Placental epigenetic gestational aging in relation to maternal sociodemographic factors and smoking among infants born extremely preterm: a descriptive study.

Social determinants of health (SDoH) are defined as the conditions in which people are born, grow, live, work, and age. The distribution of these conditions is influenced by underlying structural factors and may be linked to adverse pregnancy outcomes through epigenetic modifications of gestational tissues. A promising modification is epigenetic gestational age (eGA), which captures 'biological' age at birth. Measuring eGA in placenta, an organ critical for foetal development, may provide information about how SDoH 'get under the skin' during pregnancy to influence birth outcomes and ethnic/racial disparities. We examined relationships of placental eGA with sociodemographic factors, smoking, and two key clinical outcomes: Apgar scores and NICU length of stay. Using the Robust Placental Clock, we estimated eGA for placental samples from the Extremely Low Gestational Age Newborns cohort (N = 408). Regression modelling revealed smoking during pregnancy was associated with placental eGA acceleration (i.e., eGA higher than chronologic gestational age). This association differed by maternal race: among infants born to mothers racialized as Black, we observed greater eGA acceleration (+0.89 week, 95% CI: 0.38, 1.40) as compared to those racialized as white (+0.27 week, 95% CI: -0.06, 0.59). Placental eGA acceleration was also correlated with shorter NICU lengths of stay, but only among infants born to mothers racialized as Black (-0.08 d/week-eGA, 95% CI: -0.12, -0.05). Together, these observed associations suggest that interpretations of epigenetic gestational aging may be tissue-specific.

Low Serum Klotho Associated With All-cause Mortality Among a Nationally Representative Sample of American Adults.

α-Klotho (klotho) is a protein involved in suppressing oxidative stress and inflammation. In animal models, it is reported to underlie numerous aging phenotypes and longevity. Among a nationally representative sample of adults aged 40-79 years in the United States, we investigated whether circulating concentrations of klotho is a marker of mortality risk. Serum klotho was measured by ELISA on 10 069 individuals enrolled in the National Health and Nutrition Examination Survey between 2007 and 2014. Mortality follow-up data based on the National Death Index were available through December 31, 2015. After a mean follow-up of 58 months (range: 1-108), 616 incident deaths occurred. Using survey-weighted Cox regression models adjusted for age, sex, and survey cycle, low serum klotho concentration (<666 pg/mL) was associated with a 31% higher risk of death (compared to klotho concentration > 985 pg/mL, hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.00, 1.71, p = .05). Associations were consistent for mortality caused by heart disease or cancer. Associations of klotho with all-cause mortality did not appear to differ by most participant characteristics. However, we observed effect modification by physical activity, such that low levels of serum klotho were more strongly associated with mortality among individuals who did not meet recommendation-based physical activity guidelines. Our findings suggest that, among the general population of American adults, circulating levels of klotho may serve as a marker of mortality risk.

Cytomegalovirus seroprevalence, recurrence, and antibody levels: Associations with cadmium and lead exposures in the general United States population.

BACKGROUND: The ubiquitous metals cadmium and lead are immunotoxic, but little is known about their relations to cytomegalovirus (CMV), a widespread herpesvirus. Although CMV infections are mostly asymptomatic, congenital infections are a leading cause of birth defects. In otherwise healthy individuals, there is also some evidence linking subclinical reactivations to accelerated age-related declines in immune function and chronic disease. METHODS: Our objective was to evaluate associations of blood cadmium and lead biomarkers with CMV infection in a representative sample of the United States population. In seropositive individuals, we also examined associations with CMV-specific immunoglobulin G (IgG) antibody levels and suspected CMV recurrences. Using cross-sectional data from the 1999-2004 National Health and Nutrition Examination Surveys, we fit multivariable survey-weighted regression models accounting for potential confounding by sociodemographic and lifestyle factors and stratifying by age group to allow for heterogeneity. CMV recurrences were defined according to (1) the presence of either CMV-specific immunoglobulin M in sera or CMV viral DNA in urine, and (2) high CMV-specific IgG avidity. RESULTS: We observed null associations for blood cadmium. Increasing blood lead quartiles were related to CMV seropositivity and higher CMV IgG levels (both P trend < 0.01), but not CMV recurrence, only among individuals who were 20-29 years of age. CONCLUSION: Blood cadmium levels do not appear to be related to immunological markers of CMV infections. The possibility that lead exposures increase the risk of CMV infection and impair immune control of the virus in young adults was suggested. Prospective studies are needed to confirm.

Occupational Exposures and Cardiac Structure and Function: ECHO-SOL (Echocardiographic Study of Latinos).

Background Our objective was to determine associations of occupational exposures with cardiac structure and function in Hispanic/Latino adults. Methods and Results Employed participants were included (n=782; 52% women, mean age 52.9 years). Occupational exposures to burning wood, vehicle exhaust, solvents, pesticides, and metals at the current and longest-held job were assessed by questionnaire. Survey multivariable linear regression analyses were used to model the relationship of each self-reported exposure with echocardiographic measures of cardiac structure and function. Exposure to burning wood at the current job was associated with decreased left ventricular (LV) ejection fraction (-3.1%; standard error [SE], 1.0 [P=0.002]). When the analysis was restricted to exposure at the longest-held job, occupational exposure to burning wood was associated with increased LV diastolic volume (6.7 mL; SE, 1.6 [P<0.0001]), decreased LV ejection fraction (-2.7%; SE, 0.6 [P<0.0001]), worse LV global longitudinal strain (1.0%; SE, 0.3 [P=0.0009]), and decreased right ventricular fractional area change (-0.02; SE, 0.004 [P<0.001]). Exposure to pesticides was associated with worse average global longitudinal strain (0.8%; SE, 0.2 [P<0.0001]). Exposure to metals was associated with worse global longitudinal strain in the 2-chamber view (1.0%; SE, 0.5 [P=0.04]), increased stroke volume (3.6 mL; SE, 1.6 [P=0.03]), and increased LV mass indexed to BSA (9.2 g/m2; SE, 3.8 [P=0.01]) or height (4.4 g/m2.7; SE, 1.9 [P=0.02]). Conclusions Occupational exposures to burning wood, vehicle exhaust, pesticides, and metals were associated with abnormal parameters of LV and right ventricular systolic function. Reducing exposures to toxic chemicals and particulates in the workplace is a potential opportunity to prevent cardiovascular disease in populations at risk.

Rice Intake and Emerging Concerns on Arsenic in Rice: a Review of the Human Evidence and Methodologic Challenges.

PURPOSE OF REVIEW: Rice is a major staple food worldwide and a dietary source of arsenic. We therefore summarized the state of the epidemiologic evidence on whether rice consumption relates to health outcomes associated with arsenic exposure. RECENT FINDINGS: While epidemiologic studies have reported that higher rice consumption may increase the risk of certain chronic conditions, i.e., type 2 diabetes, most did not consider specific constituents of rice or other sources of arsenic exposure. Studies that examined rice intake stratified by water concentrations of arsenic found evidence of increasing trends in cardiovascular disease risk, skin lesions, and squamous cell skin cancers and bladder cancer associated with higher rice consumption. Further studies are needed to understand the health impacts of arsenic exposure from rice consumption taking into account all sources of rice intake and potential confounding by other dietary constituents or contaminants and arsenic exposure from sources such as water.

Placental CpG Methylation of Inflammation, Angiogenic, and Neurotrophic Genes and Retinopathy of Prematurity.

Purpose: Extremely preterm infants are at increased risk for retinopathy of prematurity (ROP). We previously identified several inflammatory proteins that were expressed early in life and are associated with an increased risk of ROP and several angiogenic and neurotrophic growth factors in the neonatal systemic circulation that are associated with a lower risk of ROP. In this paper, we report the results of a set of analyses designed to test the hypothesis that placental CpG methylation levels of 12 inflammation-, angiogenic-, and neurotrophic-associated genes predict the occurrence of prethreshold ROP in extremely preterm newborns. Methods: We used placental CpG methylation data from 395 newborns from the Extremely Low Gestational Age Newborns study. Results: Multivariable regression models revealed that placental DNA methylation of 16 CpG sites representing 8 genes were associated with prethreshold ROP. Specifically, CpG methylation in the serum amyloid A SAA1 and SAA2, brain-derived neurotrophic factor (BDNF), myeloperoxidase (MPO), C-reactive protein (CRP), angiopoietin 1 (ANGPT1), and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) genes was associated with a lower risk of prethreshold ROP. Conversely, CpG methylation at three probes within tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and in two alternative probes within the BDNF and ANGPT1 genes was associated with an increased risk of ROP. Conclusions: CpG methylation may be a useful marker for improving ROP prediction, opening the opportunity for early intervention to lessen disease severity.

Changes in blood pressure associated with lead, manganese, and selenium in a Bangladeshi cohort.

BACKGROUND: Heavy metal contamination is widespread in Bangladesh. Previous studies have observed lead increases blood pressure over time. However, the role of other metal contaminants and essential micronutrients, which could also adversely affect blood pressure or act as protective factors, is understudied. OBJECTIVES: We therefore evaluated the associations of lead, manganese, and selenium with blood and pulse pressure trajectories. METHODS: We prospectively followed placebo-assigned participants nested within a randomized trial for the prevention of arsenic-related skin cancer (n = 255). Blood lead, manganese, and selenium were measured at baseline; blood pressure was measured at baseline and at 3 biennial follow-up examinations. Mixed-effect linear regression models were used to estimate associations with average annual changes in systolic, diastolic, and pulse pressure. RESULTS: In models simultaneously adjusted for baseline blood lead, manganese, and selenium concentrations in addition to other potential confounders, lead was linearly associated with increases in systolic blood pressure, but not with diastolic blood pressure or pulse pressure. A non-linear association was observed for manganese, such that mid-range concentrations were associated with decreases in systolic, diastolic, and pulse pressure. Baseline selenium concentrations in the highest quartile were also associated with longitudinal decreases in both systolic and diastolic blood pressure, while null associations were observed with pulse pressure. In exploratory analyses, the combination of mid-range manganese and high selenium concentrations completely offset lead-associated increases in blood and pulse pressure. CONCLUSIONS: The results indicate a direct, linear association of lead exposure with systolic blood pressure, and manganese and selenium exposures within certain ranges may have a blood pressure-lowering effect in this population.

Association of occupational exposures with cardiovascular disease among US Hispanics/Latinos.

OBJECTIVE: Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in the USA. The role of occupational exposures to chemicals in the development of CVD has rarely been studied even though many agents possess cardiotoxic properties. We therefore evaluated associations of self-reported exposures to organic solvents, metals and pesticides in relation to CVD prevalence among diverse Hispanic/Latino workers. METHODS: Cross-sectional data from 7404 employed individuals, aged 18-74 years, enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were analysed. Participants from four US cities provided questionnaire data and underwent clinical examinations, including ECGs. CVD was defined as the presence of at least one of the following: coronary heart disease, atrial fibrillation, heart failure or cerebrovascular disease. Prevalence ratios reflecting the relationship between each occupational exposure and CVD as well as CVD subtypes were calculated using Poisson regression models. RESULTS: Hispanic/Latino workers reported exposures to organic solvents (6.5%), metals (8.5%) and pesticides (4.7%) at their current jobs. Overall, 6.1% of participants had some form of CVD, with coronary heart disease as the most common (4.3%) followed by cerebrovascular disease (1.0%), heart failure (0.8%) and atrial fibrillation (0.7%). For individuals who reported working with pesticides, the prevalence ratios for any CVD were 2.18 (95% CI 1.34 to 3.55), coronary heart disease 2.20 (95% CI 1.31 to 3.71), cerebrovascular disease 1.38 (95% CI 0.62 3.03), heart failure 0.91 (95% CI 0.23 to 3.54) and atrial fibrillation 5.92 (95% CI 1.89 to 18.61) after adjustment for sociodemographic, acculturation, lifestyle and occupational characteristics. Metal exposures were associated with an almost fourfold (3.78, 95% CI 1.24 to 11.46) greater prevalence of atrial fibrillation. Null associations were observed for organic solvent exposures. CONCLUSIONS: Our results suggest that working with metals and pesticides could be risk factors for CVD among Hispanic/Latino workers. Further work is needed to evaluate these relationships prospectively.

Patients at Increased Risk of Major Adverse Events Following Operative Treatment of Distal Radius Fractures: Inpatient versus Outpatient.

Purpose The purpose of this study was to compare complication rates following inpatient versus outpatient distal radius fracture ORIF and identify specific complications that occur at increased rates among inpatients. Methods Using the 2005-2013 ACS-NSQIP, we collected patient demographics, comorbidities, surgical characteristics, and 30-day postoperative complications following isolated ORIF of distal radius fractures. A propensity score matched design using an 8-to-1 "greedy" matching algorithm in a 1:4 ratio of inpatients to outpatients was utilized. Rates of minor, major, and total complications were compared. A multinomial logistic regression model was then used to assess the odds of complications following inpatient surgery. Results Total 4,016 patients were identified, 776 (19.3%) of whom underwent inpatient surgery and 3,240 (80.3%) underwent outpatient surgery. The propensity score matching algorithm yielded a cohort of 629 inpatients who were matched with 2,516 outpatients (1:4 ratio). After propensity score matching, inpatient treatment was associated with increased rates of major and total complications but not with minor complications. There was an increased odds of major complications and total complications following inpatient surgery compared with outpatient surgery. There was no difference in odds of minor complications between groups. Conclusion Inpatient operative treatment of distal radius fractures is associated with significantly increased rates of major and total complications compared with operative treatment as an outpatient. Odds of a major complication are six times higher and odds of total complications are two and a half times higher following inpatient distal radius ORIF compared with outpatient. Quality improvement measures should be specifically targeted to patients undergoing distal radius fracture ORIF in the inpatient setting.

Nondepolarizing Neuromuscular Blocking Agents, Reversal, and Risk of Postoperative Pneumonia.

BACKGROUND: Residual postoperative paralysis from nondepolarizing neuromuscular blocking agents (NMBAs) is a known problem. This paralysis has been associated with impaired respiratory function, but the clinical significance remains unclear. The aims of this analysis were two-fold: (1) to investigate if intermediate-acting NMBA use during surgery is associated with postoperative pneumonia and (2) to investigate if nonreversal of NMBAs is associated with postoperative pneumonia. METHODS: Surgical cases (n = 13,100) from the Vanderbilt University Medical Center National Surgical Quality Improvement Program database who received general anesthesia were included. The authors compared 1,455 surgical cases who received an intermediate-acting nondepolarizing NMBA to 1,455 propensity score-matched cases who did not and 1,320 surgical cases who received an NMBA and reversal with neostigmine to 1,320 propensity score-matched cases who did not receive reversal. Postoperative pneumonia incidence rate ratios (IRRs) and bootstrapped 95% CIs were calculated. RESULTS: Patients receiving an NMBA had a higher absolute incidence rate of postoperative pneumonia (9.00 vs. 5.22 per 10,000 person-days at risk), and the IRR was statistically significant (1.79; 95% bootstrapped CI, 1.08 to 3.07). Among surgical cases who received an NMBA, cases who were not reversed were 2.26 times as likely to develop pneumonia after surgery compared to cases who received reversal with neostigmine (IRR, 2.26; 95% bootstrapped CI, 1.65 to 3.03). CONCLUSIONS: Intraoperative use of intermediate nondepolarizing NMBAs is associated with developing pneumonia after surgery. Among patients who receive these agents, nonreversal is associated with an increased risk of postoperative pneumonia.

Arsenic in drinking water and prostate cancer in Illinois counties: An ecologic study.

BACKGROUND: Inorganic arsenic is a lung, bladder, and skin carcinogen. One of the major sources of exposure to arsenic is through naturally contaminated drinking water. While positive associations have been observed between arsenic in drinking water and prostate cancer, few studies have explored this association in the United States. OBJECTIVES: To evaluate the association between inorganic arsenic concentrations in community water systems and prostate cancer incidence in Illinois using an ecologic study design. METHODS: Illinois Environmental Protection Agency data on arsenic concentrations in drinking water from community water systems throughout the state were linked with county-level prostate cancer incidence data from 2007 to 2011 from the Illinois State Cancer Registry. Incidence rates were indirectly standardized by age to calculate standardized incidence ratios (SIRs) for each county. A Poisson regression model was used to model the association between county-level SIRs and mean arsenic tertile (0.33-0.72, 0.73-1.60, and 1.61-16.23ppb), adjusting for potential confounders. RESULTS: For counties with mean arsenic levels in the second tertile, the SIR was 1.05 (95% CI: 0.96-1.16). For counties with mean arsenic levels in the third tertile, the SIR was 1.10 (95% CI: 1.03-1.19). There was a significant linear dose-response relationship observed between mean arsenic levels and prostate cancer incidence (p for trend=0.003). CONCLUSIONS: In this ecologic study, counties with higher mean arsenic levels in community water systems had significantly higher prostate cancer incidence. Individual-level studies of prostate cancer incidence and low-level arsenic exposure are needed.

Demographic Predictors of NPO Violations in Elective Pediatric Surgery.

PURPOSE: The parents of pediatric patients are routinely instructed to abstain from food and liquids before elective surgeries. Our objectives were to determine if demographic factors were associated with fasting violations and to identify reasons for noncompliance. DESIGN: This was a matched case-control pilot study. METHODS: A total of 63 patients who violated fasting guidelines were identified and matched to three controls within the same surgical service. Demographic and clinical variables were evaluated as predictors of noncompliance in a multivariate regression model. Qualitative data were coded into the most commonly identified reasons for non per os (Latin)-nothing by mouth violations. FINDINGS: Parents of children who did not comply commonly reported that they did not receive or did not understand the fasting guidelines. Noncompliant patients were significantly more likely to experience surgical delays and cancellations. None of the demographic and clinical variables assessed were significantly associated with non per os (Latin)-nothing by mouth violations in this pilot study. CONCLUSIONS: Quality improvement actions may be necessary to ensure that parents receive and understand fasting guidelines for their children. This might include use of teach-back methods, modification of instructional materials, or providing follow-up information after the initial encounter.

Regional anesthesia, time to hospital discharge, and in-hospital mortality: a propensity score matched analysis.

BACKGROUND AND OBJECTIVES: The anesthetic technique used during surgery can affect postoperative length of stay and outcomes, even after controlling for other clinically important factors. This study evaluated the impact of regional anesthesia (RA) compared with general anesthesia (GA) on the amount of time between leaving the operating room and hospital discharge and the odds of in-hospital mortality. METHODS: Surgical patients admitted after surgery, who received RA, were matched to patients who received GA by propensity score in a 1:4 ratio. We measured the association between anesthetic technique and time to hospital discharge using Kaplan-Meier methods. In-hospital mortality was analyzed using a generalized estimating equation logistic regression model. RESULTS: A total of 5870 inpatient surgical cases were analyzed; 1174 cases received RA and 4696 cases received GA. The median time to hospital discharge among patients who received RA was 67.6 hours compared with 71.9 hours among patients who received GA (P < 0.0001). A total of 86 cases died in the hospital after surgery; 7 were in the RA cohort and 79 were in the GA cohort. Receiving RA during surgery was associated with 64% lesser odds of dying in the hospital (odds ratio, 0.36; 95% confidence interval, 0.16-0.75), when adjusting for the number of postoperative days spent in the hospital. CONCLUSIONS: The study data provide evidence that median time to discharge is shorter when RA is used instead of GA, controlling for other clinically important factors. Additionally, RA use during surgery was associated with a decrease in in-hospital mortality. When an appropriate option, RA may facilitate faster hospital discharge and improve patient outcomes.

Is regional anesthesia associated with reduced PACU length of stay?: A retrospective analysis from a tertiary medical center.

BACKGROUND: Postanesthesia care is a costly component of overall surgical care. In the ambulatory setting, regional anesthesia has been shown for multiple surgical procedures to either decrease postanesthesia care unit (PACU) length of stay (LOS) or completely bypass it altogether. This has not been demonstrated in a large hospital setting with a complex surgical case mix. QUESTIONS/PURPOSES: We therefore determined whether regional anesthesia was associated with a reduced PACU LOS among patients undergoing inpatient and outpatient surgery in a large tertiary-care teaching hospital. Secondary study questions included risk factors for longer PACU LOS and any possible interaction between regional and general anesthesia as it might have affected PACU LOS. METHODS: We performed a matched retrospective study on patients who had surgery at our institution and were admitted to the PACU immediately after leaving the operating room. We analyzed between January 1, 2005, and January 1, 2013, with one cohort receiving regional anesthesia, with or without general anesthesia, and the other receiving no regional anesthesia. We measured the association between regional anesthesia and time to successful PACU discharge using a Cox multivariate proportional-hazards model. RESULTS: After controlling for potentially confounding variables, including patient age, American Society of Anesthesiologists' physical classification, and duration of surgery (using multivariate analysis), there was no difference in the time to successful PACU discharge between patients who received regional anesthesia and those who did not. However, when compared to those who received general anesthesia, regional anesthesia was associated with decreased PACU LOS. Further, there was significant effect modification between regional and general anesthesia; patients who received both regional and general were more likely to be successfully discharged faster from the PACU than patients who received only general anesthesia (hazard ratio = 1.50, 95% CI = 1.46-1.55, p < 0.001). CONCLUSIONS: We demonstrated that independently, regional anesthesia is not associated with a reduced PACU LOS in an unselected population at a large tertiary-care hospital, but regional is favored when compared to general anesthesia. Whether the differences are clinically important, and in what procedures they are most pronounced, would be reasonable questions for future prospective comparative trials. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.