Publications

BACKGROUND

In California, young adult tobacco prevention is of prime importance; 63% of smokers start by the age of 18 years, and 97% start by the age of 26 years. We examined social affiliation with 'peer crowd' (eg, Hipsters) as an innovative way to identify high-risk tobacco users.

METHODS

Cross-sectional surveys were conducted in 2014 (N=3368) among young adult bar patrons in 3 California cities. We examined use rates of five products (cigarettes, e-cigarettes, hookah, cigars and smokeless tobacco) by five race/ethnicity categories. Peer crowd affiliation was scored based on respondents' selecting pictures of young adults representing those most and least likely to be in their friend group. Respondents were classified into categories based on the highest score; the peer crowd score was also examined as a continuous predictor. Logistic regression models with each tobacco product as the outcome tested the unique contribution of peer crowd affiliation, controlling for race/ethnicity, age, sex, sexual orientation and city.

RESULTS

Respondents affiliating with Hip Hop and Hipster peer crowds reported significantly higher rates of tobacco use. As a categorical predictor, peer crowd was related to tobacco use, independent of associations with race/ethnicity. As a continuous predictor, Hip Hop peer crowd affiliation was also associated with tobacco use, and Young Professional affiliation was negatively associated, independent of demographic factors.

CONCLUSIONS

Tobacco product use is not the same across racial/ethnic groups or peer crowds, and peer crowd predicts tobacco use independent of race/ethnicity. Antitobacco interventions targeting peer crowds may be an effective way to reach young adult tobacco users.

TRIAL REGISTRATION NUMBER

NCT01686178, Pre-results.

PURPOSE OF REVIEW

Studies have shown that chronic inflammatory disorders, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis are associated with an increased risk of atherosclerotic cardiovascular disease. The mechanism by which inflammation increases cardiovascular disease is likely multifactorial but changes in HDL structure and function that occur during inflammation could play a role.

RECENT FINDINGS

HDL levels decrease with inflammation and there are marked changes in HDL-associated proteins. Serum amyloid A markedly increases whereas apolipoprotein A-I, lecithin:cholesterol acyltransferase, cholesterol ester transfer protein, paraoxonase 1, and apolipoprotein M decrease. The exact mechanism by which inflammation decreases HDL levels is not defined but decreases in apolipoprotein A-I production, increases in serum amyloid A, increases in endothelial lipase and secretory phospholipase A2 activity, and decreases in lecithin:cholesterol acyltransferase activity could all contribute. The changes in HDL induced by inflammation reduce the ability of HDL to participate in reverse cholesterol transport and protect LDL from oxidation.

SUMMARY

During inflammation multiple changes in HDL structure occur leading to alterations in HDL function. In the short term, these changes may be beneficial resulting in an increase in cholesterol in peripheral cells to improve host defense and repair but over the long term these changes may increase the risk of atherosclerosis.

Tenofovir disoproxil fumarate (TDF) can cause kidney damage, but current clinical tests are insensitive for detecting toxicity. Among 884 HIV-infected men enrolled in the Multicenter AIDS Cohort Study, we measured urine biomarkers specific for tubular damage (interleukin-18, kidney injury molecule-1, procollagen type III N-terminal propeptide) and albuminuria. In adjusted analyses, each year of TDF exposure was independently associated with 3.3% higher interleukin-18 (95% CI: 0.8% to 5.8%), 3.4% higher kidney injury molecule-1 (1.1% to 5.7%), and 3.1% higher procollagen type III N-terminal propeptide (0.8% to 5.5%), but not with albuminuria (2.8%; -0.6% to 6.2%). Biomarkers of tubular damage may be more sensitive than albuminuria for detecting toxicity from TDF and other medications.

BACKGROUND

Acute cellular rejection is a major cause of morbidity after lung transplantation. Because regulatory T (Treg) cells limit rejection of solid organs, we hypothesized that donor-reactive Treg increase after transplantation with development of partial tolerance and decrease relative to conventional CD4 (Tconv) and CD8 T cells during acute cellular rejection.

METHODS

To test these hypotheses, we prospectively collected 177 peripheral blood mononuclear cell specimens from 39 lung transplant recipients at the time of transplantation and during bronchoscopic assessments for acute cellular rejection. We quantified the proportion of Treg, CD4 Tconv, and CD8 T cells proliferating in response to donor-derived, stimulated B cells. We used generalized estimating equation-adjusted regression to compare donor-reactive T cell frequencies with acute cellular rejection pathology.

RESULTS

An average of 16.5 ± 9.0% of pretransplantation peripheral blood mononuclear cell Treg cell were donor-reactive, compared with 3.8% ± 2.9% of CD4 Tconv and 3.4 ± 2.6% of CD8 T cells. These values were largely unchanged after transplantation. Donor-reactive CD4 Tconv and CD8 T cell frequencies both increased 1.5-fold (95% confidence interval [95% CI], 1.3-1.6; P < 0.001 and 95% CI, 1.2-1.6; P = 0.007, respectively) during grade A2 rejection compared with no rejection. Surprisingly, donor-reactive Treg frequencies increased by 1.7-fold (95% CI, 1.4-1.8; P < 0.001).

CONCLUSIONS

Contrary to prediction, overall proportions of donor-reactive Treg cells are similar before and after transplantation and increase during grade A2 rejection. This suggests how A2 rejection can be self-limiting. The observed increases over high baseline proportions in donor-reactive Treg were insufficient to prevent acute lung allograft rejection.

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

The American Thoracic Society (ATS), in collaboration with George Mason University, surveyed international members of the society to assess perceptions, clinical experiences, and preferred policy responses related to global climate change. A recruitment email was sent by the ATS President in October 2015 to 5,013 international members. Subsequently, four reminder emails were sent to nonrespondents. Responses were received from 489 members in 68 countries; the response rate was 9.8%. Half of respondents reported working in countries in Asia (25%) or Europe (25%), with the remainder in South America (18%), North America (Canada and Mexico) (18%), Australia or New Zealand (9%), and Africa (6%). Survey estimate confidence intervals were ± 5% or smaller. A high percentage of international ATS survey respondents judged that climate change is happening (96%), that it is driven by human activity (70%), and that it is relevant to patient care ("a great deal"/"a moderate amount") (80%). A majority of respondents also indicated they are already observing health impacts of climate change among their patients; most commonly as increases in chronic disease severity from air pollution (88%), allergic symptoms from exposure to plants or mold (72%), and severe weather injuries (69%). An even larger majority anticipated seeing these climate-related health impacts in the next two decades. Respondents further indicated that physicians and physician organizations should play an active role in educating patients, the public, and policy makers on the human health effects of climate change. International ATS respondents, like their counterparts in the U.S., observed that human health is already adversely affected by climate change, and support responses to address this situation.

Despite marked improvements in the modern treatment era, human immunodeficiency virus (HIV)-infected individuals, particularly those who initiated antiretroviral therapy (ART) at advanced disease stages, continue to have increased age-related morbidity and mortality, compared with the general population. Immune activation and inflammation persist despite suppressive ART and predict many of these morbidities. The goal of this review is to examine the evidence suggesting a link between the persistent inflammatory state and morbidity and mortality in this setting, to describe the impact of early ART initiation on these factors, and to highlight important unanswered questions for the field. We also advance a hypothesis to explain why some morbidities-and their root inflammatory drivers-may be prevented more than others by early ART initiation.

People living with HIV (PLWH) engaged in medical care represent an accessible group to focus HIV prevention efforts. In an analysis of 1,883 PLWH from 2007 and 2015, we determined the proportion at risk of HIV transmission and identified factors associated with HIV transmission risk using multivariable mixed effects logistic regression models with random intercepts. HIV transmission risk was defined by an HIV viral load > 1,500 copies/mL and self-reported unprotected sex. We found that 174 (9.2%) individuals were at risk for HIV transmission at least once. Factors associated with HIV transmission risk included younger age (adjusted OR [95% CI] per decade decrease = 2.30 [1.84, 2.89]), illicit drug use (adjusted OR = 5.36 [3.02, 9.56]), depression (adjusted OR = 1.88 [1.10, 3.21]), and education <12th grade (adjusted OR = 2.05 [1.15, 3.67]). Thus, nearly 1 in 10 HIV-infected individuals engaged in care between 2007 and 2015 were potentially at risk of transmitting HIV. Behavioral interventions to decrease HIV transmission should focus on younger, less educated patients who are depressed and actively using illicit drugs.