Thesis (L.L.M. (Law))--Rhodes University, 2006.

Thesis (Ph. D.)--Illinois State University, 1994. / Title from title page screen, viewed March 22, 2006. Dissertation Committee: Edward R. Hines (chair), Joseph J. Goleash, Douglas H. Lamb, John R. McCarthy, Anita H. Webb-Lupo. Includes bibliographical references (leaves 154-165) and abstract. Also available in print.

Thesis (Ph. D.)--Dept. of Psychology, Concordia University, 1996. / "May 1996." Includes bibliographical references (leaves 178-188). Available also on the Internet.

<b>Background:</b> The aim of this thesis was to develop an evidence-based approach to the post-marketing withdrawal of medicinal products when harms are attributed to their use. <b>Methods:</b> Electronic and non-electronic searches were conducted to identify medicinal products withdrawn from the market because of adverse reactions. Data relating to the time periods between launch, first adverse reaction reports and withdrawals, the mechanism through which the adverse reactions occurred, and the countries of withdrawal were extracted. Standard criteria were used to document the levels of evidence used by drug regulators to make the withdrawal decisions; scatter plots and two-by-two tables used to explore the trends over time. A previously published algorithm was used to examine the justification for withdrawals. To examine the benefits and harms of medicinal products before regulatory approval, searches were conducted on drug regulatory websites and scientific databases. The Cochrane criterion was used to examine the risk of bias, Review Manager Software for meta-analysis, and GRADE criterion to rate the quality of evidence. <b>Results:</b> Improvements in pharmacovigilance over the past six decades have resulted in quicker detection of harms caused by approved medicinal products; however, there have not been corresponding improvements in how quickly harmful products are withdrawn from the market following the reports of harms. Harmful drugs are significantly less likely to be withdrawn in low resource settings. The quality of evidence in drug trials for which regulatory approval decisions are based is on the whole, poor. There is a lack of consistency in the methods used by drug regulators to assess the harms of medicinal products before granting marketing licences. <b>Conclusions:</b> Universally accepted guidelines for deciding when to withdraw approved medicinal products from the market should be developed. Pharmacovigilance systems in low-resource settings should be strengthened. The methods used to assess harms in clinical trials require improvement.

Purpose: This paper aims to conceptualize impacts of higher education institutions (HEIs) on sustainable development (SD), complementing previous literature reviews by broadening the perspective from what HEIs do in pursuit of SD to how these activities impact society, the environment and the economy. Design/methodology/Approach: The paper provides a systematic literature review of peer-reviewed journal articles published between 2005 and 2017. Inductive content analysis was applied to identify major themes and impact areas addressed in the literature to develop a conceptual framework detailing the relationship between HEIs- activities and their impacts on SD. Findings: The paper identi fi es six impact areas where direct and indirect impacts of HEIs on SD may occur. The fi ndings indicate a strong focus on case studies dealing with speci fi c projects and a lack of studies analyzing impacts from a more holistic perspective. Practical implications: This systematic literature review enables decision-makers in HEIs, researchers and educators to better understand how their activities may affect society, the environment and the economy, and it provides a solid foundation to tackle these impacts. Social implications: The review highlights that HEIs have an inherent responsibility to make societies more sustainable. HEIs must embed SD into their systems while considering their impacts on society. Originality/value: This paper provides a holistic conceptualization of HEIs- impacts on SD. The conceptual framework can be useful for future research that attempts to analyze HEIs- impacts on SD from a holistic perspective.

This thesis presents a literature review of the diagnosis and treatment of lumbar spinal stenosis (LSS), including a brief description of the patient history and non-surgical options while focusing mainly on the current array of surgical techniques. LSS is defined as a narrowing of any part of the lumbar spinal canal. This narrowing places excessive pressure on both the spinal cord and peripheral nerves resulting in pain, numbness and weakness in the lower extremities. LSS has a large spectrum of potential treatment options since the disease itself has a wide range of severities. An extensive physical exam, using the appropriate clinical surveys, physical manipulations, and imaging studies, is of paramount importance in the successful diagnosis. Currently, conservative treatment, while an important first step in managing LSS, seems to be limited to a first line of defense, lasting only a short period of time. Physical therapy results appear to be beneficial for only six months to a year, and despite their increased usage in recent years, management through the use of non-steroidal anti-inflammatory drugs, opiates, and corticosteroid injections seem to provide very little benefit. Surgical treatment for LSS ultimately appears to be the most effective method in reducing pain and disability for the patient who fits the clinical and radiological findings indicative of LSS. Although current surgical options available are numerous, including different types of fusion, bone grafts, and innovative joint replacements, the most promising procedures appear to be minimally invasive lumbar disk replacement surgery and dynamic stabilization. These procedures offer the benefits of a minimally invasive surgical approach, while reducing stenosis though hardware that not only reduces pain but also allows patients to maintain spinal flexibility and natural functional motion.

The current field of cancer treatment is undergoing a revolution. The influx of novel therapies derived from basic research on the immune system has shifted the landscape of modern medicine. Immunotherapy seeks to use the body’s own immune system as a medium to terminate neoplastic cells. This is performed by manipulating the immune system into either targeting cancer antigens or breaking down barriers towards T cell infiltration. The former mechanism uses CAR-T cells as an instrument to target specific cancer neo-antigens. CAR-T cells begin as T cells derived from a patient’s immune system. These cells are removed from the body and engineered to express a chimeric antigen receptor (CAR) through a process of viral transduction. This CAR allows the T cell to recognize and bind to a specific antigen of interest. In most cases, the antigen is present on cancer cells. The T cells, now expressing the CAR receptor, are transplanted back into the body of the patient and proceed to target cancer cells. This therapy has been used in hematological malignancies to great effect. Applying CAR-T cells to solid tumors is an ongoing process, but has been difficult to establish due to the immunosuppressive aspects of the tumor microenvironment. As such, combining CAR-T cells with traditional anti-cancer therapies has been proven to be efficacious in treating patients with solid tumors. In general, immunosuppression is a large problem in the treatment of cancer. Cancer cells and the tumor microenvironment express receptors that downregulate tumor-targeting actions of the immune system. The discovery of the programmed cell death protein 1 (PD1) allowed researchers to create novel antibodies that inhibit immunosuppression. PD1 located on T cells, binds to PDL1 on cancer and stromal cells. This interaction induces exhaustion and anergy in infiltrating T cells, thereby prevent T cells from targeting cancer cells. As such, the newly approved checkpoint blockade antibodies, Nivolumab and Pembrolizumab, block this interaction and allow T cells to carry out their targeting function. CAR-T cells and checkpoint blockade have both seen immense success in clinical trials and are currently being used the clinic. Nonetheless, development of these therapies for different types of cancers is an ongoing process and one that will require immense effort on behalf of the medical and pharmaceutical establishment

BACKGROUND: Electroconvulsive therapy (ECT) is an effective intervention for major depressive disorder, especially for subsets of depression that resist more common therapies. However, ECT use is limited by its significant risk for adverse cognitive side effects. Shortening the pulse width of the current used has been demonstrated to lower this risk; however, the shorter pulse may not sufficiently elicit therapeutic effects. A systematic review was performed to determine if UBP ECT is as efficacious as BP ECT, and therefore would be a valid treatment for managing depression. METHODS: We conducted a literature search of MedLine/PubMed, Embase, Cochrane CENTRAL, and Google Scholars databases in October 2017 with the terms “depression”, “major depressive disorder”, “electroconvulsive therapy”, “ECT”, “brief”, “ultrabrief”, and “sine wave”. Studies were selected using inclusion criteria and exclusion criteria. Effects sizes were calculated from formalized mood rating pre-ECT and post-ECT, response rates and remission rates. Heterogeneity and reporting bias of the articles were also assessed. Data were analyzed using meta-analysis tools provided by the Erasmus Research Institute of Management. RESULTS: Data from 9 studies resulted in a pooled Cohen’s d = 0.16 (CI = -0.08 to 0.43, p = 0.149). The effect size alone favors BP ECT over UBP ECT in improving mood as per MADRS/HRSD ratings, but if given p > 0.05, results were non-significant. BP ECT was determined to be more efficacious then UBP ECT in terms of both achieving response and achieving remission, with a pooled ORresponse = 0.72 (CI – 0.49 to 1.05, p = 0.027) and pooled ORremission = 0.65 (CI = 0.42 to 0.98, p = 0.011). CONCLUSION: The choice to use BP ECT or UBP ECT is a balance between the burden of side effects and efficacy. These data suggest that patients with a lower risk of developing cognitive side effect and/or need urgent intervention receive BP ECT. Conversely, patients with a higher risk of developing adverse cognitive side effects and/or are not in need of urgent intervention may benefit UBP ECT. Additional studies are recommended to confirm these findings and clarify the optimal use of these two modalities of ECT.

Background: Improving care for people living with dementia when they are admitted to hospital is a national priority. Interventions have been designed and implemented to support staff to improve how they provide care to patients with dementia. However, there is limited understanding of how these interventions work in practice and what the outcomes are for patients and their family carers. Objective: To develop, test, and refine a theory-driven explanation of what supports hospital staff to provide dementia-friendly care and with what outcomes for people living with dementia and their carers. Method: A two-phase study design employing realist methodology. Phase one was a realist review which combined evidence from stakeholder interviews and literature searches. Phase two used realist evaluation to analyse data collected from two NHS Hospital Trusts in the East of England to test the theory developed in phase one. Findings: Initial scoping in the realist review identified three candidate theories which structured the literature searches and analysis. Six related context-mechanism-outcome configurations were identified and collectively made the initial programme theory. The review found that single strategies, such as dementia awareness training, would not on their own change how staff provide care for patients with dementia. An important context was for staff to understand behaviour as a form of communication. Organisational endorsement for dementia care and clarity in staff roles was important for staff to recognise dementia care as a legitimate part of their work. The realist evaluation refined the programme theory. While the study sites had applied resources for patients with dementia differently, there were crosscutting themes which demonstrated how key mechanisms and contexts influenced staff actions and patient outcomes. When staff were allocated time to spend with patients and drew on their knowledge of the patient with dementia and dementia care skills, staff could provide care in ways that reassured patients and recognised their personhood. However, accepted organisational and social norms for care practices influenced whether staff considered providing skilled dementia care was an important contribution to the work on the ward. This impacted on how staff prioritised their work, which influenced whether they recognised and addressed patient needs such as pain or hunger, made attempts to reduce distress, and if patients and carers considered they were listened to. Organisational focuses, such as risk management, influenced how patient need was defined and how staffing resources were allocated. Staff commitment to continuing in dementia care was influenced by whether or not they valued dementia care as skilled work. Discussion: Single strategies, such as the use of dementia awareness training, will not on their own improve the outcomes for patients with dementia when they are admitted to hospitals. In addition, attention needs to be paid to the role of senior managers and their knowledge of dementia to support staff to provide care in ways that recognise the needs of the person. The way dementia care is valued within an organisation has implications for how resources are organised and how staff consider their role in providing dementia care. Evidence from observations demonstrated that when staff are supported to provide good dementia care, patients experienced positive outcomes in terms of their needs being addressed and reducing distress. Dementia care needs to be recognised as skilled work by the staff and the organisation.

Background: Self-efficacy is an important determinant of physical activity. Yet it remains unclear which behaviour change techniques (BCTs) are most effective at changing self-efficacy for physical activity. This PhD thesis aimed to explore issues surrounding which individual BCTs and clusters of BCTs that are most effective in initiating and maintaining changes in self-efficacy and physical activity behaviour across different adult populations through a systematic review with meta-analysis. This thesis consists of three linked papers which examined: 1) the individual and clusters of BCTs that are most effective in initiating and maintaining changes in self-efficacy and physical activity behaviour across all adult populations, 2) the individual BCTs which are effective in initiating self-efficacy and physical activity in two clinical samples (hypertension or heart disease, and pain or arthritis), and 3) the extent of theory use in interventions and examination of BCT use across theories. Methods: One hundred and eighty randomised trials which reported changes in self-efficacy were included into the review. Intervention content was reliably coded using the BCT Taxonomy v1 by two independent coders. From the 180 randomised trials, 204 comparisons were identified for the meta-analyses and moderator analyses. Meta-regressions examined whether the presence and absence of individual BCTs and intervention characteristics were associated with effect size changes for self-efficacy and physical activity. Chi-square analyses were conducted in Journal Article Three to examine for differences in BCT use across theories. Results: In Journal Article One, lack of meaningful clustering of BCTs was found. Interventions had small but significant effects on self-efficacy for the initiation of physical activity (d=0.26; 95%CI: [0.21, 0.31]) and physical activity (d= 0.21; 95%CI: [0.17, 0.26]) across all adult populations. Small effects were also found for the maintenance of physical activity self-efficacy behaviour, and these were non-statistically significant. In Journal Article Two, the interventions had small to medium sized significant effects on the initiation of physical activity self-efficacy and behaviour in hypertension or heart disease, and pain or arthritis samples. Few BCTs were found to moderate intervention effects on self-efficacy or physical activity in either clinical sample. In Journal Article Three, theory was not used extensively in interventions. Differences in the use of BCTs were found across theories, some of which mapped onto the constructs of the adopted theoretical frameworks. Conclusions: It seems that there are no specific sets of BCTs that are effective for changing self-efficacy and physical activity across all adult populations. In addition to BCTs, there needs to be further research into how communication styles and delivery characteristics can influence intervention effectiveness. It is also important to understand how BCTs and theory can be used optimally together, as there appears to be discrepancy between what theories proposes to be effective and what empirical evidence generated by this review suggests may be effective.