ABSTRACT Atrial fibrillation (AF) is frequently detected in the setting of an acute physiologic stressor, such as medical illness or surgery. It is uncertain if AF detected in these settings (AFOTS: AF occurring transiently with stress) is secondary to a reversible trigger or is simply paroxysmal AF. This distinction is critical for clinicians and patients, as they must decide if AFOTS can be dismissed as a reversible phenomenon, or if it justifies the need for chronic therapy; in particular, anticoagulation to reduce the risk of disabling stroke. The uncertainty in the management of AFOTS is exacerbated by a poor understanding of its epidemiology. How frequently does AFOTS occur? Are there higher risk groups? What is the natural history of this condition? Across 8 chapters, this thesis systematically assesses previously published literature on this topic, focusing on patients who have an acute medical illness or have undergone noncardiac surgery, and addresses knowledge gaps therein. Chapter 1 is an introduction that outlines the justification of each of the studies in the thesis. Chapter 2 is a narrative review that defines AFOTS conceptually and outlines research priorities. Chapter 3 is a systematic review that explores the incidence and recurrence of AFOTS associated with acute medical illness. Chapter 4 is a systematic review and meta-analysis that explores the incidence and recurrence of AFOTS associated with acute noncardiac surgery. iii Chapter 5 examines the profiles of pacemaker-detected “subclinical” AF occurring before and after a hospitalization for medical illness or noncardiac surgery Chapter 6 reports the design, rationale and final results of a prospective study that aimed to provide a precise and accurate estimate of the incidence of AFOTS in critically ill patients. Chapter 7 reports the design and rationale of a matched prospective cohort study designed to estimate the rate of recurrence of AF following hospitalization with AFOTS and to compare it to similar patients who did not have AFOTS. Finally, Chapter 8 outlines the conclusions, discusses the limitations, and presents the implications of the research in this PhD thesis. / Thesis / Doctor of Philosophy (PhD) / Atrial fibrillation (AF) is the most common abnormal heart rhythm. AF is often diagnosed when a patient is hospitalized for an illness or after surgery. When AF is first found in this setting, it is unclear whether it has the same prognosis as other forms of the disease or is reversible. This thesis examines this problem and designs and executes studies to address it.

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Bipolar disorder is a serious illness affecting approximately 2-4% of the population and is one of the world’s leading causes of disability. In individuals with bipolar disorder, medical comorbidity associated with cardiovascular, respiratory and endocrine disorders is related to increased rates of mortality. Recent updates to multi-system inflammatory related conceptualizations of bipolar disorder focus on the unique power that medical illness and biological processes may play as factors associated with course and outcome in bipolar disorder. The current study examined medical comorbidity and its associations with various demographic and psychological variables in individuals with bipolar disorder, schizophrenia, and major depressive disorder with psychotic features followed for 10 years from their first hospital admission. When compared to an age, gender and race-matched control sample from the population, those with bipolar disorder had significantly higher medical comorbidity across a range of medical diagnoses both at 6 months and 10 years after first hospital admission. Ten years following initial hospitalization, individuals in all three diagnostic groups reported increased rates of diabetes (OR: 2.0 – 3.7), stroke (OR: 4.6 – 7.0) and asthma (OR: 1.9 - 3.1), and individuals with bipolar disorder reported increased rates of cancer (OR = 2.1). A number of psychological and demographic symptoms were examined for their ability to predict the development of medical illness across the assessment interval. Overall rates of medical illness were elevated both early in illness course and 10 years after diagnosis, suggesting that broad sequelae of multi-system inflammation are present early and progress over time.