No description available.

Background: Inverse-probability-of-treatment-weighted estimation (IPTW) of marginal structural models was proposed to adjust for time-varying confounders that are influenced by prior treatment use. It is unknown whether pharmacoepidemiologic studies that applied IPTW conformed to the recommendations proposed by methodological studies. In addition, no previous study has compared the performance of different analytic strategies adopted in IPTW analyses. Objectives: This project aims 1) to review the reporting practice of pharmacoepidemiologic studies that applied IPTW, 2) to compare the validity and precision of several approaches to constructing weight, 3) to use IPTW to estimate the effectiveness of glucosamine and chondroitin in treating osteoarthritis. Methods: We systematically retrieved pharmacoepidemiologic studies that were published in 2012 and applied IPTW to estimate the effect of a time-varying treatment. Under a variety of simulated scenarios, we assessed the performance of four analytic approaches what were commonly used in studies conducting IPTW analyses. Finally, using data from Osteoarthritis Initiative, we applied IPTW to estimate the long-term effectiveness of glucosamine and chondroitin on treating knee osteoarthritis. Results: The practice of reporting use of IPTW in pharmacoepidemiologic studies was suboptimal. The majority of reviewed studies did not report that the positivity assumption was assessed, and several studies used unstablized weights or did not report that the stabilized weights were used. With data simulation, we found that intention-to-treat analyses underestimated the actual treatment effect when there was non-null treatment effect and treatment non-adherence. This underestimation was linearly correlated with adherence levels. As-treated analyses that took into account the complex mechanism of treatment use generated approximately unbiased estimates without sacrificing the estimate precision when the treatment effect was non-null. Finally, after adjustment for potential confounders with marginal structural models, we found no clinically meaningful benefits of glucosamine/chondroitin in relieving knee pain, stiffness and physical function or slowing joint space narrowing. Conclusions: It may be prudent to develop best practices of reporting the use of IPTW. Studies performing intention-to-treat analyses should report the levels of adherence after treatment initiation, and studies performing as-treated analyses should take into the complex mechanism of treatment use in weight construction.

Can we fruitfully use the same macroeconomic model to forecast and to perform policy analysis? There is a tension between a model’s ability to forecast accurately and its ability to tell a theoretically consistent story. The aim of this dissertation is to propose ways to soothe this tension, combining structural and reduced-form models in order to have models that can effectively do both.

No description available.

Cognitive-behavioural based models of chronic pain contend that appraisals of harm affect the individual�s response to pain. It has been suggested that fear of pain and/or anxiety sensitivity predispose individuals to chronicity. However, other factors such as pain self-efficacy are believed to mediate between experience of pain and disability. According to this view, pain is maintained through hypervigilance towards painful sensations and subsequent avoidance. Four studies were conducted in order to evaluate the structure of fear-avoidance models of chronic pain, and also, to examine the role of hypervigilance as an underlying mechanism in maintenance of pain. In study one, using a sample of 207 consecutive patients, two models were tested. First, fear of movement model as proposed by Vlaeyen et al. (1995a) was examined. It was found that negative affectivity has direct effects on the fear and avoidance of pain, which in turn, contributes to disability. In total, fear/avoidance accounted for a significant amount of the variance of disability. In addition, severity of pain was found to increase pain disability, while itself is influenced still by negative affectivity. These findings supported the model of fear of pain as described by Vlaeyen et al. (1995a). Further, we found that self-efficacy may mediate the impact of fear of pain on disability and reduces the perceived physical disability. At the same time, self-efficacy was shown to have direct reductive impact on disability. However, both studies indicated that people who are fearful in response to pain are more likely to develop disability, although self-efficacy may play a moderating role. In the studies one, two, and three, the role of hypervigilance in over attending to pain was investigated. In study one a large sample of 168 chronic pain patients were studied. Questionnaires measuring different aspects of pain and a computerised version of the Dot-Probe Task were administered. Four types of words related to different dimensions of pain and matched neutral words were used as stimuli. Reaction times in response to the stimuli were recorded. A factorial design 3x4x2x2 and ANOVAs were employed to analyse the data. Chronic pain patients showed a cognitive bias to sensory pain words relative to affective, disability, and threat-related words. However, contrary to expectations, those high in fear of pain responded more slowly to stimuli than those less fearful of pain. These results suggest that patients with chronic pain problems selectively attend to sensory aspects of pain. However, selective attention appears to depend upon the nature of pain stimuli. For those who are highly fearful of pain they may not only selectively attend to pain-related information but also have difficulty disengaging from those stimuli. In study two, 35 chronic pain patients were compared with the same number matched healthy subjects. Both groups completed measures of fear of pain, anxiety sensitivity, depression and anxiety, in addition to dot probe task. Results indicated that both groups show similar attentional bias to sensory words in comparison with other word types. However, the level of this biasness was higher for chronic pain patients. Lack of significant differences between patients and controls is discussed in the context of possible evolutionary value of sensitivity to pain as an adaptive reaction in healthy controls, and contrary, as a maladaptive response to pain in chronic pain patients. The results of the previous research suggest that chronic pain patients demonstrate cognitive biases towards pain-related information and that such biases predict patient functioning. The forth study examined the degree to which a successful cognitive-behavioural program was able to modify the observed attentional bias towards sensory pain words. Forty-two patients with chronic pain conditions for more than three months were recruited prior to commencing a cognitive-behavioural pain management program. Participants were assessed before the program, after the program and at one-month follow-up. Results confirmed that chronic pain patients exhibited biased attention towards sensory pain-related words at pre-treatment. These biases were still evident at post-treatment, but were no longer statistically significant at follow up. Multiple regression analyses indicated that the changes in attentional bias towards sensory words between post-treatment and follow-up were predicted by pre- to post- treatment changes in fear of movement (Tampa Scale for Kinesiophobia) but not other relevant variables, such as fear of pain or anxiety sensitivity. These results demonstrate that successful cognitive-behavioural treatments can reduce selective attention, thought to be indicative of hypervigilance towards pain. Moreover, these biases appear to be changed by reducing the fear associated with movement. Theoretically, these results provide support for the fear of (re)injury model of pain. Clinically, this study supports the contention that fear of (re)injury and movement is an appropriate target of pain management and that reducing these fears causes patients to attend less to pain-related stimuli.

Work on Expert Systems has received extensive attention recently, prompting growing interest in a range of environments. Much has been made of the basic concept and the rule-based system approach typically used to construct the programs. Perhaps this is a good time then to review what we know, assess the current prospects, and suggest directions appropriate for the next steps of basic research. I'd like to do that today and propose to do it by taking you on a journey of sorts, a metaphorical trip through the State of the Art of Expert Systems. We'll wander about the landscape, ranging from the familiar territory of the Land of Accepted Wisdom, to the vast unknowns at the Frontiers of Knowledge. I guarantee we'll all return safely, so come along...

The current investigation compared the fit of three models of internalizing in middle childhood: (1) a unitary factor model, (2) a two-factor model corresponding to the DSM-IV Anxiety/Depression distinction, and (3) a two-factor model corresponding to the Fear/Distress distinction observed in structural studies of adult psychopathology (Krueger, 1999; Slade & Watson, 2006). Mothers of 344 children (50.6% female, mean age = 9.97, SD = .82) reported on childhood internalizing symptoms and personality traits. Confirmatory factor analyses revealed acceptable fit indices for all three models. The unitary factor model provided the most parsimonious fit to the data. Although the structural analyses suggested that internalizing subfactors were not differentiated in middle childhood, hierarchical regression analyses revealed that personality dimensions uniquely predicted fear and distress disorders. These results suggest that personality foreshadows later psychopathology structure before it is manifest at the symptom level.

The current investigation compared the fit of three models of internalizing in middle childhood: (1) a unitary factor model, (2) a two-factor model corresponding to the DSM-IV Anxiety/Depression distinction, and (3) a two-factor model corresponding to the Fear/Distress distinction observed in structural studies of adult psychopathology (Krueger, 1999; Slade & Watson, 2006). Mothers of 344 children (50.6% female, mean age = 9.97, SD = .82) reported on childhood internalizing symptoms and personality traits. Confirmatory factor analyses revealed acceptable fit indices for all three models. The unitary factor model provided the most parsimonious fit to the data. Although the structural analyses suggested that internalizing subfactors were not differentiated in middle childhood, hierarchical regression analyses revealed that personality dimensions uniquely predicted fear and distress disorders. These results suggest that personality foreshadows later psychopathology structure before it is manifest at the symptom level.

No description available.

Cognitive-behavioural based models of chronic pain contend that appraisals of harm affect the individual�s response to pain. It has been suggested that fear of pain and/or anxiety sensitivity predispose individuals to chronicity. However, other factors such as pain self-efficacy are believed to mediate between experience of pain and disability. According to this view, pain is maintained through hypervigilance towards painful sensations and subsequent avoidance. Four studies were conducted in order to evaluate the structure of fear-avoidance models of chronic pain, and also, to examine the role of hypervigilance as an underlying mechanism in maintenance of pain. In study one, using a sample of 207 consecutive patients, two models were tested. First, fear of movement model as proposed by Vlaeyen et al. (1995a) was examined. It was found that negative affectivity has direct effects on the fear and avoidance of pain, which in turn, contributes to disability. In total, fear/avoidance accounted for a significant amount of the variance of disability. In addition, severity of pain was found to increase pain disability, while itself is influenced still by negative affectivity. These findings supported the model of fear of pain as described by Vlaeyen et al. (1995a). Further, we found that self-efficacy may mediate the impact of fear of pain on disability and reduces the perceived physical disability. At the same time, self-efficacy was shown to have direct reductive impact on disability. However, both studies indicated that people who are fearful in response to pain are more likely to develop disability, although self-efficacy may play a moderating role. In the studies one, two, and three, the role of hypervigilance in over attending to pain was investigated. In study one a large sample of 168 chronic pain patients were studied. Questionnaires measuring different aspects of pain and a computerised version of the Dot-Probe Task were administered. Four types of words related to different dimensions of pain and matched neutral words were used as stimuli. Reaction times in response to the stimuli were recorded. A factorial design 3x4x2x2 and ANOVAs were employed to analyse the data. Chronic pain patients showed a cognitive bias to sensory pain words relative to affective, disability, and threat-related words. However, contrary to expectations, those high in fear of pain responded more slowly to stimuli than those less fearful of pain. These results suggest that patients with chronic pain problems selectively attend to sensory aspects of pain. However, selective attention appears to depend upon the nature of pain stimuli. For those who are highly fearful of pain they may not only selectively attend to pain-related information but also have difficulty disengaging from those stimuli. In study two, 35 chronic pain patients were compared with the same number matched healthy subjects. Both groups completed measures of fear of pain, anxiety sensitivity, depression and anxiety, in addition to dot probe task. Results indicated that both groups show similar attentional bias to sensory words in comparison with other word types. However, the level of this biasness was higher for chronic pain patients. Lack of significant differences between patients and controls is discussed in the context of possible evolutionary value of sensitivity to pain as an adaptive reaction in healthy controls, and contrary, as a maladaptive response to pain in chronic pain patients. The results of the previous research suggest that chronic pain patients demonstrate cognitive biases towards pain-related information and that such biases predict patient functioning. The forth study examined the degree to which a successful cognitive-behavioural program was able to modify the observed attentional bias towards sensory pain words. Forty-two patients with chronic pain conditions for more than three months were recruited prior to commencing a cognitive-behavioural pain management program. Participants were assessed before the program, after the program and at one-month follow-up. Results confirmed that chronic pain patients exhibited biased attention towards sensory pain-related words at pre-treatment. These biases were still evident at post-treatment, but were no longer statistically significant at follow up. Multiple regression analyses indicated that the changes in attentional bias towards sensory words between post-treatment and follow-up were predicted by pre- to post- treatment changes in fear of movement (Tampa Scale for Kinesiophobia) but not other relevant variables, such as fear of pain or anxiety sensitivity. These results demonstrate that successful cognitive-behavioural treatments can reduce selective attention, thought to be indicative of hypervigilance towards pain. Moreover, these biases appear to be changed by reducing the fear associated with movement. Theoretically, these results provide support for the fear of (re)injury model of pain. Clinically, this study supports the contention that fear of (re)injury and movement is an appropriate target of pain management and that reducing these fears causes patients to attend less to pain-related stimuli.