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.

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.

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.

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.

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.

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.

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.

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.

[Fetal injuries during cesarean: frequency, risk factors and prevention]. / Plaies foetales en cours de césarienne: fréquence, facteurs de risque et prévention.

During the cesarean section, the immediate proximity of the scalpel blade to the fetus exposes this latter to possible injuries. This article aims at reflecting on the measures to be developed in the prevention of fetal injuries during the cesarean section after a bibliographical analysis of the available data. Occurring in about 1% of the cesarean cases, the fetal injuries are most often minimal and localized at the scalp or the face, rarely requiring a surgical repair. Sometimes, they can have a functional, aesthetic, psychological and forensic impact. The associated risk factors substantially are the emergency cesarean, the "cutaneous incision/delivery" delay and a T- or J-shaped uterine incision. In this article we expose simple means enabling an incision of the uterine cavity, thus minimizing the fetal risk.

Impact of antimicrobial drug usage measures on the identification of heavy users, patterns of usage of the different antimicrobial classes and time-trends evolution.

Several measurement units are available to quantify antimicrobial usage in veterinary medicine, to obtain diverse measures such as the weight of active substance used, the live weight (LW) treated, the fraction of animals exposed, the number of treatments recorded or the cost represented. These measures can be applied to study practices variability between farms, to characterize patterns of usage of the different antimicrobial classes or to follow evolution of antimicrobial usage with time. An investigation was carried out to specifically explore the influence of measurement units on the conclusions obtained from such studies. Antimicrobial exposure was explored in a sample of turkey and chicken broiler flocks, using six different units [kg of active compound, treatments, days of administration, kg of LW treated, animal daily dose to treat 1 kg of LW (ADD(kg)) and euros] to compare flocks usage variability and patterns of use of the different antimicrobial classes. Time-trends evolutions of macrolides usage in turkey broilers, characterized by percentage of flocks exposed and LW treated, were also compared. In all analyses, the measure gave different results without equivalences, highlighting the necessity for care in choosing the measurement unit and caution in interpreting the figures obtained.

Postmortem condemnations of processed broiler chickens in western France.

A total of 404 broiler chicken flocks processed in 15 slaughterhouses in western France were studied to estimate the condemnation prevalence and describe the official reasons for condemnation and the main macroscopic lesions observed in a sample of the condemned carcases. The condemnation rate was 87 per 10,000 birds slaughtered (95 per cent confidence interval 79 to 95 per 10,000) but differed significantly according to the type of poultry produced (standard, light, heavy or certified). The main reasons for condemnation were emaciation and congestion, with rates of 30 and 22 per 10,000 birds slaughtered, respectively. Congestion was significantly associated with arthritis and ascites, whereas infected skin lesions were associated with bruises and abnormalities of colour, odour or conformation.

Effects of permeability transition inhibition and decrease in cytochrome c content on doxorubicin toxicity in K562 cells.

As mitochondria play a key role in the commitment to cell death, we have investigated the mitochondrial consequences of resistance to doxorubicin (DOX) in K562 cells. We found that the permeability transition pore (PTP) inhibitor cyclosporine A (CsA) failed to inhibit PTP opening in the resistant clone. Moreover, the Ca2+ loading capacity in the resistant clone was identical to that observed in the parent cells in the presence of CsA, suggesting that the PTP was already inhibited in a CsA-like manner in the resistant cells. In agreement with this proposal, the mitochondrial target of CsA cyclophilin D (CyD) decreased by half in the resistant cells. The levels of adenine nucleotide translocator, voltage anion-dependent channel, Bax, Bcl-2, Bcl-xL, AIF and Smac/Diablo, were similar in both cell lines, whereas cytochrome c content was divided by three in the resistant cells. Since P-glycoprotein inhibition did not restore DOX toxicity in the resistant cells, while DOX-induced cell death in the parent cells was prevented by either PTP inhibition or siRNA-induced decrease in cytochrome c content, we conclude that the inhibition of PTP opening and the decrease in cytochrome c content participate in the mechanism that makes K562 cells resistant to DOX.

Time-patterns of antibiotic exposure in poultry production--a Markov chains exploratory study of nature and consequences.

This article describes the use of Markov chains to explore the time-patterns of antimicrobial exposure in broiler poultry. The transition in antimicrobial exposure status (exposed/not exposed to an antimicrobial, with a distinction between exposures to the different antimicrobial classes) in extensive data collected in broiler chicken flocks from November 2003 onwards, was investigated. All Markov chains were first-order chains. Mortality rate, geographical location and slaughter semester were sources of heterogeneity between transition matrices. Transitions towards a 'no antimicrobial' exposure state were highly predominant, whatever the initial state. From a 'no antimicrobial' exposure state, the transition to beta-lactams was predominant among transitions to an antimicrobial exposure state. Transitions between antimicrobial classes were rare and variable. Switches between antimicrobial classes and repeats of a particular class were both observed. Application of Markov chains analysis to the database of the nation-wide antimicrobial resistance monitoring programme pointed out that transition probabilities between antimicrobial exposure states increased with the number of resistances in Escherichia coli strains.

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.

Accepting loss: the temporal limits of reciprocity in brown capuchin monkeys.

Delayed reciprocity is a potentially important mechanism for cooperation to occur. It is however rarely reported among animals, possibly because it requires special skills like the ability to plan a loss. We tested six brown capuchin monkeys (Cebus apella) in such skills. Subjects were studied in exchange tasks in which they had to retain a food item for a given time lag before returning it to an experimenter and obtaining a more desirable reward. Experiments showed that the subjects could wait for several minutes when allowed to return only part of the initial item. When required to return the full item intact, however, most subjects could not sustain a time lag longer than 10 s. Although the duration of waiting increased with the amount of return expected by subjects, in most cases it did not extend beyond 20 s even when the eperimenter offered a food amount 40 fold the initial item. The failure of capuchin monkeys to sustain long-lasting waiting periods may be explained by limited self-control abilities. This would prevent them achieving reciprocal altruism.

Activation of myc gene family in human lung carcinomas and during heterotransplantation into nude mice.

myc gene family activation (c-myc, L-myc, and N-myc) was examined in 26 human lung carcinomas and in their corresponding xenografts in nude mice. Of the 16 neuroendocrine (NE) carcinomas studied, amplification was observed in 4 with a c-myc probe and in 1 with both L- and N-myc probes. Overexpression was found in 1 of 7 cases studied for c-myc mRNA, in 1 of 7 cases for N-myc, and in 2 of 7 cases for L-myc. Of the 10 non-small cell lung carcinomas studied, only c-myc was amplified in 1 case and overexpressed in 5 of 7 cases. These results suggest that L- and N-myc gene activation are restricted to NE carcinomas. Over-expression of the myc gene without amplification was detected in 36% of cases. During heterotransplantation, there was a 27% change in myc gene abnormality and a 57% increase in myc expression levels, mostly in NE carcinomas (5 of 7; 71%). In a total of 42 xenografted lung carcinomas studied, 45% amplification and 77% overexpression of one of the myc genes were detected with a high prevalence of L-myc overexpression in NE carcinomas (50%) and of c-myc overexpression in non-small cell lung carcinomas (66%). Finally, 19 of 26 (73%) tumors are growing in nude mice with no myc gene amplification and 43% with no myc mRNA overexpression. Thus myc gene activation is not strictly required for heterotransplantation but seems to be a favorable factor in the maintenance and progression of lung carcinomas in vivo.

Analysis of the activation of the myc family oncogene and of its stability over time in xenografted human lung carcinomas.

In order to validate the use of the nude mouse as a model for studying lung cancers, 21 different lung cancers were xenografted onto nude mice and the tumoral DNA and RNA were analyzed for abnormality in the myc family genes (c-myc, L-myc, and N-myc). Six of 14 small cell lung cancers (SCLC) showed a 4-35-fold amplification for L-myc, 5 of 7 non-SCLC a 3-5-fold amplification for c-myc, and 1 of 14 SCLC an 80-fold amplification for N-myc. Of the 7 SCLC with amplified L- or N-myc oncogenes, 4 were of the small and large histological type, while only 5 of the 21 cases studied were of the small and large type. All xenografted tumors with amplification of one of the myc genes showed overexpression of the related mRNA. Overexpression without amplification of the myc genes was observed for 3 SCLC and 2 non-SCLC. These results indicate that the L-myc gene seems to be associated with the small and large phenotype in SCLC, whereas c-myc seems to be implicated in non-SCLC. Of the 21 lung cancers studied 14 were analyzed for myc family gene activation for serial passages into nude mice. No variation of DNA amplification was observed during long-term growth in nude mice for any of the myc oncogenes. Changes in the level of mRNA expression were observed only for c-myc; a beginning of expression in one SCLC and an increase in expression in one non-SCLC were noted in late passages when compared with early ones. The nude mouse is therefore a valuable model for the study of lung cancers "over a 4-year period at least."

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.

Invoices and farmer interviews for vaccine-exposure measurement in turkey-broiler production.

Exposure measurement in pharmaco-epidemiological studies can be based on various sources that do not always concur. However, reliability is an important criterion when selecting the method used to assess exposure and interpreting the results obtained. An analysis based on invoices might be more informative and more accurate to assess vaccines exposure (yes/no) in turkey broiler production than a questionnaire administered to farmers, which is nevertheless more feasible and less time-consuming. We compared the two methods to assess vaccination exposure in 239 turkey broiler flocks reared in 129 farms in 2000-2001. The agreement (crude agreement and kappa) was calculated, and association between discrepancy and farm and flock characteristics was investigated. Marek's-disease vaccine, Newcastle-disease vaccine, turkey haemorrhagic-enteritis vaccine and turkey-rhinotracheitis vaccine exposures were reported on the questionnaire for 2.1, 27.6, 93.0, and 98.3% of flocks, respectively, and for 2.1, 29.3, 89.4, and 86.6%, of invoices for the flocks studied, respectively. A discrepancy was observed in 24.9% of flocks. A discrepancy was observed more frequently in specialised farms without any other animal production (OR = 3.6; CI = 1.5, 8.9) and when the farmer did not know whether vaccination had been performed in the hatchery (OR = 7.1; CI = 2.6, 19.7).

Use of avilamycin for growth promotion and avilamycin-resistance among Enterococcus faecium from broilers in a matched case-control study in France.

We assessed the putative link between avilamycin-resistant Enterococcus faecium carriage and avilamycin consumption in broilers. As part of the French programme of monitoring for antimicrobial resistance, broilers sampled at slaughterhouse in 1999 and 2000 and carrying avilamycin-resistant E. faecium were matched by slaughterhouse, slaughter month and production type (free-range, standard, light) with control broilers carrying avilamycin-susceptible strains. History of antibiotics consumption (either for growth promotion or therapeutic purpose) in the broiler flocks sampled was collected from the monitoring programme and consumption of each antibiotic class was screened as a potential risk factor. Avilamycin was a risk factor for avilamycin-resistant E. faecium carriage: OR=2.3.