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Lai K.,Immunology and Infectious Diseases Unit | Lai K.,University of Newcastle | Graves S.,Pathology North Hunter | Graves S.,Australian Rickettsial Research Laboratory
Internal Medicine Journal | Year: 2013

Queensland tick typhus (QTT), caused by Rickettsia australis, is usually a relatively mild illness but can occasionally be severe. We describe three cases of probable QTT with unusual clinical features, namely splenic infarction, fulminant myopericarditis and severe leukocytoclastic vasculitis. QTT may present with uncommon clinical features in addition to the more common manifestations. A high index of suspicion enables specific antibiotic therapy that may hasten recovery. © 2013 The Authors Internal Medicine Journal © 2013 Royal Australasian College of Physicians. Source

Hiles S.A.,University of New South Wales | Baker A.L.,University of New South Wales | de Malmanche T.,Immunology | McEvoy M.,University of New South Wales | And 4 more authors.
Journal of Psychiatric Research | Year: 2015

Depression and inflammatory markers have a reliable cross-sectional association although less is known about the prospective relationship. The current study investigated whether pro-inflammatory markers are prospectively associated with depression, and whether indicators of unhealthy lifestyle, physical health and psychosocial functioning may drive this association. Participants were drawn from the Hunter Community Study, a community-dwelling cohort of individuals aged 55-85 years (N=1410). Participants completed baseline physiological assessment, health-related questionnaires, and blood sampling for the analysis of inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6. Participants completed the same depressive symptom questionnaire again after 3.5-5.5 years. Depression outcomes at follow-up were analysed dichotomously using established scale cut-off scores and continuously as a "residual score", representing the variation in follow-up depressive symptoms not explained by baseline symptoms and age. Analyses were conducted on males and females separately. At baseline, indicators of unhealthy lifestyle, physical health and psychosocial functioning were associated with depressive symptoms and inflammatory markers. For males, there were no relationships between inflammatory markers and follow-up depression outcomes. In females, IL-6 was significantly associated with depression outcomes in univariate, but not multivariate analyses. However, IL-6 significantly mediated the association between the predictors of waist-to-hip ratio, smoking and psychological coping at baseline, and follow-up depression outcomes. The results support the inflammatory hypothesis of depression, although females may be more vulnerable to effects. The findings raise the possibility that unhealthy lifestyle and psychosocial stress may drive inflammation and subsequent depressive symptoms. © 2015 Elsevier Ltd. Source

Lee F.J.,Clinical Research Program | Amin J.,University of New South Wales | Carr A.,Clinical Research Program | Carr A.,Immunology and Infectious Diseases Unit
PLoS ONE | Year: 2014

Background: A comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines. Methods: Group-based, systematic review and meta-analysis of initial antiretroviral therapy studies, in adults, of ≥48 weeks duration, reported through December 31, 2012. Size-weighted, intention-to-treat efficacy was calculated. Parameters of study design/eligibility, participant and treatment characteristics were abstracted. Multivariable, random effects, linear regression models with backwards, stepwise selection were then used to identify variables associated with efficacy. Outcome Measures: Antiviral efficacy (undetectable plasma viral load) and premature cessation of therapy. Results: 114 studies were included (216 treatment groups; 40,124 participants; mean CD4 count 248 cells/μL [SD 81]; mean HIV-1 plasma viral load log10 4.9 [SD 0.2]). Mean efficacy across all groups was 60% (SD 16) over a mean 82 weeks' follow-up (SD 38). Efficacy declined over time: 66% (SD 16) at 48 weeks, 60% (SD 16) at 96 weeks, 52% (SD 18) at 144 weeks. The most common reason for treatment cessation was participant decision (11%, SD 6.6). Efficacy was higher with 'Preferred' than 'Alternative' regimens (as defined by 2013 United States antiretroviral guidelines): 75% vs. 65%, respectively, difference 10%; 95%CI 7.6 to 15.4; p<0.001. In 98 groups (45%) reporting efficacy stratified by pre-treatment viral load (< or ≥100,000 copies/mL), efficacy was greater for the lower stratum (70% vs. 62%, respectively, difference 8.4%; 95%CI 6.0 to 10.9; p< 0.001). This difference persisted within 'Preferred' regimens. Greatest efficacy was associated with use of tenofovir-emtricitabine (vs. other nucleoside analogue backbones) and integrase strand transfer inhibitors (vs. other third drug classes). Conclusion: Initial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy, but are more effective when commenced at plasma viral loads <100,000 copies/mL. Rising viral load should be considered an indication for starting treatment. Integrase inhibitors offer a treatment advantage (vs. other third drug classes). © 2014 Lee et al. Source

Sasson S.C.,Immunology and Infectious Diseases Unit | Sasson S.C.,University of New South Wales | Oon A.,Immunology and Infectious Diseases Unit | Chagantri J.,St. Vincents Hospital | And 2 more authors.
BMC Infectious Diseases | Year: 2013

Background: Posterior reversible encephalopathy syndrome (PRES) is an uncommon pathology characterized by the acute onset of headache, vomiting, altered consciousness, seizures and focal neurological deficits. It was initially described in the setting of hypertension, uremia and immunosuppression. In the last decade there have been emerging reports of PRES in patients with advanced human immunodeficiency virus (HIV)-infection in the presence of hypertension, dialysis, hypercalcaemia and two opportunistic infections: blastomycosis and tuberculosis (TB).Case presentation: Here we present the case of a 54 year old male being treated for disseminated varicella zoster virus (VZV) and vasculopathy in the setting of HIV infection who acutely deteriorated to the point of requiring intubation. His clinicoradiological diagnosis was of PRES and he subsequently improved within 72 h with supportive management. Serial neuroimaging correlated with the clinical findings. The pathogenesis of PRES is poorly understood but is thought to stem from vasogenic oedema either as a result of loss of endothelial integrity and transudate of fluid across the blood-brain barrier, or secondary to vasospasm resulting in tissue oedema in the absence of infarction. How HIV infection impacts on this model is unclear. It is possible the HIV infection causes endothelial dysfunction and disruption of the blood-brain barrier that may be further exacerbated by infections in the central nervous system. Conclusion: The phenomenon of PRES in advanced HIV is an important clinical entity for both physicians and critical care doctors to recognize firstly given its potential mortality but also because of its favourable prognosis and reversibility with supportive care and treatment of underlying causes. © 2013 Sasson et al.; licensee BioMed Central Ltd. Source

Cysique L.A.,University of New South Wales | Cysique L.A.,Neuroscience Research Australia | Cysique L.A.,St Vincents Hospital Center for Applied Medical Research | Heaton R.K.,University of California at San Diego | And 12 more authors.
Journal of NeuroVirology | Year: 2014

The Australian HIV-infected (HIV+) population is largely comprised of high-functioning men who have sex with men (MSM). Like other English-speaking countries, Australia mostly relies on US neuropsychological normative standards to detect and determine the prevalence of neurological disorders. Whether the US neuropsychological (NP) normative standards are appropriate in Australian HIV+ MSM has not been established. Ninety virally suppressed HIV+ and 49 HIV-uninfected (HIV-) men (respectively 86 and 85% self-reported MSM; mean age 54 and 56 years, mean premorbid verbal IQ estimate 110 and 111) undertook standard NP testing. The raw neuropsychological data were transformed using the following: (1) US standards as uncorrected scaled scores and demographically corrected T scores (US norms); and (2) z scores (without demographic corrections) derived from Australian comparison group scaled scores (local norms). To determine HIV-associated neurocognitive disorder prevalence, we used a standard definition of impairment based upon a battery-wide summary score: the global deficit score (GDS). Impairment classification (GDS≥0.5) based on the local norms was best at discriminating between the two groups (HIV- = 14.3% vs. HIV+ = 53.3%; p<0.0001). This definition was significantly associated with age. Impairment classification based on the US norms yielded much lower impairment rate regardless of the HIV status (HIV- = 4.1% vs. HIV+ = 14.7%; p = 0.05), but was associated with historical AIDS, and not age. Both types of summary scores were associated with reduced independence in activities of daily living (p≤0.03). Accurate neuropsychological classifications of high (or low) functioning individuals may need country-specific norms that correct for performance-based (e.g., reading) estimates of premorbid cognition in addition to the traditional demographic factors. © Journal of NeuroVirology, Inc. 2014. Source

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