Mental Wellbeing in Prostate Cancer Treatment and Survivorship:Outcome Definition, Prognostic Factors, and Prognostic Model Development

A prostate cancer diagnosis and its subsequent management can produce numerous challenges to patients. With already significant and further improving survival rates there is a growing realisation that living longer does not always equate to living well. This means that issues pertaining to quality of life and wellbeing are of particular importance to this group of patients. The focus around this has long been on the physical sequelae of disease and treatment, but there is now an increasing amount of evidence to demonstrate the significant impact that exists on the mental wellbeing of individuals. However, whilst this is being increasingly acknowledged, less is understood about what exact mental wellbeing outcomes are of importance in this group of patients. Additionally, little is known about which specific individuals subsequently appear to have poorer mental wellbeing outcomes after their diagnosis.The current work therefore aimed to evaluate the following for patients with prostate cancer: 1) Define important mental wellbeing outcomes of interest, 2) Summarise existing quantitative evaluation methods for defined mental wellbeing outcomes, 3) Explore important prognostic factors for poorer mental wellbeing post diagnosis, and 4) Develop and internally validate a prognostic model for the development of significant mental wellbeing issues. Part 1 of this thesis sets out to define important mental wellbeing outcomes of interest and their evaluation methods through four chapters. This includes multiple independent systematic reviews of the literature and a qualitative study conducting patient interviews to explore their lived experiences post diagnosis. Through these chapters five important constructs were selected as key mental wellbeing outcomes of interest including depression, anxiety, body image perception, fear of cancer recurrence/progression, and masculinity. Additionally, for each of these outcomes the most utilised and validated quantitative psychometric tools were identified and summarised. These selected outcomes were subsequently taken forward for Part 2 of this thesis to evaluate important patient, oncological, and treatment prognostic factors associated with poorer mental wellbeing outcomes in this cohort. This included a systematic review and meta- analysis utilising prognosis research methodology, a cross-sectional survey of healthcare professionals, and a prospective multi-institutional cohort study of newly diagnosed patients entitled MIND-P. These methodologically differing studies were utilised in a triangulation approach together to identify potentially important prognostic factors for the previously selected outcomes. These highlight several potential factors of interest including age, a previous psychiatric diagnosis, mental health symptoms at baseline, co-morbidities, marital status, functional symptoms, stage at diagnosis, and undergoing hormone therapy. Lastly, Part 3 of this thesis culminates in the development and internal validation of a novel multivariable prognostic model for individual patient prediction. This focussed on a composite mental wellbeing outcome as well as risk prediction for each individual mental wellbeing outcome previously defined. Utilising candidate predictors established within Part 2 of this thesis and a sample from the MIND-P study, a final model was developed which utilised age, a previous psychiatric diagnosis, stage of disease, baseline anxiety symptoms, and baseline urinary and sexual function as predictors. The developed model demonstrated acceptable overall performance, calibration, and discrimination during its internal validation. Additionally, instability was seen to be minimal in most measures evaluated. This developed prognostic model offers a first of its kind model within prostate cancer care, and the first to evaluate multiple mental wellbeing outcomes within cancer care in general. Overall, the findings of this thesis highlight the importance of mental wellbeing for patients with prostate cancer and hence the key need to monitor these outcomes in routine follow up care for all patients. This should include the identified outcomes of interest and their respective measurement tools. Additionally, the highlighted prognostic factors and the prognostic model offer potential methods to better target screening and prevention strategies to improve mental wellbeing for these patients. However, the formal evaluation of these was beyond the scope of this thesis and hence should be considered within future research, along with the external validation and clinical utility of the developed model to better define its performance across different populations and understand its impact on outcomes when utilised prior to its widespread clinical utilisation

Integration Research for Shaping Sustainable Regional Landscapes

Ecological and social systems are complex and entwined. Complex social-ecological systems interact in a multitude of ways at many spatial scales across time. Their interactions can contribute both positive and negative consequences in terms of sustainability and the context in which they exist affecting future landscape change. Non-metropolitan landscapes are the major theatre of interactions where large-scale alteration occurs precipitated by local to global forces of economic, social, and environmental change. Such regional landscape effects are critical also to local natural resource and social sustainability. The institutions contributing pressures and responses consequently shape future landscapes and in turn influence how social systems, resource users, governments, and policy makers perceive those landscapes and their future. Science and policy for "sustainable" futures need to be integrated at the applied "on-ground" level where products and effects of system interactions are fully included, even if unobserved. Government agencies and funding bodies often consider such research as "high-risk". This paper provides some examples of interdisciplinary research that has provided a level of holistic integration through close engagement with landholders and communities or through deliberately implementing integrative and innovative on-ground experimental models. In retrospect, such projects have to some degree integrated through spatial (if not temporal) synthesis, policy analysis, and (new or changed) institutional arrangements that are relevant locally and acceptable in business, as well as at broader levels of government and geography. This has provided transferable outcomes that can contribute real options and adaptive capacity for suitable positive futures

Antikoagulation bei Vorhofflimmern

Zusammenfassung: Vorhofflimmern bewirkt eine Blutstase in den Vorhöfen, was die Thrombusbildung und in der Folge systemische Embolien begünstigt. Bei Patienten mit Vorhofflimmern stellen die Herzinsuffizienz, der Hypertonus, Diabetes mellitus, ein Alter > 75 Jahre sowie ein vorangegangener Schlaganfall die wichtigsten Risikofaktoren für ein zerebrovaskuläres Ereignis dar. Diese Risikofaktoren wurden im CHADS2-Risikoscore (Cardiac failure, Hypertension, Age, Diabetes, Stroke, 2 Punkte) zusammengefasst. Das thromboembolische Risiko variiert bei Patienten mit Vorhofflimmern beträchtlich. Die Behandlungsstrategie muss sich entsprechend am absoluten Risiko für ein thromboembolisches Ereignis und am zu erwartenden Blutungsrisiko orientieren. Patienten mit mittlerem und hohem Risiko profitieren eindeutig von einer Antikoagulation mit einem Vitamin-K-Antagonisten, wohingegen Patienten ohne Risikofaktoren mehrheitlich von einer Therapie mit Thrombozytenaggregationshemmern zu profitieren scheine

Integration Research for Shaping Sustainable Regional Landscapes

Ecological and social systems are complex and entwined. Complex social-ecological systems interact in a multitude of ways at many spatial scales across time. Their interactions can contribute both positive and negative consequences in terms of sustainability and the context in which they exist affecting future landscape change. Non-metropolitan landscapes are the major theatre of interactions where large-scale alteration occurs precipitated by local to global forces of economic, social, and environmental change. Such regional landscape effects are critical also to local natural resource and social sustainability. The institutions contributing pressures and responses consequently shape future landscapes and in turn influence how social systems, resource users, governments, and policy makers perceive those landscapes and their future. Science and policy for "sustainable" futures need to be integrated at the applied "on-ground" level where products and effects of system interactions are fully included, even if unobserved. Government agencies and funding bodies often consider such research as "high-risk." This paper provides some examples of interdisciplinary research that has provided a level of holistic integration through close engagement with landholders and communities or through deliberately implementing integrative and innovative on-ground experimental models. In retrospect, such projects have to some degree integrated through spatial (if not temporal) synthesis, policy analysis, and (new or changed) institutional arrangements that are relevant locally and acceptable in business, as well as at broader levels of government and geography. This has provided transferable outcomes that can contribute real options and adaptive capacity for suitable positive futures

Landscape Loopholes: Moments for Change

Social-ecological systems are breaking down at local, regional, and global scales, and sustainability seems an increasingly distant aspiration. Social harmony and economic systems are connected to ecological systems and climate, in multiple complex ways, at many scales. Adapting research practice to match integration opportunities within social-ecological systems could contribute foresight capabilities emerging from landscape change studies, which can be coupled with emerging policy transformation opportunities. The shaping of landscapes by human imagination and physical action creates meaningful contexts for building sustainability. However, the policy landscape is often dominated by circularity and “lock-in” to unsustainable pathways that are hard to escape. Moments for change emerge through timely convergence of circumstances, within a landscape context, that provide a window of opportunity—a “landscape loophole”—through which the transformation to more sustainable social-ecological relationships might be achieved. Creating future options redundancy (FOR) plans, a variety of possible pathways and alternative landscape futures within the characteristics and capacity of a region, could facilitate policy shifts and adaptive capacity, and reduce risk through reflexive future options. The convergence of circumstances providing loophole opportunities to escape existing lock-in might be understood, and even predicted, by closely coupling landscape sciences and policy research

Landscapes Shaped by People and Place Institutions Require a New Conservation Agenda

Formal protected area systems will always be insufficient to sustain biodiversity and ecosystem processes. The largest proportions of endangered ecosystems and rare species remain outside public conservation areas on private land, and the political and financial costs of strategic acquisitions of these areas for conservation estate are becoming unaffordable. Although biologists quite rightly continue to call for development of more comprehensive and representative reserve networks, the reality is that the coverage, connectivity, and size of protected areas will remain inadequate (Shaffer et al. 2002). Many authors and participants, as well as the conclusions, of the very comprehensive 30-year review of the Endangered Species Act (Scott et al. 2006) noted the continuing challenge and urgency of extending the conservation agenda more comprehensively across natural and working landscapes (matrix lands), most of which will remain outside any formal reserve system. New integrative approaches are needed

Impact of Changing Activation Sequence on Bipolar Electrogram Amplitude for Voltage Mapping of Left Ventricular Infarcts Causing Ventricular Tachycardia

Introduction: Wavefront direction is a determinant of bipolar electrogram amplitude that could influence identification of low amplitude regions indicating infarction or scar. Methods: To assess the importance of activation sequence on electrogram amplitude 11 patients with prior infarction and ventricular tachycardia were studied. At 819 left ventricular sites bipolar electrograms were recorded during atrial pacing and ventricular pacing, followed by unipolar pacing with a stimulus of 10 mA at 2 ms. Sites with a pacing threshold > 10 mA were designated electrically unexcitable scar. Results: Areas of low voltage (≤1.5 mV) were present in all patients. Atrial paced and ventricular paced electrogram amplitudes were strongly correlated (r = 0.77; P 50% change in electrogram amplitude at 28% of sites and a > 100% change at 10% of sites, but only 8% of sites had an electrogram amplitude classified as abnormal (≦1.5 mV) with one activation sequence and normal (> 1.5 mV) with the other activation sequence. Electrically unexcitable scar (6% of sites) was associated with lower electrogram amplitude but could not be reliably identified based on electrogram amplitude alone for either activation sequence. Conclusion: Voltage maps created with bipolar recordings using these methods should be relatively robust depictions of abnormal ventricular regions despite variable catheter orientation and activation sequences that might be produced by different rhythm