Faculty Bibliography

BACKGROUND: Intentional exposures to aerosolized Bacillus anthracis spores have caused fatalities. OBJECTIVE: To evaluate the cost-effectiveness of strategies to reduce mortality from future inhalational anthrax exposures. METHODS: Computer cohort simulation of a 100,000-person single-site exposure (worst-case scenario) and a 100-person multiple-site exposure (resembling the recent US attack). For each scenario, universal vaccination and an emergency surveillance and response (ESR) system were compared with a default strategy that assumed eventual discovery of the exposure. RESULTS: If an exposure was unlikely to occur or was small in scale, neither vaccination nor an ESR system was cost-effective. If an exposure was certain and large in scale, an ESR system was more cost-effective than vaccination ($73 v. $29,600 per life-year saved), and a rapid response saved more lives than improved surveillance. CONCLUSIONS: Strategies to reduce deaths from anthrax attacks are cost-effective only if large exposures are certain. A faster response is more beneficial than enhanced surveillance

BACKGROUND: Male veterans represent a large population at risk for acquiring or transmitting human immunodeficiency virus (HIV) infection. We sought to determine the prevalence of risky sexual behavior among veterans with and without HIV infection and to assess the relationship of intoxication before intercourse and other measures of drug and alcohol use to risky sexual behavior in this population. METHODS: We analyzed baseline data on 1009 HIV-positive (mean age 49 years) and 710 HIV-negative male veterans (mean age 55 years) who were participating in the Veterans Aging Cohort 5-Site Study (VACS 5). Participants completed a written questionnaire that included measures of alcohol and drug use and risky sexual behavior. RESULTS: Compared with HIV-negative veterans, HIV-positive veterans were more likely to report 5 or more sexual partners in the past year (14% vs. 4%, P < 0.01), less likely to report not using a condom at last intercourse (25% vs. 75%, P < 0.01), and similarly likely to report having 2 or more partners and inconsistent condom use (10% vs. 10%). Among sexually active HIV-positive veterans, intoxication before intercourse was significantly associated with having 5 or more sexual partners in the past year (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1-2.8), inconsistent condom use (OR 1.8, 95% CI 1.2-2.7), and the combined measure of 2 or more partners and inconsistent condom use (OR 1.8, 95% CI 1.1-3.0). Intoxication before intercourse was not significantly associated with these behaviors in HIV-negative veterans, although similar trends were noted. CONCLUSION: Risky sexual behavior was common among male veterans attending outpatient clinics and is more common among HIV-positive veterans who use alcohol and drugs in sexual situations. Asking HIV-positive men a single question about intoxication before intercourse could help to identify men at increased risk of engaging in risky sexual behavior, and specific advice to avoid intoxication in sexual situations could help to reduce risky sexual behavior

BACKGROUND: Studies have established that physiologic instability and services mismatching precede adverse events in hospitalized patients. In response to these considerations, the concept of a Rapid Response System (RRS) has emerged. The responding team is commonly known as a medical emergency team (MET), rapid response team (RRT), or critical care outreach (CCO). Studies show that an RRS may improve outcome, but questions remain regarding the benefit, design elements, and advisability of implementing a MET system. METHODS: In June 2005 an International Conference on Medical Emergency Teams (ICMET) included experts in patient safety, hospital medicine, critical care medicine, and METs. Seven of 25 had no experience with an RRS, and the remainder had experience with one of the three major forms of RRS. After preconference telephone and e-mail conversations by the panelists in which questions to be discussed were characterized, literature reviewed, and preliminary answers created, the panelists convened for 2 days to create a consensus document. Four major content areas were addressed: What is a MET response? Is there a MET syndrome? What are barriers to METS? How should outcome be measured? Panelists considered whether all hospitals should implement an RRS. RESULTS: Patients needing an RRS intervention are suddenly critically ill and have a mismatch of resources to needs. Hospitals should implement an RRS, which consists of four elements: an afferent, 'crisis detection' and 'response triggering' mechanism; an efferent, predetermined rapid response team; a governance/administrative structure to supply and organize resources; and a mechanism to evaluate crisis antecedents and promote hospital process improvement to prevent future events

The authors discuss techniques for Monte Carlo (MC) cohort simulations that reduce the number of simulation replications required to achieve a given degree of precision for various output measures. Known as variance reduction techniques, they are often used in industrial engineering and operations research models, but they are seldom used in medical models. However, most MC cohort simulations are well suited to the implementation of these techniques. The authors discuss the cost of implementation versus the benefit of reduced replications

OBJECTIVES: Determining the relationship between antiretroviral adherence and resistance accumulation is important for the design and evaluation of adherence interventions. Our objective was to explain heterogeneity observed in this relationship. METHODS: We first conducted a systematic review to locate published reports describing the relationship between adherence and resistance. We then used a validated computer simulation to simulate the patient populations in these reports, exploring the impact of changes in individual patient characteristics (age, CD4, viral load, prior antiretroviral experience) on the shape of the adherence-resistance (A-R) curve. RESULTS: The search identified 493 titles, of which 3 contained relevant primary data and 2 had sufficient follow-up for inclusion (HOMER and REACH cohorts). When simulating HOMER, the A-R curve had a high peak with a greatly increased hazard ratio (HR) of accumulating mutations at partial compared to complete adherence (simulation, HR 2.9; HOMER, HR 2.7). When simulating REACH, the A-R curve had a shallow peak with a slightly increased hazard of accumulating mutations at partial adherence (simulation, HR 1.2; REACH, HR 1.4). This heterogeneity was primarily attributable to differences in antiretroviral experience between the cohorts. CONCLUSIONS: Our computer simulation was able to explain much of the heterogeneity in observed A-R curves

An exposure assessment and risk characterization was conducted to better understand the potential human health significance of trace levels of perfluorooctanoate (PFO) detected in certain consumer articles. PFO is the anion of perfluorooctanoic acid (PFOA). Concentrations of PFO in the consumer articles were determined from extraction tests and product formulation information. Potential exposures during consumer use of the articles were quantified based on an assessment of behavior patterns and regulatory guidance. Health benchmarks were developed and then compared to the exposure estimates to yield margins of exposure (MOEs). A simple one-compartment model was also developed to estimate contributions of potential consumer exposures to PFO concentrations in serum. While there are considerable uncertainties in this assessment, it indicates that exposures to PFO during consumer use of the articles evaluated in this study are not expected to cause adverse human health effects in infants, children, adolescents, adult residents, or professionals nor result in quantifiable levels of PFO in human serum

BACKGROUND: Previous studies have shown that alcohol consumption is associated with decreased medication adherence, but this association may be confounded by characteristics common among those who drink heavily and those who fail to adhere (e.g., illicit drug use). Our objective was to determine whether there are temporal and dose-response relationships between alcohol consumption and poor adherence. METHODS: We administered telephone interview surveys to participants in the Veterans Aging Cohort Study, an eight-site observational study of HIV+ and matched HIV- veterans in care, to determine whether alcohol consumption on a particular day was associated with nonadherence to prescribed medications on that same day. We used the Time Line Follow Back to measure alcohol consumption and the Time Line Follow Back Modified for Adherence to measure adherence. Individuals were categorized as abstainers (no alcohol in past 30 days), nonbinge drinkers (alcohol in past 30 days but < or =four standard drinks on each day), or binge drinkers (> or =five standard drinks on at least one day). RESULTS: Among 2702 respondents, 1582 (56.6%) were abstainers, 931 (34.5%) were nonbinge drinkers, and 239 (8.9%) were binge drinkers. Abstainers missed medication doses on 2.4% of surveyed days. Nonbinge drinkers missed doses on 3.5% of drinking days, 3.1% of postdrinking days, and 2.1% of nondrinking days (p < 0.001 for trend), and this trend was more pronounced among HIV+ individuals than HIV- individuals. Binge drinkers missed doses on 11.0% of drinking days, 7.0% of postdrinking days, and 4.1% of nondrinking days (p < 0.001 for trend), and this trend was comparably strong for HIV+ and HIV- individuals. CONCLUSIONS: Among veterans in care, self-reported alcohol consumption demonstrates a temporal and dose-response relationship to poor adherence. HIV+ individuals may be particularly sensitive to alcohol consumption

PURPOSE: Effective antiretroviral therapies have improved the prognosis for patients infected with the human immunodeficiency virus (HIV). We aimed to estimate the likelihood that HIV-infected patients would die of comorbid disease. METHODS: A probabilistic simulation of antiretroviral-naive HIV-infected patients in the United States was calibrated with data from an observational cohort (N = 3545) and validated with data from a separate patient cohort (N = 12574). The simulation explicitly represents the 2 main determinants of treatment failure and subsequent death from HIV-related causes: nonadherence to combination therapy and accumulation of phenotypic resistance to combination therapy. The likelihood of deaths not directly attributable to HIV was estimated from the Collaborations in HIV Outcomes Research-US (CHORUS) cohort. RESULTS: For patients with newly diagnosed HIV infections, CD4 counts of 500 cells/mm3, and viral loads of 10000 copies/mL, the median estimated survival was 26.8 years for 30-year-olds, 24.4 years for 40-year-olds and 14.6 years for 50-year-olds. The proportion of deaths not directly attributable to HIV was 36% for 30-year-olds, 53% for 40-year-olds, and 72% for 50-year-olds. For patients with characteristics similar to CHORUS participants, the median estimated survival approached 20.4 years, the mean age at death approached 60.4 years, and 41% died of illnesses not directly attributable to HIV. These estimates of non-HIV mortality were likely conservative. CONCLUSION: As HIV-infected patients live longer, our results suggest they will experience increasing mortality from causes not directly attributable to HIV. The projected risk from comorbid disease has clinical and policy implications for future delivery of care to HIV-infected patients