Added Therapeutic Value of Medicinal Products for French and German Health Technology Assessment Organizations: A Systematic Comparison.

OBJECTIVES: Determining the price and reimbursement of a new medicine is a national competence within the Member States of the European Union that is carried out by health technology authorities and is based mainly on the added therapeutic value (ATV). The primary objective of this study was to compare the ATVs granted by the French (Haute Autorité de Santé, HAS) and the German (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWIG) authorities. The secondary objective was to analyze the reasons for the discrepancies observed. METHODS: Retrospective cohort of all ATVs assigned by HAS and IQWIG for the period 2011 to 2017. ATV assessments were classified as major, considerable, minor, no benefit, or not quantifiable. The concordance between the authorities was evaluated, and a qualitative analysis of highly discordant assessments was performed. RESULTS: One hundred and ninety-one drugs were evaluated by both agencies. The overall percentage of agreement was 50.3%. It was 73.1% for no benefit of ATVs, 37.5% for minor ATVs, 31.2% for considerable ATVs, and 5% for major ATVs. Highly conflicting assessments (n = 35) mainly concerned antineoplastic drugs (n = 14) and anti-infectives (n = 14). The main reasons for inconsistency concerned the following: a different appreciation of the subgroup analysis of efficacy data (n = 15), the appropriateness of comparators (n = 15), the surrogate endpoints (n = 10), methodological differences (n = 8), and the benefit/risk criteria that were used (n = 6). CONCLUSION: In the context of the common assessment of ATVs promoted by the European Commission, the harmonization between member states regarding the way evaluation criteria are assessed deserves to be addressed.

Do the EMA accelerated assessment procedure and the FDA priority review ensure a therapeutic added value? 2006-2015: a cohort study.

PURPOSE: The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have both implemented procedures in order to shorten review time for marketing authorizations with potential therapeutic added value, called priority review and accelerated assessment procedure, respectively. The aim of this study is to compare the new molecular entities (NME) assessed in shorter review time by both agencies and to investigate whether granting a shorter review time status subsequently predicts its therapeutic value attributed by a health technology assessment agency, the French Haute Autorité de Santé (HAS). METHODS: All NME approved by the EMA and the FDA with a therapeutic added value between 2007 and June 30, 2015 were extracted. We assessed the sensibility, the positive predictive value, and the EMA review time. RESULTS: One hundred seventy-eight NME were approved by the FDA and the EMA and a therapeutic value was available for 160 NME. Eighty-eight (55.0 %) NME were on FDA priority review, 24 (15.0 %) on EMA accelerated procedure and 43 (26.9 %) were considered of high clinical added value. The sensibility was 86.0 % for the FDA and 30.2 % for the EMA. The positive predictive value was, respectively, 42.0 and 54.2 %. Twenty-five NME on FDA priority review and of high therapeutic added value were not on EMA accelerated assessment procedure, leading to a supplementary mean EMA review time of 146 days. CONCLUSION: The EMA was restrictive to grant a shorten review time status for products with therapeutic interest during the study period.

Malnutrition and Its Determinants among Older Adults Living in French Caribbean Nursing Homes: A Cross-Sectional Study.

BACKGROUND: This study aimed to assess the prevalence of malnutrition and its determinants in older adults living in French Caribbean nursing homes. METHODS: This cross-sectional study was taken from the KASEHAD (Karukera Study of Ageing in EHPAD) study. Nutritional status was assessed with the Mini Nutritional Assessment Short-Form (MNA-SF). Clinical characteristics and scores on geriatric scales (Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Short Physical Performance Battery (SPPB), Center for Epidemiologic Studies-Depression (CESD) and Questionnaire Quality of Life Alzheimer's Disease (QoL-AD)) were extracted. Bivariate analysis and logistic models adjusted were performed to test the association between nutritional status and both socio-demographic variables and geriatric scales. RESULTS: A total of 332 older adults from six nursing homes were included in the KASEHPAD study. Among the participants, 319 had an MNA-SF score. The mean age was 81.3 ± 10.6 years, and half of the participants were men. The frequency of malnutrition (MNA-SF ≤ 7) was 27.6% (95% confidence interval (CI): 22.0-32.5) (n = 88). Based on the multivariable analysis, a low MMSE was associated with malnutrition (OR: 0.81 (0.68-0.92); p = 0.015) and there was a borderline significant link between a higher CESD score and malnutrition (OR: 1.05 (1.00-1.12); p = 0.07). CONCLUSIONS: Cognitive decline and a tendency toward depression were associated with malnutrition in nursing homes in the French West Indies. Although this study cannot establish causal relationships, the identification of these three geriatric syndromes in nursing homes is crucial for preventing adverse health events.

Comparison of quality of life of older adults living in foster families versus nursing homes. Results from the KASA studies.

OBJECTIVES: Professional foster families for dependent older adults could be an alternative to nursing homes. Engagement in the family life and close contact with a single reference person could enhance their quality of life (QOL). This study aimed to compare the Health-Related Quality of Life (HrQOL) and subjective QOL among older adults living in foster families versus those in nursing homes. DESIGN: Cross-sectional analysis from twin studies conducted in foster families (the KASAF study) and nursing homes (the KASEHPAD study). SETTING AND PARTICIPANTS: Older adults (aged 60 years or older) in French Caribbean Islands living in foster families or nursing homes. MEASUREMENTS: HrQOL was measured using the EuroQol-five dimensions (EQ5D-3L) and QOL was assessed using a Visual Analog Scale (QOL-VAS). For older adults unable to complete these scales, proxy EQ-5D-3L assessments were conducted by paramedical staff or foster caregivers. RESULTS: A total of 439 older adults, with 107 in foster families and 332 in nursing homes were included. Participants living in foster families were less often male, had less often hypertension, were more dependent or physical impaired and had lower score of cognition. In multivariate analyses, factors associated with low self-reported HRQoL (n = 240) were Mini Mental State Examination (MMSE) score (ß: -0.011; p = 0.003) and Activities of Daily Living (ADL) score (ß: 0.014; p < 0.001). A lower QOL-VAS score (n = 150) was associated with living in a nursing home compared to living in a foster family (ß: -19.48 points; p < 0.001) and with the ADL score (2.94 points; p = 0.019). In older adults with major cognitive disorders, the only factor associated with low proxy EQ-5D proxy index score (n = 136) was dependency (ß: 0.167; p < 0.001). CONCLUSION: HrQOL was similar between older adults living in nursing homes and foster families. Additionally, older adults reported a better subjective quality of life when residing in foster families. These findings suggest that the foster family model may meet the social and environmental needs of dependent older adults for whom nursing homes are not suitable.

Malnutrition and its determinants among older adults living in foster families in Guadeloupe (French West Indies). A cross-sectional study.

BACKGROUND: Foster families may represent an alternative model for dependent older adults in many countries where nursing homes are insufficiently developed. This study aimed to assess the prevalence of malnutrition and its determinants in older adults living in foster families in Guadeloupe (French West Indies). METHODS: This cross-sectional study was gathered from the KASAF (Karukera Study of Ageing in Foster families) study (n = 107, 41M/66F, Mdn 81.8 years). Nutritional status was assessed with the Mini Nutritional Assessment Short-Form (MNA-SF). Clinical characteristics and scores on geriatric scales (Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Short Physical Performance Battery (SPPB), Center for Epidemiologic Studies- Depression (CESD) and Questionnaire Quality of Life Alzheimer's Disease (QoL-AD)) were extracted. Bivariate analysis and logistic models adjusted for age and gender were performed to test the association of nutritional status with socio-demographic variables and geriatric scales. RESULTS: Thirty (28.0%) older adults were malnourished (MNA-SF score ≤7). In bivariate analysis, malnutrition was associated with an increased prevalence of cardiovascular diseases (46.7% versus 19.5%, p = 0.004), the presence of hemiplegia (30.0% versus 6.5%, p = 0.003), a poorer cognitive status (MMSE score 4.7 ± 7.1versus 9.7 ± 10.7; p = 0.031), higher risk of depression (CESD score 27.3 ± 23.0 versus 13.5 ± 14.4; p = 0.035) and dependency (ADL score 1.9 ± 1.9 versus 2.3 ± 2.1; p<0.001). Malnutrition was also associated with lower caregivers'rating of QoL (QoL-AD score 21.8 ± 6.4 versus 26.0 ± 5.7; p = 0.001) but not by older adult's rating (24.1 ± 11.2 versus 28.3 ± 7.7; p = 0.156). Similar associations were observed in logistic models adjusted for age and gender. CONCLUSION: Malnutrition was common among foster families for older adults. Special attention towards the prevention and treatment of malnutrition in older adults from cardiovascular diseases, cognitive impairment, dependency and depression is necessary in this model of dependency support.

Association between Polypharmacy and Hospitalization among Older Adults Admitted to Emergency Departments for Falls in Guadeloupe: A Retrospective Cohort Study.

Introduction: Falls are a common geriatric syndrome in older people. Falls are associated with adverse health events such as dependency, unplanned emergency admissions and death. This study aimed to identify the factors associated with fall severity, such as diabetes, hypertension, heart disease, cognitive decline and polypharmacy, as well as sociodemographic characteristics in patients aged 70 years and over admitted to the emergency department in Guadeloupe. Method: A single-center, observational, retrospective study of patients aged 70 years and over admitted to the emergency department (ED) of the University Hospital of Guadeloupe for a fall between 1 May 2018 and 30 April 2019 was conducted. Fall severity was defined as the need for hospitalization. Bivariate analysis was used to determine the associations between fall severity and sociodemographic characteristics, comorbidities, history of falls and polypharmacy (defined as the daily use of at least five drugs). Polypharmacy was analyzed as a binary variable (>5 drugs daily; yes or no) in categories (0-3 (ref.), 4-6, 7-9 and ≥10 drugs). Results: During the study period, 625 patients who attended the ED for a fall were included. The mean age was 82.6 ± 7.6 years, and 51.2% were women. Of these, 277 patients (44.3%) were admitted to the hospital, and 3 patients (0.5%) died. In the bivariate analysis, only polypharmacy was associated with hospitalization for a fall (OR: 1.63 [95% CI: 1.33-2.02]). The odds ratios for the polypharmacy categories were 1.46 [95% CI 0.99-2.14], 1.65 [1.09-2.50] and 1.48 [0.76-2.85] for 4-6, 7-9 and ≥10 drugs, respectively. Conclusions: Polypharmacy was associated with hospitalization as a proxy for fall severity. A regular review of drug prescriptions is essential to reduce polypharmacy in older adults.

Clinical Characteristics of Older Adults Living in Foster Families in the French West Indies: Baseline Screening of the KArukera Study of Aging in Foster Families (KASAF) Cohort.

Background and Objectives: Foster families for older adults could represent a transitional or alternative model to nursing homes. The aim of this study was to describe the clinical characteristics of older adults in foster families and to compare them with those of residents in nursing homes in French West Indies. Research Design and Methods: This study is a cross-sectional analysis of the KArukera Study of Aging in Foster Families (KASAF) cohort. Sociodemographic and clinical characteristics were extracted. Dependency was assessed using the Activities of Daily Living (ADL) scale and cognition using the Mini-Mental State Examination (MMSE) scale. Age, gender, ADL, and MMSE scores were compared with nursing home residents from a twin study of KASAF (n = 332). Results: A total of 107 older adults (mean age 81.8 years; 61.7% women) were recruited in 56 foster families between September 2020 and May 2021. In all, 25.5% had diabetes mellitus and 45.8% suffered from hypertension. The mean MMSE score was 9.3 ± 10.1 and 76.0% had major cognitive impairment (MMSE score <18); 12.5% were diagnosed with Parkinson's disease, and 42.0% of the residents were confined to bed or in a wheelchair, with a mean ADL score of 1.5 ± 1.8. Almost all the residents (96.3%) benefited from a medical follow-up by a nurse who visited once or twice a day. Compared to older adults living in nursing homes, those in foster families were more frequently women (61.7% vs 49.4%) and had lower ADL score (1.5 vs 2.4) and lower MMSE score (9.3 vs 11.3). Discussion and Implications: The clinical profile of foster families' residents was quite similar to that of nursing home residents in terms of demographics, dementia, and dependency. Foster families might represent an interesting strategy to address the unmet clinical and social needs of dependent older adults, especially in countries where nursing homes are not sufficiently developed. Clinical Trials Registration Number: NCT04545775.

The Health Care Trajectories of Older People in Foster Families: Protocol for an Observational Study.

BACKGROUND: With aging of the population, the search for alternative models of care adapted to older people with dependency is necessary. In this setting, foster families (1-3 older people per family) could be an alternative to nursing homes, residential care facilities, or community- and home-based care. OBJECTIVE: The KArukera Study of Ageing in Foster Families is a prospective cohort study designed to investigate the care pathways of older people with dependency in foster care over a year. The 1-year hospitalization rate (main objective), cost of hospitalization, incidence of mortality, prevalence of geriatric syndromes, and quality of life of residents will be assessed. Quality of life and burnout of their respective foster caregivers will also be studied. METHODS: This study cohort will include 250 older people living in foster families in Guadeloupe (French West Indies), as well as their respective foster caregivers. Both older people and caregivers will be interviewed concurrently on site at three time points: (1) at baseline, (2) at 6 months, and (3) at 12 months. For older people, we will collect anthropometric measures, cognitive impairment, depressive and anxiety symptoms, functional abilities, physical frailty, information on general health status, quality of life, and care pathways (hospitalization, mortality, and medical and paramedical consultations). We will also assess the quality of life and burnout symptoms of family caregivers at each follow-up. A phone update of vital status (alive or death) and care pathways of residents will be carried out at 3 and 9 months after the baseline examination. RESULTS: Recruitment opened in September 2020 and ended in May 2021, with 109 older people recruited and 56 respective foster caregivers. The 1-year follow-up was ended in June 2022. Data analyses are ongoing and the first results are expected to be published in May 2023. CONCLUSIONS: Foster families are a potentially innovative way to accommodate dependent older people. This study could help define the clinical profile of older people adapted to foster families in the transition from frailty to dependency. The effectiveness of foster families, in terms of hospitalizations and mortality, will be compared with other models of care, particularly nursing homes. In this setting, a twin study carried out in nursing homes in Guadeloupe with similar aims and outcomes will be conducted. Beyond mortality and morbidity, the numerous outcomes will allow us to assess the evolution of geriatric syndromes over time. TRIAL REGISTRATION: ClinicalTrials.gov NCT04545775; https://clinicaltrials.gov/ct2/show/NCT04545775. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40604.

Correlates of Undernutrition in Older People in Guadeloupe (French West Indies): Results from the KASADS Study.

Objectives: This study aimed to determine the risk factors for undernutrition in community-dwelling older adults in Guadeloupe (Caribbean islands). Methods: We used data from the KArukera Study of Aging-Drugs Storage (KASADS), an observational cross-sectional study of community-dwelling older people living in Guadeloupe. The Mini Nutritional Assessment (MNA) was used to assess the risk of undernutrition. An MNA-short form (SF) score ≤11 defined the risk of undernutrition. Depression was assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, cognitive function was assessed using the Mini Mental State Examination (MMSE), frailty was assessed using the Study of Osteoporotic Fractures index (SOF), and dependency was assessed using Lawton's instrumental activities of daily living (IADL) scale. Bivariate and multivariate analyses were used to determine the correlates of undernutrition. Results: The study sample comprised 115 patients aged 65 years or older; 67.8% were women, and the mean age was 76 ± 7.8 years. The prevalence of undernutrition was 21.7% (95% CI = 15.2-30.1%). In our bivariate analysis, the risk of undernutrition was associated with MMSE score, IADL score, frailty, and CES-D score. We found no significant relation between nutrition risk and other variables, such as marital status, pain, or polypharmacy. In the multivariate analysis, the factors associated with the risk of undernutrition were MMSE score (Odd-Ratio (OR): 0.74 (0.58-0.97)) and CES-D score (OR: 1.13 (1.02-1.27)). Conclusions: Cognitive decline and the risk of depression were independently associated with the risk of undernutrition in community-dwelling older people in Guadeloupe. Although we cannot imply causality in this relation, the detection of these three key geriatric syndromes in community-dwelling elders is essential to prevent adverse health outcomes. Further studies are warranted to confirm these findings.

Correlates of Health-Related Quality of Life in Community-Dwelling Older Adults in Guadeloupe (French West Indies): Results from the KASADS Study.

OBJECTIVES: The aim of this study was to determine the correlates of health-related quality of life (HRQoL) in community-dwelling older adults in Guadeloupe. METHODS: We used the Karukera Study of Aging-Drugs Storage (KASADS), an observational, cross-sectional study on community-dwelling older people living in Guadeloupe. A visual analogue scale ranging from 0 to 100 was used to assess HRQoL. RESULTS: The study sample consisted of 115 patients aged 65 years or older; 67.8% were women. Participants were 76 (±7.8) years old with a mean HRQoL of 66.2 (±20.3). The correlates of HRQoL were complaints of pain (p < 0.001) and IADL dependency (p = 0.030) after adjustment. We found no significant interactions between HRQoL and other variables such as marital status, socio-educational level and cognitive decline. CONCLUSIONS: Pain and IADL dependency were independently associated with lower HRQoL in community-dwelling older people in Guadeloupe.

Health trajectories of elderly living in French senior housing: a longitudinal perspective.

Senior housing for older adults could be an alternative or a transitional care model between home care and nursing home care. Using two longitudinal cohorts of community dwellers aged 65 years or older, we compared risks of mortality and of nursing homes admission between older adults who did or did not move to senior housing over time. In the 3C study (n = 2104, 17 years of follow-up), 143 (6.8%) participants moved into a senior housing during the follow-up. This move was associated with a lower risk of mortality (hazard ratio (HR): 0.64; 95% confidence interval (CI) 0.46-0.77) and a higher risk of nursing home admissions (HR: 1.54 (1.10-2.15)). The risks of hospitalizations (HR: 0.54 (0.40-0.73)) and falls (HR: 0.63 (0.50-0.79)) were lower. In the PAQUID study (n = 3777, 27 years of follow-up), 161 (4.3%) participants moved into a senior housing. This move was also associated with a lower mortality risk (HR: 0.72 (0.58-0.88)) and a higher risk of nursing home admissions (HR: 1.39 (1.05-1.86)). Our results showing lower risks of mortality suggest that senior housing may be a relevant model for vulnerable older adults.

Drug storage, polypharmacy and frailty syndrome in older people: an observational study.

Introduction: the increasing prevalence of polypharmacy in the older population could lead to inappropriate storage of medicines at home. Since polypharmacy is associated with frailty, the main objective of the Karukera Study of Aging - Drug Storage (KASADS) study was to investigate the association between drug storage and frailty. If such an association exists, drug storage could be a simple tool for the identification of medication vulnerability by non-medical staff in the elderly. Methods: observational, cross-sectional study in community-dwelling older adults (>65 years old). Drug storage was defined as any drug in excess compared to a medical prescription, any unused and/or expired drug, or any drug without a medical prescription. Frailty was measured with the Study of Osteoporotic Fractures (SOF) scale, and polypharmacy was defined as a prescription of at least 5 drugs. Bivariate and multivariate analyses were performed to study the associations between drugs storage, frailty, and polypharmacy. Results: during the study period (01/10/2019 to 15/03/2020), 115 elderly people were interviewed in their own homes. The average age was 76.0 ± 7.8 years old. Seventy-two percent of the participants met the criteria for polypharmacy and 30.4% were prefrail/frail. They stored an average of 14.7 ± 18.2 boxes. Drug storage was associated with polypharmacy (17.5 boxes versus 10.0; p=0.031) but not with frailty (15.6 versus 14.3; p=0.724). In multivariate analysis, drug storage was associated with not having a school degree (OR: 1.78; 95%CI: 1.13-2.79), suffering from dyslipidemia (OR: 2.00; 95% CI: 1.28-3.17) and suffering from cognitive disorders evaluated by the Mini Mental State Examination (MMSE) score (OR: 1.10; 95%CI: 1.02-1.17). Conclusion: drug storage was not significantly associated with frailty. Nevertheless, it was associated with polypharmacy and other medical outcomes, and could therefore represent a new area for research in geriatrics and pharmacy.

Comparison of mortality and hospitalizations of older adults living in residential care facilities versus nursing homes or the community. A systematic review.

Residential care facility may provide a transition between living at home and a nursing home for dependent older people or an alternative to nursing homes. The objective of this review was to compare mortality and hospitalizations of older adults living in residential care facilities with those living in nursing homes or in the community. We searched Medline, Scopus and Web of Science from inception to December 2022. Fifteen cohort studies with 6 months to 10 years of follow-up were included. The unadjusted relative risk (RR) of mortality was superior in nursing homes than in residential care facilities in 6 of 7 studies (from 1.3 to 1.68). Conversely, the unadjusted relative risk of hospitalizations was higher in residential care facilities in 6 studies (from 1.3 to 3.37). Studies conducted on persons with dementia found mixed results, the only study adjusted for co-morbidities observing no difference on these two endpoints. Compared with home, unadjusted relative risks were higher in residential care facilities for mortality in 4 studies (from 1.34 à 10.1) and hospitalizations in 3 studies (from 1.12 to 1.62). Conversely, the only study that followed older adults initially living at home over a 10-year period found a reduced risk of heavy hospital use (RR = 0.68) for those who temporarily resided in a residential care facilities. There is insufficient evidence to determine whether residential care facilities might be an alternative to nursing homes for older people with similar clinical characteristics (co-morbidities and dementia). Nevertheless, given the high rate of hospitalizations observed in residential care facilities, the medical needs of residents should be better explored.

Tetrodotoxin Poisoning in Mainland France and French Overseas Territories: A Review of Published and Unpublished Cases.

Tetrodotoxin is one of the most potent neurotoxins in the aquatic world. This review of published and unpublished reports aims to describe the poisoning cases that have occurred in mainland France and overseas territories. Six articles were included, with 13 poisoning events, individuals or collective (number (n) = 53 patients). Moreover, 13 unpublished poisoning events from toxicovigilance networks were found (n = 17). All cases happened in overseas territories: French Guyana (n = 7), New Caledonia (n = 11), Reunion (n = 35) and French Polynesia (n = 17). The median age was 36 years. The most frequent signs were neurological (81.8%), digestive (54.5%) and general (52.3%). Three cases of dysgueusia and nine cases of urogenital discomfort were observed in French Polynesia. Twelve severe cases were reported, including seven deaths. Only three events (11.5%) were documented by a tetrodotoxin assay. Two families of fish accounted for 91.6% of the poisonings: 33.3% due to the Diodontidae family and 58.3% to the Tetraodontidae family. Although rare, information and collection campaigns on tetrodotoxin poisoning are, therefore, essential.

Explanatory factors of post-traumatic distress and burnout among hospital staff 6 months after Hurricane Irma in Saint-Martin and Saint-Barthelemy.

BACKGROUND: In September 2017, the Hurricane Irma devastated the islands of Saint-Martin and Saint-Barthelemy (French West Indies). This was a particularly distressing time for the local healthcare staff in charge of rescuing the population. The aim of this study was to identify the explanatory factors of post-traumatic distress and burnout in hospital staff. METHODS: An anonymous questionnaire was sent to all 509 hospital workers of Saint-Martin and Saint-Barthelemy. Post-traumatic distress and burnout was assessed using the Post-Traumatic Stress Disorder Checklist (PCL-S) and Copenhagen Burnout Inventory (CBI) scales. Bivariate and multivariate analyses were used to determine the explanatory variables for these two psychological disorders. RESULTS: Two hundred and sixty-two questionnaires were completed (response rate of 51.7%). The explanatory factors of post-traumatic distress were female gender (OR = 12.93, 95% CI: 2.70-232.10), electricity shortages (OR = 2.92, 95% CI: 1.13-8.19) and home damage (OR = 1.16, 95% CI [1.02-1.33]). In parallel, the explanatory factors of burnout were post-traumatic distress (OR: 10.42, 95% CI: 4.72-25.58), female gender (OR = 2,41, 95% CI: 1.24-5.02) and paramedical staff (OR = 2,53, 95% CI: 1.15-6.21). In the multivariate analysis, only burnout was significantly associated with post-traumatic distress (OR = 9.26, 95% CI: 4.11-23.14). CONCLUSIONS: Six months after Irma, post-traumatic distress among hospital staff was strongly linked to burnout. This study revealed the lack of electricity as a new factor related to post-traumatic distress. It also suggested that psychological intervention should be strengthened.

Increased severity associated with tallowamine in acute glyphosate poisoning.

Context: During the re-approval process of glyphosate in Europe, it was mentioned that glyphosate-based products (GBF) were more toxic than glyphosate alone. This phenomenon was attributed to the surfactants and among them, polyethoxylated tallowamine (POEA) has been suspected to significantly contribute to the toxicity of glyphosate products. In animal data acute oral toxicity of POEA has been suggested to be greater than glyphosate toxicity in animal studies. There are no data, however, comparing the clinical signs and severity of acute human poisoning with tallowamine-containing GBF (TA) and non-tallowamine-containing GBF (NTA). The aim of this study was to compare the severity of oral poisoning between TA and NTA cases, reported to the French Poison Control Centres (PCC) over 7 years.Methods: This is a retrospective study of cases of oral exposure to GBF reported to French PCCs between January 1st, 2008 and December 12th, 2014. The formulation of every GBF was reviewed using the PCC national database of products and compositions, to identify cases involving TA, NTA, or GBF with unknown co-formulants.Results: Between 2008 and 2014, 1362 cases of GBF ingestion were registered in the PCC national database of poisoning cases. Among them, 429 were symptomatic acute cases of ingestion of GBF. There were 235 exposures to TA, 105 to NTA, and 89 to unknown GBF. There were more severe cases in the TA group than in the NTA group (p = 0.037).Discussion: The present study shows that POEA rather than other co-formulants leads to more severe symptoms in those patients ingesting GBF. The acute toxicity of POEA might be explained by its irritating properties; in experimental studies, it caused skin irritation and severe eye and mucous membranes irritation.Conclusion: In this study, severe respiratory symptoms were also more frequently reported in the TA group. The surfactant properties of POEA are likely to cause aspiration pneumonitis which is a plausible explanation for the respiratory failure complicating severe GBF poisoning cases.

Severity of manchineel fruit (Hippomane mancinella) poisoning: A retrospective case series of 97 patients from French Poison Control Centers.

In this retrospective series of 97 cases of manchineel fruit ingestion reported to French Poison Control Centers between 2009 and 2017, we investigated cases of poisoning due to manchineel fruit (from the Hippomane mancinella tree). This fruit is known to be responsible for oropharyngeal and gastrointestinal tract lesions and possibly hypotension and bradycardia (previously attributed to the presence of physostigmine). The most commonly observed clinical signs were oropharyngeal pain, abdominal pain, diarrhea and oropharyngeal irritation. No major gastrointestinal tract lesions were observed in the five cases in which upper gastrointestinal (GI) endoscopy was performed. One case of laryngeal edema and one case of bradycardia were observed, but analysis of the harvested fruits did not confirm the presence of physostigmine. Ingestion of manchineel fruit can cause mild abdominal pain and digestive irritation, requiring medical attention. Rarely, when several fruits have been ingested, severe oropharyngeal injury or hemodynamic disorders may require otorhinolaryngological consultation or cardiac monitoring for several hours, respectively.

Human exposure to banned pesticides reported to the French Poison Control Centers: 2012-2016.

In 2008, 30 active substances from plant protection products were banned from marketing in France. Nevertheless, the French Poison Control Centers continue to see cases of poisoning caused by these active substances that are no longer approved. The aim of this study was to describe the characteristics of the reported cases in mainland France and in overseas French territories, over the period 2012-2016. A total of 408 cases of human exposure were reported during the study period. The most commonly reported substances were dichlorvos (24.8%, n = 108), paraquat (23.8%, n = 97), aldicarb (14.7%, n = 60), diuron (9.6%, n = 39), dinocap (5.1%, n = 21), methomyl (4.2%, n = 17), carbofuran (3.9%, n = 16), anthraquinone (2.9%, n = 12) and carbendazim (2.7%, n = 11). The number of cases of intoxication dropped sharply between 2012 (n = 119) and 2016 (n = 47), except in the overseas French territories. Among the 72 serious cases (severe or life-threatening or with a fatal outcome), the most common substances involved were paraquat (n = 34), aldicarb (n = 24) and carbofuran (n = 7). This study suggests persistent use of carbamate insecticides, the existence of illegal imports of dichlorvos or paraquat-based products, and the use of certain banned fungicides in the professional agricultural sector. Information and collection campaigns are therefore essential after the withdrawal of marketing authorization for the plant protection products.