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Introduction/Background: Guidelines from the World Health Organization currently recommend targeting a body mass index (BMI) between 18.5 and 24.9 kg/m2 based on the lowest risk of mortality observed in epidemiological studies. However, these recommendations are based on population observations and do not take into account potential inter-individual differences. We hypothesized that genetic and non-genetic differences in adiposity, anthropometric, and metabolic measures result in inter-individual variation in the optimal BMI. Methods: Genetic variants associated with BMI as well as related adiposity, anthropometric, and metabolic phenotypes (e.g. triglyceride (TG)) were combined into polygenic risk scores (PRS), cumulative risk scores derived from the weighted contributions of each variant. 387,692 participants in the UK Biobank were split by quantiles of PRS or clinical biomarkers such as C-reactive protein (CRP), and alanine aminotransferase (ALT). The BMI linked with the lowest risk of all-cause and cause-specific mortality outcomes (“nadir value”) was then compared across quantiles (“Cox meta-regression model”). Our results were replicated using the non-linear mendelian randomization (NLMR) model to assess causality. Results: The nadir value for the BMI–all-cause mortality relationship differed across percentiles of BMI PRS, suggesting inter-individual variation in optimal BMI based on genetics (p = 0.005). There was a difference of 1.90 kg/m2 in predicted optimal BMI between individuals in the top and bottom 5th BMI PRS percentile. Individuals having above and below median TG (p = 1.29×10-4), CRP (p = 7.92 × 10-5), and ALT (p = 2.70 × 10-8) levels differed in nadir for this relationship. There was no difference in the computed nadir between the Cox meta-regression or NLMR models (p = 0.102). Conclusions: The impact of BMI on mortality is heterogenous due to individual genetic and clinical biomarker level differences. Although we cannot confirm that are results are causal, genetics and clinical biomarkers have potential use for making more tailored BMI recommendations for patients. / Thesis / Master of Science (MSc) / The World Health Organization (WHO) recommends targeting a body mass index (BMI) between 18.5 - 24.9 kg/m2 for optimal health. However, this recommendation does not take into account individual differences in genetics or biology. Our project aimed to determine whether the optimal BMI, or the BMI associated with the lowest risk of mortality, varies due to genetic or biological variation. Analyses were conducted across 387,692 individuals. We divided participants into groups according to genetic risk for obesity or clinical biomarker profile. Our results show that the optimal BMI varies according to genetic or biomarker profile. WHO recommendations do not account for this variation, as the optimal BMI can fall under the normal 18.5 - 24.9 kg/m2 or overweight 25.0 – 29.0 kg/m2 WHO BMI categories depending on individual genetic or biomarker profile. Thus, there is potential for using genetic and/or biomarker profiles to make more precise BMI recommendations for patients.

Antecedentes: el dolor lumbar (DL) y el esguince de tobillo son lesiones muy prevalentes en los bailarines de ballet. Diferentes estudios relacionan ambas lesiones, por lo que se sugiere realizar una investigación al respecto. Objetivo: determinar si existe asociación entre el esguince de tobillo y la presencia de DL en bailarines de ballet mayores de 18 años en el último año. Diseño del estudio: transversal, analítico, prospectivo y observacional. Métodos: se contactaron a 114 bailarines de diferentes escuelas y compañías de ballet de Lima, quienes respondieron una encuesta online relacionada con la presencia de DL en los últimos seis meses, los esguinces de tobillo en los últimos 12 meses, y otras variables sociodemográficas (edad, talla, peso, índice de masa corporal - IMC, años practicando ballet, y horas de práctica a la semana); así como covariables de inestabilidad de tobillo, lesión en el miembro inferior, hiperlaxitud ligamentaria, entre otras. Resultados: 47 participantes se incluyeron en el análisis del estudio, donde el 61.7 % era de sexo femenino y presentaba una mediana de 22 años de edad. Asimismo, el 57.5 % presentaba DL; y el 25.5 %, esguince de tobillo en los últimos 12 meses. Al asociar las variables al DL se encontró una relación significativa (p<0.05) con peso, IMC e inestabilidad de tobillo. Aun así, no se confirmó una asociación entre el esguince de tobillo y el DL. Conclusión: los hallazgos proporcionan un alto porcentaje de presencia de DL y una asociación significativa con respecto a padecer de inestabilidad de tobillo. / Background: low back pain (DL) and ankle sprain are very prevalent injuries in ballet dancers. Different studies relate both injuries, so it is suggested to carry out an investigation in this regard. Purpose: to determine if there is an association between ankle sprain and the presence of DL in ballet dancers older than 18 years old in the last year. Study design: analytical, prospective, observational and cross-sectional. Methods: 114 dancers from different schools and ballet companies in Lima were contacted; these responded to an online survey related to the presence of DL in the last six months, ankle sprain in the last 12 months, and other sociodemographic variables (age, height, weight, body mass index - BMI, years practicing ballet, and hours of practice per week); as well as covariates of ankle instability, lower limb injury, ligament hypermobilty, among others. Results: 47 participants were included in the study analysis, 61.7 % of which were female and were a median age of 22 years old. Also, 57.5 % had DL and 25.5 % had an ankle sprain in the last 12 months. When associating the variables to DL, a significant association (p<0.05) with weight, BMI and ankle instability was found. Nevertheless, an association between ankle sprain and DL was not confirmed. Conclusion: the findings provide a high percentage of the presence of DL and a significant association with suffering from ankle instability. / Tesis

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Grâce aux progrès médicaux, le taux de survie à 5 ans des enfants et des adolescents diagnostiqués d’un cancer est maintenant d’environ 85%. Malgré ces chiffres encourageants, à l’âge adulte, les survivants d’un cancer pédiatrique sont à risque de développer plusieurs problèmes de santé dont des maladies cardiovasculaires et des complications cardiométaboliques (CM) comme de l'hypertension, une résistance à l'insuline, de la dyslipidémie et de l'obésité abdominale. Devant cette réalité, il importe d’enrichir les connaissances quant à l’évolution et l’étiologie de ces séquelles tôt dans la trajectoire du cancer et de la survivance afin d’améliorer la prise en charge précoce des patients. Pourtant, à ce jour, seulement quelques études ont décrit la santé CM de patients à court terme après la fin des traitements et les facteurs associés au développement hâtif de ces complications demeurent méconnus. Le cancer et ses traitements causent un état pro-inflammatoire & pro-oxydant susceptible d’entraîner le développement de complications CM. En parallèle, la période de traitement est caractérisée par des changements dans les habitudes alimentaires, un comportement sédentaire et une augmentation de l’indice de masse corporelle (IMC), qui peuvent persister après la fin des traitements. À long terme chez les survivants de cancers pédiatriques, le statut d’obésité à la fin des traitements ainsi que certains biomarqueurs inflammatoires ont été associés à la présence de complications CM. De plus, la composition des HDL est différente à long terme chez les survivants de la leucémie lymphoblastique aiguë comparativement à celle de contrôles sains. Étant donné l’importance de tous ces facteurs, il est primordial de les décrire à court terme, après la fin des traitements. Par ailleurs, l’obésité au moment du diagnostic et l’augmentation de l’IMC pendant le traitement influencent négativement le pronostic et l’occurrence d’effets secondaires graves durant les traitements. Toutefois, la plupart des interventions nutritionnelles en oncologie pédiatrique ne tiennent pas en compte la problématique du gain de poids significatif durant les traitements. Ainsi, il semble important d’évaluer la possibilité d’implanter des stratégies misant sur la promotion d'habitudes de vie saines tôt après le diagnostic d’un cancer pédiatrique afin d’améliorer l'état nutritionnel, la qualité de vie et possiblement la santé CM des patients à court et à long terme. Les travaux de cette thèse ont pour but de : i) décrire la santé CM de patients en oncologie pédiatrique peu de temps après les traitements, ii) élaborer, par une revue de littérature, sur le rôle de l’état inflammatoire et oxydant relié au cancer de l’enfant et ses traitements dans le développement des complications CM, iii) évaluer les associations entre l’évolution de l’IMC durant la trajectoire de soins d’un cancer pédiatrique et les complications CM ainsi que le statut inflammatoire; vi) détailler la composition lipidique et protéique des HDL des patients peu de temps après la fin des traitements du cancer pédiatrique et; v) déterminer la faisabilité d’une intervention nutritionnelle précoce chez des enfants et des adolescents nouvellement diagnostiqués d’un cancer. Pour ce faire, deux cohortes de patients ont été recrutées dans le cadre de l’étude VIE (Valorisation, Implication, Éducation) au CHU Sainte-Justine. D’abord, 80 patients suivis en hémato-oncologie ont été rencontrés en moyenne 1,4 ± 0,8 an après la fin de leur traitement contre un cancer pédiatrique. De ce groupe, 56,3 % étaient des filles, 43,8% avaient été traités pour une leucémie. L'âge moyen lors de la rencontre était de 11,8 ans (min - max: 4,5 - 21,0). La proportion de complications CM observée était de 26,3 % pour la pression artérielle (PA) élevée, 8,1 % pour le prédiabète, 35,0 % pour la dyslipidémie et 11,5 % pour l’obésité. Les adolescents (≥ 10 ans au diagnostic) étaient plus susceptibles d'avoir une PA élevée, une dyslipidémie et de cumuler ≥ 2 complications CM que les enfants. Être en surpoids ou obèse après le traitement était associé à des niveaux plus élevés d'insuline, d’HOMA-IR, de leptine et du ratio leptine/adiponectine du plasma. Chez les patients en surpoids ou obèses à la fin du traitement, le changement de l’IMC a été relié au niveau d’adipokines (leptine et ratio leptine/adiponectine) après les traitements. De plus, les fractions de HDL3 étaient enrichies en triglycérides chez les patients présentant une dyslipidémie à l’évaluation par rapport aux normolipidiques et chez ceux ayant été traités avec des doses de doxorubicine ≥ 90 mg/m2 par rapport à des doses inférieures. Parallèlement, une intervention nutritionnelle d'un an, comprenant une évaluation initiale et six visites de suivi tous les deux mois, a été effectuée auprès de 61 participants. De ceux-ci, 51,6% étaient des garçons, l’âge moyen était de 8,5 ans et le temps moyen entre le début de l’intervention et le diagnostic était de 13,2 semaines. Après 1 an d’intervention, le taux de rétention étaient de 72,6 %, 258 rencontres ont été menées sur 362 planifiées (taux de présence 71,6%) et la moitié des participants (50,8 %) avaient participé à au moins 4 rencontres de suivi. En conclusion, peu après le traitement d’un cancer pédiatrique, la santé CM est influencée par l’âge au diagnostic et l’évolution de l’IMC pendant les traitements, et le métabolisme des HDL tant par l’âge que les doses de doxorubicine reçues. Les biomarqueurs du statut inflammatoire peuvent servir d’indicateur de la santé CM chez ces patients. Par ailleurs, l’implantation d’une intervention nutritionnelle impliquant les patients et leurs parents tôt après le diagnostic d’un cancer pédiatrique est faisable et constitue une stratégie à prioriser afin d’optimiser la santé CM de cette population à court et à long terme. Dans leur ensemble, nos travaux contribuent à améliorer la prise en charge et les méthodes d’interventions auprès des enfants et des adolescents diagnostiqués d’un cancer. / Due to medical advances, the 5-year survival rate for children and adolescents diagnosed with cancer is now approximately 85%. Despite these encouraging statistics, in adulthood, survivors of pediatric cancer are at risk of developing several health problems including cardiovascular disease and cardiometabolic complications (CM) such as hypertension, insulin resistance, dyslipidemia and abdominal obesity. In this context, it is important to increase the knowledge of the evolution and etiology of these sequelae to improve early management. However, to date, only a few studies have described the CM health of patients in the short term after the end of treatment and the factors associated with the early development of these complications remain unknown. Cancer and its treatment cause a pro-inflammatory & pro-oxidative state that can lead to the development of CM complications. In parallel, the treatment period is characterized by changes in dietary habits, sedentary behavior, and increased body mass index (BMI), which may persist after treatment ends. In the long term in pediatric cancer survivors, obesity status at the end of treatment and some inflammatory biomarkers have been associated with the presence of CM complications. In addition, HDL composition is different in long-term survivors of acute lymphoblastic leukemia compared with healthy controls. Given the importance of these factors, it is critical to describe them in the short term, after the end of treatment. In addition, obesity at diagnosis and increasing BMI during treatment negatively influence prognosis and the occurrence of serious side effects during treatment. However, most nutritional interventions in pediatric oncology do not address the issue of significant weight gain during treatment. Thus, it seems important to evaluate the possibility of implementing strategies focusing on the promotion of healthy lifestyle habits early after the diagnosis of pediatric cancer in order to improve the nutritional status, quality of life and possibly the CM health of patients in the short and long term. The work in this thesis aims to: i) describe the CM health of pediatric oncology patients shortly after treatment, ii) elaborate, through a literature review, on the role of inflammatory and oxidative status related to pediatric cancer and its treatments in the development of CM complications, iii) evaluate the associations between changes in BMI during the pediatric cancer care trajectory and CM complications as well as inflammatory status; vi) detail the lipid and protein composition of patients' HDL shortly after completion of pediatric cancer treatments and; v) determine the feasibility of early nutritional intervention in children and adolescents newly diagnosed with cancer. Two cohorts of patients were recruited as part of the VIE (Valorisation, Implication, Education) study at CHU Sainte-Justine. First, 80 patients followed in hemato-oncology were met on average 1.4 ± 0.8 year after the end of their treatment for pediatric cancer. Of this group, 56.3% were girls, 43.8% had been treated for leukemia. The mean age at encounter was 11.8 years (min - max: 4.5 - 21.0). The proportion of CM complications observed was 26.3% for high blood pressure (BP), 8.1% for prediabetes, 35.0% for dyslipidemia, and 11.5% for obesity. Adolescents (≥ 10 years of age at diagnosis) were more likely to have elevated BP, dyslipidemia, and ≥ 2 CM complications than children. Being overweight or obese after treatment was associated with higher levels of insulin, HOMA-IR, leptin, and plasma leptin/adiponectin ratio. In patients who were overweight or obese at the end of treatment, the change in BMI was related to the level of adipokines (leptin and leptin/adiponectin ratio) after treatments. In addition, HDL3 fractions were enriched in triglycerides in patients who were dyslipidemic at assessment compared with the normolipidics, and in those who had been treated with doxorubicin doses ≥90 mg/m2 compared to lower doses. In parallel, a one-year nutrition intervention, including an initial assessment and six follow-up visits every two months, was conducted with 61 participants. Of these, 51.6% were boys, the mean age was 8.5 years, and the mean time from intervention initiation to diagnosis was 13.2 weeks. After 1 year of intervention, the retention rate was 72.6%, 258 visits were held out of the 362 planned (71.6% attendance rate) and half of the participants (50.8%) had attended at least 4 follow-up visits. In conclusion, shortly after treatment of pediatric cancer, CM health is influenced by age at diagnosis and BMI changes during treatment, and HDL metabolism by both age and doses of doxorubicin received. Biomarkers of inflammatory status may serve as an indicator of CM health in these patients. Furthermore, implementation of a nutritional intervention involving patients and parents early after diagnosis of pediatric cancer is feasible and is a strategy to prioritize to optimize CM health in this population in the short and long term. Taken together, our work contributes to improve the management and intervention methods for children and adolescents diagnosed with cancer.

Introduction La randomisation mendélienne (RM) est une approche de plus en plus populaire dans les études observationnelles qui utilise des variants génétiques (habituellement des polymorphismes mononucléotidiques ou single-nucleotide polymorphisms, SNPs) associés à une exposition (hypothèse 1 ou pertinence) comme instruments pour estimer l’effet causal de cette exposition sur une issue, en assumant l’absence de confusion entre l’instrument et l’issue (hypothèse 2 ou indépendance) et l’absence d’un effet de l’instrument sur l’issue en dehors de l’exposition (hypothèse 3 ou restriction d’exclusion). Cependant, la validité des résultats de la RM est menacée par la pléiotropie, phénomène biologique par lequel un SNP affecte distinctement l’exposition et l’issue, qui est l’une des principales causes de violation de la restriction d’exclusion. Cette thèse examine certains défis méthodologiques pratiques de la RM relatifs à la vérification de la restriction d’exclusion et à la validité des résultats à travers trois principaux objectifs : 1) cartographier comment les chercheurs en RM préviennent, détectent et/ou contrôlent, et discutent des violations potentielles de la restriction d'exclusion dues notamment à la pléiotropie ; 2) évaluer la performance de la méthode basée sur la confusion positive, qui compare les estimés ponctuels de l’effet de l’exposition sur l’issue obtenus par la RM et par la régression conventionnelle, dans la détection des instruments invalides dans plusieurs contextes pratiques d’études de RM ; et 3) examiner l’impact des méthodes courantes de gestion de la médication antihypertensive dans les études de RM modélisant la pression artérielle (PA) sur l'estimation de l’effet causal et la détection des violations potentielles de la restriction d'exclusion. Méthodes Pour l’objectif 1, une revue de littérature de 128 études de RM ayant utilisé au moins un SNP sur le gène FTO (fat mass and obesity-associated) comme instrument de l’indice de masse corporelle (IMC) a été réalisée. La façon dont les auteurs préviennent, évaluent ou contrôlent, et discutent des violations potentielles de la restriction d’exclusion dues notamment à la pléiotropie a été examinée. Pour l’objectif 2, une étude de simulation statistique considérant des contextes d’études de RM utilisant comme instrument un SNP ou un score de risque génétique (genetic risk score, GRS), une issue continue ou binaire, dans des scénarios évaluant l’impact de la taille de l’échantillon et du type de pléiotropie (indirect ou direct), a été réalisée. La performance de la méthode basée sur la confusion positive a été définie comme le pourcentage de jeux de données simulés dans lesquels la méthode détectait des instruments invalides. Pour l’objectif 3, une étude de RM de l’association entre l’IMC et la PA systolique (PAS) a été réalisée. Les méthodes de gestion de la médication antihypertensive examinées étaient : (i) pas de correction, (ii) inclure la médication dans les modèles comme une covariable d’ajustement, (iii) exclure de l’analyse les sujets traités aux antihypertenseurs, (iv) ajouter une valeur constante de 15 mm Hg aux valeurs mesurées de la PAS chez les sujets traités aux antihypertenseurs, et (v) utiliser comme issue un indicateur binaire de l'hypertension. Résultats Il existe une pléthore de méthodes utilisées dans les études de RM dont certaines peuvent être sous-optimales à prévenir, détecter ou contrôler le biais dû à l’inclusion des SNPs pléiotropiques. Les simulations statistiques montrent qu’en RM utilisant un SNP comme instrument, la méthode basée sur la confusion positive est performante à détecter l’invalidité de l’instrument lorsque la pléiotropie est directe plutôt qu’indirecte, indépendamment de l’issue, mais la performance de la méthode s’améliore avec l’augmentation de taille de l’échantillon. En revanche, la méthode est moins performante à détecter l’invalidité lorsque l’instrument est un GRS, mais sa performance augmente avec la proportion des SNPs invalides inclus dans le GRS. Enfin, les estimations de la RM varient énormément selon la stratégie de gestion de la médication antihypertensive choisie, contrairement à la détection des violations de la restriction d’exclusion qui n’en est pas affectée. Conclusion Cette thèse met de l’avant certaines difficultés méthodologiques dans les applications de la RM et l’importance de la triangulation de plusieurs méthodes dans la vérification des hypothèses de RM. Le champ de la RM est en plein essor, et des nouvelles méthodes sont souvent proposées. Il devient important non seulement de les évaluer, mais aussi d’en détailler l’utilisation et les hypothèses sous-jacentes pour une utilisation optimale en complément aux méthodes existantes. / Introduction Mendelian randomization (MR) is an increasingly popular technique in observational studies that uses genetic variants (usually single-nucleotide polymorphisms, SNPs) associated with an exposure (Assumption 1 or relevance) as instruments to estimate the causal effect of that exposure on an outcome, assuming no confounding between the instrument and the outcome (Assumption 2 or independence) and no effect of the instrument on the outcome outside of its association with the exposure (Assumption 3 or exclusion restriction). However, the validity of the MR results is challenged by pleiotropy, the biological phenomenon whereby a SNP distinctly affects the exposure and the outcome, which is one of the leading causes of violation of the exclusion restriction assumption. This thesis examines some practical MR methodological challenges related to the assessment of the exclusion restriction and the validity of MR results through three main objectives: 1) to examine how MR researchers prevent, detect, and/or control for, and discuss potential violations of the exclusion restriction due especially to pleiotropy; 2) to evaluate the performance of the leveraging positive confounding (LPC) method that compares the MR and the conventional point estimates in detecting invalid instruments in several practical MR settings; and 3) to examine the impact of commonly used methods of accounting for antihypertensive medication in MR studies modeling blood pressure (BP) on the estimation of the causal effect and the detection of potential violations of the exclusion restriction. Methods For Objective 1, a literature review of 128 MR studies that used at least one SNP in the fat mass and obesity-associated (FTO) gene as an instrument for body mass index (BMI) was conducted to examined how the authors prevent, detect, or control, and discuss potential violations of the exclusion restriction, especially due to pleiotropy. For Objective 2, a simulation study considering MR analyse settings using single SNP or genetic risk score (GRS) as an instrument, continuous or binary outcome, in scenarios evaluating the impact of sample size and type of pleiotropy (indirect vs. direct) was performed. The performance of the LPC method was assessed as the percentage of simulated datasets in which the LPC method detected invalid instruments. For Objective 3, an MR study of the association between BMI and systolic BP (SBP) was performed. The methods for accounting for antihypertensive medication examined were: (i) no adjustment, (ii) include medication in the models as an adjustment covariate, (iii) exclude from the analysis subjects treated with antihypertensive medication, (iv) add a constant value of 15 mm Hg to the measured values of SBP in subjects using antihypertensive medication, and (v) use as outcome a binary indicator of hypertension. Results There exists a plethora of methods used in MR studies, some of which may be suboptimal for preventing, detecting, or controlling for bias due to the inclusion of pleiotropic SNPs. Statistical simulations show that in MR using single SNP as an instrument, the LPC method performs better at detecting invalidity of the instrument when the pleiotropy is direct than indirect, regardless of the outcome, although the performance of the method improves with increasing sample size. In contrast, the method performs less well in detecting invalidity when the instrument is a GRS, but its performance increases with the proportion of invalid SNPs included in the GRS. Finally, MR estimates change greatly depending on the chosen strategy of accounting for antihypertensive medication in contrast to the detection of exclusion restriction violations which is not impacted. Conclusion This present thesis highlights some of the methodological challenges in MR applications and the importance of triangulating multiple methods when assessing the MR assumptions. The MR field is booming, and new methods are often proposed. Therefore, it is important to evaluate these methods as well as to detail their application and underlying assumptions for optimal use as a complement to existing methods.

No description available.

Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [11C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [11C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m2) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.

This study aimed at exploring the impact of early traumatic experiences on bariatric patients with the intent to give "voice" to their experiences. The impact of morbid obesity and the lack of quality of life among those suffering from this form of chronic illness can be devastating. Meaningful support systems and bariatric surgery are therefore considered as forced behavioural interventions to remediate the impact of childhood trauma and subsequent development of morbid obesity among this group of bariatric patients. Through a process of social constructivism and dialogue between the researcher and the five participants, the co-construction according to themes was supported by a qualitative research approach and the case study method. For the analysis of the themes according to the participants' "voices", the thematic content analysis method was used to analyse the data and was finally linked to supportive literature. It is hoped that the results from this study will contribute to the development of a unique assessment and support programme to those who have to endure the burden of morbid obesity associated with early childhood trauma; and that the process prior to and post bariatric surgery will be an important contribution to finding quality of life and giving new meaning to patients after suffering through their bodies and traumatised minds. / Psychology / D.Litt. et. Phil (Psychology)

During recent decades, lumbar spinal stenosis (LSS) has become the most common indication for spine surgery, a change that coincides with a higher worldwide prevalence of overweight and obesity. Thus, surgical treatment of LSS in the overweight and obese population is common and increasing in scope. The overall aim of this thesis was to investigate whether body mass index (BMI) is related to the development of LSS, and whether BMI is linked to outcome after surgery for LSS. We further evaluated whether there are specific experiences of LSS from a patient perspective. Data were obtained for all patients registered in the Swedish Spine Register who had undergone surgery for LSS between January 1, 2006 and June 30, 2008. After adjusting for differences in baseline characteristics, patients with obesity showed both poorer results after surgery and a higher rate of dissatisfaction than patients with normal weight (odds ratio 1.73; 95% confidence interval, CI, 1.36-2.19). Furthermore, patients with obesity in the cohort reported modest weight loss at follow-up (2.0 kg; 95% CI, 1.5-2.4), and only 8% reported a clinical important weight loss 2 years after surgery. Our analysis of 389,132 construction workers, showed that overweight (incidence rate ratio, IRR 1.68; 95% CI, 1.54-1.83) and obesity (IRR 2.18; 95% CI, 1.87-2.53) were associated with an increased future risk in developing LSS when compared with patients with normal weight. To gain insight into the patients' perspective of LSS, we performed interviews with 18 patients who were on a waiting list for LSS surgery. The transcripts, analyzed with content analysis, revealed that living with LSS is a physical, mental and social challenge in which resources to cope with the condition are of major importance. In summary, obesity is associated with poorer results after surgery, and patients with obesity report modest weight loss during follow-up. In addition, obesity is associated with an increased risk to develop LSS. Our findings revealed that being a patient with LSS, naturally involves considerable suffering and pain, but it also implies being a person with his or her own resources who is able to cope with these adverse conditions.