Ancestry specific associations of a genetic risk score, dietary patterns and metabolic syndrome: a longitudinal ARIC study.

BACKGROUND: Associations have been observed among genetic variants, dietary patterns, and metabolic syndrome (MetS). A gap in knowledge is whether a genetic risk score (GRS) and dietary patterns interact to increase MetS risk among African Americans. We investigated whether MetS risk was influenced by interaction between a GRS and dietary patterns among Whites and African Americans. A secondary aim examined if molecular genetic clusterings differed by racial ancestry. METHODS: We used longitudinal data over 4-visits (1987-1998) that included 10,681 participants aged 45-64y at baseline from the Atherosclerosis Risk in Communities study (8451 Whites and 2230 African Americans). We constructed a simple-count GRS as the linear weighted sum of high-risk alleles (0, 1, 2) from cardiovascular disease polymorphisms from the genome-wide association studies catalog associated with MetS risk. Three dietary patterns were determined by factor analysis of food frequency questionnaire data: Western, healthy, and high-fat dairy. MetS was defined according to the 2016 National Cholesterol Education Program Adult Treatment Panel III criteria but used 2017 American Heart Association/American College of Cardiology criteria for elevated blood pressure. Analyses included generalized linear model risk ratios (RR), 95% confidence intervals (CI), and Bonferroni correction for multiple testing. RESULTS: The Western dietary pattern was associated with higher risk for MetS across increasing GRS tertiles among Whites (p < 0.017). The high-fat dairy pattern was protective against MetS, but its impact was most effective in the lowest GRS tertile in Whites (RR = 0.62; CI: 0.52-0.74) and African Americans (RR = 0.67; CI: 0.49-0.91). Among each racial group within GRS tertiles, the Western dietary pattern was associated with development and cycling of MetS status between visits, and the high-fat dairy pattern with being free from MetS (p < 0.017). The healthy dietary pattern was associated with higher risk of MetS among African Americans which may be explained by higher sucrose intake (p < 0.0001). Fewer genes, but more metabolic pathways for obesity, body fat distribution, and lipid and carbohydrate metabolism were identified in African Americans than Whites. Some polymorphisms were linked to the Western and high-fat dairy patterns. CONCLUSION: The influence of dietary patterns on MetS risk appears to differ by genetic predisposition and racial ancestry.

A Risk Prediction Model for Mortality Among Smokers in the COPDGene® Study.

BACKGROUND: Risk factor identification is a proven strategy in advancing treatments and preventive therapy for many chronic conditions. Quantifying the impact of those risk factors on health outcomes can consolidate and focus efforts on individuals with specific high-risk profiles. Using multiple risk factors and longitudinal outcomes in 2 independent cohorts, we developed and validated a risk score model to predict mortality in current and former cigarette smokers. METHODS: We obtained extensive data on current and former smokers from the COPD Genetic Epidemiology (COPDGene®) study at enrollment. Based on physician input and model goodness-of-fit measures, a subset of variables was selected to fit final Weibull survival models separately for men and women. Coefficients and predictors were translated into a point system, allowing for easy computation of mortality risk scores and probabilities. We then used the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) cohort for external validation of our model. RESULTS: Of 9867 COPDGene participants with standard baseline data, 17.6% died over 10 years of follow-up, and 9074 of these participants had the full set of baseline predictors (standard plus 6-minute walk distance and computed tomography variables) available for full model fits. The average age of participants in the cohort was 60 for both men and women, and the average predicted 10-year mortality risk was 18% for women and 25% for men. Model time-integrated area under the receiver operating characteristic curve statistics demonstrated good predictive model accuracy (0.797 average), validated in the external cohort (0.756 average). Risk of mortality was impacted most by 6-minute walk distance, forced expiratory volume in 1 second and age, for both men and women. CONCLUSIONS: Current and former smokers exhibited a wide range of mortality risk over a 10- year period. Our models can identify higher risk individuals who can be targeted for interventions to reduce risk of mortality, for participants with or without chronic obstructive pulmonary disease (COPD) using current Global initiative for obstructive Lung Disease (GOLD) criteria.

COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. METHODS: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. RESULTS: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. CONCLUSIONS: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop.

The role of personal and household members' substance use in health-related quality of life in women living with HIV/AIDS.

Advances in HIV treatments have led to a greater focus on health-related quality of life (HRQOL) among people living with HIV/AIDS. The current study examined factors associated with HRQOL among 378 women in HIV care. HRQOL was measured using a modified version of the 12-Item Short Form Health Survey; scores were derived for the mental and physical composite summaries (MCS and PCS). We measured personal alcohol use and drug use. Household members' substance use were assessed by asking participants about the alcohol/drug status of persons with whom they live. Multivariate generalized linear models were used to estimate the linear association between MCS and PCS scores and personal and household members' alcohol and drug use. We found lower MCS scores were significantly associated with personal alcohol use and living with someone with alcohol or/and drug problems. Lower PCS scores were not significantly associated with personal alcohol use or living with someone with alcohol or/and drug problems. Findings suggest that universal screening and targeted interventions for alcohol use by the patient or household members may offer potential strategies for improving mental health quality of life among women living with HIV/AIDS.

Social Support Networks and HIV/STI Risk Behaviors Among Latino Immigrants in a New Receiving Environment.

The objectives of this study were to: (1) describe the quantity and quality of social support networks of Latino immigrants living in a new receiving environment, and (2) determine the role such networks play in their HIV/STI risk behaviors, including substance use. Double incentivized convenience sampling was used to collect egocentric social support network data on 144 Latino immigrants. Latent class analysis was used for data reduction and to identify items best suited to measure quality and quantity of social support. Moderate and high quantity and quality of social support were protective of HIV/STI sexual risk behavior compared to low quantity and quality of support, after adjustment for gender, years in New Orleans and residing with family. Neither measure of social support was associated with binge drinking. The findings suggest that increased quantity and quality of social support decrease HIV/STI sexual risk behaviors but do not influence binge drinking. Interventions that improve the quantity and quality of social support are needed for Latino immigrants.

Transnational Mortality Comparisons Between Archipelago and Mainland Puerto Ricans.

Puerto Ricans in the US experience higher deaths from diabetes and other causes compared to non-Hispanic Whites and other Hispanic groups. We compared mortality in Puerto Rico to that of Puerto Ricans in the US as a first step to investigate if similar or worse mortality patterns originate from the sending country (Puerto Rico). Age-adjusted death rates were generated using national vital statistics databases in the US and territories for all-cause and the top ten causes of death among Hispanics in 2009. Mortality ratios in the archipelago of Puerto Rico (APR) were compared to mainland US Puerto Ricans (MPR). Rates for other ethnic/racial groups (Mexican Americans, Cubans, and non-Hispanic Whites, Blacks, American Indians, and Asians) were calculated to provide a context. APR had significantly higher all-cause mortality and death rates for diabetes, nephritis, pneumonia/influenza, and homicide/assault compared to MPR (APR/MPR ratio for all-cause: 1.08, diabetes: 2.04, nephritis: 1.84, pneumonia/influenza: 1.33, homicide/assault: 3.15). Death rates for diabetes and homicide/assault (particularly among men) were higher among APR compared to any other racial/ethnic groups in the US. In contrast, deaths from heart disease, cancer, and chronic liver disease were significantly lower for APR compared to MPR (MPR/APR ratio 0.72, 0.91, 0.41, respectively). Among APR women, death rates for these causes were also lower compared to any other group in the US. Substantial mortality variability exists between Puerto Ricans in Puerto Rico and those in the US, re-emphasizing the need to study of how socio-environmental determinants of health differ in sending and receiving countries. Explanations for disparate rates include access to and availability of healthcare and unique factors related to the migration experience of this group.

Mother-to-Child Transmission of Trypanosoma cruzi.

Among the world's most neglected tropical diseases, Chagas disease is vector-borne and caused by Trypanosoma cruzi. T cruzi infection is endemic to South and Central America as well as Mexico. Due to population migration, T cruzi is increasingly becoming a public health problem in nonendemic settings. Success with vector control strategies has led to a relative increase in the burden attributable to congenital transmission of T cruzi. In endemic settings, approximately 5% of infected pregnant women transmit to their offspring. Congenital T cruzi infection is generally asymptomatic and parasitological and serological testing is required for diagnosis. This review highlights research gaps with a focus on (1) improving screening, diagnostic, and treatment options and (2) designing epidemiologic studies to understand risk factors for congenital T cruzi.

The influence of ART on the treatment of Trichomonas vaginalis among HIV-infected women.

OBJECTIVE: Among women who are human immunodeficiency virus positive (HIV+), both prevalent and persistent infections with Trichomonas vaginalis (TV) are common. TV has been shown to increase vaginal shedding of HIV, which may influence HIV sexual and perinatal transmission, making prevention important. In 1 cohort of HIV+ women in Kenya, antiretroviral therapy (ART) use, mostly nevirapine based, was associated with lower cure rates of TV for single-dose therapy. Our goal was to repeat this study in a US-based cohort of HIV+/TV+ women and compare outcomes to those with multidose therapy. METHODS: A secondary data analysis was performed on a multicentered cohort of HIV+/TV+ women who were randomized to single-dose (2 grams) or 7-day (500 mg twice daily) multidose metronidazole (MTZ) treatment. Test of cure visit, via culture, occurred 6-12 days after treatment completion. Information was collected on sex partner treatment and sexual exposures. Persistent TV infection rates were compared for women on ART at baseline vs not on ART. RESULTS: Of the 226 women included, those on ART had more treatment failures than women not on ART (24/146 [16.4%] vs 5/80 [6.3%]; P = .03). When stratified by treatment arm, more treatment failures were seen in the single-dose arm (17/73 [23.3%] vs 3/39 [7.7%]; P = .05) than in the multidose arm (7/73 [9.6%] vs 2/41 [4.8%]; P = .39). CONCLUSIONS: ART usage was associated with a higher TV persistent infection rate among those receiving the single-dose treatment, but not the multidose, providing more evidence that multidose should be the preferred treatment for HIV+ women.

Factors affecting clinician educator encouragement of routine HIV testing among trainees.

BACKGROUND: Adoption of CDC recommendations for routine, voluntary HIV screening of all Americans age 13­64 years has been slow. One method to increase adherence to clinical practice guidelines is through medical school and residency training. OBJECTIVE: To explore the attitudes, barriers, and behaviors of clinician educators (CEs) regarding advocating routine HIV testing to their trainees. DESIGN/PARTICIPANTS: We analyzed CE responses to a 2009 survey of Society of General Internal Medicine members from community, VA, and university-affiliated clinics regarding HIV testing practices. MAIN MEASURES: Clinician educators were asked about their outpatient practices, knowledge and attitudes regarding the revised CDC recommendations and whether they encouraged trainees to perform routine HIV testing. Associations between HIV testing knowledge and attitudes and encouraging trainees to perform routine HIV testing were estimated using bivariate and multivariable logistic regression. RESULTS: Of 515 respondents, 367 (71.3%) indicated they supervised trainees in an outpatient general internal medicine clinic. These CEs demonstrated suboptimal knowledge of CDC guidelines and over a third reported continued risk-based testing. Among CEs, 196 (53.4%) reported that they encourage trainees to perform routine HIV testing. Higher knowledge scores (aOR 5.10 (2.16, 12.0)) and more positive attitudes toward testing (aOR 8.83 (4.21, 18.5)) were independently associated with encouraging trainees to screen for HIV. Reasons for not encouraging trainees to screen included perceived low local prevalence (37.2%), competing teaching priorities (34.6%), and a busy clinic environment (34.0%). CONCLUSIONS: Clinician educators have a special role in the dissemination of the CDC recommendations as they impact the knowledge and attitudes of newly practicing physicians. Despite awareness of CDC recommendations, many CEs do not recommend universal HIV testing to trainees. Interventions that improve faculty knowledge of HIV testing recommendations and address barriers in resident clinics may enhance adoption of routine HIV testing.

Disclosure of HIV status: Experiences of Patients Enrolled in an Integrated TB and HAART Pilot Programme in South Africa.

The convergence between the tuberculosis (TB) and HIV epidemics has led to studies investigating strategies for integrated HIV and TB care. We present the experiences of a cohort of 17 patients enrolled in the first integrated TB and HIV treatment pilot programme, conducted in Durban, South Africa, as a precursor to a pivotal trial to answer the question of when to start antiretroviral treatment (ART) in patients co-infected with HIV and TB. Patients' experiences with integrated TB and HIV care can provide insight about the problems or benefits of introducing HIV treatment into existing TB care in resource-constrained settings, where stigma and discrimination are often pervasive and determining factors influencing treatment uptake and coverage. Individual interviews, focus group discussions, and observations were used to understand patients' experiences with integrated TB and HIV treatment. The patients described incorporating highly active antiretroviral therapy (HAART) into their daily routine as 'easy'; however, the patients experienced difficulties with disclosing their HIV status. Non-disclosure to sexual partners may jeopardise safer-sex practices and enhance HIV transmission. Being on TB treatment created a safe space for all patients to conceal their HIV status from those to whom they did not wish to disclose. The data suggest that the context of directly observed therapy (DOT) for TB may have the added benefit of creating a safe space for introducing ART to patients who would benefit most from treatment initiation but who are not ready or prepared to disclose their HIV status to others.

FIA Score: a simple risk index for predicting fatality in aviation crashes.

BACKGROUND: Previous studies have identified a variety of risk factors for occupant fatality in aviation crashes. A simple composite index measuring the risk of fatality in a given crash, however, is lacking. METHODS: The FIA Score is a four-point (0-3) index based on the number of three risk factors for occupant fatality present in a given aviation crash: fire, instrument meteorological condition, and being away from airport. We assessed the validity of this risk index using aviation crash investigation data from the National Transportation Safety Board for the years 1983 to 2005. Sensitivity, specificity, and area under the receiver operating characteristic curve according to the type of flight operations were computed. The analysis was first limited to pilot-in-command fatality and then replicated to any fatality. RESULTS: The study sample consisted of 44,828 aviation crashes, in which 7,889 (18%) pilots-in-command were fatally injured. The pilot crash fatality rate was 3%, 18%, 62%, and 89% for FIA Scores of 0 (none of the 3 risk factors present), 1, 2, and 3 (all 3 risk factors present), respectively. The FIA Score performed consistently well in predicting pilot fatality in crashes involving different types of flight operations. The area under receiver operating characteristic curve was 0.86 (95% confidence interval [CI]: 0.78-0.95) for major airline crashes, 0.83 (95% CI: 0.80-0.85) for commuter and air taxi crashes, and 0.81 (95% CI: 0.81-0.82) for general aviation crashes. The results were similar when the outcome was measured by whether or not the crash resulted in any fatality. CONCLUSIONS: The FIA Score appears to be a valid tool for measuring fatality risk in aviation crashes. Given its simplicity, the FIA risk index should be readily applicable to trauma research and prevention.

Knowledge and acceptability of HAART among TB patients in Durban, South Africa.

From October 2002 to February 2003, we conducted semi-structured interviews on knowledge of HIV, antiretroviral treatment, and willingness to participate in voluntary counselling and testing and HAART with 54 consenting patients attending a tuberculosis (TB) clinic in Durban, South Africa. 74% of patients interviewed reported not knowing anything about antiretroviral treatment (HAART). Knowledge of antiretroviral drugs (ARVs) was restricted to use in preventing mother to child HIV transmission (MTCT). 57.4% of the patients reported having an HIV test in the past, but less than 10% were aware of their current HIV status. Patients who did not know their current HIV status expressed fear and hesitation about testing HIV positive. However, 91% of the patients expressed willingness to participate in HIV treatment given the opportunity. The findings from this study indicate that knowledge of HIV treatment is limited. As access to HAART is expanded, information about HIV treatment options will need to be disseminated. TB centres may present unique opportunities for disseminating HIV prevention, care, and treatment options.

Estimating the impact of establishing family housing on the annual risk of HIV infection in South African mining communities.

OBJECTIVE: The objective of this study was to determine the HIV-related epidemiologic impact of establishing family-style housing in mining communities in South Africa. METHODS: Modeling sex acts as independent Bernoulli trials, the estimated impact of converting to family housing arrangements on the annual risk of HIV infection is calculated and the differential effects on migrants and their partners is explored. RESULTS: Family housing could reduce HIV transmission among migrants and their partners in South Africa. Given baseline estimates, the predicted net reduction in the annual risk of HIV infection with family housing is 0.0254 and 0.0305 for short- and long-stay couples respectively. A reduction in the annual risk of HIV infection under family housing depends on the proportion of HIV negative concordance among couples. HIV-negative concordance among couples above 22% provides reductions in the annual risk of HIV infection under family housing. CONCLUSIONS: The results indicate that family housing could decrease HIV transmission among HIV-negative concordant couples, indicating that this policy alternative should be examined closely to assess its viability and use as a prevention method.