Placental cadmium, placental genetic variations, and birth size.

BACKGROUND: Maternal cadmium (Cd) burden has been associated with offspring birth size measures, yet associations of placental Cd with birth size are less clear. Further, the role of genetics in these associations has not been examined. We investigated associations of placental Cd with birth size and placental genotypes. We also examined the potential role of placental genotypes as modifiers of placental Cd and birth size associations. METHODS: Participants were 490 mother-child pairs from the Omega and Placenta Microarray studies based in Seattle, WA. Placental Cd was measured using Agilent 7500 ICP-MS. The birth size was characterized using birth weight (BW), ponderal index (PI), and head circumference (HC). Eleven placental single nucleotide polymorphisms (SNPs) related to metal transport, growth regulation, endocrine response, and cell signaling were genotyped. Adjusted multivariable linear regression models were used to examine overall and sex-specific associations of placental Cd with birth size (BW, PI and HC), as well as associations of placental genotypes with placental Cd. Effect modification of placenta Cd and birth size associations by placental SNPs was examined using interaction terms and stratified analyses. RESULTS: Mean maternal age was 33.6 years (SD = 4.4). Mean and median placental Cd levels were 4.0 ng/g tissue (SD = 2.7 ng/g tissue) and 3.6 ng/g (IQR 2.5 - 5.2 ng/g), respectively. Overall, compared with infants in the lowest quartile for placental Cd, infants in the second (ß = -102.8 g, 95% CI: -220.7, 15.1), third (ß = -83.2 g, 95% CI: -199.3, 32.9) and fourth (ß = -109.2 g, 95% CI: -225.4, 7.1) quartiles had lower BW, though associations were not statistically significant (all p-values > .05, trend p-value = .11). Among male infants, infants in the second (ß = -203.3 g, 95% CI: -379.7, -27.0) and fourth quartiles (ß = -198.3 g, 95% CI: -364.2, -32.5) had lower BW compared with those in the first quartiles (p-values < .05, trend p-value = .08). Similar relationships were not observed among female infants, though infant sex-placental Cd interaction terms were not significant. Similarly, male, but not female, infants had marginally significant positive associations between placental Cd and ponderal index (trend p-value = .06). The minor rs3811647 allele of the placental transferrin gene (NCBI Gene ID: 7018) was associated with an increase in Cd among all infants (p-value = .04). We did not find differences in associations of placental Cd with birth size markers among infants stratified by rs3811647 genotype. CONCLUSIONS: Placental Cd was inversely associated with BW among male infants. The rs3811647 SNP of the transferrin gene was associated with placental Cd.

Sacubitril/Valsartan Initiation Among Veterans Who Are Renin-Angiotensin-Aldosterone System Inhibitor Naïve With Heart Failure and Reduced Ejection Fraction.

Background Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, received US Food and Drug Administration approval in 2015 for heart failure with reduced ejection fraction (HFrEF). Our objective was to describe the sacubitril/valsartan initiation rate, associated characteristics, and 6-month follow-up dosing among veterans with HFrEF who are renin-angiotensin-aldosterone system inhibitor (RAASi) naïve. Methods and Results Retrospective cohort study of veterans with HFrEF who are RAASi naïve defined as left ventricular ejection fraction (LVEF) ≤40%; ≥1 in/outpatient heart failure visit, first RAASi (sacubitril/valsartan, angiotensin-converting enzyme inhibitor [ACEI]), or angiotensin-II receptor blocker [ARB]) fill from July 2015 to June 2019. Characteristics associated with sacubitril/valsartan initiation were identified using Poisson regression models. From July 2015 to June 2019, we identified 3458 sacubitril/valsartan and 29 367 ACEI or ARB initiators among veterans with HFrEF who are RAASi naïve. Sacubitril/valsartan initiation increased from 0% to 26.5%. Sacubitril/valsartan (versus ACEI or ARB) initiators were less likely to have histories of stroke, myocardial infarction, or hypertension and more likely to be older and have diabetes mellitus and lower LVEF. At 6-month follow-up, the prevalence of ≥50% target daily dose for sacubitril/valsartan, ACEI, and ARB initiators was 23.5%, 43.2%, and 47.1%, respectively. Conclusions Sacubitril/valsartan initiation for HFrEF in the Veterans Administration increased in the 4 years immediately following Food and Drug Administration approval. Sacubitril/valsartan (versus ACEI or ARB) initiators had fewer baseline cardiovascular comorbidities and the lowest proportion on ≥50% target daily dose at 6-month follow-up. Identifying the reasons for lower follow-up dosing of sacubitril/valsartan could support guideline recommendations and quality improvement strategies for patients with HFrEF.

Inequities in Hypertension Control in the United States Exposed and Exacerbated by COVID-19 and the Role of Home Blood Pressure and Virtual Health Care During and After the COVID-19 Pandemic.

The COVID-19 pandemic is a public health crisis, having killed more than 514 000 US adults as of March 2, 2021. COVID-19 mitigation strategies have unintended consequences on managing chronic conditions such as hypertension, a leading cause of cardiovascular disease and health disparities in the United States. During the first wave of the pandemic in the United States, the combination of observed racial/ethnic inequities in COVID-19 deaths and social unrest reinvigorated a national conversation about systemic racism in health care and society. The 4th Annual University of Utah Translational Hypertension Symposium gathered frontline clinicians, researchers, and leaders from diverse backgrounds to discuss the intersection of these 2 critical social and public health phenomena and to highlight preexisting disparities in hypertension treatment and control exacerbated by COVID-19. The discussion underscored environmental and socioeconomic factors that are deeply embedded in US health care and research that impact inequities in hypertension. Structural racism plays a central role at both the health system and individual levels. At the same time, virtual healthcare platforms are being accelerated into widespread use by COVID-19, which may widen the divide in healthcare access across levels of wealth, geography, and education. Blood pressure control rates are declining, especially among communities of color and those without health insurance or access to health care. Hypertension awareness, therapeutic lifestyle changes, and evidence-based pharmacotherapy are essential. There is a need to improve the implementation of community-based interventions and blood pressure self-monitoring, which can help build patient trust and increase healthcare engagement.

Angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use and COVID-19-related outcomes among US Veterans.

BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses. METHODS AND FINDINGS: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days). CONCLUSIONS: This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.

Characteristics and Healthcare Utilization Among Veterans Treated for Heart Failure With Reduced Ejection Fraction Who Switched to Sacubitril/Valsartan.

BACKGROUND: US guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF), who tolerate an ACEI (angiotensin-converting enzyme inhibitor) or ARB (angiotensin II receptor blocker), be switched to sacubitril/valsartan to reduce morbidity and mortality. We compared characteristics and healthcare utilization between Veterans with HFrEF who were switched to sacubitril/valsartan versus maintained on an ACEI or ARB. METHODS: retrospective cohort study of treated HFrEF (July 2015-June 2017) using Veterans Affairs data. The index date was the first fill for sacubitril/valsartan and if none, for an ACEI or ARB. Treated HFrEF was defined by (1) left ventricular ejection fraction ≤40%, (2) ≥1 in/outpatient HF encounter, and (3) ≥1 ACEI or ARB fill, all within 1-year preindex. Poisson regression models were used to compare baseline characteristics and 1:1 propensity score-matched adjusted 4-month follow-up healthcare utilization between sacubitril/valsartan switchers and ACEI or ARB maintainers. RESULTS: Switchers (1612; 4.2%) were less likely than maintainers (37 065; 95.8%) to have a history of myocardial infarction or hypertension, and more likely to be black, have a lower left ventricular ejection fraction, and higher preindex healthcare utilization. Switchers were less likely to experience follow-up all-cause hospitalizations (11.2% versus 14.0%; risk ratio 0.80 [95% CI, 0.65-0.98], P value 0.035). CONCLUSIONS: Few Veterans with treated HFrEF were switched to sacubitril/valsartan within the first 2 years of Food and Drug Administration approval. Sacubitril/valsartan use was associated with a lower risk for all-cause hospitalizations at 4 months follow-up. Reasons for lack of guideline-recommended sacubitril/valsartan initiation warrant investigation and may reveal opportunities for HFrEF care optimization.

2018 Salary Survey of AMIA Members: Factors Associated with Higher Salaries.

Greater transparency in salaries overall and in factors associated with differing salaries can help students and professionals plan their careers, discover biases and obstacles, and help advance professional disciplines broadly. In March 2018, we conducted the first salary survey of American Medical Informatics Association members. Our goal was to summarize salary information and provide a nuanced view pertaining to the diverse biomedical informatics community. To identify factors associated with higher salaries, we reviewed average salaries for different groups (physician status, academic status, and different leadership positions) by gender. We also fitted multiple linear regression models for all participants (N = 201) and for gender, physician- and academic-status subgroup. The mean (standard deviation) salary was $181,774 ($99,566). Men earned more than women on average, and especially among professionals from academic settings. More years working in informatics and full-time employment were two factors that were consistently associated with higher salary.

Impact of Deployment on Reproductive Health in U.S. Active-Duty Servicewomen and Veterans.

Reproductive-age women are a fast-growing component of active-duty military personnel who experience deployment and combat more frequently than previous service-era women Veterans. With the expansion of the number of women and their roles, the United States Departments of Defense and Veterans Affairs have prioritized development and integration of reproductive services into their health systems. Thus, understanding associations between deployments or combat exposures and short- or long-term adverse reproductive health outcomes is imperative for policy and programmatic development. Servicewomen and women Veterans may access reproductive services across civilian and military or Veteran systems and providers, increasing the need for awareness and communication regarding deployment experiences with a broad array of providers. An example is the high prevalence of military sexual trauma reported by women Veterans and the associated mental health diagnoses that may lead to a lifetime of high risk-coping behaviors that increase reproductive health risks, such as sexually transmitted infections, unintended pregnancies, and others. Care coordination models that integrate reproductive healthcare needs, especially during vulnerable times such as at the time of military separation and in the immediate postdeployment phase, may identify risk factors for early intervention with the potential to mitigate lifelong risks.

Development and evaluation of a record linkage protocol for Utah's Controlled Substance Database.

Utah's Controlled Substance Database prescription registry does not include master identifiers to link records for individual patients. We describe and evaluate a linkage protocol for Utah's Controlled Substance Database. Prescriptions (N = 22,401,506) dated 2005-2009 were linked using The Link King software and patient identifiers (e.g. names, dates of birth) for 2,232,725 patients. Review of 998 randomly selected record pairs classified 46 percent as definitely correct links and 54 percent as probably correct links. A correct link could not be confirmed for <1 percent. None were classified as probably incorrect links or definitely incorrect links. Record set reviews (N = 100 patients/set for 10 set sizes, randomly selected) classified 27-49 percent as definitely correct links and 39-63 percent as probably correct links. Fewer had too little information to confirm a link (5%-22%) or were probably incorrect (0%-6%). None were definitely incorrect. Overall, results suggest that Utah's Controlled Substance Database records were correctly linked. These data may be useful for cross-sectional and longitudinal studies of patient-controlled substance prescription histories.

In the Wrong Place with the Wrong SNP: The Association Between Stressful Neighborhoods and Cardiac Arrest Within Beta-2-adrenergic Receptor Variants.

BACKGROUND: Sudden cardiac arrest has been linked independently both to stressful neighborhood conditions and to polymorphisms in the ADRB2 gene. The ADRB2 gene mediates sympathetic activation in response to stress. Therefore, if neighborhood conditions cause cardiac arrest through the stress pathway, the ADRB2 variant may modify the association between neighborhood conditions, such as socioeconomic deprivation and incidence of cardiac arrest. METHODS: The Cardiac Arrest Blood Study Repository is a population-based repository of specimens and other data from adult cardiac arrest patients residing in King County, Washington. Cases (n = 1,539) were 25- to 100-year-old individuals of European descent who experienced out-of-hospital cardiac arrest from 1988 to 2004. Interactions between neighborhood conditions and the ADRB2 genotype on cardiac arrest risk were assessed in a case-only study design. Gene-environment independence was assessed in blood samples obtained from King County residents initially contacted by random-digit dialing. RESULTS: Fewer than 4% of study subjects resided in socioeconomically deprived neighborhoods. Nonetheless, the case-only analysis indicated the presence of supramultiplicative interaction of socioeconomic deprivation and the homozygous Gln27Glu variant (case-only odds ratio: 1.8 [95% confidence interval: 1.0, 2.9]). Interactions between population density and the homozygous Gln27Glu variant were weaker (case-only odds ratio: 1.2 [95% confidence interval: 0.97, 1.5]). CONCLUSIONS: Findings support a supramultiplicative interaction between the Gln27Glu ADRB2 variant and socioeconomic deprivation among individuals of European descent. This result is consistent with the hypothesis that the elevation in cardiac arrest risk associated with socioeconomic deprivation operates through the stress pathway.

Ethnic differences in sudden cardiac arrest resuscitation.

OBJECTIVE: Ethnic differences in sudden cardiac arrest resuscitation have not been fully explored and studies have yielded inconsistent results. We examined the association of ethnicity with factors affecting sudden cardiac arrest outcomes. METHODS: Retrospective cohort study of 3551 white, 440 black and 297 Asian sudden cardiac arrest cases in Seattle and King County, Washington, USA. RESULTS: Compared with whites, blacks and Asians were younger, had lower socioeconomic status and were more likely to have diabetes, hypertension and end-stage renal disease (all p<0.001). Blacks and Asians were less likely to have a witnessed arrest (whites 57.6%, blacks 52.1%, Asians 46.1%, p<0.001) or receive bystander cardiopulmonary resuscitation (whites 50.9%, blacks 41.4%, Asians 47.1%, p=0.001), but had shorter average emergency medical services response time (mean in minutes: whites 5.18, blacks 4.75, Asians 4.85, p<0.001). Compared with whites, blacks were more likely to be found in pulseless electrical activity (blacks 20.9% vs whites 16.6%, p<0.001), and Asians were more likely to be found in asystole (Asians 41.1% vs whites 30.0%, p<0.001). One of the strongest predictors of resuscitation outcomes was initial cardiac rhythm with 25% of ventricular fibrillation, 4% of patients with pulseless electrical activity and 1% of patients with asystole surviving to hospital discharge (adjusted OR of resuscitation in pulseless electrical activity compared with ventricular fibrillation: 0.30, 95% CI 0.24 to 0.34, p<0.001, adjusted OR of resuscitation in asystole relative to ventricular fibrillation 0.21, 95% CI 0.17 to 0.26, p<0.001). Survival to hospital discharge was similar across all three ethnicities. CONCLUSIONS: While there were differences in some prognostic characteristics between blacks, whites and Asians, we did not detect a significant difference in survival following sudden cardiac arrest between the three ethnic groups. There was, however, an ethnic difference in presenting rhythm, with pulseless electrical activity more prevalent in blacks and asystole more prevalent in Asians.

Fibromyalgia syndrome care of Iraq- and Afghanistan-deployed Veterans in Veterans Health Administration.

Little is known regarding fibromyalgia syndrome (FMS) care among Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OIF/OEF/OND) Veterans. Current recommendations include interdisciplinary, team-based combined care approaches and limited opioid use. In this study of OIF/OEF/OND Veterans who accessed Veterans Health Administration services between 2002 and 2012, we hypothesized that combined care (defined as at least 4 primary care visits/yr with visits to mental health and/or rheumatology) versus <4 primary care visits/yr only would be associated with lower risk of at least 2 opioid prescriptions 12 mo following an FMS diagnosis. Using generalized linear models with a log-link, the Poisson family, and robust standard errors, we estimated risk ratios (RRs) and 95% confidence intervals (CIs). We found that 1% of Veterans had at least 2 FMS diagnoses (International Classification of Diseases-9th Revision-Clinical Modification code 729.1) or at least 1 FMS diagnosis by rheumatology. Veterans with (vs without) FMS were more likely to be female, older, Hispanic, and never/currently married. Combined primary, mental health, and rheumatology care was associated with at least 2 opioid prescriptions (RR [95% CI] for males 2.2 [1.1-4.4] and females 2.8 [0.4-18.6]). Also, combined care was associated with at least 2 nonopioid pain-related prescriptions, a practice supported by evidence-based clinical practice guidelines. In tandem, these results provide mixed evidence of benefit of combined care for FMS. Future studies of healthcare encounter characteristics, care coordination, and benefits for Veterans with FMS are needed.

Periconceptional seafood intake and pregnancy complications.

OBJECTIVE: To investigate associations of maternal periconceptional shellfish, lean fish and fatty fish intake with risk of pregnancy complications. DESIGN: In this prospective cohort study, we collected information on intake of seafood subtypes using FFQ. We categorized seafood intake into frequencies of 1 servings/week. We ascertained gestational hypertension, pre-eclampsia, gestational diabetes and preterm birth diagnoses from medical records. Using generalized linear models with a log link, the Poisson family and robust standard errors, we estimated risk ratios and 95 % confidence intervals across seafood intake categories. SETTING: The Omega study, a study of risk factors for pregnancy complications among women recruited from prenatal clinics in Washington State, USA, 1996-2008. SUBJECTS: The current study included 3279 participants from the Omega study. RESULTS: Median (interquartile range) shellfish, lean fish and fatty fish intake was 0·3 (0-0·9), 0·5 (0-1·0) and 0·5 (0·1-1·0) servings/week, respectively. Lean fish intake of >1 servings/week (v. <0·2 servings/month) was associated with a 1·55-fold higher risk of preterm birth (95 % CI 1·04, 2·30) and was not associated with the other pregnancy complications. Higher intake of seafood (total or other subtypes) was not associated with pregnancy complications (separately or combined). CONCLUSIONS: Higher intake of lean fish, but not fatty fish or shellfish, was associated with a higher risk of preterm birth; these findings may have significance for preterm birth prevention. Studies of mechanisms and potential contributing factors (including seafood preparation and nutrient/contaminant content) are warranted.

Identification and Use of Frailty Indicators from Text to Examine Associations with Clinical Outcomes Among Patients with Heart Failure.

Frailty is an important health outcomes indicator and valuable for guiding healthcare decisions in older adults, but is rarely collected in a quantitative, systematic fashion in routine healthcare. Using a cohort of 12,000 Veterans with heart failure, we investigated the feasibility of topic modeling to identify frailty topics in clinical notes. Topics were generated through unsupervised learning and then manually reviewed by an expert. A total of 53 frailty topics were identified from 100,000 notes. We further examined associations of frailty with age-, sex-, and Charlson Comorbidity Index-adjusted 1-year hospitalizations and mortality (composite outcome) using logistic regression. Frailty (≤ 4 topics versus <4) was associated with twice the risk of the composite outcome, Odds Ratio: 2.2, 95% Confidence Interval: (2.0-2.4). This study demonstrates the feasibility of identifying frailty indicators from clinical notes and linking these to clinically relevant outcomes. Future work includes integrating frailty indicators into validated predictive tools.

Periconceptional Seafood Intake and Fetal Growth.

BACKGROUND: Previous reports of associations of maternal seafood intake with fetal growth were inconsistent. Further, little is known whether associations differ across seafood subtypes or fetal growth indices. METHODS: Among 3141 participants of the Omega study, a pregnancy cohort study, we investigated associations of periconceptional shell, lean, and fatty fish intake with fetal growth indices. We categorised food frequency questionnaire reported seafood intake into frequencies of: <0.2 servings/month, 0.2 servings/month -<0.5 servings/week, 0.5-1 servings/week, and >1 servings/week. We abstracted birthweight, birth length, and head circumference from medical records. Using generalised linear models with a log link, the Poisson family, and robust standard errors, we estimated relative risks and 95% confidence intervals (CI) for low birthweight (LBW, <2500 g) and linear regression models to estimate mean differences for continuous fetal growth indices across seafood intake categories. RESULTS: Medians (interquartile range) of shell, lean, and fatty fish intake were 0.3 (0-0.9), 0.5 (0-1.0), and 0.5 (0.1-1.0) servings/week, respectively. Lean fish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 2.2-fold higher risk of LBW (95% CI 1.2, 4.1). Shellfish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 0.6 kg/m(3) higher mean ponderal index (95% CI 0.0, 1.2 kg/m(3) ). There was no evidence for associations of total seafood or seafood subtype intake with other fetal growth indices. CONCLUSIONS: Higher intakes of lean fish and shellfish were associated with a higher risk of LBW and higher mean ponderal index, respectively. Findings highlight the importance of considerations of seafood subtype in similar investigations.

Chronic multisymptom illness among female Veterans deployed to Iraq and Afghanistan.

BACKGROUND: Chronic multisymptom illness (CMI) may be more prevalent among female Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) deployed Veterans due to deployment-related experiences. OBJECTIVES: To investigate CMI-related diagnoses among female OEF/OIF/OND Veterans. RESEARCH DESIGN: We estimated the prevalence of the International Classification of Disease-9th edition-Clinical Modification coded CMI-related diagnoses of chronic fatigue syndrome, fibromyalgia (FM), and irritable bowel syndrome (IBS) among female OEF/OIF/OND Veterans with Veterans Health Administration (VHA) visits, FY2002-2012 (n=78,435). We described the characteristics of female Veterans with and without CMI-related diagnoses and VHA settings of first CMI-related diagnoses. RESULTS: The prevalence of CMI-related diagnoses among female OEF/OIF/OND Veterans was 6397 (8.2%), over twice as high as the prevalence 95,424 (3.9%) among the totality of female Veterans currently accessing VHA (P<0.01). There were statistically significant differences in age, education, marital status, military component, service branch, and proportions of those with depression and/or post-traumatic stress disorder diagnoses across females with and without CMI-related diagnoses. Diagnoses were mainly from primary care, women's health, and physical medicine and rehabilitation clinics. CONCLUSIONS: CMI-related diagnoses were more prevalent among female OEF/OIF/OND Veterans compared with all female Veterans who currently access VHA. Future studies of the role of mental health diagnoses as confounders or mediators of the association of OEF/OIF/OND deployment and CMI are warranted. These and other factors associated with CMI may provide a basis for enhanced screening to facilitate recognition of these conditions. Further work should evaluate models of care and healthcare utilization related to CMI in female Veterans.

Infant sex-specific placental cadmium and DNA methylation associations.

BACKGROUND: Recent evidence suggests that maternal cadmium (Cd) burden and fetal growth associations may vary by fetal sex. However, mechanisms contributing to these differences are unknown. OBJECTIVES: Among 24 maternal-infant pairs, we investigated infant sex-specific associations between placental Cd and placental genome-wide DNA methylation. METHODS: We used ANOVA models to examine sex-stratified associations of placental Cd (dichotomized into high/low Cd using sex-specific Cd median cutoffs) with DNA methylation at each cytosine-phosphate-guanine site or region. Statistical significance was defined using a false discovery rate cutoff (<0.10). RESULTS: Medians of placental Cd among females and males were 5 and 2 ng/g, respectively. Among females, three sites (near ADP-ribosylation factor-like 9 (ARL9), siah E3 ubiquitin protein ligase family member 3 (SIAH3), and heparin sulfate (glucosamine) 3-O-sulfotransferase 4 (HS3ST4) and one region on chromosome 7 (including carnitine O-octanoyltransferase (CROT) and TP5S target 1 (TP53TG1)) were hypomethylated in high Cd placentas. Among males, high placental Cd was associated with methylation of three sites, two (hypomethylated) near MDS1 and EVI1 complex locus (MECOM) and one (hypermethylated) near spalt-like transcription factor 1 (SALL1), and two regions (both hypomethylated, one on chromosome 3 including MECOM and another on chromosome 8 including rho guanine nucleotide exchange factor (GEF) 10 (ARHGEF10). Differentially methylated sites were at or close to transcription start sites of genes involved in cell damage response (SIAH3, HS3ST4, TP53TG1) in females and cell differentiation, angiogenesis and organ development (MECOM, SALL1) in males. CONCLUSIONS: Our preliminary study supports infant sex-specific placental Cd-DNA methylation associations, possibly accounting for previously reported differences in Cd-fetal growth associations across fetal sex. Larger studies are needed to replicate and extend these findings. Such investigations may further our understanding of epigenetic mechanisms underlying maternal Cd burden with suboptimal fetal growth associations.

Representation of Functional Status Concepts from Clinical Documents and Social Media Sources by Standard Terminologies.

Patient-reported functional status is widely recognized as an important patient-centered outcome that adds value to medical care, research, and quality improvement. Functional status outcomes are, however, not routinely or uniformly collected in the medical record, except in certain small patient populations (e.g. geriatrics, nursing home residents). To utilize patient reported functional status for clinical research and practice, we manually collected 2,763 terms from clinical records and social media sites and modeled them on the widely used Short Form-36 Health Survey. We then examined the coverage of the Unified Medical Language System (UMLS) for these functional status terms through automated mapping. Most terms (85.9%) did not have exact matches in the UMLS. The partial matches were prevalent, however, they typically did not capture the terms' exact semantics. Our study suggests that there is a need to extend existing standard terminologies to incorporate functional status terms used by patients and clinicians.