Innovations in Evaluating Statin Benefit and Efficacy in Staphylococcus aureus Intracellular Infection Management.

An emerging therapeutic approach in the treatment of infectious disease is to augment the host response through repurposing of well-tolerated, non-antibiotic, host-directed therapeutics. Earlier retrospective studies identify a positive association between statin use and a decreased risk of death due to sepsis or bacteremia. However, more recent randomized control trials fail to detect a therapeutic benefit in these complex infection settings. It is postulated that unrecognized biases in certain observational studies may have led to an overestimation of benefit and that statin use is instead a marker for health status, wealth, and demographic characteristics which may separately affect death due to infection. What remains unresolved is that in vitro and in vivo evidence reproducibly indicates that statin pharmacology limits infection and augments immunomodulatory responses, suggesting that therapeutic benefits may be attainable in certain infection settings, such as intracellular infection by S. aureus. Carefully considering the biological mechanisms capable of driving the relationship between statins and infections and constructing a methodology to avoid potential biases in observational studies would enable the examination of protective effects against infection and limit the risk of underestimating statin efficacy. Such an approach would rely on the examination of statin use in defined infection settings based on an underlying mode-of-action and pharmacology, where the inhibition of HMG-CoA-reductase at the rate-limiting step in cholesterol biosynthesis diminishes not only cholesterol levels but also isoprenoid intermediates central to host cell invasion by S. aureus. Therapeutic benefit in such settings, if existent, may be of clinical importance.

On the measurement of health and its effect on the measurement of health inequality.

We examine the extent to which self-reported health measures suffer from income-related reporting heterogeneity and then characterize how this reporting heterogeneity affects the estimation of income-related health inequality. We run a comprehensive set of tests of reporting heterogeneity using several self-reported health measures and several clinical measures of health from the National Health and Nutritional Examination Surveys. We propose the use of a multidimensional measure using clinical indicators of health in the context of measuring income-related health inequality, and we examine the extent of income-related health inequality, as measured by the concentration index, using both self-reported measures of health and the multidimensional clinical measure. Our results confirm the existence of significant, positive, income-related reporting heterogeneity and also suggest that higher income individuals react more strongly to a change in clinical health measures. Using self-assessed health suggests that income-related health inequality is about three times larger than when using more objective, self-reported health measures and ten times larger than when using the multidimensional clinical measure of health.

Crystal Clear? The Relationship Between Methamphetamine Use and Sexually Transmitted Infections.

Public health officials have cited methamphetamine control as a tool with which to decrease HIV and other sexually transmitted infections, based on previous research that finds a strong positive correlation between methamphetamine use and risky sexual behavior. However, the observed correlation may not be causal, as both methamphetamine use and risky sexual behavior could be driven by a third factor, such as a preference for risky behavior. We estimate the effect of methamphetamine use on risky sexual behavior using monthly data on syphilis diagnoses in California and quarterly data on syphilis, gonorrhea, and chlamydia diagnoses across all states. To circumvent possible endogeneity, we use a large exogenous supply shock in the US methamphetamine market that occurred in May 1995 and a later shock stemming from the Methamphetamine Control Act, which went into effect in October 1997. While the supply shocks had large negative effects on methamphetamine use, we find no evidence that they decreased syphilis, gonorrhea, or chlamydia rates. Our results have broad implications for public policies designed to decrease sexually transmitted infection rates.

An information theory based framework for the measurement of population health.

This paper proposes a new framework for the measurement of population health and the ranking of the health of different geographies. Since population health is a latent variable, studies which measure and rank the health of different geographies must aggregate observable health attributes into one summary measure. We show that the methods used in nearly all the literature to date implicitly assume that all attributes are infinitely substitutable. Our method, based on the measurement of multidimensional welfare and inequality, minimizes the entropic distance between the summary measure of population health and the distribution of the underlying attributes. This summary function coincides with the constant elasticity of substitution and Cobb-Douglas production functions and naturally allows different assumptions regarding attribute substitutability or complementarity. To compare methodologies, we examine a well-known ranking of the population health of U.S. states, America's Health Rankings. We find that states' rankings are somewhat sensitive to changes in the weight given to each attribute, but very sensitive to changes in aggregation methodology. Our results have broad implications for well-known health rankings such as the 2000 World Health Report, as well as other measurements of population and individual health levels and the measurement and decomposition of health inequality.