Rapid, Fully Automated Digital Immunoassay for p24 Protein with the Sensitivity of Nucleic Acid Amplification for Detecting Acute HIV Infection.

BACKGROUND: Nucleic acid testing (NAT) has become the standard for high sensitivity in detecting low levels of virus. However, adoption of NAT can be cost prohibitive in low-resource settings where access to extreme sensitivity could be clinically advantageous for early detection of infection. We report development and preliminary validation of a simple, low-cost, fully automated digital p24 antigen immunoassay with the sensitivity of quantitative NAT viral load (NAT-VL) methods for detection of acute HIV infection. METHODS: We developed an investigational 69-min immunoassay for p24 capsid protein for use on a novel digital analyzer on the basis of single-molecule-array technology. We evaluated the assay for sensitivity by dilution of standardized preparations of p24, cultured HIV, and preseroconversion samples. We characterized analytical performance and concordance with 2 NAT-VL methods and 2 contemporary p24 Ag/Ab combination immunoassays with dilutions of viral isolates and samples from the earliest stages of HIV infection. RESULTS: Analytical sensitivity was 0.0025 ng/L p24, equivalent to 60 HIV RNA copies/mL. The limit of quantification was 0.0076 ng/L, and imprecision across 10 runs was <10% for samples as low as 0.09 ng/L. Clinical specificity was 95.1%. Sensitivity concordance vs NAT-VL on dilutions of preseroconversion samples and Group M viral isolates was 100%. CONCLUSIONS: The digital immunoassay exhibited >4000-fold greater sensitivity than contemporary immunoassays for p24 and sensitivity equivalent to that of NAT methods for early detection of HIV. The data indicate that NAT-level sensitivity for acute HIV infection is possible with a simple, low-cost digital immunoassay.

Fully automated ultrasensitive digital immunoassay for cardiac troponin I based on single molecule array technology.

BACKGROUND: The association between increases in cardiac troponin and adverse cardiac outcomes is well established. There is a growing interest in exploring routine cardiac troponin monitoring as a potential early indicator of adverse heart health trends. Prognostic use of cardiac troponin measurements requires an assay with very high sensitivity and outstanding analytical performance. We report development and preliminary validation of an investigational assay meeting these requirements and demonstrate its applicability to cohorts of healthy individuals and patients with heart failure. METHODS: On the basis of single molecule array technology, we developed a 45-min immunoassay for cardiac troponin I (cTnI) for use on a novel, fully automated digital analyzer. We characterized its analytical performance and measured cTnI in healthy individuals and heart failure patients in a preliminary study of assay analytical efficacy. RESULTS: The assay exhibited a limit of detection of 0.01 ng/L, a limit of quantification of 0.08 ng/L, and a total CV of 10% at 2.0 ng/L. cTnI concentrations were well above the assay limit of detection for all samples tested, including samples from healthy individuals. cTnI was significantly higher in heart failure patients, and exhibited increasing median and interquartile concentrations with increasing New York Heart Association classification of heart failure severity. CONCLUSIONS: The robust 2-log increase in sensitivity relative to contemporary high-sensitivity cardiac troponin immunoassays, combined with full automation, make this assay suitable for exploring cTnI concentrations in cohorts of healthy individuals and for the potential prognostic application of serial cardiac troponin measurements in both apparently healthy and diseased individuals.

Gender differences in asthma prevalence: variations with socioeconomic disadvantage.

BACKGROUND AND OBJECTIVE: Socioeconomic inequalities in health have been shown to vary for different diseases and by gender. This study aimed to examine gender differences in associations between asthma and socioeconomic disadvantage. METHODS: Socioeconomic variables were assessed among men and women in the North West Adelaide Health Study, a representative population cohort (n = 4060) aged 18 years and over in metropolitan South Australia. Asthma was determined from spirometry and self-reported doctor diagnosis. RESULTS: The prevalence of asthma was 12.0% (95% CI: 11.1-13.1), and was significantly higher among women (13.5%) than men (10.5%). For participants aged 18-64 years a higher prevalence of asthma was associated with an education level of secondary school or lower, or not being in the paid labour force among men, and with a gross annual household income of $20,000 or less among women. Among socioeconomically advantaged groups, the prevalence of asthma was significantly higher among women than men. CONCLUSIONS: Socioeconomic disadvantage was associated with higher asthma prevalence, although this varied by gender depending on the indicator of socioeconomic position used. Men with low education or those not employed in the paid labour force had higher asthma prevalence than more socioeconomically advantaged men. Women with low income had higher asthma prevalence than those with higher income. Among all socioeconomically advantaged groups, and also the low-income group, women experienced a higher prevalence of asthma than men.

Risks associated with low functional health literacy in an Australian population.

OBJECTIVE: To measure the level of functional health literacy (FHL) in an Australian population, and to explore the level of risk associated with level of FHL. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional, random population survey administered to 2824 South Australians aged>or=15 years, September-October 2008. MAIN OUTCOME MEASURES: Newest Vital Sign as a measure of FHL, self-reported general health status, and use of health services. RESULTS: 24% of respondents were at risk of limited FHL, and 21% had a high likelihood of inadequate FHL; this increased with age (>or=65 years, 50% v 25-44 years, 11%). In multiple logistic regression models, a high likelihood of inadequate FHL was significantly more common among those with lower education (left schoolor=65 years with inadequate FHL were more likely to have been admitted to hospital (OR, 2.2; 95% CI, 1.1-4.5). CONCLUSION: Many Australians are likely to have limited health literacy, and this is a risk to effective health care delivery and health improvement across the community.

Cholesterol-lowering therapy and the Australian Pharmaceutical Benefits Scheme: a population study.

OBJECTIVE: The Australian Pharmaceutical Benefits Scheme (PBS) expanded the criteria for eligibility for subsidised lipid-lowering therapy (LLT) in 2006. The aim of this study was to determine the use of LLT in a representative Australian population in relation to cardiovascular disease (CVD) risk, and the effectiveness of the therapy in meeting target levels. DESIGN: Cross-sectional biomedical study with telephone interviews, questionnaires, clinical measurements, and PBS dispensing data. SUBJECTS: Representative population sample of 4060 urban adults aged > or = 18 years attending for the biomedical examination in 2001. RESULTS: Of the 406 who qualified for PBS-subsidised LLT at that time, only 88 (21.5%) were actually on LLT. National Heart Foundation of Australia (NHF) recommended low-density lipoprotein cholesterol (LDL-C) levels of < 2.5 mmol/L were recorded in only 13% (528) of the population, and in 46.8% of those on LLT. Of those on LLT, 76% had total cholesterol < 5.5 mmol/L, but over 80% had total cholesterol levels above NHF-recommended levels of 4.0 mmol/L. Of the 842 classified at the highest CVD risk, only 26% were using LLT. Those aged > 60 years and on low incomes were significantly more likely to use LLT. The new PBS criteria will expand eligibility to include nearly 20% of adults. CONCLUSIONS: The majority of people at high risk of CVD were not receiving LLT, and LLT is not being used to its full effectiveness. People with low incomes or on government benefits or pensions were not less likely to use LLT than others under the PBS scheme. Whether higher copayments for those on low incomes who do not qualify for concessional payments is a significant barrier to LLT use needs further research.

Effects of area deprivation on health risks and outcomes: a multilevel, cross-sectional, Australian population study.

OBJECTIVES: Our aim was to examine the effect of local area socio-economic disadvantage after accounting for individual socio-economic status (SES), and to determine if these differ between various health and risk factor variables. METHODS: The North West Adelaide Health Study (NWAHS) is a biomedical representative population study of adults. The Index of Relative Socio-Economic Disadvantage (IRSD), produced from the Australian Bureau of Statistics (ABS) Census data at the level of Collector Districts (200 dwellings) was used as an indicator of local area disadvantage. Multi-level modeling techniques examined the effects of IRSD level on a variety of health outcomes and risk factors, after accounting for individual socio-economic factors. RESULTS: Significant, independent associations were seen between IRSD and obesity, smoking, and health-related quality of life, with 5 % to 7.2 % of the variance located at the neighborhood level. No independent associations were seen between IRSD and estimated cardiovascular disease risk, diabetes, physical activity, or at-risk alcohol use. CONCLUSIONS: Aggregated area-level characteristics make modest, but significant independent contributions to smoking, obesity and quality of life, but not for other health outcomes.

Medicare-related service use and costs among people with diagnosed and undiagnosed diabetes and respiratory conditions.

OBJECTIVE: To compare Medicare-related costs and service utilisation of people with diagnosed diabetes, asthma or chronic obstructive pulmonary disease (COPD) to those who were previously undiagnosed, and those without these conditions. DESIGN, SETTING AND PARTICIPANTS: Representative cross-sectional study of people (18+ years) living in the north-west area of Adelaide. Participants were recruited by telephone interviews. Biomedical and self-report data for 2352 participants were linked to Medicare Australia Medicare Benefits Schedule (MBS) data from 1997 to 2002. MAIN OUTCOME MEASURES: Mean number and cost (benefit paid) of MBS services for people with diagnosed and previously undiagnosed diabetes, asthma, and COPD, and those without these conditions. RESULTS: Mean (+/- SD) MBS costs were significantly greater for people diagnosed with diabetes ($4205 +/- 2596), asthma ($3307 +/- 2542), or COPD ($3779 +/- 2529) than for those without these conditions. MBS costs for people with asthma or COPD that had not yet been diagnosed were also significantly higher than for those without these conditions, although this was inconsistent across financial years. CONCLUSIONS: Diabetes, asthma, and COPD are costly conditions in terms of health service use. Costs associated with undiagnosed asthma and COPD are similar to their diagnosed states. Prevention of progression along each chronic disease continuum is likely to reduce costs.

The escalating cost and prevalence of alternative medicine.

BACKGROUND: The purpose of this study was to measure trends in the prevalence and cost of alternative medicines and alternative practitioner use in an Australian population and to obtain a profile of users and their beliefs. METHODS: In 2000, we repeated a 1993 representative population survey of persons ages 15 years or older living in South Australia, which provided 3,027 personal interviews. We assessed the rates of use, types of alternative medicine and therapists, costs, and beliefs of users and nonusers. Comparisons in usage patterns with the 1993 survey were also made. FINDINGS: In 2000, the overall use of at least one nonmedically prescribed alternative medicine (excluding calcium, iron, and prescribed vitamins) was 52.1% (CI +/- 1.8). Users were more likely to be female, be better educated, have a higher income, and be employed. Since 1993, females were using significantly more herbal medicines, ginseng, Chinese medicines, and aromatherapy oils. Many were self-prescribed. Among users, 57.2% (CI +/- 1.2) did not tell their doctor. In 2000, 23.3% of respondents had visited at least one alternative practitioner with increasing use of acupuncturists, reflexologists, aromatherapists, and herbal therapists. Most thought alternative medicines were safe but thought they were, or should be, subject to the same standards as prescribed medicines. Among respondents, 92.9% wished product information to be of standard and content similar to those supplied with pharmaceuticals. INTERPRETATION: Extrapolation of the costs to the Australian population gives an expenditure on alternative therapies in 2000 of $AUD2.3 billion and for the U.S. population an annual expenditure of $US34 billion. In Australia this represents a 120 and 62% increase in the cost of alternative medicines and therapists, respectively, since 1993. In 2000 expenditure on alternative therapies was nearly four times the public contribution to all pharmaceuticals. The public appears to have ambivalent standards for alternative therapies but wishes to be empowered with accurate information to facilitate self-prescription. The public health ramifications of an expanding alternative medicine industry are great.