It has been well-documented in the literature that there are many physical and psychological benefits to be derived from regular aerobic exercise. It has also been noted that adherence/compliance to aerobic exercise regimens tends to be quite low. Investigators have found that a number of factors tend to correlate with adherence, but it has been difficult thus far to determine a mechanism which underlies a tendency to adhere versus a tendency to drop-out. This study examined the problem of non-adherence from the perspective of Self-Efficacy Theory (Bandura, 1977). Subjects for this investigation included all patients seen during a four week period in the Cooper Clinic at the Aerobics Center in Dallas, Texas. Patients at the clinic receive a complete physical examination and health prescriptions based upon the results of their examination. During this four week period, half were administered a Self-Efficacy Questionnaire. Approximately three months later all patients seen during this four week period received a followup (adherence questionnaire in the mail). It was hypothesized that there would be a positive relationship between responses on the Self-Efficacy Questionnaire and responses on the Adherence Questionnaire. A second hypothesis stated that there would be a positive relationship between items which specifically pertained to exercise on each of the questionnaires. In addition, it was expected that there would be no difference in adherence rates between those who made self-efficacy judgments and those who did not. Results of a t-test conducted between the group which made self-efficacy judgments and the group that was not asked to make such an evaluation demonstrated no significant difference in adherence rates. A correlational analysis revealed that there was not a statistically significant relationship between total self-efficacy scores and total adherence scores. There was, however, a statistically significant relationship between levels of exercise self-efficacy and levels of exercise adherence. In addition to these main variables of interest, correlations between other variables (sex, age, percent bodyfat, etc.) were examined and discussed.

Nearly half of all youths experience a mental health disorder at some point during childhood (Merikangas et al., 2010). Pediatric psychopathology is associated with a substantial amount of impairment in the school, social, and home domains, and such symptoms can have adverse impacts on subsequent development (Beauchaine & Hinshaw, 2013; Patel, Flisher, Hetrick, & McGorry, 2007). Fortunately, a number of medications have demonstrated efficacy in treating a number of mental health conditions (Martin, Scahill, & Kratochvil, 2010). Despite these demonstrated effects, treatment response is often incomplete, and the mechanisms by which pharmacotherapy lead to behavior change are not well understood. However, research in pediatric psychopharmacology has often not considered the role of psychosocial variables, despite their promise to explain much variance in psychiatric outcomes and the robust influence they have demonstrated in psychotherapy-based behavior change (e.g., Shirk & Karver, 2011). This study investigated the role of four psychosocial variables in treatment outcome in pediatric psychiatric practice: medication adherence, therapeutic alliance, motivation for behavior change, and expectancies for positive treatment outcome. Surprising patterns of effects were found, with psychosocial variables being associated with both decreases and increases in symptomology depending on the circumstance (e.g., externalizing behavior), and many inconsistencies were observed among these patterns. While psychosocial variables are often portrayed as having uniformly positive impacts on treatment, their role in pediatric psychiatry may not be as straightforward as is commonly depicted in other diseases and therapeutic approaches. In particular, the nature of their effects on outcome may vary across symptom presentations and intervention approaches. Based on these findings, recommendations for clinical practice and future research are discussed which affect all patients, researchers, and medical providers who participate in pediatric psychiatric treatment.

Abstract The goals in diabetes care are good metabolic control, minimisation of complications due to diabetes and a good quality of life. In order to achieve these goals, it is important that persons with diabetes adhere to self-care. Internationally, there are numerous studies available about adherence to self-care among adults with diabetes, but in Finland there are hardly any, especially in nursing science. The purpose of this study was to examine adherence to self-care and also how metabolic control, social support and health locus of control beliefs are related to patient adherence. The data were gathered by questionnaires from 213 working-aged adults with insulin-treated diabetes from the Oulu Health Center or the Central Hospital of Lapland. The response rate was 76%. In order to verify the reliability and the validity of the instruments, we used correlation coefficients, factor analysis and item-total analysis. Internal consistency was checked by Cronbach's alfa. Cross-tabulations with the chi-square test of independence, correlations, One- and Two-Way ANOVA and covariate analysis were used for data analysis. Our multivariate statistical methods consisted of logistic and multiple linear regression analysis and cluster analysis. The subjects who were adherent to self-care had better metabolic control than those who neglected self-care. A fifth of the respondents were neglecting their self-care. The others undertook flexible, regimen-adherent or self-planned self-care. Poor metabolic control, smoking and living alone explained neglect of self-care. If the diabetic got support from her/his family and friends, living alone was not a predictor of neglect of self-care. Those who were adherent to self-care perceived themselves as getting more support from their family and friends than the group who neglected self-care. Those who had poor metabolic control perceived themselves as getting peer support from other persons with diabetes. Those who were adherent to self-care were responsible internals who believed both in their own action and in health care team action. Those who mainly believed in health care team action (powerful other externals) were more adherent to self-care than those with an internal or chance external health locus of control. We got evidence about the importance of adherence to self-care, and its relationship with metabolic control, social support anf HLOC beliefs. The results can be used when developing the individual patient education of persons with diabetes.

Class of 2014 Abstract / Specific Aims: Medication adherence is the extent to which patients take their medications correctly and consistently as prescribed.1 The objective of this study was to assess Accreditation Council for Pharmacy Education (ACPE)- preaccredited and accredited schools and colleges of pharmacy for adherence course content in their curricula. Methods: The survey link was sent via email to the Department of Pharmacy Practice Chair, or equivalent, at each institution. The data collected via the online survey included information regarding the details of medication adherence curriculum present at the program. All data remained confidential. Chi-square statistical test was used for analysis to compare hours of adherence education taught in older (in existence ≥ 20 years) versus newer (< 20 years) programs. Main Results: Twenty-eight programs responded among 130 inquiries (22% response rate). Of the respondents, only two colleges of pharmacy offered a course on medication adherence, one as an elective and one as required. Common adherence principles were incorporated into other pharmacy courses with the most common topics being counseling, patient education and communication skills. Older programs taught more hours (> 20 hours) focused on adherence compared to the newer programs, but they did not differ significantly (p = 0.39). Conclusion: Despite the low response rate, the findings show a lack of curricular focus on medication adherence, particularly as an individual course. Further studies are needed to identify adherence training received by student pharmacists, and to evaluate the impact of adherence-focused curriculum components on provision of patient care centered on medication adherence by pharmacy practitioners.

Magister Public Health - MPH / The government of Namibia established a comprehensive HIV/AIDS treatment and care programme in 2002. This programme provides anti-retroviral treatment to all eligible HIV patients in the public health sector. The antiretroviral treatment programme in Keetmanshoop started in October 2003. Adherence to treatment regimes in HIV care is a key factor in determining clinical outcomes and is associated with improved survival among HIV and AIDS patients. Sustained high levels of adherence (95% or more) are essential for the success of highly active antiretroviral therapy (HAART). Maintaining high adherence levels is therefore a major concern in HIV/AIDS treatment programmes. This study investigated adherence to HAART among patients in the Keetmanshoop antiretroviral therapy (ART)clinic and the factors that affect adherence.Aim of the research The aim of the research was to describe adherence to HAART and factors influencing adherence among patients in Keetmanshoop ART clinic, Namibia.Objectives: 1. To describe levels of adherence to HAART amongst clients at Keetmanshoop ART clinic. 2. To assess the changes in CD4 count and body weight of clients on HAART over a 12 month period.3. To assess factors associated with adherence to HAART.4. To analyse associations between CD4 count and adherence. 5. To analyse associations between changes in body weight and adherence. Methodology: A quantitative descriptive cross-sectional survey was used. The study population included all clients 18 years and above, who were on HAART for one year or more at the Keetmanshoop clinic. One hundred and six clients participated in the study. Data was collected through an interview with the participants and a review of clinical records. Results: Most respondents had good adherence levels; with 86.1% reporting optimal adherence levels.The respondents also showed an increase of median CD4 counts from 126 cells/μl at baseline to 304 cells/μl at 12 months and an increase in body weight from an average of 50kg at baseline to an average of 57kg at 12 months. Adherence levels were found to have an impact on CD4 cell counts and on body weight, with respondents who had sub-optimal adherence experiencing a drop in median CD4 cell counts and median body weight by 12 months.Living far from the clinic (>10km) was found to be the only factor significantly associated with sub-optimal adherence.Conclusion: The study showed a positive correlation between adherence levels and CD4 cell counts and body weight gain. In the absence of viral load, CD4 cell count testing can be used as a measure of adherence. Though most respondents appear to be adhering well to HAART, a sub-optimal adherence rate of >10% is a concern for the Keetmanshoop ART programme and will need to be addressed. There is a need for further research to determine the level of default or attrition from HAART in the programme

>Magister Scientiae - MSc / In clinical trials, adherence of the participants to the dosing instructions is a major challenge. Many researchers have identified medication adherence as a topic to further explore in order to obtain good, usable and reproducible results. In order to gain an understanding of on-the-ground issues in clinical research a survey was conducted, isolating the issue of medication adherence among participants as a discussion point. The research was conducted specifically at clinical trial sites that are involved in HIV pre-exposure prophylaxis research. The survey was conducted at clinical trial sites across South Africa among health care workers in the clinical research sector. The principle issue to be identified was the perceptions of staff and researchers with regards to the current approach to adherence measurement and possible suggestions from them on future adherence interventions strategies. This research was conducted as a qualitative analysis from February to March 2014. Eighteen responses were received. Among the respondents were investigators, medical officers, nurses and pharmacists. The results of the survey suggest that healthcare workers have a strong understanding of the importance adherence monitoring and intervention. They have many ideas on which measurement tools work and which don’t, but most importantly feel that the self-report or interview techniques are the most useful. Researchers also feel that much more can be done in order to improve the perception of the clinical research institutes in the eyes of the community and that a more active role should be taken in the community in order to improve the acceptance of the participants to the use of the product.

Doctor of Philosophy / Biochemistry and Molecular Biophysics Interdepartmental Program / Brian V. Geisbrecht / The pathogenic bacterium Staphylococcus aureus actively evades many aspects of human innate immunity by expressing a series of secreted inhibitory proteins. A number of these proteins have been shown to specifically bind to and inhibit components of the complement system. Since complement is known to play a significant role in the pathophysiology of human inflammatory diseases, our long-term goal is to understand the structure, function, and mechanism of Staphylococcal immune evasion proteins to develop complement-targeted therapeutics. Since its discovery, the extracellular adherence protein (Eap) has been shown to be a crucial component in the pathogenesis and survival of S. aureus through its ability to interact and inhibit multiple aspects of the innate immune system. We have shown that Eap inhibits the classical and lectin pathways of complement by a previously undescribed mechanism. Specifically, Eap binds with nanomolar affinity to complement protein C4b, and thereby blocks binding of the classical and lectin pathway pro-protease C2 to C4b. This effectively eliminates formation of the CP/LP C3 proconvertase, which is required for amplification of downstream complement activity and subsequent inflammatory events. The full-length, mature Eap protein from S. aureus strain Mu50 consists of four ~97 residue domains, each of which adopt a similar beta-grasp fold, and are connected to one another through short linker regions that give rise to an elongated, but structured protein. Through multiple structural and functional assays, we have identified the 3rd and 4th domains of Eap as being critical for interacting with C4b and subsequent inhibition of the complement cascade. Alternative approaches to a standard co-crystal structure of Eap34 bound to C4b provided evidence that Eap domains 3 and 4 both contain a low affinity, but saturable binding site for C4b; we were able to map these sites to the α-chain and γ-chain, specifically the metal-ion-dependent adhesion site of the C345c domain, of C4b, both of which have been previously shown to be required for pro-protease binding. To provide higher resolution information, we took advantage of the abundance of surface exposed lysines in Eap34, and employed a lysine-acetylation foot printing mass spectrometry technique. This identified seven lysines in Eap34 that undergo changes in solvent exposure upon C4b binding and confirmation of these residues was done through site-directed mutagenesis, followed by direct binding and functional assays. Together, these results provide structural and functional insight into one of the many ways that Staphylococcus aureus can evade the killing powers of the innate immune system. Future plans are directed at conducting site-specific screens to identify small molecule/peptide compounds that target the Eap34 binding site on C4b. Such molecules would constitute attractive lead compounds in the search for specific inhibitors of the classical and lectin complement pathways.

Objectives: Adherence to multiple sclerosis (MS) treatment is essential to optimize the likelihood of full treatment effect. This prospective, observational, single-center cohort study investigated adherence to fingolimod over the 2 years following treatment initiation. Two facets of adherence - implementation and persistence - were examined and compared between new and experienced users of disease-modifying treatments (DMTs). Materials and methods: Implementation rates were based on the proportion of days covered and calculated as percentages per half-yearly visits and over 2 years, captured through refill data, pill count, and self-report. Nonadherence was defined as taking less than 85.8% of prescribed pills. Implementation rates were classified as nonadherent (< 85.8%), suboptimally adherent (>= 85.8% but. 96.2%), and optimally adherent (>= 96.2%), including perfectly adherent (100%). Persistence, ie, time until discontinuation, was analyzed by Kaplan-Meier analysis. Reasons for discontinuation were recorded. Results: The cohort included 98 patients with relapsing MS, all of whom received a dedicated education session about their medication. Of these 80% were women, 31.6% had fingolimod as first DMT, and 68.4% had switched from other DMTs. The mean implementation rate over 2 years was 98.6% (IQR(1-3) 98.51%-98.7%) and did not change significantly over time; 89% of measurements were in the optimally adherent category, 45.6% in the perfectly adherent category. There was one single occurrence of nonadherence. New users of DMTs were 1.29 times more likely to be adherent than experienced users (OR 1.29, 95% CI 1.11-1.51; P < 0.001), but not more persistent. Nineteen of 98 patients discontinued fingolimod. Conclusion: The very high implementation rates displayed in this sample of MS patients suggest that facilitation by health care professionals in preserving adherence behavior may be sufficient for the majority of patients. Targeted interventions should focus on patients who are nonadherent or who stop treatment without intention to reinitiate.

Haiti reports the second highest prevalence of HIV among the Caribbean nations. People living with HIV/AIDS (PLWH) report stigmatic experiences, inadequate social support, depression, and anxiety, thereby affecting treatment adherence. This study examined the relationship between HIV-related stigma and treatment adherence, considering the effects of depression, anxiety, social support, and coping. The current study is a secondary analysis of baseline data collected from 362 PLWH from Haiti. The measures included: Community Programs for Clinical Research on AIDS (CPCRA) adherence questionnaire; Perceived Stigma scale; Brief COPE questionnaire; State-Trait Anxiety Inventory (STAI); Centers for Epidemiological Studies Depression Scale (CES-D); and modified Medical Outcome Study Social Support Survey (mMOS-SSS). Descriptive statistics were used for demographic characteristics. T tests, Person correlations, multivariable linear regressions and structural equation modeling (SEM) were used for estimating the strength of associations and mediating effects. Mean age of the sample was 35.72±8.50 years and 37.0% were men. The mean self-reported treatment adherence was 93.1 percent. About 50.2% reported high levels of perceived stigma, 58.1% reported high levels of social support, 51.1% reported high levels of coping, 45.6% reported depression and 47.2% reported anxiety. Multivariable regression showed that treatment adherence was directly associated with quality of care satisfaction scores (Beta = .032, p = .041) and inversely associated with perceived stigma (Beta = -0.049, p = .031). Depression was directly associated with perceived stigma-public view (Beta = 1.877, p = .037) and inversely associated with tangible/informational social support (Beta = 1.877, p = .020). SEM analyses showed significant associations between perceived sigma and coping (Beta = .175, p = .003), perceived sigma and anxiety (Beta = .164, p = .005), coping and anxiety (Beta = .229, p In summary, HIV-related stigma was associated with lower levels of treatment adherence, and higher levels of depression and anxiety. These findings could be informative for future large scale studies on stigma, coping, anxiety and depression and planning effective interventions for improving treatment adherence.

Introduction: Haemophilia is an inherited bleeding disorder caused by a deficiency in one of the coagulation or blood clotting factors in the blood. When injured someone with haemophilia does not bleed more intensely than a person without haemophilia, but they tend to bleed for a much longer time. For people affected by severe haemophilia, the deficiency in coagulation factor can cause spontaneous internal bleeding in joints and muscles, as well as intracranial bleeding, and bleeding in soft tissues (e.g. nosebleeds or bleeding gums). The most common form is Haemophilia A which is caused by a deficiency in factor VIII. Haemophilia B is caused by a deficiency of factor IX and tends to be less severe than haemophilia A. Haemophilia is treated by replacing the deficient coagulation factor in the blood through intravenous injections of factor concentrate. Treatment can be on-demand, where medication is used to treat a bleeding episode; or preventative, where factor replacement treatment is used to increase the concentration of coagulation factor in the blood to prevent bleeding. Most young people with severe haemophilia in the UK follow a preventative treatment regimen (prophylactic treatment or prophylaxis). Patients with severe haemophilia A usually take 3 or 4 injections per week on alternate days, whereas patients with severe haemophilia B usually take 2 or 3 injections per week. There is good evidence that prophylaxis reduces bleeds and joint damage, whilst also improving quality of life. Therefore it is imperative for future health and functioning that young people with haemophilia (YPH) follow the prophylactic regimen they agreed with their haemophilia team. However, reported adherence levels among YPH vary widely (17 - 93%). Additionally, drivers of (non)adherence among YPH specifically have not been evidenced. Aims: The overall aim of the research described in this thesis was to gain a better understanding of the extent to which YPH adhere to their prophylactic treatment, and better understand what drives their (non-)adherence. The aims of the quantitative questionnaire study were to measure levels of adherence among YPH, and to assess whether psychosocial factors that have been shown to be associated with adherence among young people with other chronic illnesses, such as self-efficacy and social support, are also associated with adherence among YPH. Based on previous research on adherence and social cognitive models of illness, it was hypothesised that: - there would be differences between adolescents and young adults in relation to psychosocial correlates of adherence. - higher perceptions of pain and impact of pain would be associated with better adherence (De Moerloose, Urbancik, Van Den Berg, & Richards, 2008; Treil, Rice, & Leissinger, 2007). - higher perceptions of chronicity, consequences and treatment control would be predictive of higher adherence (Chilcot et al., 2010; Horne & Weinman, 2002). - greater perception of necessity of prophylaxis would be predictive of higher adherence whereas concerns about prophylaxis would not be predictive (de Thurah, Nørgaard, Harder, & Stengaard-Pedersen, 2010; Horne et al., 2013; Horne & Weinman, 1999; Llewellyn, Miners, Lee, Harrington, & Weinman, 2003; Wileman et al., 2014). - greater negative mood would be associated with lower adherence scores (Cox & Hunt, 2015; Helgeson, Siminerio, Escobar, & Becker, 2009; Snell, Fernandes, Bujoreanu, & Garcia, 2014). In addition, based on evidence that lower adherence results in worse disease outcomes (Berntorp, 2009; M. J. Manco-Johnson et al., 2007), it was anticipated that non-adherence to prophylaxis would be associated with higher numbers of bleeds and hospital visits. The aims of the qualitative interview studies with YPH, parents of YPH, and haemophilia healthcare professionals were to examine perceptions and experiences in relation to prophylaxis and how they make sense of these experiences. It was anticipated that this would provide evidence to gain a better understanding of the complexities surrounding prophylaxis and of the barriers and facilitators to adherence among YPH.