Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. METHODS: This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70. RESULTS: Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 µg (n = 25), Viaskin-PT 50 µg (n = 25), laser + Viaskin-PT 25 µg (n = 5), laser + Viaskin-PT 50 µg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 µg and 50 µg (139.87 (95% CI 87.30-224.10) and 121.76 (95% CI 95.04-156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37-89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 µg (4/5 (80.0%), 95% CI 28.4-99.5) and 50 µg (22/25 (88.0%), 95% CI 68.8-97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0-26.5). CONCLUSIONS: Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT03035370) and was funded by DBV Technologies.

The lagoon geomorphology of pearl farming atolls in the Central Pacific Ocean revisited using detailed bathymetry data.

The lagoons of seven French Polynesia and Cook Islands pearl farming atolls (Raroia, Takume, Mopelia, Takapoto, Ahe, Takaroa and Manihiki) were surveyed using multibeam and mono-beam sounders. From the detailed bathymetry, morphometric variables (average and maximum depth, frequency-area of depth, lagoon area and volume) are computed and compared. Remarkable geomorphological structures highlighted by bathymetric variations include deep reticulated structures and pinnacles. The seven atolls appear very different in abundance, size and density of these entities. Considering them as markers of the geological, sedimentological and eustatic processes that shape atoll lagoons, they are discussed in the context of the general theory of atoll lagoon formations involving karstic dissolution during Pleistocene or earlier low sea-level stands. In terms of pearl farming management, accurate bathymetric maps help pearl oyster wild stock assessment, development of circulation and biogeochemical models, better lagoon zoning and strategy to remove pearl farming derelict gears.

Biological and Genetic Characterization of New and Known Necroviruses Causing an Emerging Systemic Necrosis Disease of Corn Salad (Valerianella locusta) in France.

An emerging systemic necrosis disease of corn salad was first observed in the Nantes region of France in the late 2000s. Classical virology and high-throughput sequencing approaches demonstrated that the disease is associated with four different necroviruses: tobacco necrosis virus A (TNVA), tobacco necrosis virus D (TNVD), olive mild mosaic virus (OMMV), and a novel recombinant Alphanecrovirus for which the name corn salad necrosis virus (CSNV) is proposed. Satellite tobacco necrosis virus was also frequently observed. Koch's postulates were completed for all four agents, each one alone being able to cause systemic necrosis of varying severity in corn salad. OMMV was the most frequently observed virus and causes the most severe symptoms. TNVA was the second, both in terms of prevalence and symptom severity while TNVD and CSNV were only rarely observed and caused the less severe symptoms. The emergence of this systemic disease may have been favored by the short and repeated cropping cycles used for corn salad, possibly allowing the selection of necrovirus isolates with an improved ability to systemically invade this specialty crop.

Diagnostic validity and triage concordance of a physiotherapist compared to physicians' diagnoses for common knee disorders.

BACKGROUND: Emergence of more autonomous roles for physiotherapists warrants more evidence regarding their diagnostic capabilities. Therefore, we aimed to evaluate diagnostic and surgical triage concordance between a physiotherapist and expert physicians and to assess the diagnostic validity of the physiotherapist's musculoskeletal examination (ME) without imaging. METHODS: This is a prospective diagnostic study where 179 consecutive participants consulting for any knee complaint were independently diagnosed and triaged by two evaluators: a physiotherapist and one expert physician (orthopaedic surgeons or sport medicine physicians). The physiotherapist completed only a ME, while the physicians also had access to imaging to make their diagnosis. Raw agreement proportions and Cohen's kappa (k) were calculated to assess inter-rater agreement. Sensitivity (Se) and specificity (Sp), as well as positive and negative likelihood ratios (LR+/-) were calculated to assess the validity of the ME compared to the physicians' composite diagnosis. RESULTS: Primary knee diagnoses included anterior cruciate ligament injury (n = 8), meniscal injury (n = 36), patellofemoral pain (n = 45) and osteoarthritis (n = 79). Diagnostic inter-rater agreement between the physiotherapist and physicians was high (k = 0.89; 95% CI:0.83-0.94). Inter-rater agreement for triage recommendations of surgical candidates was good (k = 0.73; 95% CI:0.60-0.86). Se and Sp of the physiotherapist's ME ranged from 82.0 to 100.0% and 96.0 to 100.0% respectively and LR+/- ranged from 23.2 to 30.5 and from 0.03 to 0.09 respectively. CONCLUSIONS: There was high diagnostic agreement and good triage concordance between the physiotherapist and physicians. The ME without imaging may be sufficient to diagnose or exclude common knee disorders for a large proportion of patients. Replication in a larger study will be required as well as further assessment of innovative multidisciplinary care trajectories to improve care of patients with common musculoskeletal disorders.

[Voluntariness and blood donation: Proceedings of an ethics seminar held at the National Institute for Blood Transfusion]. / Volontariat et don de sang : compte rendu d'un séminaire de l'Institut national de transfusion sanguine.

Voluntariness stands for one of the four pillars of ethics in blood donation; it is, however, more related to tradition than to legislation. Because it seems necessary to apply "marketing" techniques to blood collection in order to meet the needs in blood components, both in terms of quantity and quality, one wonders if this may be at the expense of this principle of voluntariness. This seminar-belonging actually to a series of seminars in Ethics in Transfusion Medicine-aimed at questioning the possible weakness of voluntariness in the field of blood donation. To achieve this goal, specialists of numerous disciplines in medical sciences, law and humanities gathered to discuss all related issues to voluntariness in blood donation.

[Blood donation: Representations and issues associated with blood product collection]. / Le don du sang : représentations et enjeux associés à la collecte de produits sanguins.

In order to answer to its aim of standardised self-sufficiency, the Établissement français du sang (main French national platform for blood donation) needs to know well the donors, what moves them, what motivates them, and the meaning that they give to their action. This knowledge allows the EFS to better understand the different sensitivities among donors, and therefore to improve the strategy regarding loyalty or/and newcomers. In this paper we follow, without attempting to be fully exhaustive, the evolution of the research regarding blood donation. The aim is to highlight the role played by social and historical representations regarding donation in general. In a given community, its norms, and its values influence both the image of donors as well as the meaning attached to the act itself of donation. Moreover, these norms have also influenced the way that research has tried to analyse this topic. The initial studies conducted in this field tried generally to understand the meaning and the symbolism attached to the act of blood donation. Later on, researchers started to focus on the assessment of notions such as generosity, and then solidarity. Nowadays, research is more focused on describing the population that gives blood. They are more scrutinised through their socio-demographic traits (who they are) than through the specific study of how they donate, the reasons behind the decision to act and the notion of satisfaction.

[Geomatics in the service of blood collection]. / La géomatique au service de la collecte de sang.

UNLABELLED: To achieve blood supply, EFS organizes mobile blood collection sessions (80% of whole blood supply), close to target blood donors. Mobile sessions planning is usually developed in partnership with organizations of voluntary blood donors, based on the experience of previous sessions. However, population moving to urban areas and lifestyles changing force to focus on objective demographic analysis to determine a prospective vision of potentialities to ensure blood supply. METHOD: For blood supply management, EFS recently implemented innovative methods of mapping, through Geographic Information System software (GIS) that allow a spatial representation of different indicators. Geomatics engineering gathers and processes spatially referenced information about blood collections and blood donors, combining data from EFS and data from IGN or INSEE. RESULTS AND CONCLUSION: The authors present some examples of geomatics applied to blood supply and a feedback on the implementation of these tools in a French region. These innovative tools enhance expertise and increase the mastery of analysis for blood supply strategies.

Challenges of controlling a large outbreak of OXA-48 carbapenemase-producing Klebsiella pneumoniae in a French university hospital.

A large outbreak of OXA-48 carbapenemase-producing Klebsiella pneumoniae at Nantes University Hospital was investigated. The index case had no history of travel or hospitalization abroad and had been hospitalized in the internal medicine department for more than one month when the epidemic strain was isolated from a urine sample in June 2013. Seventy-two secondary cases were detected by weekly screening for gastrointestinal colonization during the two phases of the outbreak from June to October 2013 (33 cases) and from November 2013 to August 2014 (39 cases). Spread of the epidemic strain was attributed to the proximity of, and staff movement between, the infectious diseases (32 cases) and the internal medicine (26 cases) departments; 14 secondary cases were also observed in the renal transplant department following the transfer of an exposed patient from the infectious diseases department. Most of the patients (90%) were colonized and no death was linked to the epidemic strain. More than 3000 contact patients were reviewed and 6000 rectal swabs were performed. Initial control measures failed to control the outbreak owing to the late detection of the index case. The late implementation of three successive cohort units, the large number of transfers between wards, and the frequent readmission of cases contributed to the incomplete success of control measures.

[Self-sufficiency, needs, prescription and safety of blood products]. / Autosuffisance, besoins, prescription et sécurité des produits sanguins labiles.

The current issues debate will bring together experts around the themes of self-sufficiency (in its national and European aspects) and of needs in cellular blood products. The point of view of the manufacturer and prescribers of blood products will be confronted.

[Which place for physicians in blood supply?]. / Quelle place pour les médecins en collecte?

Historically, blood transfusion has been divised, enhanced and organized by physicians. The special status of blood led to ensure that collection of blood and its components were placed under the supervision of a physician. Throughout its history, blood transfusion organization in France has established an exclusive exercise of the collection of blood and its components entrusted to doctors, thus creating the concept of "medicine of donation". This view is changing, and programmed exercise of this activity by nurses led to question about this profession perimeter, its necessary evolution, and finally about the place of physicians in blood supply.

Deferral from donating blood of men who have sex with men: impact on the risk of HIV transmission by transfusion in France.

BACKGROUND: In France, men who have sex with men (MSM) are permanently excluded from blood donation. This policy is felt to be discriminatory by MSM activists. Furthermore, the policy is not fully respected because some MSM do not report their sexual behaviour before donating. METHODS: We estimated the fraction of the current risk of HIV attributed to MSM. We then constructed a model based on data obtained from behavioural and epidemiological surveys to assess the impact of a new strategy in which MSM would only be deferred if they report more than one sexual partner in the last 12 months. RESULTS: Thirty-one HIV seroconversions occurred among repeat donors between 2006 and 2008, giving a risk of one in 2 440 000 donations. Fifteen of these seroconversions (48%) were MSM. If all MSM had abstained from donating blood, the risk would have been 1 in 4 700 000 donations, half the current risk. The new strategy would result in an overall HIV risk of between 1 in 3 000 000 (close to the current risk) to 1 in 650 000 donations (3·7 times higher than the current risk). CONCLUSIONS: Changing the current MSM deferral policy may increase the risk of transfusion-transmission of HIV. However, this does not take into account a possible better compliance with MSM with a less stringent policy that would be perceived as more equitable. Conversely, relaxing the policy could encourage some MSM to seek an HIV test in blood centres. Thus, further qualitative study is needed to assess possible changes in compliance linked to a new policy.

[The place and moment of blood donation: considerations on the organization of blood collection sites]. / L'espace et le moment du don: réflexions sur l'organisation des plateformes de collecte.

Conversations held with the staffs of blood collection sites at établissement français du sang (EFS) of several regions allow pinpointing their criticisms, expectations and suggestions. They concern, at the same time, the arrangement of sites and the donor circuit, the work organization and the management of the teams. This point seems major, underlining the role of local supervision, which is at once a technical expert and a manager, and the necessity to set up the conditions of a good cooperation, between professions where too many subdivisions still remain.

[Predonation interview by a trained and authorized paramedical staff: feasibility, reliability and safety]. / Entretien prédon par un personnel paramédical formé et habilité: faisabilité, fiabilité et sécurité.

INTRODUCTION: Predonation interview accounts for a major step in transfusion safety. In France, it must be performed by a physician, following a methodical questioning and a standardized questionnaire. Faced with this evolution, the value of a strictly medical expertise has been progressively losing importance. In many countries, blood donor selection is being organized by non medical trained staff (Québec, Switzerland, e.g.). A decree of April 30, 2006 allowed the Établissement français du sang to experiment a predonation interview by an authorized paramedical staff in the form of a two-phase prospective multicenter study over a year. PATIENTS AND METHODS: Phase I "experimental situation": six physician/nurse teams among three blood transfusion centres interviewed 1940 blood-donation candidates, including 253 new donors (13% out of total). Phase 2 "observational study": 3222 blood-donation candidates were interviewed either by a physician or a nurse. RESULTS: In phase I, nurses were able to make a decision without the physician's help in 1921 cases. A total of 1628 candidates were decided capable of donating blood both by physicians and nurses, 174 donors were rejected both by physicians and nurses and 69 were rejected either by physicians or nurses. In phase 2, out of 3222 blood-donation candidates, an average of 12.1% were rejected by nurses and 10% by physicians. CONCLUSION: The study reported a weaker variability among nurses. Results show that nurses were able to perform predonation interviews with high reliability, without additional risk. The reproducibility of their answers in the field of recipient-risk evaluation was better than the physicians.

[Chagas disease screening in the blood donor population]. / Dépistage de la maladie de Chagas chez les donneurs de sang.

In May 2007, the French Blood Service (Etablissement français du sang, EFS) introduced systematic screening of at-risk blood donors for anti-Trypanosoma cruzi antibodies. This concerned donors originating from an endemic area, donors with mothers originating from such an area and individuals who had lived in or travelled to endemic areas, whatever the length of their stay. Five samples out of 163,740 were positive, all from individuals originating from an endemic area. One thousand three hundred seventy-four blood donations were considered as equivocal because they had discordant results on the two Elisa tests used in screening. The authors discuss difficulties presented by routine screening of travellers and residents as well as the advantages and drawbacks of the strategy used. They present arguments in favour of its simplification.

[Why defer blood donor candidates because of an exposure risk to Chagas disease?]. / Pourquoi ajourner au don de sang des candidats au motif d'un risque de maladie de Chagas?

Various infectious agents can be transmitted by blood exposure, which comprises of transfusion, of which hemoparasites that are commonly absent from European countries but that can have infected blood donor candidates born, raised or having been living in the Tropics. Among those hemoparasites is Trypanosoma cruzi, responsible for Chagas disease. T. cruzi is responsible for acute post-transfusion infections every year in endemic areas (South America) and also, more incidently, in North America. There are situations which expose European blood donors to this risk and the present essay discusses arguments which have now been taken into consideration by certain transfusion systems such as the French one.

Overview of revised measures to prevent malaria transmission by blood transfusion in France.

Plasmodial transmission by blood donation is rare in non-endemic countries, but a very serious complication of blood transfusion. The French national blood service (Etablissement Français du Sang and Centre de Transfusion sanguine des Armees) intended to revise the measures to strengthen blood safety with regard to Plasmodiae as transmissible pathogens. To limit the risk of transmission during infusion, serious additive measures have been taken for more than a decade in France, which is the European country with the highest rate of exposure to imported plasmodial infections or malaria. These measures were revised and strengthened after the occurrence of a lethal transfusion-transmitted infection in 2002, but did not prevent another occurrence in 2006. This report examines the weaknesses of the systems and aims at emphasizing the safety measures already taken and addresses issues to best respond to that risk.

[The number of cell separators existing in France in 2003]. / Le parc de séparateurs de cellules en France en 2003.

The "2002 Apheresis" Group was commissioned by the President of the Etablissement français du sang to carry out a study on the national stock of automated apheresis devices and think about a method to harmonize techniques. The objective was twofold: to facilitate the initiation of public procurement procedures as well as to streamline the stock and to match practices. The members of the "2002 Apheresis" group first carried out an inquiry based on a nationwide questionnaire. They analyzed and compared the performances of the various separators. They also consulted suppliers on their short-term (2 years) projects. They finally met all regional apheresis correspondents. The group was then able to make suggestions to organize this activity as a part of a national apheresis scheme. Lastly, they helped devising public procurement procedures for the coming two years. This group is going to obtain a long-term recognition with the creation of a "Collection Group" conducted by the Scientific and Medical directors board at the Etablissement français du sang.

Determinants of thyroid volume in healthy French adults participating in the SU.VI.MAX cohort.

OBJECTIVE: To study the relative importance of determinants of thyroid volume. DESIGN: Cross-sectional study on a sample of subjects issued from the SU.VI.MAX cohort. SUBJECTS: 2987 French subjects (1713 women aged 35-60 years and 1274 men aged 45-60 years). None of them had previous or present thyroid disease. MEASUREMENTS: Thyroid volume was determined by ultrasound. Serum TSH and free thyroxine (fT4) were measured in duplicate. Urinary iodine and urinary thiocyanate were assayed in random morning urine samples. RESULTS: For both sexes, thyroid volume (ml) was positively correlated with weight, height, body mass index and body surface area (P = 0.0001) and negatively with age for females (P = 0.0009). When the urinary iodine concentration was adjusted for urinary thiocyanate concentration and their interaction, the thyroid volume was negatively correlated with urinary iodine (males P = 0.02, females P = 0.006) and positively correlated with urinary thiocyanate (males P = 0.0001, females P = 0.004). Mean thyroid volume was greater among active smokers than non-smokers (males P < 0.0001, females P = 0.0004) and was greater among former smokers than among non-smokers (males P = 0.0001, females = 0.004). Free T4 and thyroid volume were positively correlated for both sexes (P = 0. 0001). TSH was negatively correlated with thyroid volume for both groups (P = 0.0001). Female users of oral contraception (aged 35-45 years) had a smaller thyroid volume than non-users (P = 0.0009). CONCLUSIONS: The state of borderline iodine deficiency observed in France, in association with a slightly goitrogenic environment, may result in sustained stimulation of the thyroid, independently of TSH level, and is of paramount importance in the formation of goitre. Smoking may affect the thyroid, inducing marked long-lasting thyroid enlargement.