Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe.

Oxygenation and tissue hypoxia play critical roles in mammalian biology and contribute to aggressive phenotypes in cancerous tumors, driving research to develop accurate and easy-to-implement methods for monitoring hypoxia in living cells and animal models. This study reports the chemiluminescent probe HyCL-4-AM, which contains a nitroaromatic sensing moiety and, importantly, an acetoxymethyl (AM) ester that dramatically improves operation in cells and animals. HyCL-4-AM provides a selective 60 000-fold increase in luminescence emission in the presence of rat liver microsomes (RLM). For cellular operation, the chemiluminescence response kinetics is sharply dependent on oxygen levels, enabling highly significant and reproducible measurement of hypoxia in living cells. Whole animal imaging experiments in muscle tissue and tumor xenografts show that HyCL-4-AM can differentiate between well oxygenated muscle tissue and hypoxic tumors, demonstrating potential for monitoring tumor reoxygenation via hyperoxic treatment.

Screening for Hepatitis C in injecting drug users: a cost utility analysis.

BACKGROUND: Hepatitis C is a major public health problem of increasing importance among injecting drug users, among whom screening has been proposed. We therefore estimated the cost utility of screening for hepatitis C infection among people with a history of injecting drug use in contact with drug misuse services. METHODS: A spreadsheet-based model of screening using ELISA followed by polymerase chain reaction tests and treatment using combination therapy with interferon alpha and ribavirin was developed. Parameters were informed by literature review, expert opinion and a survey of current screening practice in England. A range of one-way sensitivity analyses were carried out to explore uncertainty in the results for cost effectiveness. RESULTS: Screening for HCV is likely to yield benefits in the population concerned at around 28,000 pounds per quality adjusted life year. This estimate is reasonably stable when explored in extensive one-way sensitivity analysis but appeared sensitive to the proportion of HCV positive people who accept biopsy or treatment and the utility gains associated with successful drug treatment. Important other areas of uncertainty include the effects of mortality from other causes on the cost effectiveness of screening in this population and the time at which symptoms would have led to presentation in the absence of a screening programme. CONCLUSION: Screening for HCV in this population is moderately cost effective, although some caution must remain in accepting this estimate given the current uncertainties in this field, and further research is required.

Screening for hepatitis C in genito-urinary medicine clinics: a cost utility analysis.

BACKGROUND/AIMS: To estimate the cost utility (cost per QALY) of screening for hepatitis C (HCV) infection in people attending genito-urinary medicine clinics in England. METHODS: An epidemiological model of screening and diagnosis was combined with a Markov chain model of treatment with combination therapy to estimate cost utility. Parameters for the model were informed by literature review, expert opinion and a survey of current screening practice. RESULTS: The base case estimate was about pound 85,000 per QALY. Selective screening is more cost effective. If screening is restricted to only 20% or 10% of attenders, cost utility is estimated as pound 39,647 and pound 34,288 per QALY. If screening is restricted only to those with a history of injecting drug use, cost utility would be pound 27,138 per QALY. Estimates are particularly sensitive to acceptance rates for screening and treatment. CONCLUSIONS: Universal screening for HCV in GUM clinics is unlikely to be cost effective. There is limited evidence to support screening of people other than those with a history of injecting drug use and even this policy should be considered with some care and in the context of further research.