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

Prognostic factors for mental wellbeing in prostate cancer:A systematic review and meta-analysis

OBJECTIVES: To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients.METHODS: We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible.RESULTS: A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p = 0.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p &lt; 0.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes.CONCLUSION: We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.</p

A desmoplakin variant associated with isolated arrhythmogenic left ventricular cardiomyopathy with rapid monomorphic ventricular tachycardia at first presentation

Arrhythmogenic cardiomyopathy (ACM) encompasses heart muscle diseases associated with potentially life-threatening ventricular tachyarrhythmias occurring out of proportion to the degree of underlying disease. The most classical disease is arrhythmogenic right ventricular cardiomyopathy (ARVC), whereas biventricular ACM as well as left-dominant forms (arrhythmogenic left ventricular cardiomyopathy, ALVC) have been increasingly recognized. Genetic variants in the desmoplakin (DSP) gene, coding for an integral part of the desmosome and the resultant disruption of intermediate filament binding, were shown to be associated with ACM, including ALVC.1 In this paper, we report a DSP variant associated with rapid sustained monomorphic ventricular tachycardia as first manifestation in a young female patient with isolated ALVC without right ventricle (RV) involvement

Non-technical skills for urological surgeons (NoTSUS) : development and evaluation of curriculum and assessment scale

In the last decade non-technical skills (NTS) have emerged as a vital area for improvement within surgery. This study aims to develop and evaluate a Non-technical Skills for Urological Surgeons (NoTSUS) training curriculum and assessment scale. This international, longitudinal and observational study began with a 3-round Delphi methodology to refine curriculum contents and rating scale. Sessions with up to four participants were delivered where each candidate undertook an independent scenario within the validated full immersion simulation environment. Candidates were assessed using both the NoTSS (Non-technical Skills for Surgeons) and NoTSUS rating scales by NTS-trained and non-trained experts. A post-training evaluation survey was distributed. 62 participants comprising trainees (n = 43) and specialists (n = 19) undertook the NoTSUS course. The NoTSS and NoTSUS scales correlated well, with a mean difference of 3.3 in the overall total (p = 0.10, r = 0.53). However, there was significant differences in scores between the NoTSS-trained and non-trained raters (n = 28, p = 0.03). A one-way ANOVA test revealed significant improvement throughout the four simulation scenarios in each session (p = 0.02). The NoTSUS curriculum received positive feedback from participants and demonstrated educational value and acceptability. The NoTSUS curriculum has demonstrated high educational value for NTS training aimed at urologists, with marked improvement throughout sessions. Correlation of NoTSUS and NoTSS scales proves its suitability for evaluating NTS in future training. Demonstration of inter-rater reliability indicates that the scale is reliable for use in assessment by expert faculty members. Furthermore, qualitative feedback from participants suggests gain of transferrable skills over the course. The online version of this article (10.1007/s00345-020-03406-6) contains supplementary material, which is available to authorized users