Background: By 2050, it is estimated that 14 million older Americans will live with Alzheimer’s disease (AD), a progressive form of dementia with unknown cause or cure. Persons with AD and related dementias (ADRD) become increasingly dependent on others as they experience cognitive decline, which concomitantly undermines individuals’ functional skills, social initiative, and quality of life. The Alzheimer’s Association advocates for interventions that address cognition, mood, behavior, social engagement, and by extension, quality of life – goals music therapists often address. Although a small but growing body of literature suggests that clinical music therapy may be effective, the evidentiary support for the use and appropriate application of music as a form of treatment with this population is currently limited. Objectives: This thesis consisted of the development of a Clinical Practice Model of music therapy for persons with ADRD. It also examined the effectiveness of a specific, protocol-based music therapy intervention, grounded in this model, relative to a verbal discussion activity. Methods: The Clinical Practice Model is theoretically grounded in the biopsychosocial model of healthcare (Engel, 1980) and Kitwood’s (1997) personhood framework, and I developed it through extensive literature review and expert input. It includes an organizational schema for applying intervention strategies, per six themes: cognition, attention, familiarity, audibility, structure, and autonomy. The initial model predicts that an intervention built upon this schema will influence social-affective responses, quality of life, and in turn, psychosocial symptoms of ADRD. I tested a singing-based music therapy intervention, grounded in this model, through a randomized clinical crossover trial. I compared participants’ responses to music therapy to a non-music verbal discussion activity, and both conditions followed a protocol. Dependent variables included: (1) affective responses (self-reported feelings, observed emotions, and observed mood), (2) social engagement, and (3) observed quality of life. Thirty-two individuals with ADRD (n = 6 men, n = 26 women) ages 65-97 years old (μ̂ = 84.13) participated in this study. I randomly assigned treatment order; each treatment occurred in small-group format, three times per week in the afternoon (25 minutes each session), for two consecutive weeks. A two-week “wash-out” period occurred between conditions. Credentialed music therapists led both study conditions. This study followed recommendations from the National Institutes of Health Behavior Change Consortium (Bellg et al., 2004) to enhance quality assurance in protocol administration and data collection. Results and Significance: I used a linear mixed model approach to analysis. Music therapy exacted a significant, positive effect on self-reported feelings, observed emotions, and constructive engagement, particularly for individuals with moderate dementia. Results also suggested that men’s feelings improved in response to music therapy only, whereas women responded positively to both conditions. Weekly observations failed to indicate a significant change in mood or quality of life across the eight-week study. Based on these findings, I revised the Clinical Practice Model to include wellbeing (an outcome more concordant with psychosocial change in response to music intervention) rather than global quality of life (affected by numerous aspects of the care milieu). In addition to the Clinical Practice Model to the music therapy profession, contributions of this thesis include a rigorous clinical study and practical implications for music therapy practice, including the importance of considering patient characteristics and careful selection and implementation of music in a music therapy intervention.

Comparative experiments, in which subjects are randomized to one of two treatments, are performed often. There is no shortage of papers testing whether a treatment effect exists and providing confidence intervals for the magnitude of this effect. While it is well understood that the object and scope of inference for an experiment will depend on what assumptions are made, these entities are not always clearly presented. We have proposed one possible method, which is based on the ideas of Jerzy Neyman, that can be used for constructing confidence intervals in a comparative experiment. The resulting intervals, referred to as Neyman-type confidence intervals, can be applied in a wide range of cases. Special care is taken to note which assumptions are made and what object and scope of inference are being investigated. We have presented a notation that highlights which parts of a problem are being treated as random. This helps ensure the focus on the appropriate scope of inference. The Neyman-type confidence intervals are compared to possible alternatives in two different inference settings: one in which inference is made about the units in the sample and one in which inference is made about units in a fixed population. A third inference setting, one in which inference is made about a process distribution, is also discussed. It is stressed that certain assumptions underlying this third type of inference are unverifiable. When these assumptions are not met, the resulting confidence intervals may cover their intended target well below the desired rate. Through simulation, we demonstrate that the Neyman-type intervals have good coverage properties when inference is being made about a sample or a population. In some cases the alternative intervals are much wider than necessary on average. Therefore, we recommend that researchers consider using our Neyman-type confidence intervals when carrying out inference about a sample or a population as it may provide them with more precise intervals that still cover at the desired rate.

Recent literature has reported the use of entropy measurements for anomaly detection purposes in IP data streams. Space efficient randomized algorithms for estimating entropy of data streams are available in the literature. However no hardware implementation of these algorithms is available. The main challenge to software implementation for IP data streams has been in storing large volumes of data, along with, the requirement of high speed at which they have to be analyzed. In this thesis, a recent randomized algorithm available in the literature is analyzed for hardware implementation. Software/hardware simulations indicate it is possible to implement a large portion of the algorithm on a low cost Xilinx Virtex-II Pro FPGA with trade-offs for real-time operation. The thesis reports on the feasibility of this algorithm's FPGA implementation and the corresponding trade-offs and limitations.

Data arising from Cluster Randomized Trials (CRTs) and longitudinal studies are correlated and generalized estimating equations (GEE) are a popular analysis method for correlated data. Previous research has shown that analyses using GEE could result in liberal inference due to the use of the empirical sandwich covariance matrix estimator, which can yield negatively biased standard error estimates when the number of clusters or subjects is not large. Many techniques have been presented to correct this negative bias; However, use of these corrections can still result in biased standard error estimates and thus test sizes that are not consistently at their nominal level. Therefore, there is a need for an improved correction such that nominal type I error rates will consistently result. First, GEEs are becoming a popular choice for the analysis of data arising from CRTs. We study the use of recently developed corrections for empirical standard error estimation and the use of a combination of two popular corrections. In an extensive simulation study, we find that nominal type I error rates can be consistently attained when using an average of two popular corrections developed by Mancl and DeRouen (2001, Biometrics 57, 126-134) and Kauermann and Carroll (2001, Journal of the American Statistical Association 96, 1387-1396) (AVG MD KC). Use of this new correction was found to notably outperform the use of previously recommended corrections. Second, data arising from longitudinal studies are also commonly analyzed with GEE. We conduct a simulation study, finding two methods to attain nominal type I error rates more consistently than other methods in a variety of settings: First, a recently proposed method by Westgate and Burchett (2016, Statistics in Medicine 35, 3733-3744) that specifies both a covariance estimator and degrees of freedom, and second, AVG MD KC with degrees of freedom equaling the number of subjects minus the number of parameters in the marginal model. Finally, stepped wedge trials are an increasingly popular alternative to traditional parallel cluster randomized trials. Such trials often utilize a small number of clusters and numerous time intervals, and these components must be considered when choosing an analysis method. A generalized linear mixed model containing a random intercept and fixed time and intervention covariates is the most common analysis approach. However, the sole use of a random intercept applies assumptions that will be violated in practice. We show, using an extensive simulation study based on a motivating example and a more general design, alternative analysis methods are preferable for maintaining the validity of inference in small-sample stepped wedge trials with binary outcomes. First, we show the use of generalized estimating equations, with an appropriate bias correction and a degrees of freedom adjustment dependent on the study setting type, will result in nominal type I error rates. Second, we show the use of a cluster-level summary linear mixed model can also achieve nominal type I error rates for equal cluster size settings.

The current study was an extension of research reported by Krohn (2010), which showed that daily credit for self-reported participation in designated credit units tended to balance participation across students (i.e., fewer non-participants, more credit-level participants, and fewer dominant participants). The purpose of the current study was to determine if similar results would be achieved by randomly selecting half of the discussion days in designated credit units for participation credit. The study was done in 3 large sections of an undergraduate class (approximately 54 students per class). Students self-recorded their in-class comments each day on specially designed record cards. At the end of each pre-selected unit, instructors randomly selected discussion days and awarded credit based on the number of comments made on the days randomly selected. Three credit points were given for each student’s first comment and two additional points for a second comment. The findings of the current study differed in several ways from those of Krohn’s (2010) comparison study. The differences mainly related to baseline percentages of different levels of participation. Compared to the current study, Krohn’s study had a higher percentage of non-participants, fewer credit-level participants, fewer frequent participants, and more dominant participants. The disparities between the baseline levels of Krohn’s study and the current study made treatment effects more difficult to achieve in the latter study. Nonetheless, there were fewer non-participants and more credit-level and frequent participants during credit units than in non-credit units. Secondarily, a survey was given at the beginning of the course to analyze student beliefs regarding participation. Using the same survey, Krohn (2010) extracted three primary factors: 1) Personal Benefits of Participation, 2) Expectation for Discussion in College Classes, and 3) Personal History and Confidence Regarding Participation. The same three factors were also examined separately and in combination in the current study. Results showed the three-factor model to predict student participation levels better than the total survey. In addition, students were given the Watson-Glaser Critical Thinking Appraisal at the onset of the course. A logistic regression indicated that exam and critical thinking scores, in combination, significantly predicted student participation levels.

Improved weight loss interventions are needed to help reduce obesity. One dietary factor that has been effective in increasing weight loss is increased dietary structure. One method for increasing dietary structure is prescribing the frequency in which eating bouts (meals and snacks) occur. Eating frequency (EF) has been inversely related to body mass index (BMI) but the impact of EF on weight loss is unclear. This randomized controlled trial examined the effect of EF on hunger, the relative-reinforcing value of food, energy intake (EI), and weight loss during a 6 month behavioral weight loss intervention. Participants (age: 51.0 ± 9.9 yrs, BMI: 35.5 ± 4.8 kg/m2, 57.8% female, 94.1% white) were randomized to one of two EF prescriptions: 1) Three Meal (n=25): three eating bouts/day; or 2) Grazing (n=26): eat at least 100 kcals every 2-3 hrs. Both groups attended 20 sessions and had identical dietary (1200–1500 kcals/day, < 30% kcals from fat) and physical activity (200 minutes/wk) goals. Hunger, relative-reinforcing value of food, diet, and anthropometric data were collected at 0 and 6 months. Using intent-to-treat analyses, Grazing reported a greater EF (eating bouts in which > 25 kcals were eaten/day) than Three Meal at 6 months (5.8 ± 1.1 eating bouts vs. 3.2 ± 0.6 eating bouts, p<0.001). On a 100-mm visual analogue scale Grazing reported significantly less hunger at 6 months as compared to 0 months (47.9 ± 18.5 mm vs. 56.3 ± 15.7 mm, p<0.05), while Three Meal did not report any changes. There were no significant differences in the relative-reinforcing value of food between groups or over time. EI and BMI were significantly (p<0.001) reduced from 0 to 6 months (EI: 0 months = 2198 ± 692 kcals/day vs. 6 months = 1266 ± 353 kcals/day; BMI: 0 months = 35.5 ± 4.8 kg/m2 vs. 6 months = 30.6 ± 4.9 kg/m2). There were no significant differences in EI or BMI between the groups. An EF of approximately six eating bouts/day may decrease hunger more so than an EF of three meals/day while consuming a low-kcal diet during a behavioral weight loss intervention.

Leadership is important to quality improvement initiatives in healthcare. However, few studies have evaluated leadership interventions to enhance nurses’ use of guideline recommendations in the field of knowledge translation. Purpose: To develop and evaluate an intervention designed to operationalize a leadership strategy composed of relations, change, and task-orientated leadership behaviours, and to examine its influence on nurses’ use of guideline recommendations in home-care nursing. Design: Sequential mixed methods pilot study with post-only cluster randomized controlled trial. Methods Phase I: Intervention Development 1. A participatory approach was used at a community healthcare organization with 23 units across the province of Ontario, Canada. The guideline selected was developed by the Registered Nurses’ Association of Ontario for the assessment and management of foot ulcers for people with diabetes. 2. Integrative literature review, qualitative interviews, and baseline chart audits were conducted. 3. Four units were randomized to control or experimental groups. 4. Clinical and management leadership teams participated in a 12-week intervention consisting of printed materials, interactive workshop, and teleconferences. Participants received summarized chart audit data, identified priority indicators for change, and created a team leadership action plan to address barriers and influence guideline use. Phase II: Evaluation 5. Chart audits compared differences in nursing process and patient outcomes. Primary outcome: eight-item nursing assessment score. 6. Qualitative interviews evaluated the intervention and leadership behaviours. Results: No significant difference was found in the primary outcome. A significant difference was observed in nurses’ documentation of five priority indicators chosen by the experimental groups (p=.02). Gaps in care included: 53%, 76%, and 94% of patients not assessed for ulcer depth, foot circulation, or neuropathy (respectively); 75% and 93% did not receive wound debridement or hydrogel dressings. Receiving data to identify priority indicators for change and developing a leadership action plan were reported as useful to guideline implementation. The experimental group described using more relations-oriented leadership behaviours conducting audit and feedback, and sending reminders. Conclusion: Findings from this pilot study suggest that leadership is a team process involving relations, change, and task-oriented behaviours enacted by managers and clinical leaders. A leadership model is proposed as a beginning taxonomy to inform future leadership intervention studies.

Unique characteristics of cluster randomized trials (CRTs) complicate the interpretation of standard research ethics guidelines. Variable interpretation by research ethics committees may further complicate review and conduct. An international web-based survey was administered to corresponding authors of 300 randomly sampled CRT publications. We investigated ethics review and consent practices, investigator experiences with ethics review, and the perceived need for CRT-specific ethics guidelines. The response rate was 64%. Ethics review and consent were under-reported in publications. Ethics approval was obtained in 91%, and consent from individual and cluster level participants in 79% and 82% of trials. Consent varied by level of experimental intervention, data collection, and cluster size. Respondents cited variability among ethics committees (46%), and negative impacts of ethics review on their studies (38%). The majority perceived a need for ethics guidelines (73%), and guidance for ethics committees (70%). CRT-specific ethics guidelines are required to ensure practices meet ethical standards.

Hypertension occurs in nearly 10% of pregnancies, and is associated with infant and maternal morbidity and mortality. Prior studies of non-pregnant adults have demonstrated the effectiveness of a variety of relaxation therapies in reducing blood pressure. A pilot randomized controlled trial was conducted, the purposes of which were 1) to provide preliminary evidence regarding the usefulness of guided imagery (GI) in reducing blood pressure in hypertensive pregnant women, and 2) to answer feasibility questions for a larger trial. Pregnant women with hypertension prior to 37 weeks gestation (n = 69) were randomized to either 15-minute periods of guided imagery (n = 34), or of quiet rest (QR) (n = 35), twice daily for four weeks or until delivery, whichever came first. Daytime ambulatory mean arterial pressure (MAP), systolic and diastolic blood pressures, anxiety, rest and GI use were measured weekly, to a maximum of four weeks. Sixty women completed at least one week in the study; 46.4% completed four weeks. Compliance was excellent. Intention to treat analysis was used. In the unadjusted analysis, women allocated to GI had significantly lower average daytime ambulatory mean MAP elevations from baseline to their last week of study participation than women allocated to quiet rest (GI: M = 1.58 mmHg, SD = 7.63; QR: M = 5.93 mmHg, SD = 6.55; t = 2.36, p = .02). However, the effect was no longer statistically significant (p = 0.14) when adjusted for baseline mean arterial pressure and gestation. There was no statistically significant difference in the numbers of women who were prescribed antihypertensive medication after randomization (GI: n = 16, QR: n = 13, X2 = 0.74, p = .46). There was also no evidence of an effect of guided imagery on anxiety. Nearly 90% (n = 26) of the guided imagery group indicated they would use it again, either in a subsequent pregnancy or during stressful life events. Given the ease of use, low cost, acceptability to women, and lack of risk of guided imagery, an adequately-powered randomized controlled trial is warranted.

The main purposes of this thesis were to evaluate a high-intensity functional weight-bearing exercise pro­gramme, regarding its applicability (attendance, achieved intensity, adverse events) as well as its effect on physical functions and activities of daily living (ADL) among older people living in residential care facilities, with a special focus on people with dementia. Furthermore, a main purpose was to systematically review the applicability and effects of physical exercise on physical functions, cognitive functions, and ADL among people with dementia. A high-intensity functional weight-bearing exercise programme that includes lower-limb strength and balance exercises in standing and walking, was evaluated in a randomised controlled trial among 191 older people, dependent in ADL, living in residential care facilities, and with a Mini-Mental State Examination (MMSE) score of ten or more. One hundred (52.4%) of the participants had dementia. Participants were randomised to an exercise programme or a control activity, consisting of 29 supervised sessions over 3 months, as well as to an intake of a protein-enriched energy supplement or a placebo drink immediately after each session. The effect on physical functions was evaluated using the Berg Balance Scale, usual and maximum gait speed, and one-repetition maximum in a leg press machine measuring lower-limb strength. The effect on ADL was evaluated using the Barthel Index. These outcome measures were followed up at 3 and 6 months by blinded assessors and analysed using the intention-to-treat principle. The evaluation of the applicability of the high-intensity functional weight-bearing exercise programme showed that there was a high rate of attendance, a relatively high achieved intensity in the exercises, and all except two adverse events were assessed as minor or temporary and none led to manifest injury or disease. No statistically significant differences were observed in applicability when comparing participants with dementia and participants without dementia. In addition, the applicability of the programme was not associated with the participants’ cognitive function. Significant long-term effects of the exercise programme were seen regarding functional balance, gait ability and lower-limb strength in comparison with the control activity. The intake of the protein-enriched energy supplement did not increase the effect of the training. Age, sex, depression, dementia disorder, nutritional status, and level of functional balance capacity did not influence the effect on functional balance of the high-intensity functional weight-bearing exercise programme. There were no significant differences between the groups regarding overall ADL performance. Analyses for each item revealed that a significantly smaller proportion of participants in the exercise group had deteriorated regarding indoor mobility at 3 and 6 months. For people with dementia, there was a significant difference in overall ADL performance in favour of the exercise group at 3 months, but not at 6 months. In a systematic review, randomised controlled trials, evaluating the effects of physical exercise among people with dementia, were identified according to pre-defined inclusion criteria. Two reviewers independently extracted predetermined data and assessed methodological quality. Ten studies were included in the review and the majority of the participants were older people with Alzheimer’s disease living in residential care facilities. Four studies reached “moderate” methodological quality and six “low”. The results showed that among older people with Alzheimer’s disease in residential care facilities, combined functional weight-bearing exercise over 12 months at an intended moderate intensity seems applicable for use regarding attendance and adverse events and there is some evidence that the exercise improves walking performance and reduces ADL decline. Furthermore, there is some evidence that walking exercise over 16 weeks performed individually, where the participant walks as far as possible during the session, reduces decline in walking performance, but adverse events need to be evaluated. In conclusion, among older people who are dependent in ADL, living in residential care facilities, and have an MMSE score of 10 or more, a high-intensity functional weight-bearing exercise programme is applicable for use and has positive long-term effects on functional balance, gait ability, and lower-limb strength and seems to reduce ADL decline related to indoor mobility. An intake of a protein-enriched energy supplement immediately after the exercise does not appear to increase the effect of the training. In people with dementia, the exercise programme may prevent decline in overall ADL performance, but continuous training may be needed to maintain that effect. The positive results regarding applicability and effects of combined functional weight-bearing exercise among people with dementia is confirmed when the scientific literature is systematically reviewed. It seems to be important that exercise interventions among people with dementia last for at least a few months and that the exercises are task-specific and intended to challenge the individual’s physical capacity. Whether physical exercise can improve cognitive functions among people with dementia remains unclear. There is a need for more exercise studies of high methodological quality among people with dementia disorders.