Religious significance of suffering and psychological position in faith

Estuda-se o vínculo psicológico entre a experiência existencial do sofrimento e a posição do sujeito em relação à fé religiosa. A investigação foi realizada com 80 enfermeiros, de ambos os sexos, com várias modalidades de adesão ao cristianismo. A hipótese foi a de que essas pessoas são obrigadas a estruturar para si mesmas uma atitude mais ou menos estável, consciente ou refletida, em relação ao sofrimento. Foi construído um questionário com uma pergunta acerca do sofrimento, (dimensões, apreensão psicológica, sentido), uma pergunta acerca da posição religiosa (central ou periférica, segura ou hesitante) e uma pergunta acerca da atribuição de conotações religiosas ao sofrimento. Os resultados não permitem enunciar uma teoria unívoca da relação entre religião e sofrimento, mas a existência de configurações singulares mais ou menos estáveis e evolutivas, segundo a orientação básica da atitude religiosa, o contexto meramente humano do sofrimento e a contextualização religiosa do sofrimento.The psychological bond between the existencial experience of suffering and the position of the subject in relation to religious faith are studied. The investigation comprised 80 nurses, from both sexes, with various degrees of adherence to Christianism. The hypothesis was that these persons are impelled to structure for themselves a more or less stable, conscious or reflected attitude towards suffering. A questionnaire was elaborated including a question concerning suffering (dimensions, psychological aprehension, meaning), a question about the religious position (central or peripheric, certain or hesitant) and a question concerning the atribution of religious conotations to suffering. Results do not allow one to enunciate a homogeneous theory on the relation between religion and suffering, but the existence of singular configurations more or less stable and evolving, according to the religious attitude basic orientation, the merely human context of suffering and the religious contextualization of suffering

Religious significance of suffering and psychological position in faith

The psychological bond between the existencial experience of suffering and the position of the subject in relation to religious faith are studied. The investigation comprised 80 nurses, from both sexes, with various degrees of adherence to Christianism. The hypothesis was that these persons are impelled to structure for themselves a more or less stable, conscious or reflected attitude towards suffering. A questionnaire was elaborated including a question concerning suffering (dimensions, psychological aprehension, meaning), a question about the religious position (central or peripheric, certain or hesitant) and a question concerning the atribution of religious conotations to suffering. Results do not allow one to enunciate a homogeneous theory on the relation between religion and suffering, but the existence of singular configurations more or less stable and evolving, according to the religious attitude basic orientation, the merely human context of suffering and the religious contextualization of suffering.Estuda-se o vínculo psicológico entre a experiência existencial do sofrimento e a posição do sujeito em relação à fé religiosa. A investigação foi realizada com 80 enfermeiros, de ambos os sexos, com várias modalidades de adesão ao cristianismo. A hipótese foi a de que essas pessoas são obrigadas a estruturar para si mesmas uma atitude mais ou menos estável, consciente ou refletida, em relação ao sofrimento. Foi construído um questionário com uma pergunta acerca do sofrimento, (dimensões, apreensão psicológica, sentido), uma pergunta acerca da posição religiosa (central ou periférica, segura ou hesitante) e uma pergunta acerca da atribuição de conotações religiosas ao sofrimento. Os resultados não permitem enunciar uma teoria unívoca da relação entre religião e sofrimento, mas a existência de configurações singulares mais ou menos estáveis e evolutivas, segundo a orientação básica da atitude religiosa, o contexto meramente humano do sofrimento e a contextualização religiosa do sofrimento

Ribavarin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing

Ribavirin is currently the standard of care for treating Lassa fever. However, the human clinical trial data supporting its use suffer from several serious flaws that render the results and conclusions unreliable. We performed a systematic review of available pre-clinical data and human pharmacokinetic data on ribavirin in Lassa. In in-vitro studies, the EC50 of ribavirin ranged from 0.6 μg/ml to 21.72 μg/ml and the EC90 ranged from 1.5 μg/ml to 29 μg/ml. The mean EC50 was 7 μg/ml and the mean EC90 was 15 μg/ml. Human PK data in patients with Lassa fever was sparse and did not allow for estimation of concentration profiles or pharmacokinetic parameters. Pharmacokinetic modelling based on healthy human data suggests that the concentration profiles of current ribavirin regimes only exceed the mean EC50 for less than 20% of the time and the mean EC90 for less than 10% of the time, raising the possibility that the current ribavirin regimens in clinical use are unlikely to reliably achieve serum concentrations required to inhibit Lassa virus replication. The results of this review highlight serious issues with the evidence, which, by today standards, would be unlikely to support the transition of ribavirin from pre-clinical studies to human clinical trials. Additional pre-clinical studies are needed before embarking on expensive and challenging clinical trials of ribavirin in Lassa fever

EClinicalMedicine

BACKGROUND: As mortality remains high for patients with Ebola virus disease (EVD) despite new treatment options, the ability to level up the provided supportive care and to predict the risk of death is of major importance. This analysis of the EVISTA cohort aims to describe advanced supportive care provided to EVD patients in the Democratic Republic of the Congo (DRC) and to develop a simple risk score for predicting in-hospital death, called PREDS. METHODS: In this prospective cohort (NCT04815175), patients were recruited during the 10(th) EVD outbreak in the DRC across three Ebola Treatment Centers (ETCs). Demographic, clinical, biological, virological and treatment data were collected. We evaluated factors known to affect the risk of in-hospital death and applied univariate and multivariate Cox proportional-hazards analyses to derive the risk score in a training dataset. We validated the score in an internal-validation dataset, applying C-statistics as a measure of discrimination. FINDINGS: Between August 1(st) 2018 and December 31(th) 2019, 711 patients were enrolled in the study. Regarding supportive care, patients received vasopressive drug (n = 111), blood transfusion (n = 101), oxygen therapy (n = 250) and cardio-pulmonary ultrasound (n = 15). Overall, 323 (45%) patients died before day 28. Six independent prognostic factors were identified (ALT, creatinine, modified NEWS2 score, viral load, age and symptom duration). The final score range from 0 to 13 points, with a good concordance (C = 86.24%) and calibration with the Hosmer-Lemeshow test (p = 0.12). INTERPRETATION: The implementation of advanced supportive care is possible for EVD patients in emergency settings. PREDS is a simple, accurate tool that could help in orienting early advanced care for at-risk patients after external validation. FUNDING: This study was funded by ALIMA

Clinical presentation, outcomes and factors associated with mortality: A prospective study from three COVID-19 referral care centres in West Africa

OBJECTIVES: The overall death toll from COVID-19 in Africa is reported to be low but there is little individual-level evidence on the severity of the disease. This study examined the clinical spectrum and outcome of patients monitored in COVID-19 care centres (CCCs) in two West-African countries. METHODS: Burkina Faso and Guinea set up referral CCCs to hospitalise all symptomatic SARS-CoV-2 carriers, regardless of the severity of their symptoms. Data collected from hospitalised patients by November 2020 are presented. RESULT: A total of 1,805 patients (64% men, median age 41 years) were admitted with COVID-19. Symptoms lasted for a median of 7 days (IQR 4-11). During hospitalisation, 443 (25%) had a SpO2 < 94% at least once, 237 (13%) received oxygen and 266 (15%) took corticosteroids. Mortality was 5% overall, and 1%, 5% and 14% in patients aged <40, 40-59 and ≥60 years, respectively. In multivariable analysis, the risk of death was higher in men (aOR 2.0, 95% CI 1.1; 3.6), people aged ≥60 years (aOR 2.9, 95% CI 1.7; 4.8) and those with chronic hypertension (aOR 2.1, 95% CI 1.2; 3.4). CONCLUSION: COVID-19 is as severe in Africa as elsewhere, and there must be more vigilance for common risk factors such as older age and hypertension

Lassa fever outcomes and prognostic factors in Nigeria (LASCOPE): a prospective cohort study

BACKGROUND: Lassa fever is a viral haemorrhagic fever endemic in parts of west Africa. New treatments are needed to decrease mortality, but pretrial reference data on the disease characteristics are scarce. We aimed to document baseline characteristics and outcomes for patients hospitalised with Lassa fever in Nigeria. METHODS: We did a prospective cohort study (LASCOPE) at the Federal Medical Centre in Owo, Nigeria. All patients admitted with confirmed Lassa fever were invited to participate and asked to give informed consent. Patients of all ages, including newborn infants, were eligible for inclusion, as were pregnant women. All participants received standard supportive care and intravenous ribavirin according to Nigeria Centre for Disease Control guidelines and underwent systematic biological monitoring for 30 days. Patients' characteristics, care received, mortality, and associated factors were recorded using standard WHO forms. We used univariable and multivariable logistic regression models to investigate an association between baseline characteristics and mortality at day 30. FINDINGS: Between April 5, 2018, and March 15, 2020, 534 patients with confirmed Lassa fever were admitted to hospital, of whom 510 (96%) gave consent and were included in the analysis. The cohort included 258 (51%) male patients, 252 (49%) female patients, 426 (84%) adults, and 84 (16%) children (younger than 18 years). The median time between first symptoms and hospital admission was 8 days (IQR 7-13). At baseline, 176 (38%) of 466 patients had a Lassa fever RT-PCR cycle threshold (Ct) lower than 30. From admission to end of follow-up, 120 (25%) of 484 reached a National Early Warning Score (second version; NEWS2) of 7 or higher, 67 (14%) of 495 reached a Kidney Disease-Improving Global Outcome (KDIGO) stage of 2 or higher, and 41 (8%) of 510 underwent dialysis. All patients received ribavirin for a median of 10 days (IQR 9-13). 62 (12%) patients died (57 [13%] adults and five [6%] children). The median time to death was 3 days (1-6). The baseline factors independently associated with mortality were the following: age 45 years or older (adjusted odds ratio 16·30, 95% CI 5·31-50·30), NEWS2 of 7 or higher (4·79, 1·75-13·10), KDIGO grade 2 or higher (7·52, 2·66-21·20), plasma alanine aminotransferase 3 or more times the upper limit of normal (4·96, 1·69-14·60), and Lassa fever RT-PCR Ct value lower than 30 (4·65, 1·50-14·50). INTERPRETATION: Our findings comprehensively document clinical and biological characteristics of patients with Lassa fever and their relationship with mortality, providing prospective estimates that could be useful for designing future therapeutic trials. Such trials comparing new Lassa fever treatments to a standard of care should take no more than 15% as the reference mortality rate and consider adopting a combination of mortality and need for dialysis as the primary endpoint. FUNDING: Institut National de la Santé et de la Recherche Médicale, University of Oxford, EU, UK Department for International Development, Wellcome Trust, French Ministry of Foreign Affairs, Agence Nationale de Recherches sur le SIDA et les hépatites virales, French National Research Institute for Sustainable Development

A standardised Phase III clinical trial framework to assess therapeutic interventions for Lassa fever

BACKGROUND: Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence. METHODOLOGY: We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology. RESULTS: A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols. CONCLUSIONS: This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level

Operational research on emerging infectious diseases in Sub-saharan Africa

Les maladies infectieuses émergentes (MIE) représentent plus que jamais un enjeu de santé mondiale et la connaissance de leur présentation clinico-biologique est indispensable pour optimiser la prise en charge, en terme de soins de support, de traitement spécifique et de contrôle des épidémies, par exemple par la vaccination. Le risque est particulièrement important sur le continent Africain, d’où les maladies émergent régulièrement et ou l’impact sur les populations fragilisées est majeur. La recherche opérationnelle représente l’un des outils pour améliorer la connaissance sur ces maladies et leur prise en charge. A titre d’exemple, 3 maladies ont tout particulièrement émergé en Afrique sub-saharienne et dans le monde ces dernières années : la fièvre de Lassa, la Maladie à Virus Ebola (MVE) et la Covid- 19. La fièvre de Lassa évolue sur le mode épidémique saisonnier principalement au Nigeria mais les connaissances sur cette maladie sont encore parcellaires. De plus, le traitement recommandé, la ribavirine, ne semble pas présenter une efficacité satisfaisante pour prendre en charge efficacement les patients. Depuis la grande épidémie de 2014-2016, la MVE survient par vagues épidémiques en Afrique de l’ouest et centrale, à la faveur d’une transmission animale ou d’une rechute chez un survivant. Malgré la découverte d’un traitement spécifique, beaucoup de questions subsistent, notamment autour des soins de support et de la prévention de l’infection chez les contacts. Enfin, la pandémie de Covid-19 qui a durement touché l’ensemble de la planète depuis plus de 2 ans à des implications spécifiques sur le continent Africain qu’il convient d’explorer. Grace à une collaboration inédite entre une ONG médicale internationale, ALIMA et une équipe de recherche clinique, l’équipe IDLIC de l’unité Inserm 1219 / PACCI, site ANRS de Côte d’Ivoire, plusieurs projets de recherche clinique sur les MIE ont été mis en place en Afrique sub-saharienne au cours des 5 dernières années. Dans cette thèse, nous présenterons certaines des études qui ont été réalisées durant cette collaboration, sur les 3 maladies citées ci-dessus. Il s’agit d’une thèse de publications, dans laquelle seront présentés 4 publications et les perspectives qui en découlent. Les études LASCOPE (publiée dans Lancet Global Health), EVISTA (en cours de révision dans e-clinical Medicine) et COVISTA (publiée dans The International Journal of Infectious Disease) sont des cohortes prospectives décrivant la présentation clinique et biologique ainsi que le standard de soins prodigué aux patients atteints de fièvre de Lassa au Nigeria, de MVE en République Démocratique du Congo (RDC) et de Covid-19 en Guinée et Burkina Faso, respectivement. La 4ème publication concerne une étude pilote menée en RDC pour évaluer la faisabilité d’une prophylaxie post exposition (PPE) par anticorps monoclonaux chez les contacts à haut risque de MVE (publiée dans The International Journal of Infectious Disease). Les perspectives de cette thèse sont multiples. Concernant la fièvre de Lassa, le principal enjeu consiste actuellement à mettre en évidence un traitement spécifique efficace et accessible dans les pays d’Afrique de l’ouest. Pour cela, un essai thérapeutique adaptatif de phase 2-3 est en train de se mettre en place dans plusieurs pays d’Afrique de l’ouest. Pour lutter contre la diffusion de la MVE, une réflexion sur les options disponibles en termes de PPE est en cours au plan international. Enfin, concernant la Covid-19, des essais thérapeutiques et vaccinaux sont en cours en Afrique sub-saharienne.Emerging infectious diseases (EIDs) are more than ever a global health issue and knowledge of their clinical and biological presentation is essential to optimize management, in terms of supportive care, specific treatment and epidemic control, for example through vaccination. The challenge is particularly important on the African continent, where diseases regularly emerge and where the impact on vulnerable populations is major. Operational research is one of the tools for improving knowledge about these diseases and their management. For example, three diseases have emerged in sub-Saharan Africa and worldwide in recent years: Lassa fever, Ebola Virus Disease (EVD) and Covid-19. Lassa fever has a seasonal epidemic pattern, mainly in Nigeria, but knowledge of the disease is still incomplete. Moreover, the recommended treatment, ribavirin, does not seem to be sufficiently effective in managing patients. Since the major epidemic of 2014-2016, EVD has been occurring in epidemic waves in West and Central Africa, through animal transmission or relapse in a survivor. Despite the discovery of a specific treatment, many questions remain, particularly around supportive care and prevention of infection in contacts. Finally, the Covid-19 pandemic that has severely affected the entire planet for more than 2 years has specific implications on the African continent that need to be explored. Thanks to an unprecedented collaboration between an international medical NGO, ALIMA, and a clinical research team, the IDLIC team of the Inserm 1219 unit / PACCI, ANRS site in Côte d'Ivoire, several clinical research projects on EVDs have been set up in sub-Saharan Africa over the last 5 years. In this thesis, we will present some of the studies that have been carried out during this collaboration, on the 3 diseases mentioned above. This is a publication thesis, in which 4 publications and their perspectives will be presented. The LASCOPE (published in Lancet Global Health), EVISTA (under review in e-clinical Medicine) and COVISTA (published in The International Journal of Infectious Disease) studies are prospective cohorts describing the clinical and biological presentation and standard of care of patients with Lassa fever in Nigeria, EVD in the Democratic Republic of the Congo (DRC) and Covid-19 in Guinea and Burkina Faso, respectively. The fourth publication concerns a pilot study conducted in the DRC to assess the feasibility of post-exposure prophylaxis (PEP) with monoclonal antibodies in high-risk contacts of EVD (published in The International Journal of Infectious Disease). The perspectives of this thesis are multiple. Concerning Lassa fever, the main challenge is currently to identify a specific treatment that is effective and accessible in West African countries. To this end, a phase 2-3 adaptive trial is being set up in several West African countries. To combat the spread of EVD, a reflection on the available options in terms of PEP is underway at the international level. Finally, on Covid-19, therapeutic and vaccine trials are ongoing in sub-Saharan Africa

La recherche opérationnelle sur les maladies infectieuses à potentiel épidémique et menaçant en Afrique Sub-saharienne

Emerging infectious diseases (EIDs) are more than ever a global health issue and knowledge of their clinical and biological presentation is essential to optimize management, in terms of supportive care, specific treatment and epidemic control, for example through vaccination. The challenge is particularly important on the African continent, where diseases regularly emerge and where the impact on vulnerable populations is major. Operational research is one of the tools for improving knowledge about these diseases and their management. For example, three diseases have emerged in sub-Saharan Africa and worldwide in recent years: Lassa fever, Ebola Virus Disease (EVD) and Covid-19. Lassa fever has a seasonal epidemic pattern, mainly in Nigeria, but knowledge of the disease is still incomplete. Moreover, the recommended treatment, ribavirin, does not seem to be sufficiently effective in managing patients. Since the major epidemic of 2014-2016, EVD has been occurring in epidemic waves in West and Central Africa, through animal transmission or relapse in a survivor. Despite the discovery of a specific treatment, many questions remain, particularly around supportive care and prevention of infection in contacts. Finally, the Covid-19 pandemic that has severely affected the entire planet for more than 2 years has specific implications on the African continent that need to be explored. Thanks to an unprecedented collaboration between an international medical NGO, ALIMA, and a clinical research team, the IDLIC team of the Inserm 1219 unit / PACCI, ANRS site in Côte d'Ivoire, several clinical research projects on EVDs have been set up in sub-Saharan Africa over the last 5 years. In this thesis, we will present some of the studies that have been carried out during this collaboration, on the 3 diseases mentioned above. This is a publication thesis, in which 4 publications and their perspectives will be presented. The LASCOPE (published in Lancet Global Health), EVISTA (under review in e-clinical Medicine) and COVISTA (published in The International Journal of Infectious Disease) studies are prospective cohorts describing the clinical and biological presentation and standard of care of patients with Lassa fever in Nigeria, EVD in the Democratic Republic of the Congo (DRC) and Covid-19 in Guinea and Burkina Faso, respectively. The fourth publication concerns a pilot study conducted in the DRC to assess the feasibility of post-exposure prophylaxis (PEP) with monoclonal antibodies in high-risk contacts of EVD (published in The International Journal of Infectious Disease). The perspectives of this thesis are multiple. Concerning Lassa fever, the main challenge is currently to identify a specific treatment that is effective and accessible in West African countries. To this end, a phase 2-3 adaptive trial is being set up in several West African countries. To combat the spread of EVD, a reflection on the available options in terms of PEP is underway at the international level. Finally, on Covid-19, therapeutic and vaccine trials are ongoing in sub-Saharan Africa.Les maladies infectieuses émergentes (MIE) représentent plus que jamais un enjeu de santé mondiale et la connaissance de leur présentation clinico-biologique est indispensable pour optimiser la prise en charge, en terme de soins de support, de traitement spécifique et de contrôle des épidémies, par exemple par la vaccination. Le risque est particulièrement important sur le continent Africain, d’où les maladies émergent régulièrement et ou l’impact sur les populations fragilisées est majeur. La recherche opérationnelle représente l’un des outils pour améliorer la connaissance sur ces maladies et leur prise en charge. A titre d’exemple, 3 maladies ont tout particulièrement émergé en Afrique sub-saharienne et dans le monde ces dernières années : la fièvre de Lassa, la Maladie à Virus Ebola (MVE) et la Covid- 19. La fièvre de Lassa évolue sur le mode épidémique saisonnier principalement au Nigeria mais les connaissances sur cette maladie sont encore parcellaires. De plus, le traitement recommandé, la ribavirine, ne semble pas présenter une efficacité satisfaisante pour prendre en charge efficacement les patients. Depuis la grande épidémie de 2014-2016, la MVE survient par vagues épidémiques en Afrique de l’ouest et centrale, à la faveur d’une transmission animale ou d’une rechute chez un survivant. Malgré la découverte d’un traitement spécifique, beaucoup de questions subsistent, notamment autour des soins de support et de la prévention de l’infection chez les contacts. Enfin, la pandémie de Covid-19 qui a durement touché l’ensemble de la planète depuis plus de 2 ans à des implications spécifiques sur le continent Africain qu’il convient d’explorer. Grace à une collaboration inédite entre une ONG médicale internationale, ALIMA et une équipe de recherche clinique, l’équipe IDLIC de l’unité Inserm 1219 / PACCI, site ANRS de Côte d’Ivoire, plusieurs projets de recherche clinique sur les MIE ont été mis en place en Afrique sub-saharienne au cours des 5 dernières années. Dans cette thèse, nous présenterons certaines des études qui ont été réalisées durant cette collaboration, sur les 3 maladies citées ci-dessus. Il s’agit d’une thèse de publications, dans laquelle seront présentés 4 publications et les perspectives qui en découlent. Les études LASCOPE (publiée dans Lancet Global Health), EVISTA (en cours de révision dans e-clinical Medicine) et COVISTA (publiée dans The International Journal of Infectious Disease) sont des cohortes prospectives décrivant la présentation clinique et biologique ainsi que le standard de soins prodigué aux patients atteints de fièvre de Lassa au Nigeria, de MVE en République Démocratique du Congo (RDC) et de Covid-19 en Guinée et Burkina Faso, respectivement. La 4ème publication concerne une étude pilote menée en RDC pour évaluer la faisabilité d’une prophylaxie post exposition (PPE) par anticorps monoclonaux chez les contacts à haut risque de MVE (publiée dans The International Journal of Infectious Disease). Les perspectives de cette thèse sont multiples. Concernant la fièvre de Lassa, le principal enjeu consiste actuellement à mettre en évidence un traitement spécifique efficace et accessible dans les pays d’Afrique de l’ouest. Pour cela, un essai thérapeutique adaptatif de phase 2-3 est en train de se mettre en place dans plusieurs pays d’Afrique de l’ouest. Pour lutter contre la diffusion de la MVE, une réflexion sur les options disponibles en termes de PPE est en cours au plan international. Enfin, concernant la Covid-19, des essais thérapeutiques et vaccinaux sont en cours en Afrique sub-saharienne