Osteoporosis-related fracture is already today a major public health problem and the number of hip fractures is expected to double to 2030. Sweden has one of the highest hip fracture incidences worldwide. This may be explained by several factors: e.g. age, genetic, climatologic, geographic and a relative vitamin D deficiency, secondary to the limited sunlight exposure especially during winter months. Intrinsic and extrinsic factors contribute to a fracture, although a prior low energy fracture is one of the strongest predictors for a subsequent one and this should be a target for secondary fracture prevention in an orthopaedic setting. Since 1993 all injured patients admitted to the emergency floor and all in-hospital fractures at Umeå University Hospital, Sweden, were registered according to the Injury Data Base, former EHLASS. There were 31,173 fracture events (one or more fractures at the same time), of which 13,931 were in patients’ ≥ 50 years old. The fracture database was co analyzed with the Northern Sweden Health and Disease Study cohort in a nested case-control study for investigations of associations between osteoporotic fracture and serum markers, lifestyle data, nutrition etc. We found that there were differences in fracture pattern depending on age and sex. Both injury mechanism and fracture site were strongly dependent of age. The most severe fragility fracture, hip fracture, had a decreasing incidence. However, the incidence curve was right-shifting leading to an increase, both in numbers and in incidence of hip fractures among the oldest female. To identify people at high risk for fractures, re-fracture patients are useful. No less than 21% of the fracture patients had suffered more than one fracture event, accounting for 38% of all fracture events. The total risk ratio for a subsequent fracture was 2.2 (2.1-2.3 95% CI). In males the highest risk for re fracture was in the age cohort 70-79 years (RR 2.7, 2.3-3.2 95% CI), in females > 90 years (RR 3.9, 3.2-4.8 95% CI). Another possible risk factor in this subarctic population is the lack of sunlight, leading to a vitamin D deficit. The overall adjusted risk of sustaining a hip fracture in this population was 2.7 (95%CI:1.3-5.4) in subjects with a serum 25 hydroxyvitamin D below 50 nmol/l. The association was, however, different according to age at baseline. Thus in subjects aged 60 years and above at baseline, the adjusted odds ratio of sustaining a hip fracture was 6.2 (1.2-32.5 95%CI) for the group of individuals with a serum 25OHD below 50 nmol/l, whereas no significant association was found in the youngest age group. In the next 30 years the ongoing demographic changes will accelerate. The World War II baby boomers will cause an age quake. We can already see signs heralding a new fracture pattern: an increasing cohort of mobile but fragile elderly, with considerable co-morbidity is now at risk for fragility fractures. In fracture patients, clinical information is sufficient to pinpoint patients with a high risk for re-fractures. It is therefore clinically important to use the information provided by the fracture event. We suggest that trauma units and primary care units should screen for risk factors and inform patients about the treatment options, and to organize fracture liaison services. This seems to be especially cost-efficient for our oldest and frailest patients. Secondary prophylaxis and follow-up treatment after cardiovascular disorders are now a matter of course worldwide, but the screening for risk factors, in order to prevent a second fracture, is often neglected. This is one of the most important issues of fracture care in the future in order to improve general health.

Background: Improved neonatal care has resulted in an increasing population of surviving infants. Neonatal morbidity in preterm infants is, however, high, and retinopathy of prematurity (ROP) is one of the major neonatal morbidities. Observations have suggested that ROP might have a different course in extremely preterm compared to more mature infants. Aims: To study the incidence, natural history and treatment of the disease, and the implications regarding screening recommendations for the population of extremely preterm infants. Methods: A national, population-based study of neonatal morbidity in infants born before 27 gestational weeks was performed in Sweden during 2004 to 2007. ROP screening started in the 5th postnatal week and continued until the retina was completely vascularized. Results: Of the 506 infants surviving until the first ROP examination, 73% developed ROP; 38% mild ROP and 35% severe ROP. Ninety-nine infants (20%) were treated. A log-linear relationship was found between severe ROP and gestational age (GA) at birth, and the risk of ROP was reduced by 50% for each week of increase in GA at birth (Paper I). Postmenstrual age (PMA) at onset of ROP was significantly related to GA at birth, as was the site of onset of ROP. ROP had a predilection to start in the nasal retina in the most immature infants. There were significant relations between PMA at onset of ROP and severity of ROP as well as between the site of onset of ROP and severe ROP (Paper III). The most immature infants had a higher risk of reaching treatment criteria for ROP, a higher risk of progression from ROP 3 to treatment criteria, and they reached these criteria at an earlier PMA than the less immature infants (Paper II). According to our results, the first examination can be postponed until a PMA of 31 weeks in infants born before 27 weeks of gestation, since onset of ROP 3 did not occur before this age, and criteria for treatment were not reached before 32 weeks. The majority of infants (75%) were treated during a limited period, i.e. before a PMA of 39 weeks (Paper IV).

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.

The aim was to contribute to the optimal use of the resting ECG by exploring, in middle-aged and elderly men, the development and regression of ECG abnormalities; the prognostic value of the ECG for cardiovascular disease compared to conventional risk factors; and the impact of age at baseline and follow-up time for prediction of cardiovascular disease. It was based on the Uppsala Study of Adult Men cohort that was started in 1970. Participants were examined at ages 50, 70, 77, and 82, with annual updates on mortality and in-hospital morbidity using national registries. The studies indicated that the prevalence of silent MI and frequency of regression of major Q/QS patterns may be higher than previously believed. Considering that persistent T wave abnormalities and ST segment depression carried twice as high a risk for future cardiovascular disease (CVD) mortality as new or reverted abnormalities, the results suggested that serial electrocardiograms (ECG) would contribute to proper risk assessment. Also, the inclusion of ischemic ECG findings significantly increased the predictive power of the Framingham score at age 70 for CVD. While hypertension and dyslipidemia were consistent long-term risk factors for myocardial infarction at ages 50 and 70, the length of follow-up period and age at baseline affected the predictive power of ECG abnormalities, fasting insulin, BMI, and smoking. For stroke, midlife values for blood pressure and ECG abnormalities retained prognostic value over long follow-up periods, even though they improved when re-measured in elderly participants. ApoB/apoA1 ratio, driven by apoA1, was associated with stroke in elderly but not middle-aged men. Hyperinsulinemia and diabetes mellitus were more specifically associated with ischemic stroke than with any-cause stroke. In summary, the resting ECG carried prognostic information beyond conventional risk factors. Even though the low prevalence of ECG abnormalities at the age of 50 calls into question the role of the ECG as a screening tool, the additional risk information it carries with it justifies its regular and repeated registration above the age of 50.

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.

The understanding that Attention Deficit/ Hyperactivity Disorder (ADHD) commonly persists into adulthood has not been widely accepted until recently. Accordingly, less is known about diagnostic and treatment prevalence or health and social outcomes of ADHD in adulthood. The objectives of this study were to: determine lifetime prevalence of ADHD diagnosis and treatment for Manitoba young adults, investigate whether a socioeconomic gradient exists within Manitoba young adults with a lifetime diagnosis of ADHD, and investigate the relationship between ADHD in Manitoba young adults and health service utilization. Using the Manitoba Population Health Research Data Repository, this cross-sectional analysis used 24 years of data (1984/85-2008/09) and included all Manitoba adults aged 18-29 during 2007/08-2008/09 with a lifetime diagnosis of ADHD. Crude prevalence was calculated for ADHD diagnosis and psychostimulant prescriptions, in addition to several demographic variables. The presence of a socioeconomic gradient in lifetime ADHD diagnosis was investigated using Poisson and negative binomial regression. Relationships between young adults with lifetime ADHD diagnosis and health service utilization for several health and social outcome variables were explored using a matched cohort design with two comparison groups and GEE regression models. In relation to previous Manitoba research on childhood ADHD, the socioeconomic gradient for ADHD diagnosis was found to dissipate into young adulthood. However, when region of residence was accounted for, a small inverse gradient in the urban population and a direct gradient in the rural population were evident. Individuals from the highest income quintile were significantly less likely to be diagnosed before age 18 than all other income quintiles. Depression, anxiety, personality disorders, conduct disorder, substance abuse, multiple types of injuries, receipt of income assistance, and reduced high school graduation were significantly correlated with lifetime ADHD diagnosis. Given the high lifetime prevalence of ADHD in Manitoba young adults, significant socioeconomic correlates for diagnosis, and multitude of adverse health and social outcomes in this population, further investigation into the trajectory of this relatively unexplored population is recommended. Furthermore, continued measurement of the provision and success of additional resources will ultimately be necessary for enhancing the health status of all Canadian adults living with ADHD.

In 2001, a population-based cross-sectional study was conducted to compare levels of total polychlorinated biphenyls (PCBs) in residents of Calcasieu Parish and Lafayette Parish, Louisiana. A demographic, lifestyle, and food consumption questionnaire was collected for each participant. Overall, weighted geometric means and medians of total serum PCB concentrations in residents of Calcasieu and Lafayette Parishes were similar among all risk subgroups. However, 15-29 year olds had higher total serum PCB weighted geometric means in Calcasieu (64.4 ppb) than did this age group in Lafayette (46.6 ppb) (p=0.0059); conversely, in the 60 and older age group, geometric means of 293.7 ppb and 392.5 ppb were observed for Calcasieu and Lafayette, respectively (p=0.0059). In general, total PCB serum levels in Calcasieu and in Lafayette Parish, Louisiana residents were similar to each other and to levels observed in the U.S. general population in this time period.

Background: Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease. The diagnosis is based on a combination of the motor signs: tremor, bradykinesia, rigidity and postural abnormalities. Mild Cognitive Impairment (MCI) is common early in the disease and a large proportion of patients with PD develop dementia (PDD). Associations between motor symptoms and cognitive decline have been suggested but the results are inconclusive due to differences in the selection of participants and variables tested. Large population based studies with comprehensive neuropsychological investigation in newly diagnosed cases with PD followed prospectively are rare. The aim of this thesis was to improve characterization and understanding of cognition in PD, and to explore the relationship to motor impairment in the early phase of PD. Methods: All new patients with suspected idiopathic parkinsonism in the catchment area (142 ooo inhabitants) were examined during a period of five years and four months. Among other investigations, a comprehensive neuropsychological evaluation was carried out in 119 of 148 patients with PD together with 30 age matched healthy controls. Assessments were repeated after one three and five years. Results: Patients performed worse than healthy controls in a majority of neuropsychological tests. MCI at the time of diagnosis were found in 36% according to recently published MCI criteria. Thirty % were cognitively impaired using another definition. One fourth of the patients developed PDD within five years after diagnosis and 25 % of those with MCI at baseline reversed back to normal cognition. Age and MCI were significant predictors of dementia. Education was an independent predictor for severe cognitive dysfunction at diagnosis but did not predict PDD. Patients with MCI converting to PDD had worse performance on visuospatial function, semantic fluency, episodic memory, mental flexibility and conceptual thinking. There were no differences in cognitive performance between patients with predominant Postural and Gait Disturbances (PIGD) and the tremor dominant subtype at the baseline investigation and belonging to the PIGD subgroup at baseline did not predict PDD. Dementia converters declined more rapidly than non-converters in posture/gait function. Associations between bradykinesia and measures of executive functions and working memory were found, and between posture and gait disturbances and visuospatial function. Some of these associations were persistent after one year. Patients receiving the dopamine agonist pramipexole performed significantly worse on a measure of verbal fluency at the one year follow up. Conclusions: The differences in proportions of cognitively impaired in the different studies emphasize the value of joint criteria for PD-MCI. Even when using such criteria, a substantial proportion of patients revert back to normal function. The increase in motor disability in patients with PDD could have several different causes that need to be further investigated. Associated motor and cognitive dysfunctions could reflect common pathophysiological processes in partly shared networks. Both dopaminergic and non-dopaminergic motor and cognitive functions seems to be involved in PDD which suggests that pharmacological treatment in PD needs to go beyond the scope of dopaminergic deficiency in search for new therapies that would also be effective for non-motor symptoms. / NYPUM

The understanding that Attention Deficit/ Hyperactivity Disorder (ADHD) commonly persists into adulthood has not been widely accepted until recently. Accordingly, less is known about diagnostic and treatment prevalence or health and social outcomes of ADHD in adulthood. The objectives of this study were to: determine lifetime prevalence of ADHD diagnosis and treatment for Manitoba young adults, investigate whether a socioeconomic gradient exists within Manitoba young adults with a lifetime diagnosis of ADHD, and investigate the relationship between ADHD in Manitoba young adults and health service utilization. Using the Manitoba Population Health Research Data Repository, this cross-sectional analysis used 24 years of data (1984/85-2008/09) and included all Manitoba adults aged 18-29 during 2007/08-2008/09 with a lifetime diagnosis of ADHD. Crude prevalence was calculated for ADHD diagnosis and psychostimulant prescriptions, in addition to several demographic variables. The presence of a socioeconomic gradient in lifetime ADHD diagnosis was investigated using Poisson and negative binomial regression. Relationships between young adults with lifetime ADHD diagnosis and health service utilization for several health and social outcome variables were explored using a matched cohort design with two comparison groups and GEE regression models. In relation to previous Manitoba research on childhood ADHD, the socioeconomic gradient for ADHD diagnosis was found to dissipate into young adulthood. However, when region of residence was accounted for, a small inverse gradient in the urban population and a direct gradient in the rural population were evident. Individuals from the highest income quintile were significantly less likely to be diagnosed before age 18 than all other income quintiles. Depression, anxiety, personality disorders, conduct disorder, substance abuse, multiple types of injuries, receipt of income assistance, and reduced high school graduation were significantly correlated with lifetime ADHD diagnosis. Given the high lifetime prevalence of ADHD in Manitoba young adults, significant socioeconomic correlates for diagnosis, and multitude of adverse health and social outcomes in this population, further investigation into the trajectory of this relatively unexplored population is recommended. Furthermore, continued measurement of the provision and success of additional resources will ultimately be necessary for enhancing the health status of all Canadian adults living with ADHD.

Aim: The overall aim of this thesis was to study health-related quality of life (HRQoL) and return to work in the first 3 years following a breast cancer diagnosis, and to identify clinical and contextual factors associated with these outcomes. Method: The four studies were part of a population-based cohort study including women identified in the Breast Cancer Quality Register in central Sweden. Of 1,573 women asked to participate, 69% (n=1,093) responded to a baseline questionnaire, 62% (n=977) responded at the 1st follow-up and 54% (n=856) participated at the 2nd follow-up (mean time 4, 16 and 38 months post-diagnosis, respectively). Studies II and IV only included women aged &lt;63 years at diagnosis. In Study IV, each woman was individually matched to five breast-cancer-free controls. Questionnaire data on HRQoL, socio-demographics and work-related variables were combined with clinical register, normative and social insurance data. Main findings: Study I: Women with breast cancer, particularly women aged &lt;50 years, experienced poorer HRQoL at baseline than normative data. Chemotherapy, lack of social support, sick leave and a poor financial situation were associated with poorer HRQoL. Study II: Compared with pre-diagnosis working time, 72% of participating women reported no change, 2% had increased their working time, 15% reported a decrease in working time and 11% did not work at the 1st follow-up. Chemotherapy, cancer-related work limitations and less value attached to work increased the odds of job discontinuation/decreased working time. Study III: During the 3 years post-diagnosis, HRQoL generally improved. Less consistent improvements were found among women on sick leave/disability pension pre-diagnosis and women reporting job discontinuation/decreased working time post-diagnosis. Study IV: The proportion of women with breast cancer on sick leave steadily decreased during the 3 years post-diagnosis, but they were more likely to be on sick leave than the controls. Chemotherapy, fatigue and pre-diagnosis sick days predicted sickness absence during the 2nd and 3rd year post-diagnosis. Conclusions: Most women with breast cancer gradually recover, but there are subgroups of women who may be particularly vulnerable. In a clinical setting, increased attention should be directed towards women undergoing chemotherapy, young women, women on sick leave/disability pension pre-diagnosis and women who do not return to work to the same extent as pre-diagnosis.