[Medical abortion at home and at hospital: a trial of efficacy and acceptability]. / Interruption volontaire de grossesse médicamenteuse à domicile et à l'hôpital : étude d'efficacité et d'acceptabilité

OBJECTIVES: To evaluate the efficacy and the acceptability of medical abortion at home and at hospital. PATIENTS AND METHODS: From 11 February 2008 to 16 July 2008, 399 patients were included in the study: 173 at home and 226 at hospital. RESULTS: Efficacy was evaluated for 305 patients because 94 were lost of follow-up (23.6%). Efficacy of medical abortion was 86.7% (124/143) at home and 95.8% (155/162) at hospital. There were one ongoing pregnancy and 25 surgical aspirations (8.6%). The family planning nurse received a phone call from five patients after mifepristone at home (2.9%) and seven patients after mifepristone at hospital (3.1%). Only one patient "at home" had an emergency consultation (0.6%) and nine patients "at hospital" (4%). Ten patients went back to their gynecologist before their appointment for follow-up (2.5%): five "at home" (2.9%) and five "at hospital" (2.2%). Thirteen patients were referred by the private provider to the hospital medical specialist. Acceptability is known for 70.2% of patients: 98% thought that medical abortion at home was acceptable and 92.9% at hospital. DISCUSSION AND CONCLUSION: The failure rate of medical abortion is higher at home and is due to aspirations for incomplete abortion. The procedure at home seems to be more acceptable than at hospital. It will be interesting to realize a prospective randomized study to compare the procedures at home and at hospital.

[Estimation of the glomerular filtration rate in elderly inpatients: comparison of four methods]. / Quelle méthode d'évaluation de la fonction rénale utiliser chez le sujet âgé hospitalisé en unité de court séjour gériatrique ? Comparaison de quatre méthodes.

PURPOSE: High variability has been observed in the estimation of the glomerular filtration rate (GFR) in older patients, according to the formula used and no single formula has been recommended to date. The aim of this study was to quantify the precision and accuracy of the GFR estimated by means of three formulas and the measurement of cystatin C. METHODS: This prospective study was conducted in an acute care geriatric unit. Participants were patients, aged 70 years and over, having a possible 24-hour urine collection. The GFR was estimated using the Cockroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD), and the Creatinine Clearance (Cl-Cr) formulas. The serum level of cystatin C was also measured. RESULTS: Eighty-one patients were included in the study. CG formula underestimated the GFR by a mean difference of 8.65 ml/min, compared with MDRD formula. Cl-Cr underestimated the GFR by a mean difference of 7.56 ml/min, compared with CG formula, and by a mean difference of 16.79 ml/min, compared with the MDRD formula. The degree of discrepancy between CG and Cl-Cr estimates, and between Cl-Cr and MDRD estimates decreased as the estimated GFR approached normal values. MDRD best matched the measurement of cystatin C, followed by CG and Cl-Cr (Kappa coefficient=0.43, 0.22 and 0.16, respectively). CONCLUSION: Our study confirms the high variability of GFR in older patients and particularly in those with abnormal renal function, depending on the formula used. Serum cystatine C level and MDRD formula appear to be the most concordant estimates of GFR in this population.

[Phase III randomised trial of adjuvant chemotherapy with cisplatin plus docetaxel versus cisplatin plus gemcitabine in resected non-small cell bronchial carcinoma with quality of life as the primary objective]. / Essai randomisé de phase III de chimiothérapie adjuvante par CDDP/docetaxel versus CDDP/gemcitabine dans les cancers bronchiques non à petites cellules réséqués avec la qualité de vie comme objectif principal.

BACKGROUND: Adjuvant chemotherapy improves survival of completely resected non-small cell lung cancer (NSCLC). However the regimen of choice is not yet defined. METHODS: The primary objective of this comparative, open, randomised multicentre trial is to compare two chemotherapy regimens (cisplatin/docetaxel versus cisplatin/gemcitabine) in the management of resected NSCLC with quality of life (QoL) evaluated at the end of treatment as the primary objective. The secondary objectives are to study the impact of these two chemotherapy regimens on overall and relapse free survival, hematological and non-hematological toxicities, and costs. The primary judgement criterion will be the assessment of end of treatment QoL by the standardised questionnaire, EORTC QLQ-C30. Secondary judgement criteria will be Qol measured by EORTC QLQ-LC13 and SF36, overall and relapse free survival, tolerance and costs. The number of subjects needed is 75 in each group, 150 in total, to detect a difference of 10 points on the EORTC QLC-C30 scores with a standard error of 20 points (alpha 0.05; power 80%). EXPECTED RESULTS: This trial will provide clinicians with data on the impact of two currently unexplored adjuvant chemotherapy regimens on quality of life, tolerance and costs in NSCLC.

Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation.

We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h(+) NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program.

Detection of minimal residual disease (MRD) has proven to provide independent prognostic information for treatment stratification in several types of leukemias such as childhood acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and acute promyelocytic leukemia. This report focuses on the accurate quantitative measurement of fusion gene (FG) transcripts as can be applied in 35-45% of ALL and acute myeloid leukemia, and in more than 90% of CML. A total of 26 European university laboratories from 10 countries have collaborated to establish a standardized protocol for TaqMan-based real-time quantitative PCR (RQ-PCR) analysis of the main leukemia-associated FGs within the Europe Against Cancer (EAC) program. Four phases were scheduled: (1) training, (2) optimization, (3) sensitivity testing and (4) patient sample testing. During our program, three quality control rounds on a large series of coded RNA samples were performed including a balanced randomized assay, which enabled final validation of the EAC primer and probe sets. The expression level of the nine major FG transcripts in a large series of stored diagnostic leukemia samples (n=278) was evaluated. After normalization, no statistically significant difference in expression level was observed between bone marrow and peripheral blood on paired samples at diagnosis. However, RQ-PCR revealed marked differences in FG expression between transcripts in leukemic samples at diagnosis that could account for differential assay sensitivity. The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels. This is likely to prove invaluable to the management of patients entered into multicenter therapeutic trials.

Acute insulin response to glucose and glucagon in subjects at risk of developing type I diabetes.

OBJECTIVE: To determine if knowledge of characteristics of insulin response to various secretagogues during the preclinical phase of type I diabetes may facilitate the diagnosis of subjects at risk. RESEARCH DESIGN AND METHODS: A test consisting of sequential intravenous challenge with glucose (0.3 g/kg) and glucagon (1 mg, 10 min after the end of glucose injection) was performed on 171 ICA- relatives of type I diabetic patients, 18 ICA+ relatives of type I diabetic patients, and 5 transiently hyperglycemic subjects. Acute response to glucose was expressed as the sum of plasma insulin at 2 and 5 min and response to glucagon as the increase in plasma insulin after 10 min. RESULTS: Responses below the lower 95% confidence interval in the ICA- population (40 and 43 microU/ml for glucose and glucagon, respectively) were considered abnormal. The two values were correlated (r = 0.62). Abnormalities coexisted in 2.3% of the ICA- group, 11% of the ICA+ group, and 100% of the transiently hyperglycemic group. All the relatives who subsequently developed diabetes or hyperglycemic subjects who required insulin exhibited combined abnormalities. Some ICA- and ICA+ relatives were tested repeatedly over a follow-up period of 1.5-4 yr. Although the intraindividual coefficient of variation for the two responses was high (28 and 30%), values tended to run parallel in both ICA+ and ICA- relatives. In 2 patients monitored for 2 and 4 yr before diabetes developed, both responses declined at the same rate. In terms of prediction of diabetes, sensitivity of combined abnormalities was high (100%). But compared with the intravenous glucose tolerance test, improvement of specificity by the double challenge was not statistically significant. CONCLUSIONS: Both insulin responses to glucose and glucagon are related. They depend on the secretory capacity of beta-cells and simultaneously become abnormal in the prediabetic phase.

Timing of nephrology referral: influence on mortality and morbidity.

To assess the influence of the timing of nephrology referral on the short- and long-term outcome of hemodialysis patients, we retrospectively studied 309 patients who had end-stage renal failure and entered the chronic hemodialysis program in Sainte-Marguerite University Hospital between January 1, 1989, and December 31, 1996. We excluded from the analysis five patients without available data on referral pattern and 34 patients with irreversible acute renal failure. Of the remaining 270 patients, 177 patients (58%) had an early referral (ER) 16 or more weeks before the start of dialysis, and 93 patients (31%) had a late referral (LR) of less than 16 weeks before dialysis. Short-time morbidity (initial emergent dialysis, pulmonary edema, severe hypertension, temporary vascular access placement for first dialysis, prolonged initial hospitalization) was significantly more frequent in LR patients. Long-term evolution (mean follow-up, 26.5 +/- 26 months) did not differ between the two groups. The number of days of hospitalization per patient-year at risk beyond the third month was 21.5 +/- 33.7 days for ER and 21.1 +/- 36 days for LR patients. Survival analysis showed no difference between the two groups: 3-month survival rates were 96% in both groups, 1-year survival rates were 90% in the ER and 89% in the LR group, and 5-year survival rates were 52% in the ER and 56% in the LR group. In a Cox hazards regression model, referral pattern was not associated with a greater risk for death. In conclusion, delayed nephrology referral generated strikingly greater initial morbidity, but long-term outcome of hemodialysis patients was not modified by delayed nephrological care.

Posttransplantation acute tubular necrosis: risk factors and implications for graft survival.

Previous studies aimed at identifying the causes, risk factors, and outcome of kidney transplant recipients with delayed graft function (DGF) have yielded controversial results. We retrospectively analyzed the causes and risk factors for DGF in 263 cadaveric kidney transplantations from November 1988 to March 1997 in one center. Causes of DGF were assessed by postoperative graft evolution and graft biopsy. Univariate and multivariate analysis were used to investigate the risk factors for DGF induced by acute tubular necrosis (ATN). Seventy-six patients (29%) had DGF, which was caused by ATN in 70 patients (92.1%) and acute rejection (AR) in 6 patients (7.9%). Therefore, we focused on risk factors and consequences for ATN-induced DGF. In monofactorial analysis, ATN was significantly associated with greater weight and presence of an atheromatous disease in both donor and recipient. Other risk factors for ATN were older age of donor, recipient American Society of Anesthesiology (ASA) physical status category IV, cold ischemia time (CIT), and transplantation using the right kidney. The multivariate analysis showed that donor and recipient weight, donor age, transplantation using the right kidney, preservation in Eurocollins solution, ASA score, and CIT were associated with ATN. The incidence of rejection and renal function were not different at 3 months or 1 and 5 years. ATN is the main cause of DGF in kidney transplant recipients. ATN is caused by donor and recipient vascular background, grafting the right kidney, and CIT. ATN does not appear to have an adverse effect on long-term kidney function.

Is a short trial of prone positioning sufficient to predict the improvement in oxygenation in patients with acute respiratory distress syndrome?

OBJECTIVE: To determine whether a 1-h trial of prone positioning is sufficient to identify responders. DESIGN: Prospective clinical cohort study in a medico-surgical ICU in a teaching hospital. PATIENTS: 49 patients with acute respiratory distress syndrome. INTERVENTIONS: A 6-h period of prone positioning. MEASUREMENTS AND RESULTS: Baseline measurements (blood gas analysis and respiratory parameters) were evaluated in supine position just prior to turning the patients prone. Measurements were then repeated 1 h after the beginning of prone positioning (PP1h) and at the end of the 6-h period of prone positioning (PP6h). The last measurements were performed 1 h after repositioning the patients supine. Prone position induced an increase in the PaO2/FIO2 ratio (p < 0.001). A response (increase in PaO2/FIO2 ratio of at least 20 % at PP1h and/or at PP6h) was observed in 37 of 49 patients (76%). Twenty-seven of these patients (73%) were responders at PP1h while 10 (27%) were responders only at PP6h- In all, two-thirds of the patients were considered persistent responders. However, whereas the PaO2/FIO2 ratio decreased significantly 1 h after repositioning the fast responders supine, the PaO2/ FIO2 ratio remained unchanged after repositioning slow responders. CONCLUSIONS: A short-term trial of prone positioning does not appear a sufficient method to identify patients who would benefit from the postural treatment.

High or low doses of almitrine bismesylate in ARDS patients responding to inhaled NO and receiving norepinephrine?

OBJECTIVE: To evaluate the effects on oxygenation and pulmonary haemodynamics of almitrine bismesylate (AB) 5 microg/kg per minute and 16 microg/kg per minute in ARDS patients responding to and receiving inhaled NO (iNO) and presenting septic shock requiring norepinephrine, while no difference was observed in a previous trial including iNO responders and nonresponders. DESIGN: Prospective, cohort study. SETTING: Adult medico-surgical intensive care unit of a university hospital. PATIENTS: Fifteen patients with ARDS receiving and responding to iNO (10 ppm) and presenting septic shock requiring norepinephrine (mean 0.5+/-0.45 microg/kg per minute, range 0.08- 2.08). INTERVENTIONS: The protocol consisted of two consecutive phases in a fixed order: continuous intravenous infusion of AB 5 microg/kg per minute for 30 min, and continuous intravenous infusion of AB 16 microg/kg per minute for 30 min. MEASUREMENTS AND MAIN RESULTS: AB 5 microg/kg per minute significantly increased PaO2/FiO2 ( P<0.05) compared with iNO alone [160 (range 77-450) mmHg vs 122 (range 70-225) mmHg]. AB 16 microg/kg per minute produced a greater increase of PaO2/FiO2 ( P<0.05) when compared with 5 microg/kg per minute [227 (range 84-501) mmHg]. AB did not improve shunt at any dose regimen. AB produced an increase in mean pulmonary arterial pressure (MPAP) from 22+/-5 to 25+/-4 mmHg ( P<0.03). MPAP did not significantly increase between the two doses. Pulmonary vascular resistances and other haemodynamic and respiratory parameters were not affected by almitrine bismesylate. CONCLUSIONS: These results suggest that it is possible to obtain a further improvement in oxygenation by increasing AB infusion rate in ARDS patients iNO responders receiving norepinephrine. Due to the potential deleterious effects of AB, this strategy should be used in the most severely hypoxaemic patients.

Kinetics of postbiopsy levels of serum free prostate-specific antigen and percent free prostate-specific antigen.

OBJECTIVES: We evaluated the effects of transrectal ultrasound-guided biopsy of the prostate on serum total and free prostate-specific antigen (PSA) and the free/total PSA ratio and factors affecting variations in PSA levels. METHODS: Serum total and free PSA levels and the free/total PSA ratio were determined in 48 men (mean age 66+/-7 years) before and 1 hour, 8 days, and 30 days after prostate biopsy. At least six cores were taken using a biopsy gun with an 18-gauge needle. The coefficient of variation of PSA was calculated as the postbiopsy/prebiopsy PSA ratio. Changes in PSA levels and the coefficient of variation were studied. RESULTS: Fifteen (31%) of 48 men had adenocarcinoma on biopsy. Total and free PSA values were significantly increased 1 hour and 8 days after biopsy, and both returned to baseline 30 days after biopsy. The free/total PSA ratio was significantly increased (55%) 1 hour after biopsy and significantly decreased (12%) 8 days after biopsy. Thirty days after biopsy, the median of the free/total PSA ratio (18%) was not significantly different from the prebiopsy ratio (16%). The median of the coefficient of variation of the free/total PSA ratio was 3, 0.7, and 1 at 1 hour, 8 days, and 30 days after biopsy, respectively. Age, prostate volume, number of cores, and digital rectal examination and histologic findings were not significantly associated with variation in percent free PSA. Variation in percent free PSA at day 8 was associated with prebiopsy total PSA value and the free/total PSA ratio. CONCLUSIONS: Prostate biopsy dramatically alters the percent free PSA. The free/total PSA ratio was decreased 8 days after biopsy and returned to prebiopsy levels in 75% of patients at 1 month after biopsy. Measurement of free PSA levels and the free/total PSA ratio should not be done within 4 weeks of prostate biopsy.

Melanoma and tumor thickness: challenges of early diagnosis.

OBJECTIVE: To test the basic assumption of campaigns for early diagnosis of melanoma, ie, prognosis is correlated with the delay in the diagnosis. DESIGN: Prospective study of the correlation between delays to diagnosis, assessed using a questionnaire, and the Breslow thickness as a prognosis marker. SETTING: Dermatology departments in France. PATIENTS: Five hundred ninety consecutive patients, referred within 12 weeks after resection of cutaneous melanoma. MAIN OUTCOME MEASURES: Assessment of 5 successive time intervals from the first time the patients realized that they had a lesion until the resection of the melanoma, and results of the correlation between each time interval and tumor thickness (Breslow). RESULTS: There is a positive but weak correlation between tumor thickness and the delay to identify a lesion as suspicious (r = 0.17; P = .009). However, this delay tends to be short for the thickest tumors. There is a negative correlation between tumor thickness and the delay to seek medical attention (r = -0.20; P<.001). This delay was shorter for nodular melanoma. No correlation is found between melanoma thickness and physicians' delays. CONCLUSIONS: Poor prognosis can be accounted for by aggressive rapidly growing tumors rather than by delays. In well-informed populations, campaigns for early diagnosis of melanoma may thus no longer have a major impact on prognosis, unless they are focused on subgroups less accessible to information and medical care.

Comparison of methadone and high dosage buprenorphine users in French care centres.

AIMS: In France, maintenance programmes for opiate users were adopted later than in other countries. Two maintenance treatments are available: methadone is only delivered in specialized centres while high dosage (HD) buprenorphine can be prescribed by all general practitioners and in specialized centres. The aim of this study was to compare the socio-demographic profiles, the practices and drug consumption patterns of the two groups attending specialized centres. METHODOLOGY: The Oppidum Programme (observation of illegal drugs and misuse of psychotropic medications), a multi-centric survey, surveys drug-dependent subjects attending specialized care centres throughout France annually. Data were collected by questionnaire on socio-demographic variables and drug use during the preceding week. RESULTS: During October 1998, 46 centres took part in the survey. The methadone group (n = 424) was older, with a better economic situation; 16% used cocaine regularly. The HD buprenorphine group (n = 616) consumed more heroin (12% vs. 8%) and engaged in more misuse, such as intravenous use, illicit acquisitions or irregular consumption. These practices were more frequent for patients consuming the drug "outwith protocol" or for patients obtaining the drug from a general practitioner. CONCLUSION: Our results suggest that patterns of consumption of methadone and buprenorphine are different in several respects: concomitant use of licit or illicit psychoactive substances, route of administration, and illegal acquisition. They also suggest that the behaviours of maintenance treatment users depend less on the nature of the maintenance drug (methadone or high dosage buprenorphine), than the nature of the delivery and monitoring practices.

Recent evolution in opiate dependence in France during generalisation of maintenance treatments.

Two maintenance drugs had been used in France since 1996, methadone and high-dosage buprenorphine. This study aimed to examine changes in drug use from observations gathered between 1995 and 1997, within the framework of the French program for the monitoring of drug dependence (OPPIDUM). This annual survey studies psychoactive substances consumed by drug addicts attending specialised drug care centres. During the last three surveys, 16 centres collected a total of 1597 patient-files. This study shows an increase in the number of patients undergoing maintenance treatment (from 14 to 69%), a reduction in the number of intravenous drug users (from 55 to 22%) and a reduction in consumption of psychoactive substances. However, poly-drug addiction behaviour continues and high-dose buprenorphine subjects frequently use the substance intravenously and in association with benzodiazepines.

Buprenorphine prescription by general practitioners in a French region.

Since 1996 French general practitioners (GPs) may prescribe sublingual buprenorphine tablets as maintenance treatment for opiate dependence. The computerised data management of the main French health reimbursement system now allows surveillance of the use of this drug, and how it is prescribed. The purpose of this study is to determine the profile of maintained patients, prescribed doses, associated psychotropic treatments and how practitioners prescribe these treatments. This study analyses the 11186 buprenorphine prescriptions electronically transmitted for reimbursement between September and December 1999 in a specific French region. It was found that the 2078 treated patients consumed a mean of 11.5 mg of buprenorphine per day and 12% of them procured prescriptions from more than two prescribers. 43% of maintained patients had an associated benzodiazepine prescription, mainly flunitrazepam, often on the same prescription form. 61% of patients had regular follow-up, others had occasional consultations (21%) and another 18% had deviant maintenance treatment (more than two prescribers or more than 20 mg per day of daily buprenorphine dose). Benzodiazepine consumption was much higher in the 'deviant group' (71.4%). 85% of buprenorphine prescriptions were made by GPs. 21% of GPs prescribed buprenorphine and 61% of those had only one or two maintained patients. Buprenorphine prescription by French GPs is a procedure with no particular requirements, allowing many patients to easily access maintenance treatments. However, a high risk of abuse exists, which demands extensive investigation and evaluation of these practices.

VATS is an adequate oncological operation for stage I non-small cell lung cancer.

OBJECTIVES: This study was designed to determine the long-term prognosis of video-assisted thoracic surgery (VATS) vs. open lung resections for patients with pathological stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The medical records of all patients who underwent lung resection for a pathological stage I NSCLC were reviewed for the period from 1990 to 1999, by screening of a database into which data were entered prospectively. There were 511 patients (430 males and 81 females) whose age averaged 63+/-10 years who underwent 515 lung resections. Our VATS experience began in 1993 with selected stage I patients, and since that date an average of one patient on four was managed with VATS. Lung resections consisted of 25 wedge resections or segmentectomies (seven VATS), 390 lobectomies (92 VATS), 19 bilobectomies (one VATS) and 81 pneumonectomies (ten VATS). Lymph node dissection was performed in all cases. RESULTS: There were significantly more females (P=0.01) and adenocarcinoma (P=0.02) in the VATS group (n=110) when compared to the open group (n=405). Tumour size averaged 4+/-2 cm in the open group and 3+/-2 cm in the VATS group (P=0.04). The distribution of T1/T2 tumours was 97/308 and 50/60, respectively (P=0.0001). At follow-up, cancer recurrence could be documented in 117 patients, with no difference of incidence between the two groups (22.5 vs. 24.5%; P=0.64). Estimated Kaplan-Meier 5-year survival rates, including the operative mortality as well as any cancer-related and unrelated death, were 62.8% (confidence interval (CI): 56.8-68.7%) vs. 62.9% (CI: 51.4-74.4%), respectively (P=0.60). The advent of VATS did not influence the patients' survival: 5-year survival rate was 63.9% (CI: 55.3-72.5%) for the period from 1990 to 1992, and 58.8% (CI: 51.7-65.9%) for the period from 1993 to 1999 (P=0.65). Subgroups survival analysis according to the T status did not show any statistically significant difference between the two groups. CONCLUSIONS: VATS lung resection with lymph node dissection achieved a 5-year survival similar to that achieved by the conventional approach. VATS is a valuable option for the management of selected patients with an early-stage NSCLC.

Postoperative complications in relation with induction therapy for lung cancer.

OBJECTIVES: The purpose of this study was to evaluate the risk of lung cancer surgery following induction chemotherapy and/or radiotherapy. METHODS: This retrospective study included 69 patients treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA, n = 25); temporary functional impairment (two stages IB and two stages IIIA (N2), n = 4); and doubtful resectability (stage IIIB (T4), n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received two to four cycles of chemotherapy (average 2.9 +/- 0.8 cycles) and 43 +/- 8 Gy (range 20--60 Gy), or chemotherapy alone in 26 patients (3 +/- 0.7 cycles). RESULTS: Exploratory thoracotomy was performed in four patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were four re-operations (6%): three for bronchial fistula and one for bleeding. Thirty-five patients (51%) required blood transfusion (4.5 +/- 3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). CONCLUSIONS: Surgery for lung cancer after induction chemotherapy and/or radiotherapy is associated with an increased risk. If the mortality seems 'acceptable', the morbidity rate, however, is high.