Activation of the Constitutive Androstane Receptor by Monophthalates.

Humans in industrialized areas are continuously exposed to phthalate plasticizers, prompting concerns of their potential toxicities. Previous studies from our laboratory and others have shown that various phthalates activate several mammalian nuclear receptors, in particular the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), and the peroxisomal proliferator-activated receptors (PPARs), although often at concentration levels of questionable relevance to human exposure. We discovered that di(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DiNP), two of the highest volume production agents, were potent activators of human CAR2 (hCAR2), a unique human CAR splice variant and, to a lesser degree, human PXR (hPXR). These diphthalates undergo rapid metabolism in mammalian systems, initially to their major monophthalate derivatives MEHP and MiNP. Although MEHP and MiNP are reported activators of the rodent PPARs, with lower affinities for the corresponding human PPARs, it remains unclear whether these monophthalate metabolites activate hCAR2 or hPXR. In this investigation, we assessed the relative activation potential of selected monophthalates and other low molecular weight phthalates against hCAR, the most prominent hCAR splice variants, as well as hPXR and human PPAR. Using transactivation and mammalian two-hybrid protein interaction assays, we demonstrate that these substances indeed activate hCARs and hPXR but to varying degrees. MEHP and MiNP exhibit potent activation of hCAR2 and hPXR with higher affinities for these receptors than for the hPPARs. The rank order potency for MEHP and MiNP was hCAR2 > hPXR > hPPARs. Results from primary hepatocyte experiments also reflect the MEHP and MiNP upregulation of the respective human target genes. We conclude that both di- and monophthalates are potently selective hCAR2 activators and effective hPXR activators. These results implicate these targets as important mediators of selective phthalate effects in humans. The striking differential affinities for these compounds between human and rodent nuclear receptors further implies that biological results obtained from rodent models may be of only limited relevance for interpolating phthalate-mediated effects in humans.

Snus use and rejection in the USA.

OBJECTIVE: To determine whether snus might become a strategy for reducing the harm associated with cigarette smoking in the USA as appears to be the case in Sweden, we examined receptivity to snus use in two cities with the greatest exposure to the major brands. METHODS: A dual frame, telephone survey and a brief mail survey were conducted in 2011 and 2012 in Indianapolis, Indiana and Dallas/Fort Worth Texas. Over 5000 adults completed surveys. Trial, ever use, current use and reasons for using or quitting snus after trial were measured. RESULTS: Among male smokers, 29.9% had ever tried snus (CI 22.7 to 38.1) and 4.2% were current users (CI 1.6 to 10.7). Among female smokers, 8.5% ever tried snus (CI 4.4 to 15.7) and current use was unknown. Current use was virtually absent among former smokers and never smokers. A major predictor of any level of snus use was current use of conventional smokeless tobacco. Those who tried and gave up snus cited curiosity (41.3%) and the fact that it was available at low or no cost (30%) as reasons for trial; reasons for not continuing included preferring another form of tobacco (75.1%) and disliking the mouth feel (34.6%). Almost all current snus users indicated that they were trying to cut down on cigarettes, but few (3.9%) were using it to quit smoking entirely. CONCLUSIONS: The low rate of adoption of snus suggests that neither the hopes nor the fears surrounding this new product are likely to be realised in the USA with the current marketing patterns.

Epidemiology of undiagnosed trichomoniasis in a probability sample of urban young adults.

T. vaginalis infection (trichomoniasis) is the most common curable sexually transmitted infection (STI) in the U.S. It is associated with increased HIV risk and adverse pregnancy outcomes. Trichomoniasis surveillance data do not exist for either national or local populations. The Monitoring STIs Survey Program (MSSP) collected survey data and specimens which were tested using nucleic acid amplification tests to monitor trichomoniasis and other STIs in 2006-09 among a probability sample of young adults (N = 2,936) in Baltimore, Maryland--an urban area with high rates of reported STIs. The estimated prevalence of trichomoniasis was 7.5% (95% CI 6.3, 9.1) in the overall population and 16.1% (95% CI 13.0, 19.8) among Black women. The overwhelming majority of infected men (98.5%) and women (73.3%) were asymptomatic. Infections were more common in both women (OR = 3.6, 95% CI 1.6, 8.2) and men (OR = 9.0, 95% CI 1.8, 44.3) with concurrent chlamydial infection. Trichomoniasis did not vary significantly by age for either men or women. Women with two or more partners in the past year and women with a history of personal or partner incarceration were more likely to have an infection. Overall, these results suggest that routine T vaginalis screening in populations at elevated risk of infection should be considered.

Exploring determinants of surrogate decision-maker confidence: an example from the ICU.

This article is an exploratory data analysis of the determinants of confidence in a surrogate decision maker who has been asked to permit an intensive care unit (ICU) patient's participation in genetic research. We pursue the difference between surrogates' and patients' confidence that the surrogate can accurately represent the patient's wishes. The article also explores whether greater confidence leads to greater agreement between patients and surrogates. Our data come from a survey conducted in three hospital ICUs. We interviewed 445 surrogates and 214 patients. The only thing that influences patients' confidence in their surrogate's decision is whether they had prior discussions with him or her; however, there are more influences operating on the surrogate's self-confidence. More confident surrogates are more likely to match their patients' wishes. Patients are more likely to agree to research participation than their surrogates would allow. The surrogates whose response did not match as closely were less trusting of the hospital staff, were less likely to allow patient participation if there were no direct benefits to the patient, had given less thought about the way genetic research is conducted, and were much less likely to have a person in their life who they would trust to make decisions for them if they were incapacitated.

Chlamydia trachomatis infection among 15- to 35-year-olds in Baltimore, MD.

BACKGROUND: Chlamydia trachomatis (Ct) is the most frequently reported infectious disease in the United States. This article reports population and subpopulation prevalence estimates of Ct and correlates of infection among 15- to 35-year-olds in Baltimore, MD. METHODS: The Monitoring STIs Survey Program (MSSP) monitored sexually transmitted infection (STI) prevalence among probability samples of residents of Baltimore, a city with high STI rates. MSSP respondents completed telephone audio computer-assisted self-interviews and provided biospecimens for STI testing. RESULTS: Among 2120 Baltimore residents aged 15 to 35 years, the estimated prevalence of chlamydia was 3.9% (95% confidence interval [CI]: 2.8, 5.0). Prevalence was 5.8% (95% CI: 4.1, 7.6) among black MSSP respondents versus 0.7% (95% CI: 0.0, 1.4) among nonblack respondents; all but 4 infections detected were among black respondents. Sexual behaviors and other factors associated with infection were far more prevalent among black than nonblack Baltimore residents. Racial disparities persisted after adjustment for sociodemographic, behavioral, and health factors. CONCLUSION: The MSSP highlights a higher Ct prevalence among young people in Baltimore than in the United States overall, with notable racial disparities in infection and associated risk behaviors. Public health efforts are needed to improve the diagnosis and treatment of asymptomatic infections in this population.

Improving epidemiological surveys of sexual behaviour conducted by telephone.

BACKGROUND: This study assesses the impact of Telephone Audio Computer-Assisted Self-Interviewing (T-ACASI) on the reporting of sensitive (mainly heterosexual) behaviours. METHODS: A randomized experiment was embedded in a telephone survey that drew probability samples of the populations of the USA (N = 1543) and Baltimore city (N = 744). Respondents were randomly assigned to have questions asked either by a T-ACASI computer or by a human telephone interviewer. RESULTS: Compared with interviewer-administered telephone surveys, T-ACASI obtained more frequent reporting of a range of mainly heterosexual behaviours that were presumed to be sensitive, including recency of anal sex [adjusted odds ratio (A-OR) = 2.00, P < 0.001), sex during menstrual period (A-OR = 1.49, P < 0.001), giving oral sex (A-OR = 1.40, P = 0.001) and receiving oral sex (A-OR = 1.36, P = 0.002), and sexual difficulties for the respondent (A-OR = 1.45, P = 0.034) and their main sex partner (A-OR = 1.48, P = 0.0). T-ACASI also obtained less frequent reporting that respondent had a 'main sex partner' (A-OR = 0.56, P = 0.011) and discussed contraception prior to first sex with that sex partner (A-OR = 0.82, P = 0.094). For both males and females, T-ACASI obtained more frequent reports of first vaginal sex occurring at early ages (before ages 12 through 15). 'For males only', T-ACASI also elicited more frequent reports that first vaginal sex had 'not' occurred at later ages (i.e. by ages 20 through 24). CONCLUSION: T-ACASI increases the likelihood that survey respondents will report sensitive heterosexual behaviours.

Impact of T-ACASI on Survey Measurements of Subjective Phenomena.

Numerous studies have shown that audio-computer-assisted self-interviewing (audio-CASI) and telephone audio-CASI (T-ACASI) technologies yield increased reporting of sensitive and stigmatized objective phenomena such as sexual and drug use behaviors. Little attention has been given, however, to the impact of these technologies on the measurement of subjective phenomena (attitudes, opinions, feelings, etc.). This article reports results for the seven subjective measurements included in the National STD and Behavior Measurement Experiment (NSBME). NSBME drew probability samples of USA and Baltimore adults (Ns = 1,543 and 744, respectively) and randomized these respondents to be interviewed by T-ACASI or telephone interviewer-administered questioning (T-IAQ). Response distributions for all subjective measurements obtained by T-ACASI diverge from those obtained by human telephone interviewers. For six of our seven ordinal-scaled measurements, this divergence involved shifting responses directionally along the ordinal scale, as opposed to a nondirectional redistribution among response categories. When interviewed by T-ACASI, respondents were more supportive of traditional gender roles and corporal punishment, less supportive of integrated neighborhoods and same-gender sex, and more likely to agree that occasional marijuana use is harmless and to describe themselves as attractive. The majority of these results suggest that telephone survey respondents may provide more "tolerant" and "socially liberal" responses to human interviewers than to a T-ACASI computer. Similarly, although the evidence is not entirely consistent, the impact of T-ACASI appears to increase with the social vulnerability of the population surveyed.

Issues in conducting epidemiologic research among elders: lessons from the MOBILIZE Boston Study.

Conducting research in elderly populations is important, but challenging. In this paper, the authors describe specific challenges that have arisen and solutions that have been used in carrying out The MOBILIZE Boston Study, a community-based, prospective cohort study in Massachusetts focusing on falls among 765 participants aged 70 years or older enrolled during 2005-2007. To recruit older individuals, face-to-face interactions are more effective than less personal approaches. Use of a board of community leaders facilitated community acceptance of the research. Establishing eligibility for potential participants required several interactions, so resources must be anticipated in advance. Assuring a safe and warm environment for elderly participants and offering a positive experience are a vital priority. Adequate funding, planning, and monitoring are required to provide transportation and a fully accessible environment in which to conduct study procedures as well as to select personnel highly skilled in interacting with elders. It is hoped that this paper will encourage and inform future epidemiologic research in this important segment of the population.

T-ACASI reduces bias in STD measurements: the National STD and Behavior Measurement Experiment.

BACKGROUND: Although telephone surveys provide an economical method for assessing patterns of diagnosed sexually transmitted diseases (STDs) and STD-related behaviors in populations, the requirement that respondents report such information to human telephone interviewers introduces an opportunity for substantial reporting bias. Telephone computer-assisted self-interviewing (T-ACASI) surveys substitute a computer for human interviewers when asking sensitive questions. METHODS: A randomized experiment was embedded in a telephone survey that drew probability samples of the populations of the United States (N = 1543) and Baltimore city (N = 744). Respondents were randomly assigned to have sensitive questions asked either by a T-ACASI computer or by a human telephone interviewer. RESULTS: Respondents interviewed by a T-ACASI computer were more likely to report STD symptoms [dysuria, genital sores, genital discharge, and genital warts; adjusted odds ratios (ORs) = 1.5-2.8] and a diagnosis of gonococcal or chlamydial infection during the past year (adjusted ORs = 3.6 and 6.1). T-ACASI respondents with a main sex partner in the past year were more likely to report that their partner has had an STD (adjusted OR = 2.4). For some measurements, the impact of T-ACASI was strongest among younger and less-educated respondents. When sampling weights were applied to project National STD and Behavior Measurement Experiment results to the populations of the United States and Baltimore, we found that reliance on data obtained by human interviewers would underestimate the annual incidence of chlamydial and gonococcal infections in these populations by factors of 2.4 to 9.7. CONCLUSIONS: Compared with human telephone interviewers, T-ACASI surveys obtain increased reporting of STD symptoms, infections, and STD-related behaviors.

SAME-GENDER SEX IN THE UNITED STATES IMPACT OF T-ACASI ON PREVALENCE ESTIMATES.

Well-conducted telephone surveys provide an economical means of estimating the prevalence of sexual and reproductive behaviors in a population. There is, however, a nontrivial potential for bias since respondents must report sensitive information to a human interviewer. The National STD and Behavior Measurement Experiment (NSBME) evaluates a new survey technology-telephone audio computer-assisted self-interviewing (T-ACASI)-that eliminates this requirement. The NSBME embedded a randomized experiment in a survey of probability samples of 1,543 U.S. and 744 Baltimore adults ages 18 to 45. Compared with NSBME respondents interviewed by human interviewers, respondents interviewed by T-ACASI were 1.5 to 1.6 times more likely to report same-gender sexual attraction, experience, and genital contact. The impact of T-ACASI was more pronounced (odds ratio = 2.5) for residents of locales that have historically been less tolerant of same-gender sexual behaviors and for respondents in households with children (odds ratio = 3.0).

Reducing bias in telephone survey estimates of the prevalence of drug use: a randomized trial of telephone audio-CASI.

AIM: To assess the impact of telephone audio computer-assisted self-interviewing (T-ACASI) on reporting of alcohol use, alcohol problems and illicit drug use in telephone surveys of the general population. Prior research suggests that illicit drug use is underreported in traditional, interviewer-administered, telephone surveys. DESIGN: Randomized experiment embedded in telephone survey of probability samples of populations of USA and Baltimore, MD. Survey respondents were randomly assigned to be interviewed either by human telephone interviewers or by T-ACASI after household screening, recruitment, and informed consent procedures were completed. SETTING: Respondents were interviewed by telephone in their homes. PARTICIPANTS: Probability samples of 1543 English-speaking adults ages 18-45 residing in telephone-accessible households in USA and 744 similarly defined adults residing in Baltimore, MD, USA. MEASUREMENTS: Nine questions on alcohol, marijuana, cocaine, and injection drug use adapted from 1994 NHSDA and four CAGE questions on alcohol problems. Crude odds ratios and odds ratios controlling for demographic factors calculated to test for differences between responses obtained by T-ACASI and human interviewers. FINDINGS: T-ACASI had mixed effects on reporting of alcohol use, but it did increase reporting of one of four CAGE alcohol problems: feeling guilty about drinking (23.0% in T-ACASI vs. 17.6% in T-IAQ, OR = 1.4, P < 0.01). T-ACASI also obtained significantly more frequent reporting of marijuana, cocaine, and injection drug use. The impact of T-ACASI was most pronounced for reporting of recent use of 'harder' drugs. Thus T-ACASI respondents were more likely to report marijuana use in the past month (10.0% vs. 5.7%, crude OR = 1.9, P < 0.001), cocaine use in the past month (2.1% vs. 0.7%, crude 3.2, P < 0.001) and injection drug use in the past five years (1.6% vs. 0.3%, crude OR = 4.8, P < 0.01). CONCLUSIONS: Telephone survey respondents were more likely to report illicit drug use and one alcohol problem when interviewed by T-ACASI rather than by human telephone interviews.

Consequences of declining survey response rates for smoking prevalence estimates.

BACKGROUND: Response rates have been declining in statewide tobacco surveys. This study investigated whether there was associated evidence of increasing bias in smoking prevalence estimates. METHODS: Demographic characteristics of respondents to tobacco surveys in Massachusetts and California were compared to population data in the early 1990s, when response rates were high, and in more recent years, when response rates were lower. State estimates of smoking prevalence at three times were compared with estimates from the Current Population Survey Tobacco Use Supplement (CPS-TUS), conducted by the U.S. Census Bureau. RESULTS: Under- and over-representation of population subgroups has not changed as response rates have declined. Smoking prevalence estimates from state surveys remain relatively close to the state-specific CPS-TUS estimates. CONCLUSIONS: There is no evidence that declining response rates have resulted in less accurate or biased estimates of smoking behavior.