“My BMI is too high for Plan B.” A changing population of women seeking ulipristal acetate emergency contraception online

ABSTRACT

Emergency contraceptive (EC) pills may be less effective for women with higher body mass index (BMI), but little is known about public response to the fact that EC may lose efficacy as weight increases. In November 2013, European authorities changed the label for a levonorgestrel EC product to warn of a reduction in effectiveness for women with higher BMI, garnering significant media coverage in the United States. Ulipristal acetate (UPA) EC may be more effective than levonorgestrel for women with BMI levels designated as obese. Among 8,019 women who received UPA from the online pharmacy KwikMed from 2011 to 2015 and self-reported their height, weight and reasons for seeking UPA online, we analyzed changes in the proportion of women in different BMI categories before and after the label change. For the 25 month-period after the label change, the proportion of women in the obese category rose by 26.7 percentage points relative to the 35 months before (B = 0.2665, p < .01). Mean BMI (25.5 versus 29.4, p < .001) and average weight (148.6 pounds versus 175.5 pounds, p < .001) of users were higher after the label change. Some women appear to have acted on the information that EC efficacy may be associated with body weight.     

Rare,Protein-Altering Variants in AS3MT and Arsenic Metabolism Efficiency: A Multi-Population Association Study

Background: Common genetic variation in the arsenic methyltransferase (AS3MT) gene region is known to be associated with arsenic metabolism efficiency (AME), measured as the percentage of dimethylarsinic acid (DMA%) in the urine. Rare, protein-altering variants in AS3MT could have even larger effects on AME, but their contribution to AME has not been investigated.Objectives: We estimated the impact of rare, protein-coding variation in AS3MT on AME using a multi-population approach to facilitate the discovery of population-specific and shared causal rare variants.Methods: We generated targeted DNA sequencing data for the coding regions of AS3MT for three arsenic-exposed cohorts with existing data on arsenic species measured in urine: Health Effects of Arsenic Longitudinal Study (HEALS, n=2,434), Strong Heart Study (SHS, n=868), and New Hampshire Skin Cancer Study (NHSCS, n=666). We assessed the collective effects of rare (allele frequency <1%), protein-altering AS3MT variants on DMA%, using multiple approaches, including a test of the association between rare allele carrier status (yes/no) and DMA% using linear regression (adjusted for common variants in 10q24.32 region, age, sex, and population structure).Results: We identified 23 carriers of rare-protein-altering AS3MT variant across all cohorts (13 in HEALS and 5 in both SHS and NHSCS), including 6 carriers of predicted loss-of-function variants. DMA% was 6–10% lower in carriers compared with noncarriers in HEALS [β=−9.4 (95% CI: −13.9, −4.8)], SHS [β=−6.9 (95% CI: −13.6, −0.2)], and NHSCS [β=−8.7 (95% CI: −15.6, −2.2)]. In meta-analyses across cohorts, DMA% was 8.7% lower in carriers [β=−8.7 (95% CI: −11.9, −5.4)].Discussion: Rare, protein-altering variants in AS3MT were associated with lower mean DMA%, an indicator of reduced AME. Although a small percentage of the population (0.5–0.7%) carry these variants, they are associated with a 6–10% decrease in DMA% that is consistent across multiple ancestral and environmental backgrounds. https://doi.org/10.1289/EHP8152     

A comparative analysis of overall survival between high-dose-rate and low-dose-rate brachytherapy boosts for unfavorable-risk prostate cancer

Purpose

External beam radiation therapy (EBRT) with low-dose-rate (LDR) brachytherapy boost has been associated with improved biochemical progression–free survival and overall survival (OS) compared with dose-escalated EBRT (DE-EBRT) alone for unfavorable-risk prostate cancer. However, it is not known whether high-dose-rate (HDR) boost provides a similar benefit. We compare HDR boost against LDR boost and DE-EBRT with respect to OS.

Infectious Diarrhea: An Overview

Rumination syndrome is the non-purposeful regurgitation of recently ingested food from the stomach to the mouth, where it is either expelled or reswallowed. Adolescent rumination syndrome (ARS) is a rare condition of which many physicians are unaware. Patients often are misdiagnosed or undergo costly testing, and as a result, diagnosis and treatment are often delayed. While ARS is not life-threatening, it does have medical and emotional effects on the patient and the patient’s family. Diagnosis of ARS is based upon the Rome III diagnostic criteria. Antroduodenal manometry, while not required for a diagnosis, can be helpful to confirm the diagnosis. The pathogenesis of this disorder is complex and not well understood. However, because of its behavioral component, treatment of ARS requires a multidisciplinary approach that includes both medical management of symptoms and implementation of strategies that address behavioral, psychological, and general quality-of-life components of the disorder.     

Lev's Syndrome: A rare case of progressive cardiac conduction disorder presenting to the emergency department

Lev's Syndrome is a rare, progressive cardiac conduction defect (PCCD) due to myocardial fibrosis first described by Maurice Lev in 1964. This condition, proposed to start in the fourth decade of life, involves a sclerotic fibro-fatty degeneration of the Bundle of His and Purkinje fibers, which Lev proposed caused increasing AV delay with age. With the prevalence of electrocardiogram (ECG) use in the emergency department (ED) for cardiac- and non-cardiac complaints, dysrhythmias can be incidentally found and confuse diagnosis and disposition. We highlight the case of an 84-year-old male who presented to the ED for acute onset of diffuse facial paresthesias with elevated blood pressure at home and was found to be significantly bradycardic on initial evaluation. On serial ECGs, the conduction rhythm changed from an initial new first-degree atrioventricular (AV) block with left bundle branch block (LBBB), to a later first-degree AV block without LBBB. Cardiology was consulted. Serial ECGs demonstrated an evolving conduction block arrhythmia consistent with Lev's Syndrome. Here we describe a case of symptomatic bradycardia found to be consistent with Lev's Syndrome.     

A Murine Monoclonal Antibody with Broad Specificity for Occupationally Relevant Diisocyanates

Diisocyanates (dNCOs) used in industrial applications are well known low molecular weight allergens. Occupational exposure is associated with adverse health outcomes including allergic sensitization and occupational asthma. In this study, we report the production and initial characterization of a dNCO-hapten specific murine IgM monoclonal antibody (mAb). Female BALB/c mice were immunized intraperitoneally with 25 μg of 4,4′-methylene diphenyl diisocyanate (MDI)-keyhole limpet hemocyanin. Following six biweekly booster immunizations, splenocytes were recovered and fused to Sp2/0-Ag14 murine myeloma cell line for hybridoma production. Hybridomas were then screened in a solid-phase indirect enzyme-linked immunosorbent assay (ELISA) against 40:1 4,4′-MDI– human serum albumin (HSA). mAb reactivity to dNCO-HSA conjugates and dNCO-HSA spiked human serum were characterized using a sandwich ELISA. One hybridoma produced a multimeric IgM mAb (15D4) that reacted with 4,4′-MDI-HSA. Sandwich ELISA analysis demonstrated comparable reactivity with other occupationally relevant dNCO-HSA adducts, including 2,4-toluene diisocyanate (TDI)-HSA, 2,6-TDI-HSA, and 1,6-hexamethylene diisocyanate (HDI)-HSA, but not other electrophilic chemical HSA conjugates. The limit of quantification (LOQ) of 4,4′-MDI-HSA, 2,4-TDI-HSA, 2,6-TDI-HSA, and 1,6-HDI-HSA sandwich ELISAs were 567.2, 172.7, 184.2, and 403.5 ng/mL (8.67, 2.60, 2.77, and 6.07 pmol/mL), respectively. In contrast, experiments using dNCO-supplemented human sera showed an increase in the detectable limit of the assay. A mAb has been produced that has potential utility for detecting mixed diisocyanate exposures in occupational environments. The mAb may have additional utility in the standardization of specific IgE detection immunoassays as well as chromatographic-mass spectrometric methods to enrich dNCO adducted HSA in the plasma of occupationally exposed workers.