A critically prolonged avalanche burial with recorded cardiac electrical activity and complete recovery - a case report.

The probability of survival in avalanche accidents is time-dependent. Critically buried victims who undergo a long burial duration (over 60 min) face a possible mortality rate of over 80%. Understanding the physiological response during critical avalanche burial is crucial for improving rescue strategies and outcomes. We present the case of a 55-year-old male skier buried under an avalanche for 4 h and 51 min in the Italian Alps. Continuous heart rate monitoring revealed distinct phases of cardiac activity during burial. Despite severe hypothermia, the victim survived without extracorporeal rewarming. This case highlights the importance of continuous monitoring and appropriate on-site management in avalanche accidents. Factors such as the presence of an air pocket may positively influence survival. This case underscores the importance of comprehensive resuscitative measures and guidelines for managing avalanche victims with prolonged burial durations.

Hepatic metabolism of chlorinated derivatives of bisphenol A (ClxBPA) and interspecies differences between rats and humans.

During chlorination treatments of drinking water, aqueous bisphenol A (BPA) can react with chlorine to form chlorinated derivatives of BPA (mono, di, tri and tetra-chlorinated derivatives) or ClxBPA. These emerging substances are endocrine disruptors associated with obesity, type II diabetes (TD2M) and myocardial infarction. ClxBPA are present in different human biological matrices but their toxicokinetics remain unknown. The aim of this study was to measure and compare the metabolic kinetics in the liver of four ClxBPA (ClBPA, Cl2BPA, Cl3BPA and Cl4BPA) between compounds and between species (Sprague-Dawley rats vs humans). To estimate their metabolic constants (Vmax, Km, Intrinsic clearance), metabolic assays were performed in hepatocyte suspensions. Assays revealed that metabolic constants of ClxBPA can greatly vary depending on substances and species. While ClBPA and Cl2BPA show similar unbound intrinsic clearances (ClintU) in rat incubation media, values for Cl3BPA and Cl4BPA are very different (3.109 and 0.684 mL/min/106 hepatocytes, respectively). Unlike in rats, human results are quite different as Cl3BPA and Cl4BPA have similar unbound intrinsic clearances, while ClBPA and Cl2BPA diverge (0.350 and 1.363 mL/min/106 hepatocytes, respectively). In both species, Cl2BPA and Cl3BPA have relatively similar clearances, and ClBPA is very different from Cl4BPA. Although we quantified the proportion of sulfo- and glucurono-metabolites, other metabolites may have been formed (e.g., glutathione, disulfate, or oxidative metabolites). This study showed that chlorination had an impact on hepatic intrinsic clearance of ClxBPA in rats and humans and measured values will be valuable for the development of PBPK models for use in exposure assessment.

Reservoir hosts experiencing food stress alter transmission dynamics for a zoonotic pathogen.

Food limitation is a universal stressor for wildlife populations and is increasingly exacerbated by human activities. Anthropogenic environmental change can significantly alter the availability and quality of food resources for reservoir hosts and impact host-pathogen interactions in the wild. The state of the host's nutritional reserves at the time of infection is a key factor influencing infection outcomes by altering host resistance. Combining experimental and model-based approaches, we investigate how an environmental stressor affects host resistance to West Nile virus (WNV). Using American robins (Turdus migratorius), a species considered a superspreader of WNV, we tested the effect of acute food deprivation immediately prior to infection on host viraemia. Here, we show that robins food deprived for 48 h prior to infection, developed higher virus titres and were infectious longer than robins fed normally. To gain an understanding about the epidemiological significance of food-stressed hosts, we developed an agent-based model that simulates transmission dynamics of WNV between an avian host and the mosquito vector. When simulating a nutritionally stressed host population, the mosquito infection rate rose significantly, reaching levels that represent an epidemiological risk. An understanding of the infection disease dynamics in wild populations is critical to predict and mitigate zoonotic disease outbreaks.

An overview of the literature on emerging pollutants: Chlorinated derivatives of Bisphenol A (ClxBPA).

CONTEXT: Bisphenol A (BPA) is a ubiquitous contaminant with endocrine-disrupting effects in mammals. During chlorination treatment of drinking water, aqueous BPA can react with chlorine to form chlorinated derivatives of BPA (mono, di, tri and tetra-chlorinated derivatives) or ClxBPA. OBJECTIVE: The aim of this study is to summarize and present the state of knowledge on human toxicological risk assessment of ClxBPA. MATERIALS AND METHODS: A search on ClxBPA in the PubMed database was performed based on studies published between 2002 and 2021. Forty-nine studies on chlorinated derivatives of BPA were found. Available information on their sources and levels of exposure, their effects, their possible mechanisms of action and their toxicokinetics data was extracted and presented. RESULTS: ClxBPA have been essentially detected in environmental aqueous media. There is evidence in toxicological and epidemiological studies that ClxBPA also have endocrine-disrupting capabilities. These emerging pollutants have been found in human urine, serum, breast milk, adipose and placental tissue and can constitute a risk to human health. However, in vitro and in vivo toxicokinetic data on ClxBPA are scarce and do not allow characterization of the disposition kinetics of these compounds. CONCLUSION: More research to assess their health risks, specifically in vulnerable populations, is needed. Some water chlorination processes are particularly hazardous, and it is important to evaluate their chlorination by-products from a public health perspective.

[Neonates exposure to parabens through medicines administered to inpatients]. / Exposition des nouveau-nés aux parabènes via les médicaments administrés durant leur hospitalisation.

OBJECTIVES: The objective of this study was to quantify parabens intake due to drug administration in neonates during hospitalization following their birth. METHOD: A monocentric prospective study was performed into a neonatalogy unit to collect all drug prescriptions. An exhaustive list of parabens containing medicines commercialized in France was completed from Theriaque® database. This list was combined with drug prescription to establish an exposure profile to parabens. For each paraben containing medicines, a HPLC-UV assay was performed to determine the average daily intake of paraben received by hospitalized neonates. RESULTS: More than 300 medicines commercialized in France contain at least one paraben. A combination of methylparaben and propylparaben was found in most cases. All hospitalized neonates (n=22) were exposed at least once to methylparaben and propylparaben through medicines while 50 % were exposed to ethylparaben. The average daily intake was higher in term newborns (572,0±249,0 versus 414,6±294,1µg/kg/j for methylparaben) but frequency was higher in prematures (65,0 versus 78,6% for methylparaben) as well as cumutives doses (1421,5±758,8 versus 8618,7±7922,3). These doses are lower than toxicological reference values but these latter do not take into account endocrine disrupting effects of these compounds. CONCLUSIONS: These results highlight medicines as a high source of exposure to parabens in hospitalized neonates. It should encourage pharmaceutical companies and health professionnal to prioritize therapeutic cares without parabens.

Demonstration of the herd effect in adults after the implementation of pneumococcal vaccination with PCV13 in children.

The purpose of this investigation was to describe the evolution of serotypes and antibiotic susceptibility of Streptococcus pneumoniae strains isolated from both adults and children from the same population area with invasive pneumococcal disease (IPD) or acute otitis media (AOM), 5 years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). From 2009 to 2015, 839 strains of S. pneumoniae strains were collected (481 from adults and 358 from children). Serotyping by latex antisera and molecular methods was performed. Antimicrobial susceptibility was tested. Compared to 2009, the total number of strains isolated in 2015 decreased in children (263 vs. 53, respectively) and in adults (220 vs. 131, respectively). Serotype coverage of PCV13 for IPD decreased significantly in adults from 67.7% (149/220) to 25.2% (33/131) and in children from 75.1% (61/81) to 18.5% (5/27). Especially, serotypes 1, 7F and 19A decreased significantly in children, while serotypes 7F and 19A decreased significantly in adults. PCV13 serotypes involved in AOM decreased significantly over the 5-year period, from 85.7% (156/182) to 38.5% (10/26), and were more susceptible to penicillin, amoxicillin and cefotaxime, p < 0.05. Serotypes 8, 9N and 10A seemed to emerge in adults, whereas any serotype prevalence was observed in children. Between 2009 and 2015, the introduction of PCV13 has resulted in a significant decrease of the number of S. pneumoniae strains isolated from IPD in children as in adults. It highlights a strong herd effect of vaccination in adults.

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: introduction, methodology and recommendation overview

"STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to develop the first Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The guidelines were developed in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The Working Group developed 12 recommendations for screening and diagnosis, 12 recommendations for treatment and 5 recommendations for models of care. Important clinical considerations accompany each recommendation. CONCLUSIONS: The Working Group recommendations for the management of neuropathic pain after SCI should be used to inform practice."

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: introduction, methodology and recommendation overview.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to develop the first Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The guidelines were developed in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The Working Group developed 12 recommendations for screening and diagnosis, 12 recommendations for treatment and 5 recommendations for models of care. Important clinical considerations accompany each recommendation. CONCLUSIONS: The Working Group recommendations for the management of neuropathic pain after SCI should be used to inform practice.

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: Recommendations for treatment.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: To develop the first Canadian clinical practice guidelines for treatment of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The CanPainSCI Working Group reviewed the evidence for different treatment options and achieved consensus. The Working Group then developed clinical considerations for each recommendation. Recommendations for research are also included. RESULTS: Twelve recommendations were developed for the management of neuropathic pain after SCI. The recommendations address both pharmacologic and nonpharmacologic treatment modalities. CONCLUSIONS: An expert Working Group developed recommendations for the treatment of neuropathic pain after SCI that should be used to inform practice.

The CanPain SCI Clinical Practice Guideline for Rehabilitation Management of Neuropathic Pain after Spinal Cord: recommendations for model systems of care.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The project objectives were to develop the first Canadian recommendations on a model of care for the management of at- and below-level neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: On the basis of a review of the Accreditation Canada standards, the Steering Committee developed questions to guide the CanPainSCI Working Group when developing the recommendations. The Working Group agreed on recommendations through a consensus process. RESULTS: The Working Group developed five recommendations for the organization of neuropathic pain rehabilitation care in people with SCI. CONCLUSIONS: The Working Group recommendations for a model of care for at- and below-level neuropathic pain after SCI should be used to inform clinical practice.

The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: screening and diagnosis recommendations.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: To develop the first Canadian clinical practice guidelines for screening and diagnosis of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient and outpatient SCI rehabilitation settings in Canada. METHODS: The CanPainSCI Working Group reviewed evidence to address clinical questions regarding screening and diagnosis of neuropathic pain after SCI. A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: Twelve recommendations, based on expert consensus, were developed for the screening and diagnosis of neuropathic pain after SCI. The recommendations address methods for assessment, documentation tools, team member accountability, frequency of screening and considerations for diagnostic investigation. Important clinical considerations accompany each recommendation. CONCLUSIONS: The expert Working Group developed recommendations for the screening and diagnosis of neuropathic pain after SCI that should be used to inform practice.

Multicenter Comparison of the Etest and EUCAST Methods for Antifungal Susceptibility Testing of Candida Isolates to Micafungin.

In vitro susceptibility of 933 Candida isolates, from 16 French hospitals, to micafungin was determined using the Etest in each center. All isolates were then sent to a single center for determination of MICs by the EUCAST reference method. Overall essential agreement between the two tests was 98.5% at ±2 log2 dilutions and 90.2% at ±1 log2 dilutions. Categorical agreement was 98.2%. The Etest is a valuable alternative to EUCAST for the routine determination of micafungin MICs in medical mycology laboratories.

Developing a Model of Care for Healing Pressure Ulcers With Electrical Stimulation Therapy for Persons With Spinal Cord Injury.

Background: Electrical stimulation therapy (EST) has been shown to be an effective therapy for managing pressure ulcers in individuals with spinal cord injury (SCI). However, there is a lack of uptake of this therapy, and it is often not considered as a first-line treatment, particularly in the community. Objective: To develop a pressure ulcer model of care that is adapted to the local context by understanding the perceived barriers and facilitators to implementing EST, and to describe key initial phases of the implementation process. Method: Guided by the Knowledge-to-Action (KTA) and National Implementation Research Network (NIRN) frameworks, a community-based participatory research (CBPR) approach was used to complete key initial implementation processes including (a) defining the practice, (b) identifying the barriers and facilitators to EST implementation and organizing them into implementation drivers, and (c) developing a model of care that is adapted to the local environment. Results: A model of care for healing pressure ulcers with EST was developed for the local environment while taking into account key implementation barriers including lack of interdisciplinary collaboration and communication amongst providers between and across settings, inadequate training and education, and lack of resources, such as funding, time, and staff. Conclusions: Using established implementation science frameworks with structured planning and engaging local stakeholders are important exploratory steps to achieve a successful sustainable best practice implementation project.

Reliable quantification of bisphenol A and its chlorinated derivatives in human urine using UPLC-MS/MS method.

Bisphenol A (BPA), a widespread man-made chemical classified as an endocrine disruptor, is increasingly considered as a major cause of concern for human health. Chlorine present in drinking water may react with BPA to form chlorinated derivatives (ClxBPA), which have demonstrated a heightened level of estrogenic activity. If many epidemiological studies report that more than 90% of people have detectable BPA levels in their urine, then no such study has been undertaken regarding ClxBPA. The purpose of this work is to propose a highly sensitive and accurate analytical method adapted to large-scale biomonitoring studies aimed at assessing exposure to BPA and ClxBPA through the use of human urine. To achieve this, we have comprehensively validated a method using salting-out assisted liquid/liquid extraction (SALLE) coupled to UPLC-MS/MS and isotope dilution quantification, to measure unconjugated BPA and ClxBPA in human urine according to the accepted guidelines. Deutered BPA as well as deutered 2,2'-DCBPA was used as internal standards. The matrix calibration curve ranged from 0.05 to 1.60 ng mL(-1) and from 0.5 to 16.0 ng mL(-1) for ClxBPA and BPA respectively, and provided good linearity (r²>0.99). This method was precise (the intra- and inter-day coefficients of variation were <20% at three different concentrations: 0.05 ng mL(-1), 0.2 ng mL(-1), 0.8 ng mL(-1) and 0.5 ng mL(-1), 2 ng mL(-1), 8 ng mL(-1) for ClxBPA and BPA, respectively) and accurate (bias ranged from -13% to +12%). The limit of quantification, validated at 0.05 ng mL(-1) and 0.5 ng mL(-1) for ClxBPA and BPA respectively when using 300 µL of urine, was found to be suitable for the concentration existing in real samples. The matrix effect and the BPA cross-contamination were also investigated in this study. The analytical method developed in this study is in accordance with the requirements applicable to biomonitoring of BPA and ClxBPA in human urine.

Does area deprivation modify the association between exposure to a nitrate and low-dose atrazine metabolite mixture in drinking water and small for gestational age? A historic cohort study.

Birth weight may be influenced by environmental and socio-economic factors that could interact. The main objective of our research was to investigate whether area deprivation may modify the association between drinking water exposure to a mixture of atrazine metabolites and nitrates during the second trimester of pregnancy and prevalence of small for gestational age (SGA) neonates. We conducted a historic cohort study in Deux-Sèvres, France between 2005 and 2010, using birth records, population census and regularly performed drinking water withdrawals at community water systems. Exposure to an atrazine metabolite/nitrate mixture in drinking water was divided into six classes according to the presence or absence of atrazine metabolites and to the terciles of nitrate concentrations in each trimester of pregnancy. We used a logistic regression to model the association between SGA and mixture exposure at the second trimester while taking into account the area deprivation measured by the Townsend index as an effect modifier and controlling for the usual confounders. We included 10,784 woman-neonate couples. The risk of SGA when exposed to second tercile of nitrate without atrazine metabolites was significantly greater in women living in less deprived areas (OR = 2.99; 95 % CI (1.14, 7.89)), whereas it was not significant in moderately and more deprived areas. One of the arguments used to explain this result is the presence of competing risk factors in poorer districts.

[Share experiment: hospital mobile pharmaceutical teams, a proven concept!]. / Partage d'expérience : les équipes pharmaceutiques mobiles à l'hôpital, un concept qui fait ses preuves !

A few months ago, the pharmacy department of the University Hospital of Poitiers was located in the basement of the hospital; communicating with care units by fax, phone or messenger. Today, drugs and medical devices, are stored in a 3400m(2) logistic platform and most of the delivery activity is robotized. Control and validation of prescriptions and dispensing activities are done by the pharmaceutical teams directly in the care units. Quality indicators allow us to improve our services regularly. A great success and interesting prospects for clinical pharmacy.

Acute gut GVHD in children: does skin involvement matter?

Gut GVHD (G-GVHD) is frequently the most severe and difficult to treat compared with skin GVHD. It is unknown if skin involvement with G-GVHD has prognostic significance. To compare the prognosis of acute isolated G-GVHD vs acute gut and skin GVHD (GS-GVHD) in children following allo-SCT. Allo-SCT recipients from Jan 2000-Dec 2009 were included and patients who underwent endoscopy and gut biopsy for G-GVHD were identified. Four hundred and fifty children (0-18 years) underwent allo-SCT during the study period. Seventy-nine (17.5%) patients underwent endoscopy and biopsy. At least stage II was required for skin involvement. Forty nine patients had G-GVHD and 30 had combined, GS-GVHD. The majority of patients received CsA and MTX for GVHD prophylaxis. Sixty-seven percent of patients with GS-GVHD had grade III-IV while only 31% had grade III-IV in the G-GVHD group. Median follow-up was 6.3 years (range 3.6-11.9 years). Relapse rate was similar in both the groups. However, children with G-GVHD had a significantly higher risk of dying from GVHD related complications (37% vs 16%) resulting in superior survival for those with skin involvement (79% vs 49% P=0.02). Extension of G-GVHD to the skin may suggest a better outcome.

Drinking-water exposure to a mixture of nitrate and low-dose atrazine metabolites and small-for-gestational age (SGA) babies: a historic cohort study.

BACKGROUND: Groundwater, surface water and drinking water are contaminated by nitrates and atrazine, an herbicide. They are present as a mixture in drinking water and with their endocrine-disrupting activity, they may alter fetal growth. OBJECTIVES: To study an association between drinking-water atrazine metabolites/nitrate mixture exposure and small-for-gestational-age(SGA). METHODS: A historic cohort study based on birth records and drinking-water nitrate and pesticide measurements in Deux-Sèvres (France) between 2005 and 2009 was carried out. Exposure to drinking-water atrazine metabolites/nitrate mixture was divided into 6 classes according to the presence or absence of atrazine metabolites and to terciles of nitrate concentrations in each trimester of pregnancy. Regression analysis of SGA by mixture exposure at second trimester was subsequently conducted. RESULTS: We included 11,446 woman-neonate couples of whom 37.0% were exposed to pesticides, while 99.9% of the women were exposed to nitrates. Average nitrate concentration was from 0 to 63.30 mg/L. In the second trimester of pregnancy, the risk of SGA was different with mixture exposure when drinking-water atrazine metabolites, mainly 2 hydroxyatrazine and desethylatrazine, were present and nitrate dose exposure increased: compared to single first tercile of nitrate concentration exposure, single second tercile exposure OR was 1.74 CI 95% [1.10; 2.75] and atrazine metabolites presence in the third tercile of nitrate concentration exposure OR was 0.87 CI 95% [0.45;1.67]. CONCLUSIONS: It is possible that the association found at the second trimester of exposure with regard to birth weight may likewise be observed before birth, with regard to the estimated fetal weight, and that it might change in the event that the atrazine metabolites dose were higher or the nitrate dose lower. It would appear necessary to further explore the variability of effects.

Response inhibition and ADHD traits: correlates and heritability in a community sample.

Endophenotypes or intermediate phenotypes are of great interest in neuropsychiatric genetics because of their potential for facilitating gene discovery. We evaluated response inhibition, latency and variability measures derived from the stop task as endophenotypes of ADHD by testing whether they were related to ADHD traits in the general population, heritable and shared genetic risk with ADHD traits. Participants were 16,099 children and adolescents, ages 6 to 18 years who visited a local science center. We measured ADHD traits using the Strengths and Weaknesses of ADHD-symptoms and Normal-Behavior (SWAN) rating scale and performance on the stop signal task (SST)-response inhibition (SSRT), response latency (GoRT), and response variability (GoRTSD). Regression analysis was used to assess the relationship of cognitive measures and ADHD traits while controlling for family, age, sex, ethnicity, socioeconomic status and treatment status. Heritability of ADHD and cognitive traits was estimated using SOLAR in 7,483 siblings from 3,507 families that included multiple siblings. Bivariate relationships between pairs of variables were examined. Individuals with greater ADHD trait scores had worse response inhibition, slower response latency, and greater variability. Younger participants and girls had inferior performance although the gender effects were minimal and evident in youngest participants. Inhibition, latency, variability, total ADHD traits, inattention and hyperactivity-impulsivity scores were significantly heritable. ADHD traits and inhibition, but not latency or variability were coheritable. In the largest study in the general population, we found support for the validity of response inhibition as an endophenotype of ADHD.