Analytical methods and biomonitoring results in hair for the assessment of exposure to endocrine-disrupting chemicals: A literature review.

Endocrine-disrupting chemicals (EDC) are compounds that alter functions of the endocrine system due to their ability to mimic or antagonize endogenous hormones, or that alter their synthesis and metabolism, causing adverse health effects. Human biomonitoring (HBM) is a reliable method to assess human exposure to chemicals through measurement in human body fluids and tissues. It identifies new sources of exposure and determines their distribution, thereby enabling detection of the most exposed populations. Blood and urine are commonly used for HBM of EDC, but their interest is limited for compounds presenting short half-lives. Hair appears as an interesting alternative insofar as it provides a large exposure window. For the present study, we evaluated the relevance of hair in determining EDC exposure. With this in mind, we undertook a literature review focusing on the bioanalytical aspects and performances of methods developed to determine EDC in hair. The literature review was performed through methodical bibliographical research. Relevant articles were identified using two scientific databases: PubMed and Web of Science, with search equations built from a combination of keywords, MeSH terms and Boolean operators. The search strategy identified 2949 articles. After duplicates were removed, and following title, abstract, and full-text screenings, only 31 were included for qualitative synthesis. Hair collection was mainly performed in the back of the head and preparation involved two processes: cutting into small pieces or grounding to powder. The off-line LC-MS/MS method remains the main technique used to assess EDC through hair. Differences regarding the validation of analytical methods and interpretation of HBM results were highlighted, suggesting a need for international harmonisation to obtain reliable and comparable results. External contamination of hair was identified as a main limitation in the interpretation of results, highlighting the need to better understand EDC transfers through hair and to develop relevant hair decontamination processes.

Assessment of Endocrine Disruptor Exposure in Hospital Professionals Using Hair and Urine Analyses: An Awareness Campaign.

BACKGROUND: In 2021, French public authorities initiated the fourth National Environmental Health Plan to prevent environment-related health risks. This plan primarily focuses on the sensitization of health professionals and health care institutions. Endocrine disruptors (EDs) are environmental factors associated with several adverse health effects, such as reproductive disorders, obesity, and cancer. This study aimed to conduct an awareness campaign among professionals at a general hospital center on the risks related to EDs. METHODS: Hospital professionals were directly involved in this study, and urine and hair samples were collected to determine bisphenol and paraben exposure levels. Analyses were performed using validated liquid chromatography-tandem mass spectrometry methods, enabling the simultaneous determination of bisphenols and parabens. A questionnaire on lifestyle habits was distributed to assess its relationship with the exposure profiles. Nineteen professionals were recruited for the study. RESULTS: Bisphenol A was detected in 95% of the urine samples, and the chlorinated derivatives of bisphenol A were between 16% and 63%. parabens showed detection frequencies between 37% and 100%, and methylparaben was quantified at an average concentration of 0.45 ± 0.46 ng/mL. In hair samples, bisphenols A, F, and S were detected at 95%-100%, chlorinated derivatives of bisphenol A were detected at 37%-68%, and parabens were detected at 100%. CONCLUSIONS: This awareness campaign may encourage health care institutions to adopt a policy of reducing endocrine disruptor exposure among their patients and professionals, who could be educated regarding the risks associated with EDs. Conducting a multicenter study to refine the results herein and establish a dynamic to prevent endocrine disruptor and environmental risks in health care systems would be valuable.

Bisphenol A and chlorinated derivatives of bisphenol A assessment in end stage renal disease patients: Impact of dialysis therapy.

Patients with end stage kidney disease treated by dialysis (ESKDD) process dialysis sessions to remove molecules usually excreted by kidneys. However, dialysis therapy could also contribute to endocrine disruptors (ED) burden. Indeed, materials like dialyzer filters, ultrapure dialysate and replacement fluid could exposed ESKDD patients to Bisphenol A (BPA) and chlorinated derivatives of BPA (ClxBPAs). Thus, our aim was to compare BPA and ClxBPAs exposure between ESKDD patients, patients with stage 5 chronic kidney disease (CKD5) not dialyzed and healthy volunteers. Then we describe the impact of a single dialysis session, according to dialysis modalities (hemodialysis therapy (HD) versus online hemodiafiltration therapy (HDF)) and materials used with pre-post BPA and ClxBPAs concentrations. The plasma levels of BPA and four ClxBPAs, were assessed for 64 ESKDD patients in pre and post dialysis samples (32 treated by HD and 32 treated by HDF) in 36 CKD5 patients and in 24 healthy volunteers. BPA plasma concentrations were 22.5 times higher for ESKDD patients in pre-dialysis samples versus healthy volunteers (2.208 ± 5.525 ng/mL versus 0.098 ± 0.169 ng/mL) (p < 0.001). BPA plasma concentrations were 16 times higher for CKD5 patients versus healthy volunteers, but it was not significant (1.606 ± 3.230 ng/mL versus 0.098 ± 0.169 ng/mL) (p > 0.05). BPA plasma concentrations for ESKDD patients in pre-dialysis samples were 1.4 times higher versus CKD5 patients (2.208 ± 5.525 ng/mL versus 1.606 ± 3.230 ng/mL) (p < 0.001). For healthy volunteers, ClxBPAs were never detected, or quantified while for CKD5 and ESKDD patients one ClxBPAs at least has been detected or quantified in 14 patients (38.8%) and 24 patients (37.5%), respectively. Dialysis therapy was inefficient to remove BPA either for HD (1.983 ± 6.042 ng/mL in pre-dialysis versus 3.675 ± 8.445 ng/mL in post-dialysis) or HDF (2.434 ± 5.042 ng/mL in pre-dialysis versus 7.462 ± 15.960 ng/mL in post dialysis) regarding pre-post BPA concentrations (p > 0.05). The same result was observed regarding ClxBPA analysis. Presence of polysulfone in dialyzer fibers overexposed ESKDD patients to BPA in pre-dialysis samples with 3.054 ± 6.770 for ESKDD patients treated with a polysulfone dialyzer versus 0.708 ± 0.638 (p = 0.040) for ESKDD patients treated without a polysulfone dialyzer and to BPA in post-dialysis samples with 6.629 ± 13.932 for ESKDD patients treated with a polysulfone dialyzer versus 3.982 ± 11.004 (p = 0.018) for ESKDD patients treated without a polysulfone dialyzer. This work is to our knowledge the first to investigate, the impact of a dialysis session and materials used on BPA and ClxBPAs plasma concentrations and to compare these concentrations to those found in CKD5 patients and in healthy volunteers.

Endocrine disruptors in dialysis therapies: A literature review.

Endocrine disrupting chemicals (EDCs) were defined as "an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects". These compounds are mainly eliminated by the renal route. However, patients with end-stage kidney disease treated by dialysis (ESKDD) can no longer eliminate these EDCs efficiently. Furthermore, EDCs exposure could occur via leaching from medical devices used in dialysis therapy. As a result, ESKDD patients are overexposed to EDCs. The aims of this study were to summarize EDCs exposure of ESKDD patients and to evaluate the factors at the origin of this exposure. To handle these objectives, we performed a literature review. An electronic search on PubMed, Embase and Web of science databases was performed. Twenty-six studies were finally included. The EDCs reported in these studies were Bisphenol A (BPA), Bisphenol S (BPS), Bisphenol B (BPB), Nonylphenol, Di(2-ethylhexyl) phthalate (DEHP), Di-n-butyl phthalate (DBP), and Butylbenzyl phthalate (BBP). Regarding the environment of dialysis patients, BPA, BPB, BPS, DEHP, DBP and nonylphenol have been found. Environmental exposure affects EDCs blood levels in ESKDD patients who are overexposed to BPA, BPS, BPB and DEHP. For ESKDD patients, dialyzers with housing in polycarbonate and fibers in polysulfone seem to overexpose them to BPA. Regarding dialysis therapy, peritoneal dialysis seems to decrease patient exposure vs hemodialysis therapy, and hemodiafiltration therapy seems to reduce this exposure vs hemodialysis therapy. Regarding DEHP, levels tend to increase during dialysis and when DEHP plasticizer is used in PVC devices. Finally, in the European Union a regulation on medical devices was adopted on 5 April 2017 and has been applied recently. This regulation will regulate EDCs in medical devices and thereby contribute to reconsideration of their conceptions and, finally, to reduction of ESKDD patients' exposure.

Characterization of pregnant women exposure to halogenated parabens and bisphenols through water consumption.

Exposure of pregnant women to endocrine disruptor compounds, such as parabens and bisphenol A is of concern for fetal transition. Their halogenated degradation products, mainly coming from water treatment plans, could be problematic as well, depending on their occurrence in drinking water in the first place. Thus, 25 halogenated compounds were synthesised in order to investigate 60 substances (Bisphenols, parabens and their degradation products) in 325 drinking water samples coming from a French cohort study of pregnant women. Analysis was performed by tandem mass spectrometry coupled to gas chromatography (GC-MS/MS) after SPE extraction and derivation of the contaminants. Results indicate that parabens (methylparaben, n-propylparaben, ethylparaben and n-butylparaben), bisphenols S, A and F, and their degradation product, 4-hydroxybenzoic acid, were detected up to several hundred ng/L in drinking water, with detection frequencies between 16% and 88%. Regarding halogenated degradation products, the highest detection frequencies were found for monochlorinated products (about 50% for 2-chlorobisphenol A), which were quantified up to several tens of ng/L. Such analytical approaches with broader spectrum of monitoring (i.e. chemical hazards and their degradation products) constitute in the beginning of a solution to exhaustively answer the questions related to the characterization of the human chemical exposome.

Assessment of the impact of pharmacist-led intervention with antibiotics in patients with bone and joint infection.

OBJECTIVES: The management of patients with bone and joint infections (BJIs) is complex. To improve this care, we carried out pharmaceutical actions in the orthopedic unit, including pharmacist-led-intervention (PLI) for patients requiring prolonged antibiotics. Few data exist regarding patient compliance, adherence and knowledge in cases of BJI. Data on hospital readmission are likewise limited, even though it is considered as a major determinant of clinical impact. The aim of this study was to assess the effectiveness of PLI regarding six-month readmissions. PATIENTS AND METHODS: Patients were assigned to two groups, both receiving standardized care. Two periods were compared: control group (CG) without PLI and interventional group (IG) with PLI throughout. The analysis was based on patient records and included: proportion of rehospitalizations at 6 months for infectious causes, reasons for antibiotic dose modification or antibiotic switch after 6 weeks, and descriptive analysis of data on pharmaceutical interventions in care pathways. RESULTS: Analysis was performed on 164 patients: 105 CG (64 %) patients and 59 IG (36 %) patients. There were no significant differences between IG and CG in patients' socio-demographic characteristics, infectious factors and antibiotic regimens. Amongst the CG patients, 23 were readmitted (22 %) versus 3 patients in the IG (5 %), (p = 0.002). There were significantly fewer treatment changes after 6 weeks (28.6 % versus 15.3 %, p = 0.05) for IG patients. CONCLUSION: In this retrospective survey, our results suggest a positive impact of PLI on 6-month readmission for all causes in BJI patients. These results need to be confirmed in a multicentric study.

Quantification of the Conjugated Forms of Dichlorobisphenol A (3,3'-Cl 2 BPA) in Rat and Human Plasma Using HPLC-MS/MS.

BACKGROUND: Bisphenol A (BPA) is a ubiquitous contaminant that has endocrine-disrupting effects. Chlorinated derivatives of BPA are formed during chlorination of drinking water and have higher endocrine-disrupting activity. Dichlorobisphenol A (Cl 2 BPA) is the most abundant chlorinated BPA derivative found in several human biological matrices. Recent in vitro experiments have shown that Cl 2 BPA is metabolized in sulpho- and glucuro-conjugated compounds. To date, no assay has been developed to quantify the sulfo- and glucuro-conjugates of 3,3'-Cl 2 BPA (3,3'-Cl 2 BPA-S and 3,3'-Cl 2 BPA-G, respectively). METHODS: A high-performance liquid chromatography-tandem mass spectrometry assay for the determination of 3,3'-Cl 2 BPA conjugated forms in plasma samples was developed and validated according to the European Medicines Agency guidelines. Quantification was performed in the multiple reaction monitoring mode for all target analytes using a SCIEX 6500 + tandem mass spectrometer with an electrospray source operating in the negative ionization mode. Chromatographic separation was achieved using a C18 column maintained at 40°C and a binary mobile phase delivered in the gradient mode at a flow rate of 0.35 mL/min. Sample was prepared via simple precipitation using acetonitrile. The assay was validated and applied to rat and human plasma samples. RESULTS: Linearity was demonstrated over the range of 0.006-25 ng/mL for 3,3'-Cl 2 BPA-G and 0.391-100 ng/mL for 3,3'-Cl 2 BPA-S. Intraday and interday bias values were in the 95%-109% range, and the imprecision <9%. Internal standard corrected matrix effects were also investigated. This method enabled quantification of the conjugated forms of 3,3'-Cl 2 BPA in plasma samples. CONCLUSIONS: This is the first report on the development and validation of an analytical method for the quantification of 3,3'-Cl 2 BPA-G and 3,3'-Cl 2 BPA-S in the plasma matrix. This study is also the first report on the in vivo occurrence of these metabolites.

Climate change and health care facilities: A risk analysis framework through a mapping review.

INTRODUCTION: Climate change (CC) has been identified as the biggest global health threat of the 21st century. Although health care facilities (HCF) play a central role in the care of populations, there has been no comprehensive assessment of the impact of CC on HCF. The objective of our study was to highlight the components of HCFs affected by CC through a mapping review of the literature. METHODS: To meet our objective, we first assessed the place of HCFs in relation to CC in the scientific literature and in the Intergovernmental Panel on Climate Change (IPCC) reports. Bibliometric data from the PubMed database were analyzed between 1979 and 2021 to assess the penetration of keywords on CC alone, and in relation to health and HCF in particular. Second, we analyzed the changes in HCF keywords in the IPCC reports. Finally, we conducted a mapping review in five databases, of the international scientific literature published between 1979 and 2019, and identified the components of HCF affected by CC using the Ishikawa diagram. RESULTS: From the 2000s, the number of publications on CC and HCF increased gradually with 137 articles in 2005, and even more sharply since 2008 with 358 articles published and 813 in 2021. Even though CC is only recently present in the biomedical literature, all climatic events (warming and heatwaves, droughts, wildfires, storms, hurricanes and cyclones, floods and sea-level rise, and other indirect effects) have had an impact on at least one component of HCF. CONCLUSION: HCFs are already impacted, in all their components, by CC. By enhancing our understanding of the impacts of CC on HCF, this work could contribute to the engagement of health professionals in the implementation of mitigation and adaptation actions, thereby limiting the consequences of CC on patient care.

A Clinical Preventive Strategy Based on a Digital Tool to Improve Access to Endocrine Disruptors Exposure Prevention: The MEDPREVED Study.

Introduction: The digitalized PREVED (PREgnancy, PreVention, Endocrine Disruptor) questionnaire was used in the clinical practices of health professionals (HP) who adhered to the MEDPREVED strategy. The objectives were to assess the strategy and to determine if it could improve access to endocrine disruptor (ED) exposure prevention. Methods: After having filled in the digital questionnaire in HP waiting rooms, patients were invited to talk about ED exposure during the consultation. HPs were previously trained in ED and had received a prevention kit for their patients. After the seven-month implementation phase, the evaluation phase consisted of five mixed assessments: interviews with: (i) patients who were young children's parents; (ii) patients in the general population; (iii) paediatricians; (iv) midwives; and a quantitative study on GPs. Assessment concerned feasibility, accessibility, and usefulness of the strategy; we then used the Levesque model to evaluate how it could improve access to ED exposure prevention. Results: The study included 69 participants. The strategy appeared feasible for the filling-out step due to digital and environment access. However, it depended on patient and HP profiles. The strategy seemed useful insofar as it facilitated reflexive investment, an intention to healthy behaviour and, rather rarely, talk about ED exposure. The beginning of this discussion depended on time, prioritizing of the topic and HP profile. The strategy has confirmed the Levesque model's limiting factors and levers to access ED prevention. Conclusions: The MEDPREVED strategy is feasible, accessible, and useful in clinical prevention practice. Further study is needed to measure the impact on knowledge, risk perception and behavior of beneficiaries of the MEDPREVED strategy in the medium and long term.

Analytical method for the biomonitoring of bisphenols and parabens by liquid chromatography coupled to tandem mass spectrometry in human hair.

Bisphenols and parabens are endocrine disruptors families widely used in daily life. They are known to be linked to numerous pathologies such as reproductive disorders, obesity, breast cancer, hypertension and asthma. Biomonitoring is an essential tool for assessing population exposure to environmental pollutants. Blood and urine are the main matrices used in human biomonitoring. However, they are not suitable to evaluate long-term exposure to endocrine disruptors with a short elimination half-life such as parabens or phenols. Hair appears to be an interesting alternative matrix allowing a wide window of exposure due to an accumulation of xenobiotics during hair growth. This study presents the development and validation of a high-performance liquid chromatography coupled to tandem mass spectrometry for the simultaneous determination of bisphenol A, its chlorinated derivatives, bisphenol F, bisphenol S and parabens in human hair. An optimised sample preparation based on acidic hydrolysis followed by liquid-liquid extraction was performed, before an analysis by ultra-high performance liquid chromatography coupled to tandem mass spectrometry in multiple reaction monitoring mode. To validate the method, recognized bioanalytical guidelines were used and calibration and quality control samples were prepared in human hair samples. Linearities were over 0.996 in the whole range of concentrations. Trueness and precision were demonstrated for each target analyte with intra-day and inter-day bias values ranging from 86 % to 118 % and relative standard deviation values ranging from 0 % to 19 %. At the same time, limits of quantification were set at 0.25 ng/g for bisphenol A and parabens, 0.05 ng/g for bisphenols F and S and 0.00625 ng/g for the chlorinated derivatives of bisphenol A. This reliable method was applied to hair samples taken from hospital professionals and allowed the quantification of these endocrine disruptors in this population. Chlorinated derivatives of bisphenol A were quantified here in hair for the first time.

Risk and asset-based strategies in health: priorities in biomedical, life and environmental science literature since the early twentieth century. A rapid review.

BACKGROUND: In biomedical, life or environmental science research, two different strategies exist depending on the starting point of the researchers: "what makes us ill? " or "what makes us healthy?". Indeed, a risk-based strategy (RBS) attempts to minimize risk factors increasing the likelihood of developing a disease, while an asset-based strategy (ABS) attempts to promote and strengthen the factors that support good health and wellbeing. We provided an up-to-date overview of both research strategies in peer-reviewed scientific literature, in the fields of human health, animal and plant health and ecosystem health, to fit with the One Health framework. More particularly, we focused on human health by studying publications related to the COVID-19 at the beginning of the pandemic. DESIGN: A rapid review of research science literature was carried out to identify in the PubMed/MEDLINE database the proportion of peer-reviewed articles adopting either a RBS or an ABS, in the main global environment fields from January 01, 1900 to December 31, 2019 and, related to COVID-19, from December 1, 2019 to May 31, 2020. RESULTS: The number of published articles resulting from our search was 1,957,905, including 91.3% with an RBS and 8.7% with an ABS. When examining each field, we found that only 10.5% of human health articles deal with ABS, 5.5% for animal health, 2.2% for ecosystem health, 1.0% for plant health and 2.7% for environmental media. We noted that articles adopting both strategies were published in all health fields. Among the articles concerning COVID-19, 5,854 (55.9%), 542 articles (5.2%) adopted RBS and ABS, respectively, while 4069 (38.9%) simultaneously presenting both strategies. CONCLUSION: Our results have allowed us to take stock of the biomedical research strategies prioritized during the twentieth century. It seems highly likely that the two strategies we have analyzed can now be chosen in such a way as to promote a balance in public health measures, at every level to guide One Health interventions aimed at helping people, animals, and plants to lead healthier lives.

Impact of perinatal environmental health education intervention on exposure to endocrine disruptors during pregnancy-PREVED study: study protocol for a randomized controlled trial.

BACKGROUND: The suspected or actual effects on health of endocrine-disrupting chemicals (EDC) and their ubiquitous presence in everyday life justify the implementation of health promotion interventions. These interventions should ideally be applied during critical windows like pregnancy. Perinatal environmental health education interventions may help to reduce EDC exposure during pregnancy. METHODS/DESIGN: PREVED (Pregnancy, PreVention, Endocrine Disruptors) is an open-label randomized controlled trial assessing the impact of environmental health education intervention on EDC exposure during pregnancy. Inclusion, consent, and randomization take place during the first trimester. The participants are randomly allocated into three groups: (i) control group (information leaflet on EDCs), (ii) intervention group in neutral location (information leaflet and workshops in a meeting room), and (iii) intervention group in contextualized location (information leaflet and workshops in a real apartment). Workshops are organized between the second and third trimesters of pregnancy. Main outcome is the percentage of participants who reported consuming manufactured/industrial food. Secondary outcomes are as follows: (i) psycho-social dimensions, (ii) EDC concentrations in urine, (iii) EDC concentration in colostrum, and (iv) percentage of participants who reported consuming paraben-free personal care products. DISCUSSION: PREVED is a ground-breaking intervention research project dedicated to perinatal environmental health education that aims to identify pollutant sources in daily life and to offer accessible and realistic alternative solutions, by promoting the sharing of know-how and experience in a positive and non-alarmist approach. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03233984 (current status: ongoing). Retrospectively registered on 31 July 2017 ( https://clinicaltrials.gov/ct2/show/NCT03233984 ) because when the first participant was enrolled in this non-drug intervention, ClinicalTrials.gov was centered in therapeutic trials. The World Health Organization Trial Registration Data Set is in Additional file 1.

Implementing a personalized pharmaceutical plan in kidney or liver transplant patients: study protocol for a stepped-wedge cluster randomized trial (GRePH).

BACKGROUND: Nowadays, the main challenge of transplantation is the improvement of long-term care, aiming at reducing treatment-related complications and at decreasing rejection rates. Patients' adherence to both treatment and hygienic-dietary measures is mandatory to achieve these objectives. Adherence to immunosuppressive drugs is estimated to be only 70%. We hypothesized that the implementation of a personalized pharmaceutical plan (PPP) would increase adherence and therefore graft survival. METHODS/DESIGN: This study is a stepped-wedge cluster randomized trial with transplantation units defining clusters. Twelve clusters from 10 university hospitals were recruited. All centres started on the same day in the control phase. Every 7 weeks, one centre will switch to the intervention phase and remain there until the end of inclusions. We plan to recruit 1716 kidney and/or liver transplant patients. The intervention phase consists in setting up the PPP: development of the patient's hospital and community pharmaceutical follow-up. In the hospital, the pharmacist will carry out drug reconciliation upon admission, daily pharmaceutical follow-up of prescriptions and pharmaceutical interviews with the patient in order to explain the modalities of taking immunosuppressive drugs and hygienic-dietary measures. After hospitalization, during the post-transplantation year, pharmaceutical meetings will take place, prior to medical consultations in order to check the patient's understanding of the prescription, his adherence, to remind them of hygienic-dietary measures and to look for adverse effects. The hospital pharmacist will also be in charge of establishing a close link with the community pharmacist (CP) and general practitioner, especially providing discharge medication reconciliation, an e-learning and a checklist. Moreover, prior to each pharmaceutical consultation, the hospital pharmacist will contact the CP to discuss patient adherence. The primary outcome is adherence to immunosuppressive treatments 1 year post-transplantation assessed by using the BAASIS questionnaire and the health insurance data from the national health data system. A medico-economic study will measure the efficiency of this plan. DISCUSSION: GRePH aims to increase adherence of liver and/or kidney transplant patients to their immunosuppressive therapies in order to reduce transplant rejections. To this end, a new clinical pharmacy model, the PPP, will be set up in 10 university hospitals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04295928 . Registered on 5 March 2020.

Accuracy of Dose Administered to Children Using Off-Labelled or Unlicensed Oral Dosage Forms.

The pediatric population suffers from a lack of age-appropriate medicines leading to unsafe situations when off-labelled or unlicensed drugs are used. Assessing the best option to administrate medicines when manipulations are required is essential in order to improve child care. This study aimed to compare the accuracy of the administered dose provided by three dosage forms and their techniques of administration. Different techniques of administration were assessed, covering three oral dosage forms (commercially available tablets, capsules, oral suspensions) using two APIs not available in a children-adapted dosage form. Techniques of administration were simulated and administered doses were determined using HPLC-UV. Means were compared to the target dose while distributions of doses were compared between each technique. For both APIs, mean administered doses obtained with capsules and tablets were significantly different from the target dose, whereas there was no statistical difference with oral suspensions. Distributions of doses showed significant difference between the three dosage forms. This study demonstrates that manipulations of solid oral dosage forms provide dramatic underdosing leading to unsafe situations. Compounded oral suspension is the best option to avoid underdosing and dose variation. This solution should be prioritized when age-appropriate commercial medicines are not available.

Comparison of the Effect on Fetal Growth of a Mixture of Atrazine and Nitrates in Drinking Water and of Active Tobacco Exposure during Pregnancy.

Active tobacco exposure during pregnancy is a known determinant of fetal growth. Nitrates and atrazine metabolites in drinking water may affect fetal growth as a mixture of endocrine disruptors (ED). We aimed to determine whether EDC have an additional effect on fetal growth compared to active tobacco exposure. A historic cohort study was carried out with a sample stratified with regard to the maternity unit, drinking water exposure, and year of birth. The women included were living in Deux-Sèvres, had given birth between 2005 and 2010 in three selected maternity units, and ultrasound data were available in their obstetrical records. Mixed linear models were used to analyze fetal weight evolution from the second trimester to the time of birth according to drinking water exposure to EDC mixture and active tobacco exposure. We included 558 mother-neonate couples, of whom 9% were exposed to high doses of the mixture and 21% to active tobacco smoking. There was no difference in fetal weight evolution according to drinking water mixture exposure (0.97 g; 95% CI [-3.01; 4.94]). We could not show a supplementary effect of mixture exposure in drinking-water on fetal growth as compared to active tobacco exposure. Further research is needed, using more precise methods to estimate EDC exposure.

Perinatal Environmental Health Education Intervention to Reduce Exposure to Endocrine Disruptors: The PREVED Project.

Environmental health promotion interventions may reduce endocrine disruptor (ED) exposure. The PREVED (PREgnancy, preVention, Endocrine Disruptors) project was developed to improve knowledge, to enhance risk perception, and to change exposure behavior. Our objective was to present the phases of the PREVED project using the RE-AIM method. PREVED intervention consisted of three workshops during pregnancy. Reach, adoption, and implementation phases were assessed with qualitative studies. Efficacy study consisted of a three-arm randomized controlled trial (RCT) on 268 pregnant women: (i) control group (leaflet), (ii) intervention group in neutral location, (iii) intervention group in contextualized location. The main outcome was the percentage evolution of participants who reported consuming canned food. Secondary outcomes were evolution of psycho-social scores, evolution of ED presence in urine, and ED presence in colostrum. The intervention adoption was centered on upper-privileged women, but implementation assessment showed that key features (highly practical intervention) seemed to be carried out and had initiated some behavior changes. A total of 268 pregnant women participated in the intervention and 230 in a randomized controlled trial (control group: 86 and intervention groups: 172). We found no significant differences in consumption of canned food and in percentage of women having a decrease of bisphenol A or parabens in urine, but we found a significant increase in the evolution of risk perception score and overall psychosocial score in intervention groups (respectively: +15.73 control versus +21.03 intervention, p = 0.003 and +12.39 versus +16.20, p = 0.02). We found a significant difference in percentage of women with butylparaben detection between control group and intervention groups (13% versus 3%, p = 0.03). PREVED intervention is the first intervention research dedicated to perinatal environmental health education in France. By sharing know-how/experience in a positive non-alarmist approach, it improved risk perception, which is key to behavior change, aiming to reduce perinatal ED exposure. Including women in precarious situations remains a major issue.

Fiber Orientation and Concentration in an Injection-Molded Ethylene-Propylene Copolymer Reinforced by Hemp.

This paper characterizes and analyzes the microstructures of injection-molded polypropylene parts reinforced with 20 wt% of hemp fibers in order to understand the process induced variations in thermomechanical properties. In-thickness fiber orientation and fiber content were determined by X-ray tomography along the flow. The fiber content along the flow path was also determined by direct fiber content measurements after matrix dissolution, showing an increase of 2%/100 mm for a 2.2 mm-thick plate due to fiber migration during the filling stage. A typical shell/core structure for fiber orientation in injection molding was observed, but with a very clear transition between the layer solidified under high shear rates and the core in which the fiber content was reduced by more than 50%. The orientation of hemp fibers is lower than the one of glass fibers, especially in thickness direction. However, the overall fiber orientation in the injection direction induces significant anisotropic thermomechanical properties, which cannot be explained by simple micromechanical models that consider isotropic mechanical properties for hemp fibers. These phenomena must be taken into account in process simulation codes for injection molding to better predict thermomechanical properties as well as part shrinkage and warpage to design molds.

Preparation and physicochemical stability of 50 mg/mL hydroxychloroquine oral suspension in SyrSpendⓇ SF PH4 (dry).

In the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, hydroxychloroquine has been proposed as a potential agent to treat patients with COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 infection. Older adults are more susceptible to COVID-19 and some patients may require admission to the intensive care unit, where oral drug administration of solid forms may be compromised in many COVID-19 patients. However, a liquid formulation of hydroxychloroquine is not commercially available. This study describes how to prepare a 50 mg/mL hydroxychloroquine oral suspension using hydroxychloroquine sulfate powder and SyrSpendⓇ SF PH4 (dry) suspending vehicle. Moreover, a fully validated stability-indicating method has been developed to demonstrate the physicochemical stability of the compounded hydroxychloroquine oral suspension over 60 days under refrigeration (5 ± 3 °C). Finally, use of the proposed oral suspension provides a reliable solution to perform safe and accurate administration of hydroxychloroquine to patients with SARS-CoV-2 infection.