Performances, feasibility and acceptability of nasopharyngeal swab, saliva and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2.

Molecular diagnosis on nasopharyngeal swabs (NPS) is the current standard for COVID-19 diagnosis, but saliva may be an alternative specimen to facilitate access to diagnosis. We compared analytic performances, feasibility and acceptability of NPS, saliva, and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A prospective, multicenter study was conducted in military hospitals in France among adult outpatients attending COVID-19 diagnosis centers or hospitalized patients. For each patient, all samples were obtained and analyzed simultaneously with RT-PCR or transcription-mediated amplification method. Clinical signs, feasibility, and acceptability for each type of sample were collected. A total of 1220 patients were included, corresponding to 1205 NPS and saliva and 771 OS. Compared to NPS, the sensitivity, specificity, and kappa coefficient for tests performed on saliva were 87.8% (95% CI 83.3-92.3), 97.1% (95% CI 96.1-98.1), and 0.84 (95% CI 0.80-0.88). Analytical performances were better in symptomatic patients. Ct values were significantly lower in NPS than saliva. For OS, sensitivity was estimated to be 61.1% (95% CI 52.7-69.4) and Kappa coefficient to be 0.69 (95% CI 0.62-0.76). OS was the technique preferred by the patients (44.3%) before saliva (42.4%) and NPS (13.4%). Instructions were perceived as simple by patients (> 90%) for saliva and OS. Finally, the painful nature was estimated to be 0.9 for OS, on a scale from 0 to 10, and to be 5.3 for NPS. Performances of OS are not sufficient. Saliva is an acceptable alternative to NPS for symptomatic patient but the process required additional steps to fluidize the sample.

COVID-19 Repeated Convalescent Plasma Collection: Analysis of 149 Donations from 88 French Military Health Workers.

BACKGROUND: Passive therapy with convalescent plasma (CP) could be an effective and safe treatment option in COVID-19 patients. Neutralizing antibodies present in CP generated in response to SARS-CoV-2 infection and directed against the receptor-binding domain of the spike protein are considered to play a major role in the viral clearance. CP infusion may also contribute to the modulation of the immune response through its immunomodulatory effect. We describe for the first time the effectiveness of a CP collection protocol from repeated donations in young patients. MATERIALS AND METHODS: We enrolled health service workers who experienced mild to moderate COVID-19 and from whom several donations have been collected. No minimal severity threshold and no biological cure criteria were required. Donors could return to a second plasma donation 14 days after the first donation. A minimal neutralizing antibody titer of 1:40 was considered for clinical use. RESULTS: Eighty-eight donors were included (median age 35 [28-48] years, 41 women), and 149 plasma products were collected. COVID-19 were mainly WHO stage 2 infections (96%). Among the 88 first donations, 76% had neutralizing antibody titers higher than or equal to 1:40. Eighty-eight percent of donors who came for a second donation had a neutralizing antibody titer of 1:40. Median durations were 15 (15-19) and 38 (33-46) days from the first to the second donation and from recovery to the second donation, respectively. Sixty-nine percent of donors who came for a third donation had a neutralizing antibody titer of 1:40. Median durations were 16 (13-37) and 54 (49-61) days from the second to the third donation and from recovery to the third donation, respectively. No significant difference was observed between the IgG ratio and the age of the donors or the time between recovery and donation. The average IgG ratio did not significantly vary between donations. When focused on repeated blood donors, no significant differences were observed either. CONCLUSION: The recruitment of young patients with a mild to moderate CO-VID-19 course is an efficient possibility to collect CP with a satisfactory level of neutralizing antibodies. Repeated donations are a well-tolerated and effective way of CP collection.

Characterizing Symptom Profiles in a Military Outpatient Cohort With COVID-19 in the Île-de-France Region.

INTRODUCTION: The emergence of coronavirus disease 2019 (COVID-19) pandemic, driven by severe acute respiratory syndrome coronavirus 2, precipitated an unprecedented public health crisis, necessitating comprehensive response worldwide. The Ile-De-France region has been particularly affected, leading to rapid health care system strain and hospital saturation. Within this context, the 1st Armed Forces Medical Centre swiftly adapted its primary care services to cater to the unique needs of military personnel, leveraging telemedicine technologies for efficient health care delivery. MATERIALS AND METHODS: This study undertook an observational retrospective analysis to characterize the epidemiological profile of soldiers seeking outpatient care for non-severe COVID-19 symptoms at the 1st Armed Forces Medical Centre's sub-centers between March and December 2020. Electronic medical records of patients were scrutinized to discern patterns in symptom presentation and evolution over time. RESULTS: The cross-section sample consisted of 519 patients, predominantly males (71%), with an average age of 38 years. Predominant symptoms reported were asthenia (43%), cephalalgia (41%), myalgia (40%), pyrexia (38%), and tussis (33%). A significant proportion of patients (33%) were asymptomatic at the follow-up consultations, marking a notable increase from initial assessments (14%). Although symptoms indicative of flu-like syndrome and sore throat exhibited regression between consultations, certain manifestations, such as anosmia, ageusia, and dyspnea, persisted without significant variance. Our analysis delineated five distinct symptom profiles within the cohort. CONCLUSIONS: This study provides valuable insights into the clinical course of non-severe COVID-19 cases among military personnel receiving outpatient care, delineating five distinct symptom profiles. This complexity underscores the challenges in predicting and managing symptomatology effectively. Our findings align with existing literature but offer a unique perspective on military cohorts. Notably, in confined military settings with predominantly young and healthy individuals, symptomatic presentations tend to be milder. Robust public health interventions, including quarantine and contact tracing, are crucial to maintaining operational readiness amidst the pandemic's challenges.

Brief report: pulmonary auscultation in the operating room: a prospective randomized blinded trial comparing electronic and conventional stethoscopes.

BACKGROUND: We compared the subjective quality of pulmonary auscultation between 2 acoustic stethoscopes (Holtex Ideal® and Littmann Cardiology III®) and an electronic stethoscope (Littmann 3200®) in the operating room. METHODS: A prospective double-blind randomized study with an evaluation during mechanical ventilation was performed in 100 patients. After each examination, the listeners using a numeric scale (0-10) rated the quality of auscultation. Auscultation quality was compared in patients among stethoscopes with a multilevel mixed-effects linear regression with random intercept (operator effect), adjusted on significant factors in univariate analysis. A significant difference was defined as P < 0.05. RESULTS: One hundred comparative evaluations of pulmonary auscultation were performed. The quality of auscultation was rated 8.2 ± 1.6 for the electronic stethoscope, 7.4 ± 1.8 for the Littmann Cardiology III, and 4.6 ± 1.8 for the Holtex Ideal. Compared with Holtex Ideal, auscultation quality was significantly higher with other stethoscopes (P < 0.0001). Compared with Littmann Cardiology III, auscultation quality was significantly higher with Littmann 3200 electronic stethoscope (ß = 0.9 [95% confidence interval, 0.5-1.3]). CONCLUSIONS: An electronic stethoscope can provide a better quality of pulmonary auscultation than acoustic stethoscopes in the operating room, yet with a magnitude of improvement marginally higher than that provided with a high performance acoustic stethoscope. Whether this can translate into a clinically relevant benefit requires further studies.

The 2009 A(H1N1) influenza pandemic in the French Armed Forces: evaluation of three surveillance systems.

BACKGROUND: The French military forces had to modify their epidemiological surveillance systems at the time of the 2009 A(H1N1) influenza pandemic. The aim of this article was to present an evaluation of the different systems used. METHODS: Two influenza surveillance systems are usually used in the French forces: one permanent (Surveillance épidémiologique des armées or SEA) and one seasonal (Système militaire d'observation de la grippe or SMOG). The pandemic required the implementation of a daily surveillance system (Surveillance quotidienne--SQ), which aimed to monitor disrupted activity owing to 2009 A(H1N1) influenza. The qualitative evaluation of these three systems during the period from September 2009 to February 2010 was performed using 11 criteria based on the list defined by Centers for Disease Control and Prevention of Atlanta. RESULTS: Although it included only 30 sentinel units vs. 320 for the other systems, the SMOG system was the best-performing system in terms of relevance, feasibility, efficacy, quality of data, usefulness, acceptability, efficiency and cost/benefits/costs ratio. The SQ proved very expensive in terms of logistics. CONCLUSION: The SQ did not bring any significant advantage compared with the weekly surveillance schemes. In the eventuality of another similar episode, influenza surveillance could be significantly improved by using the SMOG system extended to more units for better geographical coverage.

The accuracy of self-reported data concerning recent cannabis use in the French armed forces.

BACKGROUND: The aims were to evaluate the accuracy of self-report of past-month cannabis use in a representative sample of French military staff members and to evaluate the scale of the prevarication bias. METHOD: Data from three cross-sectional surveys conducted between 2005 and 2008 (n = 3493) were used. The characteristics of self-report (sensitivity, specificity, positive predictive value and negative predictive value) were computed using tetrahydrocannabinol detection in urine as the reference. RESULTS: The prevalence for past-month cannabis use was 16.1% and for positive testing was 13.4%. The discriminant power of self-report was good, with an area under the receiver operating characteristics curve 0.90. Specificity (94.5%) and negative predictive values (97.8%) were good, but sensitivity (85.7%) and positive predictive values (70.4%) were lower. The lowest sensitivity values were observed in the higher categories of personnel and in the Navy, which could reflect some prevarication in these sub-populations who might believe they were more exposed to sanctions if detected. CONCLUSIONS: Despite certain limitations of urine analysis as a reference, because of its poor detection of occasional users, our study is in favour of good accuracy of self-reported data on cannabis use, even among the military. However, our results, derived from a population study, do not enable any assumptions on the validity of self-reported data collected during individual testing procedures for the purpose of improving occupational safety.

In vitro hemostatic properties of French lyophilized plasma.

BACKGROUND: French lyophilized plasma (FLyP) is used routinely by the French Armed Forces in war settings. The authors compared concentrations of coagulation proteins and global in vitro hemostatic properties in FLyP and in the same plasma before lyophilization to assess the impact of lyophilization on coagulation properties. METHODS: Twenty-four batches of plasma before and after lyophilization were tested for coagulation proteins. Thrombin generation time, thrombin antithrombin concentration, prothrombin fragment 1 + 2, and thromboelastography were assessed. Finally, the efficiencies of FLyP and plasma before lyophilization were compared on a hemorrhagic shock hemodilution model and tested on TEG(Haemoscope Corporation, Glenview, IL). RESULTS: Prothrombin time ratio (1.1 ± 0.1 vs. 1.2 ± 0.1) and activated partial thromboplastin time (35 ± 1.3 vs. 39 ± 2.4 s) were significantly increased in FLyP (8 ± 3%, P < 0.05 and 11 ± 5%, P < 0.001, respectively). Activity of factors V (85 ± 18 vs. 51 ± 16 UI/ml) and VIII (0.77 ± 0.11 vs. 0.62 ± 0.10 UI/ml) was also diminished (25 ± 12% and 20 ± 7%, respectively); however, activity of other factors was preserved. The authors observed no alteration in the thromboelastographic parameters. Thrombin generation was preserved when induced with 5 pM tissue factor in vitro but significantly reduced when using 1 pM tissue factor. The thrombin-antithrombin complex and prothrombin fragment 1 + 2 attested for the absence of coagulation activation. This hemodilution model showed no significant difference before and after lyophilization. CONCLUSIONS: The study results account for a significant decrease of factors V and VIII in FLyP. However, the global capacity to induce clot formation in vitro seems to be preserved. The clinical relevance of these decreased factors is not known.

Mortality among active-duty male French Armed Forces, 2006-10.

BACKGROUND: In the Armed Forces, knowledge about the causes of deaths is required in order to develop prevention strategies. This study presents the main characteristics of causes of deaths among male active-duty personnel in the French Armed Forces during the 2006-10 period and compares them with the general French male population. METHODS: The data are provided by military public health surveillance. Comparisons of the specific mortality rates (MR) were performed using a Poisson regression. Standardized mortality ratios (SMRs) were calculated to compare mortality with the general French male population. RESULTS: There were 1455 deaths among male active-duty personnel during the study period [MR: 100.9 per 100,000 person-years (PY); 95% confidence interval 95.7-106.1]. The 17-24 age group was characterized by violent deaths: transport accident (MR: 45.9 per 100,000 PY) and suicide (18.8 per 100 000 PY). Overall SMRs show significantly lower MR compared with the French national MR with the exception of SMR for transport accident and suicide in the 17-24 age group. CONCLUSIONS: There is a significantly lower deficit of mortality compared with the French male general population, reflecting a strong healthy worker effect. However, health promotion programmes should continue to put emphasis on transport accident especially among the 17-24 age group.

Prehospital Lyophilized Plasma Transfusion for Trauma-Induced Coagulopathy in Patients at Risk for Hemorrhagic Shock: A Randomized Clinical Trial.

Importance: Blood transfusion is a mainstay of therapy for trauma-induced coagulopathy, but the optimal modalities for plasma transfusion in the prehospital setting remain to be defined. Objective: To determine whether lyophilized plasma transfusion can reduce the incidence of trauma-induced coagulopathy compared with standard care consisting of normal saline infusion. Design, Setting, and Participants: This randomized clinical trial was performed at multiple centers in France involving prehospital medical teams. Participants included 150 adults with trauma who were at risk for hemorrhagic shock and associated coagulopathy between April 1, 2016, and September 30, 2019, with a 28-day follow-up. Data were analyzed from November 1, 2019, to July 1, 2020. Intervention: Patients were randomized in a 1:1 ratio to receive either plasma or standard care with normal saline infusion (control). Main Outcomes and Measures: The primary outcome was the international normalized ratio (INR) on arrival at the hospital. Secondary outcomes included the need for massive transfusion and 30-day survival. As a safety outcome, prespecified adverse events included thrombosis, transfusion-related acute lung injury, and transfusion-associated circulatory overload. Results: Among 150 randomized patients, 134 were included in the analysis (median age, 34 [IQR, 26-49] years; 110 men [82.1%]), with 68 in the plasma group and 66 in the control group. Median INR values were 1.21 (IQR, 1.12-1.49) in the plasma group and 1.20 (IQR, 1.10-1.39) in the control group (median difference, -0.01 [IQR, -0.09 to 0.08]; P = .88). The groups did not differ significantly in the need for massive transfusion (7 [10.3%] vs 4 [6.1%]; relative risk, 1.78 [95% CI, 0.42-8.68]; P = .37) or 30-day survival (hazard ratio for death, 1.07 [95% CI, 0.44-2.61]; P = .89). In the full intention-to-treat population (n = 150), the groups did not differ in the rates of any of the prespecified adverse events. Conclusions and Relevance: In this randomized clinical trial including severely injured patients at risk for hemorrhagic shock and associated coagulopathy, prehospital transfusion of lyophilized plasma was not associated with significant differences in INR values vs standard care with normal saline infusion. Nevertheless, these findings show that lyophilized plasma transfusion is a feasible and safe procedure for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT02736812.

DEFI 2005: a randomized controlled trial of the effect of automated external defibrillator cardiopulmonary resuscitation protocol on outcome from out-of-hospital cardiac arrest.

BACKGROUND: Using automated external defibrillators (AEDs) that implement the Guidelines 2000 resuscitation protocol constrains administration of cardiopulmonary resuscitation (CPR) to <50% of AED connection time. We tested a different AED protocol aimed at increasing the CPR administered to patients with out-of-hospital cardiac arrest. METHODS AND RESULTS: In a randomized controlled trial, patients with out-of-hospital cardiac arrest requiring defibrillation were treated with 1 of 2 AED protocols. In the control protocol, based on Guidelines 2000, sequences of up to 3 stacked countershocks were delivered, with rhythm analyses initially and after the first and second shocks. The study protocol featured 1 minute of CPR before the first shock, shorter CPR interruptions before and after each shock, and no stacked shocks. The primary end point was survival to hospital admission. Of 5107 out-of-hospital cardiac arrest patients connected to an AED, 1238 required defibrillation, and 845 were included in the final analysis. Study patients (n=421) had shorter preshock pauses (9 versus 19 seconds; P<0.001), had shorter postshock pauses (11 versus 33 seconds; P<0.001), and received more CPR (61% versus 48%; P<0.001) and fewer shocks (2.5 versus 2.9; P<0.001) than control patients (n=424). Similar proportions survived to hospital admission (43.2% versus 42.7%; P=0.87), survived to hospital discharge (13.3% versus 10.6%; P=0.19), achieved return of spontaneous circulation before physician arrival (47.0% versus 48.6%; P=0.65), and survived to 1 year (P=0.77). CONCLUSIONS: Following prompts from AEDs programmed with a protocol similar to Guidelines 2005, firefighters shortened pauses in CPR and improved overall hands-on time, but survival to hospital admission of patients with ventricular fibrillation out-of-hospital cardiac arrest did not improve. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00139542.

Plasmodium vivax Malaria among military personnel, French Guiana, 1998-2008.

We obtained health surveillance epidemiologic data on malaria among French military personnel deployed to French Guiana during 1998-2008. Incidence of Plasmodium vivax malaria increased and that of P. falciparum remained stable. This new epidemiologic situation has led to modification of malaria treatment for deployed military personnel.

Impact of fibrinolysis on immediate prognosis of patients with out-of-hospital cardiac arrest.

Fibrinolytic therapy (FT) during out-of-hospital cardiac arrest (OHCA) has been studied in several trials, but they have produced unsatisfactory results even in the most recent Thrombolysis in Cardiac Arrest (TROICA) study. This study aimed to assess the impact of FT provided by an out-of-hospital emergency physician on the immediate prognosis of patients with OHCA. We performed a retrospective study in which the primary endpoint was survival to hospital admission. Among 5,102 patients with OHCA in Paris and the suburban area who received medical care from the Fire Brigade of Paris, 1,261 met the following inclusion criteria: age above 18 years with non-traumatic OHCA. Among 107 patients who received FT, 51 (47.7%) survived to hospital admission whereas 272 out of 1,154 (23.6%) patients who did not receive FT survived to hospital admission. A matching process based on a propensity score used to equalise potential prognosis factors in both groups demonstrated that FT was associated with more frequent survival to hospital admission (OR adjusted: 1.7; CI 95% [1.09-2.68]). This result was observed particularly in patients who were not initially shocked by automatic electrical defibrillator (AED) (OR(a) = 3.61; CI 95% [1.88-6.96]). This study showed that fibrinolysis was associated with improved survival to hospital admission, after performing a propensity analysis. FT may be beneficial in out-of-hospital arrest patients. However, any conclusions drawn are limited by the retrospective nature of the study.

Antivenin remains effective against African Viperidae bites despite a delayed treatment.

BACKGROUND: Viperidae bites represent a public health issue in Africa and are responsible for a hemorrhagic syndrome with fatal outcome in the short term. A research on Medline database does not reveal any data definitively demonstrating the efficiency of antivenom in case of delayed administration. The aim of this study, based on a 12-year survey of viperine syndromes in Republic of Djibouti, was to compare the normalization of the hemostasis disorders with an early administration of antivenin versus a delayed administration. METHODS: A retrospective study was conducted from October 1994 to May 2006 in the intensive care unit of the French military Hospital, in Djibouti. Seventy-three Viperidae-envenomed patients were included. Antivenin efficiency in correcting hemostatic disorders was analyzed in relation to time to treatment (before or after the 24th hour after the bite). RESULTS: Forty-two patients (58%) presented with bleeding. A consumptive coagulopathy was found in 68 patients (93%). Antivenin was observed to be effective in improving hemostasis, and the time to normalization of biologic parameters was similar, whether the treatment was started before or after the 24th hour after the bite. CONCLUSION: Antivenin should ideally be administered as early as possible. However, in Africa, time to treatment generally exceeds 24 hours. The results of the present evidence-based study confirm an empirical concept: a delayed time to treatment should in no way counterindicate the use of antivenin immunotherapy, in the case of African Viperidae bites.

Quality of postoperative care after major orthopedic surgery is correlated with both long-term cardiovascular outcome and troponin Ic elevation.

BACKGROUND: The aim of this study performed in patients undergoing major orthopedic surgery was to assess the impact of changes in practice on both the incidence of postoperative myocardial ischemia (PMI) detected by serial measurements of troponin Ic and long-term cardiac outcome. METHODS: During a 3-yr period, troponin Ic was measured on the first 3 days after major orthopedic surgery in a multidisciplinary hospital. After 16 months of study, postoperative care was improved. Cardiac death, myocardial infarction, and cardiac failure were considered major adverse cardiac events and were recorded during the hospital stay and the first postoperative year. The incidences of PMI and major adverse cardiac events were used as result indicators for quality of care and compared before (P1) and after (P2) quality enhancement. RESULTS: Three hundred seventy-eight surgical procedures were included (P1, 123; P2, 255). Incidences of PMI and major adverse cardiac events were 8.9 versus 3.9% (P=0.04) and 8.1 versus 1.9% (P=0.004) for P1 and P2, respectively. Using a multivariate Cox regression analysis adjusted for baseline data, independent factors associated with the occurrence of a major adverse cardiac event were phase P1 (hazard ratio=4.5; 97.8% confidence interval [CI], 1.1-17.4) and PMI (Hazard ratio=6.4; 97.8% CI, 1.6-26.4). CONCLUSIONS: Our postoperative care policy after major orthopedic surgery strongly correlated with both short-term cardiac outcome (i.e., PMI with troponin Ic release) and long-term cardiac outcome. Thus, in a given surgical population, variation of incidence of troponin Ic elevations could be used as a result indicator for postoperative care policy.

French lyophilized plasma versus normal saline for post-traumatic coagulopathy prevention and correction: PREHO-PLYO protocol for a multicenter randomized controlled clinical trial.

BACKGROUND: Post-trauma bleeding induces an acute deficiency in clotting factors, which promotes bleeding and hemorrhagic shock. However, early plasma administration may reduce the severity of trauma-induced coagulopathy (TIC). Unlike fresh frozen plasma, which requires specific hospital logistics, French lyophilized plasma (FLYP) is storable at room temperature and compatible with all blood types, supporting its use in prehospital emergency care. We aim to test the hypothesis that by attenuating TIC, FLYP administered by prehospital emergency physicians would benefit the severely injured civilian patient at risk for hemorrhagic shock. METHODS/DESIGN: This multicenter randomized clinical trial will include adults severely injured and at risk for hemorrhagic shock, with a systolic blood pressure < 70 mmHg or a Shock Index > 1.1. Two parallel groups of 70 patients will receive either FLYP or normal saline in addition to usual treatment. The primary endpoint is the International Normalized Ratio (INR) at hospital admission. Secondary endpoints are transfusion requirement, length of stay in the intensive care unit, survival rate at day 30, usability and safety related to FLYP use, and other biological coagulation parameters. CONCLUSION: With this trial, we aim to confirm the efficacy of FLYP in TIC and its safety in civilian prehospital care. The study results will contribute to optimizing guidelines for treating hemorrhagic shock in civilian settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02736812. Registered on 13 April 2016. The trial protocol has been approved by the French ethics committee (CPP 3342) and the French Agency for the Safety of Medicines and Health Products (IDRCB 2015-A00866-43).

Reproductive health and pregnancy outcomes among French gulf war veterans.

BACKGROUND: Since 1993, many studies on the health of Persian Gulf War veterans (PGWVs) have been undertaken. Some authors have concluded that an association exists between Gulf War service and reported infertility or miscarriage, but that effects on PGWV's children were limited. The present study's objective was to describe the reproductive outcome and health of offspring of French Gulf War veterans. METHODS: The French Study on the Persian Gulf War (PGW) and its Health Consequences is an exhaustive cross-sectional study on all French PGWVs conducted from 2002 to 2004. Data were collected by postal self-administered questionnaire. A case-control study nested in this cohort was conducted to evaluate the link between PGW-related exposures and fathering a child with a birth defect. RESULTS: In the present study, 9% of the 5,666 Gulf veterans who participated reported fertility disorders, and 12% of male veterans reported at least one miscarriage among their partners after the PGW. Overall, 4.2% of fathers reported at least one child with a birth defect conceived after the mission. No PGW-related exposure was associated with any birth defect in children fathered after the PGW mission. Concerning the reported health of children born after the PGW, 1.0% of children presented a pre-term delivery and 2.7% a birth defect. The main birth defects reported were musculoskeletal malformations (0.5%) and urinary system malformations (0.3%). Birth defect incidence in PGWV children conceived after the mission was similar to birth defect incidence described by the Paris Registry of Congenital Malformations, except for Down syndrome (PGWV children incidence was lower than Registry incidence). CONCLUSION: This study did not highlight a high frequency of fertility disorders or miscarriage among French PGW veterans. We found no evidence for a link between paternal exposure during the Gulf War and increased risk of birth defects among French PGWV children.

Phenotype-Specific Response of Circulating miRNAs Provides New Biomarkers of Slow or Fast Muscle Damage.

Skeletal muscle is a heterogeneous tissue composed of a continuum of contracting fibers ranging from slow-type to fast-type fibers. Muscle damage is a frequent event and a susceptibility of fast-fibers to exercise-induced damage (EIMD) or statins toxicity has been reported. Biological markers of muscle damage such as creatine kinase (CK) are not fiber-type specific and new biomarkers are needed. Some microRNAs (miRNAs) are specific to the muscle tissue, can be found in the extracellular compartment and can rise in the plasma following muscle damage. Our aim was to identify whether a set of circulating miRNAs can be used as fiber-type specific biomarkers of muscle damage in a model of traumatic (crush) injuries induced either in the slow soleus (SOL) or in the fast extensor digitorum longus (EDL) muscles of rats. A subset of miRNAs composed of miR-1-3p, -133a-3p, -133b-3p, 206-3p, -208b-3p, 378a-3p, -434-3p, and -499-5p were measured by RT-PCR in non-injured SOL or EDL muscle and in the plasma of rats 12 h after damage induced to SOL or EDL. MiR-133b-3p, -378a-3p, and -434-3p were equally expressed both in SOL and EDL muscles. MiR-1-3-p and -133a-3p levels were higher in EDL compared to SOL (1.3- and 1.1-fold, respectively). Conversely, miR-206-3p, -208b-3p, and -499-5p were mainly expressed in SOL compared to EDL (7.4-, 35.4-, and 10.7-fold, respectively). In the plasma, miR-1-3p and -133a-3p were elevated following muscle damage compared to a control group, with no difference between SOL and EDL. MiR-133b-3p and -434-3p plasma levels were significantly higher in EDL compared to SOL (1.8- and 2.4-fold, respectively), while miR-378a-3p rose only in the EDL group. MiR-206-3p levels were elevated in SOL only (fourfold compared to EDL). Our results show that plasma miR-133b-3p and -434 are fast-fiber specific biomarkers, while miR-206-3p is a robust indicator of slow-fiber damage, opening new perspectives to monitor fiber-type selective muscle damage in research and clinic.

Severe imported malaria in children in France. A national retrospective study from 1996 to 2005.

BACKGROUNDS: Malaria is a leading cause of imported febrile illnesses in pediatric travelers, but few studies have addressed severe imported pediatric malaria. We aimed to determine the risk factors and the features of imported pediatric severe malaria. METHODS: We conducted a retrospective, descriptive study using the French National Reference Center for Imported Malaria database, in children aged 0-15 years who were hospitalized with a falciparum malaria from January 1st 1996 to December 31th 2005. Uncomplicated and severe cases of falciparum malaria were compared to identify risk factors for severe cases. In the hospitals that reported more than five severe cases during the study period, we evaluated severe cases for prognostic factors and assessed the accuracy WHO criteria for predicting severity. Given the rarity of deaths, adverse outcomes were defined as requiring major therapeutic procedures (MTPs)-e.g., sedation, mechanical ventilation, nasal oxygen therapy, blood transfusions, hemodialysis, fluid resuscitation-or pediatric intensive care unit (PICU) admission. RESULTS: Of 4150 pediatric malaria cases included in the study, 3299 were uncomplicated and 851 (20.5%) were severe. Only one death was recorded during this period. Predictors for severe falciparum malaria were: age <2 years (OR = 3.2, 95% CI = 2.5-4.0, p <0.0001) and a travel in the Sahelian region (OR = 1.7, 95% CI = 1.3-2.0, p = 0.0001). Of 422 severe malaria cases, a stay in a Sahelian region, lack of chemoprophylaxis, age <2 years or thrombocytopenia <100 x 10^3/mm^3 predicted adverse outcomes. Except for the hyperparasitemia threshold of 4%, the main WHO 2000 criteria for severe malaria reliably predicted adverse outcomes. In our study, the threshold of parasitemia most predictive of a poor outcome was 8%. CONCLUSION: In imported pediatric malaria, children younger than 2 years deserve particular attention. The main WHO 2000 criteria for severity are accurate, except for the threshold of hyperparasitemia, which should be revised.

The disablement process: factors associated with progression of disability and recovery in French elderly people.

PURPOSE: To study the factors associated with progression, recovery and death from different grades of disability in elderly people. METHOD: The sample included 3198 participants of the PAQUID ('Personnes Agées QUID') cohort, aged 65 and over and community-dwellers at baseline. Subjects were re-interviewed 1, 3, 5, 8 and 10 years after baseline. A five-state Markov model was used to estimate transition intensities between four grades of disability and toward death. We used a hierarchic scale of disability, which combines basic and instrumental activities of daily living and mobility. Several explanatory variables were investigated: medical, personal and environmental factors. RESULTS: The factors associated with progression and/or no recovery of disability were cardiovascular diseases, stroke and diabetes, low cognition, visual impairment and dyspnoea (for pathologies and impairments), older age, female gender, low educational level (for risk factors), depression (for intra-individual factor) and being married, recent hospitalization and number of drugs (for extra-individual factors). Older age, male gender, tobacco consumption and living in an urban area were associated with mortality. CONCLUSIONS: These findings confirm the independent contribution of each group of variables in the disablement process and stress their different impact on progression of disability or on recovery from different grades of disability.

Is serving in the armed forces associated with tobacco or cannabis initiation? A study of onset sequences before and after joining the French armed forces.

The aim of this study was to evaluate whether joining the military could constitute a predictor of subsequent tobacco or cannabis use. Data from four cross-sectional surveys conducted between 2005 and 2009 in the French armed forces were used to constitute a retrospective cohort (n=4208). A Markov multi-state model was fitted, estimating the probabilities at 1year for all possible pathways between entry into the military profession, tobacco initiation and cannabis initiation. The model was adjusted for current substance use status. Substance initiation appeared to mainly occur before entering the services than during the service period (3.0 times greater likelihood for tobacco and 2.5 times greater likelihood for cannabis). Probabilities of primo-initiation (i.e. starting with that substance) before joining the services were similar for tobacco (3.6% at one year) and cannabis (3.5%). When the study was restrained to current users, although differences were not statistically significant, probabilities of substance primo-initiation during the service period seemed to be greater than before. While the substance use itinerary in the French general population most often begins by tobacco, military seem to have a higher propensity to cannabis primo-initiation, which could traduce more sensation-seeking behaviors. If certain results in our study could also evoke a propensity to substance initiation during the service period, we did not find evidence to verify the hypothesis of a military social inducing effect. Further research is needed to identify behavioral characteristics which could explain increased use during the service period.