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International audience; The ability of cancer cells to develop resistance to anti-cancer drugs, known as multidrug resistance, remains a major cause of tumor recurrence and cancer metastasis. This work explores the double mechanism of toxicity of (D, L-lactide-co-glycolide) acid (PLGA) nanoparticles encapsulating a molybdenum cluster compound, namely Cs(2)[{Mo(6)I(8)}(OOCC(2)F(5))(6)] (CMIF). Hemocompatibility and biocompatibility assays show the safe potential of CMIF loaded nanoparticles (CNPs) as delivery systems intended for tumor targeting for PDT of ovarian cancer with a slight hemolytic activity and a lack of toxicity up to 50 µM CMIF concentration. Cellular uptake shows a preferential uptake of CNPs in lysosomes, which is not interfering with CMIF activity. The double mechanism of CNPs consists in a production of ROS and a DNA damage activity, from 5 µM and 0.5 µM respectively (CMIF concentration). The cellular death mechanism comprises 80% of necrosis and 20% of direct apoptosis by direct DNA damages. This work confirms CMIF loaded PLGA nanoparticles as an efficient and relevant delivery system for PDT.

The diagnosis of malaria in returning travellers could be a challenge in non-endemic settings. We aimed to assess the performance of LAMP in comparison with standard conventional diagnostic methods using real-time-polymerase chain reaction (PCR) in case of discordant results.All travellers returning from malaria-endemic areas who presented to our Emergency Department (ED) from January 2017 to December 2020 with signs and symptoms suggestive for malaria were included. Blood microscopy was the reference diagnostic method applied at our laboratory with LAMP implemented as an additional method to aid in malaria diagnosis. PCR was employed only in case of between test's discordant results. Sensitivity and specificity of microscopy compared to LAMP were calculated with the confidence interval of 95%.Four-hundred and eight patients (55.6% male, median age 42 years) were screened for malaria. The diagnosis was confirmed in 49 cases (12%): 44 cases (90%) caused byIn our non-endemic setting LAMP was able to identify malaria cases with low-level parasitaemia otherwise missed by blood microscopy.

OBJECTIVE Evaluation of relevance and feasibility of universal newborn congenital cytomegalovirus infection (cCMVI) screening in saliva. DESIGN Retrospective, population-based cohort study. SETTING Clamart, France, 2016-2020. POPULATION All neonates born consecutively in our level III maternity unit. METHODS CMV PCR in saliva for all neonates at birth, and, if positive, CMV PCR in urine to confirm or exclude cCMVI. Prospective and retrospective characterisation of maternal infections. ROC curve analysis to assess saliva PCR performances. Acceptability of screening among staff members evaluated by a survey. MAIN OUTCOME MEASURES Number of cCMVI neonates; number of expected and unexpected cCMVI. RESULTS Among 15 341 tested neonates, 63 had cCMVI (birth prevalence of 0.4%, 95% CI 0.3-0.5). In 50% of cases, maternal infection was a non-primary infection (NPI) during pregnancy. cCMVI was expected or suspected (maternal primary infection [PI], antenatal or neonatal signs) in 24/63 neonates (38%), and unexpected in 39/63 neonates (62%). The best CMV saliva threshold to predict cCMVI was 356 (2.55 log) copies/ml [95% CI 2.52 log-3.18 log], with an area under the ROC curve of 0.97. Over 90% of the 72 surveyed staff members reported that the screening was easy and quick. No parent refused the screening. CONCLUSIONS Universal screening for cCMVI with CMV PCR on saliva samples is feasible and highly acceptable to parents and healthcare providers. Over half (62%) of the cases had no prenatal/neonatal signs of cCMVI or a maternal history of CMV infection during pregnancy and would probably not have been diagnosed without universal screening. TWEETABLE ABSTRACT In 62% of congenital cytomegalovirus infection cases, only universal neonatal screening in saliva can detect infection.

Nicola Squillace,1 Elena Ricci,2 Barbara Menzaghi,3 Giuseppe Vittorio De Socio,4 Simone Passerini,5 Canio Martinelli,6 Maria Sabrina Mameli,7 Paolo Maggi,8 Katia Falasca,9 Laura Cordier,5 Benedetto Maurizio Celesia,10 Elena Salomoni,11 Antonio Di Biagio,12 Giovanni Francesco Pellicanò,13 Paolo Bonfanti1 On behalf of the CISAI Study Group1Infectious Diseases Unit ASST-MONZA, San Gerardo Hospital-University of Milano-Bicocca, Monza, Italy; 2“ASIA” Foundation ONLUS, Milan, Italy; 3Unit of Infectious Diseases, ASST della Valle Olona, Busto Arsizio, Italy; 4Department of Internal Medicine 2, Infectious Diseases Unit, “Santa Maria della Misericordia” General Hospital, Perugia, Italy; 5 1st Department of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy; 6Infectious Diseases Unit, Careggi Hospital, Florence, Italy; 7Unit of Infectious Diseases, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy; 8University of Campania “Luigi Vanvitelli”, Napoli, Italy; 9Clinic of Infectious Diseases, Department of Medicine and Science of Aging, University “G. d’Annunzio” Chieti-Pescara, Chieti, Italy; 10Unit of Infectious Diseases, University of Catania, ARNAS Garibaldi, Catania, Italy; 11Infectious Diseases Unit, Santa Maria Annunziata Hospital, Usl centro, Florence, Italy; 12Infectious Diseases, San Martino Hospital Genoa, Genoa, Italy; 13Department of Human Pathology of the Adult and the Developmental Age “G. Barresi”, Unit of Infectious Diseases, University of Messina, Messina, ItalyCorrespondence: Nicola SquillaceInfectious Diseases Unit, Azienda Socio Sanitaria Territoriale di MONZA, San Gerardo Hospital-University of Milano-Bicocca, Via Pergolesi 33, Monza 20900, ItalyTel +390392339588Fax +390392339327Email nicolasquillace74@gmail.comObjective: We aimed to investigate the effect of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on the hepatic safety and metabolic profile.Methods: Consecutive HIV patients, enrolled in the Surveillance Cohort Long-term Toxicity Antiretrovirals/Antivirals (SCOLTA) project, switching from TDF to TAF were included. Changes from baseline (T0) to 6-month follow-up (T1) were evaluated using paired t-test and signed rank test.Results: A total of 190 patients switched from TDF to TAF and had one 6-month follow-up visit. They were 80% male, 74.2% at CDC stage A–B, 93.7% with undetectable HIV-viral load. Mean age was 46.7± 10.7 years, body mass index was 25.0± 3.9 kg/m2, median CD4 cell count was 634 cell/μL (interquartile range [IQR]=439– 900), aspartate aminotransferase (AST) was 23 (IQR=19– 30) IU/L, and alanine aminotransferase (ALT) was 24 (IQR=17– 34) IU/L. At T1, both AST (median=− 1, IQR=− 5– 2 IU/L, P=0.004) and ALT (median=− 2, IQR=− 7– 3 IU/L, P=0.0004) showed a significant decrease. Among 28 patients with ALT > 40 at baseline, reduction was significant both clinically (− 17, IQR=− 32–− 1) and statistically (P=0.0003). Total cholesterol levels (TC) increased (+13.4± 3.8 mg/dL, P=0.0006), as well as HDL-cholesterol (HDL-C) (+3.8± 1.2 mg/dL, P=0.02), LDL Cholesterol (LDL-C) (+7.6± 3.4, P=0.03) and glucose (+4.0± 1.8 mg/dL, P=0.02). D:A:D: and Framingham risk score did not change at 6 months after switch.Conclusion: A significant reduction of liver enzymes was observed after switching from TDF to TAF, especially in subjects with initial level of ALT > 40 IU/L. Glucose, TC, HDL-C, and LDL-C increased, with no effect on cardiovascular risk scores.Keywords: HIV, TDF, TAF, liver enzymes

International audience; Transgender men experience a disharmony between their birth sex and their intimate sense of gender belonging. Gender-affirming hormone therapy and gender-affirming surgery (GAS) are often inherently part of the gender-affirming process. In this context, we should ask whether it is better to keep or remove the uterus. Keeping the uterus and ovaries avoids a surgical procedure and a pubic scar. Furthermore, it preserves fertility and the possibility of carrying a baby. On the other hand, keeping the uterus is often psychologically unbearable for transgender men and the long-term effects of androgens on the uterus and ovaries remain uncertain. Conversely, hysterectomy and oophorectomy are part of the GAS process. New mini-invasive surgery procedures for hysterectomies decrease the risks and limit the likelihood of scars to a minimum. In practice, the data suggest that very few transgender men carry a pregnancy and/or use their oocytes after gender-reaffirming treatment. Clinicians should counsel their transgender men patients about the definitive infertility consequences of hysterectomy and oophorectomy and discuss all fertility preservation options before undertaking GAS. Individualized approaches must be preferred to systematic procedures regarding the personal decision to keep or not keep the uterus and ovaries.

International audience; (1) Background: In a period where systematic screening of CMV during pregnancy is still debated, diagnosis of non primary infection (NPI) remains challenging and an obstacle to systematic screening. Our aim is to report kinetics of serological and molecular CMV markers of NPI. (2) Methods: We identified immunocompetent pregnant women with CMV NPI as women known to be seropositive for CMV before pregnancy who gave birth to cCMV infected infants. We performed CMV-IgG, CMV-IgM, CMV-IgG avidity and CMV PCR retrospectively on sequential serum samples collected during pregnancy. (3) Results: We collected 195 serum samples from 53 pregnant women with NPI during pregnancy. For 29/53 (55%) patients, no markers of active infection were observed (stable IgG titers, negative IgM and negative PCR). CMV PCR was positive in at least one serum for 18/53 (34%) patients and median viral load was 46 copies/mL, IQR (21-65). (4) Conclusions: For more than half of patients with confirmed CMV NPI during pregnancy, available diagnostic tools are liable to fail in detecting an active infection. These should therefore not be used and universal neonatal screening for CMV remains the only way to detect all cCMV infections.

Background Developing robust evidence is a challenge for researchers working with disadvantaged or vulnerable populations. For example, research shows that young people who have transitioned from out-of-home care (OOHC) to independent adulthood often experience poor long-term outcomes. However, evidence for the aetiology of those outcomes is weak due to methodological limitations such as small sample sizes and a lack of longitudinal data. This paper details the protocol for Navigating Through Life, a study that utilises novel research methods to better understand the pathways and outcomes of young people as they leave OOHC in Western Australia (WA). Methods Navigating Through Life is a longitudinal, mixed methods, population-based study. A prospective longitudinal study of young people aged 15–25 years will follow participants’ experiences and outcomes over a two-year period. Quantitative and qualitative data is being collected from participants five times over 2 years, using standardised outcome measures and individual interviews. Outcome measures focus on key dimensions of young people’s lives (e.g., social inclusion, well-being, resilience, self-determination). Interviews examine important influences and the variable contexts into which young people have transitioned from care. In addition, retrospective population-level data for young people transitioning from OOHC will be obtained from linked Western Australian government administrative records. Using a multitude of data sources, analysis will map pathways and outcomes of young people with care experience, and comparisons will be made with other population groups within WA. Discussion Navigating Through Life exemplifies a novel utilisation of multiple data sources to research outcomes for vulnerable and difficult to reach populations, and offers insights for other complex mixed-methods longitudinal studies. Results will provide new and more comprehensive data about specific pathways that may be influential to a range of post-care outcomes. Findings will extend evidence to inform better service-delivery models that improve outcomes and reduce disparities for vulnerable young people.

Methylation profiling has become a mainstay in brain tumor diagnostics since the introduction of the first publicly available classification tool by the German Cancer Research Center in 2017. We demonstrate the capability of this system through an example of a rare case of IDH wildtype glioblastoma diagnosed in a patient previously treated for T-cell acute lymphoblastic leukemia. Our novel in-house diagnostic tool EpiDiP provided hints arguing against a radiation-induced tumor, identified a novel recurrent genetic aberration, and thus informed about a potential therapeutic target.

Surgeons management of osteochondral lesions of the talus (OLT) may be different to the published guidelines because not all treatment recommendations are feasible in every country. This study aimed to assess how OLT are managed worldwide by foot and ankle surgeons. A web-based survey was distributed to the members of 21 local and international scientific societies focused on foot and ankle or sports medicine surgery. Answers with a prevalence greater than 75% of respondents were considered a “main tendency”, whereas where prevalence exceeded 50% of respondents they were considered a “tendency”. A total of 1804 surgeons from 79 different countries returned the survey. The responses to 19 of 28 questions (68%) regarding management and treatment of OLT achieved a main tendency (> 75%) or a tendency (> 50%). Symptoms reported to be most suspicious for OLT were pain on weight-bearing (WB) and after activity (83%), deep localization of the pain (62%), and any history of trauma (55%). 89% of surgeons routinely obtain an MRI, 72% routinely get WB radiographs, and 50% perform a CT scan. When treated surgically, OLTs are managed in isolation by only 7% of surgeons, and combined with ligament repair or reconstruction by 79%; 67% report simultaneous excision of soft-tissue or bony impingements (64%). For lesions less than 10–15 mm in diameter, bone marrow stimulation (BMS) represents the first choice of treatment for 78% of surgeons (main tendency). No other treatment was recorded as a tendency. For lesions greater than 15 mm in diameter no tendencies were recorded. The BMS represented the most preferred treatment being the first choice of treatment for 41% of surgeons. OLT depth had little influence on treatment choice: 71% of surgeons treating small lesions and 69% treating large lesions would choose the same treatment regardless of whether the lesion had a depth lesser or greater than 5 mm. The management of OLT by foot and ankle surgeons from around the world remains extremely varied. The main clinical relevance of this study is that it provides updated information with regard to the management of OLT internationally, which could be used by surgeons worldwide in their decision-making and to inform the patient about available surgical options. Level IV.

Background Exposure to persistent environmental organic pollutants may contribute to the development of obesity among children. Chlordecone is a persistent organochlorine insecticide with estrogenic properties that was used in the French West Indies (1973–1993) and is still present in the soil and the water and food consumed by the local population. We studied the association between prenatal and childhood exposure to chlordecone and the adiposity of prepubertal children. Methods Within the Timoun Mother–Child Cohort Study in Guadeloupe (French West Indies), 575 children had a medical examination at seven years of age, including adiposity measurements. A Structural Equation Modeling approach was used to create a global adiposity score from four adiposity indicators: the BMI z-score, percentage of fat mass, sum of the tricipital and subscapular skinfold thickness, and waist-to-height ratio. Chlordecone concentrations were measured in cord blood at birth and in the children’s blood at seven years of age. Models were adjusted for prenatal and postnatal covariates. Sensitivity analyses accounted for co-exposure to PCB-153 and pp’-DDE. Mediation analyses, including intermediate birth outcomes, were conducted. Results Prenatal chlordecone exposure tended to be associated with increased adiposity at seven years of age, particularly in boys. However, statistical significance was only reached in the third quartile of exposure and neither linear nor non-linear trends could be formally identified. Consideration of preterm birth or birth weight in mediation analyses did not modify the results, as adjustment for PCB-153 and pp’-DDE co-exposures. Conclusion Globally, we found little evidence of an association between chlordecone exposure during the critical in utero or childhood periods of development and altered body-weight homeostasis in childhood. Nevertheless, some associations we observed at seven years of age, although non-significant, were consistent with those observed at earlier ages and would be worth investing during further follow-ups of children of the Timoun Mother–Child Cohort Study when they reach puberty.

In Western countries, Cryptosporidium parvum infection is considered a rare opportunistic parasitic disease, most commonly seen in immunocompromised patients. Although most cases have been described in Acquired ImmunoDeficiency Syndrome (AIDS) patients, an increase of cases in other immunocompromised patients has been noted. We hereby describe the case of two patients from our institution in Northern France with heavily pre-treated multiple myeloma, both of whom underwent allogeneic stem cell transplants, who presented late Cryptosporidium infections while treated on novel agents. These cases illustrate novel examples of infection in multiple myeloma as survival improves and novel treatment approaches are being applied.

Background In a previous article (10.1007/s00701-019-03888-3), preliminary results of a survey, aiming to shed light on the number of surgical procedures performed and assisted during neurosurgery residency in Europe were reported. We here present the final results and extend the analyses. Methods Board-certified neurosurgeons of European Association of Neurosurgical Societies (EANS) member countries were asked to review their residency case logs and participate in a 31-question electronic survey (SurveyMonkey Inc., San Mateo, CA). The responses received between April 25, 2018, and April 25, 2020, were considered. We excluded responses that were incomplete, from non-EANS member countries, or from respondents that have not yet completed their residency. Results Of 430 responses, 168 were considered for analysis after checking in- and exclusion criteria. Survey responders had a mean age of 42.7 ± 8.8 years, and 88.8% were male. Responses mainly came from surgeons employed at university/teaching hospitals (85.1%) in Germany (22.0%), France (12.5%), the United Kingdom (UK; 8.3%), Switzerland (7.7%), and Greece (7.1%). Most responders graduated in the years between 2011 and 2019 (57.7%). Thirty-eight responders (22.6%) graduated before and 130 responders (77.4%) after the European WTD 2003/88/EC came into effect. The mean number of surgical procedures performed independently, supervised or assisted throughout residency was 540 (95% CI 424–657), 482 (95% CI 398–568), and 579 (95% CI 441–717), respectively. Detailed numbers for cranial, spinal, adult, and pediatric subgroups are presented in the article. There was an annual decrease of about 33 cases in total caseload between 1976 and 2019 (coeff. − 33, 95% CI − 62 to − 4, p = 0.025). Variables associated with lesser total caseload during residency were training abroad (1210 vs. 1747, p = 0.083) and female sex by trend (947 vs. 1671, p = 0.111), whereas case numbers were comparable across the EANS countries (p = 0.443). Conclusion The final results of this survey largely confirm the previously reported numbers. They provide an opportunity for current trainees to compare their own case logs with. Again, we confirm a significant decline in surgical exposure during training between 1976 and 2019. In addition, the current analysis reveals that female sex and training abroad may be variables associated with lesser case numbers during residency.

Little data are available on the management of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) We conducted a retrospective study of 100 pregnant women with SARS-CoV-2 infection in 4 obstetric units in the Paris metropolitan area of France during March 12-April 13, 2020 Among patients, 52 (52%) were hospitalized, 10 (10%) in intensive care units (ICUs) Women with higher body mass indexes (BMIs;median 30 7 kg/m(2)) were more likely to be hospitalized in ICUs than other women (median BMI 26 2 kg/m(2)) Women hospitalized in ICUs had lower lymphocyte count at diagnosis (median 0 77 x 10(9) cells/L) than women not hospitalized in ICUs (median lymphocyte count 1 15 x 10(9) cells/L) All women requiring oxygen >5 L/min were intubated Clinical and laboratory evaluation of SARS-CoV-2-positive pregnant women at the time of diagnosis can identify patients at risk for ICU hospitalization

Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic1. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes1. Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a-C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a-C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.

Background: Both the percutaneous technique with arthroscopic assistance, also known as arthroscopic Broström (AB), and the arthroscopic all-inside ligament repair (AI) are widely used to treat chronic lateral ankle instability. The aim of this study was to compare the clinical outcomes of these 2 arthroscopic stabilizing techniques. Methods: Thirty-nine consecutive patients were arthroscopically treated for chronic ankle instability by 2 different surgeons. The AB group comprised 20 patients with a mean age of 30.2 (range, 18-42) years and a mean follow-up of 19.6 (range, 12-28) months. The AI group comprised 19 patients with a mean age of 30.9 (range, 18-46) years and mean follow-up of 20.7 (range, 13-32) months. Functional outcomes using the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score and visual analog pain scale (VAS) were assessed pre- and postoperatively. Range of motion (ROM) and complications were recorded. Results: In both groups the AOFAS and VAS scores significantly improved compared with preoperative values ( P < .001) with no difference ( P > .1) between groups. In the AB group the mean AOFAS score improved from 67 (range, 44-87) to 92 (range, 76-100) and the mean VAS score from 6.4 (range, 3-10) to 1.2 (range, 0-3). In the AI group the mean AOFAS score changed from 60 (range, 32-87) to 93 (range, 76-100) and the mean VAS score from 6.1 (range, 4-10) to 0.8 (range, 0-3). At the final follow-up 8 complications (40%) were recorded in the AB group. In the AI group 1 complication (5.3%) was observed ( P < .05). Conclusion: Both the AB and AI techniques are suitable surgical options to treat chronic ankle instability providing excellent clinical results. However, the AB had a higher overall complication rate than the AI group, particularly involving a painful restriction of ankle plantarflexion and neuritis of the superficial peroneal nerve. Level of Evidence: Level III, retrospective comparative study.

Purpose: This study compared the in-the-moment experiences among mothers of children with Autism Spectrum Disorders (ASD) by their household status (i.e., single versus coupled) and region of residence (i.e., regional versus major city area).Methods: An experience sampling method was employed to collect data, and a total of 40 mothers used an iOS device to record activity types and in-the-moment experiences for one week during school term. Mann-Whitney U test and multilevel analysis were conducted to compare the experiences of these mothers.Results: The analyses found the following results: 1) mothers spent most time in childcare and least time in self-care activities; 2) coupled mothers were more likely to feel supported; 3) coupled mothers were less likely to feel supported in domestic tasks; 4) mothers from major city were more likely to feel challenged in self-care activities; and 5) mothers from major city were more likely to feel supported in productivity tasks.Conclusion: Limited but significant differences between single and coupled mothers, as well as mothers from regional and major city areas, were found. Future research direction and service provisions were suggested.Implications for rehabilitationThis study shows that all mothers spent the most time on childcare and the least amount of time on self-care activities.In-the-moment experiences between single and coupled mothers, as well as mothers from major cities and mothers from regional areas, differ somewhat; however, this study builds evidence to support that these mothers' experiences are similar.The result of the study indicates that single mothers require extra support as they carry similar levels of responsibilities as coupled mothers, but without the support of a partner.Promoting a sense of control may assist all mothers to fully engage in parenting activities.

Research question The study aimed to evaluate the percentage of oocyte donors who regretted their donation at least 3 years later. Design Between December 2018 and January 2019, this single-centre study sought to contact by telephone all women who had donated oocytes during the 6-year period from 2010 to 2015 at the Lille Centre for the study and storage of eggs and spermatozoa (CECOS). Results Among 118 women, 72 responded to the questionnaire by telephone and were included in the study. The response rate was 61%. No woman regretted having donated an oocyte, and 89% said that they would do it again in the same situation. The survey distinguished two types of donors: ‘relational’ (58%) and ‘altruistic’ (42%); some of their responses differed. Ninety per cent of the women had talked about the donation to family and friends. Among them, 74% felt supported by their family and friends, and 72% by their partner. The donation was something that 76% of the women sometimes thought about; 83% felt that this donation was something useful that they had accomplished. Finally, most donors felt that oocyte donation should remain unremunerated and anonymous. Conclusions None of the donors we interviewed regretted their donation. In France, the current principles governing this donation appear satisfactory to oocyte donors.

Objective: To evaluate various signal intensity ratios in isolated congenital diaphragmatic hernia (CDH) and to compare their potential in predicting survival with that of the observed-to-expected (O/E) ratio of total fetal lung volume (TFLV) using magnetic resonance imaging (MRI) measurements. Our second objective was to evaluate the impact of operator's experience in comparing the prediction of postnatal survival by O/E-TFLV.Methods: In 75 conservatively managed CDH fetuses and in 50 who underwent fetoscopic endoluminal tracheal occlusion (FETO), the fetal lung-to-amniotic fluid, lung-to-liver, lung-to-muscle, lung-to-spinal fluid signal intensity ratios, respectively LAFSIR, LLSIR, LMSIR, and LSFSIR, were measured, as was O/E-TFLV. Receiver operating characteristic (ROC) curves were constructed and used to compare the various signal intensity ratios with O/E-TFLV in the prediction of postnatal survival. In 72 MRI lung volumes assessed by the referring radiologists in Paris and Lille and secondarily by our expert radiologist in Brussels (M.M.C.) using the same MRI examinations, ROC curves were constructed and used to compare the value of O/E-TFLV determined by the two centers in the prediction of postnatal survival.Results: In the total cohort of CDH fetuses, O/E-TFLV and LLSIR were predictive of postnatal survival whereas in the conservatively managed group O/E-TFLV, LLSIR, and LMSIR predicted postnatal survival. O/E-TFLV predicted postnatal survival far better than the signal intensity ratios: area under the ROC curve for prediction by O/E-TFLV in the total cohort was 0.866 (p

Purpose Working with students with emotional behavioral disorders is a challenging area of speech-language pathology practice. In this study, we compare and profile the narrative discourse, structural language, and social communication characteristics of adolescents attending behavioral support and mainstream schools. We also examine relationships between narratives, structural language, social communication, and behavior. Method Fifty-four students aged between 12 and 16 years participated. Twenty-seven students were from 3 Australian government Schools for Specific Purposes for students with behavioral difficulties, and 27 typically developing students were from a mainstream, government school. Students were matched for age and closely matched for sex and socioeconomic status. All students completed 3 communication assessments: oral narrative, structural language, and social communication skills. Teachers were asked to complete 2 behavioral questionnaires. Results Students in behavioral schools had significant difficulties generating narratives. Their structural language and overall social communication skills were also significantly poorer than their mainstream peers. One third of the behavioral group experienced significant difficulties across all 3 of these communication areas. Externalizing behavior was significantly related to narrative, structural language, and social communication only when the data were pooled across both groups. Conclusions Language and social communication difficulties were evident in adolescents who attend alternative school settings—behavioral schools. These findings confirm the need for speech-language pathologists to be engaged in specialist behavioral schools and provide impetus to service providers, speech-language pathologists, and educators to address relationships between behavior and communication ability.

Introduction Pregnant women are at increased risk for COVID-19, and COVID-19 vaccine is the most promising solution to overcome the current pandemic. This study was conducted to evaluate pregnant women’s perceptions and acceptance of COVID-19 vaccination. Materials & methods A cross-sectional study was conducted from February 18 to April 5 2021. An anonymous survey was distributed in 7 French obstetrics departments to all pregnant women before a prenatal visit. All pregnant women attending a follow-up consultation were asked to participate in the study. An anonymous web survey was available through a QR code and participants were asked whether or not they would agree to be vaccinated against SARS-CoV-2, and why. The questionnaire included questions on the patients’ demographics and their knowledge of COVID-19 vaccines. Results Of the 664 pregnant women who completed the questionnaire, 29.5% (95% CI 27.7; 31.3) indicated they would agree to be vaccinated against COVID-19. The main reason for not agreeing was being more afraid of potential side effects of the SARS-CoV-2 vaccine on the fetus than of COVID-19. Factors influencing acceptance of vaccination were: being slightly older, multiparity, having discussed it with a caregiver and acceptance of the influenza vaccine. Discussion Nearly one-third of pregnant women in this population would be willing to be vaccinated. In addition to studies establishing fetal safety, public health agencies and healthcare professionals should provide accurate information about the safety of COVID-19 vaccines.

Although lithium is widely used in current practice to treat bipolar disorder (BD) and treatment-resistant major depressive disorder (MDD) among older adults, little is known about its efficacy and tolerability in this population, which is generally excluded from randomized clinical trials. The objective of this study was to evaluate the efficacy and tolerability of long-term use of lithium among older adults with BD and MDD.Data from the Cohort of individuals with Schizophrenia and mood disorders Aged 55 years or more (CSA) were used. Two groups of patients with BD and MDD were compared: those who were currently receiving lithium versus those who were not. The effects of lithium on psychiatric (i.e., depressive symptoms severity, perceived clinical severity, rates of psychiatric admissions in the past-year), geriatric (overall and cognitive functioning) and physical outcomes (i.e., rates of non-psychiatric medical comorbidities and general hospital admissions in the past-year) were evaluated. All analyses were adjusted for age, sex, duration of disorder, diagnosis, smoking status, alcohol use, and use of antipsychotics, antiepileptics or antidepressants.Among the 281 older participants with BD or MDD, 15.7% were taking lithium for a mean duration of 12.5(SD = 11.6) years. Lithium use was associated with lower intensity of depressive symptoms, reduced perceived clinical global severity and lower benzodiazepine use (all p 0.05), without being linked to greater rates of medical comorbidities, except for hypothyroidism.Data were cross-sectional and data on lifetime history of psychotropic medications was not assessed.Our results suggest that long-term lithium use may be efficient and relatively well-tolerated in older adults with BD or treatment-resistant MDD.

International audience; BACKGROUND: Chlordecone is an organochlorine that was largely used as an insecticide to control a species of root borers, the Banana weevil (Cosmopolites sordidus), in the French West Indies, Guadeloupe and Martinique. Its molecules have been shown to be very persistent in the environment as pollution in soils leading to contamination of water sources and foodstuff will last for several decades. Our team previously reported associations between prenatal chlordecone exposure and poorer fine motor development at two points in time during infancy. OBJECTIVE: To document whether effects of prenatal exposure to chlordecone previously reported persists until middle-childhood, and whether deleterious effects are observed in domain of visual processing. Associations with postnatal exposure and sex-specific vulnerabilities were also investigated. METHODS: We examined 410 children from the TIMOUN mother-child cohort in Guadeloupe at 7 years of age. Concentrations of chlordecone and other environmental contaminants were measured in cord- and children’s blood at age 7 years. Fine motor function was assessed using the Bruininks Oseretsky Test of Motor Proficiency Second Edition (BOT-2). The Computerized Adaptive Testing System (CATSYS) was used to evaluated postural hand tremor, while non-verbal visuospatial processing was measured using the Stanford Binet copying (S-B copying) test. We used adjusted multiple linear regressions to test the relationship between children’s scores and both continuous and categorical blood chlordecone concentrations, adding child sex as a moderator in continuous models. RESULTS: Cord chlordecone concentrations are associated with a regular frequency pattern of subtle hand tremors in both hands, and not related to visual processing and fine motor precision. Chlordecone concentrations in blood sample collected at testing time are associated with poorer visual processing when copying geometric figures, but not significantly related to poorer fine movement precision in tasks requiring pencil, scissors and paper. No sex-specific vulnerability was reported in any of the outcomes. CONCLUSIONS: These results at school aged expand those previously reported in the same cohort during infancy at age 7- and 18 months, and corroborate the negative effects of chlordecone exposure on fine motor function in absence of intoxication. Our results support the need to continue public health efforts aimed at reducing exposure especially among women of child bearing age and young children.

Background Study aim was to evaluate the safety and durability of darunavir/cobicistat (DRV/c) in a real life setting. Methods Multicentre prospective cohort study performed in the context of SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals). Patients were evaluated at baseline, week 24 and 48. Changes were evaluated using the paired t test or signed rank test. The multivariable analysis was performed using a general linear model, after ranking of not normally distributed variables. Results A total of 249 patients were included, 72 (29%) were in DRV/c-based dual therapies (DT). Hypercholesterolemia, HC, (total cholesterol (TC) ≥ 200 mg/dL or low density-C (LDL-C) ≥ 130 or statin use) was present in 121 (48.6%) and hypertriglyceridemia, (triglycerides (TG) ≥ 200 mg/dl or fibrate use) in 41 (16.5%) patients. Blood lipid profile did not change significantly in either the global population or patients with HC. After a median observation of 17 months (IQR 13–20), 59 (25.3%) patients discontinued DRV/c, of which 13 were in DT. The durability DT resulted higher than that of triple therapy (log-rank test p = 0.01). Main reasons for stopping DRV/c were simplification (15 patients), adverse events (13 patients), planned discontinuation for treatment initiation with DAA (4 patients), treatment failure (2 patients); death (2 patients), other causes (10 patients). Twenty-six were lost to follow-up. Conclusions DRV/c was safe and well tolerated. Dual therapies showed a better profile of tolerability and a longer durability compared to triple therapies.

There is evidence that regular exercise training has the potential to improve psychological well-being among cancer survivors. However, limited findings are available for individuals with high-grade glioma (HGG; WHO grade III and IV) after neurosurgery and undergoing radiochemotherapy. Given this, endurance and strengths training were employed to investigate their impact on symptoms of depression, feelings of stress and anxiety, fatigue, insomnia, and physical fitness, compared to an active control condition.A total of 29 patients (M = 52.07, SD = 12.45, 55.2% women) participated in this randomized controlled trial (RCT). After neurosurgical treatment and during adjuvant radiotherapy and chemotherapy or combined radiochemotherapy, patients were randomly assigned to the following conditions: Endurance training (n = 10); strengths training (n = 11); active control condition (n = 8). At baseline, three weeks and six weeks later at the end of the study physical fitness was objectively measured with a 6-min walk test (6MWT) and a handgrip test. Participants completed a series of questionnaires covering sociodemographic information, symptoms of depression, stress, anxiety, fatigue, and insomnia. Further, experts rated participants' severity of symptoms of depression.Over time and compared to the strengths and active control condition, self-rated symptoms of depression, state and trait anxiety, stress and insomnia decreased in the endurance condition. Over time and compared to the endurance and active control condition, no changes on symptoms of depression, anxiety, stress, or insomnia were observed in the strengths condition. Over time and compared to the endurance and strengths condition, symptoms of depression (self-ratings), stress, insomnia and fatigue decreased in the active control condition. Fatigue increased in both exercising conditions. Over time and irrespective from the study condition, physical fitness did neither improve nor decrease.The pattern of results suggests that endurance training and an active control condition improved dimensions of depression, stress, and anxiety, while mere strengths training appeared to neither improve, nor decrease dimensions of psychological functioning. Further, exercise interventions did not change physical fitness, but increased fatigue. Overall, endurance training and an active control condition appeared to favorably impact on psychological well-being among patients with high-grade glioma after neurosurgery and undergoing radiochemotherapy.

OBJECTIVE: To evaluate the morbidity and mortality of neonates with left-sided isolated congenital diaphragmatic hernia (CDH) according to gestational age at delivery. METHODS: This was a retrospective study of fetuses diagnosed prenatally with isolated left-sided CDH that were delivered in the University Hospitals of Antoine Béclère-Bicêtre and Leuven between 1 January 2010 and 31 December 2018. The Kaplan-Meier method was used to calculate cumulative survival at 28 days after birth according to gestational age at delivery. The association between gestational age at delivery, as a continuous variable, and survival at 28 days was modeled using a fractional polynomial. Adjustment for position of the liver, management center and mode of delivery was performed. The association was also evaluated according to the severity of CDH, as defined by the observed-to-expected lung-to-head ratio (o/e-LHR), which was classified as severe (o/e-LHR 45%). RESULTS: We included 213 fetuses with isolated left-sided CDH, with a median gestational age at delivery of 38 + 2 weeks (interquartile range, 37 + 0 to 39 + 1 weeks). The survival rates at 28 days and at 6 months were 66.7% (142/213) and 64.3% (137/213), respectively. Kaplan-Meier analysis showed a higher survival rate at 28 days for babies delivered between 37 + 0 and 38 + 6 weeks than for those delivered at or after 39 + 0 weeks (log-rank test, P

Introduction Primary care provider encounters are associated with health and well-being; however, limited evidence guides optimal primary care provider rate of visit, referred to as encounter cadence. This study measures associations between primary care provider encounter cadence and diabetes outcomes among individuals newly diagnosed with type 2 diabetes mellitus. Methods In this retrospective cohort study, 7,106 people enrolled in Medicare Advantage and newly diagnosed with type 2 diabetes mellitus between July 1, 2012 and June 30, 2013 were identified and followed for 36 months. Two methods measured primary care provider encounter cadence: total primary care provider encounters (frequency) and quarters with primary care provider encounter (regularity). Logistic regression measured relationships between primary care provider encounter cadence and non-insulin diabetes medication adherence, HbA1c control, emergency department visits, and inpatient admissions. Non-insulin diabetes medication adherence was defined according to the National Committee for Quality Assurance, Healthcare Effectiveness Data and Information Set specifications and measured using healthcare claims data. Post-hoc models examined adherence and diabetes control among those nonadherent (n=5,212) and with noncontrolled HbA1c (n=326) during the encounter/cadence period. Data were extracted and analyzed in 2017. Results Adjusted models indicated that both frequency (AOR=1.08, 95% CI=1.06, 1.10) and regularity (AOR=1.18, 95% CI=1.13, 1.22) of primary care provider encounters were associated with increased odds of adherence. Post-hoc analyses indicated that more frequent (AOR=1.12, 95% CI=1.10, 1.15) and regular (AOR=1.27, 95% CI=1.22, 1.33) primary care provider encounters were associated significantly with adherence and were associated directionally with HbA1c control. Conclusions More frequent and regular primary care provider encounters are associated with an increased likelihood of non-insulin diabetes medication adherence. These findings contribute to data needed to establish evidence-based guidelines for primary care provider encounter cadence for those newly diagnosed with type 2 diabetes mellitus.

Chlordecone is an organochlorine pesticide that was extensively used to control the banana root borer population in the French West Indies until 1993. Its persistence in soil has led to widespread pollution of the environment, and human beings, including pregnant women, are still exposed to this chemical. High levels of exposure to chlordecone during gestation have been shown to cause congenital anomalies, including undescended testes in rodents. We assessed the associations between chlordecone concentrations in maternal and cord plasma and the risk of congenital anomalies in the Timoun Mother-Child Cohort Study (2004-2007) that included 1068 pregnant women in Guadeloupe. Odds ratios were estimated using unconditional logistic regression analysis, controlling for confounding factors. The median plasma concentrations in maternal and cord plasma were 0.39 μg/L and 0.20 μg/L, respectively. Thirty-six children were diagnosed with malformations according to the European Registration of Congenital Anomalies guidelines and 25 with undescended testes. There was no association between maternal or cord plasma concentration of chlordecone and the risk of overall malformations nor undescended testes. These results suggest that prenatal exposure to the currently observed environmental levels of chlordecone in French West Indies does not increase the risk of birth defects.

This study aimed to explore the appropriateness of an ICT intervention, the Therapeutic Outcomes by You application (TOBY app), from the perspectives of the parents. Parental experiences of twenty-four parents of a child with ASD who had participated in a three-month trial using the TOBY app were collected using semi-structured interviews. Thematic analysis was conducted and themes were mapped against an appropriateness framework. Collectively, parents felt the TOBY app was relevant and important to them and their children’s needs, while expressing partial support of the TOBY app as: a positive experience for them and their children, beneficial for them and their children, a socially and ecological valid intervention, and an intervention that supported change and continuation in the skills learnt.

Background: Immunity to rubella-virus (RV) is commonly determined by measuring specific IgG (RV-IgG). However, RV-IgG results may be different and even discordant, depending on the assay used. Cell-mediated immunity is not routinely investigated for diagnostic purposes. Objectives: Our aim was to investigate humoral and cellular immunity of women with negative or equivocal RV-IgG before, and after post-partum vaccination. Study design: A total of 186 pregnant women were included in the study. During pregnancy, humoral immunity was investigated with two RV-IgG immunoassays, an immunoblot and a T-cell mediated immunity test. In the post-partum vaccination period, measuring RV-IgM and RV-IgG avidity allowed us to determine whether women raised a primary or a secondary immune response. Results: Before vaccination, 52.2% women, supposed to be susceptible, had positive anti-E1 RV-IgG indicating strong evidence of previous exposure to RV. All (100%) pregant women who had a positive immunoblot before immunization raised a secondary immune response to vaccination, and 96.8% who had a negative immunoblot before immunization, raised a primary immune response to vaccination. All women who raised a primary immune response after vaccination had negative anti-E1 RV-IgG and negative cell-mediated immunity. Discussion: These results indicate that individuals can have evidence of protective immunity against rubella despite negative RV-IgG.

Purpose: Given the barriers that inconsistent terminology poses for the Speech-Language Pathology (SLP) profession, this study aimed to develop an agreed-upon taxonomy with well-defined categories for describing language assessment practices for children. Method: A taxonomy with illustrative terms for describing assessments across four aspects (modality/domain, purpose, delivery and form) was developed with reference to contemporary literature. In a three round Delphi study, SLPs with expertise in child language were asked to indicate their level of agreement with the taxonomy and provide feedback. Participants were also asked to apply the taxonomy by categorising assessments presented in case studies. Result: A total of 55 participants completed round one, while 43 and 32 completed rounds two and three respectively. Agreed consensus with the taxonomy was achieved in both rounds one and two, with at least 88% of participants agreeing with each aspect and 100% agreeing with the overall structure. In round three, an agreement was reached on 7/10 components for one case study and 4/10 for the other. Conclusion: The development of this taxonomy represents a significant step towards providing detailed terminology for describing language assessments. Future research is needed to investigate implementation strategies to facilitate consistent application of the taxonomy by SLPs.

Background/aim Increased age and cognitive decline have been linked to difficulties with activities of daily living (ADL) and instrumental activities of daily living (IADL). Cognitive decline can often be signalled by complaints about one's cognition, such as memory. With older Australians living longer, there is an increasing proportion of the population at risk of declined performance in daily tasks. The aim of this study was to identify if subjective memory complaints in later life among older women predict changes in independence in performing ADL and IADL. Methods Data were from 3721 women born 1921-1926, who completed Surveys 4-6 of the Australian Longitudinal Study on Women's Health. Memory complaints and difficulties on ADL were measured at each survey, using the Memory Complaint Questionnaire and 16 questions regarding specific ADL. Latent growth modelling examined correlations between initial scores on each measure, changes in measures, and the association between memory complaints and changes in ADL and IADL. Results There was a significant association between baseline scores for subjective memory difficulty and baseline ADL and IADL scores. Initial memory difficulty was also associated with increase in ADL and IADL difficulty. Conclusions Subjective memory complaints may be a risk factor for decline in performance on ADL. Attention to these concerns may be important in identifying functional decline in older age.

Background Chronic ankle instability (CAI) is the main complication of ankle sprains and requires surgery if non-operative treatment fails. Surgical ankle stabilisation techniques can be roughly classified into two groups, namely, repair involving retensioning and suturing of the anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) and reconstruction using a tendon graft. Arthroscopic repair and reconstruction techniques for CAI have been introduced recently. The objective of this prospective multicentre study was to assess the feasibility, morbidity, and short-term outcomes of these arthroscopic ankle-stabilisation techniques. Material and methods Consecutive patients scheduled for arthroscopic treatment of CAI were included prospectively. Of the 286 included patients, 115 underwent ligament repair and 171 ligament reconstruction. Mean follow-up was 9.6 months (range, 6–43 months). We recorded the AOFAS and Karlsson scores, patient satisfaction, complications, and time to return to sports. Results The overall patient satisfaction score was 8.5/10. The AOFAS and Karlsson scores improved significantly between the pre- and postoperative assessments, from 62.1 to 89.2 and from 55 to 87.1, respectively. These scores were not significantly different between the groups treated by repair and by reconstruction. Neurological complications occurred in 10% of patients and consisted chiefly in transient dysesthesia (with neuroma in 3.5% of patients). Cutaneous or infectious complications requiring surgical revision developed in 4.2% of patients. Discussion Arthroscopic treatment is becoming a method of choice for patients with CAI, as it allows a comprehensive assessment of the ligament lesions, the detection and treatment of associated lesions, and repair or reconstruction of the damaged ligaments. These simple, reliable, and reproducible arthroscopic techniques seem as effective as conventional surgical techniques. The rate of cutaneous complications is at least halved compared to open surgery. Conclusion Arthroscopic ankle stabilisation repair and reconstruction techniques hold considerable promise but require further evaluation to better determine the indications of repair versus reconstruction and to obtain information on long-term outcomes.

Background A high number of thrombotic complications have been reported in critically ill patients with coronavirus disease 2019 (COVID-19) and appear to be related to a hypercoagulable state. Evidence regarding detection, management, and monitoring of COVID-19–associated coagulopathy is still missing. We propose to describe the thrombus viscoelastic properties to investigate the mechanisms of hypercoagulability in patients with COVID-19. Methods Thromboelastography (TEG) was performed in 24 consecutive patients admitted to a single intensive care unit for COVID-19 pneumonia, and 10 had a second TEG before being discharged alive from the intensive care unit. Results Compared with a group of 20 healthy participants, patients with COVID-19 had significantly decreased values of reaction time, coagulation time, and lysis index and increased values of α angle, maximum amplitude, clot strength, and coagulation index. Velocity curves were consistent with increased generation of thrombin. These values persisted in surviving patients despite their good clinical course. Discussion In patients with COVID-19, TEG demonstrates a complex and prolonged hypercoagulable state including fast initiation of coagulation and clot reinforcement, low fibrinolysis, high potential of thrombin generation, and high fibrinogen and platelet contribution. The antithrombotic strategy in patients with COVID-19 during intensive care hospitalisation and after discharge should be investigated in further studies.

International audience; BACKGROUND: Maternal occupational exposure to organic solvents during pregnancy has been associated with decreased visual function in offspring. Glycol ethers (GEs) belong to oxygenated solvents and are widely used both in occupational and domestic contexts. OBJECTIVES: We aimed to assess associations between prenatal GEs exposure and contrast sensitivity in children. METHODS: Six GE alkoxy carboxylic acidic metabolites (methoxyacetic acid [MAA], ethoxyacetic acid [EAA], ethoxyethoxyacetic acid [EEAA], butoxyacetic acid [BAA], phenoxyacetic acid [PhAA], and 2-methoxypropionic acid [2-MPA]) were measured in first morning void urine samples collected from 220 early-pregnancy women, in the mother-child PELAGIE cohort (France). Trained investigators administered the Functional Acuity Contrast Test (FACT) to the 6-year-old children, providing scores for 5 spatial frequencies (1.5-18 cycles per degree (cpd)). We standardized biomarker urinary concentrations on urine sampling conditions. Values below the LOD were imputed based on log-normal distribution, generating five datasets for multiple imputation. Linear regression models were adjusted for potential confounders. RESULTS: GE metabolites were detected in 70-98% of maternal urine samples. Phenoxyacetic acid (PhAA) had the highest median concentration (0.33 mg/L), and 2-methoxypropionic acid (2-MPA) the lowest (0.01 mg/L). Children with higher prenatal PhAA concentrations had poorer FACT scores at various spatial frequencies (fourth vs. first quartile: β(18cpd) = -0.90 (95% confidence interval CI = -1.64, -0.16), β(12cpd) = -0.92 (95%CI = -1.55, -0.29) and β(1.5cpd) = -0.69 (95%CI = -1.19, -0.20)). The 2-MPA log-scale concentration was negatively associated with the FACT score at the 3-cpd stimulus. DISCUSSION: PhAA is the metabolite of ethylene glycol monophenyl ether present in many cosmetics. 2-MPA is the metabolite of an isomer of propylene glycol methyl ether commonly present in household and industrial cleaning products. Although evidence of biological plausibility is lacking, the study suggests adverse impact of ubiquitous prenatal exposure to some GE on visual functioning among children.

Peer-mediated interventions (PMIs) are often used to support children with autism spectrum disorder (ASD) to develop social skills. However, more investigation is needed to better understand the role of peers as both intervention recipients and models. Sixty-five typically developing peers who participated in a PMI for children with ASD were investigated using a randomised control trial. Play sessions of the dyads were scored using the Test of Playfulness. Results showed a significant moderate intervention effect for the peers from pre- to post-intervention; outcomes for children with ASD were not influenced by peer characteristics; and, the children demonstrated a similar pattern of play interaction. Implications for practice are discussed.Clinical Trials Registry Australian New Zealand Clinical Trials Registry, https://www.anzctr.org.au/ (ACTRN12615000008527; Universal Trial Number: U1111-1165-2708).

Background Prenatal care providers will play an important role in the acceptance of SARS-Cov-2 vaccination for pregnant women. Objective To determine the perceptions of French prenatal care providers: midwives, general practitioners (GPs) and obstetricians and gynaecologists (Ob-Gyn) regarding SARS-CoV-2 vaccination during pregnancy. Study design An anonymous online survey was sent to members of French professional societies representing prenatal practitioners. The participants were asked to answer questions on their characteristics and give their opinions of the SARS-CoV-2 vaccine for themselves and women who are pregnant or willing to become pregnant. Results Access to the survey was opened from January 11th, 2021, to March 1st, 2021. A total of 1,416 responses were collected from 749 Ob-Gyn, 598 midwives and 69 GPs. Most respondents (86.7% overall, 90.4% for Ob-GYN, 81.1% for GPs and 80.1% for midwives) agreed to receive the SARS-CoV-2 vaccine. Vaccination against SARS-CoV-2 would be offered to pregnant women by 49.4% 95%CI [48.1–50.8] of the participants. Midwives were less likely to recommend vaccination than GP and Ob-Gyn (37.5%, 50.7% and 58.8%, respectively). The multinomial logistic regression revealed that being an obstetrician, working in a group, usually offering a flu vaccine and wanting to be vaccinated against SARS-CoV-2 were positively associated with considering pregnant women for SARS-CoV-2 vaccination. Conclusion Most French prenatal healthcare providers are favourable towards vaccinating pregnant women, but a large minority express reservation. More evidence on safety and involvement by professional organisations will be important to encourage the access of pregnant women to vaccination against SARS-CoV-2.

IntroductionDespite renewed commitment to universal health coverage and health system strengthening (HSS) to improve access to primary care, there is insufficient evidence to guide their design and implementation. To address this, we conducted an impact evaluation of an ongoing HSS initiative in rural Madagascar, combining data from a longitudinal cohort and primary health centres.MethodsWe carried out a district representative household survey at the start of the HSS intervention in 2014 in over 1500 households in Ifanadiana district, and conducted follow-up surveys at 2 and 4 years. At each time point, we estimated maternal, newborn and child health coverage; economic and geographical inequalities in coverage; and child mortality rates; both in the HSS intervention and control catchments. We used logistic regression models to evaluate changes associated with exposure to the HSS intervention. We also estimated changes in health centre per capita utilisation during 2013 to 2018.ResultsChild mortality rates decreased faster in the HSS than in the control catchment. We observed significant improvements in care seeking for children under 5 years of age (OR 1.23; 95% CI 1.05 to 1.44) and individuals of all ages (OR 1.37, 95% CI 1.19 to 1.58), but no significant differences in maternal care coverage. Economic inequalities in most coverage indicators were reduced, while geographical inequalities worsened in nearly half of the indicators.ConclusionThe results demonstrate improvements in care seeking and economic inequalities linked to the early stages of a HSS intervention in rural Madagascar. Additional improvements in this context of persistent geographical inequalities will require a stronger focus on community health.

Background: Madagascar has one of the highest rates of stunting and at-risk child development in the world:50% of Malagasy children have moderate to severe stunting. In 2016, a new 10 year National Nutrition Action Plan (PNAN III), supported by the World Bank, was initiated to help address stunting and developmental delay. PIVOT, a health care NGO operating in collaboration with the MOH, conducts a longitudinal study, the IHOPE, to assess the population level impact of their collaborative health system strengthening activities on the rural district of Ifanadiana in southeastern Madagascar. We report factors associated with risk to developmental delay in children ages 3 and 4 years old in Ifanadiana district in 2016. Methods: The household survey data are from a cross-sectional analysis of a one wave of panel data in 2016, at the time of the initiation of PNAN III. Women ages 15 to 49 were interviewed, using the Multiple Indicator Cluster Survey (MICS) Early Child Development Indicator (ECDI) module, which includes questions for physical, socio-emotional, learning and literacy/numeracy domains. ECDI data were analyzed using standardized z scores for relative relationships. We assessed 2 outcomes: at risk for delayed development compared to an international standard, and lower development than peers if ECDI z scores were

The lateral ligament complex of the ankle has been extensively studied. Recently an anatomical study described a connection between anterior talofibular ligament inferior fascicle (ATFLif) and calcaneofibular ligament (CFL). The applicability and the mechanical role of these connections have not yet been studied and need to be clarified. The purpose of this study is to evaluate the connection between ATFLif and CFL through a dynamic measurement analysis.An anatomical study was performed in 13 fresh-frozen below-the-knee ankle specimens. Each specimen was dissected in a protocolized manner until the lateral ligaments were exposed. A complete injury to both ATFL's fascicles was created in the proximal third of the ligament. A displacement transducer specifically design was inserted in the CFL and in the lateral part of the calcaneus to test its lengthening. A traction of 1 kg weight (9.8 N) was applied to ATFLif while the transducer measured the lengthening that this force created in the CFL.A total of 13 ankle specimens were carefully dissected. One specimen with signals of a prior traumatic injury of the ATFLif was excluded. A total of 12 specimens were included, 7 females and 5 males with an average age of 74 years (52-88 years). The right ankle was dissected in 6 specimens. ATFL was identified as a two-fascicled ligament in all cases. The fibers connecting the ATFLif and CFL were observed in all specimens. The displacement transducer showed lengthening in the CFL in all measurements with a median of 0.59 mm (SD ± 0.34).Connecting fibers between ATFLif and CFL are robust enough to transmit tension from one structure to the other. In the case of associated proximal lesions of the ATFLif and CFL, ligaments repair with a single suture may be considered. This can be applied in surgical procedures in patients with lateral ankle instability.

International audience; Chlordecone was used intensively as an insecticide in the French West Indies. Because of its high persistence, the resulting contamination of food and water has led to chronic exposure of the general population as evidenced by its presence in the blood of people of Guadeloupe, in particular in pregnant women and newborns, and in maternal breast milk. Chlordecone is recognized as a reproductive and developmental toxicant, is neurotoxic and carcinogenic in rodents, and is considered as an endocrine-disrupting compound with well-established estrogenic and progestogenic properties both in vitro and in vivo. The question arises of its potential consequences on child neurodevelopment following prenatal and childhood exposure, in particular on behavioral sexual dimorphism in childhood. We followed 116 children from the TIMOUN mother–child cohort study in Guadeloupe, who were examined at age 7. These children were invited to participate in a 7-min structured play session in which they could choose between different toys considered as feminine, masculine, or neutral. The play session was video recorded, and the percentage of the time spent playing with feminine or masculine toys was calculated. We estimated associations between playtime and prenatal exposure to chlordecone (assessed by concentration in cord blood) or childhood exposure (determined from concentrations in child blood obtained at the 7-year follow-up), taking into account confounders and co-exposures to other environmental chemicals. We used a two-group regression model to take into account sex differences in play behavior. Our results do not indicate any modification in sex-typed toy preference among 7-year-old children in relation with either prenatal or childhood exposure to chlordecone.

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood. This work was supported by the European Community’s Seventh Framework Program [EU- FP7- HEALTH-2009-single-stage-241604]. Details of funding per cohort are available at IJE online.

Background: Dyslipidemia represents a significant non-infectious comorbidity among people living with HIV. The aim of this study is to evaluate the impact on lipid profile of switches from an efavirenz (EFV) or protease inhibitor/ritonavir (PI/r)-based regimen to a rilpivirine (RPV) or a once-daily integrase inhibitor-based regimen. Methods: We analyzed data from SCOLTA prospective database. All patients with HIV-RNA < 50 copies/ml in therapy with two NRTI + EFV or PI/r were included if they switched from EFV to dolutegravir (group EFV-DTG), elvitegravir (EFV-EVG), or RPV (EFV-RPV) and from PI/r to DTG (PI/r-DTG), PI/r to EVG (PI/r-EVG), or PI/r to RPV (PI/r-RPV). Total cholesterol (TC), TC/HDL ratio, LDL-cholesterol (LDL) and triglycerides (TG) were compared at baseline, six months and one year. Comparisons among groups were performed by a general linear model. Results: Four hundred and ninety patients were enrolled, 24.9% female, mean age 47.3 years (±10.1). According to ART switch, 11.4% were classified in group EFV-DTG, 3.9% in EFV-EVG, 23.9% in EFV-RPV, 17.6% in PI/r-DTG, 17.8% in PI/r-EVG, and 25.5% in PI/r-RPV. After adjusted analysis, TC significantly decreased in all groups but EFV-EVG, TC/HDL in all but EFV-DTG and EFV-EVG, while the reduction of TG was significant only in switches to RPV (EFV-RPV and PI/r-RPV). The one year decrease of TC, TC/HDL, LDL and TG was higher in patients with higher baseline levels of the same variable (p < .0001 for all). Conclusions: In SCOLTA, all switches from PI/r regimens gave advantages on lipid profile, while stopping EFV had consistently favorable lipid effects only if replaced by RPV.

Play is often used in interventions to improve social outcomes for children with autism spectrum disorders (ASD). Play is a primary occupation of childhood and, therefore, an important outcome of intervention. The Ultimate Guide to Play, Language and Friendship (PLF) is a peer-mediated intervention for 6-11-year-old children with ASD. A total of 68 dyads were randomized to either a 10-week treatment first or waitlist control group. Results revealed a significant moderate intervention effect from pre- to post-intervention, which was maintained to the 3-month follow-up clinic session and generalized to the home environment. The findings support that the PLF intervention can be used to positively improve play in 6-11-year-old children with ASD.Australian New Zealand Clinical Trials Registry, https://www.anzctr.org.au/ (ACTRN12615000008527; Universal Trial Number: U1111-1165-2708).

International audience; Background: Heat stress during pregnancy may limit fetal growth, with ramifications throughout the life course. However, critical exposure windows are unknown, and effects of meteorological variability have not been investigated.Objectives: We aimed to identify sensitive windows for the associations of mean and variability of temperature and humidity with term birthweight.Methods: We analyzed data from two French mother–child cohorts, EDEN and PELAGIE (n = 4771), recruited in 2002–2006. Temperature exposure was assessed using a satellite-based model with daily 1-km2 resolution, and relative humidity exposure data were obtained from Météo France monitors. Distributed lag models were constructed using weekly means and standard deviation (SD, to quantify variability) from the first 37 gestational weeks. Analyses were then stratified by sex. Results for each exposure were adjusted for the other exposures, gestational age at birth, season and year of conception, cohort and recruitment center, and individual confounders.Results: There was no evidence of association between term birthweight and mean temperature. We identified a critical window in weeks 6–20 for temperature variability (cumulative change in term birthweight of −54.2 g [95% CI: −102, −6] for a 1 °C increase in SD of temperature for each week in that window). Upon stratification by sex of the infant, the relationship remained for boys (weeks 1–21, cumulative change: −125 g [95% CI: −228, −21]). For mean humidity, there was a critical window in weeks 26–37, with a cumulative change of −28 g (95% CI: −49, −7) associated with a 5% increase in humidity for each week. The critical window was longer and had a stronger association in boys (weeks 29–37; −37 g, 95% CI: −63, −11) than girls (week 14; −1.8 g, 95% CI: −3.6, −0.1).Discussion: Weekly temperature variability and mean humidity during critical exposure windows were associated with decreased term birthweight, especially in boys.

Background Cytomegalovirus (CMV) is the most frequent cause of congenital viral infection. Approximately 1 % of newborns are congenitally infected and in up to 10 % of them the consequences are severe. Antenatal and postnatal treatments, although promising, are still under evaluation. Hygiene counseling to prevent CMV infection is important and should be systematic. Objective To evaluate health care providers’ awareness of CMV maternal and congenital infection in France. Study design A questionnaire on CMV infection was sent in 2018 by e-mail to obstetricians, pediatricians, midwives and laboratory physicians, and members of medical or midwifery associations. We evaluated their knowledge concerning CMV epidemiology, transmission, symptoms in adults, newborns and long-term effects (scores from 0 to 30) and compared the results with those of our 2012 published study. Results Of the 597 respondents who completed the questionnaire, 91 % were unaware of the precise transmission route of CMV, 33 % wrongly thought thatin utero therapy for congenital CMV infection was a current standard of care in France, and less than half were familiar with the HAS (Haute Autorite de Sante) and CNGOF (College National des Gynecologues et Obstetriciens Francais) recommendations. When respondents' knowledge of CMV was greater, patients were given more hygiene counseling. Between 2011 and 2018, knowledge improved among doctors and midwives concerning the route of transmission, the symptoms in adults, and the long-term effects of CMV infection. Conclusions Knowledge is improving among healthcare providers, but gaps remain. To bridge these gaps, health care providers should improve their knowledge about congenital CMV by various means: medical reviews, continuing medical education, meetings, conferences, the Internet. Moreover, greater knowledge will allow for more effective counseling of pregnant women, as recommended by HCSP and CNGOF in France.

International audience; Until recently the in utero environment of pregnant women was considered sterile. Recent high-sensitivity molecular techniques and high-throughput sequencing lead to some evidence for a low-biomass microbiome associated with the healthy placenta. Other studies failed to reveal evidence for a consistent presence of bacteria using either culture or molecular based techniques. Comparing conflicting "placental microbiome" studies is complicated by the use of varied and inconsistent protocols. Given this situation, we undertook an evaluation of the in utero environment sterility using several controlled methods, in the same study, to evaluate the presence or absence of bacteria and to explain contradictions present in the literature. Healthy pregnant women (n = 38) were recruited in three maternity wards. Placenta were collected after cesarean section with or without Alexis ® and vaginal delivery births. For this study we sampled fetal membranes, umbilical cord and chorionic villi. Bacterial presence was analyzed using bacterial culture and qPCR on 34 fetal membranes, umbilical cord and chorionic villi samples. Shotgun metagenomics was performed on seven chorionic villi samples. We showed that the isolation of meaningful quantities of viable bacteria or bacterial DNA was possible only outside the placenta (fetal membranes and umbilical cords) highlighting the importance of sampling methods in studying the in utero environment. Bacterial communities described by metagenomics analysis were similar in chorionic villi samples and in negative controls and were dependent on the database chosen for the analysis. We conclude that the placenta does not harbor a specific, consistent and functional microbiota.

IntroductionAn amphibious assault ship was deployed on 22 March in Corsica to carry out medical evacuation of 12 critical patients infected with COVID-19. The ship has on-board hospital capacity and is the first time that an amphibious assault ship is engaged in this particular condition. The aim is to evaluate the feasibility and safety of prolonged medical evacuation of critical patients with COVID-19.MethodsWe included 12 patients with confirmed COVID-19 infection: six ventilated patients with acute respiratory distress syndrome and six non-ventilated patients with hypoxaemia. Transfer on an amphibious assault ship lasted 20 hours. We collected patients’ medical records: age, comorbidities, COVID-19 history and diagnosis, ventilation supply and ventilator settings, and blood gas results. We calculated oxygen consumption (OC).ResultsAll patients had a medical history. The median delay from onset of symptoms to hospitalisation was 8 (7–10) days. The median Sequential Organ Failure Assessment score on admission was 3 (2–5). There was no significant increase in oxygen during ship transport and no major respiratory complication. There was no significant increase in arterial oxygen pressure to fractional inspired oxygen ratio among ventilated patients during ship transport. Among ventilated patients, the median calculated OC was 255 L (222–281) by hours and 5270 L (4908–5616) during all ship transport. Among non-ventilated patients, the median calculated OC was 120 L (120–480) by hours and 2400 L (2400–9600) during all ship transport.ConclusionThe present work contributes to assessing the feasibility and safety condition of critical COVID-19 evacuation on an amphibious assault ship during an extended transport. The ship needs to prepare a plan and a specialised intensive team and conduct patient screening for prolonged interhospital transfers.