Background: Examining factors unique to major head injury (HI) etiogenesis can help reduce the burden of injury by identifying factors amenable to prevention. Objectives: To describe the epidemiology of HI in Nova Scotia. Risk and protective factors unique to HI were also examined specific to falls and Motor Vehicle Collision (MVC) injuries. Methods: Descriptive analyses and regression models were used to examine the socio-demographic profile of HI and associated risk factors using data from the Nova Scotia Trauma Registry. Results: Regression analyses for MVC-related injury found age, injury place, vehicle type and lack of safety restraint to be independently associated with an increased risk of HI. For falls-related injuries, age, time of trauma, injury mechanism and place were significant factors for a HI event. Conclusion: While HI share many similar characteristics to other major injuries, prevention programs must be aware of both common and unique risk factors for head injuries.

Abstract A population-based study to investigate the epidemiological, genetic and clinical features of neurofibromatoses (NF) in Northern Finland was carried out between 1989–1996. The area concerned was that served by Oulu University Hospital, with a total population of 733 037. A total of 197 patients with neurofibromatosis type 1 (NF1), five with neurofibromatosis type 2 (NF2) and eight with segmental neurofibromatosis (NF5) fulfilling the diagnostic criteria were identified among several hundred patients examined on account of a possible NF diagnosis. The 197 NF1 patients came from 119 families. 77 of these cases were sporadic, 117 familial, and three were mothers of children suffering from NF1 who were themselves diagnosed as having segmental NF. The male/female ratio was 0.93 (95 males and 105 females). The geographical distribution of the patients roughly corresponded to that of the general population in the area. The overall prevalence of NF1 was 23/100 000, with a peak prevalence of 34/100 000 in the age group 10 to 19 years. The overall birth incidence of NF1 was estimated to be 27/100 000, with the highest figure, 37/100 000, recorded in the six-year period 1990–1995. The mean age at the time of diagnosis was 20 ± 16 years in the whole population and 6 ± 4 years in the children born in the 1980's. A new mutation was suspected in 49% of the NF1 cases (96/197), and a mutation rate of 4.37 ± 0.72 × 10-5 was obtained for the period 1960–1995. The relative fitness of the NF1 patients was 0.48, being reduced more in the affected males (0.24) than in the females (0.72). The mean maternal and paternal ages of the sporadic patients were 30 ± 6 and 33 ± 6 years, respectively, which is significantly higher than in the general population. Two cases with a deletion of the NF1 gene were identified, one encompassing the loci from EVI-20 to INT-38 and the other the INT-27 locus, representing 3% of the 66 cases analysed. In seven familial cases the parental origin of the new mutation could be verified and linkage studies showed that the oldest affected individual in the family had inherited the mutation from the father in 6/7 cases. In one family seven members in three generations were affected with a rare spinal neurofibromatosis, and a linkage to the NF1 gene was shown. Of these seven patients, four are included among the 197 studied here while the other three lived outside the area. The diagnostic features of the 164 NF1 patients aged from three months to 73 years who were examined clinically included café au lait spots (CLS) in 96% of cases, freckles in 87%, neurofibromas in 69%, plexiform neurofibromas in 20%, Lisch nodules in 70%, optic glioma (asymptomatic) in 20% and pseudarthrosis in 3%. 56% of the cases had an affected first degree relative. A plexiform neurofibroma was diagnosed in 33 individuals and this became a malignant peripheral nerve sheath tumour(MPNST) during the seven years of monitoring in 15% of cases (5/33). Hyperintense T2 lesions in a MRI scan of the brain were found in 94% of the children under the age of six years who had had such a scan (n = 17) and in 84% of those under 16 years (n = 50). Symptoms related to NF1 which needed medical intervention, rehabilitation or follow-up were diagnosed in about 2/3 of the cases, and in 38% of cases such medical problems of this kind had been treated before NF1 was actually diagnosed. All these findings emphasise the need for a multidisciplinary approach to the follow-up of neurofibromatoses.

Es tracta d'un estudi epidemiològic de les neoplàsies limfoides a Tarragona. Es donen dades d'incidència, mortalitat, supervivència i prevalença en base poblacional de les 3.258 neoplàsies limfoides del Registre de Càncer de Tarragona durant el període 1980-2004 ( 354 limfomes de Hodgkin, 1605 limfomes no-Hodgkin (LNH), 676 mielomes múltiples, 188 leucèmies limfàtiques agudes i 435 leucèmies limfàtiques cròniques). S'ha estudiat la tendència temporal de la incidència i la seva projecció a 2010 i 2015 per a cada grup de malalties. Els LNH s'han classificat histològicament d'acord amb la classificació de l'OMS de les neoplàsies hematològiques, i s'han establert comparacions internacionals. Les principals conclusions han estat que les neoplàsies limfoides a Tarragona mostren un patró epidemiològic occidentalitzat, amb una progressiva millora en la seva supervivència relativa, i que existeix, almenys parcialment, una relació temporal entre la epidèmia de la SIDA i la dels LNH. / This is an epidemiological study of lymphoid neoplasms in Tarragona, a southern region of Catalonia with a population over 800.000. It gives details of incidence, mortality, survival and prevalence in a population basis of 3,258 lymphoid malignancies recorded in the Tarragona Cancer Registry during the period 1980 to 2004 (354 Hodgkin's lymphoma, 1605 non-Hodgkin's lymphoma (NHL), 676 multiple myeloma, 188 acute lymphocytic leukemia and 435 chronic lymphocytic leukemia). We have studied the incidence time trend and its projection to 2010 and 2015 for each disease group. The NHL were classified histologically according to WHO classification of hematologic malignancies, and their relative frequency were compared internationally. The main conclusions were that the lymphoid malignancies in Tarragona show a westernized epidemiological pattern, with a progressive improvement in their relative survival and that there is at least partially, a temporal relationship between the AIDS and the NHL epidemics.

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.

Autism prevalence studies have often relied on administrative prevalence or clinical diagnosis as case-identification strategies. We report the incidence of clinical diagnoses of autism spectrum disorders (ASD), versus research-identified autism among residents of Olmsted County, Minnesota, age =21 years, from 1976-1997. The incidence of clinically diagnosed ASD (with 95% CI) was 1.5 per 100,000 (0.0-3.7) in 1980-1983 and 33.1 (22.8-43.3) in 1995-1997, a 22.1-fold increase. In contrast, the incidence of research-identified autism increased from 5.5 (1.4-9.5) per 100,000 to 44.9 (32.9-56.9), an 8.2-fold increase. Only 46.8% of research-identified cases received a clinical diagnosis of ASD. These findings demonstrate the potential for misleading interpretation of results from epidemiologic studies that rely on clinical diagnosis of autism to identify cases.

Background: This thesis is composed of three studies. In the first paper, we tested the association of metformin use with prostate cancer incidence. In the second paper, we examined the association of metformin use with all-cause and prostate cancer specific mortality. The final paper explored the benefit of detailed pathology review to predict mortality among diabetic men with prostate cancer. Methods: A total of 5306 incident diabetic men older than 66 who subsequently developed prostate cancer were identified using the Ontario Diabetes Database and the Ontario Cancer Registry between 1994-2008. The association of metformin use and risk of prostate cancer and its grade was tested with a nested case-control design using a conditional logistic regression model. We used a cohort design with a time dependent Cox-proportional hazard model to examine the association of metformin use and mortality. Finally, we employed a c-statistic and Net Reclassification Improvement analysis to study the impact of pathology abstraction on predicting mortality. Results: The data suggest metformin use was not associated with the risk of prostate cancer or its grade at presentation. However, each additional 6 month of metformin use was associated with a 24% decrease in prostate-cancer-specific and 8% decrease in all-cause mortality. Pathology abstraction improved the accuracy in predicting all-cause and prostate-cancer specific mortality. Conclusions: In our study metformin use was not associated with a decreased risk of prostate cancer, but had a significant impact on all-cause and prostate cancer specific mortality. These results may serve as proof of concept in designing an interventional study of metformin to delay progression in prostate cancer.

Background: This thesis is composed of three studies. In the first paper, we tested the association of metformin use with prostate cancer incidence. In the second paper, we examined the association of metformin use with all-cause and prostate cancer specific mortality. The final paper explored the benefit of detailed pathology review to predict mortality among diabetic men with prostate cancer. Methods: A total of 5306 incident diabetic men older than 66 who subsequently developed prostate cancer were identified using the Ontario Diabetes Database and the Ontario Cancer Registry between 1994-2008. The association of metformin use and risk of prostate cancer and its grade was tested with a nested case-control design using a conditional logistic regression model. We used a cohort design with a time dependent Cox-proportional hazard model to examine the association of metformin use and mortality. Finally, we employed a c-statistic and Net Reclassification Improvement analysis to study the impact of pathology abstraction on predicting mortality. Results: The data suggest metformin use was not associated with the risk of prostate cancer or its grade at presentation. However, each additional 6 month of metformin use was associated with a 24% decrease in prostate-cancer-specific and 8% decrease in all-cause mortality. Pathology abstraction improved the accuracy in predicting all-cause and prostate-cancer specific mortality. Conclusions: In our study metformin use was not associated with a decreased risk of prostate cancer, but had a significant impact on all-cause and prostate cancer specific mortality. These results may serve as proof of concept in designing an interventional study of metformin to delay progression in prostate cancer.

Abstract The aim of this study was to examine lifestyle risk factors for low bone mass, falls and fractures, and to determine the effect of 30-month exercise trial on bone mass, balance, muscle strength and gait in elderly women. Reliability of an inclinometric method for assessing postural sway was evaluated. Data on risk factors, falls and fractures were collected by questionnaires, and calcaneus and radius bone mass were measured from 1,222 women. Lifetime physical activity, low occupational physical activity, type 2 diabetes, hypertension, hormone replacement, thyroid hormone and thiazide use were associated with increased bone mass, while low current physical activity, high coffee intake and late menarche were associated with low bone mass in lean women. Factors associated with fractures were: low lifetime habitual physical activity, diabetes, living alone and calcaneum bone mass. One hundred and sixty women with low femoral neck bone mass were randomly assigned to the exercise group (n = 84) or to the control group (n = 76). The outcomes included radius, proximal femur and calcaneus bone mass, postural sway, muscle strength, gait speed and endurance. Bone mineral density (BMD) at proximal femur decreased in the control group, while no change occurred in the exercise group. Mean trochanter bone mineral content (BMC) decreased more in the control group. The women in the exercise group improved their performance in walking speed and endurance, body sway and leg strength compared to the control group. There were six falls that resulted in fractures in the exercise group and 16 in the control group. The inclinometric method proved to be reliable. In conclusion, lifestyle factors are determinants of bone mass in lean elderly women. Long-term exercise has a site-specific effect on BMC but not on BMD in elderly women. Weight-bearing exercise can modify risk factors for fractures, and may even prevent fall-related fractures in elderly women.

Class of 2016 Abstract / Objectives: To compare health-related quality of life (HRQoL) among stroke survivors by gender and race/ethnicity to identify gender and racial/ethnic disparities. Methods: This study adopted a retrospective cross-sectional research design utilizing data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS), a state-based telephone survey administered to noninstitutionalized United States citizens. Inclusion criteria for this project were adults aged 50 or older who: participated in the 2013 BRFSS survey; indicated they had ever been told by a provider that they had experienced a stroke (of any type); and reported data on seven questions aimed to assess HRQoL (general, physical, and mental health; life satisfaction; emotional support; activity limitations; and sleep quality). Chi square tests and logistic regression models were used to compare HRQoL responses by gender and race/ethnicity. Results: In the 2013 BRFSS database 20,391 of 491,773 respondents reported experiencing stroke. Of those, 16,561 met the inclusion criteria. The majority were female (61.1%) and identified their race/ethnicity as white (78.6%). Logistic regression analysis revealed females were more likely than males to report worse outcomes across the following three HRQoL domains: activity limitations (AOR=0.752, 95% CI 0.617-0.918); mental health (AOR=1.398, 95% CI: 1.110-1.761); and general health (AOR=0.764, 95% CI: 0.588-0.993). Minority populations (African American, Hispanic, and Other) were more likely to report activity limitations (AOR=0.766, 95%CI: 0.614-0.955) and fair/poor general health (AOR=1.837, 95%CI: 1.324-2.549). Conclusions: Analysis identified gender and racial/ethnic disparities in HRQoL indicators among stroke survivors. Females and minority populations were more likely to report poorer outcomes.