Andrew O. Westfall

Putative contributors to the secular increase in obesity: exploring the roads less traveled

Objective:To investigate plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices.Design:A narrative review of data and published materials that provide evidence of the role of additional putative factors in contributing to the increasing prevalence of obesity.Data:Information was drawn from ecological and epidemiological studies of humans, animal studies and studies addressing physiological mechanisms, when available.Results:For at least 10 putative additional explanations for the increased prevalence of obesity over the recent decades, we found supportive (although not conclusive) evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations.Conclusion:Undue attention has been devoted to reduced physical activity and food marketing practices as postulated causes for increases in the prevalence of obesity, leading to neglect of other plausible mechanisms and well-intentioned, but potentially ill-founded proposals for reducing obesity rates.

Missed Visits and Mortality among Patients Establishing Initial Outpatient HIV Treatment

BACKGROUND Dramatic increases in the number of patients requiring linkage to treatment for human immunodeficiency virus (HIV) infection are anticipated in response to updated Centers for Disease Control and Prevention HIV testing recommendations that advocate routine, opt-out HIV testing. METHODS A retrospective analysis nested within a prospective HIV clinical cohort study evaluated patients who established initial outpatient treatment for HIV infection at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic from 1 January 2000 through 31 December 2005. Survival methods were used to evaluate the impact of missed visits during the first year of care on subsequent mortality in the context of other baseline sociodemographic, psychosocial, and clinical factors. Mortality was ascertained by query of the Social Security Death Index as of 1 August 2007. RESULTS Among 543 study participants initiating outpatient care for HIV infection, 60% missed a visit within the first year. The mortality rate was 2.3 deaths per 100 person-years for patients who missed visits, compared with 1.0 deaths per 100 person-years for those who attended all scheduled appointments during the first year after establishing outpatient treatment (P = .02). In Cox proportional hazards analysis, higher hazards of death were independently associated with missed visits (hazard ratio, 2.90; 95% confidence interval, 1.28-6.56), older age (hazard ratio, 1.58 per 10 years of age; 95% confidence interval, 1.12-2.22), and baseline CD4+ cell count < 200 cells/mm(3) (hazard ratio, 2.70; 95% confidence interval, 1.00-7.30). CONCLUSIONS Patients who missed visits within the first year after initiating outpatient treatment for HIV infection had more than twice the rate of long-term mortality, compared with those patients who attended all scheduled appointments. We posit that early missed visits are not causally responsible for the higher observed mortality but, rather, identify those patients who are more likely to exhibit health behaviors that portend increased subsequent mortality.

Distribution of Health Care Expenditures for HIV-Infected Patients

BACKGROUND Health care expenditures for persons infected with human immunodeficiency virus (HIV) in the United State determined on the basis of actual health care use have not been reported in the era of highly active antiretroviral therapy. METHODS Patients receiving primary care at the University of Alabama at Birmingham HIV clinic were included in the study. All encounters (except emergency room visits) that occurred within the University of Alabama at Birmingham Hospital System from 1 March 2000 to 1 March 2001 were analyzed. Medication expenditures were determined on the basis of 2001 average wholesale price. Hospitalization expenditures were determined on the basis of 2001 Medicare diagnostic related group reimbursement rates. Clinic expenditures were determined on the basis of 2001 Medicare current procedural terminology reimbursement rates. RESULTS Among the 635 patients, total annual expenditures for patients with CD4+ cell counts <50 cells/microL (36,533 dollars per patient) were 2.6-times greater than total annual expenditures for patients with CD4+ cell counts > or =350 cells/microL (13,885 dollars per patient), primarily because of increased expenditures for nonantiretroviral medication and hospitalization. Expenditures for highly active antiretroviral therapy were relatively constant at approximately 10,500 dollars per patient per year across CD4+ cell count strata. Outpatient expenditures were 1558 dollars per patient per year; however, the clinic and physician component of these expenditures represented only 359 dollars per patient per year, or 2% of annual expenses. Health care expenditures for patients with HIV infection increased substantially for those with more-advanced disease and were driven predominantly by medication costs (which accounted for 71%-84% of annual expenses). CONCLUSIONS Physician reimbursements, even with 100% billing and collections, are inadequate to support the activities of most clinics providing HIV care. These findings have important implications for the continued support of HIV treatment programs in the United States.

Early Retention in HIV Care and Viral Load Suppression: Implications for a Test and Treat Approach to HIV Prevention

BackgroundAfter HIV diagnosis and linkage to care, achieving and sustaining viral load (VL) suppression has implications for patient outcomes and secondary HIV prevention. We evaluated factors associated with expeditious VL suppression and cumulative VL burden among patients establishing outpatient HIV care. MethodsPatients initiating HIV medical care from January 2007 to October 2010 at the University of Alabama at Birmingham and University of Washington were included. Multivariable Cox proportional hazards and linear regression models were used to evaluate factors associated with time to VL suppression (<50 copies/mL) and cumulative VL burden, respectively. Viremia copy-years, a novel area under the longitudinal VL curve measure, was used to estimate 2-year cumulative VL burden from clinic enrollment. ResultsAmong 676 patients, 63% achieved VL <50 copies per milliliter in a median 308 days. In multivariable analysis, patients with more time-updated “no show” visits experienced delayed VL suppression (hazard ratio = 0.84 per “no show” visit, 95% confidence interval = 0.76 to 0.92). In multivariable linear regression, visit nonadherence was independently associated with greater cumulative VL burden (log10 viremia copy-years) during the first 2 years in care (Beta coefficient = 0.11 per 10% visit nonadherence, 95% confidence interval = 0.04 to 0.17). Across increasing visit adherence categories, lower cumulative VL burden was observed (mean ± standard deviation log10 copy × years/mL); 0%–79% adherence: 4.6 ± 0.8; 80%–99% adherence: 4.3 ± 0.7; and 100% adherence: 4.1 ± 0.7 log10 copy × years/mL, respectively (P < 0.01). ConclusionsHigher rates of early retention in HIV care are associated with achieving VL suppression and lower cumulative VL burden. These findings are germane for a test and treat approach to HIV prevention.

Prevalence and Correlates of Coronary Calcification in Black and White Young Adults The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Abstract—Whereas cardiovascular risk factor levels are substantially different in black and white Americans, the relative rates of cardiovascular disease in the 2 groups are not always consistent with these differences. To compare the prevalence of coronary calcification, an indicator of coronary atherosclerosis, in young adult blacks and whites, we performed electron-beam computed tomography of the heart in 443 men and women aged 28 to 40 years recruited from a population-based cohort. The presence of calcium, defined as at least 1 focus of at least 2.05 mm2 in area and >130 Hounsfield units in density within the coronary arteries, was identified in 16.1% of black men, 11.8% of black women, 17.1% of white men, and 4.6% of white women (P =0.04 for comparison across groups). Coronary calcium was associated with age and male sex, and after adjustment for age, race, and sex, coronary calcium was positively associated with body mass index, weight, systolic blood pressure, total cholesterol, low density lipoprotein cholesterol, triglycerides, and fasting insulin and negatively associated with education (all P <0.05). Independent risk factors included male sex, body mass index, and low density lipoprotein cholesterol. Race was not significantly associated with coronary calcium in men or women, before or after adjustment for risk factors. Coronary calcification is associated with increased levels of cardiovascular risk factors in young adults, and its prevalence is not significantly different in blacks and whites.

Measuring Retention in HIV Care: The Elusive Gold Standard

Background:Measuring retention in HIV primary care is complex, as care includes multiple visits scheduled at varying intervals over time. We evaluated 6 commonly used retention measures in predicting viral load (VL) suppression and the correlation among measures. Methods:Clinic-wide patient-level data from 6 academic HIV clinics were used for 12 months preceding implementation of the Centers for Disease Control and Prevention/Health Resources and Services Administration (CDC/HRSA) retention in care intervention. Six retention measures were calculated for each patient based on scheduled primary HIV provider visits: count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit constancy, and the HRSA HIV/AIDS Bureau (HRSA HAB) retention measure. Spearman correlation coefficients and separate unadjusted logistic regression models compared retention measures with one another and with 12-month VL suppression, respectively. The discriminatory capacity of each measure was assessed with the c-statistic. Results:Among 10,053 patients, 8235 (82%) had 12-month VL measures, with 6304 (77%) achieving suppression (VL <400 copies/mL). All 6 retention measures were significantly associated (P < 0.0001) with VL suppression (odds ratio; 95% CI, c-statistic): missed visit count (0.73; 0.71 to 0.75, 0.67), missed visit dichotomous (3.2; 2.8 to 3.6, 0.62), visit adherence (3.9; 3.5 to 4.3,0.69), gap (3.0; 2.6 to 3.3, 0.61), visit constancy (2.8; 2.5 to 3.0, 0.63), and HRSA HAB (3.8; 3.3 to 4.4, 0.59). Measures incorporating “no-show” visits were highly correlated (Spearman coefficient = 0.83–0.85), as were measures based solely on kept visits (Spearman coefficient = 0.72–0.77). Correlation coefficients were lower across these 2 groups of measures (range = 0.16–0.57). Conclusions:Six retention measures displayed a wide range of correlation with one another, yet each measure had significant association and modest discrimination for VL suppression. These data suggest there is no clear gold standard and that selection of a retention measure may be tailored to context.

Increased regimen durability in the era of once-daily fixed-dose combination antiretroviral therapy

Introduction:Data on initial antiretroviral regimen longevity predates the arrival of newer nucleoside reverse transcriptase inhibitor backbones and once-daily regimens. Modern regimens are thought to possess greater tolerability and convenience. We hypothesized this would translate into greater durability. Methods:Retrospective study of antiretroviral-naive patients starting treatment at the University of Alabama at Birmingham 1917 HIV/AIDS Clinic 1 January 2000–31 July 2007. Two periods of antiretroviral initiation were identified, prior and after August 2004 (arrival of once-daily fixed-dose regimens). Kaplan–Meier survival analyses of regimen durability by time period and regimen characteristics were performed. Staged Cox proportional hazards models evaluated the roles of dosing complexity and composition in explaining differences in regimen durability between study periods. Results:Overall 542 patients started antiretroviral drugs (n = 309, January 2000–July 2004; n = 233, August 2004–July 2007). Median durability was 263 days longer in after August 2004 regimens. Regimens started before August 2004 had increased hazards for discontinuation relative to after August 2004 regimens [hazard ratio (HR) = 1.44; 95% confidence interval (CI) = 1.03–2.02]. Time period of initiation lost statistical significance when the model included dosing frequency (HR = 1.92 for at least twice daily vs. daily; 95% CI = 1.29–2.88). As regimen composition variables were added, time period and dosing frequency lost significance. Increased hazards of discontinuation were observed with didanosine or stavudine relative to abacavir or tenofovir use (HR = 1.92; 95% CI = 1.29–2.88) and all third drugs compared with non-nucleoside reverse transcriptase inhibitor-based regimens (triple-nucleoside reverse transcriptase inhibitor HR = 1.76; 95% CI = 1.14–2.73; unboosted-protease inhibitor HR = 1.58; 95% CI = 1.02–2.46; boosted-protease inhibitor HR = 1.57; 95% CI = 1.02–2.41). Affective mental health disorders increased the hazard of discontinuation in all models. ConclusionDurability of contemporary once-daily fixed-dose antiretroviral regimens has significantly eclipsed the duration of earlier antiretroviral drug options. Our results indicate this is due to both more convenient dosing and improved tolerability of modern antiretroviral regimens.

Universal Definition of Loss to Follow-Up in HIV Treatment Programs: A Statistical Analysis of 111 Facilities in Africa, Asia, and Latin America

Based on a statistical analysis of 111 facilities in Africa, Asia, and Latin America, Benjamin Chi and colleagues develop a standard loss-to-follow-up (LTFU) definition that can be used by HIV antiretroviral programs worldwide.

Health-related quality of life and virologic outcomes in an HIV clinic.

Objective: The purpose of this study was to describe the relationship between viral load and health-related quality of life (HRQOL) in a cohort of persons with human immunodeficiency virus (HIV) infection. Design: We evaluated HRQOL measurements in a clinical cohort of HIV-positive patients recruited from a university-associated HIV primary care clinic. HRQOL instruments included the medical outcomes survey-short form-36(MOS-SF-36) from which mental and physical component summary scores (MCS and PCS) and subscale scores were calculated. Results: Significant negative associations were found between viral load and SF-36 PCS, physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), role-emotional (RE), and vitality (VT). Similar negative associations were found between CD4 cell count and SF-36 summary and subscale scores, with the notable exception of bodily pain. Multivariate analyses controlling for the effects of CD4 cell count and other clinical variables indicated viral load as an independent predictor of SF-36 PCS, RP, BP and VT scores. Conclusions: The relationship between viral load, a measure of HIV disease activity, and several dimensions of the SF-36, a patient-focused measure of HRQOL, appears to be strong and independent of CD4 cell count. These findings suggest that having a lower viral load positively impacts the quality of life of HIV-positive patients.

Benefit of adherence with bisphosphonates depends on age and fracture type: results from an analysis of 101,038 new bisphosphonate users.

The relationship between high adherence to oral bisphosphonates and the risk of different types of fractures has not been well studied among adults of different ages. Using claims data from a large U.S. health care organization, we quantified adherence after initiating bisphosphonate therapy using the medication possession ratio (MPR) and identified fractures. Cox proportional hazards models were used to evaluate the rate of fracture among nonadherent persons (MPR < 50%) compared with highly adherent persons (MPR ≥ 80%) across several age strata and a variety of types of clinical fractures. In conjunction with fracture incidence rates among the nonadherent, these estimates were used to compute the number needed to treat with high adherence to prevent one fracture, by age and fracture type. Among 101,038 new bisphosphonate users, the proportion of persons with high adherence at 1, 2, and 3 yr was 44%, 39%, and 35%, respectively. Among 65‐ to 78‐yr‐old persons with a physician diagnosis of osteoporosis, the crude and adjusted rate of hip fracture among the nonadherent was 1.96 (95% CI, 1.48–2.60) and 1.74 (95% CI, 1.30–2.31), respectively, resulting in a number needed to treat with high adherence to prevent one hip fracture of 107. The impact of high adherence was substantially less for other types of fractures and for younger persons. Analysis of adherence in a non–time‐dependent fashion artifactually magnified differences in fracture rates between adherent and nonadherent persons. The antifracture effectiveness associated with high adherence to oral bisphosphonates varied substantially by age and fracture type. These results provide estimates of absolute fracture effectiveness across age subgroups and fracture types that have been minimally evaluated in clinical trials and may be useful for future cost‐effectiveness studies.