Faculty Bibliography

Gestational trophoblastic disease (GTD), a rare complication of pregnancy, includes both benign and malignant forms, the latter collectively referred to as gestational trophoblastic neoplasia (GTN). When metastatic, the lungs are the most common site of initial spread. Beta-human chorionic gonadotropin, elaborated to some extent by all forms of GTD, is useful in facilitating disease detection, diagnosis, monitoring treatment response, and follow-up. Imaging evaluation depends on whether GTD manifests in one of its benign forms or whether it has progressed to GTN. Transabdominal and transvaginal ultrasound with duplex Doppler evaluation of the pelvis are usually appropriate diagnostic procedures in either of these circumstances, and in posttreatment surveillance. The appropriateness of more extensive imaging remains dependent on a diagnosis of GTN and on other factors. The use of imaging to assess complications, typically hemorrhagic, should be guided by the location of clinical signs and symptoms. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

OBJECTIVE:To estimate prevalence of past-month marijuana, cocaine, and nonmedical prescription opioid (NPO) use and determine employment-related correlates of drug use among construction trade/extraction workers (CTEW). METHODS:We analyzed ten years of data (2005-2014) from 293,492 adults (age≥18) in the National Survey on Drug Use and Health, comparing CTEW and non-CTEW. RESULTS:CTEW were 5.6% (n = 16,610) of the sample. Compared to non-CTEW, CTEW were significantly more likely to report past-month marijuana (12.3% vs. 7.5%), cocaine (1.8% vs. 0.8%), and/or NPO use (3.4% vs. 2.0%; Ps<.001). Among CTEW, past-week unemployment and working for >3 employers was associated with increased odds of marijuana and NPO use. Missing 1-2 days in the past month because the participant did not want to go into work was associated with increased odds for use of marijuana, cocaine, and NPO use. Missing 3-5 days of work in the past month because sick or injured was associated with double the odds (aOR = 2.00 [95% CI: 1.33-3.02]) of using NPO. Having written drug policies was associated with reduced odds for cocaine use, and workplace tests for drug use during hiring and random drug testing were also associated with lower odds of marijuana use. CONCLUSIONS:CTEW are a high-risk population for drug use. Precarious employment is associated with higher prevalence of drug use while some workplace drug policies were associated with lower prevalence. Coupled with reports of high overdose mortality among CTEW, these findings suggest that prevention and harm reduction programming is needed to prevent drug-related morbidity and mortality among CTEW.

Observational studies in glaucoma patients can provide important evidence on treatment effects, especially for combination therapies which are often used in reality. But the success relies on the reduction of selection bias through methods such as propensity score (PS) weighting. The objective of this study was to assess the effects of five glaucoma treatments (medication, laser, non-laser surgery (NLS), laser + medication, and NLS + medication) on 1-year intraocular pressure (IOP) change. Data were collected from 90 glaucoma subjects who underwent a single laser, or NLS intervention, and/or took the same medication for at least 6 months, and had IOP measures before the treatment and 12-months after. Baseline IOP was significantly different across groups (p = 0.007) and this unbalance was successfully corrected by the PS weighting (p = 0.81). All groups showed statistically significant PS-weighted IOP reductions, with the largest reduction in NLS group (-6.78 mmHg). Baseline IOP significantly interacted with treatments (p = 0.03), and at high baseline IOP medication was less effective than other treatments. Our findings showed that the 1-year IOP reduction differed across treatment groups and was dependent on baseline IOP. The use of PS-weighted methods reduced treatment selection bias at baseline and allowed valid assessment of the treatment effect in an observational study.

Introduction/UNASSIGNED:Smoking prevalence is high in Viet Nam, yet tobacco dependence treatment (TDT) is not widely available. Methods/UNASSIGNED:We conducted a quasi-experimental study that compared the effectiveness of health care provider advice and assistance (ARM 1) vs. ARM 1 plus village health worker (VHW) counseling (ARM 2) on abstinence at 6-month follow-up. This study was embedded in a larger two-arm cluster randomized controlled trial (RCT) conducted in 26 community health centers (CHCs) in Viet Nam. Subjects (N=1,318) were adult patients who visited any participating CHC during the parent RCT intervention period and were self-identified as current tobacco users (cigarettes and/or waterpipe). Results/UNASSIGNED:At 6-month follow-up, abstinences rates in ARM 2 were significantly higher than ARM 1 (25.7% vs. 10.5%; p<.001). In multivariate analyses smokers in ARM 2 were almost three times more likely to quit compared with those in ARM 1 (adjusted odds ratio [AOR]=2.96, 95% confidence interval [CI]=1.78-4.92). Compared to cigarette-only smokers, waterpipe-only smokers (AOR=0.4, 95% CI=0.26-0.62) and dual users (AOR=0.62, 95% CI=0.45-0.86) were less likely to achieve abstinence, however the addition of VHW counseling (ARM 2) was associated with higher quit rates compared with ARM 1 alone for all smoker types. Conclusion/UNASSIGNED:A team approach in TDT programs that offers a referral system for health care providers to refer smokers to VHW-led cessation counseling is a promising and potentially scalable model for increasing access to evidence-based TDT and increasing quit rates in LMICs. TDT programs may need to adapt interventions to improve outcomes for waterpipe users.

The goal of this study was to assess biomarkers of exposure to glyphosate and assess potential associations with renal function in children. Glyphosate is used ubiquitously in agriculture worldwide. While previous studies have indicated that glyphosate may have nephrotoxic effects, few have examined potential effects on kidney function in children. We leveraged three cohorts across different phases of child development and measured urinary levels of glyphosate. We evaluated associations of glyphosate with three biomarkers of kidney injury: albuminuria (ACR), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury marker 1 (KIM-1). Multivariable regression analyses examined associations of glyphosate with kidney injury biomarkers controlling for covariates. We identified glyphosate in 11.1% of the total participants. The herbicide was detected more frequently in the neonate population (30%). Multivariable regression models failed to identify significant associations of log-transformed glyphosate with any of the kidney injury biomarkers, controlling for covariates age, sex, and maternal education. While we confirm detectability of glyphosate in children's urine at various ages and stages of life, there is no evidence in this study for renal injury in children exposed to low levels of glyphosate. Further studies of larger sample size are indicated to better understand putative deleterious effects of the herbicide after different levels of exposure.

It is well-established that children from low-income, under-resourced families are at increased risk of altered social development. However, the biological mechanisms by which poverty-related adversities can "get under the skin" to influence social behavior are poorly understood and cannot be easily ascertained using human research alone. This study utilized a rodent model of "scarcity-adversity," which encompasses material resource deprivation (scarcity) and reduced caregiving quality (adversity), to explore how early-life scarcity-adversity causally influences social behavior via disruption of developing stress physiology. Results showed that early-life scarcity-adversity exposure increased social avoidance when offspring were tested in a social approach test in peri-adolescence. Furthermore, early-life scarcity-adversity led to blunted hypothalamic-pituitary-adrenal (HPA) axis activity as measured via adrenocorticotropic hormone (ACTH) and corticosterone (CORT) reactivity following the social approach test. Western blot analysis of brain tissue revealed that glucocorticoid receptor levels in the dorsal (but not ventral) hippocampus and medial prefrontal cortex were significantly elevated in scarcity-adversity reared rats following the social approach test. Finally, pharmacological repletion of CORT in scarcity-adversity reared peri-adolescents rescued social behavior. Our findings provide causal support that early-life scarcity-adversity exposure negatively impacts social development via a hypocorticosteronism-dependent mechanism, which can be targeted via CORT administration to rescue social behavior.

Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from pre-diagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10mg/L compared to <1mg/L (OR=1.67, 95% CI=1.12, 2.48). A CRP concentration >10mg/L was positively associated with risk of mucinous (OR=9.67, 95% CI=1.10, 84.80) and endometrioid carcinoma (OR=3.41, 95% CI=1.07, 10.92), and suggestively positive, though not statistically significant, for serous (OR=1.43, 95% CI=0.82, 2.49) and clear cell carcinoma (OR=2.05, 95% CI=0.36, 11.57; p-heterogeneity=0.20). Heterogeneity was observed with oral contraceptive use (p-interaction=0.03), where the increased risk was present only among ever users (OR=3.24, 95% CI=1.62, 6.47). The present study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis, and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma.

RATIONALE/BACKGROUND:Many studies have linked short-term exposure to ozone (O3) with morbidity and mortality, but epidemiological evidence of associations between long-term ozone exposure and mortality is more limited. OBJECTIVES/OBJECTIVE:We investigated associations of long-term (annual or warm season average) O3 exposure with all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study, a large prospective cohort of U.S. adults with 17 years of follow-up from 1995 to 2011. METHODS:The cohort (N=548,780) was linked to census tract-level estimates for O3. Associations between long-term O3 exposure (averaged values from 2002-2010) and multiple causes of death were evaluated using multivariate Cox proportional hazards models, adjusted for both individual- and census tract-level covariates, as well as potentially confounding co-pollutants and temperature. MEASUREMENTS AND MAIN RESULTS/RESULTS:Long-term annual average exposure to O3 was significantly associated with deaths due to cardiovascular disease (per 10 ppb, HR=1.03; 95% CI: 1.01-1.06), ischemic heart disease (HR=1.06; 95% CI: 1.02-1.09), respiratory disease (HR=1.04; 95% CI: 1.00-1.09), and chronic obstructive pulmonary disease (HR=1.09; 95% CI: 1.03-1.15) in single-pollutant models. The results were robust to alternative models and adjustment for co-pollutants (fine particulate matter and nitrogen dioxide), although some evidence of confounding by temperature was observed. Significantly elevated respiratory disease mortality risk associated with long-term O3 exposure was found among those living in locations with high temperature (p-interaction<0.05). CONCLUSIONS:This study found that long-term exposure to O3 is associated with increased risk for multiple causes of mortality, suggesting that establishment of annual and/or seasonal federal O3 standard(s) are needed to more adequately protect public health from ambient O3 exposures.

Using data from a large international sample (N = 385) of first-time expectant parents, the current analysis investigated whether parents demonstrated diurnal cortisol linkage in late pregnancy and whether self-reported psychological stress moderated this linkage. At approximately 36 weeks gestation, mothers and fathers collected saliva samples in their home at three times on two consecutive days and reported on their psychological stress. Results from multilevel models indicated that there was significant positive within-couple diurnal cortisol linkage on average for the whole sample. However, this linkage was moderated by maternal self-reported psychological stress. Specifically, for couples with higher maternal psychological stress, cortisol linkage was strong. Conversely, for couples with lower maternal psychological stress, maternal and paternal cortisol were unrelated. These findings suggest that among higher-maternal-stress couples, lower paternal cortisol may buffer maternal cortisol, whereas higher paternal cortisol may amplify maternal cortisol. Our results support the idea that interpersonal psychological and physiological stress in close relationships is interdependent and mutually influenced. Further, our findings contribute to the field's understanding of interpersonal processes during pregnancy, which may have health-related implications in the prenatal and postnatal periods for both parents and the developing child.