Bachelor of Arts, University of Pennsylvania (2000)
Master of Science, University of Pennsylvania (2001)
Doctor of Philosophy, University of California Berkeley (2010)
We examined whether early gestational exposures to pesticides were associated with an increased risk of anencephaly, spina bifida, cleft lip with or without cleft palate (CLP), or cleft palate only. We used population-based data along with detailed information from maternal interviews. Exposure estimates were based on residential proximity to agricultural pesticide applications during early pregnancy. The study population derived from the San Joaquin Valley, California (1997-2006). Analyses included 73 cases with anencephaly, 123 with spina bifida, 277 with CLP, and 117 with cleft palate only in addition to 785 controls. A total of 38% of the subjects were exposed to 52 chemical groups and 257 specific chemicals. There were relatively few elevated odds ratios with 95% confidence intervals that excluded 1 after adjustment for relevant covariates. Those chemical groups included petroleum derivatives for anencephaly, hydroxybenzonitrile herbicides for spina bifida, and 2,6-dinitroaniline herbicides and dithiocarbamates-methyl isothiocyanate for CLP. The specific chemicals included 2,4-D dimethylamine salt, methomyl, imidacloprid, and ?-(para-nonylphenyl)-?-hydroxypoly(oxyethylene) phosphate ester for anencephaly; the herbicide bromoxynil octanoate for spina bifida; and trifluralin and maneb for CLP. Adjusted odds ratios ranged from 1.6 to 5.1. Given that such odds ratios might have arisen by chance because of the number of comparisons, our study showed a general lack of association between a range of agricultural pesticide exposures and risks of selected birth defects.
View details for DOI 10.1093/aje/kwt324
View details for Web of Science ID 000333246800011
View details for PubMedID 24553680
Bloodstream infections (BSI) remain a leading cause of morbidity and mortality among infants admitted to neonatal intensive care units (NICUs). At the time of evaluation for suspected BSI, presenting signs may be non-specific. We sought to determine the clinical signs and risk factors associated with laboratory-confirmed BSI among infants evaluated for late-onset sepsis in a tertiary NICU.This prospective cohort study included infants greater than 3 days of age admitted to a level 4 NICU from July 2006 to October 2009 for whom a blood culture was drawn for suspected sepsis. Clinicians documented presenting signs at the time of culture. Laboratory-confirmed BSI was defined as per the National Healthcare Safety Network. Multivariate analyses were performed using a logistic regression random effects model.680 eligible episodes of suspected BSI were recorded in 409 infants. Enteral contrast within the preceding 48 hours was the most significant risk factor for laboratory-confirmed BSI (Odds Ratio: 9.58 [95% confidence interval: 2.03-45.19]) followed by presence of a central venous catheter. Apnea and hypotension were the most strongly associated presenting signs.Among infants evaluated in a tertiary NICU, recent exposure to enteral contrast was associated with increased odds of developing BSI. Apnea and hypotension were the most strongly associated clinical signs of infection.
View details for DOI 10.1097/INF.0000000000000386
View details for PubMedID 24776516
Birth defects are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some structural anomalies, although evidence is limited and several anomalies have not been investigated previously.We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 26 congenital birth defect phenotypes with respect to quartiles of seven ambient air pollutant and traffic exposures in California during the first 2 months of pregnancy, 1997 to 2006 (874 cases and 849 controls). We calculated odds ratios (adjusted for maternal race/ethnicity, education, and vitamin use; aOR) for 11 phenotypes that had at least 40 cases.Few odds ratios had confidence intervals that did not include 1.0. Odds of esophageal atresia were increased for the highest versus lowest of traffic density (aOR?=?2.8, 95% confidence interval [CI], 1.1-7.4) and PM10 exposure (aOR 4.9; 95% CI, 1.4-17.2). PM10 was associated with a decreased risk of hydrocephaly (aOR= 0.3; 95% CI, 0.1-0.9) and CO with decreased risk of anotia/microtia (aOR?=?0.4; 95% CI, 0.2-0.8) and transverse limb deficiency (aOR?=?0.4; 95% CI, 0.2-0.9), again reflecting highest versus lowest quartile comparisons.Most analyses showed no substantive association between air pollution and the selected birth defects with few exceptions of mixed results. Birth Defects Research (Part A) 97:730-735, 2013. © 2013 Wiley Periodicals, Inc.
View details for DOI 10.1002/bdra.23175
View details for PubMedID 24108522
Congenital anomalies are a leading cause of infant morbidity and mortality. Studies suggest associations between environmental contaminants and some anomalies, although evidence is limited.We used data from the California Center of the National Birth Defects Prevention Study and the Children's Health and Air Pollution Study to estimate the odds of 27 congenital heart defects with respect to quartiles of seven ambient air pollutant and traffic exposures in California during the first 2 months of pregnancy, 1997-2006 (n?=?822 cases and n?=?849 controls).Particulate matter 10 microns (PM10 ) was associated with pulmonary valve stenosis [adjusted odds ratio (aOR)Fourth Quartile ?=?2.6] [95% confidence intervals (CI) 1.2, 5.7] and perimembranous ventricular septal defects (aORThird Quartile ?=?2.1) [95% CI 1.1, 3.9] after adjusting for maternal race/ethnicity, education and multivitamin use. PM2.5 was associated with transposition of the great arteries (aORThird Quartile ?=?2.6) [95% CI 1.1, 6.5] and inversely associated with perimembranous ventricular septal defects (aORFourth Quartile ?=?0.5) [95% CI 0.2, 0.9]. Secundum atrial septal defects were inversely associated with carbon monoxide (aORFourth Quartile ?=?0.4) [95% CI 0.2, 0.8] and PM2.5 (aORFourth Quartile ?=?0.5) [95% CI 0.3, 0.8]. Traffic density was associated with muscular ventricular septal defects (aORFourth Quartile ?=?3.0) [95% CI 1.2, 7.8] and perimembranous ventricular septal defects (aORThird Quartile ?=?2.4) [95% CI 1.3, 4.6], and inversely associated with transposition of the great arteries (aORFourth Quartile ?=?0.3) [95% CI 0.1, 0.8].PM10 and traffic density may contribute to the occurrence of pulmonary valve stenosis and ventricular septal defects, respectively. The results were mixed for other pollutants and had little consistency with previous studies.
View details for DOI 10.1111/ppe.12055
View details for PubMedID 23772934
Congenital anomalies are a leading cause of infant mortality and are important contributors to subsequent morbidity. Studies suggest associations between environmental contaminants and some anomalies, although evidence is limited. We aimed to investigate whether ambient air pollutant and traffic exposures in early gestation contribute to the risk of selected congenital anomalies in the San Joaquin Valley of California, 1997-2006. Seven exposures and 5 outcomes were included for a total of 35 investigated associations. We observed increased odds of neural tube defects when comparing the highest with the lowest quartile of exposure for several pollutants after adjusting for maternal race/ethnicity, education, and multivitamin use. The adjusted odds ratio for neural tube defects among those with the highest carbon monoxide exposure was 1.9 (95% confidence interval: 1.1, 3.2) compared with those with the lowest exposure, and there was a monotonic exposure-response across quartiles. The highest quartile of nitrogen oxide exposure was associated with neural tube defects (adjusted odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). The adjusted odds ratio for the highest quartile of nitrogen dioxide exposure was 1.7 (95% confidence interval: 1.1, 2.7). Ozone was associated with decreased odds of neural tube defects. Our results extend the limited body of evidence regarding air pollution exposure and adverse birth outcomes.
View details for DOI 10.1093/aje/kws367
View details for Web of Science ID 000318801200006
View details for PubMedID 23538941
Traffic-related air pollution is recognized as an important contributor to health problems. Epidemiologic analyses suggest that prenatal exposure to traffic-related air pollutants may be associated with adverse birth outcomes; however, there is insufficient evidence to conclude that the relation is causal. The Study of Air Pollution, Genetics and Early Life Events comprises all births to women living in 4 counties in California's San Joaquin Valley during the years 2000-2006. The probability of low birth weight among full-term infants in the population was estimated using machine learning and targeted maximum likelihood estimation for each quartile of traffic exposure during pregnancy. If everyone lived near high-volume freeways (approximated as the fourth quartile of traffic density), the estimated probability of term low birth weight would be 2.27% (95% confidence interval: 2.16, 2.38) as compared with 2.02% (95% confidence interval: 1.90, 2.12) if everyone lived near smaller local roads (first quartile of traffic density). Assessment of potentially causal associations, in the absence of arbitrary model assumptions applied to the data, should result in relatively unbiased estimates. The current results support findings from previous studies that prenatal exposure to traffic-related air pollution may adversely affect birth weight among full-term infants.
View details for DOI 10.1093/aje/kws148
View details for Web of Science ID 000310371200010
View details for PubMedID 23045474
Analyses from double-blind randomized trials have reported lower mortality among participants who were more adherent to placebo compared with those who were less adherent. We explored this phenomenon by analyzing data from the placebo arm of the Heart and Estrogen/Progestin Replacement Study (HERS), a randomized, double-blind, placebo-controlled trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the HERS. Secondary aims included assessment of the association between placebo adherence and cause-specific morbidity and mortality.Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication during each individual's participation in the study, whereas those with "lower placebo adherence" took less than 75%. The primary outcome was in-study all-cause mortality.More adherent participants had significantly lower total mortality compared with less adherent participants (hazard ratio, 0.52; 95% confidence interval, 0.29-0.93). Adjusting for available confounders did not change the magnitude or significance of the estimates. Analyses revealed that the association of higher adherence and mortality might be explained, in part, by time-dependent confounding.Analyses of the HERS data support a strong association between adherence to placebo study medication and mortality. Although probably not due to simple confounding by healthy lifestyle factors, the underlying mechanism for the association remains unclear. Further analyses of this association are necessary to explain this observation.
View details for DOI 10.1016/j.amjmed.2012.02.014
View details for Web of Science ID 000306741300025
View details for PubMedID 22840666
Induction of labor is on the rise in the U.S., increasing from 9.5 percent in 1990 to 22.1 percent in 2004. Although, it is not entirely clear what proportion of these inductions are elective (i.e. without a medical indication), the overall rate of induction of labor is rising faster than the rate of pregnancy complications that would lead to a medically indicated induction. However, the maternal and neonatal effects of induction of labor are unclear. Many studies compare women with induction of labor to those in spontaneous labor. This is problematic, because at any point in the management of the woman with a term gestation, the clinician has the choice between induction of labor and expectant management, not spontaneous labor. Expectant management of the pregnancy involves nonintervention at any particular point in time and allowing the pregnancy to progress to a future gestational age. Thus, women undergoing expectant management may go into spontaneous labor or may require indicated induction of labor at a future gestational age.The Stanford-UCSF Evidence-Based Practice Center examined the evidence regarding four Key Questions: What evidence describes the maternal risks of elective induction versus expectant management? What evidence describes the fetal/neonatal risks of elective induction versus expectant management? What is the evidence that certain physical conditions/patient characteristics are predictive of a successful induction of labor? How is a failed induction defined?We performed a systematic review to answer the Key Questions. We searched MEDLINE(1966-2007) and bibliographies of prior systematic reviews and the included studies for English language studies of maternal and fetal outcomes after elective induction of labor. We evaluated the quality of included studies. When possible, we synthesized study data using random effects models. We also evaluated the potential clinical outcomes and cost-effectiveness of elective induction of labor versus expectant management of pregnancy labor at 41, 40, and 39 weeks' gestation using decision-analytic models.Our searches identified 3,722 potentially relevant articles, of which 76 articles met inclusion criteria. Nine RCTs compared expectant management with elective induction of labor. We found that overall, expectant management of pregnancy was associated with an approximately 22 percent higher odds of cesarean delivery than elective induction of labor (OR 1.22, 95 percent CI 1.07-1.39; absolute risk difference 1.9, 95 percent CI: 0.2-3.7 percent). The majority of these studies were in women at or beyond 41 weeks of gestation (OR 1.21, 95 percent CI 1.01-1.46). In studies of women at or beyond 41 weeks of gestation, the evidence was rated as moderate because of the size and number of studies and consistency of the findings. Among women less than 41 weeks of gestation, there were three trials which reported no difference in risk of cesarean delivery among women who were induced as compared to expectant management (OR 1.73; 95 percent CI: 0.67-4.5, P=0.26), but all of these trials were small, non-U.S., older, and of poor quality. When we stratified the analysis by country, we found that the odds of cesarean delivery were higher in women who were expectantly managed compared to elective induction of labor in studies conducted outside the U.S. (OR 1.22; 95 percent CI 1.05-1.40) but were not statistically different in studies conducted in the U.S. (OR 1.28; 95 percent CI 0.65-2.49). Women who were expectantly managed were also more likely to have meconium-stained amniotic fluid than those who were electively induced (OR 2.04; 95 percent CI: 1.34-3.09). Observational studies reported a consistently lower risk of cesarean delivery among women who underwent spontaneous labor (6 percent) compared with women who had an elective induction of labor (8 percent) with a statistically significant decrease when combined (OR 0.63; 95 percent CI: 0.49-0.79), but again utilized the wrong control group and did not appropriately adjust for gestational age. We found moderate to high quality evidence that increased parity, a more favorable cervical status as assessed by a higher Bishop score, and decreased gestational age were associated with successful labor induction (58 percent of the included studies defined success as achieving a vaginal delivery anytime after the onset of the induction of labor; in these instances, induction was considered a failure when it led to a cesarean delivery). In the decision analytic model, we utilized a baseline assumption of no difference in cesarean delivery between the two arms as there was no statistically significant difference in the U.S. studies or in women prior to 41 0/7 weeks of gestation. In each of the models, women who were electively induced had better overall outcomes among both mothers and neonates as estimated by total quality-adjusted life years (QALYs) as well as by reduction in specific perinatal outcomes such as shoulder dystocia, meconium aspiration syndrome, and preeclampsia. Additionally, induction of labor was cost-effective at $10,789 per QALY with elective induction of labor at 41 weeks of gestation, $9,932 per QALY at 40 weeks of gestation, and $20,222 per QALY at 39 weeks of gestation utilizing a cost-effectiveness threshold of $50,000 per QALY. At 41 weeks of gestation, these results were generally robust to variations in the assumed ranges in univariate and multi-way sensitivity analyses. However, the findings of cost-effectiveness at 40 and 39 weeks of gestation were not robust to the ranges of the assumptions. In addition, the strength of evidence for some model inputs was low, therefore our analyses are exploratory rather than definitive.Randomized controlled trials suggest that elective induction of labor at 41 weeks of gestation and beyond may be associated with a decrease in both the risk of cesarean delivery and of meconium-stained amniotic fluid. The evidence regarding elective induction of labor prior to 41 weeks of gestation is insufficient to draw any conclusion. There is a paucity of information from prospective RCTs examining other maternal or neonatal outcomes in the setting of elective induction of labor. Observational studies found higher rates of cesarean delivery with elective induction of labor, but compared women undergoing induction of labor to women in spontaneous labor and were subject to potential confounding bias, particularly from gestational age. Such studies do not inform the question of how elective induction of labor affects maternal or neonatal outcomes. Elective induction of labor at 41 weeks of gestation and potentially earlier also appears to be a cost-effective intervention, but because of the need for further data to populate these models our analyses are not definitive. Despite the evidence from the prospective, RCTs reported above, there are concerns about the translation of such findings into actual practice, thus, there is a great need for studying the translation of such research into settings where the majority of obstetric care is provided.
View details for PubMedID 19408970
Saw palmetto is commonly used by men for lower-urinary tract symptoms. Despite its widespread use, very little is known about the potential toxicity of this dietary supplement.The Saw palmetto for Treatment of Enlarged Prostates (STEP) study was a randomized clinical trial performed among 225 men with moderate-to-severe symptoms of benign prostatic hyperplasia, comparing a standardized extract of the saw palmetto berry (160 mg twice daily) with a placebo over a 1-year period. As part of this study, detailed data were collected on serious and non-serious adverse events, sexual functioning, and laboratory tests of blood and urine. Between-group differences were assessed with mixed-effects regression models.There were no significant differences observed between the saw palmetto and placebo-allocated participants in the risk of suffering at least one serious adverse event (5.4% vs. 9.7%, respectively; p=0.31) or non-serious symptomatic adverse event (34.8% vs. 30.1%, p=0.48). There were few significant between-group differences in sexual functioning or for most laboratory analyses, with only small differences observed in changes over time in total bilirubin (p=0.001), potassium (p=0.03), and the incidence of glycosuria (0% in the saw palmetto group vs. 3.7% in the placebo group, p=0.05).Despite careful assessment, no evidence for serious toxicity of saw palmetto was observed in this clinical trial. Given the sample size and length of this study, however, these data do not rule out potential rare adverse effects associated with the use of saw palmetto.
View details for DOI 10.1016/j.ctim.2007.10.005
View details for Web of Science ID 000257378700005
View details for PubMedID 18534327
Despite ethical imperatives, informing research participants about the results of the studies in which they take part is not often performed. This is due, in part, to the costs and burdens of communicating with each participant after publication of the results.Following the closeout and publication of a randomized clinical trial of saw palmetto for treatment of symptoms of benign prostatic hyperplasia, patients were invited back to the research center to participate in a group presentation of the study results.Approximately 10% of participants attended one of two presentation sessions. Reaction to the experience of the group presentation was very positive among the attendees.A group presentation to research participants is an efficient method of communicating study results to those who desire to be informed and was highly valued by those who attended. Prospectively planning for such presentations and greater scheduling flexibility may result in higher attendance rates.Clinicaltrials.gov #NCT00037154.
View details for DOI 10.1186/1745-6215-9-16
View details for Web of Science ID 000255477300001
View details for PubMedID 18355417
Insomnia affects approximately one-third of the adult population and contributes to increased rates of absenteeism, health care use, and social disability. Extracts of the roots of valerian (Valeriana officinalis) are widely used for inducing sleep and improving sleep quality. A systematic review of randomized, placebo-controlled trials of valerian for improving sleep quality is presented. An extensive literature search identified 16 eligible studies examining a total of 1093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% confidence interval, 1.2-2.9), but there was evidence of publication bias in this summary measure. The available evidence suggests that valerian might improve sleep quality without producing side effects. Future studies should assess a range of doses of standardized preparations of valerian and include standard measures of sleep quality and safety.
View details for DOI 10.1016/j.amjmed.2006.02.026
View details for Web of Science ID 000242488800003
View details for PubMedID 17145239
There is no standard method of identifying adverse events in clinical trials.To determine whether 3 different methods of questioning patients about adverse events in a clinical trial affect the frequency of reported events.Randomized, single-blind, controlled trial.A Veterans Administration medical center, San Francisco, California.Men 50 years of age or older who had benign prostatic hyperplasia.Frequency of self-reported medical problems.The authors randomly assigned 214 men who were undergoing a 1-month, single-blind, placebo run-in period during an existing clinical trial to 3 groups to test different self-administered methods of assessing medical problems at the end of the run-in period. The first group was asked an open-ended question; the second group was asked an open-ended, defined question; and the third group was given a checklist of 53 common side effects.All 214 patients completed the study. Patients assigned to the checklist group reported a total of 238 adverse events; in comparison, patients who were asked an open-ended question or an open-ended, defined question reported 11 and 14 adverse events, respectively (P < 0.001). The percentage of patients reporting any adverse event was also much higher in the group assigned to the checklist (77%) than in the first group (14%) or second group (13%) (P < 0.001).The study included only relatively healthy, well-educated, middle-aged men and assessed only self-reported medical problems after the participants had taken placebo for 1 month. All personnel overseeing the study were aware of the group assignments.Different methods of collecting patient data regarding adverse events lead to large differences in the reported rates of adverse events in clinical trials, potentially reducing the validity of comparisons between the side effect profiles of drugs and other interventions.
View details for Web of Science ID 000235543100004
View details for PubMedID 16490911
Ginkgo biloba (ginkgo) is a herbal remedy used by over 2% of the adult population in the United States. Several review articles have suggested that ginkgo may increase the risk of bleeding.To report a case of bleeding associated with using ginkgo, to systematically review the literature for similar case reports, and to evaluate whether using ginkgo is causally related to bleeding.We searched MEDLINE, EMBASE, IBIDS, and the Cochrane Collaboration Database from 1966 to October 2004 with no language restrictions.Published case reports of bleeding events in persons using ginkgo were selected. Two reviewers independently abstracted a standard set of information to assess whether ginkgo caused the bleeding event.Fifteen published case reports described a temporal association between using ginkgo and a bleeding event. Most cases involved serious medical conditions, including 8 episodes of intracranial bleeding. However, 13 of the case reports identified other risk factors for bleeding. Only 6 reports clearly described that ginkgo was stopped and that bleeding did not recur. Bleeding times, measured in 3 reports, were elevated when patients were taking ginkgo.A structured assessment of published case reports suggests a possible causal association between using ginkgo and bleeding events. Given the widespread use of this herb and the serious nature of the reported events, further studies are needed. Patients using ginkgo, particularly those with known bleeding risks, should be counseled about a possible increase in bleeding risk.
View details for PubMedID 16050865
To examine the safety and efficacy of citrus aurantium, an herb now commonly used as a substitute for ephedra in dietary supplements marketed to promote weight loss, we conducted a systematic review. An extensive search of MEDLINE, EMBASE, BIOSIS, and the Cochrane Collaboration Database identified only 1 eligible randomized placebo controlled trial, which followed 20 patients for 6 weeks, demonstrated no statistically significant benefit for weight loss, and provided limited information about the safety of the herb.
View details for DOI 10.1016/j.amjcard.2004.07.137
View details for Web of Science ID 000225207700036
View details for PubMedID 15541270