Disease risk and mortality prediction in intensive care patients with pneumonia. Australian and New Zealand practice in intensive care (ANZPIC II)

This study of ventilated patients investigated pneumonia risk factors and outcome predictors in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units within Australia and New Zealand. For community acquired pneumonia, mortality increased with immunosuppression (OR 5.32, CI 95% 1.58-17.99, P < 0. 01), clinical signs of consolidation (OR 2.43, CI 95% 1.09-5.44, P = 0. 03) and Sepsis-Related Organ Failure Assessment (SOFA) scores (OR 1.19, CI 95% 1.08-1.30, P < 0. 001) but improved if appropriate antibiotic changes were made within three days of intensive care unit admission (OR 0.42, CI 95% 0.20-0.86, P = 0.02). For hospital-acquired pneumonia, immunosuppression (OR 6.98, CI 95% 1.16-42.2, P = 0.03) and non-metastatic cancer (OR 3.78, CI 95% 1.20-11.93, P = 0.02) were the principal mortality predictors. Alcoholism (OR 7.80, CI 95% 1.20-1750, P < 0.001), high SOFA scores (OR 1.44, CI 95% 1.20-1.75, P = 0.001) and the isolation of high risk organisms including Pseudomonas aeruginosa, Acinetobacter spp, Stenotrophomonas spp and methicillin resistant Staphylococcus aureus (OR 4.79, CI 95% 1.43-16.03, P = 0.01), were associated with increased mortality in ventilator-associated pneumonia. The use of non-invasive ventilation was independently protective against mortality for patients with community-acquired and hospital-acquired pneumonia (OR 0.35, CI 95% 0.18-0.68, P = 0.002). Mortality was similar for patients requiting both invasive and non-invasive ventilation and non-invasive ventilation alone (21% compared with 20% respectively, P = 0.56). Pneumonia risks and mortality predictors in Australian and New Zealand ICUs vary with pneumonia type. A history of alcoholism is a major risk factor for mortality in ventilator-associated pneumonia, greater in magnitude than the mortality effect of immunosuppression in hospital-acquired pneumonia or community-acquired pneumonia. Non-invasive ventilation is associated with reduced ICU mortality. Clinical signs of consolidation worsen, while rationalising antibiotic therapy within three days of ICU admission improves mortality for community-acquired pneumonia patients.

Kidney and related chronic disease profiles and risk factors in three remote Australian Aboriginal communities

Morbidities and deaths from noncommunicable chronic diseases are greatly increased in remote Australian Aboriginal communities, but little is known of the underlying community-based health profiles. We describe chronic-disease profiles and their risk factors in 3 remote communities in the Northern Territory. Consenting adults (18+ years of age) in 3 communities participated in a brief history and examination between 2000 and mid-2003 as part of a systematic program to improve chronic-disease awareness and management. Participation was 67%,128%, and 62% in communities A, B, and C, respectively with a total of 1070 people examined. Current smokers included 41% of females and 72% of males. Most men were current drinkers, but most women were not. Parameters of body weight differed markedly by community, with mean body mass index (BMC) varying from 21.4 to 27.9 kg/m(2). Rates of chronic diseases were excessive but differed markedly; an almost threefold difference in the likelihood of any morbidity existed between communities A and C. Rates increased with age, but the greatest numbers of people with morbidities were in the middle-aged group. Most people had multiple morbidities with tremendous overlap. Hypertension and kidney disease appear to be early manifestations of the integrated chronic-disease syndrome, while diabetes is a late manifestation or complication. Substantial numbers of new cases of disease were identified by testing, and blood pressure improved in treated people with hypertension. Wide variations occur in body habitus, risk factors, and chronic-disease rates among communities, but an overwhelming need for effective smoking interventions exists in all. Systematic screening is useful in identifying high-risk individuals, most at early treatable stages there. Findings are very important for estimating current treatment needs, future burdens of disease, and for needs-based health services planning. Resources required will vary according to the burden of disease. (C) 2005 by the National Kidney Foundation, Inc.

Identification of a novel frameshift mutation in the giant muscle filament titin in a large Australian family with dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is an etiologically heterogeneous cardiac disease characterized by left ventricular dilation and systolic dysfunction. Approximately 25-30% of DCM patients show a family history of mainly autosomal dominant inheritance. We and others have previously demonstrated that mutations in the giant muscle filament titin (TTN) can cause DCM. However, the prevalence of titin mutations in familial DCM is unknown. In this paper, we report a novel heterozygous 1-bp deletion mutation (c.62890delG) in TTN that cosegregates with DCM in a large Australian pedigree (A3). The TTN deletion mutation c.62890delG causes a frameshift, thereby generating a truncated A-band titin due to a premature stop codon (p.E20963KfsX10) and the addition of ten novel amino acid residues. The clinical phenotype of DCM in kindred A3 demonstrates incomplete penetrance and variable expressivity. Finally, protein analysis of a skeletal muscle biopsy sample from an affected member did not reveal the predicted truncated titin isoform although the aberrant mRNA was present, suggesting posttranslational modification and degradation of the truncated protein. The identification of a novel disease-causing mutation in the giant titin gene in a third large family with DCM indicates that mutations in titin may account for a significant portion of the genetic etiology in familial DCM.