Faculty Bibliography

Clinicians may defer antiretroviral treatment for patients with suboptimal adherence. We used a validated computer simulation of HIV disease progression to compare alternative treatment thresholds for patients with suboptimal adherence. Earlier treatment increased life expectancy across a wide adherence range (50%-100% of doses taken). Delaying treatment for patients with suboptimal adherence may not always be appropriate

BACKGROUND: Practice guidelines rarely consider comorbid illness, and resulting overuse of health services may increase costs without conferring benefit. OBJECTIVE: To individualize a framework for inferring when patients with comorbid illness are not likely to benefit from colorectal cancer screening guidelines. METHODS: We modified the 'payoff time' framework (the minimum time until a guideline's cumulative benefits exceed its cumulative harms) to increase its applicability to a wide range of primary care patients. We show how it may inform colorectal (CR) cancer screening decisions for 3 typical patients in general practice for whom CR screening would be recommended by current guidelines: (1) 60-year-old man with diabetes, congestive heart failure, lung disease, stroke, and substantial frailty; (2) 60-year-old woman with diabetes and obesity, without other comorbidity or frailty; and (3) 50-year-old woman with inflammatory bowel disease. RESULTS: For patient 1, the payoff time for CR screening (minimum time until benefits exceed harms) is 7.3 years, and for patient 2, the payoff time for CR screening is 5.4 years. Evidence is insufficient to estimate the payoff time for patient 3. Because patient 1's estimated life expectancy is 3.7 years (less than his payoff time), he is unlikely to benefit from CR screening. Because patient 2's estimated life expectancy exceeds 10 years (greater than her payoff time), she may benefit from CR screening. Because evidence is insufficient to estimate the payoff time for patient 3, the payoff time framework does not inform decision making. CONCLUSION: The payoff time framework may identify patients for whom particular clinical guidelines are unlikely to confer benefit, and has the potential to decrease unnecessary health care

It is unknown whether smoking confers similar mortality risk in HIV-positive as in HIV-negative patients. We compared overall mortality stratified by HIV and smoking of 1,034 HIV-positive block-matched to 739 HIV-negative veterans, enrolled 2001-2002 in the Veterans Aging Cohort 5 Site Study. Adjusted incidence rate ratios (IRR) for mortality were calculated using Poisson regression. Mortality was significantly increased in HIV-positive veterans according to both smoking status and pack-years in unadjusted and adjusted analyses (adjusted IRR 2.31, 95% confidence interval [CI] 1.53-3.49 for HIV-positive current smokers and IRR 1.32, 95% CI 0.67-2.61 for HIV-negative current smokers). Comorbid diseases were also significantly increased according to smoking status and pack-years. Current smoking is associated with poor outcomes; even lower levels of exposure appear to be detrimental in HIV-infected veterans. These findings support the need for improvements in smoking cessation and for studies of mechanisms and diseases underlying increased mortality in smokers with HIV

BACKGROUND: The decrement in utility attributable to side effects from combination antiretroviral therapy (CART) is unknown and likely to influence clinical decisions regarding CART initiation and cost-effectiveness. OBJECTIVE: To quantify the decrement in utility attributable to side effects from CART. METHODS: We estimated SF-6D utilities (quality-of-life weights on a scale from 0.29 [worst possible health] to 1.00 [perfect health]) from SF-12 scores among patients with HIV in the Veterans Aging Cohort Study by using a published and validated conversion algorithm. We then compared utilities among patients who: 1) did not have bothersome symptoms while taking CART; 2) had bothersome symptoms that they thought might be due to CART; and 3) had bothersome symptoms that they were confident were due to CART; we controlled for other characteristics known to influence quality of life and stratified analyses by CD4 count. RESULTS: Among 1864 patients with available data, symptoms perceived to be attributable to CART were associated with a mean (95% confidence interval) decrement in utility of 0.06 (0.05, 0.08) points in univariate analyses and 0.08 (0.06, 0.10) in multivariable analyses, clinically significant differences that are comparable to utility decrements reported for partial impotence or mild angina. Other significant predictors of changes in SF-6D utilities were hazardous alcohol consumption, recent drug use, cigarette smoking, homelessness, and African American race (R(2) = 0.12). Stratifying by CD4 count, symptoms attributable to CART side effects decreased utility by 0.03 to 0.08 points. CONCLUSIONS: Symptoms perceived to be related to CART are associated with a substantial decrement in utility

BACKGROUND: The optimal threshold for initiating HIV treatment is unclear. OBJECTIVE: To compare different thresholds for initiating HIV treatment. DESIGN: A validated computer simulation was used to weigh important harms from earlier initiation of antiretroviral therapy (toxicity, side effects, and resistance accumulation) against important benefits (decreased HIV-related mortality). DATA SOURCES: Veterans Aging Cohort Study (5742 HIV-infected patients and 11 484 matched uninfected controls) and published reports. TARGET POPULATION: Individuals with newly diagnosed chronic HIV infection and varying viral loads (10,000, 30,000, 100,000, and 300,000 copies/mL) and ages (30, 40, and 50 years). TIME HORIZON: Unlimited. PERSPECTIVE: Societal. INTERVENTION: Alternative thresholds for initiating antiretroviral therapy (CD4 counts of 200, 350, and 500 cells/mm3). OUTCOME MEASURES: Life-years and quality-adjusted life-years (QALYs). RESULTS OF BASE-CASE ANALYSIS: Although the simulation was biased against earlier treatment initiation because it used an upper-bound assumption for therapy-related toxicity, earlier treatment increased life expectancy and QALYs at age 30 years regardless of viral load (life expectancies with CD4 initiation thresholds of 500, 350, and 200 cells/mm3 were 18.2 years, 17.6 years, and 17.2 years, respectively, for a viral load of 10,000 copies/mL and 17.3 years, 15.9 years, and 14.5 years, respectively, for a viral load of 300,000 copies/mL), and increased life expectancies at age 40 years if viral loads were greater than 30 000 copies/mL (life expectancies were 12.5 years, 12.0 years, and 11.4 years, respectively, for a viral load of 300,000 copies/mL). RESULTS OF SENSITIVITY ANALYSIS: Findings favoring early treatment were generally robust. LIMITATIONS: Results favoring later treatment may not be valid. The findings may not be generalizable to women. CONCLUSION: This simulation suggests that earlier initiation of combination antiretroviral therapy is often favored compared with current recommendations

CONTEXT: Occurrence of in-hospital cardiac arrest and survival patterns have not been characterized by time of day or day of week. Patient physiology and process of care for in-hospital cardiac arrest may be different at night and on weekends because of hospital factors unrelated to patient, event, or location variables. OBJECTIVE: To determine whether outcomes after in-hospital cardiac arrest differ during nights and weekends compared with days/evenings and weekdays. DESIGN AND SETTING: We examined survival from cardiac arrest in hourly time segments, defining day/evening as 7:00 am to 10:59 pm, night as 11:00 pm to 6:59 am, and weekend as 11:00 pm on Friday to 6:59 am on Monday, in 86,748 adult, consecutive in-hospital cardiac arrest events in the National Registry of Cardiopulmonary Resuscitation obtained from 507 medical/surgical participating hospitals from January 1, 2000, through February 1, 2007. MAIN OUTCOME MEASURES: The primary outcome of survival to discharge and secondary outcomes of survival of the event, 24-hour survival, and favorable neurological outcome were compared using odds ratios and multivariable logistic regression analysis. Point estimates of survival outcomes are reported as percentages with 95% confidence intervals (95% CIs). RESULTS: A total of 58,593 cases of in-hospital cardiac arrest occurred during day/evening hours (including 43,483 on weekdays and 15,110 on weekends), and 28,155 cases occurred during night hours (including 20,365 on weekdays and 7790 on weekends). Rates of survival to discharge (14.7% [95% CI, 14.3%-15.1%] vs 19.8% [95% CI, 19.5%-20.1%], return of spontaneous circulation for longer than 20 minutes (44.7% [95% CI, 44.1%-45.3%] vs 51.1% [95% CI, 50.7%-51.5%]), survival at 24 hours (28.9% [95% CI, 28.4%-29.4%] vs 35.4% [95% CI, 35.0%-35.8%]), and favorable neurological outcomes (11.0% [95% CI, 10.6%-11.4%] vs 15.2% [95% CI, 14.9%-15.5%]) were substantially lower during the night compared with day/evening (all P values < .001). The first documented rhythm at night was more frequently asystole (39.6% [95% CI, 39.0%-40.2%] vs 33.5% [95% CI, 33.2%-33.9%], P < .001) and less frequently ventricular fibrillation (19.8% [95% CI, 19.3%-20.2%] vs 22.9% [95% CI, 22.6%-23.2%], P < .001). Among in-hospital cardiac arrests occurring during day/evening hours, survival was higher on weekdays (20.6% [95% CI, 20.3%-21%]) than on weekends (17.4% [95% CI, 16.8%-18%]; odds ratio, 1.15 [95% CI, 1.09-1.22]), whereas among in-hospital cardiac arrests occurring during night hours, survival to discharge was similar on weekdays (14.6% [95% CI, 14.1%-15.2%]) and on weekends (14.8% [95% CI, 14.1%-15.2%]; odds ratio, 1.02 [95% CI, 0.94-1.11]). CONCLUSION: Survival rates from in-hospital cardiac arrest are lower during nights and weekends, even when adjusted for potentially confounding patient, event, and hospital characteristics

BACKGROUND: In the United States, $50,000 per Quality-Adjusted Life-Year (QALY) is a decision rule that is often used to guide interpretation of cost-effectiveness analyses. However, many investigators have questioned the scientific basis of this rule, and it has not been updated. METHODS: We used 2 separate approaches to investigate whether the $50,000 per QALY rule is consistent with current resource allocation decisions. To infer a lower bound for the decision rule, we estimated the incremental cost-effectiveness of recent (2003) versus pre-'modern era' (1950) medical care in the United States. To infer an upper bound for the decision rule, we estimated the incremental cost-effectiveness of unsubsidized health insurance versus self-pay for nonelderly adults (ages 21-64) without health insurance. We discounted both costs and benefits, following recommendations of the Panel on Cost-Effectiveness in Health and Medicine. RESULTS: Our base case analyses suggest that plausible lower and upper bounds for a cost-effectiveness decision rule are $183,000 per life-year and $264,000 per life-year, respectively. Our sensitivity analyses widen the plausible range (between $95,000 per life-year saved and $264,000 per life-year saved when we considered only health care's impact on quantity of life, and between $109,000 per QALY saved and $297,000 per QALY saved when we considered health care's impact on quality as well as quantity of life) but it remained substantially higher than $50,000 per QALY. CONCLUSIONS: It is very unlikely that $50,000 per QALY is consistent with societal preferences in the United States

BACKGROUND: Screening for hazardous drinking may fail to detect a substantial proportion of individuals harmed by alcohol. We investigated whether considering an individual's usual drinking quantity or threshold for alcohol-induced cognitive impairment improves the prediction of nonadherence with prescribed medications. METHOD: Cross-sectional analysis of participants in a large, multi-site cohort study. We used the timeline followback to reconstruct 30-day retrospective drinking histories and the timeline followback modified for adherence to reconstruct 30-day medication adherence histories among 3,152 individuals in the Veterans Aging Cohort Study, 1,529 HIV infected and 1,623 uninfected controls. We categorized daily alcohol consumption by using quantity alone, quantity after adjustment for the individual's mean daily alcohol consumption, and self-reported level of impairment corresponding to each quantity. A standard drink was defined as 14 g of ethanol. Nonadherence was defined as the proportion of days with > or =1 medication doses missed or taken > or =2 hours late, and clinically significant nonadherence was defined as > or =5% absolute increase in the proportion of days with nonadherence. RESULTS: The mean adjusted- and impairment-based methods showed greater discrimination of nonadherence risk compared to the measure based on quantity alone (quantity-based categorization, 3.2-fold increase; quantity adjusted for mean daily consumption, 4.6-fold increase, impairment-based categorization, 3.6-fold increase). The individualized methods also detected greater numbers of days with clinically significant nonadherence associated with alcohol. Alcohol was associated with clinically significant nonadherence at a lower threshold for HIV infected versus uninfected patients (2 standard drinks vs. 4 standard drinks) using quantity-based categorization, but this difference was no longer apparent when individualized methods were used. CONCLUSIONS: Tailoring screening questions to an individual's usual level of alcohol consumption or threshold for impairment improves the ability to predict alcohol-associated medication nonadherence

The interpersonal-psychological theory of suicidal behavior (Joiner, 2005) proposes that the need to belong is fundamental; when met it can prevent suicide and when thwarted it can substantially increase the risk for suicide. We investigate one source of group-wide variation in belongingness among college students--changes in the social composition of college campuses across academic semesters--as an explanation for variation in suicidal ideation across the academic year. Our results indicate that in a sample of college students at a large southern state university (n = 309), suicidal ideation varied across academic semesters, with highest levels in summer compared to both spring and fall. Differences in suicidal ideation between summer and spring were, in large part, accounted for by belongingness. Theoretical, as well as practical, implications are discussed regarding mechanisms for seasonal variation in suicidal ideation