Impact of drug consumption rooms on non-fatal overdoses, abscesses and emergency department visits in people who inject drugs in France: results from the COSINUS cohort.

BACKGROUND: The effectiveness of drug consumption rooms (DCRs) for people who inject drugs (PWID) has been demonstrated for HIV and hepatitis C virus risk practices, and access to care for substance use disorders. However, data on other health-related complications are scarce. Using data from the French COSINUS cohort, we investigated the impact of DCR exposure on non-fatal overdoses, abscesses and emergency department (ED) visits, all in the previous 6 months. METHODS: COSINUS is a 12-month prospective cohort study of 665 PWID in France studying DCR effectiveness on health. We collected data from face-to-face interviews at enrolment, and at 6 and 12 months of follow-up. After adjusting for other correlates (P-value < 0.05), the impact of DCR exposure on each outcome was assessed using a two-step Heckman mixed-effects probit model, allowing us to adjust for potential non-randomization bias due to differences between DCR-exposed and DCR-unexposed participants, while taking into account the correlation between repeated measures. RESULTS: At enrolment, 21%, 6% and 38% of the 665 participants reported overdoses, abscesses and ED visits, respectively. Multivariable models found that DCR-exposed participants were less likely to report overdoses [adjusted coefficient (95% CI): -0.47 (-0.88; -0.07), P = 0.023], abscesses [-0.74 (-1.11; -0.37), P < 0.001] and ED visits [-0.74 (-1.27; -0.20), P = 0.007]. CONCLUSION: This is the first study to show the positive impact of DCR exposure on abscesses and ED visits, and confirms DCR effectiveness in reducing overdoses, when adjusting for potential non-randomization bias. Our findings strengthen the argument to expand DCR implementation to improve PWID injection environment and health.

Improving sample preheating capabilities for dynamic loading on high-pulsed power drivers.

The CEA operates several High-Pulsed Power (HPP) drivers for dynamic loading experiments. The aim of these experiments is to provide quantitative information about the response of various materials of interest, mainly under quasi-isentropic compression. In order to improve our ability to explore these materials' behavior over a wide range of thermodynamic paths and starting from various non-ambient conditions, we developed a device capable of pre-heating both metallic and nonmetallic samples up to several hundred degrees prior to loading. This device is based on conductive heating and on a configuration that allows homogeneous heating with unprecedented temperature stability on our HPP platforms. Moreover, it is designed to allow efficient sample heating, within extremely severe electromagnetic environments associated with such platforms. The main features of this preheating device, whose design was guided by extensive thermal simulations, are presented, along with various technical solutions that enabled its insertion in a reliable experimental configuration on our HPP drivers. The results obtained from preliminary experiments on a composite material (carbon fibers embedded in epoxy resin) and on a high purity copper sample preheated to 323 K and 573 K, respectively, are presented. The performance and robustness of this heating device are potentially valuable for extending the range of studies in dynamic loading experiments for various materials under ramp compression using HPP drivers.

Early postoperative oral fluid intake in paediatric day case surgery influences the need for opioids and postoperative vomiting: a controlled randomized trial†.

Background: In children younger than 4 yr, it is difficult to distinguish the cause of postoperative distress, such as thirst, pain, and emergence delirium. This may lead to inappropriate treatment, such as administration of opioids. The aim of this study was to evaluate the influence of early postoperative oral fluid intake on the use of opioid analgesics and the incidence of postoperative vomiting (POV) after paediatric day case surgery. Methods: After ethics committee approval and with parental informed consent, planned day surgery patients aged 6 months to 4 yr were randomized to the liberal group (LG), in which apple juice (10 ml kg−1) was offered first if the Face Legs Activity Cry COnsolability (FLACC) score was ≥4 in the PACU, or to the control group (CG), in which children were treated after surgery according to the institutional opioid protocol, and drinking was allowed only upon the return to the ward. Bayesian statistical analysis was used to compare POV incidence and opioid use across groups. Results: Data from 231 patients were analysed. The incidence of POV in the LG and the CG was 11.40 and 23.93%, respectively. An opioid was needed in 14.04% (mean total dose: 0.18 mg kg−1) and 35.89% (mean total dose: 0.20 mg kg−1) of the patients in the LG and the CG. The PACU stay was 53.45 and 65.05 min in the LG and the CG, respectively (all differences were statistically significant). Conclusions: In our paediatric outpatient setting, early postoperative oral fluid intake was associated with a reduction in opioid use and POV incidence. These results deserve confirmation in other settings. Clinical trial registration: NCT02288650.

Guidance on the Selection of Appropriate Indicators for Quantification of Antimicrobial Usage in Humans and Animals.

An increasing variety of indicators of antimicrobial usage has become available in human and veterinary medicine, with no consensus on the most appropriate indicators to be used. The objective of this review is therefore to provide guidance on the selection of indicators, intended for those aiming to quantify antimicrobial usage based on sales, deliveries or reimbursement data. Depending on the study objective, different requirements apply to antimicrobial usage quantification in terms of resolution, comprehensiveness, stability over time, ability to assess exposure and comparability. If the aim is to monitor antimicrobial usage trends, it is crucial to use a robust quantification system that allows stability over time in terms of required data and provided output; to compare usage between different species or countries, comparability must be ensured between the different populations. If data are used for benchmarking, the system comprehensiveness is particularly crucial, while data collected to study the association between usage and resistance should express the exposure level and duration as a measurement of the exerted selection pressure. Antimicrobial usage is generally described as the number of technical units consumed normalized by the population at risk of being treated in a defined period. The technical units vary from number of packages to number of individuals treated daily by adding different levels of complexity such as daily dose or weight at treatment. These technical units are then related to a description of the population at risk, based either on biomass or number of individuals. Conventions and assumptions are needed for all of these calculation steps. However, there is a clear lack of standardization, resulting in poor transparency and comparability. By combining study requirements with available approaches to quantify antimicrobial usage, we provide suggestions on the most appropriate indicators and data sources to be used for a given study objective.

Note: Spin-exchange optical pumping in a van.

The advent of spin-hyperpolarization techniques designed to overcome the sensitivity issue of nuclear magnetic resonance owing to polarization transfer from more ordered systems has recently raised great enthusiasm. However, the out-of-equilibrium character of the polarization requires a close proximity between the area of production and the site of use. We present here a mobile spin-exchange optical pumping setup that enables production of laser-polarized noble gases in a standalone mode, in close proximity to hospitals or research laboratories. Only compressed air and mains power need to be supplied by the host laboratory.

Home administration of bortezomib in multiple myeloma is cost-effective and is preferred by patients compared with hospital administration: results of a prospective single-center study.

BACKGROUND: Subcutaneous (s.c.) administration of bortezomib is the most widely used route of administration for the treatment of patients with multiple myeloma. No study has as yet prospectively evaluated home versus hospital administration of s.c. bortezomib with respect to patient preference and cost. PATIENTS AND METHODS: In this prospective trial, myeloma patients received the first administration of s.c. bortezomib of each cycle in the outpatient unit of the Department of Hematology. When possible, all subsequent doses of bortezomib within each cycle were provided at home. A cost analysis was carried out to compare the average cost of an injection of bortezomib in the outpatient unit and at home. In order to compare hospital and home administration of bortezomib for preference and satisfaction, patients had to complete 2 simple questionnaires analyzing 16 criteria, such as quality of life, well-being, social life, satisfaction, safety, quality of care, the reduction in personal transportation time, and personal anxiety. Each item was analyzed using a Likert scale. RESULTS: Fifty patients were studied. Overall, a total of 1043 s.c. injections of bortezomib were carried out, 655 (62.8%) at home, and 388 (35.2%) in the outpatient unit. The cost analysis showed that the total cost of one s.c. injection of bortezomib in the outpatient unit was €1510.09 versus €1224.57 for the home administration, which represents a reduction of €285.52, i.e. 20% of the cost of the hospital administration. The evaluation of patient preference and satisfaction showed that home administration improved the quality of life in 84% of the patients, increased well-being in 78%, and improved the activities of daily living in 72% of the cases. Overall, 98% of the patients noted their preference for home administration over the hospital administration of bortezomib. CONCLUSION: Home administration of s.c. bortezomib is cost-effective and is preferred by myeloma patients compared with hospital administration.

Characteristics of a molybdenum X-pinch X-ray source as a probe source for X-ray diffraction studies.

X-ray emission from a molybdenum X-pinch has been investigated as a potential probe for the high pressure states made in dynamic compression experiments. Studies were performed on a novel 300 kA, 400 ns generator which coupled the load directly to a low inductance capacitor and switch combination. The X-pinch load consisted of 4 crossed molybdenum wires of 13 µm diameter, crossed at an angle of 62°. The load height was 10 mm. An initial x-ray burst generated at the wire crossing point, radiated in the soft x-ray range (hυ < 10 keV). This was followed, 2-5 ns later, by at least one harder x-ray burst (hυ > 10 keV) whose power ranged from 1 to 7 MW. Time integrated spectral measurements showed that the harder bursts were dominated by K-alpha emission; though, a lower level, wide band continuum up to at least 30 keV was also present. Initial tests demonstrated that the source was capable of driving Laue diffraction experiments, probing uncompressed samples of LiF and aluminium.

Comparability of river quality assessment using macrophytes: a multi-step procedure to overcome biogeographical differences.

This paper exposes a new methodological approach to solve the problem of intercalibrating river quality national methods when a common metric is lacking and most of the countries share the same Water Framework Directive (WFD) assessment method. We provide recommendations for similar works in future concerning the assessment of ecological accuracy and highlight the importance of a good common ground to make feasible the scientific work beyond the intercalibration. The approach herein presented was applied to highly seasonal rivers of the Mediterranean Geographical Intercalibration Group for the Biological Quality Element Macrophytes. The Mediterranean Group of river macrophytes involved seven countries and two assessment methods with similar acquisition data and assessment concept: the Macrophyte Biological Index for Rivers (IBMR) for Cyprus, France, Greece, Italy, Portugal and Spain, and the River Macrophyte Index (RMI) for Slovenia. Database included 318 sites of which 78 were considered as benchmarks. The boundary harmonization was performed for common WFD-assessment methods (all countries except Slovenia) using the median of the Good/Moderate and High/Good boundaries of all countries. Then, whenever possible, the Slovenian method, RMI was computed for the entire database. The IBMR was also computed for the Slovenian sites and was regressed against RMI in order to check the relatedness of methods (R(2)=0.45; p<0.00001) and to convert RMI boundaries into the IBMR scale. The boundary bias of RMI was computed using direct comparison of classification and the median boundary values following boundary harmonization. The average absolute class differences after harmonization is 26% and the percentage of classifications differing by half of a quality class is also small (16.4%). This multi-step approach to the intercalibration was endorsed by the WFD Regulatory Committee.

Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program.

S6 kinases (S6Ks) are mechanistic target of rapamycin substrates that participate in cell growth control. S6Ks phosphorylate ribosomal protein S6 (rpS6) and additional proteins involved in the translational machinery, although the functional roles of these modifications remain elusive. Here we analyze the S6K-dependent transcriptional and translational regulation of gene expression by comparing whole-genome microarray of total and polysomal mouse liver RNA after feeding. We show that tissue lacking S6Ks 1 and 2 (S6K1 and S6K2), displays a defect in the ribosome biogenesis (RiBi) transcriptional program after feeding. Over 75% of RiBi factors are controlled by S6K, including Nop56, Nop14, Gar1, Rrp9, Rrp15, Rrp12 and Pwp2 nucleolar proteins. Importantly, the reduced activity of RiBi transcriptional promoters in S6K1;S6K2(-/-) cells is also observed in rpS6 knock-in mutants that cannot be phosphorylated. As ribosomal protein synthesis is not affected by these mutations, our data reveal a distinct and specific aspect of RiBi under the control of rpS6 kinase activity, that is, the RiBi transcriptional program.

Least Disturbed Condition for European Mediterranean rivers.

The present report describes a three-step approach that was used to characterize and define thresholds for the Least Disturbed Condition in Mediterranean streams of four different types, regarding organic pollution and nutrients, hydrological and morphological alterations, and land use. For this purpose, a common database composed of national reference sites (929 records) from seven countries, sampled for invertebrates, diatoms and macrophytes was used. The analyses of reference sites showed that small (catchment <100 km(2)) siliceous and non-siliceous streams were mainly affected by channelization, bank alteration and hydropeaking. Medium-sized siliceous rivers were the most affected by stressors: 25-43% of the samples showed at least slight alterations regarding channelization, connectivity, upstream dam influence, hydropeaking and degradation of riparian vegetation. Temporary streams were the least affected by hydromorphological changes, but they were nevertheless affected by alterations in riparian vegetation. There were no major differences between all permanent stream types regarding water quality, but temporary streams showed lower values for oxygenation (DO) and wider ranges for other variables, such as nitrates. A lower threshold value for DO (60%) was determined for this stream type and can be attributed to the streams' natural characteristics. For all other river types, common limits were found for the remaining variables (ammonium, nitrate, phosphate, total P, % of artificial areas, % of intensive and extensive agriculture, % of semi-natural areas in the catchment). These values were then used to select the list of reference sites. The biological communities were characterized, revealing the existence of nine groups of Mediterranean invertebrate communities, six for diatoms and five for macrophytes: each group was characterized by specific indicator taxa that highlighted the differences between groups.

Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid.

Interleukin-22 (IL-22) is mainly produced at barrier surfaces by T cells and innate lymphoid cells and is crucial to maintain epithelial integrity. However, dysregulated IL-22 action leads to deleterious inflammation and is involved in diseases such as psoriasis, intestinal inflammation, and cancer. IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We show both in rats and mice that, in the steady state, the main source of IL-22BP is constituted by a subset of conventional dendritic cells (DCs) in lymphoid and non-lymphoid tissues. In mouse intestine, IL-22BP was specifically expressed in lamina propria CD103(+)CD11b(+) DC. In humans, IL-22BP was expressed in immature monocyte-derived DC and strongly induced by retinoic acid but dramatically reduced upon maturation. Our data suggest that a subset of immature DCs may actively participate in the regulation of IL-22 activity in the gut by producing high levels of IL-22BP.

Bayesian network as an aid for Food Chain Information use for meat inspection.

Current ante mortem inspection involves a check of relevant Food Chain Information (FCI) transmitted by the farmer to the slaughterhouse on a regulatory FCI document. Since 2000, a farm sanitary form with FCI data has been used for all consignments of broiler chickens in France. However, the FCI needs to be standardized for the collection and interpretation of data. A study was conducted to develop an expert system, undertaken to elaborate on a simple decision support system capable of predicting whether the flocks will present a high condemnation risk, based on FCI. For this, 'optimal' (i.e. on-farm survey data) and 'worthy' (i.e. farmers' declaration on existing farm sanitary form) data quality conditions were considered to estimate the lower and upper reference bounds of the confidence that the decision-makers could have in such a tool. Chicken broiler flocks (404) were randomly selected in 15 slaughterhouses located in Western France in 2005. Condemnation proportion and farm sanitary form were collected for each selected flock. Information about health history and technical performances were also specifically collected on farm. Condemnation risk category was modelled from the on-farm collected information, using a Bayesian network and assuming this represented the optimal data quality conditions. Corresponding information declared by the farmer on the existing farm sanitary form was secondly used in the network to evaluate the impact of the uncertainty of such information on the condemnation classification obtained with the expert system. The learnt Bayesian network had 16 explanatory variables pertaining to technical characteristics and sanitary features of the flock. Using a threshold of 1% of condemned carcases to define high risk, the network sensitivity and specificity were 55% and 93%, respectively, corresponding to positive and negative predictive values of 70% and 87%. When declared existing information was used in the network, the sensitivity and specificity were 16% and 96%, respectively, corresponding to positive and negative predictive values of 57% and 80%. Results suggested that the predictive network developed may be insufficient for correctly classifying chicken flocks for targeting of management procedures, and in its current form, the expert system may be unlikely to be implemented in the field. However, it could help to improve the standardization of both form design and FCI interpretation at a national level.

Methicillin-resistant Staphylococcus aureus ST398 contamination and transmission in pigs after a low dose inoculation.

AIMS: Methicillin-resistant Staphylococcus aureus (MRSA) ST398 has recently been described as a zoonotic agent. Its transmission between animals seems to be a pivotal factor in its emergence and dissemination. This experimental trial was performed to describe MRSA ST398 contamination and transmission in pigs after a low dose inoculation. METHODS AND RESULTS: Twelve specific pathogen-free (SPF) pigs were randomly divided between two separate pens. Three pigs in each pen received a nasal inoculation of 2 × 10(4) colony-forming units per animal, and three naïve pigs were left in contact with them. Every 2 days and at necropsy, different samples were screened for MRSA. It was detected in nasal swabs from five inoculated and three naïve contact pigs, as early as 1 day after inoculation. MRSA was also found in environmental wipes but never in faecal samples. At necropsy, MRSA was detected in the lymph nodes of two contact pigs and in the tonsils and lymph nodes of three inoculated pigs. Twelve other SPF pigs were included as negative control in a separate room. CONCLUSION: This experiment showed that inoculation of a low dose of MRSA ST398 could lead to the horizontal transmission of the bacterium between pigs, the contamination of mandibular lymph nodes and the contamination of the environment without faecal carriage. SIGNIFICANCE AND IMPACT OF THE STUDY: The minimal inoculated dose via nasal route to observe transmission of MRSA ST398 between pigs is equal or lower to 2 × 10(4) colony-forming units per animal, and faecal excretion seems not to be a necessary condition for horizontal transmission.

Multiblock modelling to assess the overall risk factors for a composite outcome.

Research in epidemiology may be concerned with assessing risk factors for complex health issues described by several variables. Moreover, epidemiological data are usually organized in several blocks of variables, consisting of a block of variables to be explained and a large number of explanatory variables organized in meaningful blocks. Usual statistical procedures such as generalized linear models do not allow the explanation of a multivariate outcome, such as a complex disease described by several variables, with a single model. Moreover, it is not easy to take account of the organization of explanatory variables into blocks. Here we propose an innovative method in the multiblock modelling framework, called multiblock redundancy analysis, which is designed to handle most specificities of complex epidemiological data. Overall indices and graphical displays associated with different interpretation levels are proposed. The interest and relevance of multiblock redundancy analysis is illustrated using a dataset pertaining to veterinary epidemiology.

Pharmacodynamic modeling of in vitro activity of marbofloxacin against Escherichia coli strains.

A mathematical pharmacodynamic model was developed to describe the bactericidal activity of marbofloxacin against Escherichia coli strains with reduced susceptibility levels (determined using MICs) under optimal and intestinal growth conditions. Model parameters were estimated using nonlinear least-square curve-fitting procedures for each E. coli strain. Parameters related to bactericidal activity were subsequently analyzed using a maximum-effect (E(max)) model adapted to account for a direct and a delayed effect. While net growth rates did not vary significantly with strain susceptibility, culture medium had a major effect. The bactericidal activity of marbofloxacin was closely associated with the concentration and the duration of exposure of the bacteria to the antimicrobial agent. The value of the concentration inducing a half-maximum effect (C(50)) was highly correlated with MIC values (R(2) = 0.87 and R(2) = 0.94 under intestinal and optimal conditions, respectively). Our model reproduced the time-kill kinetics with good accuracy (R(2) of >0.90) and helped explain observed regrowth.

Factors associated with mortality of broilers during transport to slaughterhouse.

In recent years, broiler mortality during transport to the slaughterhouse has become a cause for concern because of animal welfare considerations and associated economic losses. A descriptive and analytical epidemiological study was carried out to estimate the extent of DoA in poultry broiler production in the main producing regions of France and to determine factors influencing the DoA rate. Data regarding animal characteristics and rearing, catching, transport and lairage conditions were collected on farm and at the slaughterhouse for 404 chicken broiler flocks processed during 2005. The average DoA rate was 0.18% (from 0% to 1.4%). Variables found to be associated (P < 0.05) with the DoA rate in a multivariable negative binomial model were flock cumulative mortality on farm, the catching system (mechanical being more at risk than manual), the density in crates (more space allowance being associated with less mortality) and climatic conditions (rain and wind being associated with more DoA). Mortality during transport is thus related to all production steps from the farm to the slaughterhouse. Efforts have therefore to be made by all professionals to contain mortality on farm and during catching and transportation.

Risk and indicators of condemnation of male turkey broilers in western France, February-July 2006.

A field study was conducted to estimate the sanitary condemnation proportion in male turkey broiler flocks, to describe the reasons for condemnation and the related macroscopic lesions, and to investigate whether primary production information would predict the risk of condemnation. Male turkey standard broiler flocks (117) were randomly selected in the 13 slaughterhouses located in Western France, from February to July 2006. The flocks were monitored from their arrival at the slaughterhouse until the results of the post mortem sanitary inspection. Information about rearing conditions, health history, catching and loading conditions, transportation to the slaughterhouse and slaughtering was also collected. Sampling design was considered in the calculations and the condemnation proportion was modelled using a negative binomial regression, accounting for clustering within slaughterhouse. The within-flock weighted average condemnation proportion was 1.8% (95% confidence interval, 1.3-2.3%). Emaciation, arthritis-polyarthritis and congestion were the main reported official reasons for condemnation, representing 76% of the condemned carcases. Three variables were significantly associated with increased risk of condemnation: observed locomotor disorders on the farm, high cumulative mortality 2 weeks before slaughter, and clinical signs observed by the Veterinary Services during the ante mortem inspection at the slaughterhouse. The final model explained 35% of the total variation in condemnation risk. Half of this explained variation could be attributed to locomotor disorders observed during rearing. The sensitivity and specificity of the model to predict a high flock condemnation risk were 80% and 74%, respectively, when using an optimum threshold of 0.95% to define high risk. The results of this study suggested that the variables found to be associated with condemnation proportion were markers of increased risk and could be used as indicators. These risk indicators can easily be retrieved from the pre-existing regulatory document transmitted before flock arrival at the slaughterhouse and could be used to screen flocks before slaughter, according to their expected risk of condemnation.

Risk factors for sanitary condemnation in broiler chickens and their relative impact: application of an original multiblock approach.

An innovative and well-adapted statistical method, called multiblock redundancy analysis, is proposed for a complex health-event analysis to account for the thematic block organization of variables. The outcome block contained the condemnation rates of 404 broiler chicken flocks, distinguishing infectious and traumatic condemnation categories. Explanatory variables were organized in blocks related to the different production stages (farm structure and routine husbandry practices; on-farm flock history and characteristics; catching, transport and lairage conditions; slaughterhouse and inspection features). The aim was to determine risk factors for both condemnation categories, and the relative impact of the different production stages on the whole condemnation rate. Results showed that significant factors were either specific to one condemnation category or related to both categories, and each of the explanatory blocks was involved in the explanation of infectious and traumatic condemnation rates. On-farm flock information explained 40% of the overall condemnation process whereas the other explanatory blocks had similar relative impacts.

[Endometriosis of the ischio-rectal excavation at the contact of the sciatic nerve: a case report of neurolysis by pararectal incision]. / Endométriose de la fosse ischiorectale au contact du nerf sciatique: à propos d'un cas de neurolyse par voie pararectale.

Localisation of endometriosis on the sciatic nerve is exceptional. We report the case of a patient presenting an endometriotic nodule of the left ischio-rectal excavation, with an extension contiguous to the sciatic nerve, responsible of invalidating sciatalgia. Two laparoscopies did not allow to localise the lesion. Finally the endometriotic nodule was treated by a direct access of the left ischio-rectal excavation through a pararectal incision. In this article we discuss the means to localise such lesion and the surgical approach to propose.