Peripheral arterial disease (PAD) is a significant cause of morbidity and mortality in both economically developed and developing countries. Although the risk factors for PAD are well described, patients with PAD who develop critical lower limb ischaemia (CLI) are frequently asymptomatic prior to the development of CLI and the factors that determine outcomes in these patients are unclear. In the present thesis I therefore evaluated a number of potential novel risk approaches in patients with CLI, both for the development of CLI, as well as approaches that may better predict outcomes in CLI. Atherosclerotic disease, the major pathophysiological process responsible for PAD, is now well recognized as causing an increased large artery pulse wave velocity (PWV) and central aortic pulse pressure (PPc). However, through the presence of arterial stenoses proximal to the femoral artery, carotid-femoral PWV may be reduced in advanced PAD. I therefore aimed to determine whether in the context of increases in central aortic pulse pressure (PPc), decreases in carotid-femoral pulse wave velocity (PWV) predicts the presence of advanced PAD. Applanation tonometry and vascular ultrasound were employed to assess carotid-femoral PWV, PPc and carotid intima-media thickness (IMT) in 1030 randomly selected healthy adults from a community sample and 217 patients with CLI. With adjustments for confounders, participants with CLI had an increased carotid IMT (p<0.0001) and PPc (p<0.0001), but a markedly reduced PWV (m/sec)(CLI=4.38±3.14, Community sample=6.78±2.47, p<0.0001). PWV was strongly correlated with PPc (r=0.53, p<0.0001) in the community sample, but not in CLI (r=-0.04). A stiffness mismatch index (PPc/PWV) showed increased values in participants with CLI over the full adult age range assessed. With carotid IMT, PPc or aortic augmentation index in the same regression model, an increase in the stiffness mismatch index (PPc/PWV) was independently associated with CLI (p<0.0001) and a PPc/PWV value>upper 95% confidence interval in the community sample strongly predicted CLI (odds ratio=27.1, p<0.0001). In conclusion, in the context of an increased PPc,carotid-femoral PWV is markedly reduced in CLI. These results suggest that a stiffness mismatch index (PPc/PWV) may be a new risk marker for advanced PAD.As infection with the human immunodeficiency virus (HIV) is common in South Africa, and this is increasingly translating into cardiovascular disease including CLI, it is important to be able to detect those HIV positive patients whom will develop CLI. Although ankle-brachial index may detect PAD, more general screening tools to detect those at risk of cardiovascular events are required. In this regard, carotid IMT measurements may be useful.The extent to which human HIV is associated with increases in IMT independent of conventional cardiovascular risk factors is unclear. Hence, I evaluated whether independent of conventional risk factors, an increased carotid IMT occurs in African HIV infected patients with chronic critical limb ischemia (CLI). Carotid IMT was measured in 217 sequentially recruited patients with CLI, 25 of whom were HIV positive and in 430 randomly selected controls from a community sample. As compared to HIV negative patients with CLI, HIV positive patients were younger (49±10 vs. 64±11 years, p<0.0001) and had a markedly lower prevalence of hypertension and diabetes mellitus (p<0.0001), but a similar proportion of patients smoked (76% vs. 67%). However, as compared to patients with CLI who were HIV negative, HIV positive patients had a similar increase in carotid IMT (HIV positive=0.75±0.14 mm; HIV negative=0.79±0.14 mm; Controls=0.64±0.15, p<0.0001 versus Controls) even after adjustments for age, sex and conventional risk factors (HIV positive=0.75.±0.13 mm; HIV negative=0.73±0.15 mm, Controls=0.66±0.15, p<0.005). IMT was similarly increased in HIV positive patients with CLI as compared to HIV negative patients with CLI when assessed in men, smokers, and black African patients only (p<0.05-0.0001), or in those who were receiving highly active antiretroviral therapy (n=12, 0.74±0.10 mm) as compared to those not receiving therapy (0.75±0.15 mm). As compared to controls,the age- sex- and conventional risk factor-adjusted odds of having an IMT≥0.8 mm was similarly increased in patients with CLI who were HIV positive (odds ratio=8.89, CI=2.79-28.32, p=0.0002) as those who were HIV negative (odds ratio=2.70 CI=1.51-4.81, p<0.001).In conclusion, these results suggest that despite being of a younger age, with or without conventional risk factor adjustments, marked increases in carotid IMT in HIV is a risk factor for CLI. Thus, carotid IMT measurements may be a useful screening tool to detect those patients with HIV at risk of CLI. Although asymptomatic decreases in left ventricular (LV) ejection fraction (EF) predict long-term mortality and decreased patency of endovascular interventions in patients undergoing vascular surgery, in patients with chronic critical lower limb ischemia (CLI), the prevalence of asymptomatic decreases in EF and the characteristic features thereof are unclear. I performed echocardiography in 93 sequentially recruited patients with CLI without symptoms of heart failure and 698 randomly recruited participants from a community sample.As compared to the community sample, patients with CLI had markedly reduced multivariate adjusted EF (CLI=56±12%, Community sample=67±11%, p<0.0001), LV midwall fractional shortening (FSmid)(p<0.0001), stroke volume index (SV)(p<0.0001), cardiac output index (CO)(p<0.05), and increased total peripheral resistance index (TPR)(p<0.05). In contrast to only 1/698 community participants, 26/93 (28%) patients with CLI had an EF<40%, of which only 5 had a previous myocardial infarction; and CLI was associated with a reduced EF independent of clinical evidence of coronary artery disease (CAD) and additional confounders (odds ratio=250, p<0.0001). In patients with CLI with an EF<40%, CO, SV and FSmid were all substantially reduced (p<0.0001), pro-brain natriuretic peptide concentrations and E/A were increased (p<0.05), whilst LV end diastolic volume index was marginally increased (p<0.05) as compared to those with an EF≥55%. Pro-brain natriuretic peptide had a poor sensitivity and specificity for the detection of an EF <40%. In conclusion, CLI is associated with a high prevalence of reduced EF independent of clinical evidence of heart failure, CAD and additional confounders, the main mechanism of which is a markedly reduced myocardial systolic function. This translates into decreased CO and increased TPR, alterations that may contribute toward increased mortality or reduced patency of endovascular interventions after vascular surgery.In conclusion, the results of this thesis suggest that longitudinal studies should be conducted to evaluate whether an arterial mismatch index (PPc/PWV) can predict the development of CLI independent of alternative cardiovascular risk factors; whether carotid IMT may be used to predict those at a high risk of cardiovascular events including CLI in HIV positive patients; and whether the presence of asymptomatic low LV EF may predict outcomes after surgery for CLI. Furthermore, the results of this thesis suggest that clarity is required to identify the exact large artery changes that characterize HIV positive patients with advanced PAD in South Africa.

The ICD is currently under revision and this study is the first phase of the electronic field trials for ICD-11 for psychotic disorders. The present study compared ICD-10 and ICD-11 with regards to changes made to the diagnostic guidelines and changes amongst specific disorders. Of specific interest was clinicians’ ability to accurately diagnose disorders that can present with overlapping features. We found that both diagnostic systems were accurate in differentiating disorders that have the potential to be easily confused. For some of the diagnostic guidelines that were undergoing substantial changes from ICD-10 to ICD-11, we did find improvements in the proposed guidelines. Subsequent studies will expand on our findings prior to the release of ICD-11. However, based on our initial findings, the proposed changes do appear to be increasing clinical utility of the diagnostic guidelines.

Accuracy in applying diagnostic concepts is one of the most important aspects of any mental health professional’s work. Inaccuracy in diagnosing, or misdiagnosing, can lead to numerous problems including inappropriate and potentially harmful treatment, inaccurate prognosis, stigma, and wasted or misutilized resources. For mental health professionals, inaccuracy in diagnosing can happen both intentionally and unintentionally. The severity of a person’s symptoms or the level of functional impairment the person is experiencing are two factors which can easily confound diagnostic accuracy. The present study sought to determine how each of these factors contribute to diagnostic accuracy independently and in conjunction with one another. Participants were invited the complete the current study online and were presented with two vignettes representing varying levels of symptom severity and functional impairment severity. We asked participants to rate the severity of each (symptoms and impairment), to provide diagnostic opinions, and to provide treatment recommendations. We found that in rating the severity of symptoms or impairment, and in providing diagnoses, the presence of one (symptoms or impairment) tended to overshadow the absence of the other. However, severity ratings of either symptom or impairment severity were predictive of rates in diagnosing and recommending treatment. Additionally, we found that regardless of the presence of a diagnosis, most participants believe that the person represented in the vignette would benefit from treatment. Based on these findings, it seems when conceptualizing case vignettes, professionals may be viewing symptoms and functional impairment as more interchangeable than as different components of a diagnosis.

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<p> Medical diagnosis is a complex task, that requires integrating several sources and types of information: a patient's description of their symptoms, lab results, and perhaps even 'gut feelings' regarding potential diagnoses. From a cognitive psychology perspective, diagnosis is a type of categorization and as such has been typically divided into processes that are deliberate, rule oriented, and available to conscious control (often called analytic processing) and processes that are rapid, outside of conscious awareness, and typically based on similarity (often referred to as non-analytic processing).</p> <p> Traditionally, similarity has referred to whole-case similarity between a current and previously encountered case. However, this pattern matching to an entire previous case does not differentiate between diagnostic and non-diagnostic information, a distinction that is made clear in the rules taught to medical professionals. Since medicine does rely extensively on diagnostic rules, the research presented in this thesis will examine the effect of similarity of features relevant to the application of a diagnostic rule as well as the effect of similarity from patient identity, which is mnemonically salient but diagnostically irrelevant.</p> <p> The work presented in this thesis specifically examines the role of similarity in the categorization, or diagnostic decisions of novices. Medical students start training with the best available rules, standard diagnostic rules likely to be used in future practice. In the experiments reported in this thesis, participants are trained to competence on diagnostic rules using prototypical written case vignettes of simplified psychiatric diagnoses. Participants then evaluate cases in which clinical information supports two possible diagnoses, but in which either diagnostic features or diagnostically irrelevant identity information is similar to those seen in training. The results of these experiments indicate a strong reliance on familiar of rule-relevant symptom descriptions (i.e. similarity within the application of a diagnostic rule), supporting an adaptive role of similarity within the application of an analytical decision rule. Further, the influence of familiar diagnostically irrelevant information (i.e. similarity within the context of patient identity) demonstrates the maintenance of non-diagnostic information within memory, and the possibility of matching to a previous exemplar on rule-irrelevant features. Familiarity, whether diagnostically relevant or not, increases the probability that clinically relevant features are mentioned in support of a diagnosis, which may indicate the disambiguation of features following previous experience with that feature, and a strong influence of familiar but non-diagnostic information on the interpretation of features.</p> <p> This thesis supports a model of medical decision making in which there is an effect of similarity to previous instantiations of clinically relevant features. That is, similarity is a basic component of decision making that is not limited to matching on entire previous instances. Previous research has suggested that analytic and non-analytic reasoning are competing or fundamentally separate processes, whereas the demonstration of similarity within the application of a diagnostic rule suggests that not only is similarity an adaptive strategy for learners, but the differentiation between similarity based and rule based processes may be less clear than previously suggested.</p> / Thesis / Doctor of Philosophy (PhD)

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<p>This study addresses differential diagnosis and treatment in psychiatry based on sex differences. It attempts to explain why women are diagnosed and treated differently from men, and to investigate the nature of psychiatric practice, in this regard.</p> <p>For the investigation, the thesis is in three parts. First, an analysis of the data on diagnosis and treatment of mental illness, so called. Secondly, and analysis of three theories which attempt to account for the phenomenon of psychiatric social control, i.e . the medical model of mental illness, labelling theory and feminism. Finally, a theoretical framework is presented which attempts to avoid the inadequacies of the other theoretical approaches to the problem.</p> <p>The fundamental argument in the thesis is that psychiatry acts to suppress those not directly involved in wage labour. It acts to redefine the social problems generated by capital as the indivudal problems of its victims.</p> / Master of Arts (MA)

Social anxiety disorder (SAD) is defined by persistent, irrational anxiety in social situations while generalized anxiety disorder (GAD) is characterized by excessive worry unrelated to any specific situation. These two disorders share some features and are frequently comorbid in children and adults. The current study sought to examine this comorbidity and compare the disorders on a number of dimensions in a clinical sample of children and adolescents. It was hypothesized that SAD would be accompanied by higher levels of social anxiety and behavioral inhibition and lower levels of family expressiveness and social functioning than GAD. GAD was hypothesized to be accompanied by higher levels of worry, physiological symptoms, and anxiety sensitivity and lower levels of school functioning as compared to SAD. Youth with both disorders were hypothesized to function more poorly on all dimensions as compared to either disorder alone. Participants were drawn from a sample of 397 (137 female) youth who underwent psychoeducational assessment. A series of analyses of variance, discriminant function analyses, and factor analyses were performed using the entire sample, and repeated by gender and age group. Results indicated youth with GAD had higher levels of harm avoidance as compared to youth with social anxiety disorder. However, the diagnostic groups did not differ on other features. Moreover, results of factor and discriminant function analyses did not distinguish between the two groups. The pattern of results was similar when examined for gender and age, although some differences emerged. Overall, results suggest SAD and GAD overlap significantly in children, with less overlap in adolescents. This raises questions regarding the validity of current child anxiety taxonomies. Future research should further examine this phenomenon, including longitudinal samples and a wider range of diagnoses. / Ph. D.