Background: Life expectancy (LE) estimation is an important part of both screening and treatment decision-making for potentially curable prostate cancer. Clinicians’ estimation of patient life expectancy is typically made using population-based life tables and intuition and it is often inaccurate. This study explores methods to improve LE prediction by formally considering patient co-morbid illness status, in addition to age, in the development of a LE prediction tool. Methods: We conducted a population-based retrospective cohort study of patients from the Ontario Cancer Registry who were curative treatment candidates, identified between 1990-1998. We analyzed data on three sub-populations of this cohort, and we used LE estimates from the Ontario Life Tables. Each model utilized Cox proportional hazards analysis, and/or the declining exponential approximation of LE, to estimate the survival experience of potential curative treatment candidates, including the impact due to both age and co-morbid illness status. We developed five separate models, tested them using a random subset of the cohort study sample, and compared their predictive accuracy by measuring both discriminative ability and calibration to determine the ‘best’ model. We also conducted a supplementary analysis using logistic regression to develop a model to predict the probability of 10-year survival. Results: The ‘best’ of our models demonstrated a c-index of 0.65 and very good calibration. Further analysis revealed that our ‘best’ model violated the Cox PH assumption for age and it’s predictions consistently over-estimated observed LE. Supplementary analysis of the logistic regression prediction model demonstrated a c-index of 0.70. Conclusions: Our exploration of methods to predict LE resulted in modest predictive accuracy. However, based on the results of the logistic regression model, we conclude that the results of our LE prediction models are reasonable, and obtaining a high level of predictive accuracy may not be possible given just age and co-morbidities as predictors. Further studies should continue to explore these and other methods for LE prediction. External validation of the ‘best’ model from the current study is required before the model and its accompanying LE reference tables can be recommended for use in a clinical setting for screening or treatment decision-making. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2011-04-07 19:11:34.216

The incarceration of mentally ill youth is a serious problem not receiving the same attention as in adults. In this study, we examine the prevalence of psychopathology and level of behavioral symptomatology in incarcerated youth versus youth receiving community mental health services or hospitalization. We randomly recruited youth from middle South Carolina served by a local CMHC (n = 60), youth served by the state adolescent inpatient program (n = 50), and youth in the S.C. Dept. of Juvenile Justice facilities from the same region (n = 75). We used the DISC-PC 2.3 to evaluate DSM-III-R diagnoses and the CBCL and YSR to evaluate behavioral symptomatology. On the DISC, incarcerated youth had significantly higher mean number of diagnoses and symptoms than CMHC youth, but lower numbers than hospitalized youth. Level of "caseness" (at least one diagnosis) was 86% in hospital youth, 72% in incarcerated youth, and 60% in CMHC youth. The groups differed in CBCL mean total T, internalizing T, and externalizing T scores as well as mean YSR internalizing T scores. Our results indicate the comparability in level of psychopathology in incarcerated and community-treated populations of youth, and the need to develop diversionary programs to prevent the entry of such youth into the juvenile justice system.

The purpose of the study was to describe and analyze the living condition for individuals with co-morbidity in different spheres of life based on a survey conducted in Blekinge county council. The aim has also been to examine the relation between individuals with co-morbidity and the care and support that is available under current legislation. The study examined how two hypotheses about comorbidity is related to different spheres of life as well as health care and support. Both hypotheses was confirmed by the results of the study. Individuals with co-morbidity has often a troublesome living situations and they do not receive adequate care and support. The study's perhaps most unexpected result is the result that emerged in addition to the hypotheses. The young group of people with co-morbidity is high and the group has a great need for extended care and support activities in all areas of life. Individuals with co-morbidity needs to be a continued research focus, especially the young persons.

Background. Rheumatoid arthritis (RA) is an autoimmune disease mainly affecting the joints but has also extra articular manifestations and an increased cardiovascular (CV) co-morbidity. Rheumatoid factor (RF) and antibodies against citrullinated proteins/peptides (ACPA) are diagnostically important and are related to a more severe disease. The aetiology is unknown but RA is considered a complex disease caused by both genetic and environmental factors. The heritability is estimated to be 60% with the main contribution from the HLA region. The relative homogeneity of the population in northern Sweden due to low immigration and founder effects has shown to be suitable for genetic studies. Objectives. The aim of this thesis has been to identify genes contributing to the susceptibility of RA and the CV co-morbidity in particular. To achieve this, multi-case families from the four northern most counties of Sweden were collected for linkage studies to identify susceptibility genes. Association studies with genetic polymorphisms in genes, involved in inflammation or being of importance for atherothrombotic manifestations (ATM) in the general population, were performed in RA-patients concerning ATM e.g. myocardial infarction, angina pectoris with intervention, stroke/TIA, deep vein thrombosis/pulmonary embolism (DVT/PE) at follow-up. Methods & Results. 47 families with 134 affected and 216 unaffected relatives were included in a genome-wide linkage study (GWL) performed with microsatellite markers at an average of 10cM resolution analysed using ABI PRISM 3730 DNA sequencer and non-parametric multipoint linkage in the Merlin program. Eight linked loci were identified with HLA as the most significant and a novel region on chromosome 14. In a follow-up analysis on a custom Illumina chip, with 13 additional families, yielding a total of 198 affected and 197 unaffected relatives. The majority of the 1536 single nucleotide polymorphisms (SNPs) used in the Illumina follow-up analyses was focused on chromosome 14. Statistical analyses with linkage and transmission disequilibrium test narrowed the region to 4 cM, a region containing multiple plausible RA candidate genes (Paper I). In Paper II  serum samples from 163 affected and 157 first degree relatives were analysed with EliA ACPA assay on ImmunoCAP250 for ACPA (IgA, IgG, IgM) and RF (IgA, IgM) isotypes. Both concentrations and frequencies were increased among the relatives compared with controls but lower compared with RA-patients and with a different relative distribution of the isotypes. The genetic contribution to ATM was studied in Paper III and IV using selected SNPs analysed using ABI PRISM 7900HT sequence detector system. In Paper III, RA-patients (n=467) were compared with age and sex matched controls (n=696) with respect to SNPs in tumor necrosis factor receptor II (TNFRII)(M196R), ß-fibrinogen -455 (G-455A), plasminogen activator inhibitor type-1 (PAI-1) (4G/5G) and Factor XIIIA (Val34Leu). Hypertension was predicted by TNFRII R allele and to a higher extent in combination with the A-allele in ß-fibrinogen. The 4G allele in PAI-1 was more frequent in patients with ischemic heart disease (IHD) and the FXIIIA Leu34 variant in patients with DVT/PE. In Paper IV, the minor allele of the polymorphism in growth differentiation factor 15 (GDF15) was found to be associated with RA (n=696) per se but also to ATM, a SNP in the 9p21.3 locus was also associated with ATM. A significant association to stroke was found in female patients homozygote for the minor allele of GDF15. Stoke among male patients was significantly associated with carrying the major allele of two SNPs in the CD40 gene. DVT/PE was associated with the minor allele of GDF15. Conclusion. A novel locus on chromosome 14 of importance for RA susceptibility in northern Sweden was found. The minor allele of TNFRII separately and together with the minor allele of ß-fibrinogen -455 was associated with hypertension and the 4G allele in PAI-1 was associated with IHD and  the Leu34 variant was associated with DVT/PE in RA patients. The GDF15 minor allele was associated with RA per se, ATM and DVT/PE in RA patients and a genotype in the SNP on 9p21.3 was associated with ATM. Stroke among females was associated with GDF15 and stroke among males with two SNPs in CD40.

Research Objectives: Chronic obstructive pulmonary disease (COPD) is a major cause of disability and death worldwide. The prevalence of depression and anxiety in COPD patients is generally higher than those reported in other chronic illnesses, and these mental diseases significantly affect the health expenditures and the course of the diseases on elderly COPD patients. The COPD patients with co-morbid depression, anxiety or other chronic diseases are more impaired and have 50% to 100% higher medical costs than those without depression and anxiety. COPD affects approximately 1.8 million people in Taiwan every year, however, little studies have examined the impacts of mental diseases on elderly COPD patients. This study aims to investigate the depression and anxiety status on COPD patients¡¦ medical care utilizations and health outcomes. Study Design: This study analyzed the nationally representative research database from National Health Insurance program between 2002 and 2006 in Taiwan, by exploring outpatient visits, hospitalizations, and medical expenditures of COPD and its associated co-morbidities. The data analyses were carried out by Chi-square test, multiple linear regression and multivariate logistic regression. Population Studied: Patient aged over 65 with primary diagnosis of COPD and co-morbidity diseases based on ICD-9-CM in Taiwan. To investigate the complications in COPD patients, four diseases such as diabetes, hypertension, heart failure and ischemic heart disease were included in the analyses. Principle Findings: Among the 5,735 COPD patients (59.81%, male), most of them were aged over 80 (28.67%) , and lived in urban areas (62.28%) in northern Taiwan (43.71%). The results indicated that those who were suffered from depression or anxiety increased medical utilization and costs. Multiple linear regression model showed that age, and hospital level significantly affect the expenditures for medicine of COPD patients with depression or anxiety (p¡Õ0.001). Multivariate logistic regression model presented that number of complications significantly affect the probability of hospitalization among the COPD patients with mental diseases (p¡Õ0.001). Conclusions¡G COPD symptoms were usually getting worsen over time and depression or anxiety affect the COPD patients significantly, though the mental diseases are usually under-estimated. The study results demonstrated that COPD patients suffered from depression and anxiety increased the risks on longer length of stay, higher medical expenditures and more complications. WHO predicts that COPD will become the third leading cause of death worldwide by 2030. Since mental diseases may worsen elderly COPD patients¡¦ health outcomes, physicians are advised to pay more attention to these types of patients. With on time and appropriate treatments, thus may help to improve quality of care and reduce medical expenditures for these patients.

Despite the widespread prevalence of bombing in Iraq, no study has investigated its psychological impact on civilians. This thesis aimed to address this gap in the literature. Four studies were conducted consequently using civilians in Iraq. The first study aimed to explore the subjective experience in response to the bombing attack. A qualitative approach was taken and twenty semi-structured interviews were employed and analysed using Interpretative Phenomenological Analysis (IPA). This identified seven categories including interpersonal relationships, loss of self, changes in attachment, shattering of world assumptions. Subsequent studies were then conducted to understand these themes as possible predictors of PTSD and psychiatric comorbidity in regards to bombing attacks. The second study was a prospective longitudinal design aimed to investigate the trajectory of PTSD symptoms, psychiatric comorbidity, and attachment styles among survivors. It also aimed to examine the role of a variety of variables, namely shattering of world assumptions, altered self-capacity, perceived social support to predict PTSD and psychiatric comorbidity. One hundred and eighty Iraqi civilians were recruited and assessed approximately 1 month and 5 months after their experience of being in a bombing attack using a battery of questionnaires. A control group data (n=178) of people who had not been exposed to a bombing was also collected. Results indicated that 19.4% and 57.2% of the participants met the screening criteria for partial and full PTSD symptoms at T1, which declined overtime. The bombing group displayed significantly higher rates of psychiatric comorbidity and insecure attachment than the control group. After controlling for the severity of bombing attack, controllability of events and affect dysregulation significantly predicted both PTSD and psychiatric co-morbidity symptoms. None of these dimensions predicted PTSD and psychiatric co-morbidity at T2. The complementary study 3 looked further at selected predictors indicated by the findings of study 1, namely death anxiety, coping strategies, religious coping and meaning in life. This study employed a longitudinal design in which 185 participants were recruited and assessed approximately 2 months and 7 months after bombing using a package of self-report questionnaires. Results indicated that religious coping and cognitive avoidance had a significant role to play in predicting PTSD and psychiatric comorbidity shortly after the bombing. Death anxiety was also emerged another picture in predicting PTSD and psychiatric comorbidity through mediators, namely religious coping and searching for meaning in life. Literature showed that PTSD and psychological distress are treatable after people had received various forms of professional and personal strategies. Study 4 employed mixed methods in order to provide further understanding regarding the helpful coping strategies that participants had attempted to use to manage their psychological distress. Six participants (n=3 recovered well, n=3 still struggle) were recruited for the qualitative phase and 243 for the quantitative. Social support was found as the most frequent and helpful strategy to manage post-bombing distress, followed by avoiding thinking about the bombing and religious strategies. Different psycho-social factors that hinder or foster recovery between participants were also highlighted. In conclusion, the findings confirmed related studies that, following bombing, there is a high risk that victims develop PTSD and psychiatric co-morbidity symptoms which decline to some extent over time. A variety of factors, such as social support and religious strategies were identified as helpful. However, these were also related to the victims’ prior attachment strategies. Implications for assisting victims and the population of Iraq are offered, in particular the need to support families and friends (social networks) in the context of very limited professional sources of support in a country where terrorism is rife.

Rationale. Alcohol use disorders (AUDs) and tobacco dependence are frequently identified as co-morbid. Although less than 20% of the general population smokes, over 80% of people with AUDs are considered daily smokers. In fact, people with AUDs are more likely to die from smoking-related health issues, than from alcohol related health issues. Surprisingly, there is very little evidence that alcohol and nicotine are concurrently self-administered in pre-clinical models. We hypothesized that low doses of nicotine that enhancing responding for other rewards would be self-administered and enhance self-administration of alcohol. Objective. The goal of this study was to determine if low-doses of nicotine, typically not self-administered alone, would promote alcohol self-administration in a concurrent access paradigm. Method. Alcohol preferring rats (females) were requested from the University of Indiana Medical School breeding facility. They were randomly assigned to one of three groups – NIC-Alone, ALC-Alone, or ALC+NIC. All rats were fluid restricted and shaped to lick for water at two sipper tubes that could record lick responses and deliver aliquiots of fluid into the sipper tube via a solenoid valve. After shaping, rats were instrumented for IV self-administration. During self-administration tests, rats in the ALC-Alone received access to oral ethanol (15% v/v) for meeting the schedule of reinforcement at one sipper tube (e.g., right) and saline infusions for meeting the schedule of reinforcement at the other sipper tube (e.g., left). The NIC-Alone group received IV nicotine infusions (15 ug/kg/inf) and oral licorice (1%) for meeting the schedule of reinforcement at one sipper tube (e.g., left) and oral water for meeting the schedule of reinforcement at the other sipper tube (e.g., right). The ALC+NIC group received IV nicotine and oral licorice for meeting the schedule of reinforcement on the left sipper, and oral ethanol for meeting the schedule of reinforcement on the right sipper. Price manipulations for nicotine were performed by adjusting the schedule of reinforcement on the sipper associated with nicotine infusions. Results. During acquisition, nicotine did not enhance alcohol self-administration – alcohol intake was comparable between ALC-Alone and ALC+NIC rats. In addition, alcohol did not enhance nicotine self-administration as responding for NIC was comparable between ALC+NIC and NIC-Alone rats. However, when the price of nicotine was manipulated, alcohol created a greater demand for nicotine, as indicated by higher rates of nicotine consumption with increases in price. Manipulating the price of nicotine did not alter demand for alcohol. Conclusion. The interaction between alcohol and nicotine reinforcers may depend on changes in demand for nicotine. Future studies should investigate whether demand for alcohol is altered by concurrently available nicotine infusions. *the first and second authors contributed equally to this project

Yes / Objectives: Longitudinal evidence documenting health conditions in spousal caregivers of people with dementia and whether these influence caregivers’ outcomes is scarce. This study explores type and number of health conditions over two years in caregivers of people with dementia and subgroups based on age, sex, education, hours of care, informant-rated functional ability, neuropsychiatric symptoms, cognition of the person with dementia, and length of diagnosis in the person with dementia. It also explores whether over time the number of health conditions is associated with caregivers’ stress, positive experiences of caregiving, and social networks Methods: Longitudinal data from the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort were used. Participants comprised spousal caregivers (n = 977) of people with dementia. Self-reported health conditions using the Charlson Comorbidity Index, stress, positive experiences of caregiving, and social network were assessed over two years. Mixed effect models were used Results: On average participants had 1.5 health conditions at baseline; increasing to 2.1 conditions over two years. More health conditions were reported by caregivers who were older, had no formal education, provided 10 + hours of care per day, and/or cared for a person with more neuropsychiatric symptoms at baseline. More baseline health conditions were associated with greater stress at baseline but not with stress over time. Over two years, when caregivers’ health conditions increased, their stress increased whereas their social network diminished Discussion: Findings highlight that most caregivers have their own health problems which require management to avoid increased stress and shrinking of social networks / Economic and Social Research Council (ESRC) and the National Institute for Health and Care Research (NIHR) - grant ES/L001853/2. Alzheimer’s Society, grant number 348, AS-PR2-16-001. Sabatini was supported by an ESRC Postdoctoral fellowship (ES/X007766/1).

Background Rheumatoid arthritis (RA) is a systemic progressive destructive joint disease with an increased risk for co-morbidity and premature death if untreated. Cardiovascular disease (CVD) is the main cause of death but also other co-morbid conditions contribute to the patient’s shorter life expectancy. Inflammation is important for the development of CVD, but knowledge of its relationship with other co-morbidities is sparse. Early disease modifying anti rheumatic drugs (DMARDs) can suppress disease activity and improve the long-term outcome. The aim of this thesis was to evaluate prospectively aspects of disease activity and severity in a large cohort of patients with early RA. Predictive and prognostic markers, e.g., antibodies against citrullinated proteins/peptides (ACPAs), occurring in early disease and with implications for disease outcome and co-morbidity were evaluated. Methods Patients with early RA (i.e., symptomatic for ≤12 months) have, since December 1995, been consecutively included in a large survey of prospective and observational studies on the progression of RA and the development of co-omorbidity. Autoantibodies, inflammatory, genetic markers and radiographs have been analyzed. In paper I, 210 RA patients and 102 controls were followed regularly for two years. The predictive value of four different ACPAs in relation to disease activity and radiological progression was evaluated. In Paper II (n = 700) and in Papers III-IV (n =950), patients with early RA from the four northern-most counties of Sweden were followed regularly for 5 years. Data on risk factors and co-morbidity was collected, according to the study protocol, from clinical records and self-reported questionnaires from patients at inclusion into the study cohort and after five years. The predictive value of traditional and potential disease related risk factors for new cardiovascular events (CVE) was evaluated (II). In Paper III, the impact of age at the onset RA, stratified as being young onset RA (<58 years; YORA) and late onset RA (≥58 years; LORA) on disease activity, severity and chosen treatment, was evaluated. In Paper IV, the development of new co-morbidities after RA onset and their relation to inflammatory activity was assessed. Results The presence of anti-mutated citrullinated vimentin (MCV ) antibodies was associated with a more severe disease course, estimated by disease activity score, erythrocyte sedimentation rate (ESR) and swollen joint count after 24 months, compared with anti-CCP2, anti-CCP3, and anti CCP3.1 antibodies. In Paper II, the incidence of a new CVE during 5 years was explained by several of the traditional CV risk factors, and potentiated by a high disease activity. Treatment with DMARDs decreased the risk. In Paper III, LORA patients were associated with greater disease activity/severity at disease onset and over time compared with YORA who were more often ACPA positive. YORA patients were treated earlier with DMARDs, whilst LORA patients were more often treated with corticosteroids and less so with DMARDs early in the course of their disease. In Paper IV, 53%of patients already had one or more co-morbidities already at the onset of RA. After 5 years, 41% of the patients had developed at least one new co-morbidity. ESR at baseline and accumulated disease activity were associated with a new co-morbidity after five years. Conclusion Early RA patients sero-positive for anti- MCV antibodies appeared to have a higher disease activity over time. The occurrence of a new CVE in early RA patients was predicted by traditional risk factors for CVD which were potentiated by a high disease activity. Treatment with DMARDs decreased the risk. Patients with young onset of RA were associated with a higher frequency of ACPA. Late onset of RA was associated with higher disease activity/severity at inclusion and over time. However, LORA patients were more often treated with corticosteroids and less so with DMARDs early in the disease course. Development of a new co-morbidity during the five years following diagnosis was related to ESR.

Background. General population data were used to study co-morbidities between lifetime social phobia and mood disorders. Methods. Data come from the US National Comorbidity Survey (NCS). Results. Strong associations exist between lifetime social phobia and major depressive disorder (odds ratio 2·9), dysthymia (2·7) and bipolar disorder (5·9). Odds ratios increase in magnitude with number of social fears. Reported age of onset is earlier for social phobia than mood disorders in the vast majority of co-morbid cases. Temporally-primary social phobia predicts subsequent onset of mood disorders, with population attributable risk proportions of 10–15%. Social phobia is also associated with severity and persistence of co-morbid mood disorders. Conclusions. Social phobia is a commonly occurring, chronic and seriously impairing disorder that is seldom treated unless it occurs in conjunction with another co-morbid condition. The adverse consequences of social phobia include increased risk of onset, severity and course of subsequent mood disorders. Early outreach and treatment of primary social phobia might not only reduce the prevalence of this disorder itself, but also the subsequent onset of mood disorders.