Search

BackgroundThe risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status.MethodsWe followed a cohort of 10 083 human immunodeficiency virus (HIV)-infected persons in Kaiser Permanente Northern California (n = 2099) from 2004 to 2010 and the Veterans Aging Cohort Study (n = 7984) from 2004 to 2012. Within the first year of ART, we determined occurrence of (1) liver aminotransferases >200 U/L and (2) severe ALI (coagulopathy with hyperbilirubinemia). We used Cox regression to determine hazard ratios (HRs) with 95% confidence intervals (CIs) of endpoints among initiators of nucleos(t)ide analogue combinations, antiretroviral classes, and ART regimens, all stratified by viral hepatitis status.ResultsLiver aminotransferases >200 U/L developed in 206 (2%) persons and occurred more frequently among HIV/viral hepatitis-coinfected than HIV-monoinfected persons (116.1 vs 20.7 events/1000 person-years; P < .001). No evidence of differential risk was found between initiators of abacavir/lamivudine versus tenofovir/emtricitabine among coinfected (HR, 0.68; 95% CI, .29-1.57) or HIV-monoinfected (HR, 1.19; 95% CI, .47-2.97) groups. Coinfected patients had a higher risk of aminotransferases >200 U/L after initiation with a protease inhibitor than nonnucleoside reverse-transcriptase inhibitor (HR, 2.01; 95% CI, 1.36-2.96). Severe ALI (30 events; 0.3%) occurred more frequently in coinfected persons (15.9 vs 3.1 events/1000 person-years; P < .001) but was too uncommon to evaluate in adjusted analyses.ConclusionsWithin the year after ART initiation, aminotransferase elevations were infrequently observed and rarely led to severe ALI. Protease inhibitor use was associated with a higher risk of aminotransferase elevations among viral hepatitis-coinfected patients.

BackgroundPolybrominated diphenyl ethers (PBDE), which are used as flame retardants, have been found to be higher in residents of California than of other parts of the United States.ObjectivesWe aimed to investigate the role of immigration to California on PBDE levels in Latino children.MethodsWe compared serum PBDE concentrations in a population of first-generation Mexican-American 7-year-old children (n = 264), who were born and raised in California [Center for Health Analysis of Mothers and Children of Salinas (CHAMACOS) study], with 5-year-old Mexican children (n = 283), who were raised in the states in Mexico where most CHAMACOS mothers had originated (Proyecto Mariposa).ResultsOn average, PBDE serum concentrations in the California Mexican-American children were three times higher than their mothers' levels during pregnancy and seven times higher than concentrations in the children living in Mexico. The PBDE serum concentrations were higher in the Mexican-American children regardless of length of time their mother had resided in California or the duration of the child's breast-feeding. These data suggest that PBDE serum concentrations in these children resulted primarily from postnatal exposure.ConclusionsLatino children living in California have much higher PBDE serum levels than their Mexican counterparts. Given the growing evidence documenting potential health effects of PBDE exposure, the levels in young children noted in this study potentially present a major public health challenge, especially in California. In addition, as PBDEs are being phased out and replaced by other flame retardants, the health consequences of these chemical replacements should be investigated and weighed against their purported fire safety benefits.

BackgroundExposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children.ObjectivesWe investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California.MethodsChildren were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners' Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale.ResultsPrenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: β = 0.7 points; 95% confidence interval (CI), 0.2-1.2; ADHD: β = 1.3; 95% CI, 0.4-2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7-15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1-10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention.ConclusionsIn utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys.

BackgroundExposure to polybrominated diphenyl ether (PBDE) flame retardants is widespread, with 97% of Americans having detectable levels. Although PBDEs have been associated with reproductive and hormonal effects in animals, no human studies have examined their association with fertility.ObjectivesThis study was designed to determine whether maternal concentrations of PBDEs in serum collected during pregnancy are associated with time to pregnancy and menstrual cycle characteristics.MethodsPregnant women (n = 223) living in a low-income, predominantly Mexican-immigrant community in California were interviewed to determine how many months they took to become pregnant. Blood samples were collected and analyzed for PBDEs. PBDE concentrations were lipid adjusted and log10 transformed. Analyses were limited to PBDE congeners detected in > 75% of the population (BDEs 47, 99, 100, 153). Cox proportional hazards models modified for discrete time were used to obtain fecundability odds ratios (fORs) for the association of PBDEs and time to pregnancy.ResultsWe detected all four congeners in > 97% of women. Increasing levels of BDEs 47, 99, 100, 153 and the sum of these four congeners were all associated with longer time to pregnancy. We observed significantly reduced fORs for BDE-100 [adjusted fOR = 0.6; 95% confidence interval (CI), 0.4-0.9], BDE-153 (adjusted fOR = 0.5; 95% CI, 0.3-0.8), and the sum of the four congeners (adjusted fOR = 0.7; 95% CI, 0.5-1.0). PBDEs were not associated with menstrual cycle characteristics.ConclusionsWe found significant decreases in fecundability associated with PBDE exposure in women. Future studies are needed to replicate and confirm this finding.

We examined pregnancy outcomes in New York City (NYC) and upstate New York after the September 11, 2001 World Trade Center disaster.Using birth certificate data for NY residents (n = 1,660,401 births), we estimated risk of low birthweight (LBW:

OBJECTIVE. We investigated the relationship between prenatal exposure to dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) and neurodevelopment of Mexican farm-workers&apos; children in California. METHODS. Participants from the Center for the Health Assessment of Mothers and Children of Salinas study, a birth cohort study, included 360 singletons with maternal serum measures of p,p&apos;-DDT, o,p&apos;-DDT, and p,p&apos;-DDE. Psychomotor development and mental development were assessed with the Bayley Scales of Infant Development at 6, 12, and 24 months. RESULTS. We found a ~2-point decrease in Psychomotor Developmental Index scores with each 10-fold increase in p,p&apos;-DDT levels at 6 and 12 months (but not 24 months) and p,p&apos;-DDE levels at 6 months only. We found no association with mental development at 6 months but a 2- to 3-point decrease in Mental Developmental Index scores for p,p&apos;-DDT and o,p&apos;-DDT at 12 and 24 months, corresponding to 7- to 10-point decreases across the exposure range. Even when mothers had substantial exposure, breastfeeding was usually associated positively with Bayley scale scores. CONCLUSIONS. Prenatal exposure to DDT, and to a lesser extent DDE, was associated with neurodevelopmental delays during early childhood, although breastfeeding was found to be beneficial even among women with high levels of exposure. Countries considering the use of DDT should weigh its benefit in eradicating malaria against the negative associations found in this first report on DDT and human neurodevelopment. www.pediatrics.org/cgi/doi/10.1542/ peds.2005-3117 doi:10.1542/peds.2005-3117 Key Words dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, organochlorine, pesticides, neurodevelopment, Bayley Scales of Infant Development Abbreviations CHAMACOS--Center for the Health Assessment of Mothers and Children of Salinas DAP--dialkyl phosphates HCB--hexachlorobenzene HOME--Home Observation for Measurement of the Environment LOD--limit of detection MDI--Mental Developmental Index DDT--dichlorodiphenyltrichloroethane PDI--Psychomotor Developmental Index DDE--dichlorodiphenyldichloroethylene PCB--polychlorinated biphenyl [beta]-HCCH-[beta]-hexachlorocyclohexane PPVT--Peabody Picture Vocabulary Test CI--confidence interval Accepted for publication Feb 15, 2006, IN 2001, >90 countries signed the Stockholm Convention on Persistent Organic Pollutants, committing to eliminate the use of 12 persistent organic pollutants of greatest concern to the ecology and health [...]

There is no evidence that babies born on the weekend in California hospitals are more likely to die than those born on weekday. This was the conclusion of a study of 1,615,041 births in California between 1995 and 1997. Other studies have shown that adults with a serious illness are more likely to die if admitted to a hospital on a weekend.

Background & Aims Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy’s Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample. Methods We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania. Results Hy’s Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval [CI], 0.76–0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71–0.99) and a specificity value of 0.76 (95% CI, 0.75–0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52–1.00) in the validation analysis. Conclusions Hy’s Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and total bilirubin level that identifies patients at increased risk for ALF with high sensitivity. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "PBDE concentrations in women's serum and fecundability," by Kim G. Harley.