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1.
Article in English | MEDLINE | ID: mdl-38045485

ABSTRACT

Background: Asthma is a leading cause of childhood morbidity in the U.S. and a significant public health concern. The prenatal period is a critical window during which environmental influences, including maternal occupational exposures, can shape child respiratory health. Cleaning chemicals are commonly encountered in occupational settings, yet few studies have examined the potential link between prenatal occupational exposures to cleaning chemicals and risk of childhood wheeze and asthma. Methods: We evaluated the potential influence of maternal occupational exposure to cleaning chemicals during pregnancy on pediatric asthma and wheeze at child age 4-6 years in 453 mother-child pairs from two longitudinal pregnancy cohorts, TIDES and GAPPS, part of the ECHO prenatal and early childhood pathways to health (ECHO-PATHWAYS) consortium. Maternal occupational exposure to cleaning chemicals was defined based on reported occupation and frequency of occupational use of chemicals during pregnancy. Child current wheeze and asthma outcomes were defined by parental responses to a widely-used, standardized respiratory outcomes questionnaire administered at child age 4-6 years. Multivariable Poisson regression with robust standard errors was used to estimate relative risk (RR) of asthma in models adjusted for confounding. Effect modification by child sex was assessed using product interaction terms. Results: Overall, 116 mothers (25.6%) reported occupational exposure to cleaning chemicals during pregnancy, 11.7% of children had current wheeze, and 10.2% had current asthma. We did not identify associations between prenatal exposure to cleaning chemicals and current wheeze [RRadjusted 1.03, 95% confidence interval (CI): 0.56, 1.90] or current asthma (RRadjusted 0.89, CI: 0.46, 1.74) in the overall sample. Analyses of effect modification suggested an adverse association among females for current wheeze (RR 1.82, CI: 0.76, 4.37), compared to males (RR 0.68, CI: 0.29, 1.58), though the interaction p-value was >0.05. Conclusion: We did not observe evidence of associations between maternal prenatal occupational exposure to cleaning chemicals and childhood wheeze or asthma in the multi-site ECHO-PATHWAYS consortium. We leveraged longitudinal U.S. pregnancy cohorts with rich data characterization to expand on limited and mixed literature. Ongoing research is needed to more precisely characterize maternal occupational chemical exposures and impacts on child health in larger studies.

3.
J Thorac Cardiovasc Surg ; 154(2): 572-582, 2017 08.
Article in English | MEDLINE | ID: mdl-28526502

ABSTRACT

OBJECTIVE: Patients with a borderline left ventricular hypoplasia in the hypoplastic left heart syndrome variant or an unbalanced atrioventricular canal who undergo initial single-ventricle palliation may be candidates for biventricular (BiV) conversion following left ventricle (LV) recruitment procedures. We investigated associations among preoperative parameters and postoperative outcomes in patients undergoing BiV conversion. METHODS: We performed a retrospective review of patients who underwent BiV conversion to determine variables associated with clinical outcomes. Predictor variables included cardiac diagnosis, age and weight, LV dimension, LV end diastolic volume, LV mass, preoperative LV end diastolic pressure (LVEDP), and preoperative left atrial pressure. Primary outcome was a composite of death, heart transplant, or BiV takedown. RESULTS: Of 51 patients, 11 experienced primary outcome (22%). Patients with hypoplastic left heart syndrome variant were more likely to experience primary outcome than those with an unbalanced atrioventricular canal (30% vs 6%; P = .03). Receiver operating characteristic analysis demonstrated that preoperative LVEDP had good predictive accuracy in classifying patients with and without the primary outcome (area under the curve, 0.757; 95% confidence interval, 0.594-0.919; P = .012). The Youden J-index indicated a cutoff of LVEDP ≥ 13 mm Hg as optimal for predicting the primary outcome. Multivariable Cox regression demonstrated that LVEDP ≥ 13 mm Hg (adjusted hazard ratio, 4.00; P = .037) and postoperative right ventricle pressure > 3/4 (adjusted hazard ratio, 21.75; P < .001) were significantly associated with primary outcome, independent of age, weight, and diagnosis. CONCLUSIONS: Elevated preoperative LVEDP is a risk factor for suboptimal postoperative hemodynamic parameters and adverse outcome following BiV conversion from single-ventricle palliation.


Subject(s)
Cardiac Surgical Procedures , Heart Ventricles/surgery , Hemodynamics , Hypoplastic Left Heart Syndrome/surgery , Blood Pressure , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Cardiac Surgical Procedures/mortality , Child, Preschool , Female , Heart Transplantation/statistics & numerical data , Heart Ventricles/abnormalities , Hemodynamics/physiology , Humans , Hypoplastic Left Heart Syndrome/mortality , Hypoplastic Left Heart Syndrome/physiopathology , Kaplan-Meier Estimate , Male , Retrospective Studies , Risk Factors , Treatment Outcome
4.
J Thorac Cardiovasc Surg ; 154(2): 607-615, 2017 08.
Article in English | MEDLINE | ID: mdl-28366551

ABSTRACT

OBJECTIVE: To determine the short- and intermediate-term outcomes following vascular ring division by video-assisted thoracoscopic (VATS) or thoracotomy approach. METHODS: This study is a retrospective review of patients with double aortic arch or right aortic arch with aberrant left subclavian artery and left ligamentum (RAA with LSCA/LL) who underwent division via left thoracotomy or VATS approach at a single institution. Outcome measures included operation duration (OR time), hospital length of stay (LOS), postoperative complications, and freedom from reintervention. RESULTS: A total of 200 patients underwent vascular ring division by VATS (n = 115) or thoracotomy (n = 85). Of 200 patients, 125 (56%) displayed respiratory symptoms at presentation, 29 (11%) displayed digestive tract symptoms, and 41 (32%) displayed both. Median follow-up was 2.1 years (interquartile range: 1 month to 7.1 years). Overall cohort mortality was 1 (0.5%) of 200 at 11 years after surgery. Fifteen (7.5%) experienced immediate postoperative complications. At follow-up visit within 1 month after surgery, 92 (74%) of 125 patients reported improvement in symptoms. Freedom from reintervention was 96% and 90% at 5 years and 10 years, respectively. Among patients with RAA with LSCA/LL (n = 113), VATS was associated with shorter LOS compared with thoracotomy (1.2 vs 3.4 days; P < .001), but rates of complications were not significantly different (9% vs 4%, P = .68). CONCLUSIONS: Vascular ring division by either thoracotomy or VATS can be performed with low rates of complication and need for reintervention. Compared with thoracotomy, VATS is associated with shorter operative duration and hospital LOS among patients with RAA with LSCA/LL.


Subject(s)
Thoracic Surgery, Video-Assisted , Thoracotomy , Vascular Ring/surgery , Child , Child, Preschool , Female , Humans , Infant , Length of Stay/statistics & numerical data , Male , Operative Time , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Reoperation/statistics & numerical data , Retrospective Studies , Thoracic Surgery, Video-Assisted/adverse effects , Thoracic Surgery, Video-Assisted/methods , Thoracic Surgery, Video-Assisted/mortality , Thoracotomy/adverse effects , Thoracotomy/methods , Thoracotomy/mortality , Time Factors , Vascular Ring/mortality
5.
Am J Reprod Immunol ; 73(4): 362-71, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25394884

ABSTRACT

PROBLEM: Diabetes confers an increased risk of preeclampsia, but its pathogenic role in preeclampsia is poorly understood. The objective of this study was to elucidate the effects of excess glucose on trophoblast function and whether any changes could be reversed by metformin. METHOD OF STUDY: The human first trimester trophoblast cell line (Sw.71) was treated with glucose at 5, 10, 25, and 50 mm, in the presence and absence of metformin. Trophoblast migration was quantified and supernatant cytokine, chemokine, and angiogenic factors measured. RESULTS: Increasing concentrations of glucose significantly increased trophoblast secretion of the inflammatory cytokines/chemokines: IL-1ß, IL-6, IL-8, GRO-α, RANTES, and G-CSF; significantly increased trophoblast secretion of the anti-angiogenic factors sFlt-1 and sEndoglin; and significantly decreased trophoblast migration. Excess glucose-induced trophoblast IL-1ß production was inhibited by disabling the Nalp3/ASC inflammasome. Metformin partially reduced the glucose-induced inflammatory response, but had no effect on the anti-angiogenic or antimigratory response. CONCLUSION: Excess glucose induced a pro-inflammatory, anti-angiogenic, and antimigratory state in first trimester trophoblast cells. Glucose-induced trophoblast IL-1ß secretion was mediated by the inflammasome. Glucose-induced inflammation was partially reversed by metformin. These findings demonstrate the pleiotropic effects of hyperglycaemia on the trophoblast, providing potential explanations for the strong link between diabetes and preeclampsia.


Subject(s)
Diabetes Complications/metabolism , Glucose/metabolism , Metformin/pharmacology , Pre-Eclampsia/drug therapy , Pre-Eclampsia/metabolism , Trophoblasts/drug effects , Trophoblasts/metabolism , Angiogenesis Inducing Agents/metabolism , Antigens, CD/metabolism , Carrier Proteins/metabolism , Cell Line , Cell Movement/drug effects , Chemokine CCL5/metabolism , Chemokine CXCL1/metabolism , Diabetes Complications/drug therapy , Diabetes Mellitus/metabolism , Endoglin , Female , Granulocyte Colony-Stimulating Factor/metabolism , Humans , Inflammation/drug therapy , Inflammation/metabolism , Interleukins/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Placenta/drug effects , Placenta/metabolism , Pregnancy , Pregnancy Trimester, First/drug effects , Pregnancy Trimester, First/metabolism , Receptors, Cell Surface/metabolism , Uterus/drug effects , Uterus/metabolism , Vascular Endothelial Growth Factor Receptor-1/metabolism
6.
Chest ; 143(5): 1312-1320, 2013 May.
Article in English | MEDLINE | ID: mdl-23287970

ABSTRACT

BACKGROUND: COPD and hypertension both increase the risk of congestive heart failure (CHF). Current clinical trials do not inform the selection of combination antihypertensive therapy among patients with COPD. We performed a comparative effectiveness study to investigate whether choice of dual agent antihypertensive therapy is associated with risk of hospitalization for CHF among patients with these two conditions. METHODS: We identified a cohort of 7,104 patients with COPD and hypertension receiving care within Veterans Administration hospitals between January 2001 and December 2006, with follow-up through April 2009. We included only patients prescribed two antihypertensive medications. We used Cox proportional hazard models for statistical analysis. RESULTS: Compared with ß-blockers plus an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, patients prescribed a thiazide diuretic plus a ß-blocker (adjusted hazard ratio [HR], 0.49; 95% CI, 0.32-0.75), a thiazide plus an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (adjusted HR, 0.50; 95% CI, 0.35-0.71), and a thiazide plus a calcium channel blocker (adjusted HR, 0.55; 95% CI, 0.35-0.88) had a significantly lower risk of hospitalization for CHF. After stratification by history of CHF, we found that this association was isolated to patients without a history of CHF. Adjustment for patient characteristics and comorbidities had a small effect on risk of hospitalization. Choice of antihypertensive medication combination had no significant association with risk of COPD exacerbation. CONCLUSIONS: Among patients with comorbid hypertension and COPD requiring two antihypertensive agents, combination therapy that includes a thiazide diuretic was associated with a significantly lower risk of hospitalization for CHF among patients without a history of CHF.


Subject(s)
Antihypertensive Agents/therapeutic use , Heart Failure/epidemiology , Hypertension/drug therapy , Hypertension/epidemiology , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Adrenergic beta-Antagonists/therapeutic use , Aged , Aged, 80 and over , Algorithms , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Calcium Channel Blockers/therapeutic use , Cohort Studies , Comorbidity , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Hypertension/complications , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Retrospective Studies , Risk Factors , Sodium Chloride Symporter Inhibitors/therapeutic use , Treatment Outcome
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