A multidisciplinary and structured investigation of three suspected clusters of transverse upper limb reduction defects in France.

INTRODUCTION: Between 2019-2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France, where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. METHODS: The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases' homes concerning their plant product use. RESULTS: After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. DISCUSSION: Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred.

A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study.

OBJECTIVES: In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. METHODS: Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. RESULTS: From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006). CONCLUSION: We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

Targeted vaccination campaigns of teenagers after two clusters of B invasive meningococcal disease in Brittany, France, 2017.

BACKGROUND: In December 2016, three cases of serogroup B invasive meningococcal disease, including two children from the same middle school (11 to 15 years old pupils), occurred in the department (administrative district) Côtes-d'Armor (Brittany, France). They were infected by a rare strain (B:P1.7-2,4:F5-9:cc162), covered by the 4CMenB vaccine (Bexsero®). Four months later, two cases due to the same strain occurred in a high school in the same area (15 to 19 years old students). In accordance with French recommendations, vaccination was proposed to students of both schools and to all individuals aged 11-19 years living or studying in the hyperendemic area. We describe these vaccination campaigns, from the alert to the impact evaluation. METHODS: The target population included 8884 people: 579 in the middle school, 2007 in the high school and 6298 in the community. In both schools, vaccination sessions were organized directly on site. In the community, teenagers were vaccinated by general practitioners. The vaccination campaign took place from May to October 2017. An active pharmacovigilance follow-up was set up to document adverse effects of the vaccine. RESULTS: Considering the whole target population, the vaccination coverage was estimated at 43% for 1 dose and 34% for 2 doses. Higher vaccination coverage was observed in the schools (79% in the middle school and 42% in the high school for 2 doses) than in the community (27% for 2 doses). The reported adverse effects were consistent with the safety profile of the vaccine and no severe adverse effect was reported. CONCLUSIONS: This vaccination campaign was the third one implemented with Bexsero® in France and constitutes a reproducible approach for future targeted vaccination campaigns. No additional cases of the same strain have occurred since the end of the campaigns in the area.

The Comparative Role of the Anterior Cruciate Ligament and Anterolateral Structures in Controlling Passive Internal Rotation of the Knee: A Biomechanical Study.

PURPOSE: To determine the respective functions of the anterior cruciate ligament (ACL) and the anterolateral structures (ALSs) in controlling the tibia's passive internal rotation (IR) with respect to the femur, under uniaxial rotation. METHODS: To test the function of the ACL and the anterolateral ligament (ALL) in IR, we designed a sequential transection study of the ACL and the anterolateral structures (including the ALL) in 24 cadaveric knees divided in 2 groups. Two sequences were conducted successively: group 1 (12 knees) in which the ACL was sectioned first followed by the ALS, and group 2 (12 knees) with reversed transections. Each knee, in neutral rotation position and at flexion angle of 30°, was subjected to a 5 Nm torsion torque of IR. IR was measured using a rotatory laximeter, the Rotam with a gyroscope's measurement accuracy of 0.1°. Laxities were compared using paired t test within each group and using t test between groups. Fisher exact test was used to compare proportions. RESULTS: In group 1, IR increased from 22.1° ± 10.6° to 25.7° ± 10.9° after ACL transection then to 28.1° ± 10.5° after we sectioned the ALS. In group 2, IR increased from 22.5° ± 8.9° to 25.2° ± 8.4° after sectioning the ALS, then to 29.1° ± 8.8° after we sectioned the ACL. Total postsectioning increase in IR was 6.4° ± 2° in group 1, and 6.55° ± 0.9° in group 2. The IR increase after each stage of transection and final IR were statistically significant (P < .001). CONCLUSIONS: In a pure rotational cadaveric test model, the ACL and the ALS contribute to resistance to passive IR of the knee. CLINICAL RELEVANCE: In some specific clinical cases, peripheral lesions may be considered, and injuries to these structures may need to be addressed to improve results controlling postoperative IR.

Objective evaluation of anterior knee laxity; comparison of the KT-1000 and GNRB® arthrometers.

PURPOSE: Accurate measurement of laxity after anterior cruciate ligament (ACL) rupture is usually performed with the KT-1000 arthrometer, and reproducibility and reliability are discussed. A new arthrometer, the GNRB(®), has been recently developed in an attempt to improve intra- and inter-examiner reproducibility. The aim of this diagnostic study was to evaluate the intra- and inter-examiner reproducibility of the GNRB(®) and the KT-1000. METHODS: Three protocols were designed to evaluate and compare the two arthrometers. Fifteen physiotherapists conducted tests on 15 subjects with healthy knees. The intra- and inter-reproducibility of the two tests were compared by analysis of variance and the F-test. RESULTS: Measure reproducibility was significantly worst with the KT-1000 than with the GNRB(®) (machine effect, P < 0.001) regardless of operator experience. There was no significant difference between experienced and inexperienced examiners with the GNRB(®) (no 'examiners effect'). Regardless of the machine, there was a 'side effect' with healthy knees. CONCLUSION: This clinical study demonstrates the superior intra- and inter-examiner reproducibility of the GNRB(®) over the KT-1000. There appears to be some technological advantages to using the GNRB(®) including pressure control of the patella, accuracy of the displacement transducer, control of the load on the calf, and control of hamstring activity. LEVEL OF EVIDENCE: Diagnostic study, Level I.

Environmental and urinary markers of prenatal exposure to drinking water disinfection by-products, fetal growth, and duration of gestation in the PELAGIE birth cohort (Brittany, France, 2002-2006).

Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation, its impact on fetal growth remains an open question. The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction (FGR) and preterm birth in the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006. Exposure was assessed by estimating levels of trihalomethanes (THMs) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early pregnancy in a nested case-control design that compared 174 FGR cases, 114 preterm births, and 399 controls. Higher uptake of THMs (especially brominated THMs) was associated with a higher risk of FGR. Women with TCAA detected in their urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the detection limit (adjusted odds ratio = 1.8, 95% confidence interval: 0.9, 3.7) and had an odds ratio for preterm birth below 1 (adjusted odds ratio = 0.8, 95% confidence interval: 0.3, 2.6). Results from this prospective study, the first to use a biomarker of disinfection by-product exposure, suggest that prenatal exposure affects fetal growth, but the causal agent or agents remain to be identified.

Down syndrome time-clustering in January 1987 in Belarus: link with the Chernobyl accident?

The Chernobyl accident (April 26, 1986) exposed a large part of the Belarus population to ionizing radiation. We analyzed the time trends of Down syndrome (DS) in Belarus to evaluate whether either brief exposure at high dose rates during the plume passage or continuous exposure at low doses and dose rates of the residents of contaminated areas had any detectable impact on DS prevalence at birth. DS data came from the Belarus National Registry of Congenital Malformations (1981-2001). We observed a significant peak of DS in January 1987 (26 cases observed and 9.84 expected; observed/expected ratio=2.64; 95% CI=1.72-3.76), but found no positive long-term time trends in contaminated or control areas. The time occurrence of the January peak, high dose rates during the plume passage and experimental data showing a radiosensitive phase of oogenesis around conception time in mammals suggest that the January peak may be linked to the Chernobyl plume.

Sources of variability in levels and exposure to trihalomethanes.

In the framework of a cohort study of pregnant women conducted in Brittany (France), we assessed the exposure to trihalomethanes (THM) during pregnancy in a subset by evaluating (1) potential sources of variability in household THM levels; (2) the between- and within-subject variability in THM levels; (3) THM levels in swimming pools; and (4) the role of water-related habits on total THM uptake. We visited 109 women from the ongoing cohort study at home for an interview and collection of tap water from October to December 2004. Forty-three of them were re-contacted to obtain a second tap water sample in April-May 2005. We designed a questionnaire to collect individual information on source and amount of drinking water, frequency of showering, bathing, and swimming pool attendance, and household characteristics. We obtained 282 THM measurements, 152 specifically for the study and 130 from a regulatory agency. Personal information and environmental data were combined using two methodologies (method 1 using regulatory data and method 2 using our THM measurements) with a different set of assumptions. We calculated ingestion, showering, bathing, and swimming pool THM uptakes and added up those uptakes to calculate total THM uptake. Average THM levels from our measurements in October, November-December, and April-May were 61.3, 45.1, and 54.5 microg/l, respectively. Geographical variability was low and characteristics of the household did not influence THM levels. Within-subject variability in THM levels was three times higher than between-subject variability. Average THM level in swimming pools was 80.4 microg/l. Average water consumption during pregnancy was 1.9l/day. The source of the household drinking water was 90% bottled, 8% municipal, and 2% from other sources. Forty-seven per cent attended swimming pools during pregnancy. Using method 1, the geometric mean of total THM uptake was 0.93 microg/day. Showering contributed 64%, swimming in pools 23%, bathing 12%, and drinking water 1% to the total THM uptake. In a setting with low geographical variability and limited environmental measurements, individual data is highly relevant to determine personal THM exposure and uptake. In a population that mainly drinks bottled water (e.g., pregnant women), individual THM uptakes are dominated by inhalation and dermal absorption during, showering, swimming in pools, and bathing.

Association between first injection risk behaviors and hepatitis C seropositivity among injecting drug users.

HCV infection is rapidly acquired after drug addicts first inject drug intravenously. The risk behaviors accompanying the first intravenous substance injection are not well known. We used in 1997 a structured questionnaire to investigate the relationships between risk behaviors at the first injection and current reported HCV status. We interviewed 151 injecting drug users from four treatment centers and one prison in Paris. Risk markers for reported HCV seroconversion were explored by use of logistic regression models. One hundred and forty-three injecting drug users (95%) agreed to participate in the study. At the first injection, 50% shared preparation equipment; 22% borrowed and 26% lent injecting equipment. At the time of the study, 46% reported that they were HCV-positive. Sharing preparation equipment (odds ratio=3.1; 95% confidence interval: 1.2-7.8) and lending injection equipment (odds ratio=3.0; 95% confidence interval: 1.1-8.5) during the first injection were independently associated with reported HCV seropositivity. The high-risk behaviors accompanying the first intravenous injection of drugs justifies the implementation of specific prevention measures, aimed at young drug users who have not started to inject.