Introduction: This study evaluated long-term outcomes of young survivors of colorectal cancer including survival, development of acute illnesses, and childbirth. Methods: Persons aged 20-44 diagnosed with colorectal cancer and surviving at least five years were identified using the Ontario Cancer Registry and compared to randomly selected controls. Outcomes included death, admission to hospital for acute illness, and childbirth in women, determined by linkage to provincial administrative data. Results: There were 917 cancer survivors in this study. Survivors were more likely to die (HR 8.2, 95%CI [5.8, 11.6]), and require admission to hospital for acute illness (rate ratio 3.4, 95%CI [2.9, 4.1]) than controls. There was no difference in admissions for childbirth in women (HR 0.6, 95%CI [0.3, 1.4]). Conclusions: Five-year survivors of colorectal cancer remain at high risk of long-term death and illness. Aggressive surveillance for recurrent malignant disease is necessary to mitigate risk of death.

Introduction: This study evaluated long-term outcomes of young survivors of colorectal cancer including survival, development of acute illnesses, and childbirth. Methods: Persons aged 20-44 diagnosed with colorectal cancer and surviving at least five years were identified using the Ontario Cancer Registry and compared to randomly selected controls. Outcomes included death, admission to hospital for acute illness, and childbirth in women, determined by linkage to provincial administrative data. Results: There were 917 cancer survivors in this study. Survivors were more likely to die (HR 8.2, 95%CI [5.8, 11.6]), and require admission to hospital for acute illness (rate ratio 3.4, 95%CI [2.9, 4.1]) than controls. There was no difference in admissions for childbirth in women (HR 0.6, 95%CI [0.3, 1.4]). Conclusions: Five-year survivors of colorectal cancer remain at high risk of long-term death and illness. Aggressive surveillance for recurrent malignant disease is necessary to mitigate risk of death.

Stroke is a major cause of premature death and disability throughout the world and atrial fibrillation (AF) is one of the most common preventable causes of stroke. AF affects about 10% of individuals aged ≥80 years, but warfarin is substantially under-used in this age group despite being effective in preventing AF-related thromboembolic events. AF-related ischaemic strokes tend to be severe and incur high care costs, and non-cerebral systemic embolism secondary to AF is also a major clinical burden. Despite that, there are few population-based studies on AF-related ischaemic stroke, and no recent study of the burden of AF-related thromboembolism and the population impact of under-treatment. I have used data from the Oxford Vascular Study (OXVASC), a prospective, population-based incidence study of vascular disease in all territories, which was started in April 2002 and is on-going. The study population comprises of 92,728 individuals registered with 100 family physicians in nine general practices and uses multiple overlapping methods of “hot” and “cold” pursuit to achieve near-complete ascertainment of all patients with acute vascular events. There are several findings described by the research in this thesis which have important implications for public health and can be utilised to improve secondary prevention in stroke. First, I have shown that one-third of all incident embolic events were related to AF and 60% of AF-related embolic events occurred at ≥80 years. Second, I have shown that only 9% of patients aged ≥80 years with incident embolic event related to known prior AF were on premorbid warfarin, and consequently three quarters of those previously independent were dead or disabled six months post event. Third, I have shown that there has been no reduction in age-specific incidence of AF-related ischaemic stroke in Oxfordshire over the last 25 years. Fourth, I have shown that assuming age-specific incidence does not continue to rise, if prevention is not improved, the number of embolic events at age ≥80 years would be expected to treble by 2050 (72,975 AF-related embolic events), with 84% of events at all ages occurring at age ≥80. Fifth, I have shown through a meta-analysis that one in five incident strokes had a history of prior AF of which only 19% were on premorbid warfarin, and AF was related to one in three incident ischaemic strokes. Sixth, I have shown that 1 in 5 stroke patients with known prior AF subsequently became institutionalised and incurred high acute and long-term care costs. Seventh, I have shown that one in five patients with undetermined cerebral ischaemic event subsequently had AF-related late recurrent stroke. Eighth, I have shown that even though TIA or ischaemic stroke patients who subsequently turned out to have new AF at follow-up had significantly higher baseline NT-proBNP compared to non-AF group, its utility is limited by low sensitivity and specificity. Ninth, I have shown in another meta-analysis that the duration of cardiac monitoring after cerebral ischaemic events was the main determinant of the observed rate of pAF, and that 5-7 days of monitoring may be adequate in unselected patient populations. Finally, I have shown that using 5-day event loop recording in clinic patients with TIA and minor ischaemic stroke could detect 12% new AF and the delay in monitoring did not reduce the sensitivity of pAF detection.

This thesis examined the factors correlated with rapid and benign progression of disease in a group of 1452 Parkinsons disease (PD) patients. The data were collected in a movement disorders clinic at the Royal University Hospital, University of Saskatchewan run by Dr. Alex Rajput and Dr. Ali Rajput. This data is a clinical dataset of PD patients collected from 1970 through to February, 2005. This was a retrospective cases-only study, with anticipated analytical follow-up if any correlations were detected between progression type of PD and the many independent variables available in the dataset. <p>Rapid progression was defined as those subjects who reached Hoehn and Yahr stage 3 within three years or H&Y stage 4 or 5 within five years. Subjects who remained in Hoehn and Yahr stage 1 or 2, ten years after onset of disease, were defined as having benign progression. The study analyzed demographic and clinical findings at first visit to this clinic associated with rapid and benign progression of PD. <p> Analysis revealed that, at first clinic visit, benign progression was positively associated with disease duration (OR=1.41; 95% CI 1.27, 1.57), male sex (OR=3.23; 95% CI 1.70, 6.16), and current smoking habit (OR=2.33; 95% CI 0.67, 8.11). Benign progression was negatively associated with older age of onset (OR=0.36; 95% CI 0.25, 0.50), past history of smoking (OR=0.46; 95% CI 0.24, 0.89), current or past use of levodopa (OR=0.45; 95% CI 0.21, 0.98), and mild to severe rigidity (OR=0.43; 95% CI 0.23, 0.80). <p>Analysis also revealed that, at first clinic visit, rapid progression was positively associated with older age of onset (OR=2.45; 95% CI 1.80, 3.33) and mild to severe rigidity (OR=1.73; 95% CI 1.02, 2.94). Rapid progression was negatively associated with disease duration (OR=0.52; 95% CI 0.44, 0.62), male sex (OR=0.58; CI 0.35, 0.95), and mild to severe resting tremor (OR=0.47; CI 0.28, 0.77). <p>The results of this study indicate that age of onset, disease duration, male sex, and rigidity are good potential predictors of disease progression in PD because they have opposite associations with rapid and benign progression. History of levodopa use was negatively associated with benign progression and as such may be good indicator of non-benign progression. Although previous studies found no predictive value for smoking history, the current study reported a unique association between smoking history and benign progression. Past smoking history was negatively associated with benign progression. While there was a positive association with current smoking history, the result was not statistically significant. Resting tremor was negatively associated with rapid progression and as such may be a good indicator of non-rapid progression. <p> Disease characteristics collected at first clinic visit are useful in predicting the course of progression of PD. With more rapid progression of PD closer and more frequent follow-up of patients may be necessary.

This thesis examined the factors correlated with rapid and benign progression of disease in a group of 1452 Parkinsons disease (PD) patients. The data were collected in a movement disorders clinic at the Royal University Hospital, University of Saskatchewan run by Dr. Alex Rajput and Dr. Ali Rajput. This data is a clinical dataset of PD patients collected from 1970 through to February, 2005. This was a retrospective cases-only study, with anticipated analytical follow-up if any correlations were detected between progression type of PD and the many independent variables available in the dataset. <p>Rapid progression was defined as those subjects who reached Hoehn and Yahr stage 3 within three years or H&Y stage 4 or 5 within five years. Subjects who remained in Hoehn and Yahr stage 1 or 2, ten years after onset of disease, were defined as having benign progression. The study analyzed demographic and clinical findings at first visit to this clinic associated with rapid and benign progression of PD. <p> Analysis revealed that, at first clinic visit, benign progression was positively associated with disease duration (OR=1.41; 95% CI 1.27, 1.57), male sex (OR=3.23; 95% CI 1.70, 6.16), and current smoking habit (OR=2.33; 95% CI 0.67, 8.11). Benign progression was negatively associated with older age of onset (OR=0.36; 95% CI 0.25, 0.50), past history of smoking (OR=0.46; 95% CI 0.24, 0.89), current or past use of levodopa (OR=0.45; 95% CI 0.21, 0.98), and mild to severe rigidity (OR=0.43; 95% CI 0.23, 0.80). <p>Analysis also revealed that, at first clinic visit, rapid progression was positively associated with older age of onset (OR=2.45; 95% CI 1.80, 3.33) and mild to severe rigidity (OR=1.73; 95% CI 1.02, 2.94). Rapid progression was negatively associated with disease duration (OR=0.52; 95% CI 0.44, 0.62), male sex (OR=0.58; CI 0.35, 0.95), and mild to severe resting tremor (OR=0.47; CI 0.28, 0.77). <p>The results of this study indicate that age of onset, disease duration, male sex, and rigidity are good potential predictors of disease progression in PD because they have opposite associations with rapid and benign progression. History of levodopa use was negatively associated with benign progression and as such may be good indicator of non-benign progression. Although previous studies found no predictive value for smoking history, the current study reported a unique association between smoking history and benign progression. Past smoking history was negatively associated with benign progression. While there was a positive association with current smoking history, the result was not statistically significant. Resting tremor was negatively associated with rapid progression and as such may be a good indicator of non-rapid progression. <p> Disease characteristics collected at first clinic visit are useful in predicting the course of progression of PD. With more rapid progression of PD closer and more frequent follow-up of patients may be necessary.

We carried out a population-based study on low-grade diffuse gliomas in the Canton of Zurich, Switzerland (population 1.16 million). From 1980 to 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 122 (12.4%) were low-grade (WHO grade II). The incidence rates adjusted to the World Standard Population, per million population per year, were 2.28 for low-grade diffuse astrocytomas, 0.89 for oligoastrocytomas, and 2.45 for oligodendrogliomas. The survival rate (mean follow-up 7.5±4.8 years) was highest for patients with oligodendroglioma (78% at 5 years, 51% at 10 years), followed by those with oligoastrocytoma (70% at 5 years, 49% at 10 years) and fibrillary astrocytoma (65% at 5 years, 31% at 10 years). Survival of patients with gemistocytic astrocytoma was poor, with survival rates of 16% at 5 years and 0% at 10 years. Younger patients (<50 years) survived significantly longer than older patients (>50 years; P=0.013). DNA sequencing, performed in 84% of cases, revealed that TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but were infrequent (13%) in oligodendrogliomas. The presence of TP53 mutations was associated with shorter survival of patients with low-grade diffuse gliomas (log-rank test; P=0.047), but when each histological type was analyzed separately, an association was observed only for oligoastrocytoma (P=0.05). Loss on 1p and 19q were assessed by quantitative microsatellite analysis in 67% of cases. These alterations were frequent in oligodendrogliomas (1p, 57%; 19q, 69%), less common in oligoastrocytomas (lp, 27%; 19q, 45%), rare in fibrillary astrocytomas (lp, 7%; 19q, 7%), and absent in gemistocytic astrocytomas. None of these alterations were predictive of survival. These results establish the frequency of key genetic alterations in low-grade diffuse gliomas at a population-based level. Multi-variate Cox's regression analysis indicates that only age and histological type, but not genetic alterations, are significant predictive factors.

Made available in DSpace on 2016-03-22T17:27:39Z (GMT). No. of bitstreams: 1 LUCIANO SOUZA.pdf: 168635 bytes, checksum: 94c46027ad00ab09128c27fe9b95c3a6 (MD5) Previous issue date: 2006-10-31 / The aim of this study was to identify factors associated to high depressive sintomatology in adolescents with ages between 11 and 15 years in Pelotas - south of Brazil. In this cross-sectional population-based investigation, 79 of the 448 sections of Pelotas were randomly selected. All of the residences of the selected sections were visited seeking to the youths who answered to a self-report and secret questionnaire that contained a scale for depressive symptoms - Children's Depression Inventory (CDI). In total, 1265 adolescents were located for the research team and 1145 answered to the questionnaire. The prevalence found for high depressive sintomatology was 2,1%. After logistic regression adjusted to a hierarchical model, a worse socioeconomic condition of environment, history of academic disapproval, absence of religious practice, to have taken drunkenness in the last month as well as the indicative of conduct disorder, increased the adolescents chances to present high depressive sintomatology. Therefore, the needs of a review on public politics that approach the themes associated to the depressive sintomatology are evidence / O objetivo deste estudo foi identificar os fatores associados à elevada sintomatologia depressiva em adolescentes com idades entre 11 e 15 anos em Pelotas sul do Brasil. Nesta investigação transversal de base populacional, 79 dos 448 setores censitários de Pelotas foram selecionados aleatoriamente. Todas as residências dos setores selecionados foram visitadas visando à captação de jovens que respondessem a um questionário auto-aplicado e sigiloso que continha uma escala para aferição da sintomatologia depressiva Children's Depression Inventory (CDI). No total, 1265 adolescentes foram localizados pela equipe de pesquisa sendo que 1145 responderam ao questionário. A prevalência de elevada sintomatologia depressiva encontrada foi de 2,1%. Após a regressão logística ajustada a um modelo hierárquico, uma pior condição sócio-econômica da ambiente, história de reprovação acadêmica, ausência de prática religiosa, ter tomado porre no último mês assim como o indicativo de transtorno de conduta, aumentaram as chances dos adolescentes em estudo apresentarem elevada sintomatologia depressiva. Portanto, se evidenciam as necessidades de reformulações de políticas públicas que abordem os temas associados à sintomatologia depressiva.

Clostridium difficile colitis (CDC) is associated with a higher risk of acute death among hospitalized ulcerative colitis (UC) patients. However, the risk of colectomy with CDC in these patients has varied across studies. No study has assessed the long-term health impact of CDC in UC patients. Therefore, the present study evaluated the impact of CDC on five-year health outcomes of hospitalized UC patients based on Ontario health administrative data. No overall association was observed between CDC and five-year risks of colectomy or death in overall cohort. However, patients who were discharged from hospital without undergoing colectomy demonstrated marginally higher five-year risks of colectomy and hospital re-admission. Mortality risk and length of stay during index hospitalization were also higher in patients with CDC. Analysis of a parallel cohort of UC patients derived using a published case definition corroborated most of these results, but demonstrated a higher five-year mortality risk with CDC.

Clostridium difficile colitis (CDC) is associated with a higher risk of acute death among hospitalized ulcerative colitis (UC) patients. However, the risk of colectomy with CDC in these patients has varied across studies. No study has assessed the long-term health impact of CDC in UC patients. Therefore, the present study evaluated the impact of CDC on five-year health outcomes of hospitalized UC patients based on Ontario health administrative data. No overall association was observed between CDC and five-year risks of colectomy or death in overall cohort. However, patients who were discharged from hospital without undergoing colectomy demonstrated marginally higher five-year risks of colectomy and hospital re-admission. Mortality risk and length of stay during index hospitalization were also higher in patients with CDC. Analysis of a parallel cohort of UC patients derived using a published case definition corroborated most of these results, but demonstrated a higher five-year mortality risk with CDC.

Le Lymphome à Cellules du Manteau (LCM) est une entité récemment identifiée qui se caractérise par la translocation génétique t(11 ;14)(q13 ;q32) et compte pour 2 à 10 % de tous les Lymphomes non-Hodgkiniens. Avec une survie médiane entre 3 et 5 ans après le diagnostic, le LCM est une pathologie agressive et malgré les récentes avancées thérapeutiques, peu d’informations sont disponibles concernant ses facteurs pronostiques. Certaines études ont analysé le rôle des caractéristiques clinicopathologiques et des nouvelles stratégies thérapeutiques, mais on connait peut le rôle des facteurs environnementaux et du mode de vie sur le pronostic des patients atteints de LCM. Entre 2008 et 2012, le groupe LYSA a mené en France deux essais cliniques prospectifs multicentriques : LM manteau 2010 SA "RiBVD" (NCI01457144) et Manteau 2007 SJ "LyMa" (NCT00921414). Après une comparaison de ces patients avec les patients de population générale, l’effet de facteurs socioéconomiques et des habitudes de vie sur la survie des patients a été étudié à l’aide d’un questionnaire qualitatif administré à tous les volontaires après le diagnostic. Nos résultats suggèrent qu’un faible niveau d’éducation, un indice de masse corporelle élevé et de la consommation d’alcool sont associés à un risque de décès plus élevé chez les patients atteints de LCM. Toutefois, l’étude de tels facteurs et de leur influence sur un sous-type de LNH aussi rare requiert des échantillons d’étude de taille plus importante. L’élargissement des critères d’inclusion des patients dans les essais cliniques permettrait de sélectionner davantage de patients mais aussi des patients mieux représentatifs de la population générale. Enfin, l’intégration systématique de ce type de questionnaire dans les protocoles d’essais cliniques serait aussi un atout majeur. / Mantle Cell Lymphoma (MCL) is a recently defined entity, typically characterised by the genetic translocation t(11 ;14)(q13 ;q32) and counting for 2 - 10% of all non-Hodgkin Lymphomas. With a median survival between 3 and 5 years after diagnosis, MCL is an agressive disease and despite the recent therapeutic advances little in know about its prognostic factors. Some studies had investigated clinicopathological features and new treatment strategies, but there is a lack of knowledge regarding the impact of lifestyle and environnemental factors on outcome of MCL patients. From 2008 to 2012, the LYSA Group conducted in France two prospective multi center clinical trials on MCL : LM manteau 2010 SA "RiBVD" (NCI01457144) and Manteau 2007 SJ "LyMa" (NCT00921414). After a comparison of these patients with population-based data, socioeconomic factors, lifestyle factors and their influence on survival had been investigated through a qualitative survey administrated to each volunteer after diagnosis. Our findings suggest that low educational attainment, low body body mass index and alcohol consumption are associated with a higher risk of death in MCL. However, to investigate lifestyle factors in this rare NHL subtype, larger studies should be carried out. Clinical trial inclusion criteria must be widen to select more patients and patients more representative of general population. Implementation of these epidemiological studies in clinical practice should be considered.