Clinical Evolution and Risk Factors of Hospitalized Patients with COVID-19, Haiti, March-June 2020

In December 2019, a coronavirus epidemic emerged in China. Within months, the epidemic was considered a public health emergency of international concern. In Haiti, the first laboratory-confirmed cases of COVID-19 were reported on March 19, 2020, in a context where there was some limitations of knowledge on the modes of transmission, the severity, the clinical characteristics and the risk factors of the disease. This study has made it possible to characterize the epidemic and investigate the associations between the risk factors, co morbidities, and clinical evolution of the disease. To develop the epidemiological and clinical profile of patients with COVID-19 in Haiti, data were collected from the clinical records of patients hospitalized for COVID-19 from March 16 to June 16, 2020, in 22 healthcare facilities. Univariate, bivariate, and logistic regression model analyses were performed to describe and explore the risk factors, comorbidities, and treatments associated with patients’ clinical evolution. Statistical significance was determined using a 95% confidence interval or p-value of ?0.05.  Diabetes and high blood pressure were the main comorbidities that had a statistically significant association with the severe form of the disease and the occurrence of death. The likelihood of dying increased with age, and patients in the severe form were almost four times more likely to die. The administration of ceftriaxone to patients was significantly related to recovery from the disease. Diabetes, high blood pressure, and age were the major risk factors for the severity and mortality of people infected with COVID19. Ceftriaxone administration was protective against recovery

Safety and efficacy of co-administered diethylcarbamazine, albendazole and ivermectin during mass drug administration for lymphatic filariasis in Haiti: Results from a two-armed, open-label, cluster-randomized, community study

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti

How do 66 European institutional review boards approve one protocol for an international prospective observational study on traumatic brain injury? Experiences from the CENTER-TBI study

Abstract: Background: The European Union (EU) aims to optimize patient protection and efficiency of health-care research by harmonizing procedures across Member States. Nonetheless, further improvements are required to increase multicenter research efficiency. We investigated IRB procedures in a large prospective European multicenter study on traumatic brain injury (TBI), aiming to inform and stimulate initiatives to improve efficiency. Methods: We reviewed relevant documents regarding IRB submission and IRB approval from European neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI). Documents included detailed information on IRB procedures and the duration from IRB submission until approval(s). They were translated and analyzed to determine the level of harmonization of IRB procedures within Europe. Results: From 18 countries, 66 centers provided the requested documents. The primary IRB review was conducted centrally (N = 11, 61%) or locally (N = 7, 39%) and primary IRB approval was obtained after one (N = 8, 44%), two (N = 6, 33%) or three (N = 4, 23%) review rounds with a median duration of respectively 50 and 98 days until primary IRB approval. Additional IRB approval was required in 55% of countries and could increase duration to 535 days. Total duration from submission until required IRB approval was obtained was 114 days (IQR 75–224) and appeared to be shorter after submission to local IRBs compared to central IRBs (50 vs. 138 days, p = 0.0074). Conclusion: We found variation in IRB procedures between and within European countries. There were differences in submission and approval requirements, number of review rounds and total duration. Research collaborations could benefit from the implementation of more uniform legislation and regulation while acknowledging local cultural habits and moral values between countries

Occurrence and timing of withdrawal of life-sustaining measures in traumatic brain injury patients: a CENTER-TBI study

Funder: National Institute for Health Research (UK)Abstract: Background: In patients with severe brain injury, withdrawal of life-sustaining measures (WLSM) is common in intensive care units (ICU). WLSM constitutes a dilemma: instituting WLSM too early could result in death despite the possibility of an acceptable functional outcome, whereas delaying WLSM could unnecessarily burden patients, families, clinicians, and hospital resources. We aimed to describe the occurrence and timing of WLSM, and factors associated with timing of WLSM in European ICUs in patients with traumatic brain injury (TBI). Methods: The CENTER-TBI Study is a prospective multi-center cohort study. For the current study, patients with traumatic brain injury (TBI) admitted to the ICU and aged 16 or older were included. Occurrence and timing of WLSM were documented. For the analyses, we dichotomized timing of WLSM in early (< 72 h after injury) versus later (≥ 72 h after injury) based on recent guideline recommendations. We assessed factors associated with initiating WLSM early versus later, including geographic region, center, patient, injury, and treatment characteristics with univariable and multivariable (mixed effects) logistic regression. Results: A total of 2022 patients aged 16 or older were admitted to the ICU. ICU mortality was 13% (n = 267). Of these, 229 (86%) patients died after WLSM, and were included in the analyses. The occurrence of WLSM varied between regions ranging from 0% in Eastern Europe to 96% in Northern Europe. In 51% of the patients, WLSM was early. Patients in the early WLSM group had a lower maximum therapy intensity level (TIL) score than patients in the later WLSM group (median of 5 versus 10) The strongest independent variables associated with early WLSM were one unreactive pupil (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.3–12.4) or two unreactive pupils (OR 5.8, CI 2.6–13.1) compared to two reactive pupils, and an Injury Severity Score (ISS) if over 41 (OR per point above 41 = 1.1, CI 1.0–1.1). Timing of WLSM was not significantly associated with region or center. Conclusion: WLSM occurs early in half of the patients, mostly in patients with severe TBI affecting brainstem reflexes who were severely injured. We found no regional or center influences in timing of WLSM. Whether WLSM is always appropriate or may contribute to a self-fulfilling prophecy requires further research and argues for reluctance to institute WLSM early in case of any doubt on prognosis

Informed consent procedures in patients with an acute inability to provide informed consent

Purpose: Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedur

P2 Investigation of the phytochemical composition and anti-inflammatory properties of Afzelia africana leaves

Introduction: Afzelia africana is a large tree that is widespread in West Africa. Its bark is used in traditional medicine to treat rheumatism, edema, and pain. In our previous researches, we studied the phytochemical characteristics of the aqueous extract of trunk bark, which showed a high content of phenolic compounds and particularly flavonoids, which are known to have anti-inflammatory properties. This extract has been formulated as a topical hydrogel, and preclinical animal studies on the chronic and acute inflammation model have demonstrated anti-inflammatory activity comparable to that of diclofenac with an inhibition rate of 85.31%. With the aim of industrial production of improved traditional medicine, while preserving biodiversity, we investigated whether the leaves of A. africana could advantageously replace the trunk back. The objectives were to first study the phytochemically composition of the aqueous and hydroethanolic extracts of the leaves in comparison to that of the trunk bark, and then to evaluate its anti-inflammatory activity in an animal model. Methodology: The main families of secondary metabolites were investigated in the aqueous and hydroethanolic extracts. The polyphenol and flavonoid contents were determined by spectrophotometric assay, and the results were expressed as gallic acid equivalents and quercetin equivalents, respectively. Anti- inflammatory activity was determined using an acute ear inflammation model induced by topical application of xylene in mice. Mice were divided into four groups. In the negative control group, mice were not treated; betamethasone was used as a positive control; aqueous and hydroethanolic extracts were administered at a dose of 20 mg per ear. Doses were administered topically to mice. The contralateral ear served as a control. All animals were sacrificed 0.5, 1, and 4 hours after xylene, and then two ears were cut along the pinna. The pinna was harvested and weighed. The inhibition rate was calculated in the different groups. Structural changes in the inner ear wall after xylene application were evaluated by histology on sections of the animals' ears. Results: The results showed that, the aqueous leaf extract of A. Africana has a similar secondary metabolite composition to the trunk bark extract, containing tannins, alkaloids, flavonoids, steroids, coumarins, and quinones. The aqueous and hydroethanolic leaf extracts contained similar levels of total polyphenols, with 196.44 ± 4.22 and 214.58 ± 1.78 mg/g in gallic acid equivalents, respectively. The hydroethanolic leaf extract contained significantly higher levels of flavonoids than the aqueous leaf extract, with 59.16 ± 0.22 mg/g in   quercetin equivalents compared to 32.23 ± 4.22 mg/g. In addition, the flavonoid content of the aqueous leaf extract was comparable to that of the trunk bark, with 25.8 mg/g ± 0.26. Treatment with the aqueous and hydroethanolic extracts of A. Africana leaves significantly inhibited ear edema 0.5, 1, and 4 hours after xylene application, with inhibition percentages of 44.49% and 12.39% after 0.5 hour, 80.26% and 80.67% after 1 hour, and 63.97% and 49.44% after 4 hours respectively. These inhibition percentages were comparable to those of animals treated with betamethasone, which had inhibition percentages of 56.38%, 75.30%, and 76.39% after 0.5, 1, and 4 hours, respectively. Conclusion: The trunk bark of A. Africana is used in traditional medicine to treat inflammatory diseases and pain. Its topical application inspired us to study the phytochemical composition and anti-inflammatory activity of the trunk bark. Although it demonstrated an interesting anti-inflammatory potential, in order to protect this precious resource, we investigated the potential of the leaves. The phytochemical study showed that, as for the trunk bark, the leaves have a high content of active metabolites, particularly polyphenols, which are known for their anti-inflammatory potential. The anti-inflammatory activity of the leaf extracts has been demonstrated, making the leaves a good candidate for the development of improved traditional medicines

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI

Background: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. Methods: A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. Results: A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. Conclusions: Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. Trial registration: ClinicalTrials.gov NCT02210221.</p

Arithmetic and Memorial Practices by and around Sophie Germain in the 19th Century

International audienceSophie Germain (1776-1831) is an emblematic example of a woman who produced mathematics in the first third of the nineteenth century. Self-taught, she was recognised for her work in the theory of elasticity and number theory. After some biographical elements, I will focus on her contribution to number theory in the context of the mathematical practices and social positions of the mathematicians of her time. I will then analyse some receptions and uses of Germain's life and scientific work under the French Third Republic