The Bayesian microbial subtyping attribution model: robustness to prior information and a proposition.

Attributing foodborne illnesses to food sources is essential to conceive, prioritize, and assess the impact of public health policy measures. The Bayesian microbial subtyping attribution model by Hald et al. is one of the most advanced approaches to attribute sporadic cases; it namely allows taking into account the level of exposure to the sources and the differences between bacterial types and between sources. This step forward requires introducing type and source-dependent parameters, and generates overparameterization, which was addressed in Hald's paper by setting some parameters to constant values. We question the impact of the choices made for the parameterization (parameters set and values used) on model robustness and propose an alternative parameterization for the Hald model. We illustrate this analysis with the 2005 French data set of non-typhi Salmonella. Mullner's modified Hald model and a simple deterministic model were used to compare the results and assess the accuracy of the estimates. Setting the parameters for bacterial types specific to a unique source instead of the most frequent one and using data-based values instead of arbitrary values enhanced the convergence and adequacy of the estimates and led to attribution estimates consistent with the other models' results. The type and source parameters estimates were also coherent with Mullner's model estimates. The model appeared to be highly sensitive to parameterization. The proposed solution based on specific types and data-based values improved the robustness of estimates and enabled the use of this highly valuable tool successfully with the French data set.

A qualitative risk assessment methodology for scientific expert panels.

Risk assessment can be either quantitative, i.e. providing a numeric estimate of the probability of risk and the magnitude of the consequences, or qualitative, using a descriptive approach. The French Agency for Food, Environmental and Occupational Health and Safety (ANSES), formerly the French Food Safety Agency (AFSSA), bases its assessments on the opinions of scientific panels, such as the ANSES Animal Health Scientific Panel (AH-SP). Owing to the lack of relevant data and the very short period of time usually allowed to assess animal health risks on particular topics, this panel has been using a qualitative risk method for evaluating animal health risks or crises for the past few years. Some experts have drawn attention to the limitations of this method, such as the need to extend the range of adjectives used for the lower probabilities and to develop a way to assess consequences. The aim of this paper is to describe the improved method now established by the AH-SP, taking into account the limitations of the first version. The authors describe a new set of levels for probabilities, as well as the items considered when addressing either animal or human health consequences.

The application of risk analysis in aquatic animal health management.

Risk analysis has only been regularly used in the management of aquatic animal health in recent years. The Agreement on the Application of Sanitary and Phytosanitary measures (SPS) stimulated the application of risk analysis to investigate disease risks associated with international trade (import risk analysis-IRA). A majority (9 of 17) of the risk analyses reviewed were IRA. The other major focus has been the parasite of Atlantic salmon--Gyrodactylus salaris. Six studies investigated the spread of this parasite, between countries, rivers and from farmed to wild stocks, and clearly demonstrated that risk analysis can support aquatic animal health policy development, from international trade and biosecurity to disease interaction between wild and farmed stocks. Other applications of risk analysis included the spread of vertically transmitted pathogens and disease emergence in aquaculture. The Covello-Merkhofer, risk analysis model was most commonly used and appears to be a flexible tool not only for IRA but also the investigation of disease spread in other contexts. The limitations of the identified risk assessments were discussed. A majority were qualitative, partly due to the lack of data for quantitative analysis, and this, it can be argued, constrained their usefulness for trade purposes (i.e. setting appropriate sanitary measures); in other instances, a qualitative result was found to be adequate for decision making. A lack of information about the disease hazards of the large number of fish species traded is likely to constrain quantitative analysis for a number of years. The consequence assessment element of a risk analysis was most likely to be omitted, or limited in scope and depth, rarely extending beyond examining the evidence of susceptibility of farmed and wild species to the identified hazard. The reasons for this are discussed and recommendations made to develop guidelines for a consistent, systematic and multi-disciplinary approach to consequence assessment. Risk analysis has improved decision making in aquatic animal health management by providing a transparent method for using the available scientific information. The lack of data is the main constraint to the application of risk analysis in aquatic animal health. The identification of critical parameters is an important output from risk analysis models which should be used to prioritise research.

Validation of in situ hybridisation and histology assays for the detection of the oyster parasite Marteilia refringens.

An in situ hybridisation technique has been developed for the detection of infection in oysters with Marteilia refringens with particular emphasis on light infections or confirmation of suspected cases by means of histology. Although validation of new diagnostic methods is usually achieved by comparison with standard techniques, in our case the sensitivity and specificity of the standard (histology) had not previously been established. Another point to consider is that surveillance and monitoring frequently target populations displaying different levels of prevalence under different field conditions. The objective of our study was to evaluate the sensitivity and specificity values of in situ hybridisation and histology for the detection of M. refringens, based on 3 populations of flat oysters, free of the disease and with mild and high levels of prevalence. A blind assay of 200 individuals from each population was performed using both techniques. Results were analysed by means of the classical approach and latent models (maximum likehood and Bayesian approach). Assumptions and results were found to vary slightly with the different statistical approaches. The more realistic estimate by the Bayesian approach shows a link between the level of prevalence and the sensitivity of the techniques. Values of sensitivity and specificity for histology were 0.7 and 0.99 respectively, and 0.9 and 0.99 respectively in the case of in situ hybridisation. Some uncertainty remains regarding these values because the study does not take into account the severity of infection or the developmental stages of the parasite actually present in each individual. This work provides valuable information with regard to the choice and potential use of those 2 diagnostic methods currently recommended by international standards.

Fertilization failure after subzonal sperm insertion associated with defective fusional capacity of acrosome-reacted spermatozoa.

A case of an isolated impairment of the ability of acrosome-reacted spermatozoa to fuse with the oocyte is reported. This impairment was associated with fertilization failure after subzonal sperm insertion even though elevated numbers of spermatozoa were inserted per oocyte. This observation shows the need for further studies into the relationship between the acrosome reaction and the sperm-oocyte fusion to better understand the advantages and the limitations of subzonal sperm insertion in different types of sperm pathology.

Interpretation of plasma luteinizing hormone assay for the collection of mature oocytes from women: definition of a luteinizing hormone surge-initiating rise.

Analysis of plasma luteinizing hormone (LH) assays (4 assays per day) permits the discernment of the onset of the physiologic effects of ovulatory release. This threshold value of LH plasma concentration (LH surge-initiating rise, LH SIR) is determined for each cycle in terms of the average baseline level of the previous day. The chronology of follicle and oocyte maturation after LH SIR is similar to that which follows chorionic gonadotropin (hCG) administration: none of the 20 patients, compared with 2 out of 10, had ovulated when laparoscopy was performed 30 to 35 hours and 36 to 38 hours after LH SIR time, respectively; 1 out of 3, 9 out of 14, and 5 out of 5 patients had an in vitro fertilized egg when oocytes were collected 30 to 32, 33 to 35, and 36 to 38 hours after LH SIR time, respectively. Thus the oocyte can be collected 34 to 35 hours after the LH SIR; at this point ovulation has not occurred and the oocyte is capable of being fertilized.

Impact of a multidisciplinary approach to the control of antibiotic prescription in a general hospital.

We examined the impact of a rational antibiotic prescription programme based on a multidisciplinary consultative approach in a 600-bed hospital. The programme involved four measures: (1). drawing up of a local prescribing consensus with all prescribers; (2). a restricted prescriptions policy for the most expensive antibiotics; (3.assessment of the prescription of these antibiotics by regular audits; and (4). institutional training and information for prescribers. The impact of the programme was assessed by comparing actual prescriptions with the criteria of the local consensus, compliance with the restrictive prescription policy, changes in the average daily cost of antibiotic therapy per inpatient and changes in the local ecology of methicillin-resistant Staphylococcus aureus (MRSA), Enterobacteriaceae producing extended-spectrum beta-lactamases (EPESB) and ceftazidime-resistant Pseudomonas species (CRP). Using a participatory consensual approach, 182 reference recommendations were established (104 for adults, 78 for children), corresponding to 85% of the clinical settings encountered in the hospital. Six audits, conducted since June 1997, show that the rate of unjustified prescriptions first fell significantly (from 6 to 0%, P<0.001), then increased significantly (from 0 to 3%, P<0.05) before stabilizing at 3%. The cost of antimicrobials per inpatient day fell significantly (from US dollars 13.8 in 1997 to US dollars 11 in 2000, P<0.001). The prevalence of MRSA and CRP remained stable, while that of EPESB fell significantly (P<0.001). This multidisciplinary consultative approach thus reduced antibiotic costs, contributed to infection control, and improved the quality of antibiotic prescription.

Vibrio carchariae, a pathogen of the abalone Haliotis tuberculata.

Since 1997, mass mortality of the abalone Haliotis tuberculata L. has occurred in the natural environment along the French coast. The outbreak of disease started on the south coast of Brittany near Concarneau in 1997, then spread to the north of Brittany (in 1998) and the west coast of Normandy (Golfe de St. Malo in 1999). Between 60 and 80% of the abalone died. In 1999, mortality also affected a land-based abalone farm in Normandy during the summer. At this farm, a Vibrio sp. was isolated in abundance from abalone that had just died. The disease was experimentally reproduced by inoculation or by introducing the pathogen into the surrounding water. This vibrio, identified by genotypic and phenotypic characters, is related to V carchariae. It is similar to the V carchariae, responsible for mortality in the Japanese abalone Sulculus diversicolor supratexta, but some phenotypic characters differentiate both strains. In 2000, healthy abalone placed in 2 sites on the north and south coasts of Brittany died, and the pathogen V carchariae could be isolated from dead individuals, demonstrating that the pathogen was probably the cause of the abalone disease that has been occurring since 1997 in Brittany.

[Evaluation of low molecular weight heparin prescription at the Centre Hospitalier Intercommunal de Créteil]. / Evaluation de la prescription des héparines de bas poids moléculaire au Centre Hospitalier Intercommunal de Créteil.

Low-molecular-weight heparin (LMWH) represents a great expense in general hospitals. At the Centre Hospitalier Intercommunal de Créteil (CHIC), the Quality Assessment Council had set up a study on the prescription of LMWH in order to assess concordance between prescriptions and local guidelines on the preventive uses of LMWH. Adherence to the consensus was found in 73 per cent of cases, overprescription in 10 per cent of cases and underprescription in 26 per cent of cases. It is planned to modify the local consensus, taking into account some clinical situations highlighted by this study, and to perform another evaluation in the near future.

[Analysis of mode of failure, their effects and criticality: improving of the hospital drug prescribing process]. / Analyse des modes de défaillances, de leurs effets et de leur criticité: amélioration de la prescription des médicaments à l'hôpital.

Failure Mode, Effects, and Criticality Analysis (FMECA) is used in industry to prevent process or product failures. We studied the feasibility of this method in hospital organizations. FMECA was used to improve drug prescription in two medical wards. Failure modes were identified and classified hierarchically. Corrective actions were taken. Involvement of all the professionals concerned in this process was obtained, and has resulted in real acceptance of the proposed changes and in their effective realization.

[Drug administration to paediatric inpatient]. / L'administration des médicaments à l'enfant hospitalisé.

OBJECTIVE: Available commercial drugs in France are often unsuitable for children. The aim of this study was, for every medicinal form orally or parenterally administered, to identify and to quantify difficulties met by the nurses administering drugs to paediatric inpatients and to propose solutions to main identified problems. MATERIAL AND METHOD: The study was realized in 14 hospitals by direct observation. The observer, provided with a questionnaire, followed during a time slot of at least 2 h for one or several nurses and raised all the oral or injectable administrations. RESULTS: One thousand and nine hundred forty-six observations were performed. The children were 12.6 +/- 17 months old, and weighed 8.5 +/- 9.4 kg. Injectable drugs: half of the observations showed a posology and a mode of dilution not corresponding to the summary of product characteristics. Eight percent of orally administered drugs were injectable drugs. In 35.5% of cases, administered amount was lower than the quarter of the present quantity in the therapeutic unity. The rest of the therapeutic unity was thrown (77.2% of cases). Liquid oral forms: liquid oral forms were ready for use regarding 83.8% of cases. The medicine was readministered to the same patient (23.5%), and/or administered to other patients (80.0%). Capsules: 66.9% of the administered capsules were prepared by the hospital pharmacies. The pharmacies organized with an unit dose drug dispensing system produced significantly more preparations than those working by global distribution (P < 0.0001). In 58.4% of cases, the administered capsule was an off-label drug. Tablets: 46% of drug administration concerned a tablet without pediatric indication. 46.7% of tablets were cut, 74% were crushed. Bags: in 35.2% of observations, the bag was not administered in its entirety. CONCLUSION: Our study confirms the unsuitability of drugs to paediatric inpatients, the necessity of recommendations of good practices in the administration of drugs to paediatric inpatients, and proposes corrective actions.

[Human in vitro fertilisation. Preliminary results (author's transl)]. / La fécondation humaine "in vitro". Premiers résultats.

We here report the results of our first attempts at fertilising the human oocyte in vitro. No external hormonal stimulation was used to induce follicular growth or maturation of the oocyte. Nine oocytes were obtained laparoscopically in ten women in the pre-ovulation hours. They were incubated in a synthetic culture medium in the presence of freshly ejaculated spermatozoa. Five oocytes were fertilised normally, of which three were cultured just up to the stage of 4-6 blastomeres. The three failures of fertilisation can be put down to poor quality of the gametes. The discussion is carried on about the quality of the oocyte and of the embryo and justifies further studies to deepen our knowledge before embarking on embryo transplant.

[Recovery of preovulatory human oocytes (author's transl)]. / Recueil d'ovocytes humains en phase préovulatoire. Intérêt du dosage radio-immunologique rapide de la LH plasmatique.

Rapid radio-immune assaying of LH was carried out four times daily on 52 women in the preovulatory phase of the cycle. This method enables the precise detection of the LH surge and recovery of the mature oocyte by laparoscopic aspiration of the follicular content, just before ovulation, which is between 28 and 36 hours after the start of the LH surge. The oocytes was recovered in 27 out of 41 patients with a normal cycle (66%). The rate of recovery per follicle aspirated is comparable in a natural cycle to that after treatment with Clomid (80 to 84%).

[Impact of a multidisciplinary approach for monitoring prescribing of antibiotics in a hospital]. / Impact d'une approche pluridisciplinaire pour la maîtrise de la prescription des antibiotiques dans un établissement hospitalier.

OBJECTIVE: The aim of this study was to examine the impact of a rationalized antibiotic prescription program in a 600-bed hospital. PATIENTS AND METHODS: The program was based on a local consensus policy, developed with the prescribers themselves, together with individual nominative dispensing (IDN) of the most costly antibiotics, and training/information programs aimed at institutional prescribers. The impact of the program was assessed in terms of the relevance of prescriptions (6-monthly audits), changes in the overall cost of anti-infectives, the average daily cost per hospital patient, and changes in the pattern of antimicrobial resistance among pathogens isolated in the institution. RESULTS: Reference recommendations were established for most clinical settings encountered in the hospital (104 for adults, 78 for children). The four audits conducted since June 1996 show that the rate of unjustified prescriptions has remained below 6%. The cost of antimicrobials has fallen regularly, both in absolute terms and as a proportion of total drug costs. Finally, resistance rates among the different pathogens studied have fallen or remained stable. CONCLUSION: Rationalization of antimicrobial chemotherapy in a short-stay hospital necessitates an institution-based policy with long-term objectives, a large initial investment and, above all, a participative approach among all prescribers.

[Revascularization of arteries of the leg by bypass in chronic arteriopathies of the lower limbs. Apropos of 50 cases]. / Revascularisation des artéred de jambe par pontage dans les art-57eriopathies chroniques des membres inférieurs. a propos de 50 cas

The authors report 50 by-pass operations followed up for from 6 months to 4 years, which were designed to restore the blood supply via the leg arteries in peripheral arterial disease of the lower limbs. 40 patients were at stages III and IV; acute ischemia required emergency operation in 6 cases. 2 Patients died immediately after operation. 30 by-passes remained permeable. A cure of the trophic disorder and a functional improvement were obtained in 39 patients with only 8 subsequent amputations. In the light of the world literature and their personal experience they discuss the main pronostic factors and the indications for this method which has proved to be a remarkable progress in the treatment of severe arterial disease of the lower limbs.

Quantitative approach of risk management strategies for hepatitis a virus-contaminated oyster production areas.

It is not yet known whether using the new molecular tools to monitor hepatitis A virus (HAV) in shellfish production areas could be useful for improving food safety. HAV contamination can be acute in coastal areas, such as Brittany, France, where outbreaks of hepatitis A have already occurred and have been linked to the consumption of raw shellfish. A quantitative probabilistic approach was carried out to estimate the mean annual risk of hepatitis A in an adult population of raw oyster consumers. Two hypothetical scenarios of contamination were considered, the first for a rare and brief event and the second for regular and prolonged episodes of contamination. Fourteen monitoring and management strategies were simulated. Their effects were assessed by the relative risk reduction in mean annual risk. The duration of closure after abnormal detection in the shellfish area was also considered. Among the strategies tested, results show that monthly molecular reverse transcription PCR monitoring of HAV is more useful than bacterial surveys. In terms of management measures, early closure of the shellfish area without waiting for confirmatory analysis was shown to be the most efficient strategy. When contamination is very short-lived and homogeneous in the shellfish production area, waiting for three negative results before reopening the area for harvest is time wasting. When contamination is not well identified or if contamination is heterogeneous, it can be harmful not to wait for three negative results. In addition, any preventive measures, such as improving sewage treatment or producing shellfish in safer areas, that can reduce contamination by at least 2 log units are more efficient and less costly. Finally we show that controlling and managing transferred shellfish are useful and can play an important role in preventing cases. Qualitative results from HAV monitoring can advantageously supplement other measures that improve the safety of shellfish products in exposed areas.

A risk-based sampling plan for monitoring of histamine in fish products.

In 2008, the French Institute for Public Health Surveillance reported an increase in the number of histamine food poisoning outbreaks and cases in France. The aim of this study was to propose a new monitoring plan for characterizing consumers' exposure to histamine through fishery products. As fish products of concern are numerous, we proposed that the number of samples allocated for a fish category be chosen based on the risk associated with the category. Point risk estimates of histamine poisoning were assessed with the Risk Ranger tool. Fresh fish with high histidine content was found to contribute most to the number of cases. The (estimated) risks associated with the consumption of canned and deep-frozen fish appear marginal as compared with the risk associated with fresh fish with high histidine concentrations. Accordingly, we recommend excluding canned and deep-frozen fish from the monitoring plan, although these risk estimates can be biased. Within a category, samples were proportional to the relative food consumption of the different fishes. The spatial and seasonal consumption patterns were also taken into account for the design of the new monitoring plan. By testing appropriate numbers of samples from categories of fish products of concern, this plan will permit investigation of trends or comparison of product categories presenting risks of histamine poisoning.

Effect of pentoxifylline on sperm movement characteristics in normozoospermic and asthenozoospermic specimens.

Preliminary evidence has suggested that the phosphodiesterase inhibitor pentoxifylline augments the fertilizing potential of asthenozoospermic sperm samples, presumably by improving sperm movement. Here, we used computer-assisted sperm movement analysis to compare the effects of pentoxifylline in normozoospermic and asthenozoospermic specimens. The study focused on the following issues: the changes in individual movement characteristics in response to pentoxifylline, the rapidity of the response, the effect of sperm capacitation on the response, the persistence of the response after drug removal and the variability of responses among asthenozoospermic individuals. Data obtained show that (i) pentoxifylline increases the curvilinear velocity, path velocity, straight-line velocity, lateral head displacement, beat cross frequency and sperm hyperactivation in both normozoospermic and asthenozoospermic specimens, (ii) pentoxifylline does not modify the percentage of motile spermatozoa, (iii) the pentoxifylline effect reaches a maximum within 10 min of treatment in fresh semen as well as in capacitated sperm suspensions and persists for at least 2 h after drug removal and (iv) pentoxifylline improves the movement characteristics in most asthenozoospermic individuals. Results are discussed with regard to methods of therapeutic application of pentoxifylline as an enhancer of sperm movement in assisted reproductive technology.