Quantifying the natural history of breast cancer.

BACKGROUND: Natural history models of breast cancer progression provide an opportunity to evaluate and identify optimal screening scenarios. This paper describes a detailed Markov model characterising breast cancer tumour progression. METHODS: Breast cancer is modelled by a 13-state continuous-time Markov model. The model differentiates between indolent and aggressive ductal carcinomas in situ tumours, and aggressive tumours of different sizes. We compared such aggressive cancers, that is, which are non-indolent, to those which are non-growing and regressing. Model input parameters and structure were informed by the 1978-1984 Ostergotland county breast screening randomised controlled trial. Overlaid on the natural history model is the effect of screening on diagnosis. Parameters were estimated using Bayesian methods. Markov chain Monte Carlo integration was used to sample the resulting posterior distribution. RESULTS: The breast cancer incidence rate in the Ostergotland population was 21 (95% CI: 17-25) per 10 000 woman-years. Accounting for length-biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were aggressive. Larger tumours, 21-50 mm, had an average sojourn of 6 years (95% CI: 3-16 years), whereas aggressive ductal carcinomas in situ took around half a month (95% CI: 0-1 month) to progress to the invasive ≤10 mm state. CONCLUSION: These tumour progression rate estimates may facilitate future work analysing cost-effectiveness and quality-adjusted life years for various screening strategies.

Blood lead levels and enzymatic biomarkers of environmental lead exposure in children in Cordoba, Argentina, after the ban of leaded gasoline.

Lead (Pb) is a developmental neurotoxicant found in industrial activities, many of them already prohibited worldwide. This study aimed to evaluate current blood Pb (PbB) levels in children in Cordoba, Argentina, and to compare these with similar studies performed before Pb was banned in gasoline in 1996. We also sought to identify mechanistically relevant biomarkers by measuring δ-aminolevulinic acid dehydratase (δ-ALAD), superoxide dismutase (SOD), and catalase (CAT) activities. We finally aimed to determine whether sociodemographic characteristics are associated with Pb toxicity. Blood samples collected from 161 healthy children between September 2009 and February 2010 revealed mean PbB levels of 2.58 ± 0.30 µg/dl. Enzymatic δ-ALAD, CAT, and SOD activities showed no significant variations when plotted against PbB levels. Finally, children living in the suburbs have higher PbB levels than their city counterparts, while low socioeconomic status increased δ-ALAD inhibition compared with that of middle-income children. Overall, these results evidenced a substantial reduction in exposure to Pb in this pediatric population over a decade after Pb was restricted in gasoline and reveal the importance of pursuing novel biomarkers of toxicity along with the sociodemographic profile to complement Pb diagnosis.

No improvement in lung cancer care: the management of lung cancer in 1996 and 2002 in New South Wales.

BACKGROUND: Patterns-of-care studies emphasize significant variation in the management of lung cancer. The aim of the study was to compare the patterns of care for patients diagnosed with lung cancer in 1996 and 2002 within three health areas in New South Wales. METHODS: Treatment data were collected from medical records and treating doctors for the calendar year 1996 and between 1 November 2001 and 31 December 2002. Patients were residents of either south-western Sydney, Hunter or Northern Sydney health areas at the time of diagnosis. chi(2)-tests were used to investigate changes in treatment patterns between the two time periods. An adjusted odds ratio for treatment in 2002 relative to 1996 was calculated using logistic regression. RESULTS: Data were available for 738 and 567 cases in 1996 and 2002, respectively. Cancer-specific therapy was given within 6 months of diagnosis to 62 and 64% of patients, respectively. Adjusting for health area, age, sex, pathology and performance status, the odds ratio (OR) of treatment in 2002 relative to 1996 was 1.03 (95% confidence interval (CI) 0.78-1.35). When stage was included, the odds of treatment in 2002 relative to 1996 for non-small-cell lung cancer (n = 950) was 1.21 (95%CI 0.87-1.68). After adjustment for potential confounders, patients diagnosed with small-cell lung cancer (n = 176) were substantially less likely to receive treatment in 2002 compared with patients diagnosed in 1996 (OR = 0.11; 95%CI 0.04-0.34). CONCLUSION: The odds of receiving treatment in 2002 and 1996 were similar. However, patients diagnosed with small-cell lung cancer in 2002 were significantly less likely to receive treatment. Overall, this study suggests there has been no change in lung cancer care in New South Wales. Further work is required to determine what proportion of persons with lung cancer should receive cancer-specific treatment so that clinical practices can be judged appropriately.

Cost-effectiveness of current and optimal treatment for adult asthma.

BACKGROUND: This article is part of a project to determine the cost-effectiveness of averting the burden of disease. We used population data to investigate the costs and benefits of allocating resources to optimal treatment for asthma in adults, using a burden of disease framework. METHODS: We calculated the population burden of asthma in the absence of any treatment as years lived with disability (YLD), ignoring the years of life lost. We then estimated the proportion of burden averted with current interventions, the proportion that could be averted with optimally implemented current evidence-based guidelines and the direct treatment cost-effectiveness ratio in dollarA per YLD averted for both current and optimal treatment. RESULTS: The direct treatment cost of current treatment of adult asthma in Australia was dollar A452 million and averted 25% of the burden with a cost-effectiveness ratio of dollar A14 000/YLD averted. Optimal treatment and optimal compliance would cost dollar A627 million and avert 69% of the burden with a cost-effectiveness ratio of dollar A7000/YLD averted. CONCLUSION: Implementation of optimal treatment for asthma is affordable, will be more cost-effective and will significantly decrease disability.