The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ...ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel.
The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2).
Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis.
Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.
A multistate analysis found Maine had the second highest average annual increase in maternal opioid use disorder (OUD) at delivery hospitalization during 1999–2012. The objective of our analysis was ...to estimate the prevalence, maternal characteristics, and geographic distribution of OUD at delivery hospitalization in Maine using recent state-level data.
Serially collected cross-sectional population-based data.
We used diagnosis and procedure codes to identify deliveries among hospital discharges in Maine, 2009–2018 (n = 120,764), and to categorize deliveries according to the prevalence of maternal OUD and selected conditions. We assessed linear trends in OUD at delivery and calculated prevalence ratios (PR) for co-occurring maternal conditions.
The prevalence of maternal OUD per 1000 deliveries in Maine increased from 22.7 in 2009 to 34.9 in 2018 (linear trend P value < 0.01), with a mean annual increase of 1.6 (95% confidence interval CI: 0.9 to 2.4). The following conditions were more prevalent among women with OUD at delivery: hepatitis C, PR = 45.8 (95% CI: 38.8 to 54.2); other drug abuse or dependence, PR = 16.8 (13.4 to 20.9); alcohol abuse and dependence, PR = 8.5 (5.8 to 12.5); nicotine use, PR = 6.0 (5.9 to 6.2); cannabis use, PR = 5.2 (4.6 to 5.9); anxiety, PR = 2.7 (2.5 to 3.2); and depression, PR = 2.7 (2.4 to 3.1). Women with OUD at delivery were also more likely to reside in small rural areas (27.3% vs 22.5%) and deliver in a hospital with a level III nursery (50.6% vs 34.9%).
Maternal OUD now accounts for 1 in 29 deliveries in Maine and commonly occurs with other medical conditions. Prevention and treatment of OUD among reproductive age women in Maine remains needed.
•Maternal opioid use disorder increased among deliveries in Maine during 2009–2018.•Maternal opioid use disorder now accounts for 1 in 29 hospital deliveries.•It co-occurs with other maternal health conditions, such as hepatitis C.•Prevention and treatment of opioid use disorder among women in Maine remains needed.
Per- and polyfluoroalkyl substances (PFAS) and phthalates are 2 families of environmental endocrine disruptors that may be associated with areal lower bone mineral density (aBMD).
To examine ...associations between serum PFAS and urinary phthalate biomarker concentrations and their mixtures with aBMD Z-scores in adolescents.
We examined serial cross-sectional data from male (n = 453) and female (n = 395) 12- to 19-year-old participants in the 2011 through 2016 National Health and Nutrition Examination Survey with measures of serum PFAS, urinary phthalate metabolites, and dual-energy X-ray absorptiometry aBMD Z-scores (total body less head). In sex-specific models, we used linear regression to examine associations of individual PFAS and phthalate biomarkers with aBMD Z-scores, and Bayesian kernel machine regression to examine the association of the overall PFAS/phthalate biomarker mixture with aBMD Z-scores. We replicated the analysis, stratifying by race/ethnicity.
Participants were (mean ± SD) 15 ± 2.1 years of age. In males, each doubling of serum perfluorooctanoate (PFOA), perfluorooctane sulfonate, urinary mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate, and the overall PFAS/phthalate mixture was associated with a lower aBMD Z-score (eg, for PFOA: -0.24; 95% CI, -0.41 to -0.06). Serum PFOA and urinary MiBP were associated with higher aBMD Z-scores in females (eg, for PFOA: 0.09; 95% CI, -0.07 to 0.25). Findings did not differ by race/ethnicity.
Certain PFAS and phthalates may be associated with reduced bone mineral density in adolescent males. Bone mineral density tracks across the life course, so if replicated in longitudinal cohorts, this finding may have implications for lifelong skeletal health.
The aim of this study is to examine age at menarche across sexual orientation groups.
Data were obtained from 131,090 female participants, born 1947–2001, in 3 longitudinal studies—the Growing Up ...Today Study and Nurses’ Health Study 2 and 3. We estimated the association between sexual orientation and age at menarche using regression models adjusted for age, race/ethnicity, birthweight, height, and body mass index.
Compared to heterosexual participants, sexual minorities were younger at menarche. Sexual minorities were more likely to have early menarche (≤11 years) and less likely to have late menarche (≥14 years) compared to heterosexual girls. As an example of this pattern, Nurses’ Health Study 3 bisexual participants were >30% more likely than heterosexuals to have early versus average menarche (odds ratio 1.37, 95% confidence interval 1.09–1.72).
Sexual minority girls have a younger age at menarche than heterosexual girls and may benefit from screening for adverse outcomes associated with early menarche.
Phthalates may adversely influence body composition by lowering anabolic hormones and activating peroxisome-proliferator activated receptor gamma. However, data are limited in adolescence when body ...mass distributions rapidly change and bone accrual peaks. Also, potential health effects of certain phthalate/replacements e.g., di-2-ethylhexyl terephthalate (DEHTP) have not been well studied.
Among 579 children in the Project Viva cohort, we used linear regression to evaluate associations of urinary concentrations of 19 phthalate/replacement metabolites from mid-childhood (median: 7.6 years; 2007–2010) with annualized change in areal bone mineral density (aBMD) and lean, total fat, and truncal fat mass as measured by dual-energy X-ray absorptiometry between mid-childhood and early adolescence (median: 12.8 years). We used quantile g-computation to assess associations of the overall chemical mixture with body composition. We adjusted for sociodemographics and tested for sex-specific associations.
Urinary concentrations were highest for mono-2-ethyl-5-carboxypentyl phthalate median (IQR): 46.7 (69.1) ng/mL. We detected metabolites of most replacement phthalates in a relatively small number of participants e.g., 28% for mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP; metabolite of DEHTP). Detectable (vs. non-detectable) MEHHTP was associated with less bone and greater fat accrual in males and greater bone and lean mass accrual in females e.g., change in aBMD Z-score/year (95% CI): −0.049 (−0.085, −0.013) in males versus 0.042 (0.007, 0.076) in females; pinteraction<0.01. Children with higher concentrations of mono-oxo-isononyl phthalate and mono-3-carboxypropyl phthalate (MCPP) had greater bone accrual. Males with higher concentrations of MCPP and mono-carboxynonyl phthalate had greater accrual of lean mass. Other phthalate/replacement biomarkers, and their mixtures, were not associated with longitudinal changes in body composition.
Concentrations of select phthalate/replacement metabolites in mid-childhood were associated with changes in body composition through early adolescence. As use of phthalate replacements such as DEHTP may be increasing, further investigation can help better understand the potential effects of early-life exposures.
•We studied phthalate biomarkers in childhood and body composition through adolescence.•Children with higher MONP and MCPP concentrations had greater bone accrual.•MCPP, MCNP, and MEHTTP had sex-specific associations with body composition.•The chemical biomarker mixture was not associated with change in body composition.•We advance the literature by incorporating DXA outcomes and chemical replacements.
Tetrachloroethylene (PCE) is a common contaminant in both occupational and community settings. High exposure levels in the workplace have been shown to have adverse impacts on reproduction and ...development but few epidemiological studies have examined these effects at the lower levels commonly seen in community settings. We were presented with a unique opportunity to examine the reproductive and developmental effects of prenatal exposure to PCE-contaminated drinking water resulting from the installation of vinyl-lined water pipes in Massachusetts and Rhode Island from the late 1960s through 1980. This review describes the methods and findings of two community-based epidemiological studies, places their results in the context of the existing literature, and describes the strengths and challenges of conducting epidemiological research on a historical pollution episode. Our studies found that prenatal exposure to PCE-contaminated drinking water is associated with delayed time-to-pregnancy, and increased risks of placental abruption, stillbirths stemming from placental dysfunction, and certain birth defects. No associations were observed with pregnancy loss, birth weight, and gestational duration. Important strengths of this research included the availability of historical data on the affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little opportunity for recall bias and confounding. Challenges arose mainly from the retrospective nature of the exposure assessments. This research highlights the importance of considering pregnant women and their developing fetuses when monitoring, regulating, and remediating drinking water contaminants.
It is unclear whether differences in health outcomes by racial and ethnic groups among World Trade Center (WTC) rescue and recovery workers reflect those of the population of New York State (NYS) or ...show distinct patterns. We assessed cancer incidence in WTC workers by self-reported race and ethnicity, and compared it to population figures for NYS.
A total of 61,031 WTC workers enrolled between September 11, 2001 and January 10, 2012 were followed to December 31, 2015. To evaluate the association between race/ethnicity and cancer risk, Poisson regression analysis was used to estimate hazard ratios (HR) adjusted for WTC exposure, age, calendar year, sex and, for lung cancer, cigarette smoking.
In comparison to Whites, Black workers had a higher incidence of prostate cancer (HR = 1.99, 95% CI = 1.69-2.34) and multiple myeloma (HR = 3.57, 95% CI = 1.97-6.45), and a lower incidence of thyroid (HR = 0.41, 95% CI = 0.22-0.78) and colorectal cancer (HR = 0.57; 95% CI = 0.33-0.98). Hispanic workers had a higher incidence of liver cancer (HR = 4.03, 95% CI = 2.23-7.28). Compared with NYS population, White workers had significantly higher incidence of prostate cancer (HR = 1.26, 95% CI = 1.18-1.35) and thyroid cancer (HR = 1.80, 95% CI = 1.55-2.08), while Black workers had significantly higher incidence of prostate cancer (HR = 1.22, 95% CI = 1.05-1.40).
Cancer incidence in WTC workers generally reflects data from the NYS population, but some differences were identified that merit further investigation.
Thrombotic thrombocytopenic purpura (TTP) is an uncommon syndrome characterized by reversible, systemic aggregation of platelets in the microcirculation and disseminated microvascular thrombosis. ...Surgery may precipitate TTP and has been associated with relapse in some patients. However, relapse of this life-threatening disorder is unpredictable. We report a patient with an antecedent history of TTP who experienced a relapse after elective cardiac surgery. In this case, decreased von Willebrand factor (vWF)-cleaving metalloproteinase activity and an inhibitor of this endogenous enzyme were demonstrated preoperatively. These findings suggest that decreased vWF-cleaving metalloproteinase activity and/or the presence of its inhibitor may predict an increased risk for surgical-associated relapse of TTP.
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