If you can't comply with dialysis, how do you expect me to trust you with transplantation? Australian nephrologists' views on indigenous Australians' 'non-compliance' and their suitability for kidney transplantation

<p>Abstract</p> <p>Introduction</p> <p>Indigenous Australians suffer markedly higher rates of end-stage kidney disease (ESKD) but are less likely than their non-Indigenous counterparts to receive a transplant. This difference is not fully explained by measurable clinical differences. Previous work suggests that Indigenous Australian patients may be regarded by treating specialists as 'non-compliers', which may negatively impact on referral for a transplant. However, this decision-making is not well understood. The objectives of this study were to investigate: whether Indigenous patients are commonly characterised as 'non-compliers'; how estimations of patient compliance factor into Australian nephrologists' decision-making about transplant referral; and whether this may pose a particular barrier for Indigenous patients accessing transplants.</p> <p>Methods</p> <p>Nineteen nephrologists, from eight renal units treating the majority of Indigenous Australian renal patients, were interviewed in 2005-06 as part of a larger study. Thematic analysis was undertaken to investigate how compliance factors in specialists' decision-making, and its implications for Indigenous patients' likelihood of obtaining transplants.</p> <p>Results</p> <p>Specialists commonly identified Indigenous patients as both non-compliers and high-risk transplant candidates. Definition and assessment of 'compliance' was neither formal nor systematic. There was uncertainty about the value of compliance status in predicting post-transplant outcomes and the issue of organ scarcity permeated participants' responses. Overall, there was marked variation in how specialists weighed perceptions of compliance and risk in their decision-making.</p> <p>Conclusion</p> <p>Reliance on notions of patient 'compliance' in decision-making for transplant referral is likely to result in continuing disadvantage for Indigenous Australian ESKD patients. In the absence of robust evidence on predictors of post-transplant outcomes, referral decision-making processes require attention and debate.</p

ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells

L-selectin on T-cells is best known as an adhesion molecule that supports recruitment of blood-borne naïve and central memory cells into lymph nodes. Proteolytic shedding of the ectodomain is thought to redirect activated T-cells from lymph nodes to sites of infection. However, we have shown that activated T-cells re-express L-selectin before lymph node egress and use L-selectin to locate to virus-infected tissues. Therefore, we considered other roles for L-selectin proteolysis during T cell activation. In this study, we used T cells expressing cleavable or non-cleavable L-selectin and determined the impact of L-selectin proteolysis on T cell activation in virus-infected mice. We confirm an essential and non-redundant role for ADAM17 in TCR-induced proteolysis of L-selectin in mouse and human T cells and show that L-selectin cleavage does not regulate T cell activation measured by CD69 or TCR internalisation. Following virus infection of mice, L-selectin proteolysis promoted early clonal expansion of cytotoxic T cells resulting in an 8-fold increase over T cells unable to cleave L-selectin. T cells unable to cleave L-selectin showed delayed proliferation in vitro which correlated with lower CD25 expression. Based on these results, we propose that ADAM17-dependent proteolysis of L-selectin should be considered a regulator of T-cell activation at sites of immune activity

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Alexithymia profiles and depression, anxiety, and stress

Background: Alexithymia is a multidimensional trait comprised of difficulties identifying feelings, difficulties describing feelings, and externally orientated thinking. It is regarded as an important risk factor for emotional disorders, but there are presently limited data on each specific facet of alexithymia, or the extent to which deficits in processing negative emotions, positive emotions, or both, are important. In this study, we address these gaps by using the Perth Alexithymia Questionnaire (PAQ) to comprehensively examine the relationships between alexithymia and depression, anxiety, and stress symptoms. Methods: University students (N = 1250) completed the PAQ and the Depression Anxiety Stress Scales-21. Pearson correlations, hierarchical regressions, and latent profile analysis were conducted. Results: All facets of alexithymia, across both valence domains, were significantly correlated with depression, anxiety, and stress symptoms (r = 0.27–0.40). Regression analyses indicated that the alexithymia facets, together, could account for a significant 14.6 %–16.4 % of the variance in depression, anxiety, and stress. Difficulties identifying negative feelings and difficulties identifying positive feelings were the strongest unique predictors across all symptom categories. Our latent profile analysis extracted eight profiles, comprising different combinations of alexithymia facets and psychopathology symptoms, collectively highlighting the transdiagnostic relevance of alexithymia facets. Limitations: Our study involved a student sample, and further work in clinical samples will be beneficial. Conclusions: Our data indicate that all facets of alexithymia, across both valence domains, are relevant for understanding depression, anxiety, and stress. These findings demonstrate the value of facet-level and valence-specific alexithymia assessments, informing more comprehensive understanding and more targeted treatments of emotional disorder symptoms

Alexithymia or general psychological distress? Discriminant validity of the Toronto Alexithymia Scale and the Perth Alexithymia Questionnaire

Background Alexithymia is an important transdiagnostic risk factor for emotion-based psychopathologies. However, it remains unclear whether alexithymia questionnaires actually measure alexithymia, or whether they measure emotional distress. Our aim here was to address this discriminant validity concern via exploratory factor analysis (EFA) of the 20-item Toronto Alexithymia Scale (TAS-20) and the Perth Alexithymia Questionnaire (PAQ). Method United States general community adults (N = 508) completed the TAS-20, PAQ, and the Depression Anxiety Stress Scales-21 (DASS-21). EFA was used to examine the latent dimensions underlying these measures' scores. Results Our EFA extracted two higher-order factors, an “alexithymia” factor and a “general distress” factor (i.e., depression, anxiety, stress). All PAQ scores loaded cleanly on the alexithymia factor, with no cross-loadings on the distress factor. However, for the TAS-20, Difficulty Identifying Feelings (DIF) facet scores cross-loaded highly on the distress factor. Limitations Our sample consisted of general community adults; future work in clinical settings will be useful. Conclusions Our data indicate that the PAQ has good discriminant validity. However, the TAS-20 appears to have significant discriminant validity problems, in that much of the variance in its DIF facet reflects people's current levels of distress, rather than alexithymia. The TAS-20, which has traditionally been the most widely used alexithymia questionnaire, may therefore not be the optimal alexithymia tool. Our findings add to the body of evidence supporting the validity and utility of the PAQ and suggest that, moving forward, it is a superior option to the TAS-20 for alexithymia assessments.</p

The Perth Alexithymia Questionnaire-Short Form (PAQ-S): A 6-item measure of alexithymia

Background: Alexithymia is a trait characterized by difficulties identifying feelings, difficulties describing feelings, and externally orientated thinking. It is widely regarded as an important transdiagnostic risk factor for a range of psychopathologies, including depressive and anxiety disorders. Whilst several well-validated psychometric measures of alexithymia exist, these are relatively lengthy, thus limiting their utility in time-pressured settings. In this paper, we address this gap by introducing and validating a brief 6-item version of the Perth Alexithymia Questionnaire, called the Perth Alexithymia Questionnaire-Short Form (PAQ-S). Method: Across two studies with adult samples (Study 1 N = 508 United States community; Study 2 = 378 Australian college students), we examined the psychometric properties of the PAQ-S in terms of its factor structure, reliability, and concurrent/criterion validity. Results: In exploratory and confirmatory factor analyses, all PAQ-S items loaded well on a single general alexithymia factor. The PAQ-S total score had high reliability, and correlated as expected with the long-form of the PAQ, as well as other established markers of alexithymia, emotion regulation, and affective disorder symptoms. Limitations: Our samples were general community or college student samples from two Western countries; future validation work in clinical samples and more diverse cultural groups is thus needed. Conclusions: The PAQ-S retains the psychometric strengths of the PAQ. As such, the PAQ-S can be used as a quick, robust measure of overall alexithymia levels. The introduction of the PAQ-S hence enables valid assessments of alexithymia in a more diverse range of settings and research designs