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Trigeminal neuralgia, considered by many the worst pain that humankind can experience, has been called “the suicide disease.” Neuroablative procedures are good options when conservative treatment fails to promote pain relief or in those whose side effects are unbearable. The objective was to compare the effectiveness and safety of trigeminal percutaneous radiofrequency ablation in classical refractory trigeminal neuralgia in a prospective, randomized, double-blind, sham-controlled clinical trial. We included 30 consecutive patients with classical trigeminal neuralgia who had failed to respond to drug treatment. The patients were randomly assigned into two groups: a thermal radiofrequency and a sham group. The thermal radiofrequency group were submitted to a 75°C lesion for 60 seconds after proper sensory and motor stimulation. All steps were carried out in the sham group except the thermal lesion. Patients were evaluated using the Numerical Rating Scale (NRS), the 36-Item Short-Form Health Survey questionnaire, and anticonvulsant dose. After 1 month, the mean NRS score decreased from 9.2 to 0.7 in the radiofrequency group and from 8.9 to 5.8 in the sham group. This significant reduction was measurable starting at day one after the procedure and remained significant throughout the first month. Changing groups was allowed after one month, after which the pain reduction was similar between the two groups. Percutaneous trigeminal radiofrequency ablation results in statistically and clinically significant greater pain relief than the sham procedure after 1 month of follow-up. These results support using radiofrequency nerve ablation as a treatment for refractory trigeminal neuralgia.

Purpose Young patients represent a particularly vulnerable group regarding vocational prognosis after an acquired brain injury (ABI). We aimed to investigate how sequelae and rehabilitation needs are associated with vocational prognosis up to 3 years after an ABI in 15–30-year-old patients. Methods An incidence cohort of 285 patients with ABI completed a questionnaire on sequelae and rehabilitation interventions and needs 3 months after the index hospital contact. They were followed-up for up to 3 years with respect to the primary outcome “stable return to education/work (sRTW)”, which was defined using a national register of public transfer payments. Data were analyzed using cumulative incidence curves and cause-specific hazard ratios. Results Young individuals reported a high frequency of mainly pain-related (52%) and cognitive sequelae (46%) at 3 months. Motor problems were less frequent (18%), but negatively associated with sRTW within 3 years (adjusted HR 0.57, 95% CI 0.39–0.84). Rehabilitation interventions were received by 28% while 21% reported unmet rehabilitation needs, and both factors were negatively associated with sRTW (adjusted HR 0.66, 95% CI 0.48–0.91 and adjusted HR 0.72, 95% CI 0.51–1.01). Conclusions Young patients frequently experienced sequelae and rehabilitation needs 3 months post ABI, which was negatively associated with long-term labor market attachment. The low rate of sRTW among patients with sequelae and unmet rehabilitation needs indicates an untapped potential for ameliorated vocational and rehabilitating initiatives targeted at young patients.

Background The cardiovascular disease (CVD) burden among patients with oesophageal cancer (EC) treated with curative intent is unclear. Purpose To determine CVD incidence and all-cause mortality in patients with EC. Material and methods Danish national health registries were used to identify patients diagnosed with primary EC between 2008 and 2018. Each EC patient was matched with ten individuals from the general population. The primary endpoint was a CVD hospital contact (CVD-HC), either admission or outpatient contact. Secondary endpoints were all-cause mortality and five specific CVD endpoints evaluated separately: atrial fibrillation, ischemic heart disease, heart failure, perimyocarditis, and venous thromboembolism. Using registries, all endpoints were assessed up to ten years following the EC diagnosis. Results The study included 1,525 patients with EC matched to 15,250 individuals from the general population. Patients with EC had a post-diagnosis one-year adjusted hazard ratio (HR) of CVD-HCs of 6.1 (95% CI: 5.6 to 6.8) compared with the general population. During the next nine years, the risk of CVD-HC was comparable between the two cohorts with an adjusted HR of 1.0 (95% CI: 0.9 to 1.3) (Figure 1). Patients with EC, particularly those with prevalent CVD (29%) had a high risk of ischemic heart disease with a one-year HR of 6.2 (95% CI: 3.7 to 10.4). The risk of venous thromboembolism and atrial fibrillation was 14-fold and four-fold elevated within the first year after EC diagnosis compared to the general population. After EC diagnosis, all-cause mortality was, as expected, increased in patients with EC compared with the general population. However, prevalent CVD among patients with EC did not appear to be associated with higher all-cause mortality. Conclusion CVD morbidity was transiently increased in the first year following EC diagnosis compared with the general population. All-cause mortality risks were high but did not appear to be affected by prevalent CVD. The very high risk of CVD in curatively treated patients with EC calls for healthcare initiatives to advance preventive and post-treatment strategies. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Cancer SocietyCarpenter Jorgen Holm and Wife Elisa F. Hansen's Memorial Scholarship

Los estudios transversales se caracterizan por la medición simultánea de la exposición y el outcome de interés. Son el diseño idóneo para estimar prevalencias, analizar la precisión diagnóstica de una prueba y validar instrumentos, para lo cual es esencial controlar los sesgos de información, selección y confusión ya sea por diseño o por análisis. Asimismo, es crucial escoger la medida de asociación idónea para cada outcome de interés, llámese el odds ratio para eventos raros y la razón de prevalencias para los eventos frecuentes. Finalmente, para su redacción y publicación se recomienda revisar las guías STROBE y STARD

Background: Data on the association between quality of heart failure (HF) care and outcomes among patients with incident HF are sparse. We examined the association between process performance measures and clinical outcomes in patients with incident HF with reduced ejection fraction. Methods: Patients with incident HF with reduced ejection fraction (n=10 966) between January 2008 and October 2015 were identified from the Danish HF Registry. Data from public registries were linked. Multivariable regression analyses were used to assess the association between 6 guideline-recommended HF care processes (New York Heart Association assessment, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, exercise training, and patient education) and all-cause and HF readmission, all-cause and HF hospital days, and mortality within 3 to 12 months after HF diagnosis. The associations were analyzed according to the percentages of all relevant performance measures fulfilled for the individual patient (0%–50% [reference group], >50%–75%, and >75%–100%) and for the individual performance measures. Results: Fulfilling >75% to 100% of the performance measures (n=5341 [48.7%]) was associated with lower risk of all-cause readmission (adjusted hazard ratio, 0.78 [95% CI, 0.68–0.89]) and HF readmission (adjusted hazard ratio, 0.71 [95% CI, 0.54–0.92]), lower use of all-cause hospital days (adjusted mean ratio, 0.73 [95% CI, 0.70–0.76]) and HF hospital days (adjusted mean ratio, 0.79 [95% CI, 0.70–0.89]), and lower mortality (adjusted hazard ratio, 0.42 [95% CI, 0.32–0.53]). A dose-response relationship was observed between fulfilling more performance measures and mortality (adjusted hazard ratio, 0.62 [95% CI, 0.49–0.77] fulfilling >50%–75% of the measures). Fulfilling individual performance measures, except mineralocorticoid receptor antagonist therapy, was associated with lower adjusted all-cause readmission, lower adjusted use of all-cause and HF hospital days, and lower adjusted mortality. Conclusions: Fulfilling more process performance measures was associated with better clinical outcomes in patients with incident HF with reduced ejection fraction.

Purpose Analysis of patients with pre-operative 3 T multiparametric prostate MRI (mpMRI) to determine reliable MRI-based risk predictors of patients at risk for positive surgical margins (PSM) in robotic assisted radical prostatectomy (RPE). Methods Consecutive patients with 3 T mpMRI and subsequent RPE from 01/2015 to 12/2018 were retrospectively included. Patients were compared regarding clinical and MRI related parameters such as length of capsular tumor contact (LCC) and distance to the membranous urethra (UD). Results Forty-nine of 179 patients (27%) had PSM in 70 different localizations, with the majority located at the capsule (57%, 40/70), mostly apical and/or posterior. The second most often PSM occurred at the apical urethra (22%, 15/70). PCA was visible on mpMRI at the localization of PSM in 93% at the capsule and in 80% at the urethra. PSA, PI-RADS classification, extraprostatic extension (EPE), and seminal vesicles infiltration (SVI) on MRI were significantly higher / more frequent in patients with PSM. LCC (AUC 0.710), EPE (AUC 0.693), and UD (1-AUC 0.673) predicted PSM (overall). An UD of ≤ 3.5 mm showed the highest accuracy of 95% (J = 0.946) for PSM at the urethra and a LCC of ≥ 22.5 mm with 77% (J = 0.378) for PSM at the capsule. Conclusion PSM occurred mostly in the apex and/or posteriorly at the capsule or at the apical urethra. LCC was the best MRI predictor for PSM at the capsule and UD for tumors with PSM at the apical urethra. Using these MRI parameters readers might pre-operatively determine PCA localizations at risk for PSM.

This study investigates preoperative lymph node metastases (LNM) detection accuracy by MRI and CT in patients with prostate cancer (PCA).All patients with preoperative MRI, CT or both and subsequent radical prostatectomy (RPE) and lymphadenectomy (LA) were included in this retrospective cohort study. Prostate specific antigen (PSA), PI-RADS, ISUP grade group, clinical and pathological tumor (T) stage was compared between negative and positive nodal (N) stage. LNM were assessed with size and localization and weather they were preoperatively detected or not. In patients with preoperative CT and MRI, the results were compared intermodally. The reference standard was the histopathological results after RPE and LA.A total of 228 patients were analysed including 24 patients with confirmed LNM (N1; 11%). PSA (median 9.7 vs. 14 ng/ml), PI-RADS (median 4 vs. 5), ISUP (median 2 vs. 4), and cT/pT-stage (median T2 vs. T3) was significantly higher in patients with LNM. No LNM were found in patients with ISUP-1-PCA. MRI was able to detect 67% of patients with LNM. Lymph node metastases presented on MRI predominantly small, round-shaped, located parailiacally with a minimum SAD of 4 mm (vs. CT SAD of 8 mm). In comparison, MRI was superior to CT in the detection of LNM (sensitivity 81% vs. 33%; specificity 99% vs. 97).LNM were very rare in patients with PSA 10 ng/ml, PI-RADS ≤ 4, and ≤ cT2. MRI could detect LNM up to 4 mm with a moderate sensitivity and high specificity. Thus, MRI might optimise the preoperative diagnostic and therapy planning of patients with PCA, whereas CT was clearly limited for N-stage assessment.

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.

Background: Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. Methods: In the international, prospective, cohort International Ovarian Tumor Analysis Phase 5 (IOTA5) study, patients aged 18 years or older with at least one adnexal mass who had been selected for surgery or conservative management after ultrasound assessment were recruited consecutively from 36 cancer and non-cancer centres in 14 countries. Follow-up of patients managed conservatively is ongoing at present. In this 2-year interim analysis, we analysed patients who were selected for conservative management of an adnexal mass judged to be benign on ultrasound on the basis of subjective assessment of ultrasound images. Conservative management included ultrasound and clinical follow-up at intervals of 3 months and 6 months, and then every 12 months thereafter. The main outcomes of this 2-year interim analysis were cumulative incidence of spontaneous resolution of the mass, torsion or cyst rupture, or borderline or invasive malignancy confirmed surgically in patients with a newly diagnosed adnexal mass. IOTA5 is registered with ClinicalTrials.gov, number NCT01698632, and the central Ethics Committee and the Belgian Federal Agency for Medicines and Health Products, number S51375/B32220095331, and is ongoing. Findings: Between Jan 1, 2012, and March 1, 2015, 8519 patients were recruited to IOTA5. 3144 (37%) patients selected for conservative management were eligible for inclusion in our analysis, of whom 221 (7%) had no follow-up data and 336 (11%) were operated on before a planned follow-up scan was done. Of 2587 (82%) patients with follow-up data, 668 (26%) had a mass that was already in follow-up at recruitment, and 1919 (74%) presented with a new mass at recruitment (ie, not already in follow-up in the centre before recruitment). Median follow-up of patients with new masses was 27 months (IQR 14–38). The cumulative incidence of spontaneous resolution within 2 years of follow-up among those with a new mass at recruitment (n=1919) was 20·2% (95% CI 18·4–22·1), and of finding invasive malignancy at surgery was 0·4% (95% CI 0·1–0·6), 0·3% (

BACKGROUND The demographic change and an increasing multimorbidity of patients represent increasing challenges for the adequate prehospital treatment of emergency patients. The incorporation of supplementary telemedical concepts and systems can lead to an improved guideline-conform treatment. Beneficial evidence of telemedical procedures is only known for isolated disease patterns; however, no mobile telemedical concept exists which is suitable for use in the wide variety of different clinical situations. AIM This article presents a newly developed and evaluated total telemedical concept (TemRas) that encompasses organizational, medical and technical components. The use of intelligent and robust communication technology and the implementation of this add-on system allows the telemedical support of the rescue service for all emergencies. METHODS After development of the telemedical rescue assistance system, which includes organizational, medical and technical components, a telemedical centre and six ambulances in five different districts in North-Rhine Westphalia were equipped with this new tool. During the evaluation phase of 1 year in the routine emergency medical service the rate of complications as well as differences between urban and rural areas were analyzed with respect to different target parameters. RESULTS Between August 2012 and July 2013 a total of 401 teleconsultations were performed during emergency missions and 24 during secondary interhospital transfers. No complications due to teleconsultation were observed. The mean duration (±SD) of teleconsultations was longer in rural areas than in urban areas with 28.6±12.0 min vs. 25.5±11.1 min (p

All biological risk factors that have been previously identified to increase the risk of thrombosis in adults, have also been studied in neonates with arterial Ischemic Stroke (NAIS), but most studies were retrospective and included relatively low numbers of affected children. We therefore could not suggest recommendations with a strong level of evidence and only expert proposals potentially useful for clinical practice will be presented in this text. Despite these limitations, the extensive analysis of published data supported that factor V Leiden (FVL) and increased levels of Lp(a) could be significant risk factors for NAIS. Importantly, these 2 risk factors cannot be considered as having provoked NAIS, and moreover, they do not influence the prognosis and the immediate treatment. However, since the FVL may have an impact for the prescription of a thromboprophylaxis when the neonate will become adult, to look for its presence in affected patients may be justified. For clinical practice, the following propositions can be applied: 1. Routine testing for thrombophilia (AT, PC PS deficiency, FV Leiden or FII20210A) or for detecting other biological risk factors such as antiphospholipid antibodies, high FVIII, homocystein or Lp(a) levels, MTHFR thermolabile variant, should not be considered in neonates with NAIS. 2. Testing for FV Leiden can be performed in case of documented family history of venous thromboembolic disease. 3. Testing neonates for the presence of antiphospholipid antibodies (APA) is mandatory in case of clinical events suggesting antiphospholipid syndrome in the mother (vascular thrombosis, and/or pregnancy morbidity). 4. Routine testing for thrombophilia is not proposed in both parents in case of early death of the neonate, apart from APA in the mother.

Background Ceftaroline is a broad spectrum antibiotic used to treat complicated skin and soft tissues infections and community acquired pneumonia. To prevent emergence of resistant strains and conserve its effectiveness, ceftaroline prescription should be limited to specific recommended cases. Purpose The aim of this study was to evaluate proper use and effectiveness of ceftaroline in our establishment. Material and methods This was a retrospective study performed between January 2014 and December 2015. Patients who received ceftaroline and their biological and clinical data were collected by extraction from our prescription software (DXCARE and CLINISOFT). Seven items analysed the ‘correct use’ of ceftaroline: clinical setting, indication, referred germ, sensibility to other antibiotics, dosage, advice from an infectious disease and type of treatment (empiric, prophylactic or reassessed). Four items evaluated the ‘effectiveness’: treatment time, time for negative culture result, minimum inhibitory concentration (MIC) and healing of the infection. Results During the period, 13 patients received ceftaroline; 1 patient’s record was unusable. Prescriptions for ceftaroline were off-label in 83.3% (10/12, in the majority for osteo-articular infection), and 83.3% (10/12) of prescriptions were documented with identification of a methicillin resistant staphylococcal (once associated with Escherichia coli and another with Haemophilus parainfluenza ). Each time, germs were resistant to glycopeptides. Dosage was adapted to renal function for 83.3% of cases and the last 2 cases benefited from pharmaceutical intervention to obtain adequate posology. Advice from an infectiologist was given for each treatment initiation. Average and median treatment time were, respectively, 15.5 days and 10 days. Average time to culture negative result was 9.2 days, but was assessed for osteo-articular and not documented infections (7/12). Ceftaroline MIC was measured in 6 cases and was strictly below 1 mg/mL. All patients were cured of their infection, with a minimum step back 6 months. No adverse reactions were observed during the study. Conclusion This study showed important off-label use for ceftaroline but specialist advice was systematically requested due to the complexity of the patients. In all cases, patients were cured of their infection. Despite the off-label prescriptions, ceftaroline was used properly, with good therapeutic efficacy in our institution. A multicentre study should be performed to compare practices between several hospitals. No conflict of interest

International audience; Neonatal arterial ischemic stroke (NAIS) is a rare event that occurs in approximately one in 5000 term or close-to-term infants. Most affected infants will present with seizures. Although a well-recognized clinical entity, many questions remain regarding diagnosis, risk factors, treatment, and follow-up modalities. In the absence of a known pathophysiological mechanism and lack of evidence-based guidelines, only supportive care is currently provided. To address these issues, a French national committee set up by the French Neonatal Society (Société française de néonatologie) and the national referral center (Centre national de référence) for arterial ischemic stroke in children drew up guidelines based on an HAS (Haute Autorité de santé [HAS]; French national authority for health) methodology. The main findings and recommendations established by the study group are: (1) among the risk factors, male sex, primiparity, caesarean section, perinatal hypoxia, and fetal/neonatal infection (mainly bacterial meningitis) seem to be the most frequent. As for guidelines, the study group recommends the following: (1) the transfer of neonates with suspected NAIS to a neonatal intensive care unit with available equipment to establish a reliable diagnosis with MRI imaging and neurophysiological monitoring, preferably by continuous video EEG; (2) acute treatment of suspected infection or other life-threatening processes should be addressed immediately by the primary medical team. Persistent seizures should be treated with a loading dose of phenobarbital 20mg/kg i.v.; (3) MRI of the brain is considered optimal for the diagnosis of NAIS. Diffusion-weighted imaging with apparent diffusion coefficient is considered the most sensitive measure for identifying infarct in the neonatal brain. The location and extent of the lesions are best assessed between 2 and 4 days after the onset of stroke; (4) routine testing for thrombophilia (AT, PC PS deficiency, FV Leiden or FII20210A) or for detecting other biological risk factors such as antiphospholipid antibodies, high FVIII, homocysteinemia, the Lp(a) test, the MTHFR thermolabile variant should not be considered in neonates with NAIS. Testing for FV Leiden can be performed only in case of a documented family history of venous thromboembolic disease. Testing neonates for the presence of antiphospholipid antibodies should be considered only in case of clinical events arguing in favor of antiphospholipid syndrome in the mother; (5) unlike childhood arterial ischemic stroke, NAIS has a low 5-year recurrence rate (approximately 1 %), except in those children with congenital heart disease or multiple genetic thrombophilia. Therefore, initiation of anticoagulation or antithrombotic agents, including heparin products, is not recommended in the newborn without identifiable risk factors; (6) the study group recommends that in case of delayed motor milestones or early handedness, multidisciplinary rehabilitation is recommended as early as possible. Newborns should have physical therapy evaluation and ongoing outpatient follow-up. Given the risk of later-onset cognitive, language, and behavioral disabilities, neuropsychological testing in preschool and at school age is highly recommended.; L’accident vasculaire cérébral ischémique artériel néonatal (AVCian) est une pathologie rare. Afin d’actualiser les connaissances sur ce sujet, un groupe de travail multidisciplinaire s’est constitué sous l’égide de la Société française de néonatologie et le Centre national de référence de l’AVC de l’enfant afin de proposer des recommandations sur les facteurs de risque, les modalités de transfert et de prise en charge pré-hospitalière, les modalités diagnostiques et thérapeutiques, le traitement, le pronostic et la prise en charge à court et moyen terme. Ces recommandations ont été réalisées selon la méthodologie de la Haute autorité de santé et en fonctions des thématiques proposées par un comité d’experts. Les principales recommandations issues de ce travail sont : (1) l’orientation du patient vers une unité de réanimation ou de soins intensifs néonatals disposant d’une imagerie par résonance magnétique (IRM) facilement accessible et de la possibilité de réaliser une surveillance continue par électro-encéphalogramme ; (2) le phénobarbital est le médicament de première ligne pour le traitement des crises convulsives ; (3) l’IRM réalisée entre j2 et j4 après la survenue de l’AVCian est la meilleure technique pour confirmer le diagnostic et préciser son extension ; (4) un facteur biologique de risque thrombotique ne doit pas être systématiquement recherché après un AVCian, sauf en cas d’antécédent thrombotique veineux familial ; (5) un traitement thrombolytique n’est pas recommandé ; (6) une prise en charge rééducative précoce est recommandée en cas de déficience motrice évidente.

Introduction Le posaconazole est un antifongique triazole utilise majoritairement dans le cadre des prophylaxies fongiques. Il se decline sous trois formes galeniques : la solution buvable, la forme injectable et les comprimes. La forme comprime est commercialisee en France depuis 2015 et presente un profil pharmacocinetique plus avantageux que la solution buvable. L’objectif de cette etude est de faire un etat des lieux des posaconazolemies obtenues chez nos patients sous posaconazole comprime et d’evaluer la possibilite d’une adaptation posologique. Materiels et methodes Il s’agit d’une etude retrospective effectue entre janvier 2016 et novembre 2017. Les patients ayant recu uniquement du posaconazole en comprime a la dose initiale de 300 mg apres dose de charge dans le cas des prophylaxies d’infections fongiques ont ete inclus. Un tableur comprenant les donnees anthropometriques et biologiques (TGO/TGP, albuminemie) des patients, les posaconazolemies et les evenements indesirables a ete utilise. Resultats Durant cette periode, 139 patients ont recu du posaconazole comprime avec un sexe ratio de 0,49 H/F, un âge moyen de 50,4 ± 15,9 ans et un indice de masse corporel (IMC) moyen de 24,7 ± 4,8 kg/m2 (n = 110). Parmi les 478 dosages initiaux effectues, 400 etaient superieur au seuil minimal efficace. Quatre-vingt-sept patients avaient des concentrations toujours superieur a 0,7 mg.L−1 (2,05 ± 1,04 mg.L−1), 39 avaient des concentrations ± superieur a 0,7 mg.L−1 et 13 patients n’ont jamais atteints une posaconazolemie seuil de 0,7 mg.L−1. Il n’existait pas de difference significative entre l’âge, le sexe, l’IMC, le taux d’albumine, de TGO et de TGP entre nos patients ayant ou non atteint la concentration cible (p > 0,05). Parmi les 87 patients, 23 patients ont beneficie d’une diminution de posologie a 200 mg (n = 22) et 100 mg (n = 1). Leurs posaconazolemies initiales etaient de 2,33 mg.L−1 (1,44–4,37 mg.L−1). Dix-huit patients sont restes a des concentrations residuelles satisfaisantes pour l’ensemble de leurs dosages. Quinze evenements indesirables ont ete declares avec 12 troubles hepatiques (cholestase et cytolyse hepatique), 2 hypokaliemies et 1 trouble de la conduction avec des posaconazolemies moyennes de 1,47 ± 0,96 mg.L−1 (dont 5 patients avec une posaconazolemies > 1,5 mg.L−1 et 4 avec des concentrations inferieures a 0,7 mg.L−1) Conclusion Le posaconazole sous forme comprime presente un profil pharmacocinetique interessant. Il reste indispensable de doser les concentrations residuelles de cette molecule au vue de l’absence de profil patient identifie et du nombre de sous dosage constate. Une diminution de posologie semble etre coherente pour les patients presentant une posaconazolemie initiale superieur a 1,5 mg.L−1.

Introduction Les mucormycoses sont associees a une forte mortalite, leur diagnostic reste difficile. La detection d’ADN circulant par PCR permet un diagnostic plus precoce et une optimisation therapeutique. Cet outil est utilise sur notre centre a la fois comme biomarqueur diagnostic chez les patients immunodeprimes symptomatiques mais aussi en screening systematique des patients a haut risque, en particulier les patients brules. Materiels et methodes Il s’agit d’un suivi observationnel descriptif monocentrique de l’utilisation de la PCR mucorales et de sa place dans la strategie de diagnostic et de suivi therapeutique des mucormycoses. Les kits Machery-Nagel et Ademtech pour l’extraction ainsi qu’une q-PCR detectant l’ADN de Mucor/Rhizomucor, Lichtheimia et Rhizomucor ont ete respectivement utilises pour le serum et les biopsies sur notre centre. Resultats Entre avril 2017 et novembre 2018, 691 PCR mucor chez 170 patients ont ete realisees sur notre centre. Quatre cent soixante-cinq PCR (67 %) etaient demandees dans le cadre d’un screening systematique chez 117 patients a risque : 405 (chez des patients brules a plus de 20 % de surface corporelle, 59 chez des patients avec plaie a risque (traumatisme agricole, polytraumatisme) et 1 chez un transplante d’organe avec PCR mucor du donneur positive. Deux cent vingt-six PCR (33 %) etaient demandees pour diagnostic chez 53 patients symptomatiques, majoritairement des patients atteints d’hemopathies malignes (n = 30, 56 %) ou transplantes d’organe (n = 10, 19 %). Au moins une PCR sang, LBA ou tissu revenait positive chez 23 patients (13,5 %). Une mucormycose etait confirmee chez 10 patients : 1 infection disseminee a Lichtheimia chez une enfant de 3 ans avec leucemie, 1 pneumonie a Rhizomucor chez un homme de 35 ans avec leucemie, 1 pneumonie a Rhizopus chez un homme de 57 ans avec leucemie, 1 rhinosonusite a Rhizopus chez une patiente de 64 ans avec un diabete de type 2, 1 osteite tibiale a Rhizopus apres AVP chez un homme de 38 ans, 1 surinfection de brulure chez un homme de 33 ans, 1 pneumonie a Rhizomucor chez une patiente de 66 ans transplantee cardiaque, 1 surinfection de lesions de purpura fulminans a Lichtheimia chez une femme de 28 ans et 1 osteite du bassin a Rhizomucor apres AVP moto chez une homme de 28 ans. Le delai median entre la positivite de la PCR et la culture etait de 6 jours (2–16 jours). Le diagnostic n’etait pas confirme chez 13 patients, il s’agissait pour 12 patients de PCR positives sur biopsie de tissus exposes a une contamination environnementale chez des patients immunocompetents et pour 1 patient d’une reaction croisee avec une fusariose chez une patiente avec hemopathie maligne. Conclusion Dans notre experience, la PCR mucorales permet d’ameliorer la precocite du diagnostic. Son interpretation dans le cadre d’une strategie de screening peut en revanche etre difficile.