<p>Context: It is unclear whether the construct of a randomized controlled trial (RCT) itself could confer benefit or harm to trial participants beyond any effect of the experimental treatment under study (trial effect).</p> <p>Objective: To determine whether there is a trial effect appreciated by RCT participants (insiders) compared to similar patients who do not participate (outsiders). Although we are most interested in the pragmatic comparison of insiders to outsiders, we will also conduct the explanatory comparison of insiders to outsiders when the intervention is the same.</p> <p>Data Sources: We searched electronic health research databases, including CENTRAL (1960-2010), MEDLINE (1966-2010), EMBASE(1980-2010) and PsycINFO (1880- 2010).</p> <p>Study Selection: Eligible studies included those that reported the outcomes of insiders and a group of parallel or consecutive outsiders and reported the same health outcome at the same endpoint.</p> <p>Results: We included 147 articles out of the 42493 identified in our initial search. Five out of the 147 studies randomized patients to be insiders or outsiders, the remaining were observational designs. The heterogeneity of our overall result was reduced by grouping studies based on whether the intervention being investigated was effective and whether treatment inside and outside of the RCT was the same or different. There was no significant difference in outcomes between insiders and outsiders when the experimental intervention was ineffective (standard mean difference [95% confidence interval]: -0.03 [-0.1, 0.04]), or when it was effective and received by both insiders and outsiders (0.04 [-0.04,0.13]). If the experimental intervention was effective but was not administered to outsiders, they experienced worse health outcomes (-0.36 [-0.61, -0.12]).</p> <p>Conclusions: There is no evidence to support any benefit or harm associated with trial participation. There is some evidence that better outcomes are experienced by insiders who had access to effective treatments not offered or available to outsiders.</p> / Master of Health Sciences (MSc)

Pretrial release (PTR) is the permanent or temporary freedom from incarceration for criminal defendants awaiting adjudication of their cases in court. From Anglo Saxon times in England, people accused of non-capital crimes were generally permitted to remain free until judicial officials could hear the charges against them. In America, pretrial release has been advocated by the courts since the colonial era. The U. S. Constitution requires that bail not be excessive, but leaves governments free to decide how bail laws are administered. The study briefly traces the historical developments of PTR up to the present time. The study then centers on the PTR process of three Oregon counties (Multnomah, Washington, and Yamhill) and observes the decisions of judges, release assistance officers, and jailers in relation to the release outcomes for a study group (N=619) who were booked into jails of the three counties in 1993. Background data on defendants in the study include gender, race, the crimes for which they were arrested, criminal history, and the disposition of the current charges. Seventy-one percent of the defendants received PTR. Significant factors in the release outcome, as shown by logistic and multiple regression analyses, were probation violation status, felony in the current charge, narcotics offenses in the current charge, and charged with multiple offenses. Gender and race were not strong influences on the release outcome. Hispanic defendants (N = 108) in the study, however, were detained in jail longer than Whites (N=394). Hispanics were less likely than Whites to be released on the same day of arrest and served generally longer jail terms than Whites under similar sentences. Possible explanations are that Hispanics were more frequently charged with distributing narcotics and charged with multiple offenses. Implications suggest further studies on minorities in judicial and corrections settings. The study has applications in judicial and corrections policies on the early release of inmates, an important issue as jails become increasingly overcrowded.

Purpose: Transitioning into retirement may be a suitable period to help adults establish an active lifestyle. One innovative approach to promote PA may be through multimedia-based programs. This experiment aimed to explore the feasibility DVD and videogame-based exercise programs in promoting physical activity (PA) in adults transitioning into retirement. Underlying motivations, functional fitness, quality of life, and elicited beliefs from participating in the exercise programs were also explored. Methods: Twenty-seven adults were randomized into either a nine-week exercise DVD (n = 9), exergame (n = 9), or waitlisted control group (n = 9). Main outcomes include adherence was based on attendance during the in-lab component and participant logs during the in-home component. PA levels were measured through accelerometery and assessed at baseline, four-, nine- and 12-weeks. Secondary outcomes related to motivation were assessed at baseline, three- and nine-weeks. Tertiary outcomes such as physiological/functional fitness and quality of life outcomes were assessed at pre- and post-intervention. Results: During the in-lab portion, t-tests showed that adherence was slightly higher in the exergame group than the DVD group (t16 = -0.06, p = .96; d = .31). Repeated measures of analysis showed that the group x time interaction for moderate-to-vigorous physical activity (MVPA) (F2,24 = 0.87, p = .52; η2 = .05), while overall PA saw negligible changes (F2,24 = 0.16, p = .85; η2 = .01). At the end of the intervention, overall adherence was similar between both exercise groups (t16 = -0.06, p = .96; d = .03). The group by time interaction effect yielded a moderate effect size for MVPA (F2,24 = 1.07, p = .36; η2 = .08) and overall PA (F2,24 = 1.11, p = .35; η2 = .08). Overall PA only increased in the exergame group (d = .74). The exergame group saw major decreases in instrumental attitude (d = .64), injunctive norm (d = .79), perceived behavioural control (d = .40) and intention (d = .90). Both exercise groups enhanced strength, mobility, and aerobic endurance outcomes (d = .33-.98), as well as several quality of life domains (d = .32-.89). At the post-intervention follow-up, both exercise groups were more active than the control group (d = .49-1.03). Two-thirds of the DVD group adopted DVD-based exercise, while a third of exergame group adopted videogame-based exercise. Conclusions: With a high adoption rate, DVD-based exercise programs may be a feasible and acceptable approach to promote PA levels. Participants in both groups were generally satisfied, indicating that the exercise program was enjoyable, comprehensive, and a simple and convenient way to exercise at home. Improvements to important functional and quality of life domains were also identified. Further research will be required to fully test the effectiveness of exercise DVDs and exergames on adherence and PA behaviour in adults transitioning into retirement. / Graduate / 0384 / christopher.yao7@gmail.com

Thesis (M.Tech.: Chiropractic)--Durban University of Technology, 2009 / Objective: The efficacy of manipulation as compared to placebo in the treatment of two groups of weight trainers with Acromioclavicular (AC) Joint Dysfunction. Methods: Twenty patients (n=20), using randomised sampling were allocated to two intervention groups. Patients in each group received four treatments each over a two-week period and assessed at initial, one week, two weeks and one month follow ups. Objective measures included Algometer and Inclinometer readings. Numerical Pain Rating Scales (NRS), Shoulder Rating Questionnaire (SRQ) and the Shoulder Pain and Disability Index (SPADI) measured subjective outcomes. Results: Manipulation demonstrated significant improvement in objective findings. Subjective outcomes did not show significant difference between the manipulation and placebo groups. Conclusion: Manipulation, when compared to placebo, can be considered as an effective treatment intervention for the treatment of AC joint dysfunction with particular reference to objective outcomes. Although, caution needs to be utilised in accepting this outcome due to limitations in sample size, subjective measure sensitivity and specificity as well as the stringency of the inclusion and exclusion criteria.

This study examines the compatibility of the Law of Criminal Procedure of 2001 in Saudi Arabia with the international human rights standards, and provides recommendations for criminal procedure reforms. The recent developments in the Saudi Arabian criminal justice system make it important to examine the right to a fair trial within the legal system of Saudi Arabia. This study starts by examining the international human rights standards related to the right to a fair trial and the right to a fair trial under the Saudi Arabian legal system. The study then examines the extent to which Shariah law recognizes the international human rights standards related to the right to a fair trial. This will involve the sources of Shariah and the school of thought in the Islamic jurisprudence as well as the crimes and punishments in Islamic law. The main argument is highlighted in Chapters Four and Five of this research, the former of which study the pre-trial process in the Saudi Law of Criminal Procedure in the light of international human rights standards, and the latter has evaluated the right to a fair trial under Saudi Arabia legal system. Various cases are examined in these two chapters, and the sources of those cases vary in terms of the level; for instance, some of them were provided by the General Court in Riyadh; others were provided by the Supreme Judicial Council; and others were obtained from the Modawanat-Al-Ahkam, which is the publication of the Ministry of Justice containing a variety of cases. Cases in the international domain were brought mainly from the Working Group of Arbitrary Detention in the HRC. The study provides suggestions necessary for the Law of Criminal Procedure in relation to specific articles.

This thesis examines the interpretation and application of the Criminal Justice Act 2003 (UK), Part 11 Chapter 1, which came into force on 15 December 2004. Part 11 Chapter 1 concerns evidence of bad character, a concept approximately comparable with common law similar fact evidence, in relation to all parties who may be connected with a criminal trial. The admission and use of similar fact evidence has often been the subject of controversy, and the significant changes made by the CJA 2003 have attracted their own body of support and criticism. The nine chapters of this thesis attempt an in-depth study into the impact of the legislation on the robustness and effectiveness of the criminal trial, and consider whether the criminal trial is suited to the level of exposure of bad character now facilitated by the CJA. In particular, the thesis focuses upon the key provisions governing the uses of bad character evidence of the defendant: the seven gateways set out in s 101 of the CJA. The operation of those gateways and their accompanying explanatory provisions is examined through a combination of engagement with the Law Commission’s Report 273 (which preceded the enactment of the legislation), the range of Court of Appeal cases dealing with the legislation, and academic commentary. It was foreshadowed by commentators and early case law that the new provisions might not be easy to interpret or apply, and subsequent cases have borne out this prediction. An analysis of the bad character provisions suggests that, even though the CJA was intended to provide clarity in regulation, it has itself led to confusion in some important respects. Certain central terms lack definition, and some provisions have unintended consequences. The case law reflects this in its frequent, often brief, and sometimes inconsistent analysis of the specific parts of the legislation, which can make it difficult to determine the defendant’s guilt or innocence in a precise and scrupulous manner.

Systematic reviews have consistently found that moderate intensity physical activity levels at or above a threshold value of 150 minutes per week reliably deliver cardiovascular, metabolic and musculo-skeletal health benefits. As a result, this threshold value has been widely adopted as an aspirational, public health goal throughout the world. However, while epidemiological and laboratory studies have established clear links between physical activity and sleep outcomes, the evidence base does not yet provide guidelines on minimum levels of exercise likely to reduce insomnia symptoms and improve sleep quality. Such a guideline, if evidence based, could greatly clarify advice, and accelerate the use of physical activity goals to improve sleep outcomes in behavioural sleep medicine and public health. This thesis examined the current public-health recommendation of 150 minutes of moderate intensity activity per week in relation to sleep outcomes. To commence, it established a population-level pattern of the relationship between levels of physical activity and sleep quality by reviewing relevant epidemiological evidence. Exploratory analyses were then conducted using data from an ongoing longitudinal study of physical activity and health outcomes among older people (aged 65 years and above) in which respondents were classified as walking at or above, or below the recommended threshold of 150 minutes per week. In regression models controlling for health and demographic factors, these analyses showed that higher levels of walking were significantly and independently associated with a lower likelihood of either reporting insomnia symptoms (OR = 0.67 (95% CI = 0.45 0.91) p=0.04), or experiencing poor sleep efficiency (OR = 0.70 (95% CI = 0.52 0.94 p=0.02). Using the same data, the predictive validity of this activity threshold was then confirmed in a 27-year survival analysis which showed a significantly decreased all-cause mortality risk associated with the higher level of walking (HR = 0.75 (95% CI = 0.65 - 0.86) p<0.01). These findings offered proof of concept that physical activity-sleep relationships operated on a continuum, with sleep benefits possible even at relatively low levels of activity. Experimental evidence on the acute and sustained effects of physical activity on sleep quality was then analysed and discussed. Outcomes from this review, together with the preliminary analyses described above, were then used to inform the design of a randomised controlled trial to investigate the effects on sleep quality of increasing physical activity to currently recommended levels among sedentary people with insomnia. A total of 41 sedentary adults meeting DSM-IV criteria for insomnia (30 female; mean age 59.8??9.5) were randomised to a physical activity group (???150 minutes moderate intensity activity/week) or a waiting list control group. The principal outcome was Insomnia Severity Index (ISI) change 6 months post baseline; secondary outcomes were anxiety (using the State Trait Anxiety Inventory) and depression (Beck Depression Inventory II). Physical activity was assessed using Actigraph GTX3+ accelerometers. Outcomes were assessed in univariate general linear models, adjusted for baseline confounders. Activity and sleep assessments did not differ at baseline. At 6 months post baseline the intervention group engaged in 213 min/week of moderate intensity PA, compared to the control group (82 min/week). Compared to the control group, the intervention group showed significant improvement in the ISI score at 6 months F(1,28) = 5.16, p=0.03), adjusted means difference = 3.37, with an adjusted Cohen's d =.78 (95% CI 0.10 1.45). There was a significant improvement in trait anxiety, and depression outcomes post-intervention, F(6,28)=4.41, p=0.05, and F(6,28)=5.61, p=0.02, respectively. The results showed that increasing activity in line with current guidelines could deliver clinically significant improvements in sleep quality and mood outcomes among inactive adults with insomnia. While the effect sizes are modest, the pattern of results reported here allow for two conclusions with clear implications for public health: 1) measures to increase levels of physical activity above the currently recommended threshold of 150 minutes per week could usefully be added to other approaches to insomnia management; and 2) the likelihood of improved sleep quality should be routinely added to those evidence-based cardiovascular and metabolic benefits most frequently associated with increased physical activity in behaviour change initiatives.

In cluster randomized trials (CRTs), groups are randomized to treatment arms rather than individuals while the outcome is assessed on the individuals within each cluster. Individuals within clusters tend to be more similar than in a randomly selected sample, which poses issues with dependence, which may lead to underestimated standard errors if ignored. To adjust for the correlation between individuals within clusters, two main approaches are used to analyze CRTs: cluster-level and individual-level analysis. In a cluster-level analysis summary measures are obtained for each cluster and then the two sets of cluster-specific measures are compared, such as with a t-test of the cluster means. A mixed model which takes into account cluster membership is an example of an individual-level analysis. We used a simulation study to quantify and compare power and bias of these two methods. We further take into account the effect of missing data. Complete datasets were generated and then data were deleted to simulate missing completely at random (MCAR) and missing at random (MAR) data. A balanced design, with two treatment groups and two time points was assumed. Cluster size, variance components (including within-subject, within-cluster and between-cluster variance) and proportion of missingness were varied to simulate common scenarios seen in practice. For each combination of parameters, 1,000 datasets were generated and analyzed. Results of our simulation study indicate that cluster-level analysis resulted in substantial loss of power when data were MAR. Individual-level analysis had higher power and remained unbiased, even with a small number of clusters.

Background: Clinical trials represent a significant percentage of the time and cost to bring a drug through the development process and to Food and Drug Administration approval. Despite how critical these trials are to the drug development process, many studies are underpowered due to low accrual. This translates to valuable questions regarding the safety and effectiveness of new agents being left unanswered, requiring additional time and studies. A call for reform of the industry has been made by stakeholders in the clinical research enterprise; however, national change is slow. Thus sites that conduct clinical research must find methods to increase efficiency within the burdensome system currently in place. Throughout cancer centers adhering to the National Cancer Institute (NCI) Cancer Center Support Grant guidelines, efficiencies have been explored individually; however, there is a gap in knowledge on what factors affect sites system-wide. This dissertation seeks to examine factors that affect clinical trial efficiency in the areas of study activation looking at the outcome of local clinical trial accrual. Methods: Protocol and site-specific clinical trial administration data was collected regarding closed, interventional treatment and supportive care clinical trials from cancer centers adhering to NCI Cancer Center Support Grant guidelines during a five-year time period (2009-2014). Study characteristic analyses and hierarchical regression modeling was used to explore the effect of feasibility committee use and protocol workload on the outcomes of clinical trial accrual and time to activate a clinical trial. Sensitivity analyses were utilized when considering protocol workload to account for studies that had not yet closed to accrual, and thus were not included in this dataset. In addition, protocol- and site-specific variables were used to build regression models used to predict clinical trial accrual. Sensitivity, specificity, and accuracy were compared to the current standard, the institutional disease team. Results: Sixteen centers contributed a total of 5,787 protocols (range 93-697 studies). These studies accrued 49,319 subjects. Of all studies, 1,053 (18%) accrued zero subjects. Disease teams predicted 221% of actual accrual. Seven institutions submitted protocol workload information for 2,133 studies (36.9%) and 14,229 accruals (28.9%). Controlling for effect modifiers and interactions, and adjusting for institution, a statistically significant increase in clinical trial accrual and decrease in activation time was seen with the use of a feasibility committee. Regulatory protocol workload was significantly associated with clinical trial accrual and activation time; however, a single, definitive protocol workload was not identified that both minimized activation time and maximized clinical trial accrual. Protocol workload most often maximized accrual at workloads of between 3.5 and 5.0 protocols per staff member/FTE and minimized activation time at workloads between 1.0 and 1.9 protocols per staff member/FTE. Regression models predicted accrual more accurately than disease teams at all 16 centers, with site-specific models consistently having the best performance (versus an adjusted, hierarchical model). Conclusion: Despite institutional differences in variable association with accrual and activation times, the utilization of a feasibility committee was shown to improve clinical trial accrual as well as decrease activation time. Using systematic methods for examining study activation and accrual efficiencies resulted in the development of models that predicted clinical trial accrual better than the current standard (disease team prediction) at all participating centers. Further research is needed to better define and determine optimal workload. This information and these models may better inform study planning and resource allocation decisions by local stakeholders (administrators and investigators) in the clinical research enterprise.

This thesis describes the development of separate assays to measure coenzyme Q₁₀ (CoQ₁₀) and vitamin K. Coenzyme Q is essential for the mitochondrial electron transport chain, and vitamin K for the blood coagulation cascade. Vitamin K deficiency is associated with haemorrhagic disease of the new-born, and CoQ₁₀ deficiency with HMG-CoA-reductase inhibitor (statin) therapy and heart failure. Coenzyme Q and vitamin K are usually measured by HPLC, using electrochemical and ultraviolet, and electrochemical and fluorescence detection, respectively. For vitamin K1, the limit of detection achieved using fluorescence and electrochemical detection was 0.28 and 0.12 nmol/L, respectively. Sensitivity of fluorescence detection is improved by using protic solvents in the mobile phase, and platinum-black catalysed alcohol reduction. The lipophilicity and low endogenous concentrations of vitamin K1 hinder its measurement, and further work is required to produce a rapid, reliable and robust assay for its measurement in human plasma. The limits of detection achieved using fluorescence, ultraviolet and electrochemical detection to measure CoQ₁₀ were 29, 4.8, and 0.34 nmol/L, respectively. Plasma CoQ₁₀ is not stable during long term storage at -13 ℃, but at -80 ℃ it is stable for at least 18 months. The reference interval for plasma total CoQ₁₀ in the New Zealand population is 0.47 - 1.80 µmol/L. There is no clinical requirement for stratification of the reference interval according to gender. Coenzyme Q₁₀ in human plasma is homeostatically controlled, varying little over a two month interval in healthy young males. Coenzyme Q₁₀ supplements have significantly different bioavailability, with the median increase in plasma CoQ₁₀ ranging from 0.14 to 0.59 µmol/L for seven different supplement brands. There is a large inter-individual variation in CoQ₁₀ absorption, and hence plasma concentrations should be monitored during supplementation. A plateau in CoQ₁₀ absorption, from a single dose, at approximately 200 mg suggests that the maximum dose ingested at one time should be 200 mg or less. Q-Gel capsules containing 30 mg of CoQ₁₀ are twice as effective at raising blood CoQ₁₀ as 100 mg capsules. Plasma CoQ₁₀ in patients with chronic heart failure are significantly lowered by approximately 33% when these patients receive Atorvastatin for six weeks. The absolute decrease in CoQ₁₀ showed a significant correlation with worsening endothelial function (r = + 0.548, p = 0.011). Coenzyme Q₉ was shown to be present in human plasma with a reference interval of 8.8 - 47.0 nmol/L.