Publications

Iran is facing unprecedented dual drug use and HIV epidemics. We conducted a cross-sectional survey to obtain HIV prevalence and risk behavior data from injection drug users (IDU) in Tehran. We used respondent-driven sampling (RDS) to recruit IDU through successive waves starting with 24 "seeds," conducted anonymous face-to-face interviews and HIV testing and counseling, and used RDSAT to adjust data. During 44 weeks, 1,726 study referral coupons resulted in 645 (37 %) IDU referrals, of whom 548 (85 %) were enrolled. From those enrolled, 84 % were incarcerated, 47 % employed, 55 % single, 27 % under 30 years of age, and 26 % homeless. The adjusted HIV prevalence was 26.6 % (95 % confidence interval 21.3-32.1), and was higher among certain IDU subgroups (e.g., those who sharing injection paraphernalia). Our estimates of HIV prevalence were higher than some other estimates; however, repeated surveys using similar methodology are needed to monitor the trend of HIV epidemic over time.

OBJECTIVES

To evaluate predictors of dual use of cigarettes with smokeless tobacco or e-cigarettes.

METHODS

Adult smokers (N = 1324) completed online cross-sectional surveys. Logistic regression evaluated predictors of dual use and cigarette quit attempts.

RESULTS

Smokeless tobacco dual use was associated with past attempts to quit smoking by switching to smokeless products. E-cigarette dual use was associated with using stop-smoking medication and strong anti-tobacco industry attitudes. Ever use of stop-smoking medication was associated with quit attempts among dual e-cigarette users and cigarette-only users.

CONCLUSIONS

Dual users are more likely than cigarette-only users to endorse certain cessation-related attitudes and behaviors. This may provide an opportunity for clinicians or others to discuss evidence-based strategies for smoking cessation.

BACKGROUND

Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children.

METHODS

Sparse dried blood spot samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from 3 resource-rich countries (RRC) were utilized to develop the PK models.

RESULTS

Concentrations in 330 dried blood spot from 163 Ugandan children aged 0.7-7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5-12 years. Among Ugandan children, 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008), respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (P<0.001) with a trend toward greater bioavailability when malnourished. Children receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z scores were associated with reduced risk of virologic failure (P=0.034, P=0.068, respectively).

CONCLUSIONS

Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessments, to further assess causes of virologic failure in Ugandan children.

Transforming growth factor-β (TGF-β) plays a central role in driving tissue fibrosis. TGF-β is secreted in a latent form, held latent by noncovalent association of the active cytokine with a peptide derived from cleavage of the N-terminal domain of the same gene product, and needs to be activated extracellularly to exert any of its diverse biological effects. We have shown that two of the three mammalian isoforms of TGF-β, TGF-β1 and TGF-β3, depend on interactions with cell surface integrins for activation. We found that the integrin αvβ6 is highly induced on injured alveolar epithelial cells, potently induces TGF-β activation, and is critical for the development of pulmonary fibrosis and acute lung injury. However, although TGF-β drives fibrosis in virtually every anatomic site, αvβ6-mediated TGF-β activation is much more restricted. For example, αvβ6 is not induced on injured hepatocytes and plays little or no role in cirrhosis induced by repetitive hepatocyte injury. Fibroblasts are highly contractile cells that express multiple integrins closely related to αvβ6, which share the promiscuous αv subunit, so we reasoned that perhaps one or more of these αv integrins on fibroblasts might substitute for αvβ6 and activate the TGF-β required to drive liver fibrosis. Indeed, deletion of the αv subunit from activated fibroblasts protected mice from carbon tetrachloride-induced liver fibrosis. Importantly, these same mice were protected from bleomycin-induced pulmonary fibrosis and renal fibrosis caused by unilateral ureteral obstruction, despite the presence of epithelial αvβ6 in these mice. These results suggest that the generation and maintenance of sufficient quantities of active TGF-β to cause tissue fibrosis in multiple organs probably depends on at least two sources-TGF-β activation by injured epithelial cells that drives fibroblast expansion and activation and an amplification step that involves TGF-β activation by an αv integrin on activated fibroblasts. These results suggest that intervening at either of these steps could be useful for the treatment of fibrotic diseases.

RATIONALE

Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear.

OBJECTIVES

To determine the impact of occupational exposures on COPD morbidity.

METHODS

A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years.

MEASUREMENTS AND MAIN RESULTS

An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04-1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (-26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (-3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03).

CONCLUSIONS

Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.

OBJECTIVE

Prior studies have established disparities by race/ethnicity and socioeconomic status (SES) in the kind, quantity, and technical quality of systemic lupus erythematosus (SLE) care and outcomes. In this study we evaluate whether disparities exist in assessments of interactions with health care providers and health plans and whether such interactions affect the technical quality of SLE care.

METHODS

Data derive from the Lupus Outcomes Study (LOS). Principal data collection is an annual structured phone interview including items from the Consumer Assessment of Health Plans and Interpersonal Processes of Care Scale measuring dimensions of health care interactions. We use general estimating equations to assess whether disparities exist by race/ethnicity and SES in being in the lowest quartile of ratings of such interactions and whether ratings in the lowest quartile of interactions are associated with technical quality of care after adjustment for sociodemographic and disease characteristics.

RESULTS

In the 2012 LOS interview, there were 793 respondents, of whom 640 had ≥1 visit to their principal SLE provider. Nonwhite race/ethnicity and education were not associated with low ratings on any dimension of provider or system interaction; poverty was associated only with low ratings of health plan interactions. After adjustment for demographics, SLE status, and health care variables, ratings in the lowest quartile on all dimensions were associated with significantly lower technical quality of care.

CONCLUSION

Ratings in the lowest quartile on all dimensions of interactions with providers and the health care system were associated with lower technical quality of care, potentially resulting in poorer SLE outcomes.