Faculty Bibliography

In March 2013 a state judge invalidated New York City's proposal to ban sales of sugar-sweetened beverages larger than 16 ounces; the case is under appeal. This setback was attributable in part to opposition from the beverage industry and racial/ethnic minority organizations they support. We provide lessons from similar tobacco industry efforts to block policies that reduced smoking prevalence. We offer recommendations that draw on the tobacco control movement's success in thwarting industry influence and promoting public health policies that hold promise to improve population health.

BACKGROUND: There is increasing evidence of the role that exposure to industrial chemicals plays in the development of childhood disease. The USA and the European Union (EU) have taken divergent policy approaches to managing this issue, and economic estimates of disease costs attributable to environmental exposures in children are available in the USA but not the EU. We undertook the first economic evaluation of the impacts of childhood environmental chemical exposures in the EU. METHODS: We used a cost-of-illness approach to estimate health care system costs, and used environmentally attributable fraction modelling to estimate the proportion of childhood disease due to environmental exposures. We analysed data on exposures, disease prevalence and costs at a country level, and then aggregated costs across EU member states to estimate overall economic impacts within the EU. RESULTS: We found the combined environmentally attributable costs of lead exposure, methylmercury exposure, developmental disabilities, asthma and cancer to be $70.9 billion in 2008 (range: $58.9-$90.6 billion). These costs amounted to ~0.480% of the gross domestic product of the EU in 2008. CONCLUSIONS: Childhood chemical exposures present a significant economic burden to the EU. Our study offers an important baseline of disease costs before the implementation of Registration, Evaluation and Authorization of Chemicals, which is important for studying the impacts of this policy regime.

Epidemiologic studies that evaluated genetic susceptibility to the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1,078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-medial thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (>/= 40.4 mug/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 mum (95% CI=14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (beta=-5.1 mum, 95% CI=-31.6, 21.3) or arsenic exposure alone (beta=7.2 mum, 95% CI=-3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend<0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04-1.59), 1.41 (95% CI: 1.15-1.74), 1.46 (95% CI: 1.19-1.79), and 1.56 (95% CI: 1.27-1.91). Compared to those with relatively little absolute urinary As change during follow-up (-10.40 to 41.17mug/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80-1.22) and 0.80 (95% CI: 0.65-0.99) for those whose urinary As decreased by >47.49mug/l and 10.87 to 47.49mug/l since last visit, respectively, and 1.17 (95% CI: 0.94-1.45) and 1.36 (95% CI: 1.10-1.66) for those with between-visit increases of 10.40 to 41.17mug/l and >41.17mug/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As.

BACKGROUND: Support for cannabis ("marijuana") legalization is increasing in the United States (US). Use was recently legalized in two states and in Uruguay, and other states and countries are expected to follow suit. This study examined intentions to use among US high school seniors if cannabis were to become legally available. METHODS: Data from the last five cohorts (2007-2011) of high school seniors in Monitoring the Future, an annual nationally representative survey of students in the US were utilized. Data were analyzed separately for the 6116 seniors who reported no lifetime use of cannabis and the 3829 seniors who reported lifetime use (weighted Ns). We examined whether demographic characteristics, substance use and perceived friend disapproval towards cannabis use were associated with (1) intention to try cannabis among non-lifetime users, and (2) intention to use cannabis as often or more often among lifetime users, if cannabis was legal to use. RESULTS: Ten percent of non-cannabis-using students reported intent to initiate use if legal and this would be consistent with a 5.6% absolute increase in lifetime prevalence of cannabis use in this age group from 45.6% (95% CI=44.6, 46.6) to 51.2% (95% CI=50.2, 52.2). Eighteen percent of lifetime users reported intent to use cannabis more often if it was legal. Odds for intention to use outcomes increased among groups already at high risk for use (e.g., males, whites, cigarette smokers) and odds were reduced when friends disapproved of use. However, large proportions of subgroups of students normally at low risk for use (e.g., non-cigarette-smokers, religious students, those with friends who disapprove of use) reported intention to use if legal. Recent use was also a risk factor for reporting intention to use as often or more often. CONCLUSION: Prevalence of cannabis use is expected to increase if cannabis is legal to use and legally available.

STUDY OBJECTIVE: To evaluate next-morning driving performance after middle-of-the-night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST). DESIGN: Single-center, four-period, randomized, double-blind, placebo-controlled, crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS: Forty healthy volunteers (20 females). INTERVENTIONS: Single dose of ZST administered in the middle of the night at 3 and 4 h before driving, zopiclone 7.5 mg at bedtime 9 h before driving, and placebo. MEASUREMENTS: Performance in a 100-km standardized highway driving test in normal traffic measuring standard deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes in SDLP > 2.5 cm were considered to reflect clinically relevant driving impairment. RESULT: For ZST, Max McNemar symmetry analyses showed that the proportion of drivers classified as impaired was increased 3 h after dosing (P < 0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P = 0.0174] at 4 h). The morning after zopiclone, 45% of the drivers were classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001). There were no significant sex differences in effects of ZST and zopiclone. CONCLUSION: Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal risk of impairing driving performance in the morning >/= 4 hours after middle-of-the night use. When taken 3 hours before driving, the drug may have impairing effects so caution should be exercised if medication is taken other than as indicated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01106859; Trial Name: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet; http://clinicaltrials.gov/ct2/show/NCT01106859. CITATION: Vermeeren A; Vuurman EF; Leufkens TR; Van Leeuwen CJ; Van Oers AC; Laska E; Rico S; Steinberg F; Roth T. Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use. SLEEP 2014;37(3):489-496.

ABSTRACT. Background: With rising rates of prescription drug abuse and associated overdose deaths, there is great interest in having accurate and efficient screening tools that identify nonmedical use of prescription drugs in health care settings. The authors sought to gain a better understanding of how patients interpret questions about misuse of prescription drugs, with the goal of improving the accuracy and acceptability of instruments intended for use in primary care. Methods: A total of 27 English-speaking adult patients were recruited from an urban safety net primary care clinic to complete a cognitive interview about a 4-item screening questionnaire for tobacco, alcohol, illicit drugs, and misuse of prescription drugs. Detailed field notes were analyzed for overall comprehension of the screening items on illicit drug use and prescription drug misuse, the accuracy with which participants classified drugs into these categories, and whether the screening response correctly captured the participant's substance use behavior. Results: Based on initial responses to the screening items, 6 (22%) participants screened positive for past-year prescription drug misuse, and 8 (30%) for illicit drug use. The majority (26/27) of participants correctly interpreted the item on illicit drug use, and appropriately classified drugs in this category. Eleven (41%) participants had errors in their understanding of the prescription drug misuse item. The most common error was classifying use of medications without abuse potential as nonmedical use. All cases of misunderstanding the prescription drug misuse item occurred among participants who screened negative for illicit drug use. Conclusions: The results suggest that terminology used to describe misuse of prescription medications may be misunderstood by many primary care patients, particularly those who do not use illicit drugs. Failure to improve upon the language used to describe prescription drug misuse in screening questionnaires intended for use in medical settings could potentially lead to high rates of false-positive results.

d-Cycloserine (DCS) has been shown to enhance memory and, in a previous trial, once-weekly DCS improved negative symptoms in schizophrenia subjects. We hypothesized that DCS combined with a cognitive remediation (CR) program would improve memory of a practiced auditory discrimination task and that gains would generalize to performance on unpracticed cognitive tasks. Stable, medicated adult schizophrenia outpatients participated in the Brain Fitness CR program 3-5 times per week for 8weeks. Subjects were randomly assigned to once-weekly adjunctive treatment with DCS (50mg) or placebo administered before the first session each week. Primary outcomes were performance on an auditory discrimination task, the MATRICS cognitive battery composite score and the Scale for the Assessment of Negative Symptoms (SANS) total score. 36 subjects received study drug and 32 completed the trial (average number of CR sessions=26.1). Performance on the practiced auditory discrimination task significantly improved in the DCS group compared to the placebo group. DCS was also associated with significantly greater negative symptom improvement for subjects symptomatic at baseline (SANS score >/=20). However, improvement on the MATRICS battery was observed only in the placebo group. Considered with previous results, these findings suggest that DCS augments CR and alleviates negative symptoms in schizophrenia patients. However, further work is needed to evaluate whether CR gains achieved with DCS can generalize to other unpracticed cognitive tasks.

In the United States, more than 115,000 patients are wait-listed for organ transplants despite that there are 12,000 patients each year who die or become too ill for transplantation. One reason for the organ shortage is that candidates for donation must die in the hospital, not the emergency department (ED), either from neurologic or circulatory-respiratory death under controlled circumstances. Evidence from Spain and France suggests that a substantial number of deaths from cardiac arrest may qualify for organ donation using uncontrolled donation after circulatory determination of death (uDCDD) protocols that rapidly initiate organ preservation in out-of-hospital and ED settings. Despite its potential, uDCDD has been criticized by panels of experts that included neurologists, intensivists, attorneys, and ethicists who suggest that organ preservation strategies that reestablish oxygenated circulation to the brain retroactively negate previous death determination based on circulatory-respiratory criteria and hence violate the dead donor rule. In this article, we assert that in uDCDD, all efforts at saving lives are exhausted before organ donation is considered, and death is determined according to "irreversible cessation of circulatory and respiratory functions" evidenced by "persistent cessation of functions during an appropriate period of observation and/or trial of therapy." Therefore, postmortem in vivo organ preservation with chest compressions, mechanical ventilation, and extracorporeal membrane oxygenation is legally and ethically appropriate. As frontline providers for patients presenting with unexpected cardiac arrest, emergency medicine practitioners need be included in the uDCDD debate to advocate for patients and honor the wishes of the deceased.