Preconception ovarian reserve and placenta-mediated pregnancy complications among infertile women.

RESEARCH QUESTION: Are preconception ovarian reserve markers, such as Anti-Mullerian hormone and antral follicle count, associated with preeclampsia and placenta mediated pregnancy complications among women with unexplained infertility who conceive with superovulation? DESIGN: This is a secondary analysis of women with unexplained infertility who had a singleton live birth after enrollment in the Analysis of Multiple Intrauterine Gestations after Ovarian Stimulation (AMIGOS) trial that randomized couples to superovulation with letrozole, clomiphene, or gonadotropins with insemination for up to 4 cycles. RESULTS: Compared to controls (N = 156), women who developed preeclampsia (N = 17) had lower Anti-Mullerian hormone levels (2.24 ± 1.20 vs. 2.89 ± 2.32, p = 0.07) and lower antral follicle count (18 ± 7.67 vs. 21 ± 11.43, p = 0.16); though these differences were not statistically significant. There was no relationship between Anti-Mullerian hormone (OR: 1.00, 95% CI: 0.76-1.25) or antral follicle count (OR: 0.98, 95% CI 0.93-1.04) with preeclampsia and between Anti-Mullerian hormone (OR: 1.00, 95% CI: 0.83-1.17) and antral follicle count (OR: 1.00, 95% CI: 0.97-1.04) with placenta medicated pregnancy complications after adjusting for age, BMI and race. CONCLUSIONS: Preconception ovarian reserve markers are not associated with preeclampsia and placenta mediated pregnancy complications among women with unexplained infertility who conceive with superovulation with insemination.

Essential statistical principles of clinical trials of pain treatments.

This article presents an overview of fundamental statistical principles of clinical trials of pain treatments. Statistical considerations relevant to phase 2 proof of concept and phase 3 confirmatory randomized trials investigating efficacy and safety are discussed, including (1) research design; (2) endpoints and analyses; (3) sample size determination and statistical power; (4) missing data and trial estimands; (5) data monitoring and interim analyses; and (6) interpretation of results. Although clinical trials of pharmacologic treatments are emphasized, the key issues raised by these trials are also directly applicable to clinical trials of other types of treatments, including biologics, devices, nonpharmacologic therapies (eg, physical therapy and cognitive-behavior therapy), and complementary and integrative health interventions.

Types and prevalence of HIV-related opportunistic infections/conditions among HIV-positive patients attending Kenyatta National Hospital in Nairobi, Kenya.

BACKGROUND: Although antiretroviral therapy (ART) has resulted in significant decrease in opportunistic infections (OIs), OIs continue to cause significant morbidity and mortality among HIV patients. OBJECTIVE: To determine the prevalence and types of HIV/AIDS-related OIs among patients attending Kenyatta National Hospital (KNH) in Nairobi, Kenya. METHODS: A cross-sectional study was conducted from May to August 2010 among patients ≥19 years. An interviewer-administered questionnaire was used to collect data on socio-demographic factors, HIV and OIs. CD4 data were extracted from clinical records. RESULTS: Most patients (72%) had lived with HIV for ≤ 5 years and 78.8% had an OI. The 3 most common OIs were TB (35%), Herpes Zoster (HZ; 15.4%) and oral thrush (OT; 8%). Years of HIV infection significantly predicted TB (p=0.01). Patients with CD4 ≤ 349 were almost twice as likely to have TB, than those with CD4 ≥500. Type of occupation predicted OT (p=0.04) with skilled workers less likely to have OT. Patients with primary/vocational/technical education were >3 times more likely to have HZ than those with tertiary education. CONCLUSION: Due to the complex management of HIV and its associated OIs, appropriate implementation of the recommended guidelines for care and prevention among patients at KNH is important.

Are there really only 2 kinds of people in the world? Evaluating the distribution of change from baseline in pain clinical trials.

It is often assumed that there are 2 types of pain patients: those who respond well to efficacious pain therapies and those who do not respond at all, with few people in the middle. This assumption is based on research that claims that changes in pain intensity have a bimodal distribution. The claim of bimodality has led to calls for a change in how pain clinical trials are designed and analyzed, eg, performing "responder" analyses instead of comparing group mean values to evaluate the treatment effect. We analyzed data from 4 clinical trials, 2 each of duloxetine and pregabalin, for chronic musculoskeletal and neuropathic pain conditions to critically examine the claim of bimodality of the distribution of change in pain intensity. We found that the improper construction of histograms, using unequal bin widths, was the principal flaw leading to the bimodality claim, along with the use of the oft-criticized baseline observation carried forward method for imputing missing data also serving as a contributing factor. Properly constructed histograms of absolute change in pain intensity using equal bin widths, combined with more principled methods for handling missing data, resulted in distributions that had a more unimodal appearance. Although our findings neither support nor refute the hypothesis that distinct populations of "responders" and "nonresponders" to pain interventions exist, the analyses presented in earlier work do not provide support for this hypothesis, nor for the recommendation that pain clinical trials prioritize "responder" analyses, a less efficient analysis strategy.

WITHDRAWN: Size Does Matter, But It Isn't Everything: The Challenge of Modest Treatment Effects in Chronic Pain Clinical Trials.

Available online This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort.

Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography-tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1-2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1-2% lower estrogen (E1, E2, E3) levels, but 1-2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4-18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1-2% higher (no difference in estrogens). Androgen concentrations were 18-30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.

Allostatic load, a measure of chronic physiological stress, is associated with pregnancy outcomes, but not fertility, among women with unexplained infertility.

STUDY QUESTION: Among infertile women undergoing ovarian stimulation, is allostatic load (AL), a measure of chronic physiological stress, associated with subsequent fertility and pregnancy outcomes? SUMMARY ANSWER: AL at baseline was not associated with conception, spontaneous abortion or live birth, however, it was significantly associated with increased odds of pre-eclampsia and preterm birth among women who had a live birth in the study. WHAT IS KNOWN ALREADY: Several studies have linked AL during pregnancy to adverse outcomes including preterm birth and pre-eclampsia, hypothesizing that it may contribute to well-documented disparities in pregnancy and birth outcomes. However, AL biomarkers change over the course of pregnancy, raising questions as to whether gestational AL assessment is a valid measure of cumulative physiologic stress starting long before pregnancy. To better understand how AL may impact reproductive outcomes, AL measurement in the non-pregnant state (i.e. prior to conception) is needed. STUDY DESIGN, SIZE, DURATION: A secondary data analysis based on data from 836 women who participated in Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), a multi-center, randomized clinical trial of ovarian stimulation conducted from 2011 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovulatory women with unexplained infertility (ages 18-40) were enrolled and at baseline, biological and anthropometric measures were collected. AL scores were calculated as a composite of the following baseline variables determined a priori: BMI, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, dehydroepiandrosterone sulfate, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein and HOMA score. Participants received ovarian stimulation for up to four cycles and if they conceived, were followed throughout pregnancy. We fit multi-variable logistic regression models examining AL (one-tailed and two-tailed) in relation to the following reproductive outcomes: conception, spontaneous abortion, live birth, pre-eclampsia, preterm birth and low birthweight. MAIN RESULTS AND THE ROLE OF CHANCE: Adjusting for covariates, a unit increase in two-tailed AL score was associated with 62% increased odds of pre-eclampsia (OR: 1.62, 95% CI: 1.14, 2.38) 44% increased odds of preterm birth (OR: 1.44, 95% CI: 1.02, 2.08), and 39% increased odds of low birthweight (OR: 1.39, 95% CI: 0.99, 1.97). The relationship between AL and preterm birth was mediated by pre-eclampsia (P = 0.0003). In one-tailed AL analyses, associations were similar, but slightly attenuated. AL was not associated with fertility outcomes (conception, spontaneous abortion, live birth). LIMITATIONS, REASONS FOR CAUTION: Results may not be generalizable to fertile women who conceive naturally or women with other types of infertility. Comparisons to previous, related work are difficult because variables included in AL composite measures vary across studies. AL may be indicative of overall poor health, rather than being specific to chronic physiological stress. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that chronic physiological stress may not impact success of ovarian stimulation, however, they confirm and extend previous work suggesting that AL is associated with adverse pregnancy outcomes. Physiological dysregulation due to chronic stress has been proposed as a possible mechanism underlying disparities in birth outcomes, which are currently poorly understood. Assessing biomarkers of physiological dysregulation pre-conception or in early pregnancy, may help to identify women at risk of adverse pregnancy outcomes, particularly pre-eclampsia. STUDY FUNDING/COMPETING INTEREST(S): Support for AMIGOS was provided by: U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10HD055925. Support for the current analysis was provided by T32ES007271, R25HD075737, P30ES001247 and P30ES005022. This research was made possible by funding by American Recovery and Reinvestment Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD, NIEHS or NIH. E.B., W.V., O.M., R.A., M.R., V.B., G.W.B., C.C., E.E., S.K., R.U., P.C, H.Z., N.S. and S.T. have nothing to disclose. R.L. reported serving as a consultant to Abbvie, Bayer, Kindex, Odega, Millendo and Fractyl and serving as a site investigator and receiving grants from Ferring. K.H. reported receiving grants from Roche Diagnostics and Ferring. R.R. reported a grant from AbbVie. M.D. reported being on the Board of Directors of and a stockholder in Advanced Reproductive Care. TRIAL REGISTRATION NUMBER: Clinical Trials.gov number: NCT01044862.

Prevalence of Single and Multiple Leading Causes of Death by Race/Ethnicity Among US Adults Aged 60 to 79 Years.

INTRODUCTION: Diabetes, cancer, cardiovascular disease (CVD) (coronary artery disease, heart attack, and angina pectoris), and chronic lung disease (emphysema, chronic bronchitis, and chronic obstructive pulmonary disease) are major causes of death in the United States. The objective of this study was to assess racial/ethnic differences in the prevalence of these conditions as cause of death among people aged 60 to 79 years with one or more of these conditions. METHODS: We used data on the prevalence of major chronic conditions from the National Health Interview Survey on 56,290 adults aged 60 to 79 years who reported having any of the chronic conditions assessed in the National Health Interview Survey for 2006 through 2014. We compared trends with age for 11 single and multiple conditions. Analyses employed multinomial logistic regression models. RESULTS: Hispanics and non-Hispanic blacks had the greatest prevalence of diabetes, and non-Hispanic whites had the greatest prevalence of cancer and chronic lung disease. The prevalence of multiple chronic diseases in an individual varied less by race/ethnicity. An exception was the prevalence of having both diabetes and CVD, which was higher among Hispanics and non-Hispanic blacks than non-Hispanic whites. Non-Hispanic blacks aged 65 years and 75 years had higher odds of having diabetes and cancer than non-Hispanic whites at the same ages. Hispanics had lower odds of having CVD with cancer or chronic lung disease than non-Hispanic whites. Women had a lower age-specific prevalence than men for most of the 11 single and multiple conditions. Most chronic diseases showed an inverse relationship with education and a higher prevalence in the South than in other regions. CONCLUSION: Strong racial/ethnic differences exist in the prevalence of single chronic conditions, but differences are lower for prevalence of multiple conditions. Comparing races/ethnicities, the same disease dyads and triads may occur more often in different orders.

First-Trimester Urinary Bisphenol A Concentration in Relation to Anogenital Distance, an Androgen-Sensitive Measure of Reproductive Development, in Infant Girls.

INTRODUCTION: Evidence from animal models suggests that prenatal exposure to bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is associated with adverse reproductive outcomes in females. Exposure during early gestation, a critical period for reproductive development, is of particular concern. Anogenital distance (AGD) is a sensitive biomarker of the fetal hormonal milieu and a measure of reproductive toxicity in animal models. In some studies, the daughters of BPA-exposed dams have shorter AGD than controls. Here, we investigate this relationship in humans. METHODS: BPA was assayed in first-trimester urine samples from 385 participants who delivered infant girls in a multicenter pregnancy cohort study. After birth, daughters underwent exams that included two measures of AGD (AGD-AC: distance from center of anus to clitoris; AGD-AF: distance from center of anus to fourchette). We fit linear regression models to examine the association between specific gravity-adjusted (SPG-adj) maternal BPA concentrations and infant AGD, adjusting for covariates. RESULTS: BPA was detectable in 94% of women. In covariate-adjusted models fit on 381 eligible subjects, the natural logarithm of SpG-adj maternal BPA concentration was inversely associated with infant AGD-AC [ß=−0.56, 95% confidence interval (CI): −0.97, −0.15]. We observed no association between maternal BPA and infant AGD-AF. CONCLUSION: BPA may have toxic effects on the female reproductive system in humans, as it does in animal models. Higher first-trimester BPA exposure was associated with significantly shorter AGD in daughters, suggesting that BPA may alter the hormonal environment of the female fetus. https://doi.org/10.1289/EHP875.

Effect of environmental exposure to hydrogen sulfide on central nervous system and respiratory function: a systematic review of human studies.

BACKGROUND: Assessment of the health effects of low-level exposure to hydrogen sulfide (H2S) on humans through experiments, industrial, and community studies has shown inconsistent results. OBJECTIVE: To critically appraise available studies investigating the effect of H2S on the central nervous system (CNS) and on respiratory function. METHODS: A search was conducted in 16 databases for articles published between January 1980 and July 2014. Two researchers independently evaluated potentially relevant papers based on a set of inclusion/exclusion criteria. RESULTS: Twenty-seven articles met the inclusion criteria: 6 experimental, 12 industry-based studies, and 10 community-based studies (one article included both experimental and industry-based studies). The results of the systematic review varied by study setting and quality. Several community-based studies reported associations between day-to-day variations in H2S levels and health outcomes among patients with chronic respiratory conditions. However, evidence from the largest and better-designed community-based studies did not support that chronic, ambient H2S exposure has health effects on the CNS or respiratory function. Results from industry-based studies varied, reflecting the diversity of settings and the broad range of H2S exposures. Most studies did not have individual measurements of H2S exposure. DISCUSSION: The results across studies were inconsistent, justifying the need for further research.

Risk-Adjusted In-Hospital Mortality Models for Congestive Heart Failure and Acute Myocardial Infarction: Value of Clinical Laboratory Data and Race/Ethnicity.

OBJECTIVE: To examine the impact of key laboratory and race/ethnicity data on the prediction of in-hospital mortality for congestive heart failure (CHF) and acute myocardial infarction (AMI). DATA SOURCES: Hawaii adult hospitalizations database between 2009 and 2011, linked to laboratory database. STUDY DESIGN: Cross-sectional design was employed to develop risk-adjusted in-hospital mortality models among patients with CHF (n = 5,718) and AMI (n = 5,703). DATA COLLECTION/EXTRACTION METHODS: Results of 25 selected laboratory tests were requested from hospitals and laboratories across the state and mapped according to Logical Observation Identifiers Names and Codes standards. The laboratory data were linked to administrative data for each discharge of interest from an all-payer database, and a Master Patient Identifier was used to link patient-level encounter data across hospitals statewide. PRINCIPAL FINDINGS: Adding a simple three-level summary measure based on the number of abnormal laboratory data observed to hospital administrative claims data significantly improved the model prediction for inpatient mortality compared with a baseline risk model using administrative data that adjusted only for age, gender, and risk of mortality (determined using 3M's All Patient Refined Diagnosis Related Groups classification). The addition of race/ethnicity also improved the model. CONCLUSIONS: The results of this study support the incorporation of a simple summary measure of laboratory data and race/ethnicity information to improve predictions of in-hospital mortality from CHF and AMI. Laboratory data provide objective evidence of a patient's condition and therefore are accurate determinants of a patient's risk of mortality. Adding race/ethnicity information helps further explain the differences in in-hospital mortality.

Prevalence of metabolic syndrome and associated cardiovascular risk factors in Guatemalan school children.

Guatemala is experiencing a nutritional and lifestyle transition. While chronic malnutrition is prevalent, overweight, obesity and chronic diseases have increased substantially in the country. This study was conducted to investigate the prevalence of metabolic syndrome and the associated cardiovascular risk factors in the pre-adolescent Guatemalan population. A cross-sectional study was conducted among 302 Guatemalan children (8-13 years old) attending public and private schools in the Municipality of Chimaltenango. Demographic data and anthropometric and blood pressure measurements were collected. A blood sample was taken after an 8 h overnight fast and analyzed for glucose, triglyceride and high-density lipoprotein cholesterol levels. The data were analyzed to identify factors associated with metabolic syndrome and with its components. The prevalence of metabolic syndrome in the study population was 2.0 %. However, approximately 54 % of the children had at least one component of metabolic syndrome, while none had four or five of the components. The three most prevalent risk factors were high triglycerides (43.4 %), low HDL cholesterol (17.2 %) and obesity (12.3 %). Boys were more likely to be obese than girls and rural children were more likely to have higher triglyceride levels than urban children. Although the prevalence of metabolic syndrome is low, the fact that majority of the children already have at least one component of metabolic syndrome is cause for concern since components of metabolic syndrome can continue into adulthood and increase the risk for chronic diseases later in life. Therefore, immediate action should be taken to address the problem.