Mutation of the p53 gene is the most common genetic alteration in human cancers. The mutant p53 protein is more stable than the wild type and can be detected by immunohistology. The objective of the current study was to evaluate the immunohistological detection of p53 protein in prostate cancer and its utility as a prognostic indicator. We used a monoclonal anti-p53 antibody and immunostained primary prostate adenocarcinomas (stages Al to Dl) from 109 patients with a mean follow-up of 3.8 years (range, 1.3 to 9.3 years). Immunoreactivity for p53 was seen in 23 cancers (21%). There were 12 instances of progression (14%) among the p53-negative cancers versus seven (30%) among the p53-positive group. Survival analysis using three univariate statistical tests showed that p53 reactivity (P < .03), Gleason score (P < .01), and stage (P < .05) had significant effects on time to progression of prostate cancer. Multivariate analyses showed that Gleason score was significant with all three tests; p53 reactivity was significant with the Wilcoxon test but only approached significance by the log rank and Cox tests. When the analyses included only patients with Gleason scores 2 to 7 (N = 94), univariate analyses showed that p53 reactivity was strongly related to progression of prostate cancer (P < .007). Stage also was significant (P < 0.04), but Gleason score was not. Multivariate analyses showed only p53 reactivity to be significant (P < .007). In conclusion, mutation of the p53 gene may be involved in prostate cancer carcinogenesis. p53 reactivity marks an aggressive subset of prostate cancer and appears to be an independent prognostic indicator that is particularly valuable among the low to intermediate grade cancers.

Student Number : 9411363J - PhD thesis - School of Medicine - Faculty of Health Sciences / This study on non-compliance with chemotherapy in the oncology patient with a good prognosis was done in the Johannesburg Hospital in South Africa. 114 compliant and 33 non compliant oncology patients with a good prognosis showed significant differences (at the 5% level) on the MCMI2 on the following scales: Disclosure, Debasement, Avoidance, Passive Aggressive, Self-defeating, Schizotypal, Anxiety, Dysthymia, Alcohol Dependence and Major Depression. In a Linear Discriminant Function Analysis . two variables, Debasement and Schizotypal were selected that linearly affected compliance significantly. A linear discriminant model was constructed from the two variables which could predict non compliance in these patients 72.5% of the time. The next step was to construct a treatment model , an intervention which would have some impact on improving compliance. After trial and error with various methods, a Medical Trauma Debriefing Model was worked out and used, based on the Wits Trauma Intervention Model, which up to this time had been used for trauma debriefing of people who had experienced trauma due to violence and abuse on a criminal or political level. This is in accordance with recent studies which are beginning to show the link between PTSD and medical non-compliance. It is suggested that Medical Trauma Debriefing, as a preventative measure, be incorporated automatically and routinely into the treatment of certain medical and surgical conditions, especially in Oncology.

PhD Thesis / Background: The home care population is a cohort of medically complex older adults at risk for cardiac arrest and poor post-cardiac arrest health outcomes. Research Question: What is the prognosis of cardiac arrest among patients receiving home care, and what pre-arrest features and geriatric syndromes (e.g., frailty) are prognostic of survival and post-cardiac arrest health? Methods: Following a systematic review and meta-analysis that evaluated the prognostic association between frailty and post-cardiac arrest outcomes, a population-based retrospective cohort was created of adults (≥18 years) who received cardiac arrest care at a hospital in Ontario, Canada, between 2006 and 2018. Patients receiving home care and nursing home residents were identified using the Home Care Dataset and the Continuing Care Reporting System. Arrests were analyzed overall and within distinct sub-groups of in-hospital (IHCA) and out-of-hospital cardiac arrests (OHCA). The primary outcome for this thesis was 30-day survival post-cardiac arrest. Frailty was measured using the Clinical Frailty Scale and a valid frailty index. The odds of survival from cardiac arrest were estimated using multivariable logistic regression. Prognostic models were internally validated using bootstrap resampling (n= 2000). Results: We found high certainty evidence for an association between the Clinical Frailty Scale and death prior to hospital discharge after IHCA (OR = 2.93; 95% CI = 2.43 – 3.53) after adjusting for age as a minimum confounder. Our retrospective cohort contained 86,836 unique adult cardiac arrests, of which 39,610 were OHCA and 47,226 were IHCA. Patients receiving home care represented 10.7% of the cohort and were less likely to survive to hospital discharge (RD = -6.4; 95%CI = -7.4– -5.2) and one-year (RD = -12.8; 95%CI = -14.6 – -10.9) post-cardiac arrest compared to community-dwelling individuals receiving no support in the community. Frail patients receiving home care had worse odds of 30-day survival when measured with the CFS (OR=0.78; 95%CI = 0.61-0.98) and a frailty index (OR=0.89; 95%CI = 0.85-0.95), after adjusting for age, sex, and arrest setting. My prognostic model out-performed the two valid frailty measures and demonstrated fair discriminative accuracy (AUROC = 0.66; 95%CI=0.65-0.65) and good calibration (Slope = 0.95) for group-level prognostication when internally validated among patients receiving home care. Conclusion:Patients receiving home care have a worse absolute risk of death when compared to community-dwelling individuals receiving no community-based support services. Frailty is associated with survival and post-cardiac arrest declines in cognition and function when evaluated in patients receiving home care. The prognostic model developed within my thesis outperformed the ability of frailty to predict 30-day survival and is suitable for group-level prognostication. / Dissertation / Doctor of Philosophy (PhD) / The proportion of older adults receiving home care is growing. The home care population is frail and medically complex, with a greater risk for cardiac arrest. This thesis aims to evaluate the prognosis and prognostic factors influencing survival and other health outcomes, to develop a statistical model that can predict 30-day survival post-cardiac arrest. Findings from my research demonstrate that patients receiving home care have worse survival outcomes post-cardiac arrest compared to well-being older adults living in the community. In my research, frailty was associated with survival and declines in post-cardiac arrest functional independence and cognitive performance among patients receiving home care. Our statistical model performed better than valid frailty measures and had respectable accuracy for group-level prognostication. The home care population is ideally positioned for proactive and shared decision-making about end-of-life care preferences, bearing in mind their receipt of detailed and routine health assessments.

Yes / Osteopontin (OPN) plays an important role in cancer progression, however its prognostic significance and its downstream factors are largely elusive. In this study, we have shown that expression of OPN was significantly higher in bladder cancer specimens with higher T-stage or tumor grades. In addition, a high level of OPN was significantly associated with poorer survival in two independent bladder cancer patient cohorts totaling 389 bladder cancer patients with available survival data. We further identified Matrix metallopeptidase 9 (MMP9) and S100 calcium-binding protein A8 (S100A8) were both downstream factors for OPN in bladder cancer specimens and bladder cancer cell lines. Expression of OPN was significantly positively associated with that of MMP9 and S100A8, while overexpression of OPN resulted in upregulation of MMP9 and S100A8, and knockdown of OPN showed consistent downregulation of MMP9 and S100A8 expression levels. Importantly, expression levels of both MMP9 and S100A8 were significantly associated with higher T-stage, higher tumor grade and a shorter survival time in the bladder cancer patients. Interestingly, OPN expression only predicted survival in MMP9-high, but not MMP9-low subgroups, and in S100A8-low but not S100A8-high subgroups. Our results suggest that OPN, MMP9 and S100A8 all play a significant role in bladder cancer progression and are potential prognostic markers and therapeutic targets in bladder cancer. The mechanistic link between these three genes and bladder cancer progression warrants further investigation. / University of Macau Multi-Year Research Grant (MYRG2015-00065-FHS)

Bibliography: leaves 187-211. / 288 leaves : col. ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / An observational retrospective study to determine if any difference exists in the soft tissue profile of Class II division 1 patients before and after treatment with three different functional appliances; the activator with headgear, the Clark Twin Block, and the Frankel. / Thesis (M.D.S.)--University of Adelaide, Dept. of Dentistry, 1999

Bibliography: leaves 187-211. / 288 leaves : col. ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / An observational retrospective study to determine if any difference exists in the soft tissue profile of Class II division 1 patients before and after treatment with three different functional appliances; the activator with headgear, the Clark Twin Block, and the Frankel. / Thesis (M.D.S.)--University of Adelaide, Dept. of Dentistry, 1999

Traumatic brain injury (TBI) constitutes a major health problem and is a leading cause of long-term disability and death. Patients with severe traumatic brain injury, S-TBI, comprise a heterogeneous group with varying complexity and prognosis. The primary aim of this thesis was to increase knowledge about clinical course and outcome with regard to prognostic factors. Papers I, II and III were based on data from a prospective multicentre observational study from six neurotrauma centers (NCs) in Sweden and Iceland of patients (n=103-114), 18-65 years with S-TBI requiring neurosurgical intensive care or collaborative care with a neurosurgeon (the “PROBRAIN” study).  Paper IV and V were performed on a regional subset (n=37). In Paper I, patients with posttraumatic disorders of consciousness (DOC) were assessed as regards relationship between conscious state at 3 weeks and outcomes at 1 year. The number of patients who emerged from minimally conscious state (EMCS) 1 year after injury according to status at 3 weeks were: coma (0/6), unresponsive wakeful syndrome (UWS) (9/17), minimally conscious state (MCS) (13/13), anaesthetized (9/11). Outcome at 1 year was good (Glasgow Outcome Scale Extended (GOSE&gt;4) in half of the patients in MCS (or anaesthetized) at 3 weeks, but not for any of the patients in coma or UWS.    In Paper II, the relationships between clinical care descriptors and outcome at 1 year were assessed. A longer length of stay in intensive care, and longer time between discharge from intensive care and admission to inpatient rehabilitation, were both associated with a worse outcome on the GOSE. The number of intervening care units between intensive care and rehabilitation, was not significantly associated with outcome at 1 year.  In Paper III, the clinical course of cognitive and emotional impairments as reflected in the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) and the Hospital Anxiety and Depression Scale (HADS) were assessed from 3 weeks to 1 year together with associations with outcomes GOSE and Rancho Los Amigos Cognitive Scale-Revised (RLAS-R) at 1 year. Cognition improved over time and appeared to be stable from 3 months to 1 year.  In Paper IV, clinical parameters, the clinical pathways from injury to 3 months after discharge from the NC in relation to outcomes 3 months post-injury. Ratings on the RLAS-R improved significantly over time. Eight patients had both “superior cognitive functioning” on the RLAS-R and “favourable outcome” on the GOSE. Acute transfers to the one regional NC was direct and swift, transfers for postacute rehabilitation scattered patients to many hospitals/hospital departments, not seldom by several transitional stages.  In Paper V, an initial computerized tomography of the brain (CTi) and a further posttraumatic brain CT after 24 hours (CT24) were evaluated according to protocols for standardized assessment, the Marshall and Rotterdam classifications. The CT scores only correlated with clinical outcome measures (GOSE and RLAS-R) at 3 months, but failed to yield prognostic information regarding outcome at 1 year. A prognostic model was also implemented, based on acute data (CRASH model). This model predicted unfavourable outcomes for 81% of patients with bad outcome and for 85% of patients with favourable outcome according to GOSE at 1 year. When assessing outcomes per se, both GOSE and RLAS-R improved significantly from 3 months to 1 year.  The papers in this study point both to the generally favourable outcomes that result from active and aggressive management of S-TBI, while also underscore our current lack of reliable instruments for outcome prediction. In the absence of an ability to select patients based on prognostication, the overall favourable prognosis lends support for providing active rehabilitation to all patients with S-TBI. The results of these studies should be considered in conjunction with the prognosis of long-term outcomes and the planning of rehabilitation and care pathways. The results demonstrate the importance of a combination of active, acute neurotrauma care and intensive specialized neurorehabilitation with follow-up for these severely injured patients.

published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy

published_or_final_version / Surgery / Master / Master of Philosophy

published_or_final_version / Surgery / Doctoral / Doctor of Philosophy