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1.
  • Albutt, Katherine, et al. (author)
  • 'We are all serving the same Ugandans' : A nationwide mixed-methods evaluation of private sector surgical capacity in Uganda
  • 2019
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:10
  • Journal article (peer-reviewed)abstract
    • Introduction Half of all Ugandans (49%) turn to the private or private-not-for-profit (PNFP) sectors when faced with illness, yet little is known about the capacity of these sectors to deliver surgical services. We partnered with the Ministry of Health to conduct a nationwide mixed-methods evaluation of private and PNFP surgical capacity in Uganda. Methods A standardized validated facility assessment tool was utilized to assess facility infrastructure, service delivery, workforce, information management, and financing at a randomized nationally representative sample of 16 private and PNFP hospitals. Semi-structured interviews were conducted to qualitatively explore facilitating factors and barriers to surgical, obstetric and anaesthesia (SOA) care. Hospitals walk-throughs and retrospective reviews of operative logbooks were completed. Results Hospitals had a median of 177 beds and two operating rooms. Ten hospitals (62.5%) were able to perform all Bellwether procedures (cesarean section, laparotomy and open fracture treatment). Thirty-day surgical volume averaged 102 cases per facility. While most hospitals had electricity, oxygen, running water, and necessary equipment, many reported pervasive shortages of blood, surgical consumables, and anesthetic drugs. Several themes emerged from the qualitative analysis: (1) geographic distance and limited transportation options delay reaching care; (2) workforce shortages impede the delivery of surgical care; (3) emergency and obstetric volume overwhelm the surgical system; (4) medical and non-medical costs delay seeking, reaching, and receiving care; and (5) there is poor coordination of care with insufficient support systems. Conclusion As in Uganda's public sector, barriers to surgery in private and PNFP hospitals in Uganda are cross-cutting and closely tied to resource availability. Critical policy and programmatic developments are essential to build and strengthen Ugandan surgical capacity across all sectors.
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2.
  • Carrick, Richard T., et al. (author)
  • Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe
  • 2024
  • In: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645.
  • Journal article (peer-reviewed)abstract
    • Background and Aims Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC.Methods This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed.Results One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans.Conclusions North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.
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3.
  • de Water, E., et al. (author)
  • Prenatal metal mixture concentrations and reward motivation in children
  • 2022
  • In: Neurotoxicology. - : Elsevier. - 0161-813X .- 1872-9711. ; 88, s. 124-133
  • Journal article (peer-reviewed)abstract
    • Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6–8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2nd and 3rd trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (ß = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (ß = 0.23, p = 0.01), and between subsequent presses (ß = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2nd and 3rd trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement.
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4.
  • Engdahl, Elin, et al. (author)
  • DNA methylation at GRIN2B partially mediates the association between prenatal bisphenol F exposure and cognitive functions in 7-year-old children in the SELMA study
  • 2021
  • In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 156
  • Journal article (peer-reviewed)abstract
    • Background: Accumulating evidence suggests that prenatal chemical exposure triggers epigenetic modifications that could influence health outcomes later in life. In this study, we investigated whether DNA methylation (DNAm) levels at the glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B) gene underlies the association between prenatal exposure to an endocrine disrupting chemical (EDC), bisphenol F (BPF), and lower cognitive functions in 7-year-old children. Methods: Data from 799 children participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) pregnancy cohort was analyzed. Prenatal BPF exposure was assessed by measuring BPF levels in maternal urine. At age 7, DNAm of three CpG sites in a regulatory region of the GRIN2B gene was analyzed from buccal swabs using bisulfite-Pyrosequencing. Cognitive functions, including full-scale IQ and four subscales, were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Associations between prenatal BPF exposure and GRIN2B DNAm, as well as between GRIN2B DNAm and cognitive functions, were determined using regression models adjusted for potential confounders. Generalized structural equation models (gSEM) were used to evaluate if GRIN2B DNAm mediates the association between prenatal BPF exposure and cognitive functions at 7 years of age. Results: Prenatal BPF exposure was positively associated with GRIN2B DNAm levels at the third CpG site (CpG3), while CpG3 methylation was inversely associated with cognitive test scores. Mediation analyses showed that CpG3 methylation exerted 6–9% of the association between BPF exposure and full-scale IQ, as well as verbal comprehension and perceptual reasoning in boys, while not significant in girls. Conclusions: This study is the first to identify locus-specific DNAm as a mediating factor underlying an epidemiological association between prenatal EDC exposure and cognitive functions in childhood. It also confirms previous findings, that GRIN2B DNAm is responsive to environmental exposures.
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5.
  • Galvan-Valencia, Oscar, et al. (author)
  • Associations of salivary aldosterone levels during pregnancy with maternal blood pressure and birth weight-for-gestational age in a Mexico City birth cohort
  • 2024
  • In: Journal of Perinatology. - : Springer Nature. - 0743-8346 .- 1476-5543. ; 44:5, s. 643-649
  • Journal article (peer-reviewed)abstract
    • ObjectiveTo determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA).MethodsWe measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels.ResultsLog-aldosterone was positively associated with diastolic BP (beta = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (beta = -0.12, 95% CI: -0.26, 0.02) and highest (beta = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (beta = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03.ConclusionHigher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.
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6.
  • Gennings, Chris, et al. (author)
  • Using Metrics of a Mixture Effect and Nutrition from an Observational Study for Consideration towards Causal Inference
  • 2022
  • In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:4
  • Journal article (peer-reviewed)abstract
    • Environmental exposures to a myriad of chemicals are associated with adverse health effects in humans, while good nutrition is associated with improved health. Single chemical in vivo and in vitro studies demonstrate causal links between the chemicals and outcomes, but such studies do not represent human exposure to environmental mixtures. One way of summarizing the effect of the joint action of chemical mixtures is through an empirically weighted index using weighted quantile sum (WQS) regression. My Nutrition Index (MNI) is a metric of overall dietary nutrition based on guideline values, including for pregnant women. Our objective is to demonstrate the use of an index as a metric for more causally linking human exposure to health outcomes using observational data. We use both a WQS index of 26 endocrine-disrupting chemicals (EDCs) and MNI using data from the SELMA pregnancy cohort to conduct causal inference using g-computation with counterfactuals for assumed either reduced prenatal EDC exposures or improved prenatal nutrition. Reducing the EDC exposure using the WQS index as a metric or improving dietary nutrition using MNI as a metric, the counterfactuals in a causal inference with one SD change indicate significant improvement in cognitive function. Evaluation of such a strategy may support decision makers for risk management of EDCs and individual choices for improving dietary nutrition.
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7.
  • Horton, Megan K., et al. (author)
  • Using the delayed spatial alternation task to assess environmentally associated changes in working memory in very young children
  • 2020
  • In: Neurotoxicology. - : Elsevier. - 0161-813X .- 1872-9711. ; 77, s. 71-79
  • Journal article (peer-reviewed)abstract
    • Background: Working memory (WM) is critical for problem solving and reasoning. Beginning in infancy, children show WM capacity increasing with age but there are few validated tests of WM in very young children. Because rapid brain development may increase susceptibility to adverse impacts of prenatal neurotoxicant exposure, such as lead, tests of WM in very young children would help to delineate onset of developmental problems and windows of susceptibility. Purpose: Our objective was to assess the feasibility of administering a Delayed Spatial Alternation Task (DSAT) to measure WM among 18- and 24-month old children enrolled in an ongoing longitudinal birth cohort study and compare DSAT performance with age and general cognitive development. We further explored whether prenatal lead exposure impacted DSAT performance. Methods: We assessed 457 mother-child pairs participating in the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) Study in Mexico City. The DSAT and Bayley Scales of Infant Development (BSID-III) were administered at 18- and 24-months. Lead was measured in maternal blood collected during pregnancy (MBPb) and in a subsample of children at 24-months (CBPb). We regressed DSAT measures on MBPb and CBPb, child sex, and maternal age, education, socioeconomic status, and household smoking. We compared DSAT performance to BSID-III performance with adjusted residuals. Results: 24-month children perform better on the DSAT than 18-month children; 24-month subjects reached a higher level on the DSAT (3.3 (0.86) vs. 2.4 (0.97), p < 0.01), and had a higher number of correct responses (20.3 vs. 17.2, p < 0.01). In all DSAT parameters, females performed better than males. Maternal education predicted better DSAT performance; household smoking predicted worse DSAT performance. A higher number of correct responses was associated with higher BSID-III Cognitive scales at 18 months (r = 0.20, p < 0.01) and 24 months (r = 0.27, p < 0.01). MBPb and CPBb did not significantly predict DSAT performance. Conclusion: Improved performance on the DSAT with increasing age, the positive correlation with the BSID-III cognitive and language scales and the correlation with common sociodemographic predictors of neurodevelopment demonstrate the validity of the DSAT as a test of infant development.
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8.
  • Iversen, Katherine R., et al. (author)
  • Decentralization and Regionalization of Surgical Care: A Review of Evidence for the Optimal Distribution of Surgical Services in Low- and Middle-Income Countries
  • 2019
  • In: International Journal of Health Policy and Management. - 2322-5939. ; 8:9, s. 521-537
  • Research review (peer-reviewed)abstract
    • Background: While recommendations for the optimal distribution of surgical services in high-income countries (HICs) exist, it is unclear how these translate to resource-limited settings. Given the significant shortage and maldistribution of surgical workforce and infrastructure in many low- and middle-income countries (LMICs), the optimal role of decentralization versus regionalization (centralization) of surgical care is unknown. The aim of this study is to review evidence around interventions aimed at redistributing surgical services in LMICs, to guide recommendations for the ideal organization of surgical services.Methods: A narrative-based literature review was conducted to answer this question. Studies published in English between 1997 and 2017 in PubMed, describing interventions to decentralize or regionalize a surgical procedure in a LMIC, were included. Procedures were selected using the Disease Control Priorities’ (DCP3) Essential Surgery Package list. Intervention themes and outcomes were analyzed using a narrative, thematic synthesis approach. Primary outcomes included mortality, complications, and patient satisfaction. Secondary outcomes included input measures: workforce and infrastructure, and process measures: facility-based care, surgical volume, and referral rates.Results: Thirty-five studies were included. Nine (33%) of the 27 studies describing decentralization showed an improvement in primary outcomes. The procedures associated with improved outcomes after decentralization included most obstetric, gynecological, and family planning services as well as some minor general surgery procedures. Out of 8 studies on regionalization (centralization), improved outcomes were shown for trauma care in one study and cataract extraction in one study.Conclusion: Interventions aimed at decentralizing obstetric care to the district hospital and health center levels have resulted in mortality benefits in several countries. However, more evidence is needed to link service distribution to patient outcomes in order to provide recommendations for the optimal organization of other surgical procedures in LMICs. Considerations for the optimal distribution of surgical procedures should include the acuity of the condition for which the procedure is indicated, anticipated case volume, and required level of technical skills, resources, and infrastructure. These attributes should be considered within the context of each country.
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9.
  • Jauregui, Alejandra, et al. (author)
  • Physical activity, sedentary time and cardiometabolic health indicators among Mexican children
  • 2020
  • In: Clinical Obesity. - : Wiley-Blackwell. - 1758-8103 .- 1758-8111. ; 10:1
  • Journal article (peer-reviewed)abstract
    • We examined the independent associations of moderate to vigorous physical activity (MVPA) and sedentary time (ST) with cardiometabolic indicators in Mexican children (4-6 years of age). We conducted a cross-sectional study (n = 400) using the measures of MVPA and ST (7-day accelerometry) and the following indicators: % body fat, waist circumference, body mass index (BMI) z-score, glycated haemoglobin, blood glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, leptin, adiponectin and resting blood pressure. We examined the independent associations of MVPA and ST with cardiometabolic indicators through confounder-adjusted and mutually adjusted (including both MVPA and ST) linear regression models. Confounder-adjusted models showed that MVPA was associated with higher BMI z-scores and lower adiponectin levels in girls and lower body fat among boys. ST was associated with higher body fat, in the full sample, and lower LDL cholesterol among boys. After mutually adjusting for MVPA and ST, MVPA (10-minute increase) remained significantly associated with BMI z-score in girls (beta = 0.187, 95% CI: 0.019, 0.356) and ST (60-minute increase) remained significantly associated with higher body fat (beta = 1.11%, 95% CI: 0.019, 2.203) among boys and higher glycated haemoglobin (beta = 0.047% points, 95% CI: 0.000, 0.094) in the full sample. In preschool-aged children, the objective measures of ST and MVPA were associated with small differences in cardiometabolic health indicators. ST was unfavourably associated with some cardiometabolic indicators even after adjusting for MVPA, and thus appeared to have a more significant role than MVPA, especially in boys. Future longitudinal studies should confirm these results.
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10.
  • Levin-Schwartz, Yuri, et al. (author)
  • Exosomal miRNAs in urine associated with children's cardiorenal parameters : A cross-sectional study
  • 2021
  • In: Epigenetics. - : Future Medicine Ltd. - 1559-2294 .- 1559-2308. ; 13:7, s. 499-512
  • Journal article (peer-reviewed)abstract
    • Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & Methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4-6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q < 0.1. Specifically, three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio and one with decreased estimated glomerular filtration rate. Conclusions: These results highlight urinary exo-miRs as early-life biomarkers of children's cardiorenal health.
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