Faculty Bibliography

BACKGROUND: Cigarette smoking is an important risk factor for morbidity and mortality in HIV-positive patients on combination antiretroviral therapy. OBJECTIVE: To determine whether awareness of smoking differs between HIV and non-HIV providers, and to identify factors associated with failure to recognize current smoking. DESIGN: Observational study. PARTICIPANTS: 801 HIV-positive and 602 HIV-negative patients, 72 HIV and 71 non-HIV providers enrolled in the Veterans Aging Cohort 5 Site Study. MEASUREMENTS: Data sources included patient and provider questionnaires; electronic medical records; and the national administrative VA database. We calculated sensitivity, specificity, and measures of agreement between patient- and provider-reported smoking, and examined factors associated with failure to recognize current smoking using logistic regression. RESULTS: Whereas most providers were correct when they identified a patient as a current smoker (specificity > or = 90%), HIV providers missed current smoking more often (sensitivity 65% for HIV vs. 82% for non-HIV). Kappa scores for current smoking were significantly lower for HIV compared to non-HIV providers (0.55 vs. 0.75, p < .001). In models adjusted for age, gender, race, and other differences, patient HIV status and provider specialty in infectious diseases were independent predictors of a provider's failure to recognize current smoking. Comorbid illnesses, cough/dyspnea, degree of immune competence and HIV viral suppression did not impact recognition of current smoking. Only 39% of HIV providers reported confidence in their ability to influence smoking cessation compared to 62% of non-HIV providers (p = .049). CONCLUSIONS: Interventions to increase HIV provider awareness of current smoking and skills to influence smoking cessation are needed. Efforts should also target patient populations with smoking-related comorbid diseases who would especially benefit from smoking cessation

OBJECTIVE: HIV mutation accumulation has great implications for pharmacoeconomics and clinical care, yet scarcity of data has hindered its representation in decision analytic models. Our objective is to determine the accuracy with which mutation accumulation and other unmeasured parameters could be estimated during model calibration. METHODS: We used a second-order Monte Carlo simulation of HIV natural history that had been calibrated by varying two unmeasured parameters (mutation accrual rate and probability of adherence) to minimize differences between estimated and observed clinical outcomes (time to treatment failure and survival). We compared these estimated values first with only those results that had been already published at the time of model calibration, and second including results that were published after model calibration. RESULTS: The value for mutation accrual rate assigned during calibration was 0.014 mutations per month for antiretroviral-naive patients, at the lower bound of the results for nine heterogeneous studies published at the time of calibration (pooled 95% confidence interval [CI] 0.014-0.039 mutations per month). In contrast, this estimate accurately anticipated results from 11 larger and more homogeneous studies published after calibration (pooled 95% CI for antiretroviral-naive patients, 0.012-0.015 mutations per month). The value for probability of adherence assigned during calibration (75%) was also within the range of published results (pooled 95% CI 62-76%). CONCLUSION: Estimates for unobserved parameters derived during model calibration were not only within the range of clinical observations, but anticipated with accuracy clinical results that were not yet available. It may be feasible to use models to estimate unobserved parameters

OBJECTIVES: We aimed to determine adherence, virological, and immunological outcomes one year after starting a first combination antiretroviral therapy (ART) regimen. DESIGN: Observational; synthesis of administrative, laboratory, and pharmacy data. Antiretroviral regimens were divided into efavirenz, nevirapine, boosted protease inhibitor (PI), and single PI categories. Propensity scores were used to control for confounding by treatment assignment. Adherence was estimated from pharmacy refill records. SETTING: Veterans Affairs Healthcare System, all sites. PARTICIPANTS: HIV-infected individuals starting combination ART with a low likelihood of previous antiretroviral exposure. INTERVENTIONS: None. OUTCOMES: The proportion of antiretroviral prescriptions filled as prescribed, a change in log HIV-RNA, the proportion with log HIV-RNA viral suppression, a change in CD4 cell count. RESULTS: A total of 6394 individuals unlikely to have previous antiretroviral exposure started combination ART between 1996 and 2004, and were eligible for analysis. Adherence overall was low (63% of prescriptions filled as prescribed), and adherence with efavirenz (67%) and nevirapine (65%) regimens was significantly greater than adherence with boosted PI (59%) or single PI (61%) regimens (P < 0.001). Efavirenz regimens were more likely to suppress HIV-RNA at one year (74%) compared with nevirapine (62%), boosted PI (63%), or single PI (53%) regimens (all P < 0.001), and this superiority was maintained when analyses were adjusted for baseline clinical characteristics and propensity for treatment assignment. Efavirenz also yielded more favorable immunological outcomes. CONCLUSION: HIV-infected individuals initiating their first combination ART using an efavirenz-based regimen had improved virological and immunological outcomes and greater adherence levels

BACKGROUND: Evidence is accumulating to suggest that clinical guidelines should be modified for patients with comorbidities, yet there is no quantitative and objective approach that considers benefits together with risks. METHODS: We outline a framework using a payoff time, which we define as the minimum elapsed time until the cumulative incremental benefits of a guideline exceed its cumulative incremental harms. If the payoff time of a guideline exceeds a patient's comorbidity-adjusted life expectancy, then the guideline is unlikely to offer a benefit and should be modified. We illustrate the framework by applying this method to colorectal cancer screening guidelines for 50-year-old men with human immunodeficiency virus (HIV) and 60-year-old women with congestive heart failure (CHF). RESULTS: We estimated that colorectal cancer screening payoff times for 50-year-old men with HIV would range from 1.9 to 5.0 years and that colorectal cancer screening payoff times for 60-year-old women with CHF would range from 0.7 to 2.9 years. Because the payoff times for 50-year-old men with HIV were lower than their life expectancies (12.5-24.0 years), colorectal cancer screening may be beneficial for these patients. In contrast, because payoff times for 60-year-old women with CHF were sometimes greater than their life expectancies (0.6 to >5 years), colorectal cancer screening is likely to be harmful for some of these patients. CONCLUSION: Use of a payoff time calculation may be a feasible framework to tailor clinical guidelines to the comorbidity profiles of individual patients

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