Contexte : Les auto-soins sont essentiels dans la gestion des maladies chroniques. Ils sont influencés par la culture, les valeurs, la littératie, le soutien des proches et l’accès aux soins. Ce mémoire vise à explorer les expériences d’auto-soins en lien avec les maladies chroniques et divers facteurs aux Indonésiens qui vivent à Montréal. Méthodes : Une approche descriptive qualitative a été utilisée. Huit adultes (hommes et femmes) vivant avec des maladies ont participé. Une analyse thématique a été réalisée. Résultats : Trois thèmes ont émergé : 1) « Qu’est-ce qui favorise les auto-soins chez les Indonésiens? » permet de saisir les différentes sources de soutien et stratégies qui ont aidé les participants à gérer leur maladie; 2) « Défis des auto-soins et de vivre avec une maladie chronique » met en évidence les principaux défis et aux émotions vécues lié aux maladies chroniques; 3) « Attentes par rapport aux auto-soins et au soutien » révèle les déceptions à l’égard des auto-soins et du soutien. Conclusion : Ensemble les thèmes mettent en évidence plusieurs éléments à prendre en compte pendant les soins aux Indonésiens, incluant l’importance de la foi et de la religion, être serviable a une place importante dans les auto-soins, les auto-soins sont un processus d’apprentissage, les auto-soins sont vécus différemment dans le pays d’accueil, le soutien social peut se poursuivre au niveau transnational, les professionnels de la santé doivent fournir des soins plus personnalisés. Mots-clés : auto-gestion, auto-entretient, autosurveillance, diabète, hypertension, arthrite, maladie rénale chronique, immigrants / Background: Self-care is an essential aspect of chronic disease management. This experience is shaped by culture and values, health knowledge/literacy, support from others and access to care. We aimed to explore the chronic illness self-care experiences and various influencing factors among Indonesian immigrants living in Montreal. Methods: We used a qualitative descriptive approach. Eight men and women, living with various chronic illnesses, participated. We conducted a thematic analysis. Results: Three broad themes were identified: 1) “What’s Helpful for Indonesian’ Self-care” captures the different sources of support and/or ways of being and doing that helped the participants manage and monitor their illness and feel well and healthy, both physically and emotionally; 2) “Self-care Challenges and Responses to Living with a Chronic Illness” highlights the key challenges that participants faced while living with a chronic illness and provides a description of how participants responded to living with an illness; 3) “Expectations regarding Self-care and Support” reveals some of the participants’ disappointments regarding their own self-care and/or support. Conclusion: Taken together the themes highlight several important points regarding the self-care experiences of Indonesian immigrants that should be considered during care. These include the importance of faith and religion for Indonesians in self-care; being helpful has an important place in self-care; self-care is a learning process; self-care; including family support, is experienced differently in Canada compared to being in Indonesia; social support may continue transnationally; and there is a need for health care professionals to provide more personalized care. Keywords: self-management, self-maintenance, self-monitoring, chronic illness, diabetes, hypertension, arthritis, chronic kidney disease, immigrants

Cette thèse avait pour but d'illustrer l'intérêt de méthodes statistiques avancées lorsqu'on s'in­ téresse aux associations entre différents facteurs et la progression de la maladie rénale chronique (MRC). Dans un premier temps, une revue de la littérature a été effectuée alin d'identifier les méthodes classiquement utilisées pour étudier les facteurs de progression de la MRC ; leurs limites et des méthodes permettant de mieux prendre en compte ces limites ont été discutées. Notre second travail s'est concentré sur les analyses de données de survie et la prise en compte de la censure par intervalle, qui survient lorsque l'évènement d'intérêt est la progression vers un stade spécifique de la MRC, et le risque compétitif avec le décès. Une comparaison entre des modèles de survie standards et le modêle illness-death pour données censurées par intervalle nous a permis d'illustrer l'impact de la modélisation choisie sur les estimations à la fois des effets des facteurs de risque et des probabilités d'évènements, à partir des données de la cohorte NephroTest. Les autres travaux ont porté sur les analyses de données longitudinales de la fonction rénale. Nous avons illustré l'intérêt du modèle linéaire mixte dans ce contexte et présenté son extension pour la prise en compte de sous-populations de trajectoires de la fonction rénale différentes. Nous avons ainsi identifier cinq classes, dont une avec un déclin très rapide et une autre avec une amélioration de la fonction rénale au cours du temps. Des perspectives de travaux liés à la prédiction permettent enfin de lier les deux types d'analyses présentées dans la thèse. / The objective of this thesis was to illustrate the benefit of using advanced statistical methods to study associations between risk factors and chrouic kidney disease (CKD) progression. In a first time, we conducted a literature review of statistical methods used to investigate risk factors of CKD progression, identified important methodological issues, and discussed solutions. In our sec­ ond work, we focused on survival analyses and issues with interval-censoring, which occurs when the event of interest is the progression to a specifie CKD stage, and competing risk with death. A comparison between standard survival models and the illness-death mode! for interval-censored data allowed us to illustrate the impact of modeling on the estimates of both the effects of risk factors and the probabilities of events, using data from the NephroTest cohort. Other works fo­ cused on analysis of longitudinal data on renal function. We illustrated the interest of linear mixed mode! in this context and presented its extension to account for sub-populations with different trajectories of renal function. We identified five classes, including one with a strong decline and one with an improvement of renal function over time. Severa! perspectives on predictions bind the two types of analyses presented in this thesis.

The progressively increasing prevalence of the Metabolic Syndrome (MetS) has emerged as a major global health concern since the MetS is associated with an increased risk for cardiovascular morbidity and mortality. Central obesity represents a key feature of the MetS and is strongly related to all MetS comorbidities. Dysregulation of adipose tissue-derived proteins, so called adipokines, has been implied to partially contribute to these effects. Recently, fibroblast growth factor-21 (FGF-21) has been introduced as a novel insulin sensitizing and weight reducing adipokine with potential therapeutic properties. However, data on FGF-21 elimination are rather limited. Therefore, FGF-21 regulation in relation to renal function has been investigated in a patient population with chronic kidney disease (CKD, study population 1), as well as one with acute kidney impairment (study population 2). In study population 1 (n = 499), patients were distributed into five CKD subgroups according to estimated glomerular filtration rate (eGFR). Median FGF-21 serum concentrations progressively increased from CKD stage 1 to stage 5 and highest values of FGF-21 were detected in stage 5 (1: 86.4 ng/l; 2: 206.4 ng/l; 3: 289.8 ng/l; 4: 591.3 ng/l; 5: 1918.1 ng/l). Furthermore, eGFR remained the strongest predictor for FGF-21 levels in multivariate analysis. For study population 2 (n = 32), blood samples were obtained before elective unilateral partial or total nephrectomy, as well as within 30 hours after surgery. In this population FGF-21 levels significantly increased after surgery (325.0 ng/l) as compared to before surgery (255.5 ng/l). Furthermore, relative changes of FGF-21 were independently and positively predicted by relative changes of creatinine in this cohort. These results are in accordance with the hypothesis that FGF-21 is eliminated by the kidneys and that the extent of kidney dysfunction substantially contributes to serum FGF-21 levels. However, additional animal experiments and prospective clinical studies are needed to further elucidate the role of the kidneys in FGF-21 physiology.

Chronic kidney disease (CKD) is a life-threating disease which arises as a frequent consequence of diabetes and hypertension. Since it is going on silently, CKD often progresses to the end-stage renal disease. It is therefore necessary to combat this disease especially due to the fact that the world population is growing old. The aim of this work was to determine the contribution of selected vasoactive systems contributing to the maintenance of high blood pressure in the developmental and established phase of CKD. Two models of CKD were used: 5/6 nephrectomy in Ren-2 transgenic rats (TGR) and stenosis of renal artery (2K1C) in Wistar rats. We demonstrated that renin-angiotensin system does not play so important role in blood pressure maintenance in both CKD models. By contrast, a more important role has sympathetic nervous system. During both the developmental and established phase of CKD, vasoconstrictor systems prevail above vasodilator NO-synthase effects. In fact, the role of NO-dependent vasodilation gradually decreased in nephrectomized TGR rats, while it was unchanged in Wistar rats with 2K1C hypertension.

La presente tesis tiene por finalidad identificar los obstáculos excesivos que limitan la importación de dispositivos médicos en la subpartida nacional 90.18.39.00.10 con descripción comercial “los demás conjuntos para hemodiálisis, transfusiones o similares” en el periodo 2019. Los productos comprendidos en la subpartida mencionada están dirigidos al tratamiento de la insuficiencia renal dentro del sistema de salud peruano. En el primer capítulo, se detalla el marco teórico, términos relevantes, los antecedentes de investigación nacionales e internacionales, así como el sustento legal en el cual está enmarcada la presente investigación. En el segundo capítulo, se detalla el plan de investigación, lo cual abarca la realidad problemática, los objetivos e hipótesis principales y específicos. Asimismo, contiene también la justificación de la investigación teórica, práctica y metodológica. El tercer capítulo, detalla la metodología de trabajo. Es decir, el enfoque aplicado, siendo en esta ocasión del tipo cualitativo explicativo. Adicionalmente, se menciona las limitaciones, la población, la muestra, la recolección de datos y los aspectos éticos. En el cuarto capítulo, se lleva a cabo el desarrollo y análisis de resultados. En ese sentido, se detalla la información obtenida mediante la técnica de entrevista de profundidad, manejando un programa de atlas TI. Para el presente documento, se ha elaborado una muestra de las empresas representativas y se ha entrevistado al responsable de comercio exterior y al personal químico farmacéutico. Finalmente, en el quinto, sexto y séptimo capítulo, se presentan la discusión, consideraciones finales y recomendaciones. / The purpose of this thesis is to identify the excessive obstacles that limit the importation of medical devices in the national subheading 90.18.39.00.10 with a commercial description "the other sets for hemodialysis, transfusions or similar" in the period 2019. The products included in the mentioned subheading are aimed at the treatment of kidney failure within the Peruvian health system. In the first chapter, the theoretical framework, relevant terms, the national and international research background are detailed, as well as the legal basis in which this research is framed. In the second chapter, the research plan is detailed, which includes the problematic reality, the main and specific objectives and hypotheses. Likewise, it also contains the justification of the theoretical, practical and methodological research. The third chapter details the work methodology. That is to say, the applied approach, this time being of the qualitative explanatory type. Additionally, the limitations, the population, the sample, the data collection and the ethical aspects are mentioned. In the fourth chapter, the development and analysis of results is carried out. In this sense, the information obtained through the in-depth interview technique is detailed, using an Atlas TI program. For this document, a sample of representative companies has been prepared and the person in charge of foreign trade and the chemical-pharmaceutical staff have been interviewed. Finally, in the fifth, sixth and seventh chapters, the discussion, final considerations and recommendations are presented. / Tesis

Objetivo: Se evaluó la utilidad de la razón TG/HDL-c como factor predictor de eventos cardiovasculares y mortalidad en pacientes adultos con enfermedad renal crónica (ERC) en hemodiálisis. Método: Se llevó a cabo una revisión sistemática en las bases Medline, Scopus, Embase, Web of Science y Pubmed para identificar los estudios tipo cohorte relevantes sobre eventos cardiovasculares y mortalidad en pacientes con ERC sometidos a hemodiálisis y el rol del TG/HDL-c como factor de riesgo. Resultado: Se evaluaron cuatro estudios tipo cohorte, con un total de 52 579 pacientes con ERC en hemodiálisis. De estos, tres estudios conducidos en poblaciones asiáticas asociaron la razón TG/HDL-c elevada como un factor de riesgo para eventos cardiovasculares y mortalidad y un estudio conducido en Estados Unidos de América que poseía el mayor porcentaje de la muestra (50 673 pacientes), asoció el marcador como un factor protector. La razón TG/HDL-c elevada se asocia a una mejor supervivencia en pacientes hemodializados y existe una consistente asociación inversa gradual entre TG/HDL-c y mortalidad en todos los subgrupos de análisis. Encontrándose, en la categorización por deciles de la variable de exposición, una disminución de 21% de riesgo de mortalidad cardiovascular y una disminución del 15% para mortalidad por todas las causas en el decil más alto en comparación con el grupo de referencia. (D10 aHR= 0.79: IC95% (0.69- 0.91) y D10 aHR= 0.85: IC95% (0.78- 0.92). Conclusiones: La razón TG/HDL-c se evidencia como un factor protector para desenlaces cardiovasculares y para mortalidad en la población americana y como un factor de riesgo para los mismos en la población proveniente de Asia. Por lo que, los resultados no son concluyentes para su aplicación en cualquier contexto. / Objective: The usefulness of the TG/HDL-c ratio as a predictor of cardiovascular events and mortality in adult patients with chronic kidney disease (CKD) on hemodialysis was evaluated. Method: A systematic review was carried out in the Medline, Scopus, Embase, Web of Science and Pubmed databases to identify the relevant cohort studies on cardiovascular events and mortality in CKD patients undergoing hemodialysis the role of TG/HDL-c as a risk factor. Result: Four cohort-type studies were evaluated, with a total of 52,579 CKD patients on hemodialysis. Of these, three studies conducted in Asian populations associated the elevated TG/HDL-c ratio as a risk factor for cardiovascular events and mortality, and one study conducted in the United States of America had the highest percentage of the sample (50 673 patients), associated the marker as a protective factor. The elevated TG/HDL-c ratio is associated with better survival in hemodialysis patients, and there is a consistent gradual inverse association between TG/HDL-c and mortality in all analysis subgroups. Finding, in the decile categorization of the exposure variable, a 21% decrease in the risk of cardiovascular mortality and a 15% decrease in all-cause mortality in the highest decile compared to the reference group. (D10 aHR=0.79; 95% CI:0.69-0.91 and D10 aHR=0.85; 95%CI:0.78-0.92. Conclusions: The TG/HDL-c ratio is a protective factor for cardiovascular outcomes and mortality in the American population and a risk factor for them in the population from Asia. Therefore, the results are not conclusive for their application in any context. / Tesis

Indiana University-Purdue University Indianapolis (IUPUI) / Living donors have contributed about 6,000 kidneys per year in the past 10 years, but more than 100,000 individuals are still waiting for a kidney transplant. Living kidney donors undergo a major surgical procedure without direct medical benefit to themselves, but comprehensive follow-up information on living donors’ health is unfortunately limited. Expert recommendations suggest capturing clinical information beyond traditional sources to improve surveillance of co-morbid conditions from living kidney donors. Currently the United Network for Organ Sharing is responsible for collecting and reporting follow-up data for all living donors from U.S. transplant centers. Under policy implemented in February of 2013, transplant centers must submit follow-up date for two years after donation, but current processes often yield to incomplete and untimely reporting. This dissertation uses a statewide Health Information Exchange as a new clinical data source to 1) retrospectively identify a cohort of living kidney donors, 2) understand their follow-up care patterns, and 3) observe selected clinical outcomes including hypertension, diabetes and post-donation renal function.

Contexte : Les patients âgés atteints de néphropathie diabétique ne reçoivent souvent pas un traitement pharmacologique optimal. Les directives de pratique clinique actuelles n'intègrent pas le concept de soins personnalisés. Les algorithmes d'aide à la décision clinique (ADC) qui tiennent compte à la fois des preuves et des soins personnalisés pour améliorer les résultats des patients peuvent améliorer les soins aux personnes âgées. L'objectif de cette recherche est de concevoir et de valider un algorithme ADC pour la prescription d'inhibiteurs du système rénineangiotensine- aldostérone (ISRAA) pour les patients âgés atteints de diabète. Méthodes : La conception de l'algorithme ADC comprenait trois phases principales. Dans la première phase, nous avons recherché, examiné et évalué les preuves actuelles sur plusieurs sujets liés aux décisions de prescription pour les patients âgés et à l'adhésion des cliniciens aux directives de pratique. Nous avons également procédé à un examen systématique et à une méta-analyse d'essais cliniques randomisés afin de déterminer les valeurs du nombre de patients à traiter (NPT) et du délai d'obtention d'un avantage (DOA) applicables à notre population cible en vue de leur utilisation dans l'algorithme. Dans la deuxième phase, nous avons exploré les points de vue des patients et des prestataires de soins de santé sur les outils ADC en menant des entretiens avec les patients et une enquête transversale auprès des prestataires de soins de santé. Dans la troisième et dernière phase, les résultats des études réalisées dans les phases un et deux ont été utilisés pour informer le développement de l'algorithme ADC qui a ensuite été validé dans une étude Delphi. Résultats : Nous avons créé un algorithme ADC qui couvrait 16 scénarios possibles. Neuf scénarios correspondaient à des recommandations de méta-analyses, tandis que cinq scénarios correspondaient à des directives de pratique clinique. Pour les neuf cas, nous avons généré 36 recommandations personnalisées et neuf recommandations générales sur la base des valeurs NPT et DOA calculées et appariées. En outre, nous avons pris en compte l'espérance de vie et la capacité fonctionnelle du patient. L'algorithme a été validé lors de trois tours d'une étude Delphi. Conclusion : Nous avons conçu un algorithme de CDS fondé sur des preuves qui intègre des considérations souvent négligées dans les directives de pratique clinique, notamment l'espérance de vie restante, la charge médicamenteuse et l'état fonctionnel. Les prochaines étapes consistent à le tester dans le cadre d'un essai clinique afin d'étudier s'il est capable d'atteindre des objectifs cliniques prévisibles et réalistes, de maintenir la qualité de vie des personnes âgées et de réduire l'utilisation et le coût du système de santé. / Background: Older patients with diabetic nephropathy often do not receive optimal pharmacological treatment. Current clinical practice guidelines do not incorporate the concept of personalized care. Clinical decision support (CDS) algorithms that consider both evidence and personalized care to improve patient outcomes can improve the care of older adults. The aim of this research is to design and validate a CDS algorithm for prescribing renin-angiotensin aldosterone system inhibitors (RAASi) for older patients with diabetes. Methods: The design of the CDS algorithm included three main phases. In phase one, we searched, reviewed, and evaluated current evidence on several topics related to prescribing decisions for older patients and clinicians' adherence to practice guidelines. We also conducted a systematic review and a meta-analysis of randomized clinical trials to determine the number needed to treat (NNT) and time-to-benefit (TTB) values applicable to our target population for use in the algorithm. In phase two, we explored the views of patients and healthcare providers on CDS tools through conducting patient interviews and a cross-sectional survey of healthcare providers. In the third and final phase, findings from studies completed in phases one and two were used to inform the development of the CDS algorithm which was then validated using modified Delphi methodology. Results: We have created a CDS algorithm that covered 16 possible scenarios. There were nine scenarios matched to meta-analysis recommendations, while five scenarios were matched to clinical practice guidelines. For the nine cases, we have generated 36 personalized and nine general recommendations based on the calculated and matched NNT and TTB values. In addition, we have considered the patient’s life expectancy and functional capacity. The algorithm was validated in three rounds of a modified Delphi study. Conclusion: We designed an evidenceinformed CDS algorithm that integrates considerations often overlooked in clinical practice guidelines, including remaining life expectancy, medication burden, and functional status. The next steps include testing in a clinical trial to study if it is able to achieve predictable and realistic clinical goals, maintaining quality of life in older adults, and reducing healthcare system use and cost.

In recent years the number of electronic healthcare records (EHRs)has increased rapidly. EHR represents a systematized collection of patient health information in a digital format. EHR systems maintain diagnoses, medications, procedures, and lab tests associated with the patients at each time they visit the hospital or care center. Since the information is available into multiple visits to hospitals or care centers, the EHR can be used to increasing quality care. This is especially useful when working with chronic diseases because they tend to evolve. There have been many deep learning methods that make use of these EHRs to solve different prediction tasks. Transformers have shown impressive results in many sequence-to-sequence tasks within natural language processing. This paper will mainly focus on using transformers, explicitly using a sequence of visits to do prediction tasks. The model presented in this paper is called CondBEHRT. Compared to previous state-of-art models, CondBEHRT will focus on using as much available data as possible to understand the patient’s trajectory. Based on all patients, the model will learn the medical ontology between diagnoses, medications, and procedures. The results show that the inferred medical ontology that has been learned can simulate reality quite well. Having the medical ontology also gives insights about the explainability of model decisions. We also compare the proposed model with the state-of-the-art methods using two different use cases; predicting the given codes in the next visit and predicting if the patient will be readmitted within 30 days.

Chronic kidney disease (CKD) is defined as glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 for 3 months and is characterized by progressive loss of renal function. The second leading cause of CKD is hypertension. More than half of CKD patients also suffer from hypertension. Arteries and arterioles adjust to the fluctuations in the systematic blood pressure through a mechanism called autoregulation. In the kidneys, autoregulation protects the delicate glomeruli capillaries from high blood pressure and occurs through myogenic constriction (MC). MC refers to contraction of arterioles in response to an increase in the blood pressure. Chronically hypertensive individuals and animal models have an enhanced MC, leading to minimal renal injury despite their elevated blood pressure. Experimental and clinical evidence point to a role for the MC in the pathogenesis of the CKD, however, the mechanism through which preglomerular arterial MC contributes to CKD has not been fully elucidated. This thesis showed that augmented MC in chronically hypertensive animal models was due to increased thromboxane A2 prostaglandin that was not released from the endothelium (Chapter 2). Nevertheless, inhibiting MC while also reducing the blood pressure prevented salt-induced renal injury even though the blood pressure was still not normalized compared to the normotensive controls (Chapter 3). The resulting improvement in renal structure and function could be attributed to the reduction in the blood pressure, albumin, and uromodulin (UMOD) excretion (Chapter 3). UMOD is a kidney-specific glycoprotein that, based on a genome-wide association study have the strongest association to CKD (Chapter 3). Comparing two CKD hypertensive animal models further revealed that CKD progression was independent of the blood pressure and strongly associated with UMOD excretion levels (Chapter 4). Collectively, the data discussed in this thesis demonstrates potential therapeutic targets in CKD hypertensive animal models. / Dissertation / Doctor of Philosophy (PhD)