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Background Renal disease has become one of the most important comorbidities observed in the human immunodeficiency virus ( HIV)-infected patient cohort. Data are lacking on the current screening and management of renal disease in patients with HIV. We evaluated HIV-infected Australian adults in primary care to determine current practices. Methods This prospective, multicentre observational study included two rounds of data collection; the first was followed by an educational programme. Outcomes included screening for renal disease; management of risk factors for kidney disease and other comorbidities associated with renal disease. Results Fifty-three general practitioners participated with 733 patients enrolled. Most were male (94%); almost 40% were 41-50 years of age, and 6% and 84% were receiving antiretroviral therapy. Comorbidities were common; 19% had hypertension, 5% were diabetic, 32% were dyslipidaemic, and 40% were smokers. Estimated glomerular filtration rate was commonly measured in both rounds of data collection (96% vs 95%). Proteinuria was assessed less frequently; this improved after education (48% vs 71%). Almost 10% of patients tested had proteinuria on urinalysis. Of the 45 patients (6%) with renal impairment (estimated glomerular filtration rate <60 m L/min), none was referred for assessment by a renal specialist. Conclusions This large observational study provides important information on renal disease in HIV-infected patients, an area with a paucity of clinical data. Current screening and management practices fall short of suggested guidelines. Failure to refer patients to specialists is a major deficiency. Improvements with education suggest the need to promote awareness of guidelines in primary care doctors. [ABSTRACT FROM AUTHOR]

Several cellular pathways are implicated in the pathogenesis of pulmonary arterial hypertension (PAH) and attempts to arrest disease progression with a single drug would not be expected to succeed in the medium term. In clinical practice, combination therapy is often used in patients deteriorating on monotherapy, despite the absence of firm evidence from randomized controlled controls. From January 2005 to August 2009, 112 patients with World Health Organisation Functional Class (FC) II-IV PAH deteriorating on monotherapy received non-parenteral combination therapy at six Australian PAH expert hospitals. Combination therapy included bosentan, sitaxentan, ambrisentan, iloprost and sildenafil. Data were prospectively collected for survival status, 6-min walk distance, FC and echocardiographic parameters at the start of monotherapy through to commencement of combination therapy and at 6-monthly intervals thereafter. After varying periods of monotherapy (18.7 ± 13.4 months), survival estimates on combination therapy were 88%, 71% and 61% for the additional 1, 2 and 3 years respectively. Survival on dual therapy in patients with idiopathic PAH/familial PAH was 93% at 1 year and 79% at 2 years, and for scleroderma-related PAH, 72% at 1 year and 48% at year 2 after initiation of combination therapy. In survivors, dual therapy reversed the deterioration in FC, from 3.1 ± 0.6 on monotherapy to 2.2 ± 0.6 at 12 months. Similarly, dual therapy improved 6-min walk distance from 316 ± 119 m to 406 ± 129 m at 12 months, and sequential echocardiography demonstrated a fall in pulmonary artery systolic pressure and improved right ventricular function. Dual non-parenteral therapy appears safe and effective and should be considered for PAH patients who are deteriorating on monotherapy to improve long-term outcomes. [ABSTRACT FROM AUTHOR]

The Bosentan Patient Registry (BPR) was a prospective, multicentre, Australian registry funded by Actelion Pharmaceuticals. The primary aim of the registry was to collect survival data in patients with pulmonary arterial hypertension (PAH) treated with bosentan. The BPR was initiated in 15 specialized PAH centres. All patients on or starting bosentan were invited to enrol. Treating physicians notified the registry if patients discontinued bosentan, because of either a change in therapy, transplantation, intervention or death. Survival data were validated against the Australian Institute of Health and Welfare National Death Index. Between 2004 and 2007, a total of 528 patients (mean age 59 ± 17 years) were enrolled representing 69% of patients either previously taking or initiated on bosentan during that time. The BPR population was generally older with more advanced functional deficit than patients enrolled in randomized, placebo-controlled trials. Aetiology was idiopathic (iPAH) in 58% and connective tissue disease related (scleroderma (SSc)-PAH) in 42%. For iPAH patients, World Health Organisation functional classes II, III and IV at enrolment was 8.2%, 66.4% and 20.5%, and for the SSc-PAH cohort, 3.2%, 75.8% and 17.9% respectively. The observed annual mortality was 11.8% in patients with iPAH and 16.6% in patients SSc-PAH. This large Australian registry provides 'real life' information on the characteristics and management of PAH in clinical practice. Treatment with bosentan improved survival outcomes in both iPAH and SSc-PAH compared with historical controls. Age, disease severity and aetiology were critical factors in determining clinical outcomes. [ABSTRACT FROM AUTHOR]

Aim: Healthy adult ageing of the human neuromuscular system is comprised of changes that include atrophy, weakness and slowed movements with reduced spinal motor neurone output expressed by lower motor unit discharge rates (MUDRs). The latter observation has been obtained mostly from hand and lower limb muscles. The purpose was to determine the extent to which elbow flexor and extensor contractile properties, and MUDRs in six old (83 ± 4 years) and six young (24 ± 1 years) men were affected by age, and whether any adaptations were similar for both muscle groups. Methods: Maximal isometric voluntary contraction (MVC), voluntary activation, twitch contractile properties, force–frequency relationship and MUDRs from sub-maximal to maximal intensities were assessed in the elbow flexors and extensors. Results: Both flexor and extensor MVCs were significantly ( P < 0.05) less (∼42% and ∼46% respectively) in the old than in the young. Contractile speeds and the force–frequency relationship did not show any age-related differences ( P > 0.05). For the elbow flexors contraction duration was ∼139 ms and for the extensors it was ∼127 ms for both age groups ( P > 0.05). The mean MUDRs from 25% MVC to maximum were lower (∼10% to ∼36%) in the old than in the young ( P < 0.01). These age-related differences were larger for biceps (Cohen’s d = 8.25) than triceps (Cohen’s d = 4.79) brachii. Conclusion: Thus, at least for proximal upper limb muscles, mean maximal MUDR reductions with healthy adult ageing are muscle specific and not strongly related to contractile speed. [ABSTRACT FROM AUTHOR]

Background: We sought to determine the prevalence of pulmonary complications and especially pulmonary arterial hypertension (PAH) in an Australian scleroderma population. Methods: Between July 2005 and June 2007, physicians in Western Australia were asked to refer patients with scleroderma specifically for pulmonary hypertension screening. All patients were assessed for PAH and other respiratory conditions using echocardiography, lung function testing and clinical assessments. Right heart catheterization was carried out in patients with evidence of increased right ventricular systolic pressure. Results: Of the 184 patients analysed, 44 had possible PAH on echocardiography. Right heart catheterization confirmed the diagnosis in 24 (13%). Diffuse interstitial lung disease was found in 32 patients representing a point prevalence of 17.4%. The severity of PAH at diagnosis varied according to whether the patients were referred for screening (group A) or for diagnostic (group B) purposes. The 6-min-walk test distance and median pulmonary vascular resistance were significantly worse in group B versus group A (324 vs 402 m; P= 0.02 and 884 dynes/s per cm−5 vs 486 dynes/s per cm−5; P < 0.01, respectively). Conclusion: Screening may result in earlier diagnosis of PAH with, in general more mild disease. This is important, given that early treatment for PAH while patients are less symptomatic is associated with improved exercise tolerance and pulmonary haemodynamics: indices indicative of disease progression and clinical worsening. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors (PPI) have been linked to higher risk of Clostridium difficile infection (CDI). The relevance of this association in hospitals with low disease activity, where an outbreak strain is nondominant, has been assessed in relatively few studies. Aim To assess the association of PPI and CDI in a setting of low disease activity. Methods A retrospective cohort study was conducted at two hospitals. Patients admitted for ≥7 days receiving antibiotics were included. Demographics, exposure to PPI, antibiotics and other drugs in relation to diagnosis of CDI were assessed by univariate and multivariate analyses. Results Of 14 719 patients, 149 (1%) first episode CDI were documented; PPI co-exposure increased CDI [1.44 cases/100 patients vs. 0.74 cases/100 non-exposed (OR: 1.96, 95% CI: 1.42–2.72)]. By logistic regression, PPI days (adjusted OR: 1.01 per day, 95% CI: 1.00–1.02), histamine-2 blockers, antidepressants, antibiotic days, exposure to medications, age, admission service and length of admission were significant predictors. Conclusions A statistically significant increase in CDI was observed in antibiotic recipients who received PPI, but the absolute risk increase is modest. In settings of with low rates of CDI, the benefit of PPI therapy outweighs the risk of developing CDI. These data support programmes to decrease inappropriate use of PPI in hospitalized patients. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Screening and Management of Renal Disease in Human Immunodeficiency Virus-Infected Patients in Australia" in the 2013; 43 issue is presented.

Background: Pulmonary hypertension (PH) is a condition that affects more than 25 million individuals worldwide and causes premature disability and death. Despite advances in our understanding of this condition, education and training of health professionals has not kept pace with the rapid changes in diagnosis and treatment. The net effects of this gap between advancing knowledge and limited educational opportunity likely include clinically significant delays in both the diagnosis and commencement of effective evidence-based treatment - an unacceptable outcome for patients with a lethal condition. Aim: The Actelion Clinical Excellence Programme (ACEP) is an e-learning postgraduate curriculum, the purpose of which is to educate and mentor healthcare professionals, both theoretically and practically, in the diagnosis and treatment of patients with all forms of PH. This article reports on the development and delivery of the programme and outcomes from its first year of operation. Results: Forty-three healthcare professionals from 22 institutions were enroled in the first iteration of the programme. In the 6 months from May to October 2011, participants successfully completed 285 lectures and/or activities. Overall, the programme was considered easily accessible, comprehensive in terms of both quality and quantity, provided an efficient means of self-paced learning, and was a highly regarded as reference source. Ninety-five per cent of participants said that they intended to change their clinical practice as a result of the information presented in the programme. Conclusion: ACEP represents a successful physician-industry partnership, which has resulted in a significant impact on clinical teaching and awareness of PH. [ABSTRACT FROM AUTHOR]

To determine the potential regulatory mechanisms involved in synovial cell interleukin-1 (IL-1) release, the ability of gamma-interferon (gamma-IFN) to influence IL-1 release was assessed. Rat synovial cells cultured in the presence of a variety of stimuli, including lipopolysaccharide (LPS), failed to release IL-1. However, pretreatment of synovial cells with gamma-IFN, followed by LPS stimulation, resulted in increased levels of intracellular IL-1 as well as release of IL-1 from the cell. The level of IL-1 release was dependent on the concentration of both gamma-IFN and LPS, and on length of exposure to the gamma-IFN. The kinetic and dose requirements for gamma-IFN-dependent IL-1 release were similar to those for Ia antigen expression, but LPS was necessary for IL-1 messenger RNA induction, intracellular IL-1 accumulation, and IL-1 release. In addition, sequential treatment, i.e., gamma-IFN followed by LPS, was essential for IL-1 induction. Substitution of phorbol ester or calcium ionophore for gamma-IFN did not result in similar IL-1 release. In addition, induction of IL-1 messenger RNA by another stimulus was not sufficient to result in IL-1 release following LPS treatment. These results suggest that release of IL-1 by rat synovial cells requires the production of a regulatory signal, which is inducible by gamma-IFN.

Cellular interactions involved in the chronic inflammatory response, characteristic of those found in the joints of rheumatoid arthritis patients, were investigated by examining the effect of interleukin-1 (IL-1), tumor necrosis factor alpha, and gamma-interferon on the regulation of IL-1 gene expression and production by synovial fibroblasts. Biologically active IL-1 was detected in lysates of IL-1-treated rat and human fibroblasts that had been isolated from synovial tissue by collagenase digestion. Northern blot analysis of RNA isolated from these cells revealed the expression of IL-1 alpha and IL-1 beta transcripts. Neither the IL-1 transcripts nor the biologic activity of IL-1 was found in untreated synovial fibroblasts. The messenger RNA induction in synovial cells was followed by a time- and dose-dependent expression of intracellular IL-1 activity. Human monocytes and human skin fibroblasts also responded to IL-1 treatment by producing IL-1-specific transcripts. These observations suggest that IL-1 plays a key role in stimulating immune and inflammatory responses and in sustaining those responses through continued production at sites of inflammation.