Background: Glaucoma is a chronic, progressive eye disease and the second cause of blindness in the world. To measure the patients’ perspective in randomised controlled trials (RCTs), patient-reported outcome measures (PROMs) are increasingly being used. However, the use of PROMs in glaucoma trials is low suggesting there may be a reluctance to use PROMs. Objectives: To explore three methodological challenges of using PROMs in RCTs in glaucoma: 1) PROM selection; 2) characterising glaucoma severity; and 3) interpreting PROM scores in terms of minimal important difference (MID). Methods: Vision PROMs used in glaucoma studies were identified and content validated using a systematic review approach and categorised by a new PROM taxonomy. Existing visual field staging systems (VFSSs) based on standard automated perimetry were systematically identified and quality assessed with a new tool developed for this review using a consensus method. The performance of four high quality visual field staging systems were evaluated and referenced against an experienced ophthalmologist in a diagnostic test accuracy study. A pilot study using the social comparison approach was undertaken to test the feasibility of an anchor-based approach in determining the MID of a vision PROM in a glaucoma population. Results: Thirty-three vision PROMs were identified and categorised, according to content into impairment, disability, status and satisfaction measures. Twenty-three VFSSs were identified but evaluation of quality assessment, particularly performance, was affected by poor VFSS reporting. The diagnostic accuracy study demonstrated suboptimal performance of the four highest quality staging systems. The pilot study to determine the MID for a vision PROM found the social comparison method to be a feasible approach in a glaucoma population. Conclusion: This thesis demonstrated how to select a PROM and identified difficulties with characterising glaucoma severity. Future research needs include development of robust methods for characterising glaucoma severity and full scale evaluation of MIDs in PROMs in glaucoma.

Missing data are a problem for any clinical trial outcome but are particularly an issue for quality of life (QoL) outcomes.  To investigate the problem of missing data and methods to deal with it, this thesis uses a novel approach, illustrated using seven completed trials. Data from postal reminders were used to investigate the missing data mechanism and test the accuracy of imputation procedures (as the true value was in fact known).  The previously analysis for five of the seven example trials was an analysis of covariance adjusting for baseline QoL and other patient characteristics.  Alternative analysis strategies taking account of other interim responses are considered and contrasted with the published analyses.  The economic impact of the different data collection methods is explored using two economic decision rules. Different analysis strategies were shown to have an impact on the result of the trial.  There is no single best way of dealing with missing data, but some recommendations for researchers are provided.  The role of reminders is shown to be extremely important as the reminder system is a cost-effective use of resources to maintain the sample size, decreasing the amount of missing data and reducing the threat of bias.  Data collected by reminders can be used to inform the selection of potential imputation methods, again reducing bias.  The aim of any trial is to obtain an unbiased as possible estimate of treatment difference to help inform and improve clinical practice to the benefit of patients; the use of reminders may be pivotal in this.

This study explored potential patterns of association among the demographic characteristics, identification practices, educational interventions, and educational outcomes for students with serious emotional disturbance (SED) as well as specifically investigated the impact of age at identification with SED and the presence of co-occurring disabilities. Data was gathered from the educational records of students with SED in seven rural to semi-rural districts in Texas. Demographic information included gender, ethnicity, age at identification with SED, and identification with co-occurring disabilities. Identification variables that were investigated include the five federal qualifying criteria for SED, IQ score, and BASC and/or CBCL scores. Intervention variables that were explored included placement setting, restrictiveness of placement setting, type of related services provided, parental attendance at multidisciplinary team meetings, number of multidisciplinary team meetings, and total time spent in special education as a student with SED. Outcome variables that were examined included achievement levels in reading and math, attendance, special education status, and grade retention. Results suggested that earlier identification with SED is related to placement in less restrictive settings, achievement within two years of grade level in reading, and lower average number of absences. The presence of co-occurring disabilities in addition to SED is associated with placement in more restrictive settings and with achievement that is two or more years below grade level in reading and math. Additional findings and implications for future research as well as for current practice are discussed.

Given the high rates of premature termination in training clinics, research aimed at understanding client attrition is urgently needed. Recent investigations in this area have implicated expectations of psychotherapy as a strong predictor of premature termination; however, this phenomenon has only been studied from the perspective of client expectations to date. There is reason to believe clinician expectations for the duration and effectiveness of psychotherapy may further impact the likelihood of their clients terminating prematurely. This study sought to address this gap in the literature by examining the association of clinicians' expectations to clients' psychotherapy outcomes and termination status in a training clinic setting. Clinicians were found to hold significantly higher expectations for client improvement than would be expected, and these high expectations were found to be positively correlated with clinically significant change in clients. Implications for improving client retention and treatment outcome in training clinics are discussed.

Given the alarmingly high rates of premature termination in training clinics, research aimed at understanding the course of change and treatment outcomes in training clinics deserves considerable attention. Additionally, more research is needed to understand the effectiveness of psychotherapy training and whether more training is actually associated with better client outcomes. Thus, this study sought to investigate whether clinicians' level of training and experience were related to a variety of clients' outcomes (e.g., well-being, symptom reduction, and life functioning) based on the phase model of psychotherapy. Unfortunately, confirmatory factor analysis of the OQ45.2 did not support the three-factor conceptual model paralleling the phase model. Rather, a two-factor model of best fit was identified. Neither clinicians' level of clinical training nor therapeutic orientation were found to be related to client improvements. However, this finding may have been attenuated by limited variance in client outcomes. Implications for clinical training and future outcome research methodologies are discussed.

Gene expression studies are of growing importance in the field of medicine. In fact, subtypes within the same disease have been shown to have differing gene expression profiles (Golub et al., 1999). Often, researchers are interested in differentiating a disease by a categorical classification indicative of disease progression. For example, it may be of interest to identify genes that are associated with progression and to accurately predict the state of progression using gene expression data. One challenge when modeling microarray gene expression data is that there are more genes (variables) than there are observations. In addition, the genes usually demonstrate a complex variance-covariance structure. Therefore, modeling a categorical variable reflecting disease progression using gene expression data presents the need for methods capable of handling an ordinal outcome in the presence of a high dimensional covariate space. In this research we present a method that combines the stereotype regression model (Anderson, 1984) with an elastic net penalty (Friedman et al., 2010) as a method capable of modeling an ordinal outcome for high-throughput genomic datasets. Results from applying the proposed method to both simulated and gene expression data will be reported and the effectiveness of the proposed method compared to a univariable and heuristic approach will be discussed.

Psychological and contextual factors play an important role in the development and maintenance of chronic spine-related pain, and effective treatment of pain-related conditions requires an understanding of how these factors contribute to pain and disability. The present study examined the relative contributions of spine pathology, psychological complications, and demographic factors to perceived pain intensity and disability in patients with chronic spine-related pain. Because most patients were assessed in the context of a compensable injury, exaggeration of symptoms and disability was systematically controlled for using multiple validity indicators. A high prevalence of psychological complications was observed in the present sample. Analysis indicated that psychological factors were not significantly related to pain intensity, but were significantly related to reported pain-related disability. Further, psychological factors were found to predict pain-related disability beyond demographics, medical findings, and pain intensity. Clinical implications of these findings are discussed.

Student Number : 0413807K - MSc research report - School of Public Health - Faculty of Health Sciences / Tuberculosis ranks among the top ten causes of global mortality. Globally it kills nearly 2 million people each year and is the second leading cause of death after Human Immune Deficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS).Tuberculosis (TB) is primarily an illness of the respiratory system, and is spread by coughing and sneezing from an infectious person. Nearly a third of the world’s population is infected with the bacilli that causes TB and are at risk of developing tuberculosis (TB).1, 2 Left untreated, each person with active TB disease will infect on average between 10 and 15 people every year. In 2004, estimated per capita TB incidence was stable or falling in five out of six World Health Organization (WHO regions, but growing at 0.6% per year globally. The exception is the African region, where TB incidence was still rising.3, 4 HIV increases the risk of developing TB and accounts for much of the increase in countries where prevalence is high. 4 Co-infection is common and could be as high as 70% in high-burdened countries. Gains made in global TB control in the 1970 and 80s are being dramatically reversed by the effect of HIV/AIDS. HIV is the main reason for failure to meet Tuberculosis (TB) control targets in high HIV settings.3 Drug-resistant TB is a major problem. Resistance to single anti-tuberculosis drugs have been reported in almost every country surveyed. To make the situation worse, drugs resistant to all the major anti-TB drugs have emerged. 4 Drug-resistant TB is caused by inconsistent or partial treatment, when patients do not take all their medicines regularly for the required period because they start to feel better, because doctors and health workers prescribe the wrong treatment regimens, or because the drug supply is unreliable. A particularly dangerous form of drug-resistant TB is multidrug-resistant TB (MDR-TB), which is defined as the disease caused by TB bacilli resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs.4, 5

This was a two phase study exploring lay perspectives of medicines for dementia. In phase one, participants were recruited from 4 local branches of the Alzheimer's Society in the southwest to take part in a single focus group or interview. In total 5 people with dementia and 23 carers participated. The aim was to explore perceptions of medicines on day-to-day life. Findings fell into 3 superordinate themes: On Being a Carer; Interacting with Healthcare Professionals and Living with a Degenerative Illness. Participants described great variability in access to medicines and in outcomes of consultations with healthcare professionals. Ageism and therapeutic nihilism were commonly encountered. Phase Two was a longitudinal study exploring the impact of medicines for dementia in early stage disease using a case study approach. Seven case studies were recruited via memory clinics; with four receiving a medicine for dementia and three not. Case study participants were followed over a 13-month period. The superordinate themes were: Living with a Memory Problem or Dementia; Interacting with Healthcare Professionals and Medicines for Dementia. Even in the early stages of a dementia spousal relationships were negatively affected. Medicines for dementia enabled renegotiation of spousal relationships and adjustment and acceptance to take place. The Mini-Mental State Examination was perceived to tell only half the story and was insensitive to improvements in alertness, initiative, engagement with the individuals' lifeworld and ability to maintain and engage in social relationships. Overall both phases found access to medicines for dementia a complicated and long procedure. The methods for assessing response were perceived as threatening and unrealistic. There was a perceived need for greater education about dementia and its treatment for healthcare professionals, people with dementia and their carers. It was identified that pharmacists could take a more proactive role in providing a pharmaceutical care service.

Thesis (M.S.)--Boston University