Faculty Bibliography

Effective combination antiretroviral therapy (ART) has enabled human immunodeficiency virus (HIV) infection to evolve from a generally fatal condition to a manageable chronic disease. This transition began two decades ago in high-income countries and has more recently begun in lower income, HIV endemic countries (HIV-ECs). With this transition, there has been a concurrent shift in clinical and public health burden from AIDS-related complications and opportunistic infections to those associated with well-controlled HIV disease, including cardiovascular disease (CVD). In the current treatment era, traditional CVD risk factors and HIV-related factors both contribute to an elevated risk of myocardial infarction, stroke, heart failure, and arrhythmias. In HIV-ECs, the high prevalence of persons living with HIV and growing prevalence of CVD risk factors will contribute to a growing epidemic of HIV-associated CVD. In this review, we discuss the epidemiology and pathophysiology of cardiovascular complications of HIV and the resultant implications for public health efforts in HIV-ECs.

OBJECTIVES: To identify the patient-safety hazards of current medication labeling standards for immigrant and language-minority families. SUMMARY: The Latino population in the United States has increased by more than 40% over the past decade and the total child population born to Latino parents will surpass one-half of the population in many states. With recent health care and immigration policies, this demographic shift has a disproportional effect on the Latino families. Research shows that recent Latin American immigrants face disparities when encountering the U.S. pharmacy system. A review of these disparities shows how new policies should be informed when considering new pharmacy regulations to better address the cultural needs of recent Latin American families to improve medication understanding and adherence. CONCLUSION: To date, research and regulatory requirements for medication safety in the United States have attended insufficiently to the patient-safety risk inherent in providing complex English-language labels to non-English-speaking families, many of whom have limited literacy in their native language. As families move, this patient-safety risk is increased by shifts in pharmacies, which often have different medication-labeling standards. It is important to examine how recent immigrant parents are addressing the medication needs for their children based on their cultural norms and how those cultural practices and acculturation into the U.S. health care system may affect their risk for injury. New research and policy efforts may help to address these barriers to safe medication use.

BACKGROUND: Lung cancer in never smokers is a significant contributor of cancer mortality worldwide. In this analysis, we explored the role of nine human polyomaviruses, including JC virus (JCV), BK virus (BKV) and Merkel cell virus (MCV), in lung cancer development in never smokers as there are data to support that polyomaviruses are potentially carcinogenic in the human lung. METHODS: We used multiplex serology to detect serum antibodies to polyomaviruses in a nested case-control design combining lung cancer cases and controls from four cohort studies - NYU Women's Health Study (NYU-WHS), Janus Serum Bank, Shanghai Women's Health Study and Singapore Chinese Health Study (SCHS). RESULTS: The final analyses included 511 cases and 508 controls. Seroprevalence for each polyomavirus showed significant heterogeneity by study, but overall there were no statistically significant differences between cases and controls. In total, 69.1% of the cases and 68.7% of the controls were seropositive for JCV VP1 antibody. Seropositivity for BKV was higher at 89.0% in cases and 89.8% in controls and lower for MCV at 59.3% in cases and 61.6% in controls. Similar results were obtained after adding an additional retrospective case-control study (Xuanwei study) to the analysis. CONCLUSIONS: Our results do not support the hypothesis that seropositivity for polyomaviruses is associated with increased lung cancer risk in never smokers. Future research to evaluate relationship between polyomavirus infection and lung carcinogenesis should focus more on evaluating the presence of virus or viral nucleic acids (DNA or RNA) in lung tumour samples.British Journal of Cancer advance online publication, 15 September 2016; doi:10.1038/bjc.2016.285 www.bjcancer.com.

BACKGROUND:The optimal systolic blood pressure (SBP) treatment goal is in question, with SPRINT (Systolic Blood Pressure Intervention Trial) suggesting benefit for 120 mm Hg. However, achieving an SBP this low may reduce diastolic blood pressure (DBP) to levels that could compromise myocardial perfusion. OBJECTIVES:This study sought to examine the independent association of DBP with myocardial damage (using high-sensitivity cardiac troponin-T [hs-cTnT]) and with coronary heart disease (CHD), stroke, or death over 21 years. METHODS:The authors studied 11,565 adults from the ARIC (Atherosclerosis Risk In Communities) cohort, analyzing DBP and hs-cTnT associations as well as prospective associations between DBP and events. RESULTS:Mean baseline age was 57 years, 57% of patients were female, and 25% were black. Compared with persons who had DBP between 80 to 89 mm Hg at baseline (ARIC visit 2), the adjusted odds ratio of having hs-cTnT ≥14 ng/l at that visit was 2.2 and 1.5 in those with DBP <60 mm Hg and 60 to 69 mm Hg, respectively. Low DBP at baseline was also independently associated with progressive myocardial damage on the basis of estimated annual change in hs-cTnT over the 6 years between ARIC visits 2 and 4. In addition, compared with a DBP of 80 to 89 mm Hg, a DBP <60 mm Hg was associated with incident CHD and mortality, but not with stroke. The DBP and incident CHD association was strongest with baseline hs-cTnT ≥14 ng/l (p value for interaction <0.001). Associations of low DBP with prevalent hs-cTnT and incident CHD were most pronounced among patients with baseline SBP ≥120 mm Hg. CONCLUSIONS:Particularly among adults with an SBP ≥120 mm Hg, and thus elevated pulse pressure, low DBP was associated with subclinical myocardial damage and CHD events. When titrating treatment to SBP <140 mm Hg, it may be prudent to ensure that DBP levels do not fall below 70 mm Hg, and particularly not below 60 mm Hg.

Environmental health studies have examined associations between context and health with individuals as statistical units. However, investigators have been unable to investigate momentary exposures, and such studies are often vulnerable to confounding from, for example, individual-level preferences. We present a Global Positioning System (GPS)-based methodology for segmenting individuals' observation periods into visits to places and trips, enabling novel life-segment investigations and case-crossover analysis for improved inferences. We analyzed relationships between built environments and walking in trips. Participants were tracked for 7 days with GPS receivers and accelerometers and surveyed with a Web-based mapping application about their transport modes during each trip (Residential Environment and Coronary Heart Disease (RECORD) GPS Study, France, 2012-2013; 6,313 trips made by 227 participants). Contextual factors were assessed around residences and the trips' origins and destinations. Conditional logistic regression modeling was used to estimate associations between environmental factors and walking or accelerometry-assessed steps taken in trips. In case-crossover analysis, the probability of walking during a trip was 1.37 (95% confidence interval: 1.23, 1.61) times higher when trip origin was in the fourth (vs. first) quartile of service density and 1.47 (95% confidence interval: 1.23, 1.68) times higher when trip destination was in the fourth (vs. first) quartile of service density. Green spaces at the origin and destination of trips were also associated with within-individual, trip-to-trip variations in walking. Our proposed approach using GPS and Web-based surveys enables novel life-segment epidemiologic investigations.

BACKGROUND:Many adolescents are exposed to a significant amount of sexual content in the media. This has far-reaching effects on their sexual practices as this exposure is occurring at a period when most adolescents are often not sure of the choices to make, and the choices they make during adolescence affect their health when they become adults. The aim of this study was to assess the association between exposure of in-school adolescents to sexual content in the electronic media and their sexual intentions. METHODS:In this cross-sectional study, information was obtained from 750 senior secondary school students in private and public schools using interviewer-administered questionnaire. Sexual media content in the movies, music video and Internet was assessed using a modified version of the sexual media diet tool. The dependent variable was sexual intention; the main independent variable was exposure to sexually explicit content in the media and confounders that were controlled for selected individual (age, sex, religiosity, self-esteem and attachment to parents), family (parents' marital status, parents' type of marriage, hands-on parenting and parent-adolescent communication on sex) and environmental factors (school connectedness and influence from peers) which were previously reported to be associated with sexual intentions of adolescents. Chi-square test was used to determine associations between sexual content of the electronic media and adolescents' sexual intentions, and confounders were controlled for using logistic regression analysis. RESULTS:Thirty-six percent of respondents were exposed to overtly explicit sexual content from all forms of media in the 3 months prior to this study. Twenty-four percent of the adolescents indicated their intention to have sex within 12 months following the study. Predictors of sexual intention were as follows: moderate [odds ratio, OR=2.21 (95% confidence interval, CI: 1.22-3.99)] and high exposure to sexual content in the media [OR=3.02 (95% CI: 1.69-5.43]; attending a public school [OR=2.19 (95% CI: 1.26-3.83)]; moderate peer pressure [OR=2.36 (95% CI: 1.41-3.95)] and high peer pressure [OR=10.32 (95% CI: 2.94-36.31)]; and previous history of sexual intercourse [OR=3.89 (95% CI: 2.25-6.76)]. CONCLUSION/CONCLUSIONS:Many adolescents were exposed to sexually explicit content in the media and this had a strong association with sexual intention. Interventions to censor sexually explicit content in the media are required to protect adolescents from the consequences of early exposure to sex.

Photovoice is a participatory action research method in which people are given cameras and asked to take pictures of specific issues within their community. It is often used among marginalised populations. This method helps people capture specific issues within their community using photographs, critically discuss these issues within a group and present their findings to inform policies within their community. Photovoice has been used in developed countries and among adult participants; however, the extent to which it has been used in developing countries and among adolescent participants is yet to be extensively reported. In this paper, we describe the use of photovoice among male and female adolescents aged 15-19 years who participated in the qualitative phase (phase I) of the Well-being of Adolescents in Vulnerable Environments (WAVE) study in Ibadan, Nigeria. The main study was conducted among adolescents residing in disadvantaged communities within five global cities (Baltimore, USA; Ibadan, Nigeria; Johannesburg, South Africa; New Delhi, India and Shanghai, China). Our findings revealed that adolescents in Ibadan were very eager to participate, remained fully engaged throughout the process and the data obtained were rich and detailed. Some challenges encountered with using this method were that younger adolescents had a tendency to attain saturation when taking pictures much earlier than older adolescents; however, they equally discussed the pictures taken enthusiastically. Overall, our findings affirm that photovoice as a data collection method can be successfully used in research among adolescents in developing countries like Nigeria.

BACKGROUND: The majority of studies examining the role of neighborhoods and hypertension-related outcomes have been quantitative in nature and very few studies have examined specific disadvantaged populations, including low-income housing residents. The objective of this study was to use qualitative interviews to explore low-income Black women's perceptions of their neighborhoods and to understand how those perceptions may affect their health, especially as it relates to blood pressure. METHODS: Seventeen Black female participants, living in public housing communities in New York City, completed one semi-structured, audiotaped interview in July of 2014. All interviews were transcribed, coded, and analyzed for emerging themes using N'Vivo 10 software. RESULTS: Three major themes emerged: (1) social connectedness, (2) stress factors, and (3) availability of food options. For example, factors that caused stress varied throughout the study population. Sources of stress included family members, employment, and uncleanliness within the neighborhood. Many participants attributed their stress to personal issues, such as lack of employment and relationships. In addition, the general consensus among many participants was that there should be a greater density of healthy food options in their neighborhoods. Some believed that the pricing of fresh foods in the neighborhoods should better reflect the financial status of the residents in the community. CONCLUSIONS: Various neighborhood influences, including neighborhood disorder and lack of healthy food options, are factors that appear to increase Black women's risk of developing high blood pressure. Implications of this research include the need to develop interventions that promote good neighborhood infrastructure (e.g. healthy food stores to encourage good nutrition habits and well-lit walking paths to encourage daily exercise), in addition to interventions that increase hypertension awareness in low-income neighborhoods.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10-15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10-9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10-8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10-8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10-4-2.0x10-3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.