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Supplemental material, sj-pptx-2-tar-10.1177_17534666221130217 for Healthcare resource consumption prior to asthma-related death: a nationwide descriptive study by Laurent Guilleminault, Michael Mounié, Agnès Sommet, Claire Camus, Alain Didier, Laurent L. Reber, Nadège Costa and Cécile Conte in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-3-tar-10.1177_17534666221130217 for Healthcare resource consumption prior to asthma-related death: a nationwide descriptive study by Laurent Guilleminault, Michael Mounié, Agnès Sommet, Claire Camus, Alain Didier, Laurent L. Reber, Nadège Costa and Cécile Conte in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-pptx-1-tar-10.1177_17534666221130217 for Healthcare resource consumption prior to asthma-related death: a nationwide descriptive study by Laurent Guilleminault, Michael Mounié, Agnès Sommet, Claire Camus, Alain Didier, Laurent L. Reber, Nadège Costa and Cécile Conte in Therapeutic Advances in Respiratory Disease

This thesis presents a pharmacoepidemiology approach to describe drug utilization in lymphomas during their whole care pathway. The use of the French claims database (Système National d'Informations Inter-Régimes de l'Assurance Maladie (SNIIRAM)) allows to exhaustively quantify this drug utilization in real life conditions. This thesis consists of three mains objectives. First, we aimed to develop validated algorithms for the identification of incident cases of lymphoma. For the validation, we used data from a regional Cancer Registry as the gold standard. The purpose of this validation study was to enhance validity of future studies conducted on lymphomas in the SNIIRAM database. The results of this study associated to strengths of this database demonstrate that this approach is of great interest to conduct pharmacoepidemiological or medico-economic studies in lymphomas. Second, we aimed to estimate the incidence of use of psychotropic drugs during the active treatment phase of lymphoma in comparison with control groups. Indeed, the increased probability of developing anxio-depressive disorders after diagnosis could lead to an increased initiation of psychotropic drugs and a potential inappropriate chronic use of these drugs after initiation. Such inappropriate chronic use can unnecessarily expose patients to adverse event. For this aim, we conducted a new-user cohort study using data from the SNIIRAM database. The results of this study revealed that the initiation rate of these drugs is higher than in the general population or for life-threatening diseases such as myocardial infarction. Moreover, we observed an inappropriate prolonged use for a significant fraction of patients (20% to more than 50% according to therapeutic class). On the basis of these findings, the third objective was to identify factors associated with prolonged use of these drugs during survivorship. This study was conducted using data from the General Sample of Beneficiaries (EGB). [...]; Ces travaux de thèse présentent une approche de pharmaco-épidémiologie explorant l'exposition médicamenteuse chez des patients atteints de lymphome tout au long de leur parcours de soin. L'utilisation des données du Système National d'Information Inter-régimes de l'Assurance Maladie (SNIIRAM) nous a permis de quantifier cette exposition médicamenteuse et de déterminer les facteurs associés dans le contexte de la vie réelle. Les travaux de recherche réalisés au cours de cette thèse répondaient à 3 objectifs. Dans un premier objectif, nous avons souhaité valider l'utilisation du SNIIRAM à des fins de recherche pour améliorer la robustesse des futures études menées sur le lymphome. Après avoir défini plusieurs algorithmes d'identification des cas incidents de lymphome, nous avons testé leur validité par confrontation aux données cliniques exhaustives du Registre des cancers du Tarn. Les paramètres de performance obtenus permettent de considérer les données disponibles dans le SNIIRAM comme un outil puissant pour mener des études pharmaco-épidémiologiques ou médico-économiques sur le Lymphome. Le second objectif était d'explorer l'existence d'une surconsommation de médicaments psychotropes au cours de la phase active de traitement par rapport à une population témoin, sous l'hypothèse d'une initiation accrue de ces médicaments pour pallier les complications psychologiques associées à la prise en charge du Lymphome. Par ailleurs, la chronicisation fréquemment observée de ce type de consommation peut conduire à terme à des complications potentiellement évitables. Pour répondre à cet objectif, nous avons réalisé une étude selon une approche " new-user design ", à partir d'une cohorte de patients incidents de lymphome identifiés dans les données du SNIIRAM à l'échelon régional. Nous avons observé un taux d'initiation supérieur au taux observé en population générale ou chez des patients atteints d'autres pathologies mettant en jeu le pronostic vital (infarctus du myocarde). En fonction de la classe thérapeutique étudiée, 20 à plus de 50% des patients restaient exposés de façon inappropriée (au-delà des recommandations) à ces médicaments. Le troisième objectif a donc été d'explorer les déterminants associés à une utilisation prolongée de médicaments psychotropes dans la phase de l'après-cancer à partir des données de l'Echantillon généraliste des bénéficiaires (EGB). [...]

This thesis presents a pharmacoepidemiology approach to describe drug utilization in lymphomas during their whole care pathway. The use of the French claims database (Système National d'Informations Inter-Régimes de l'Assurance Maladie (SNIIRAM)) allows to exhaustively quantify this drug utilization in real life conditions. This thesis consists of three mains objectives. First, we aimed to develop validated algorithms for the identification of incident cases of lymphoma. For the validation, we used data from a regional Cancer Registry as the gold standard. The purpose of this validation study was to enhance validity of future studies conducted on lymphomas in the SNIIRAM database. The results of this study associated to strengths of this database demonstrate that this approach is of great interest to conduct pharmacoepidemiological or medico-economic studies in lymphomas. Second, we aimed to estimate the incidence of use of psychotropic drugs during the active treatment phase of lymphoma in comparison with control groups. Indeed, the increased probability of developing anxio-depressive disorders after diagnosis could lead to an increased initiation of psychotropic drugs and a potential inappropriate chronic use of these drugs after initiation. Such inappropriate chronic use can unnecessarily expose patients to adverse event. For this aim, we conducted a new-user cohort study using data from the SNIIRAM database. The results of this study revealed that the initiation rate of these drugs is higher than in the general population or for life-threatening diseases such as myocardial infarction. Moreover, we observed an inappropriate prolonged use for a significant fraction of patients (20% to more than 50% according to therapeutic class). On the basis of these findings, the third objective was to identify factors associated with prolonged use of these drugs during survivorship. This study was conducted using data from the General Sample of Beneficiaries (EGB). [...], Ces travaux de thèse présentent une approche de pharmaco-épidémiologie explorant l'exposition médicamenteuse chez des patients atteints de lymphome tout au long de leur parcours de soin. L'utilisation des données du Système National d'Information Inter-régimes de l'Assurance Maladie (SNIIRAM) nous a permis de quantifier cette exposition médicamenteuse et de déterminer les facteurs associés dans le contexte de la vie réelle. Les travaux de recherche réalisés au cours de cette thèse répondaient à 3 objectifs. Dans un premier objectif, nous avons souhaité valider l'utilisation du SNIIRAM à des fins de recherche pour améliorer la robustesse des futures études menées sur le lymphome. Après avoir défini plusieurs algorithmes d'identification des cas incidents de lymphome, nous avons testé leur validité par confrontation aux données cliniques exhaustives du Registre des cancers du Tarn. Les paramètres de performance obtenus permettent de considérer les données disponibles dans le SNIIRAM comme un outil puissant pour mener des études pharmaco-épidémiologiques ou médico-économiques sur le Lymphome. Le second objectif était d'explorer l'existence d'une surconsommation de médicaments psychotropes au cours de la phase active de traitement par rapport à une population témoin, sous l'hypothèse d'une initiation accrue de ces médicaments pour pallier les complications psychologiques associées à la prise en charge du Lymphome. Par ailleurs, la chronicisation fréquemment observée de ce type de consommation peut conduire à terme à des complications potentiellement évitables. Pour répondre à cet objectif, nous avons réalisé une étude selon une approche " new-user design ", à partir d'une cohorte de patients incidents de lymphome identifiés dans les données du SNIIRAM à l'échelon régional. Nous avons observé un taux d'initiation supérieur au taux observé en population générale ou chez des patients atteints d'autres pathologies mettant en jeu le pronostic vital (infarctus du myocarde). En fonction de la classe thérapeutique étudiée, 20 à plus de 50% des patients restaient exposés de façon inappropriée (au-delà des recommandations) à ces médicaments. Le troisième objectif a donc été d'explorer les déterminants associés à une utilisation prolongée de médicaments psychotropes dans la phase de l'après-cancer à partir des données de l'Echantillon généraliste des bénéficiaires (EGB). [...]

Every year in France, about 2000 cases of abdominal injuries are due to car crashes. These injuries are often severe and 20% of them are lethal. They require long and expensive treatments because half of cases needs surgery. Among abdominal organs, liver is one of the most frequently and severely injured: haemorrhage and infectious risks are real. To improve hepatic injuries prevention, the definition of efficient safety devices should be based on a comprehensive knowledge of liver structures behaviour and injury mechanisms. Thus the aim of this thesis was to build a predictive tool for hepatic injuries in crash situation. To achieve this point, we performed experimental uniaxial compressions of human livers with various loading velocities. We then observed the visco-hyperelastic behaviour of the liver and its failure modes at the global scale and also at the cells scale. After that, we chose a theoretical framework which was adapted both to the observed behaviour and to the damage and rupture description. We finally built a finite element model which integrate a precise description of liver structures (parenchyma, capsule and vascular trees), the theoretical behaviours deduced from the experimental phase, the failure of the different tissues and the fluid action within the vascular structures. After the model calibration and validation with experimental observations, this FEM makes up the wanted predictive tool for hepatic injuries. This tool can be used both with slow and rapid loading velocities. When integrated into a more complete model of the human body, this predictive tool will allow a better understanding of liver injuries mechanisms and then an improvement in their prevention and treatment., Chaque année en France, on dénombre environ 2000 cas de lésions de la région abdominale lors d'accidents de la route. Ces lésions sont très souvent sévères, mortelles dans 20% des cas, et nécessitent un traitement médical délicat, long et coûteux car il fait appel à la chirurgie dans un cas sur deux. Parmi ces lésions, celles du foie font partie des plus fréquentes mais aussi des plus graves à cause de leur risque hémorragique et sceptique élevé. Une voie d'amélioration de leur prévention passe alors par la conception de systèmes de protection plus efficaces basée sur une connaissance détaillée du comportement de ces structures et des mécanismes lésionnels mis en jeu lors d'un choc. L'objectif de ce travail a donc été de construire un outil numérique de prédiction des lésions hépatiques en situation d ' impact. Pour cela, nous avons tout d'abord réalisé une étude expérimentale de compression uniaxiale de foies humains à différentes vitesses pour observer le compot1ement visco-hyperélastique du foie et comprendre ses modes de rupture tant à l'échelle globale qu'à l'échelle cellulaire. Ensuite, nous avons fixé un cadre théorique adapté à la fois au comportement observé et à la description de l'endommagement et de la rupture. Enfin, nous avons construit un modèle éléments finis intégrant une description fine des sous-structures du foie (parenchyme, capsule et arbres vasculaires), les comportements théoriques déduits de la phase expérimentale, la rupture des différents tissus et la présence de fluide dans les structures vasculaires. Une fois calibré et validé par rapport aux observations expérimentales, ce modèle constitue l'outil de prédiction lésionnelle voulu, applicable à la fois pour des vitesses lentes et pour des vitesses rapides. Intégré clans des modèles plus complets du corps humain, cet outil permettra de mieux comprendre les mécanismes lésionnels du foie et ainsi d'améliorer leur prévention mais aussi leur traitement.

Background: Lymphomas are costly diseases that suffer from a lack of detailed economic information, notably in a real-world setting. Decision-makers are increasing the search for Real-World Evidence (RWE) to assess the impact, in real-life, of healthcare management and to support their public decisions. Thus, we aimed to assess the real-world net costs of the active treatment phases of adult Hodgkin Lymphoma (HL), Follicular Lymphoma (FL) and Diffuse Large B Cell Lymphoma (DLBCL). Methods: We performed a retrospective cohort study using population-based data from a national representative sample of the French population covered by the health insurance system. Cost analysis was performed from the French health insurance perspective and took into account direct and sick leave compensation costs (€2,018). Healthcare costs were studied over the active treatment phase. We used multivariate modeling to adjust cost differences between lymphoma subtypes. Results: Analyses were performed on 224 lymphoma patients and 896 controls. The mean additional monthly costs due to HL, FL and DLBCL patients were respectively €5,188, €3,242 and €7,659 for the active treatment phase. The main additional cost driver was principally inpatient stay (hospitalization costs and costly cancer-related drugs), followed by outpatient medication and productivity loss. When adjusted, DLBCL remains significantly the most costly lymphoma subtype. Conclusion: This study provides an accurate assessment of the main lymphoma subtypes related cost with high magnitude of details in a real-world setting. We underline where potential cost saving could be realized via the use of biosimilar medication, and where lymphoma management could be improved with the early management of adverse events.KEY POINTSThis is one of the first studies which assess the additional cost of lymphoma in Europe, according the main sub-types of lymphoma and with real-world database.The additional monthly cost due to HL, FL and DLBCL patients were respectively €5,188, €3,242 and €7,659 for the active treatment phase and the main additional cost driver was principally inpatient stay (i.e. hospitalization costs and additional inpatient medicines, notably rituximab), followed by outpatient medication and productivity loss.This study provides an accurate and detailed lymphoma subtype cost description and comparison which supply data for efficiency evaluations and will allow French health policy to improve lymphoma management. This is one of the first studies which assess the additional cost of lymphoma in Europe, according the main sub-types of lymphoma and with real-world database. The additional monthly cost due to HL, FL and DLBCL patients were respectively €5,188, €3,242 and €7,659 for the active treatment phase and the main additional cost driver was principally inpatient stay (i.e. hospitalization costs and additional inpatient medicines, notably rituximab), followed by outpatient medication and productivity loss. This study provides an accurate and detailed lymphoma subtype cost description and comparison which supply data for efficiency evaluations and will allow French health policy to improve lymphoma management.

Background: Lymphomas are costly diseases that suffer from a lack of detailed economic information, notably in a real-world setting. Decision-makers are increasing the search for Real-World Evidence (RWE) to assess the impact, in real-life, of healthcare management and to support their public decisions. Thus, we aimed to assess the real-world net costs of the active treatment phases of adult Hodgkin Lymphoma (HL), Follicular Lymphoma (FL) and Diffuse Large B Cell Lymphoma (DLBCL). Methods: We performed a retrospective cohort study using population-based data from a national representative sample of the French population covered by the health insurance system. Cost analysis was performed from the French health insurance perspective and took into account direct and sick leave compensation costs (€2,018). Healthcare costs were studied over the active treatment phase. We used multivariate modeling to adjust cost differences between lymphoma subtypes. Results: Analyses were performed on 224 lymphoma patients and 896 controls. The mean additional monthly costs due to HL, FL and DLBCL patients were respectively €5,188, €3,242 and €7,659 for the active treatment phase. The main additional cost driver was principally inpatient stay (hospitalization costs and costly cancer-related drugs), followed by outpatient medication and productivity loss. When adjusted, DLBCL remains significantly the most costly lymphoma subtype. Conclusion: This study provides an accurate assessment of the main lymphoma subtypes related cost with high magnitude of details in a real-world setting. We underline where potential cost saving could be realized via the use of biosimilar medication, and where lymphoma management could be improved with the early management of adverse events.KEY POINTSThis is one of the first studies which assess the additional cost of lymphoma in Europe, according the main sub-types of lymphoma and with real-world database.The additional monthly cost due to HL, FL and DLBCL patients were respectively €5,188, €3,242 and €7,659 for the active treatment phase and the main additional cost driver was principally inpatient stay (i.e. hospitalization costs and additional inpatient medicines, notably rituximab), followed by outpatient medication and productivity loss.This study provides an accurate and detailed lymphoma subtype cost description and comparison which supply data for efficiency evaluations and will allow French health policy to improve lymphoma management. This is one of the first studies which assess the additional cost of lymphoma in Europe, according the main sub-types of lymphoma and with real-world database. The additional monthly cost due to HL, FL and DLBCL patients were respectively €5,188, €3,242 and €7,659 for the active treatment phase and the main additional cost driver was principally inpatient stay (i.e. hospitalization costs and additional inpatient medicines, notably rituximab), followed by outpatient medication and productivity loss. This study provides an accurate and detailed lymphoma subtype cost description and comparison which supply data for efficiency evaluations and will allow French health policy to improve lymphoma management.