Prevalence of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Spatial Association With Quarries in a Region of Northeastern France: A Capture-Recapture and Geospatial Analysis.

OBJECTIVE: Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs. METHODS: Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture-recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region. RESULTS: Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture-recapture analysis was 6.4 (95% confidence interval [95% CI] 3.6-11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3-93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3-34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7-35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 [95% CI 1.66-3.80]), and geographic-weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed. CONCLUSION: In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease.

[Evaluation of an automated system of immunofluorescence analysis in daily practice]. / Évaluation des performances d'un système automatisé de lecture d'immunofluorescence en pratique quotidienne.

Since a few years indirect immunofluorescence (IIF) enjoys automated screening. These automated systems give an interpretation for the detection of anti-nuclear (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) and take images in the case of the research of anti-tissue antibodies. We propose an evaluation of the Image Navigator® system for all these kinds of research. 1,435 sera samples are included: 810 for ANA detection, 450 for ANCA detection, 175 for anti-tissue antibodies research. Visual interpretation using microscope is compared to automated interpretation and visual interpretation using the pictures. Sensibility of the automated interpretation to artifacts is assessed too. Accordance between automated interpretation and visual interpretation using microscope is moderate (kappa=0.46) in the case of ANA detection, poor in the case of ANCA detection (kappa=0.30). Accordance between visual interpretation using microscope and visual interpretation using pictures is strong for ANA (kappa=0.79) and for ANCA (kappa=0.63), very strong for anti-tissues antibodies (kappa=0.87). The blur of more than one photography interferes with the interpretation of the system (p<0.01). In any case, a second reading is necessary. The results of our study validate the use of the pictures for the interpretation of AAN but require visual interpretation using microscope for ANCA. The screening of anti-tissue antibodies can be achieved using pictures.

Testing for Drugs in Exhaled Breath Collected With ExaBreath in a Drug Dependence Population: Comparison With Data Obtained in Urine After Liquid Chromatographic-Tandem Mass Spectrometric Analyses.

BACKGROUND: Exhaled breath is commonly used in alcohol testing but has been recently demonstrated by scientists from Sweden, Switzerland, and the United States to contain a large number of both volatile and nonvolatile substances that can be measured using dedicated devices. ExaBreath is a sampling device that collects the bio-aerosols particles from the donor. Approximately 1-2 minutes exhaled breath is enough for the test. The device collects the very small bio-aerosols on a filter, which is consecutively incubated into methanol to release the drugs at the laboratory. METHODS: Eighteen drug addicts from a methadone substitution program were recruited for this study. There were 5 women and 13 men, aged 25-50 years. The daily methadone dosage ranged from 10 to 120 mg, mostly as syrup. Urine (in plastic tubes with no preservative) and exhaled breath were simultaneously collected. In both fluids, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) were tested using a specific liquid chromatographic-tandem mass spectrometric method, whereas all other compounds were screened by liquid chromatographic-tandem mass spectrometric method using a home made library of more than 800 compounds. Linearity, imprecision, and limit of quantitation were established. In each analytical batch, low and high controls were included. RESULTS: All 18 urine specimens tested positive for methadone and EDDP. Several other compounds were also identified, including morphine, THC-COOH, benzoylecgonine, nicotine, some antidepressants, and neuroleptics. Methadone and EDDP were identified in exhaled breath from all 18 patients, with concentrations in the range 11-1470 and 29-818 pg per filter, respectively. In 13 cases, the ratio methadone/EDDP in exhaled breath was >1 (range 0.4-2.8). Except nicotine (n = 7), no other substance was detectable in exhaled breath. CONCLUSION: This study gives further support to the possibility of using exhaled breath as a new matrix to document exposure to drugs.

Case report of ivabradine intoxication.

Ivabradine is a drug used for the treatment of angina and chronic heart failure in cases of intolerance or insufficiency of response to beta-blocker treatment. A 47-year-old man was admitted to the emergency department of the hospital for a voluntary intoxication with 280 mg of ivabradine: he presented drowsiness and a mild sinusal bradycardia (50 bpm) associated with a well-tolerated low blood pressure at 100/50 mmHg. No complication was noted and he was discharged from the hospital on Day 3. A method for ivabradine assay in serum was obtained using liquid chromatography coupled with a mass spectrometry detection method. After a deproteinization step using QuECHERS salts and acetonitrile, a chromatographic separation was performed using a 5-µm 50 × 2.1 mm Xterra® column (Waters, France). Detection was performed using an LTQ linear ion-trap mass spectrometer equipped with an electrospray ionization source used in a positive ionization mode (ThermoFisher Scientific, San Jose CA, USA) and a detection in full MS(2) scan. The limit of quantification of ivabradine was 10 µg/L, and the method was linear up to 1000 µg/L. The ivabradine concentration in the patient's serum was 375 µg/L. This concentration value was >30 times those measured after therapeutic doses intakes. Nevertheless, the bradycardia was no more severe than the one observed with therapeutic dosage. In conclusion, this case tends to show an absence of correlation between blood concentration and severity of the troubles in cases of overdosage.