Meningiomas in patients with long-term exposition to progestins: Characteristics and outcome.

OBJECTIVE: The aim of this study was to describe progestin-associated meningiomas' characteristics, outcome and management. MATERIAL AND METHODS: We included 53 patients operated on and/or followed in the department for meningioma with progestin intake longer than one year and with recent drug discontinuation. RESULTS: Cyproterone acetate (CPA), nomegestrol acetate (NomA), and chlormadinone acetate (ChlA) were involved in most cases. Mean duration of progestin drugs intake was 17.5 years. Tumors were multiple in 66% of cases and were located in the anterior and the medial skull base in 71% of cases. Transitional subtype represented 16/25 tumors; 19 meningiomas were WHO grade I and 6 were grade II. The rate of transitional subtype and skull base location was significantly higher compared to matched operated meningioma general population. No difference was observed given WHO classification. But Ki67 proliferation index tends to be lower and 5/6 of the WHO grade II meningiomas were classified as WHO grade II because of brain invasion. Strong progesterone receptors expression was observed in most cases. After progestin discontinuation, a spontaneous visual recovery was observed in 6/10 patients. Under CPA (n=24) and ChlA/NomA (n=11), tumor volume decreased in 71% and 18% of patients, was stabilized in 25% and 64% of patients, and increased in 4% and 18% of patients, respectively. Volume outcome was related to meningioma location. CONCLUSIONS: Outcome at progestins discontinuation is favorable but different comparing CPA versus ChlA-NomA and comparing tumor location. Long-term follow-up is required. In most cases, simple observation is recommended and surgery should be avoided.

Minimally invasive posterior fixation and anterior debridement-fusion for thoracolumbar spondylodiscitis: A 40-case series and review of the literature.

INTRODUCTION: Pyogenic spondylodiscitis is a rare disease, but incidence is increasing. Reported failure rates following conservative management range from 12% to 18%. The purpose of this study was to determine the safety and efficacy of posterior percutaneous pedicle screw fixation combined with anterior debridement and fusion (ADF) for infective spondylodiscitis in the thoracic and/or lumbar spine. METHODS: The retrospective study cohort comprised all patients without neurological deficit who underwent minimally invasive posterior and anterior surgery between April 2008 and April 2016 for thoracic and/or lumbar spondylodiscitis. RESULTS: Forty patients were eligible (16 female: 40%). The lumbar region was affected in 31 cases (77.5%). Source of infection was identified in only 22 cases (55%) and bacteriological identification was obtained in 32 cases (80%). Mean hospital stay was 14.8 days (range, 6-39 days). Complete recovery was achieved in 39 patients (97.5%) at 3 months' follow-up. Mean preoperative local kyphosis angle was 16.1o, versus 14o at 1-year (P>0.05). 36 patients (90%) had at least 1 year's follow-up, and fusion was obtained for all these cases. CONCLUSION: Two-stage minimally invasive surgery is effective and safe for the treatment of single or two-level thoracolumbar spondylodiscitis. It could be an alternative to conventional open surgery or conservative treatment.

Distinct Profiles of Consumers of Psychoactive Substances in People Attending French Sexual Transmitted Infections Centers.

The objective of this cross-sectional survey was to assess the prevalence of psychoactive substance use (PSU) in people attending 11 French Sexual Transmitted Infection Centers, and to specify their profiles (PSU and link with risky sexual behaviors) using the ascending hierarchical clustering method. Among the 5220 individuals who completed the survey, 55.6% were men and the median age was 24 years [IQR: 20-31]. Among the participants, 2751 (52.7%) reported PSU at least once in their life. Ascending hierarchical clustering identified seven distinct profiles of participants based on their PSU. This study shows a high prevalence of PSU and alcohol consumption in this young population. Moreover, subgroup analysis allowed identifying groups of psychoactive substance users who presented specific risks or vulnerabilities and who should be priority targets for interventions, particularly sexual minority groups.

Implementing screening, brief intervention and referral to treatment in a French cohort of people living with HIV: a pilot study.

OBJECTIVES: Screening, brief intervention and referral to treatment (SBIRT) is an evidence-based practice used to identify, reduce and prevent problematic use and abuse of, and dependence on, tobacco, alcohol and psychoactive substances. To date, the pertinence of this practice among people living with HIV (PLHIV) is unknown. In this pilot study, we aimed to assess the acceptability of SBIRT in a cohort of HIV-infected out-patients who were asked about their consumption of alcohol, tobacco and psychoactive substances. METHODS: A monocentric study was performed at the University Hospital of Montpellier. In a 6-month period, 20 trained physicians screened for the consumption of alcohol [using the Alcohol Use Disorders Identification Test (AUDIT)], tobacco (using the Short Fagerstrom Test) and psychoactive substances [using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) V3.0] via an auto-questionnaire and proposed a brief intervention to patients with misusage. RESULTS: One thousand and eighteen PLHIV completed the questionnaire, and 861 [84.6%; 95% confidence interval (CI) 82.2-86.7%] PLHIV returned it to the physician. Among the latter, 650 patients wished to discuss the answers with their physician (75.5%; 95% CI 72.5-78.3%), and brief interventions were realized in 405 patients (62.3%). CONCLUSIONS: SBIRT is a simple screening and harm reduction tool that is well accepted by PLHIV in out-patient clinics. This method could be implemented in routine HIV care to screen and manage patients systematically for harmful substance use.

Surgical management of post-traumatic atlantoaxial rotatory fixation due to C2 facet fracture: 5 clinical cases.

PURPOSE: Report the results of surgical treatment of post-traumatic atlantoaxial rotatory fixation (AARF) due to C2 articular facet fracture in adults. MATERIAL AND METHODS: The records of five patients treated since 2009 for AARF due to a C2 articular facet fracture were analyzed retrospectively. Three women and two men with an average age of 60 years (27-82) were included, one of whom initially had neurological deficits. In all cases, the surgical strategy consisted of posterior fixation: Harms-type in four cases and trans-articular with hooks in one case. RESULTS: Dislocations due to fracture of the C2 articular facet are rare in adults; various treatment strategies have been described. In our experience, posterior screw fixation leads to satisfactory clinical and radiological outcomes. Fusion is not necessary in these cases because the dislocation is related to an asymmetric fracture without ligament damage. CONCLUSION: Posterior fixation provides satisfactory reduction of these injuries and leads to satisfactory bone union. This surgical treatment can be performed early on after the trauma and is an interesting alternative to conservative treatment.

Long term reference change value of creatinine in HIV-positive patients with anti-retroviral therapy: A new tool in clinical practice.

BACKGROUND: The use of reference change value (RCV) instead of reference interval emerged as an alternative approach for longitudinal interpretation of biological marker. Follow-up of creatinine variation in HIV-positive adults remains a challenge in order to prevent renal complications. OBJECTIVES: To determine the long term RCV of creatinine in HIV-positive adults receiving anti-retroviral therapy (ART) according to the use of tenofovir or ritonavir. DESIGN AND METHODS: Longitudinal study of 24 months that include 124 HIV-positive patients followed in HIV outpatient unit. Plasma creatinine was measured at 0, 6, 12 and 24 months in order to calculate the RCV. RESULTS: In the whole group, a 24-month RCV of creatinine was 22.5%. Whatever the ART, the index of individuality was <0.6. Significantly higher RCV of creatinine was observed in patients receiving the association tenofovir and ritonavir (28%) compared to the patients receiving i) tenofovir without ritonavir (21.9%), ii) no tenofovir but ritonavir (22.2%), and iii) no tenofovir and no ritonavir (19.7%). CONCLUSIONS: The low value of index of individuality pinpointed that RCV should be used to identify critical change in serial creatinine results in HIV-positive adults. RCV of creatinine under ART was around 20% but reached 28% in case of association of tenofovir and ritonavir.

Therapeutic drug monitoring of posaconazole in hematology adults under posaconazole prophylaxis: influence of food intake.

Posaconazole (PCZ) is given at 200 mg three times daily as a fungal prophylaxis in neutropenic hematologic malignancy patients. A relationship between exposure, plasma concentration, and efficacy is suggested. The objectives of this prospective study were to analyze the PCZ plasma concentration in hematology adults at high risk of developing invasive fungal infections (IFIs), and factors that could have an impact on the PCZ plasma concentration. PCZ plasma concentrations were measured after 2, 7, 10, 14, and 21 days of PCZ prophylaxis. Factors such as gender, age, body weight, posology, treatment duration, mucositis, proton pump inhibitor (PPI) use, and food intake were studied. Sixty-three patients were included, with a median age of 52 years (range 17-70) and a median weight of 75 kg (range 47-150). The median PCZ plasma concentration of the 63 patients ranged from 0.42 to 0.48 mg/L. At day 2, 30% of PCZ plasma concentration were under 0.35 mg/L, and at day 7, 74% were <0.70 mg/L. PCZ plasma concentrations were not affected by gender, age, body weight, or treatment duration. We found that food intake had a high influence on PCZ plasma concentrations (p = 0.0049). PCZ was well tolerated. One patient has developed a probable IFI, probably related to a low exposure to PCZ. PCZ therapeutic drug monitoring (TDM) is essential in order to early detect patients with low concentrations, to assess the etiology of such results, and to decide on the treatment strategy to apply.

Methotrexate pharmacokinetics in childhood acute lymphoblastic leukaemia: a prognostic value?

WHAT IS KNOWN AND OBJECTIVE: In industrialized countries, acute lymphoblastic leukaemia (ALL) is the most frequent cancer in children aged less than 15 years. High-dose methotrexate is a common component of many chemotherapeutic protocols for childhood with ALL. Our objective was to retrospectively evaluate the pharmacokinetics and plasma levels of high-dose methotrexate as it relates to event-free survival (EFS) in children with ALL. METHODS: Relapsed patients and subjects in EFS were compared for MTX serum concentrations 24, 36, 48 and 72 h after the start of 24 h infusion. Clearance (Cl), area under the curve (AUC) and volume of distribution (V(d) ) of the drug were estimated by the NONMEM computer program and also compared between both groups. RESULTS AND DISCUSSION: Among 69 children included, 54 (78·3%) were still in EFS, whereas 15 (21·7%) relapsed. The difference between relapsed and EFS patients for the pharmacokinetic parameters studied was not significant. On the contrary, the cohort studied was representative and known prognostic factors for relapse in ALL were significantly associated with relapse. WHAT IS NEW AND CONCLUSION: Serum concentrations and pharmacokinetic parameters of MTX are not associated with outcome in ALL. Prognoses based on single-drug pharmacokinetic estimates within a complex multiple-agent protocol appear to be unreliable. However, therapeutic drug monitoring of high-dose methotrexate remains a useful tool for early detection of impaired elimination and for avoiding systemic toxicity.

[Infectious adverse events related to misuse of high-dose buprenorphine: a retrospective study of 42 cases]. / Complications infectieuses induites par le mésusage de la buprénorphine haut dosage (Subutex): analyse rétrospective de 42 observations.

PURPOSE: Misuse of high-dose buprenorphine (HDB), mainly by injection, is responsible of frequent infectious adverse events. METHODS: This is a retrospective study of infectious complications occurring in patients using HDB by injection. Forty-two cases were identified (29 men and ten women) and the data were collected between March 1999 and December 2008. RESULTS: The infectious complications included cutaneous infections (27 cases), endocarditis (nine cases), osteoarticular infections (four spondylodiscitis and one sacroiliitis), and a vascular embolism with decrease in visual acuity. CONCLUSION: The results of HDB maintenance treatment must be improved, both from the point of view of substitution and to limit its misuse by intravenous route injection. Health professionals have to play an important role in drug addict patients' education and supervision, to prevent buprenorphine injection and related infectious complications.

Inherited long QT syndrome revealed by antifungals drug-drug interaction.

A 14-year-old Tahitian girl with acute myeloid leukaemia and a suspected mucormucosis infection was treated with intravenous voriconazole and caspofungin. Because of worsening of fungal infection, voriconazole was switched to posaconazole. During the switch, the patient presented with QT interval prolongation with 'torsades de pointes' and reversible cardiac arrest. Voriconazole plasma level measured 15 h after the last administration was 7 mg/L. Genotyping suggested that the patient was an extensive metabolizer with respect to CYP2C9 and CYP2C19. The association of antifungal agents with pro-arrhythmogenic drugs and other risk factors led to torsades de pointes and the revealing of inherited QT syndrome.

Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist?

OBJECTIVE: To improve the definition of the various clinical patterns of patients with drug-induced cutaneous side-effects with systemic symptoms, and their possible relationships with the triggering medication, with the ultimate goal of helping in the identification of the causal drug in difficult situations when the patient is taking several drugs. METHODS: Cases of drug-induced cutaneous side-effects associated with various systemic syndromes related to anticonvulsants (carbamazepine, phenytoin and phenobarbitone), minocycline, allopurinol, abacavir and nevirapine were collected retrospectively from the French Pharmacovigilance database (FPD) over a period of 15 years (1985-2000). The clinical patterns typical of the causative drugs were described and compared with data from the literature. RESULTS: Two hundred and sixteen patients with symptoms and signs consistent with cutaneous drug reactions with systemic symptoms were reported to the FPD during this period of time. Their pattern was similar to published data for these drugs, with fever, cutaneous eruption, hepatic abnormalities and eosinophilia being the most prominent but inconstant symptoms. There are clues suggesting that some particular lesional patterns may exist for some drugs. CONCLUSIONS: Although some trends emerge from these retrospective data, they suggest that no clear, unified outline can currently be defined for these multi-organ drug-induced reactions. Instead, a constellation of various symptoms and signs were recorded, that might be sorted in different patterns according to the causal drug, a finding that might indeed improve accurate identification of the causative drug in patients receiving several principal medications at a time. A national prospective study systematically collecting standardized data is required better to define the outlines of these severe adverse drug reactions and to evaluate prognostic data.

Low plasma levels of dehydroepiandrosterone sulphate in HIV-positive patients coinfected with hepatitis C virus.

OBJECTIVES: To evaluate plasma levels of dehydroepiandrosterone sulphate (DHEAS) in a cohort of HIV-infected patients and to analyse factors associated with DHEAS levels. METHODS: We conducted a cross-sectional survey in the Nîmes University Hospital cohort of HIV-infected patients in south-eastern France. All HIV-infected patients with at least one outpatient visit between 1 January and 1 September 2002 were included in the study. Sociodemographic, clinical, therapeutic, immuno-virological and plasma DHEAS level data were collected during this period. Hepatitis C virus (HCV) coinfection was defined as the presence of HCV antibody with positive RNA. To identify factors associated with plasma DHEAS levels, Spearman's rank correlation and univariate and multivariate linear regression analyses were used. RESULTS: The DHEAS plasma level was measured in 137 patients (104 men and 33 women), 37 (27.0%) of whom were HCV coinfected. The median age of the patients was 39.1 years [interquartile range (IQR): 34.9-48.7] for women and 41.8 years (36.5-47.7) for men. The median DHEAS level was 5.5 micromol/L (IQR: 2.3-8.8) for the whole sample of 137 patients, and was lower in women (2.4 micromol/L; 1.5-6.6) than in men (6.1 micromol/L; 2.5-9.0) (P<0.01), and lower in patients coinfected with HCV (2.1 micromol/L; 0.6-6.7) than in those not coinfected (6.6 micromol/L; 3.0-9.1) (P<0.01). Of all prognostic factors studied in the variance covariance analysis, three factors were associated with DHEAS: age, gender and HCV coinfection. Subgroup analysis revealed that the age-adjusted mean of the DHEAS level was lower in HCV coinfected patients for both women (1.3+/-1.1 micromol/L) and men (4.0+/-0.7 micromol/L), compared with patients not HCV coinfected (women, 5.3+/-0.7 micromol/L; men, 7.2+/-0.4 micromol/L) (P<0.01). CONCLUSIONS: This is the first report of the determination of DHEAS plasma levels in HIV/HCV coinfected patients. When age and sex were taken into account, the DHEAS plasma level was found to be significantly lower in HCV coinfected patients. To date, the pathophysiology of such findings is unknown.

Performance analysis of a rapid HPLC determination with the solvent demixing extraction of HIV antiproteases and efavirenz in plasma.

A rapid and simple high-performance liquid chromatographic method without internal standardization is evaluated for the drug-level monitoring of most marketed antiproteases and efavirenz. Following plasma deproteinization with acetonitrile, the analytes are extracted into the solvent while it is demixed by the addition of a saturating amount of neutral salt. The organic supernatant is diluted by half with water up to the polarity of the mobile phase before being injected. The isocratic mobile phase is unbuffered water-acetonitrile (52:48), and the stationary phase is LiChrospher 100 RP-8 (5 microm). Analytes are eluted between 4 min (amprenavir and indinavir) and 20 min (nelfinavir). A spreadsheet program including analysis of variance (ANOVA) and regression is used for both the overall validation of milligrams-per-liter determinations and the performance evaluation of analytical steps from chromatographic raw data. Extraction shows acceptable 5% repeatability and nearly 100% recovery, although it is somewhat concentration-dependent. The calibration function is better fitted by bilogarithmic than arithmetical regression, and the ANOVA of raw data is found quite predictive of the quality of the final determinations.

Long-term assessment of neuropsychiatric adverse reactions associated with efavirenz.

OBJECTIVES: The Sensio study objectives were to assess the outcome of neuropsychiatric adverse reactions (NPAR) that develop after initiation of efavirenz (EFV) therapy, to ascertain the late NPAR after a 3-month treatment period, to evaluate the impact of NPAR on patients' quality of life (QoL) in a real-life population. METHODS: During a 6-month period, consecutive HIV-infected adult outpatients receiving an ongoing EFV therapy for at least 3 months were asked to fill in a specifically designed self-administered questionnaire addressing sleep disturbances, behavioural changes, mood disturbances, anxiety, cognitive disorders, hallucinations, dizziness and the general impact on patients' QoL. RESULTS: A total of 174 questionnaires were analyzed. The main late emergent NPAR were sleep disorders: abnormal dreams 24.7%, nocturnal waking 19.6%, trouble falling asleep 17.8%; cognitive disorders: memory disorders 23.0%, impaired concentration 18.9%; anxiety 15.5%; mood disorders: sadness 19.3%, suicidal ideations 9.2%. Global neuropsychic discomfort was moderate to severe in 23% of patients after a 3-month treatment period. CONCLUSION: NPAR occur mainly during the first month of EFV therapy but often persist thereafter. A significant percentage of patients reported suicidal ideations at the time of the study. Our results suggest the need for routine screening for NPAR among patients receiving EFV therapy and better management.

Chronic cough induced by abacavir apart from a context of hypersensitivity.

We report the case of an HIV-infected woman, who presented with chronic and productive cough without sign of hypersensitivity (fever, cutaneous eruption, gastrointestinal disorders), while taking abacavir. All complementary exams being negative, the involvement of abacavir has been suspected. So the drug was stopped leading to a rapid disappearance of cough. It is the first report of chronic cough with abacavir apart of a context of hypersensitivity reaction.

[Inhaled corticoids and systemic secondary effects: controversies]. / Corticoïdes inhalés et effets secondaires systémiques: controverses.

Studies that compare the systemic impact of inhaled corticosteroids (CI) abound in the literature often with contradictory results. Most of the studies report secondary biological effects in the suprarenal function without clinical effect due to taking high doses of inhaled corticosteroids. Surveillance of the secondary effects on bone is difficult to demonstrate. Finally, speed for recognition in asthmatic children during the first year of treatment is slowed down but the level at adult age is not affected. The variability of these results is associated with the former taking of corticosteroids by the general route. Administration of corticosteroids by the systemic route, therefore makes difficult the evaluation of secondary effects due only taking inhaled corticosteroids.