The purpose of the current study was to develop a manualized treatment for fibromyalgia syndrome (FM) and to examine the efficacy of the treatment in a randomized controlled clinical trial. FM is a chronic musculoskeletal pain disorder characterized by tender points and generalized pain. Depression, chronic fatigue, and sleep disturbance are common. A biopsychosocial model served as a framework for understanding FM by integrating psychological, social, and physical factors. Cognitive-behavioural therapy (CBT), an empirically validated treatment for arthritis, has also been used with FM patients in an attempt to improve pain control, reduce disability, and increase self-efficacy. Overall, the attention/placebo controlled studies employing CBT as a treatment for FM show that it is not superior to a credible attention placebo. The current study attempted to combine the necessary components of CBT with interpersonal therapy to address relational patterns and personality characteristics that can affect ability to cope with chronic pain. One hundred and five women diagnosed with FM by a rheumatologist were randomly assigned to the CBT-interpersonal treatment condition or an attention-control condition. There were 8 treatment groups with a mean of 6-7 participants in each. The treatment consisted of weekly 2-hour sessions over 8 consecutive weeks. Outcome measures included: FM impact, pain, health care utilization, depression, coping, and self-efficacy. An intention-to-treat analysis was conducted. Results showed that the impact of FM symptoms was reduced following treatment compared to the control group and this was statistically and clinically significant, but was not maintained at 3-month follow-up. Significant improvements were also observed in coping strategies, some of which were maintained at follow-up. Importantly, self-efficacy improved significantly following treatment compared to the control group. Self-efficacy beliefs have been related to pain, coping efforts, disability, and psychological functioning. Directions for future research may include a focus on long-term maintenance of treatment gains that may be mediated by improvements in self-efficacy. There is strong evidence that changes in self-efficacy are enduring and affect changes in health behaviours and health status.

The purpose of the current study was to develop a manualized treatment for fibromyalgia syndrome (FM) and to examine the efficacy of the treatment in a randomized controlled clinical trial. FM is a chronic musculoskeletal pain disorder characterized by tender points and generalized pain. Depression, chronic fatigue, and sleep disturbance are common. A biopsychosocial model served as a framework for understanding FM by integrating psychological, social, and physical factors. Cognitive-behavioural therapy (CBT), an empirically validated treatment for arthritis, has also been used with FM patients in an attempt to improve pain control, reduce disability, and increase self-efficacy. Overall, the attention/placebo controlled studies employing CBT as a treatment for FM show that it is not superior to a credible attention placebo. The current study attempted to combine the necessary components of CBT with interpersonal therapy to address relational patterns and personality characteristics that can affect ability to cope with chronic pain. One hundred and five women diagnosed with FM by a rheumatologist were randomly assigned to the CBT-interpersonal treatment condition or an attention-control condition. There were 8 treatment groups with a mean of 6-7 participants in each. The treatment consisted of weekly 2-hour sessions over 8 consecutive weeks. Outcome measures included: FM impact, pain, health care utilization, depression, coping, and self-efficacy. An intention-to-treat analysis was conducted. Results showed that the impact of FM symptoms was reduced following treatment compared to the control group and this was statistically and clinically significant, but was not maintained at 3-month follow-up. Significant improvements were also observed in coping strategies, some of which were maintained at follow-up. Importantly, self-efficacy improved significantly following treatment compared to the control group. Self-efficacy beliefs have been related to pain, coping efforts, disability, and psychological functioning. Directions for future research may include a focus on long-term maintenance of treatment gains that may be mediated by improvements in self-efficacy. There is strong evidence that changes in self-efficacy are enduring and affect changes in health behaviours and health status.

In this thesis we use greedy randomize adaptive search procedure (GRASP) to solve the traveling salesman problem (TSP). Starting with nearest neighbor method to construct the initial TSP tour, we apply the 2-opt and the path-relinking method for the initial tour improvement. To increase 2-opt search speed, fixed-radius near neighbor search and don0t − look bit techniques are introduced. For the same reason a new efficient data structure, the reverse array, is proposed to represent the TSP tour. Computational results show that GRASP gives fairly good solutions in a short time.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (p. 108-112).

Most individuals who die by suicide have contact with a physician in the year before their death. There are no randomized trials that have evaluated suicide intervention training for medical students or physicians. The objective of this study was to determine the effectiveness of a gatekeeper training program on suicide intervention behavior using Objective Structured Clinical Examinations (OSCEs) in medical students. A randomized controlled trial design was used. Participants were 112 undergraduate medical students at the University of Manitoba. The 2-day Applied Suicide Intervention Skills Training (ASIST) program was completed by half of the participants, according to a stratified block randomization design. Scores on OSCEs and scores on the Suicide Intervention Response Inventory (SIRI-2) were used as objective measures of intervention behaviors. There was a a significant Group-by-Time interaction on OSCE data, demonstrating that medical students who received ASIST performed significantly better than medical students who received training as usual (p<.001). The two groups did not differ significantly from each other on the SIRI-2 (p=.78). ASIST training improved the ability of medical students to detect and intervene with a standardized suicidal patient as assessed by OSCEs, compared to medical school training as usual. This study provides support for ASIST training for medical students to develop skills in recognition and management of suicidal patients. / October 2015

Despite the rapid development of palliative care teams, evidence for their effectiveness in oncology care is lacking. This thesis reviews and contributes towards this evidence, focusing on the randomized controlled trial as a research method. We conducted a systematic review of 22 trials reviewed that measured effectiveness of specialized palliative care. Family satisfaction with care improved in seven of 10 studies, but only four of 13 trials assessing quality of life and one of 14 assessing symptoms showed a benefit of the intervention. Conclusions were limited by methodologic problems in all of the trials. We conducted a phase II study of the efficacy of a palliative care team for symptom control and satisfaction of 150 patients with advanced cancer. Symptom severity (Edmonton Symptom Assessment System Distress Score) improved at one week and one month, as did patient satisfaction (all p<0.0001). We investigated factors associated with symptom severity and response for patients enrolled in the phase II study. Symptoms at baseline were worse for women and those with worse performance status (both p<0.005); female gender and worse baseline symptom severity independently predicted symptom improvement (both p<0.05). We planned and initiated an RCT of the effectiveness of an early palliative care intervention for improvement of health-related quality of life (HRQL) and satisfaction with care. Using baseline data from this RCT, we examined factors associated with HRQL in patients with advanced cancer. The strongest determinants of overall HRQL (combined FACT-G total score and FACIT-Sp Meaning and Peace subscore) were increased age (p<0.001), good performance status (p<0.001) and survival time >6 months (p=0.001). Compared to patients receiving cancer treatment, those awaiting new treatment had worse emotional well-being (p<0.001) while those on surveillance or whose treatment had been stopped had worse existential well-being (p=0.03). Male gender predicted better emotional and physical well-being and lower income predicted worse social well-being. Lastly, we developed recommendations for those planning an RCT in a palliative care population, incorporating information from the studies presented. Although such RCTs are challenging to conduct, they are feasible and necessary to improve the evidence base for the treatment of patients with advanced cancer.

Despite the rapid development of palliative care teams, evidence for their effectiveness in oncology care is lacking. This thesis reviews and contributes towards this evidence, focusing on the randomized controlled trial as a research method. We conducted a systematic review of 22 trials reviewed that measured effectiveness of specialized palliative care. Family satisfaction with care improved in seven of 10 studies, but only four of 13 trials assessing quality of life and one of 14 assessing symptoms showed a benefit of the intervention. Conclusions were limited by methodologic problems in all of the trials. We conducted a phase II study of the efficacy of a palliative care team for symptom control and satisfaction of 150 patients with advanced cancer. Symptom severity (Edmonton Symptom Assessment System Distress Score) improved at one week and one month, as did patient satisfaction (all p<0.0001). We investigated factors associated with symptom severity and response for patients enrolled in the phase II study. Symptoms at baseline were worse for women and those with worse performance status (both p<0.005); female gender and worse baseline symptom severity independently predicted symptom improvement (both p<0.05). We planned and initiated an RCT of the effectiveness of an early palliative care intervention for improvement of health-related quality of life (HRQL) and satisfaction with care. Using baseline data from this RCT, we examined factors associated with HRQL in patients with advanced cancer. The strongest determinants of overall HRQL (combined FACT-G total score and FACIT-Sp Meaning and Peace subscore) were increased age (p<0.001), good performance status (p<0.001) and survival time >6 months (p=0.001). Compared to patients receiving cancer treatment, those awaiting new treatment had worse emotional well-being (p<0.001) while those on surveillance or whose treatment had been stopped had worse existential well-being (p=0.03). Male gender predicted better emotional and physical well-being and lower income predicted worse social well-being. Lastly, we developed recommendations for those planning an RCT in a palliative care population, incorporating information from the studies presented. Although such RCTs are challenging to conduct, they are feasible and necessary to improve the evidence base for the treatment of patients with advanced cancer.

One of the most fundamental computational problems in biology is that of inferring evolutionary histories of groups of species from sequence data. Such evolutionary histories, known as phylogenies are usually represented as binary trees where leaves represent extant species, whereas internal nodes represent their shared ancestors. As the amount of sequence data available to biologists increases, very fast phylogenetic reconstruction algorithms are becoming necessary. Currently, large sequence alignments can contain up to hundreds of thousands of sequences, making traditional methods, such as Neighbor Joining, computationally prohibitive. To address this problem, we have developed three novel fast phylogenetic algorithms. The first algorithm, QTree, is a quartet-based heuristic that runs in O(n log n) time. It is based on a theoretical algorithm that reconstructs the correct tree, with high probability, assuming every quartet is inferred correctly with constant probability. The core of our algorithm is a balanced search tree structure that enables us to locate an edge in the tree in O(log n) time. Our algorithm is several times faster than all the current methods, while its accuracy approaches that of Neighbour Joining. The second algorithm, LSHTree, is the first sub-quadratic time algorithm with theoretical performance guarantees under a Markov model of sequence evolution. Our new algorithm runs in O(n^{1+γ(g)} log^2 n) time, where γ is an increasing function of an upper bound on the mutation rate along any branch in the phylogeny, and γ(g) < 1 for all g. For phylogenies with very short branches, the running time of our algorithm is close to linear. In experiments, our prototype implementation was more accurate than the current fast algorithms, while being comparably fast. In the final part of this thesis, we apply the algorithmic framework behind LSHTree to the problem of placing large numbers of short sequence reads onto a fixed phylogenetic tree. Our initial results in this area are promising, but there are still many challenges to be resolved.

Maternal and child undernutrition are a significant problem in the developing world, with serious consequences for human health and socio-economic development. In Cambodia, 55% of children, 43% of women of reproductive age, and 50% of pregnant women are anemic. Current prevention and control practices rely on supplementation with iron pills or large-scale food fortification, neither of which are affordable or feasible in rural Cambodia. In the study areas, 97% of women did not meet their daily iron requirements. The current research focuses on the design and evaluation of an innovative iron supplementation technique. A culturally acceptable, inexpensive and lightweight iron ingot was designed to resemble a fish species considered lucky in Khmer culture. The ingot, referred to as ‘try sabay’ or ‘happy fish’, was designed to supply iron at a slow, steady rate. Iron leaching was observed in water and soup samples prepared with the iron fish when used concurrently with an acidifier. More than 75% of daily iron requirements can be met with regular use. Its use in the common pot of soup or boiled water provides supplementation to the entire family. The effectiveness of the iron fish was investigated in a randomized community trial involving 310 women in rural Cambodia. Blood samples were taken at baseline and every three months thereafter, over a 12-month trial period. Significant increases in hemoglobin concentrations were observed in women allocated an iron fish when compared to controls throughout the study, with an endline difference of 11.6 g/L. Significant improvements in serum ferritin concentration were observed at 9 months (6.9 ng/mL) and endline (30.8 ng/mL) in women who used an iron fish regularly when compared to the control group. Overall, use of the iron fish led to a two-fold reduction in the prevalence of anemia. The supplement was used daily by 94% of the households at the end of the trial. The study highlights the acceptability and effectiveness of a fish-shaped iron ingot as a means of improving dietary iron content. It offers a promising, simple solution to iron deficiency anemia if the project can be scaled-up for use throughout the country. / Canadian Institutes of Health Research; International Development Research Centre; University of Guelph

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