Effect of investigation intensity and treatment differences on prostate cancer survivor's physical symptoms, psychological well-being and health-related quality of life: a two country cross-sectional study.

Aim: To investigate effects on men's health and well-being of higher prostate cancer (PCa) investigation and treatment levels in similar populations. Participants: PCa survivors in Ireland where the Republic of Ireland (RoI) has a 50% higher PCa incidence than Northern Ireland (NI). Method: A cross-sectional postal questionnaire was sent to PCa survivors 2–18 years post-treatment, seeking information about current physical effects of treatment, health-related quality of life (HRQoL; EORTC QLQ-C30; EQ-5D-5L) and psychological well-being (21 question version of the Depression, Anxiety and Stress Scale, DASS-21). Outcomes in RoI and NI survivors were compared, stratifying into ‘late disease’ (stage III/IV and any Gleason grade (GG) at diagnosis) and ‘early disease’ (stage I/II and GG 2–7). Responses were weighted by age, jurisdiction and time since diagnosis. Between-country differences were investigated using multivariate logistic and linear regression. Results: 3348 men responded (RoI n=2567; NI n=781; reflecting population sizes, response rate 54%). RoI responders were younger; less often had comorbidities (45% vs 38%); were more likely to present asymptomatically (66%; 41%) or with early disease (56%; 35%); and less often currently used androgen deprivation therapy (ADT; 2%; 28%). Current prevalence of incontinence (16%) and impotence (56% early disease, 67% late disease) did not differ between RoI and NI. In early disease, only current bowel problems (RoI 12%; NI 21%) differed significantly in multivariate analysis. In late disease, NI men reported significantly higher levels of gynaecomastia (23% vs 9%) and hot flashes(41% vs 19%), but when ADT users were analysed separately, differences disappeared. For HRQoL, in multivariate analysis, only pain (early disease: RoI 11.1, NI 19.4) and financial difficulties (late disease: RoI 10.4, NI 7.9) differed significantly between countries. There were no significant between-country differences in DASS-21 or index ED-5D-5L score. Conclusions: Treatment side effects were commonly reported and increased PCa detection in RoI has left more men with these side effects. We recommended that men be offered a PSA test only after informed discussion.

Time use, daily activities, and health-related quality of life of school-going late adolescents in Cork city and county: A cross-sectional study

Aim: This thesis examines a question posed by founding occupational scientist Dr. Elizabeth Yerxa (1993) – “what is the relationship between human engagement in a daily round of activity (such as work, play, rest and sleep) and the quality of life people experience including their healthfulness” (p. 3). Specifically, I consider Yerxa’s question in relation to the quotidian activities and health-related quality of life (HRQoL) of late adolescents (aged 15 - 19 years) in Ireland. This research enquiry was informed by an occupational perspective of health and by population health, ecological, and positive youth development perspectives. Methods: This thesis is comprised of five studies. Two scoping literature reviews informed the direction of three empirical studies. In the latter, cross-sectional time use and HRQoL data were collected from a representative sample of 731 school-going late adolescents (response rate 52%) across 28 schools across Cork city and county (response rate 76%). In addition to socio-demographic data, time use data were collected using a standard time diary instrument while a nationally and internationally validated instrument, the KIDSCREEN-52, was used to measure HRQoL. Variable-centred and person-centred analyses were used. Results: The scoping reviews identified the lack of research on well populations or an adolescent age range within occupational therapy and occupational science; limited research testing the popular assumption that time use is related to overall well-being and quality of life; and the absence of studies that examined adolescent 24-hour time use and quality of life. Established international trends were mirrored in the findings of the examination of weekday and weekend time use. Aggregate-level, variable-centred analyses yielded some significant associations between HRQoL and individual activities, independent of school year, school location, family context, social class, nationality or diary day. The person-centred analysis of overall time use identified three male profiles (productive, high leisure and all-rounder) and two female profiles (higher study/lower leisure and moderate study/higher leisure). There was tentative support for the association between higher HRQoL and more balanced time use profiles. Conclusion: The findings of this thesis highlight the gendered nature of adolescent time use and HRQoL. Participation in daily activities, singly and in combination, appears to be associated with HRQoL. However, the nature of this relationship is complex. Individually and collectively, adolescents need to be educated and supported to create health through their everyday patterns of doing.

Cancer associated malnutrition: prevalence of cachexia, sarcopenia and impact on treatment outcomes, survival and health related quality of life

Malnutrition, sarcopenia and cancer cachexia (CC) are prevalent among cancer patients and can have detrimental effects on clinical outcomes such as quality of life (QoL) and overall survival. Cachexia is associated with lower tolerance for chemotherapy, which limits the total dose that can be delivered, the number of symptomatic responses and any survival advantage that might be accrued. Moreover, for the majority who do not respond, cachexia may be exacerbated by systemic chemotherapy, thus increasing the net symptom burden experienced by patients. The multitude of interactions between cancer location, treatments, nutritional status and QoL has never been thoroughly explored in an Irish cancer cohort. The objectives of this thesis were to further understand nutritional status, especially body composition in ambulatory cancer patients and determine the relationship between nutritional status using different assessment criteria and QoL, chemotherapy toxicity and survival among cancer patients undergoing chemotherapy. Results aimed to identify baseline factors that may be predictive of poor outcome, toxicities to chemotherapy and disease-free and overall survival. This thesis broadly divides into two sections. The first section (Chapters 3 & 4) focuses on improving our knowledge of the nutritional status of Irish cancer outpatients using a cross sectional study design. A study of 517 patients referred for chemotherapy was conducted using computed tomography (CT) imaging (body composition) and a survey that documented oncologic data, weight loss (WL) data and QoL data. We revealed that a significant proportion of Irish cancer patients undergoing chemotherapy experience unintentional WL over the previous 6 months (62%), sarcopenia (45%) and CC (43%), and the distribution of WL and nutritional risk were associated with site of primary tumour and treatment intent. Patients that had sarcopenia, nutritional risk, or CC had significantly reduced functional abilities, more symptoms and adverse global QoL. In the second section of this thesis (Chapters 5 & 6) the potential link between developing toxicity to antineoplastic regimens in patients with sarcopenia was conducted by way of retrospective studies. A retrospective serial CT analysis defined the prevalence of sarcopenia in patients with metastatic renal cell carcinoma (mRCC) and metastatic castrate resistant prostate cancer (mCRPC), which was then correlated with dose limiting toxicities of sunitinib and docetaxel respectively. Sarcopenia was prevalent in patients with mRCC and mCRPC, was an occult condition in patients with normal/high BMI, was associated with less treatment days, was a significant predictor of DLT in patients receiving sunitinib and a significant predictor of neutropenia and neurosensory toxicities in patients receiving docetaxel. This thesis attempted to address the underlying research deficiencies in Irish oncology nutritional data at national level. The findings from this thesis have implications for the planning of cancer care interventions and indicate that further research is required to improve nutritional screening, in particular for CC and sarcopenia, in the hope that timely intervention can improve both patient-centered and oncologic outcomes.

Youth-Physical Activity Towards Health: evidence and background to the development of the Y-PATH physical activity intervention for adolescents

Background: Despite known benefits of regular physical activity for health and well-being, many studies suggest that levels of physical activity in young people are low, and decline dramatically during adolescence. The purpose of the current research was to gather data on adolescent youth in order to inform the development of a targeted physical activity intervention. Methods: Cross-sectional data on physical activity levels (using self report and accelerometry), psychological correlates of physical activity, anthropometic characteristics, and the fundamental movement skill proficiency of 256 youth (53% male, 12.40 ± 0.51 years) were collected. A subsample (n = 59) participated in focus group interviews to explore their perceptions of health and identify barriers and motivators to participation in physical activity. Results: Findings indicate that the majority of youth (67%) were not accumulating the minimum 60 minutes of physical activity recommended daily for health, and that 99.5% did not achieve the fundamental movement skill proficiency expected for their age. Body mass index data showed that 25% of youth were classified as overweight or obese. Self-efficacy and physical activity attitude scores were significantly different (p < 0.05) between low, moderate and high active participants. Active and inactive youth reported differences in their perceived understanding of health and their barriers to physical activity participation, with active youth relating nutrition, exercise, energy and sports with the definition of ‘being healthy’, and inactive youth attributing primarily nutritional concepts to ‘being healthy’. Conclusions: Data show a need for targeting low levels of physical activity in youth through addressing poor health related activity knowledge and low fundamental movement skill proficiency. The Y-PATH intervention was developed in accordance with the present study findings; details of the intervention format are presented.

Vascular calcification and mineral bone disorder in chronic kidney disease

Chronic Kidney Disease (CKD), osteoporosis and mild hyponatremia are all prevalent chronic conditions that may coexist and are often under-recognized. Mineral-Bone Disorder begins early in the natural history of CKD and results in complex abnormalities of bone which ultimately confers a well-established increased risk of fragility fractures in End Stage Kidney Disease. Hyponatremia is a novel, usually renal mediated metabolic perturbation, that most commonly occurs independently of the stage of renal dysfunction but which may also predispose to increased fracture risk. The extent -if any- to which either early stages of renal dysfunction or the presence of hyponatremia contribute to fracture occurrence in the general population, independently of osteoporosis, is unclear. Renal transplantation is the treatment of choice for ESKD and although it restores endogenous renal function it typically fails to normalize either the long term cardiovascular or fracture risk. One potential mechanism contributing to these elevated long-term risks and to diminished Health Related Quality of Life is persistent, post-transplant hyperparathyroidism. In this study we retrospectively examine the association of renal function and serum sodium with Bone Mineral Density and fracture occurrence in a retrospective cohort of 1930 female members of the general population who underwent routine DXA scan. We then prospectively recruited a cohort of 90 renal transplant recipients in order to examine the association of post transplant parathyroid hormone (PTH) level with measures of CKD Mineral Bone Disorder, including, DXA Bone Mineral Density, Vascular Calcification (assessed using both abdominal radiography and CT techniques, as well as indirectly by carotid-femoral Pulse Wave Velocity) and Quality of Life (using the Short Form-12 and a PTH specific symptom score). In the retrospective DXA cohort, moderate CKD (eGFR 30-59ml/min/1.73m2) and hyponatremia (<135mmol/L) were associated with fracture occurrence, independently of BMD, with an adjusted Odds Ratio (95% Confidence Interval), of 1.37 (1.0, 1.89) and 2.25 (1.24, 4.09) respectively. In the renal transplant study, PTH was independently associated with the presence of osteoporosis, adjusted Odds Ratio (95% Confidence Interval), 1.15 (per 10ng/ml increment), (1.04, 1.26). The presence of osteoporosis but not PTH was independently associated with measures of vascular calcification, adjusted ß (95% Confidence Interval), 12.45, (1.16, 23.75). Of the eight quality-of-life domains examined, post-transplant PTH (per 10ng/ml increment), was only significantly and independently associated with reduced Physical Functioning, (95% Confidence Interval), 1.12 (1.01, 1.23). CKD and hyponatremia are both common health problems that may contribute to fracture occurrence in the general population, a major on-going public health concern. PTH and decreased Bone Mineral Density may signal sub-optimal long-term outcomes post renal transplantation, influencing bone and vascular health and to a limited extent long term Health Related Quality of Life