Renal-related adverse effects of intravenous contrast media in computed tomography

PubMed Central

Leow, Kheng Song; Wu, Yi Wei; Tan, Cher Heng

2015-01-01

Renal-related adverse effects of intravascular contrast media (CM) include contrast-induced nephropathy in computed tomography and angiography. While large retrospective studies have been published, the exact pathogenesis of this condition is still unknown. We review the main international guidelines, including the American College of Radiology white paper and the guidelines of European Society of Urogenital Radiology, Royal College of Radiologists and Canadian Association of Radiologists, as well as their references, regarding this subject. We present a simplified, concise approach to renal-related adverse effects of CM, taking into consideration the basis for each recommendation in these published guidelines. This will allow the reader to better understand the rationale behind appropriate patient preparation for cross-sectional imaging. PMID:25917468

Early plasma exchange improves outcome in PR3-ANCA-positive renal vasculitis.

PubMed

Gregersen, Jon W; Kristensen, Tilde; Krag, Søren R P; Birn, Henrik; Ivarsen, Per

2012-01-01

Plasma exchange (PE) has been shown to improve renal outcome in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and severe renal failure; however the effect of PE in AAV with moderate renal impairment is controversial. A single-centre, retrospective one-year follow-up study, including patients with renal AAV and eGFR <60 ml/min/1.73 m2. Since 2007, all patients with renal AAV and eGFR <60 ml/min/1.73 m2 had PE in addition to induction therapy with cyclophosphamide and prednisolone. Patients admitted from 1999 to 2007 that did not receive PE served as controls. The primary outcome was the combination of death, end-stage renal disease, and relapses after one year. A significant reduction in the primary endpoint was observed following the addition of PE (25% vs. 43%, p=0.04). Furthermore, a greater improvement in renal function after one year was observed among surviving PE treated patients not on dialysis (ΔeGFR 36.1 vs. 19.7 ml/min, p=0.03). There was a significant reduction in serious adverse events in the PE treated group (4% vs. 30%, p=0.02) despite no differences in types and doses of induction immunosuppressive therapy. The advantageous effect of PE was related to the presence of anti-proteinase3 (PR3)-antibodies and also evident among patients with plasma creatinine less than 500 μM. This study suggests the use of PE in addition to standard induction treatment with cyclophosphamide and glucocorticoids to patients with renal PR3-AAV and an estimated-GFR <60 ml/min/1.73m2.

Concealed renal failure and adverse drug reactions in older patients with type 2 diabetes mellitus.

PubMed

Corsonello, Andrea; Pedone, Claudio; Corica, Francesco; Mazzei, Bruno; Di Iorio, Angelo; Carbonin, Pierugo; Incalzi, Raffaele Antonelli

2005-09-01

In elderly patients serum creatinine may be normal despite decreased glomerular filtration rate (GFR). The aim of this study was to evaluate the prevalence of this "concealed" renal failure, i.e., renal failure with normal serum creatinine levels, in elderly diabetic patients, and to verify whether it is a risk factor for adverse drug reactions (ADR) to hydrosoluble drugs. We used data on 2257 hospitalized patients with type 2 diabetes mellitus enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. On the basis of serum creatinine and calculated GFR, patients were grouped as follows: normal renal function (normal serum creatinine levels and normal GFR), concealed (normal serum creatinine levels and reduced GFR), or overt (increased creatinine levels and reduced GFR) renal failure. GFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The outcome of the study was the incidence of ADR to hydrosoluble drugs during the hospital stay. The relationship between renal function and ADR was evaluated using Cox regression analysis including potential confounders. Concealed renal failure was observed in 363 (16.1%) of patients studied. Patients with concealed or overt renal failure were older, had more frequently cognitive impairment and polypharmacy, and had lower serum albumin levels than did those with normal renal function. Both concealed (hazard ratio = 1.90; 95% confidence interval, 1.04-3.48; p =.036) and overt (hazard ratio = 2.23; 95% confidence interval, 1.40-3.55; p =.001) renal failure were significantly associated with ADR to hydrosoluble drugs. The use of more than four drugs also qualified as an independent risk factor for ADRs to hydrosoluble drugs during hospital stay. Older diabetic patients should be systematically screened to ascertain the presence of concealed renal failure in an attempt to optimize the pharmacological treatment and reduce the risk of ADRs.

Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies.

PubMed

Hung, Szu-Chun; Lai, Yi-Shin; Kuo, Ko-Lin; Tarng, Der-Cherng

2015-05-05

Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease (CKD). However, the relationship between volume overload and adverse outcomes in CKD is not fully understood. A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end-stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD. We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high-salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor-α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes. Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Late renal transplant failure: an adverse prognostic factor at initiation of peritoneal dialysis.

PubMed

Sasal, J; Naimark, D; Klassen, J; Shea, J; Bargman, J M

2001-01-01

Early renal transplant failure necessitating a return to dialysis has been shown to be a poor prognostic factor for survival. Little is known about the outcome of patients with late transplant failure returning to dialysis. It was our clinical impression that late transplant failure (>2 months) carries an increased morbidity and mortality risk in patients returning to dialysis. To determine whether patients with a failed renal transplant have an outcome different to those on dialysis who have never received a kidney transplant. Peritoneal dialysis (PD) unit in a teaching hospital. All failed renal transplant patients (fTx) in the Toronto Hospital Peritoneal Dialysis program between 1989 and 1996 were identified. This cohort of 42 fTx patients was compared with a cohort of randomly selected never-transplanted PD patients (non-Tx). The PD program was selected because of the availability of well-documented patient archival material. The non-Tx group was matched for age and presence of diabetes. Data were collected until retransplantation, change of dialysis modality or center, death, or until June 1998. There was no difference at initiation of PD between groups in serum albumin, residual renal function, or mean serum parathyroid hormone level. The mean low-density lipoprotein level was significantly higher in the fTx cohort. The duration of dialysis before Tx in fTx patients accounted for the increased total length of dialysis in fTx (mean 15 months). However, post-Tx the duration of PD was similar for both groups (30.7 months for fTx vs 31.6 months for non-Tx). The fTx group had a considerably worse outcome than the non-Tx group. The time to first peritonitis, subsequent episodes of peritonitis, catheter change, or transfer to hemodialysis occurred at a much faster rate in fTx patients. The most dramatic difference was in survival. There were 3 deaths in the non-Tx group and 12 in the fTx group (p < 0.01). The mean age at time of death in the fTx group was 47.5 years

Outcomes of ultrasound guided renal mass biopsies.

PubMed

Sutherland, Edward L; Choromanska, Agnieszka; Al-Katib, Sayf; Coffey, Mary

2018-06-01

The purpose of this study was to evaluate the rate of nondiagnostic ultrasound-guided renal mass biopsies (RMBs) at our institution and to determine what patient, procedural, and focal renal mass (FRM) factors were associated with nondiagnostic ultrasound-guided RMBs. Eighty-two ultrasound-guided renal mass biopsies performed between January 2014 and October 2016 were included in our study. Biopsy outcomes (diagnostic vs. nondiagnostic) and patient, procedural, and FRM characteristics were retrospectively reviewed and recorded. Univariate statistical analyses were performed to identify biopsy characteristics that were indicative of nondiagnostic biopsy. Ultrasound-guided RMBs were diagnostic in 70 out of 82 cases (85%) and non-diagnostic in 12 cases (15%). Among the diagnostic biopsies, 54 (77%) were malignant cases, 94% of which were renal cell carcinoma (RCC). Of the 12 nondiagnostic cases, the final diagnosis was RCC in 4 cases and angiomyolipoma in one case; seven of the nondiagnostic cases were lost to follow-up. A weak association (p = 0.04) was found between the number of needle passes and the biopsy outcome. None of the remaining collected RMB characteristics showed a significant correlation with a diagnostic or nondiagnostic RMB. Six patients (7%) experienced complications. Ultrasound-guided renal mass biopsy is a safe and effective method for the diagnosis of renal masses with a low rate of nondiagnostic outcomes. A nondiagnostic biopsy should not be treated as a surrogate for a diagnosis since a significant number of patients with nondiagnostic biopsies have subsequently been shown to have renal malignancies. Repeat biopsy should be considered in such cases.

Adverse outcome pathways: a concise introduction for toxicologists

PubMed Central

Vergauwen, Lucia; Hengstler, Jan G.; Angrish, Michelle; Whelan, Maurice

2018-01-01

Adverse outcome pathways are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use adverse outcome pathways, have been published in the last few years. The present paper provides a synopsis of the main principles related to the adverse outcome pathway framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology. PMID:28660287

Impact of cardio-renal syndrome on adverse outcomes in patients with Fabry disease in a long-term follow-up.

PubMed

Siegenthaler, M; Huynh-Do, U; Krayenbuehl, P; Pollock, E; Widmer, U; Debaix, H; Olinger, E; Frank, M; Namdar, M; Ruschitzka, F; Nowak, A

2017-12-15

Fabry disease (FD) is a rare X-linked lysosomal storage disease with a deficiency of α-galactosidase A leading to progressive sphingolipid accumulation in different organs, among them heart and kidney. We evaluated the impact of cardio-renal syndrome (CRS) on the incidence of major cardiovascular complications and death in a prospective FD cohort. A total of 104 genetically proven FD patients were annually followed at the University Hospitals Zurich and Bern. The main outcome was a composite of incident renal replacement therapy (RRT), hospitalisation due to decompensated Heart Failure, new onset atrial fibrillation, pacemaker/ICD implantation, stroke/TIA and death. Estimated glomerular filtration rate (eGFR) and left ventricular myocardial mass index (LVMMI) where explored as the primary exposure variables. During the median follow-up of 103 [59-155] months, events occurred in 27 patients. In a Cox regression analysis, both higher LVMMI and lower eGFR were independently associated with a greater risk of developing adverse events after adjustment for multiple confounders (HR 1.67 [1.04-2.73] P=0.03 per SD increase in LVMMI, HR 0.45 [0.25-0.83], P=0.01 per SD decrease in eGFR). In patients with CRS, the risk to develop events was significantly increased if adjusted for demographics and RRT (HR 4.46 [1.07-18.62], P=0.04), approaching significance if additionally adjusted for hypertension (HR 4.05 [0.95-17.29], P=0.06). In Kaplan-Meier-Analysis, the poorest event-free survival was observed among patients with CRS. CRS was associated with a high risk to develop cardiovascular complications and death, emphasizing the importance of its prevention and early recognition. A focus on cardio-reno-protective therapies is crucial. Copyright © 2017 Elsevier B.V. All rights reserved.

Strategic approaches to adverse outcome pathway development

EPA Science Inventory

Adverse outcome pathways (AOPs) are conceptual frameworks for organizing biological and toxicological knowledge in a manner that supports extrapolation of data pertaining to the initiation or early progression of toxicity to an apical adverse outcome that occurs at a level of org...

The Complement System and Adverse Pregnancy Outcomes

PubMed Central

Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

2015-01-01

Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study.

PubMed

Imai, E; Chan, J C N; Ito, S; Yamasaki, T; Kobayashi, F; Haneda, M; Makino, H

2011-12-01

The renal and cardiovascular protective effects of angiotensin receptor blocker (ARB) remain controversial in type 2 diabetic patients treated with a contemporary regimen including an angiotensin converting enzyme inhibitor (ACEI). We examined the effects of olmesartan, an ARB, on primary composite outcome of doubling of serum creatinine, endstage renal disease and death in type 2 diabetic patients with overt nephropathy. Secondary outcome included composite cardiovascular outcomes, changes in renal function and proteinuria. Randomisation and allocation to trial group were carried out by a central computer system. Participants, caregivers, the people carrying out examinations and people assessing the outcomes were blinded to group assignment. Five hundred and seventy-seven (377 Japanese, 200 Chinese) patients treated with antihypertensive therapy (73.5% [n = 424] received concomitant ACEI), were given either once-daily olmesartan (10-40 mg) (n = 288) or placebo (n = 289) over 3.2 ± 0.6 years (mean±SD). In the olmesartan group, 116 developed the primary outcome (41.1%) compared with 129 (45.4%) in the placebo group (HR 0.97, 95% CI 0.75, 1.24; p = 0.791). Olmesartan significantly decreased blood pressure, proteinuria and rate of change of reciprocal serum creatinine. Cardiovascular death was higher in the olmesartan group than the placebo group (ten vs three cases), whereas major adverse cardiovascular events (cardiovascular death plus non-fatal stroke and myocardial infarction) and all-cause death were similar between the two groups (major adverse cardiovascular events 18 vs 21 cases, all-cause deaths; 19 vs 20 cases). Hyperkalaemia was more frequent in the olmesartan group than the placebo group (9.2% vs 5.3%). Olmesartan was well tolerated but did not improve renal outcome on top of ACEI. ClinicalTrials.gov NCT00141453.

Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

PubMed

Ng, Chau Yee; Yeh, Yu-Ting; Wang, Chuang-Wei; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Ya-Ching; Chang, Wan-Chun; Lin, Yu-Jr; Chang, Chee-Jen; Su, Shih-Chi; Fan, Wen-Lang; Chen, Der-Yuan; Wu, Yeong-Jian Jan; Tian, Ya-Chung; Hui, Rosaline Chung-Yee; Chung, Wen-Hung

2016-07-01

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using

Gastroschisis: antenatal sonographic predictors of adverse neonatal outcome.

PubMed

Page, Rachael; Ferraro, Zachary Michael; Moretti, Felipe; Fung, Karen Fung Kee

2014-01-01

The aim of this review was to identify clinically significant ultrasound predictors of adverse neonatal outcome in fetal gastroschisis. A quasi-systematic review was conducted in PubMed and Ovid using the key terms "gastroschisis," "predictors," "outcome," and "ultrasound." A total of 18 papers were included. The most common sonographic predictors were intra-abdominal bowel dilatation (IABD), intrauterine growth restriction (IUGR), and bowel dilatation not otherwise specified (NOS). Three ultrasound markers were consistently found to be statistically insignificant with respect to predicting adverse outcome including abdominal circumference, stomach herniation and dilatation, and extra-abdominal bowel dilatation (EABD). Gastroschisis is associated with several comorbidities, yet there is much discrepancy in the literature regarding which specific ultrasound markers best predict adverse neonatal outcomes. Future research should include prospective trials with larger sample sizes and use well-defined and consistent definitions of the adverse outcomes investigated with consideration given to IABD.

Putative adverse outcome pathways relevant to neurotoxicity

PubMed Central

Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

2016-01-01

The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

1991 Gulf War exposures and adverse birth outcomes.

PubMed

Arnetz, Bengt; Drutchas, Alexis; Sokol, Robert; Kruger, Michael; Jamil, Hikmet

2013-01-01

We studied 1991 Gulf War (GW)-related environmental exposures and adverse birth outcomes in Iraqis. A random cross-sectional sample of 307 Iraqi families that immigrated to the United States responded to a structured interview covering socioeconomics, lifestyle, environmental exposures, and birth outcome. Data per each family was collected either from the man or the woman in the respective family. The respondents were divided into those that resided in Iraq during and following the GW (post-GW, n=185) and those that had left before (pre-GW, n=122). The primary outcome was lifetime prevalence of adverse birth outcomes, ie, congenital anomalies, stillbirth, low birth weight, and preterm delivery and its relationship to GW exposures. Mean number of adverse birth outcomes increased from 3.43 (SD=2.11) in the pre-GW to 4.63 (SD=2.63) in the post-GW group (P<.001). Mean chemical (Ch) and nonchemical (NCh) environmental exposure scores increased from pre-GW scores of 0.38 units (SD=1.76) and 0.43 (SD=1.86), respectively, to post-GW scores of 5.65 units (SD=6.23) and 7.26 (SD=5.67), P<.001 between groups for both exposures. There was a significant dose-response relationship between Ch environmental exposure (P=.001), but not NCh exposure, and number of adverse birth outcomes. Exposure to burning oil pits and mustard gas increased the risks for specific adverse birth outcomes by 2 to 4 times. Results indicate that Gulf War Ch, but not NCh exposures are related to adverse birth outcomes. Pregnancies in women with a history of war exposures might benefit from more intensive observation.

Developing and applying the adverse outcome pathway ...

EPA Pesticide Factsheets

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis to predict effects for structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed.A variety of cellular and molecular processes are known to be critical to normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of principles of the description and assessment of MOA and AOPs, examples of adverse out

Pregnancy in women with renal disease. Yes or no?

PubMed Central

Edipidis, K

2011-01-01

Women with renal disease who conceive and continue pregnancy, are at significant risk for adverse maternal and fetal outcomes. Although advances in antenatal and neonatal care continue to improve these outcomes, the risks remain proportionate to the degree of underlying renal dysfunction. The aim of this article, is to examine the impact of varying degrees of renal insufficiency on pregnancy outcome, in women with chronic renal disease and to provide if possible, useful conclusions whether and when, a woman with Chronic Kidney Disease (CKD), should decide to get pregnant. This article, reviews briefly the normal physiological changes of renal function during pregnancy, and make an attempt to clarify the nature and severity of the risks, in the settings of chronic renal insufficiency and end stage renal disease, including dialysis patients and transplant recipients. PMID:21897751

Panniculectomy Outcomes in Patients with End-Stage Renal Disease in Preparation for Renal Transplant.

PubMed

Mundra, Leela S; Rubio, Gustavo A; AlQattan, Husain T; Thaller, Seth R

2018-06-01

End-stage renal disease (ESRD) is associated with increased cardiovascular risk factors, electrolyte imbalances, and iron deficiency anemia. These factors may increase the risk of adverse outcomes in patients undergoing panniculectomy. There is a paucity of data regarding outcomes in patients with ESRD undergoing panniculectomy. The purpose of this study is to investigate whether ESRD is associated with increased rate of complications following a panniculectomy. The Nationwide Inpatient Sample database (2006-2011) was used to identify patients who underwent a panniculectomy. Among this cohort, patients diagnosed with end-stage renal disease were identified. Patients excluded from the study were emergency admissions, pregnant women, patients less than 18 years old, and patients with concurrent nephrectomy or kidney transplants. Demographic factors, comorbidities, and postoperative complications were evaluated. Chi-squared and risk-adjusted multivariate logistic regression analyses were performed to determine whether end-stage renal disease was associated with increased rate of postoperative complications. A total of 34,779 panniculectomies were performed during the study period. Of these, 613 (1.8%) were diagnosed with ESRD. Patients with ESRD were older (mean age 58.9 vs. 49.3, p < 0.01) and more likely to have Medicare (63.5 vs. 18.4%, p < 0.01). They had higher rates of comorbidities, including diabetes, hypertension, congestive heart failure, chronic lung disease, chronic anemia, liver disease, peripheral artery disease, obesity, and coagulopathies (p < 0.01). The procedure was more likely to occur at a large, teaching hospital (p < 0.01). Postoperatively, patients with ESRD had a higher rate of death (3.3 vs. 0.2%, p < 0.01), wound complications (10.6 vs. 6.2%, p < 0.01), venous thromboembolism (4.9 vs. 0.8%, p < 0.01), blood transfusions (25.3% vs. 7.0%, p < 0.01), non-renal major medical complications (40.0% vs. 8.4%), and longer hospital

Intimate Partner Violence, PTSD, and Adverse Health Outcomes

ERIC Educational Resources Information Center

Dutton, Mary Ann; Green, Bonnie L.; Kaltman, Stacey I.; Roesch, Darren M.; Zeffiro, Thomas A.; Krause, Elizabeth D.

2006-01-01

The high prevalence of adverse health outcomes related to intimate partner violence (IPV) is well documented. Yet we know little about the pathways that lead to adverse health outcomes. Research concerning the psychological, biological, neurological, behavioral, and physiological alterations following exposure to IPV--many of which are associated…

Significant Adverse Events and Outcomes After Medical Abortion

PubMed Central

Cleland, Kelly; Creinin, Mitchell D.; Nucatola, Deborah; Nshom, Montsine; Trussell, James

2013-01-01

Objective To analyze rates of significant adverse events and outcomes in women having a medical abortion at Planned Parenthood health centers in 2009 and 2010, and to identify changes in the rates of adverse events and outcomes between the 2 years. Methods In this database review we analyzed data from Planned Parenthood affiliates that provided medical abortion in 2009 and 2010, almost exclusively using an evidence-based buccal misoprostol regimen. We evaluated the incidence of six clinically significant adverse events (hospital admission, blood transfusion, emergency room treatment, intravenous antibiotics administration, infection, and death) and two significant outcomes (ongoing pregnancy and ectopic pregnancy diagnosed after medical abortion treatment was initiated). We calculated an overall rate as well as rates for each event and identified changes between the 2 years. Results Amongst 233,805 medical abortions provided in 2009 and 2010, significant adverse events or outcomes were reported in 1,530 cases (0.65%). There was no statistically significant difference in overall rates between years. The most common significant outcome was ongoing intrauterine pregnancy (0.50%); significant adverse events occurred in 0.16% of cases. One patient death occurred due to an undiagnosed ectopic pregnancy. Only rates for emergency room treatment and blood transfusion differed by year, and were slightly higher in 2010. Conclusion Review of this large dataset reinforces the safety of the evidence-based medical abortion regimen. PMID:23262942

Risks of Adverse Events in Advanced CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Grams, Morgan E; Yang, Wei; Rebholz, Casey M; Wang, Xue; Porter, Anna C; Inker, Lesley A; Horwitz, Edward; Sondheimer, James H; Hamm, L Lee; He, Jiang; Weir, Matthew R; Jaar, Bernard G; Shafi, Tariq; Appel, Lawrence J; Hsu, Chi-Yuan

2017-09-01

People with advanced chronic kidney disease are at risk for the development of end-stage renal disease (ESRD), but also many other adverse outcomes, including cardiovascular disease (CVD) events and death. Determination of risk factors that explain the variability in prognosis and timing of these adverse outcomes can aid patient counseling and medical decision making. Prospective research cohort. 1,798 participants with estimated glomerular filtration rates (eGFRs)<30mL/min/1.73m 2 in the CRIC Study were followed up for a median of 5.5 years. Age, race, sex, eGFR, proteinuria, diabetes mellitus, body mass index, ejection fraction, systolic blood pressure, history of CVD, and smoking history. ESRD, CVD (congestive heart failure, stroke, myocardial infarction, and peripheral artery disease), and death. Baseline age of the cohort was 60 years, 46% were women, and 46% were African American. Although 52.3% of participants progressed to ESRD during follow-up, the path by which this occurred was variable. For example, predicted 1-year probabilities for a hypothetical 60-year-old white woman with eGFR of 30mL/min/1.73m 2 , urine protein excretion of 1.8g/d, and no diabetes or CVD (risk characteristics similar to the average participant) were 3.3%, 4.1%, and 0.3%, for first developing CVD, ESRD, and death, respectively. For a 40-year-old African American man with similar characteristics but higher systolic blood pressure, the corresponding 1-year probabilities were 2.4%, 13.2%, and 0.1%. For all participants, the development of ESRD or CVD increased the risk for subsequent mortality, with no differences by patient race or body mass index. The CRIC population was specifically recruited for kidney disease, and the vast majority had seen a nephrologist. The prognosis and timing of adverse outcomes in chronic kidney disease vary by patient characteristics. These results may help guide the development of personalized approaches for managing patients with advanced CKD. Copyright

Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens.

PubMed

Nkhoma, Ella T; Rosenblatt, Lisa; Myers, Joel; Villasis-Keever, Angelina; Coumbis, John

2016-01-01

Tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs). This cohort study used US health insurance data spanning the years 2008-2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF). Renal adverse outcomes were identified using renal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Bone adverse outcomes were identified using ICD-9-CM diagnosis codes for fracture. Incidence rates (IRs) and associated 95% confidence intervals (CIs) were estimated assuming a Poisson distribution, and outcomes between STRs were compared using IR ratios (IRRs) and IR differences (IRDs). We identified 9876 and 10,383 eligible patients for the renal and fracture analyses, respectively. Observed IRs for renal adverse outcomes were 9.7, 10.5, 13.6, and 18.0 per 1000 person-years among those receiving EFV/FTC/TDF, RPV/FTC/TDF, or EVG/COBI/FTC/TDF, or all HIV patients, respectively. Corresponding values for IRs of fracture were 3.4, 3.6, 7.2, and 4.4 per 1000 person-years, respectively. Renal adverse outcomes with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRD -3.96; 95% CI: -7.31, -1.06). No IRR differences were identified for the renal analysis. Fractures with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRR 0.47; 95% CI: 0.27, 0.81 and IRD -3.85; 95% CI: -5.02, -2.78). In this large real-world database, observed IRs for renal adverse outcomes with TDF-containing STRs were lower

Computational Approaches for Identifying Adverse Outcome Pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) provide a framework for organizing toxicity information to improve predictions of the potential adverse impact of environment stressors on humans or wildlife populations, but these benefits are currently limited by the small number of AOPs currentl...

Adverse Outcome Pathways – Tailoring Development to Support Use

EPA Science Inventory

Adverse Outcome Pathways (AOPs) represent an ideal framework for connecting high-throughput screening (HTS) data and other toxicity testing results to adverse outcomes of regulatory importance. The AOP Knowledgebase (AOP-KB) captures AOP information to facilitate the development,...

Adverse outcome pathway (AOP) development I: Strategies and principles

EPA Science Inventory

An adverse outcome pathway (AOP) is a conceptual framework that organizes existing knowledge concerning biologically plausible, and empirically-supported, links between molecular-level perturbation of a biological system and an adverse outcome at a level of biological organizatio...

Adverse Outcome Pathway (AOP) Network Development for Fatty Liver

EPA Science Inventory

Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk re...

Vitamin D and renal outcome: the fourth outcome of CKD-MBD? Oshima Award Address 2015.

PubMed

Hamano, Takayuki

2018-04-01

Bone fracture, cardiovascular events, and mortality are three outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD), and the umbrella concept originally described for dialysis patients. The reported association of serum phosphorus or fibroblast growth factor 23 (FGF23) levels with renal outcome suggests that the fourth relevant outcome of CKD-MBD in predialysis patients is renal outcome. We found that proteinuria of 2+ or greater with a dipstick test was associated with low vitamin D status due to urinary loss of 25-hydroxyvitamin D (25D). Moreover, active vitamin D or its analogues decrease proteinuria. Given our finding that maxacalcitol does not repress renin, the reduction of proteinuria by this agent is likely due to direct upregulation of the nephrin and podocin in podocytes. Moreover, this agent downregulates the mesenchymal marker desmin in podocytes and blocks transforming growth factor-beta autoinduction, leading to attenuation of renal fibrosis in a unilateral ureteral obstructive (UUO) model. These facts are reminiscent of the suppression of epithelial-mesenchymal transition (EMT) by vitamin D. EMT blockage may explain our finding that vitamin D prescription in renal transplant recipients is associated with a lower incidence of cancer. We also reported that low vitamin D status and high FGF23 levels predict a worse renal outcome. However, administration of massive doses of 25D exacerbates renal fibrosis in UUO kidneys in 1alpha-hydroxylase knockout mice. Moreover, FGF23 inhibits 1alpha-hydroxylase in proximal tubules and monocytes. Taken together, local 1,25(OH) 2 D in the kidney tissue but not 25D seems to protect the kidney.

Can MR Measurement of Renal Artery Flow and Renal Volume Predict the Outcome of Percutaneous Transluminal Renal Angioplasty?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Binkert, Christoph A.; Debatin, Jorg F.; Schneider, Ernst

2001-07-15

Purpose: Predicting therapeutic benefit from percutaneous transluminal renal angioplasty (PTRA) in patients with renal artery stenosis (RAS) remains difficult. This study investigates whether magnetic resonance (MR)-based renal artery flow measurements relative to renal parenchymal volume can predict clinical outcome following PTRA.Methods: The data on 23 patients (13 men, 10 women; age range 47-82 years, mean age 64 years) were analyzed. The indication for treatment was hypertension (n = 18) or renal insufficiency (n = 5). Thirty-four cases of RAS were identified: bilateral disease was manifest in 11 and unilateral disease in 12 patients. The MR imaging protocol included a breath-hold,more » cardiac-gated cine phase-contrast sequence for renal flow measurement and a fast multiplanar spoiled gradient-echo sequence for renal volume measurement. MR measurements were performed on the day prior to and the day following PTRA. Clinical success was defined as (a) a reduction in diastolic blood pressure > 15% or (b) a reduction in serum creatinine > 20%. Kidneys were categorized as normal volume or low volume. A renal flow index (RFI) was calculated by dividing the renal flow (ml/min) by the renal volume (cm{sup 3}).Results: Clinical success was observed in 11 patients. Twelve patients did not benefit from angioplasty. Normal kidney volume was seen in 10 of 11 responders and in 8 of 12 nonresponders, resulting in a sensitivity of 91%, specificity of 33%, a positive predictive value (PPV) of 56% and a negative predictive value (NPV) of 80%. A RFI below a threshold of 1.5 ml/min/cm{sup 3} predicted successful outcome with 100% sensitivity, 33% specificity, 58% PPV, and 100% NPV. The combination of normal renal volume and a RFI below 1.5 ml/min/cm{sup 3} identified PTRA responders with a sensitivity of 91%, a specificity of 67%, a PPV of 71%, and a NPV of 89%. PTRA resulted in a greater increase in renal flow in responders compared with nonresponders (p < 0.001).Conclusion

High truncated-O-glycan score predicts adverse clinical outcome in patients with localized clear-cell renal cell carcinoma after surgery.

PubMed

NguyenHoang, SonTung; Liu, Yidong; Xu, Le; Zhou, Lin; Chang, Yuan; Fu, Qiang; Liu, Zheng; Lin, Zongming; Xu, Jiejie

2017-10-03

Truncated O-glycans, including Tn-antigen, sTn-antigen, T-antigen, sT-antigen, are incomplete glycosylated structures and their expression occur frequently in tumor tissue. The study aims to evaluate the abundance of each truncated O-glycans and its clinical significance in postoperative patients with localized clear-cell renal cell carcinoma (ccRCC). We used immunohistochemical testing to analyze the expression of truncated O-glycans in tumor specimens from 401 patients with localized ccRCC. Truncated-O-glycan score was built by integrating the expression level of Tn-, sTn- and sT-antigen. Kaplan-Meier survival and Cox regression analysis were done to compare clinical outcomes in subgroups. Receiver operating characteristic (ROC) was applied to assess the impact of prognostic factors on overall survival (OS) and recurrence-free survival (RFS). The results identified Tn-, sTn-, sT-antigen as independent prognosticators. The OS and RFS were shortened among the 198 (49.4%) patients with high Truncated-O-glycan score than among the 203 (50.6%) patients with low score (hazard ratio for OS, 7.060; 95% confidence interval [CI]: 2.765 to 18.027; p <0.001; for RFS, 4.612; 95% CI: 2.141 to 9.931; p <0.001). There is no difference between low-risk patients and high-risk patients in low score group ( p = 0.987). High-risk patients with low score showed a better prognosis than low-risk patient with high score ( p = 0.029). The Truncated-O-glycan score showed better prognostic value for OS (AUC: 0.739, p = 0.003) and RFS (AUC: 0.719, p = 0.003) than TNM stage. In summary, the high Truncated-O-glycan score could predict adverse clinical outcome in localized ccRCC patients after surgery.

Smoking and Adverse Maternal and Child Health Outcomes in Brazil

PubMed Central

2013-01-01

Introduction: Numerous studies from high-income countries document the causal relationship between cigarette smoking during pregnancy and adverse maternal and child health (MCH) outcomes. Less research has been conducted in low and middle income countries, but a burgeoning literature can be found for Brazil. Methods: We review Brazilian studies of the prevalence of maternal smoking, the relative risk of smoking-attributable adverse MCH outcomes, and present new estimates for these outcomes, using the attributable fraction method. Results: We found that Brazilian studies of the relative risks of smoking-attributable adverse MCH outcomes were broadly consistent with previous reviews. Based on a comparison of maternal smoking over time, smoking during pregnancy has declined by about 50% over the last 20 years in Brazil. For 2008, we estimate that 5,352 cases of spontaneous abortion, 10,929 cases of preterm birth, 20,717 cases of low birth weight, and 29 cases of sudden infant death syndrome are attributable to maternal smoking. Between 1989 and 2008, the percent of smoking-attributable adverse MCH outcomes in Brazil was at least halved. Conclusions: The results show that over a 20-year period, during which Brazil implemented numerous effective tobacco control measures, the country experienced a dramatic decrease in both maternal smoking prevalence and smoking-attributable adverse MCH outcomes. Countries that implement effective tobacco control measures can expect to reduce both maternal smoking and adverse MCH outcomes, thereby improving the public health. PMID:23873977

Cardiovascular Disease Outcomes Related to Early Stage Renal Impairment Following Liver Transplantation.

PubMed

VanWagner, Lisa B; Montag, Samantha; Zhao, Lihui; Allen, Norrina B; Lloyd-Jones, Donald M; Das, Arighno; Skaro, Anton I; Hohmann, Samuel; Friedewald, John J; Levitsky, Josh

2018-03-20

In the general population, even mild renal disease is associated with increased cardiovascular (CV) complications. Whether this is true in liver transplant recipients (LTR) is unknown. This was a retrospective cohort study of 671 LTR (2002-2012) from a large urban tertiary care center and 37,322 LTR using Vizient hospitalization data linked to the United Network for Organ Sharing. The MDRD4 equation estimated GFR (eGFR). Outcomes were 1-year CV complications (death/hospitalization from myocardial infarction, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism or stroke) and mortality. Latent mixture modeling identified trajectories in eGFR in the first LT year in the 671 patients. Mean(SD) eGFR was 72.1(45.7) ml/min/1.73m. Six distinct eGFR trajectories were identified in the local cohort (n=671): qualitatively Normal-Slow Decrease (4% of cohort), Normal-Rapid Decrease (4%), Mild-Stable (18%), Mild-Slow Decrease (35%), Moderate-Stable (30%), and Severe-Stable (9%). In multivariable analyses adjusted for confounders and baseline eGFR, the greatest odds of 1-year CV complications were in the Normal-Rapid Decrease group (OR, 95% CI: 10.6, 3.0-36.9). Among the national cohort, each 5-unit lower eGFR at LT was associated with a 2% and 5% higher hazard of all-cause and CV-mortality, respectively (p<0.0001) independent of multiple confounders. Even mild renal disease at the time of LT is a risk factor for posttransplant all-cause and CV mortality. More rapid declines in eGFR soon after LT correlate with risk of adverse CV outcomes, highlighting the need to study whether early renal preservation interventions also reduce CV complications.

Outcome of renal transplantation with and without intra-operative diuretics.

PubMed

Hanif, F; Macrae, A N; Littlejohn, M G; Clancy, M J; Murio, E

2011-01-01

This paper presents an e-survey of current clinical practice of use of intra-operative diuretics during renal transplantation in the United Kingdom and a study to compare outcome of renal transplants carried out with or without intra-operative diuretics in our centre. An e-mail questionnaire to renal transplant surgeons exploring their practice of renal transplantation with or without intra-operative diuretics, the type of a diuretic/s if used and the relevant doses. An observational study comparing the outcome of renal transplant recipients, group no-diuretics (GND, n = 80) carried out from 2004 to 2008 versus group diuretics (GD n = 69) renal transplant recipients who received intra-operative diuretics over a one year period is presented. Outcome measures were incidence of delayed graft function and a comparison of graft survival in both groups. Forty surgeons answered from 18 transplant centres with a response rate of 67%. 13 surgeons do not use diuretics. Mannitol is used by 10/40, Furosemide 6/40 and 11 surgeons use a combination of both. In comparative study there was no significant overall difference in one year graft survival of GD versus GND (N = 65/69, 94% and 75/80, 94% respectively, p = 0.08) and the incidence of delayed graft function was also comparable (16/69, 23% and 21/80, 26% respectively, p = 0.07). The donor characteristics in both groups were comparable. The study showed variation in clinical practice on the use of intra-operative diuretics in renal transplantation and it did not demonstrate that the use of diuretics can improve renal graft survival. Copyright © 2011 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Authentic leadership and nurse-assessed adverse patient outcomes.

PubMed

Wong, Carol A; Giallonardo, Lisa M

2013-07-01

Our purpose was to test a model examining relationships among authentic leadership, nurses' trust in their manager, areas of work life and nurse-assessed adverse patient outcomes. Although several work environment factors have been cited as critical to patient outcomes, studies linking nursing leadership styles with patient outcomes are limited suggesting the need for additional research to investigate the mechanisms by which leadership may influence patient outcomes. Secondary analysis of data collected in a cross-sectional survey of 280 (48% response rate) registered nurses working in acute care hospitals in Ontario was conducted using structural equation modelling. The final model fit the data acceptably (χ(2) = 1.30, df = 2, P = 0.52, IFI = 0.99, CFI = 1.00, RMSEA = 0.00). Authentic leadership was significantly associated with decreased adverse patient outcomes through trust in the manager and areas of work life. The findings suggest that nurses who see their managers as demonstrating high levels of authentic leadership report increased trust, greater congruence in the areas of work life and lower frequencies of adverse patient outcomes. Managers who emphasize transparency, balanced processing, self-awareness and high ethical standards in their interactions with nurses may contribute to safer work environments for patients and nurses. © 2013 John Wiley & Sons Ltd.

Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity

EPA Science Inventory

Constructing, Quantifying, and Validating an Adverse Outcome Pathway for Vascular Developmental Toxicity The adverse outcome pathway (AOP) for embryonic vascular disruption1 leading to a range of adverse prenatal outcomes was recently entered into the AOP wiki and accepted as par...

Detection of Asymptomatic Renal Calcifications in Astronauts Using a Novel Ultrasound Protocol

NASA Technical Reports Server (NTRS)

Garcia, Kathleen; Sargsyan, Ashot; Reyes, David; Locke, James

2017-01-01

Ultrasound (US) specifically looking for asymptomatic renal calcifications that may be renal stones is typically not done in the terrestrial setting. Standard abdominal US without a renal focus may discover incidental, mineralized renal material (MRM); however punctate solid areas of MRM is less than 3 mm are usually considered subclinical. Detecting these early calcifications before they become symptomatic renal stones is critical to prevent adverse medical and mission outcomes during spaceflight.

Accelerating Adverse Outcome Pathway (AOP) development via computationally predicted AOP networks

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. Ho...

Adverse Outcome Pathway Network Analyses: Techniques and benchmarking the AOPwiki

EPA Science Inventory

Abstract: As the community of toxicological researchers, risk assessors, and risk managers adopt the adverse outcome pathway (AOP) paradigm for organizing toxicological knowledge, the number and diversity of adverse outcome pathways and AOP networks are continuing to grow. This ...

An “ADME Module” in the Adverse Outcome Pathway Knowledgebase

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework has generated intense interest for its utility to organize knowledge on the toxicity mechanisms, starting from a molecular initiating event (MIE) to an adverse outcome across various levels of biological organization. While the AOP fra...

Adverse Outcome Pathways: From Research to Regulation - Scientific Workshop Report

EPA Science Inventory

An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify...

Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology

EPA Science Inventory

A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course p...

Adverse psychological outcomes following colposcopy and related procedures: a systematic review.

PubMed

O'Connor, M; Gallagher, P; Waller, J; Martin, C M; O'Leary, J J; Sharp, L

2016-01-01

Although colposcopy is the leading follow-up option for women with abnormal cervical cytology, little is known about its psychological consequences. We performed a systematic review to examine: (1) what, if any, are the adverse psychological outcomes following colposcopy and related procedures; (2) what are the predictors of adverse psychological outcomes post-colposcopy; and (3) what happens to these outcomes over time. Five electronic databases (PubMed, PsychINFO, CINAHL, Web of Science, Scopus) were searched for studies published in English between January 1986 and February 2014. Eligible studies assessed psychological wellbeing at one or more time-points post-colposcopy. Two reviewers independently screened titles and abstracts. Full texts of potentially eligible papers were reviewed. Data were abstracted from, and a quality appraisal performed of, eligible papers. Twenty-three papers reporting 16 studies were eligible. Colposcopy and related procedures can lead to adverse psychological outcomes, particularly anxiety. Ten studies investigated predictors of adverse psychological outcomes; management type and treatment had no impact on this. Seven studies investigated temporal trends in psychological outcomes post-colposcopy; findings were mixed, especially in relation to anxiety and distress. Studies were methodologically heterogeneous. Follow-up investigations and procedures for abnormal cervical cytology can cause adverse psychological outcomes among women. However, little is known about the predictors of these outcomes or how long they persist. There is a need for a more standardised approach to the examination of the psychological impact of colposcopy, especially longer-term outcomes. Follow-up investigations for abnormal cervical cytology can cause adverse psychological outcome among women. © 2015 Royal College of Obstetricians and Gynaecologists.

Adverse Outcome Pathway (AOP) Network Development for ...

EPA Pesticide Factsheets

Adverse outcome pathways (AOPs) are descriptive biological sequences that start from a molecular initiating event (MIE) and end with an adverse health outcome. AOPs provide biological context for high throughput chemical testing and further prioritize environmental health risk research. According to the Organization for Economic Co-operation and Development guidelines, AOPs are pathways with one MIE anchored to an adverse outcome (AO) by key events (KEs) and key event relationships (KERs). However, this approach does not always capture the cumulative impacts of multiple MIEs on the AO. For example, hepatic lipid flux due to chemical-induced toxicity initiates from multiple ligand-activated receptors and signaling pathways that cascade across biology to converge upon a common fatty liver (FL, also known as steatosis) outcome. To capture this complexity, a top-down strategy was used to develop a FL AOP network (AOPnet). Literature was queried based on the terms steatosis, fatty liver, cirrhosis, and hepatocellular carcinoma. Search results were analyzed for physiological and pathophysiological organ level, cellular and molecular processes, as well as pathway intermediates, to identify potential KEs and MIEs that are key for hepatic lipid metabolism, maintenance, and dysregulation. The analysis identified four apical KE nodes (hepatic fatty acid uptake, de novo fatty acid and lipid synthesis, fatty acid oxidation, and lipid efflux) juxtaposed to the FL AO. The apic

Developing and applying adverse outcome pathways: What you need to know

EPA Science Inventory

Adverse outcome pathways (AOPs) are a conceptual framework for organizing existing information concerning the predictive linkages between the initiation or early progression of a biological perturbation in an organism and the adverse outcome(s) of regulatory relevance (e.g., impa...

Adverse pregnancy outcomes following syphilis treatment in pregnancy in the UK.

PubMed

Wallace, Harriet E; Isitt, Catherine E; Broomhall, Harriet M; Perry, Alison E; Wilson, Janet D

2016-10-01

Syphilis infection in pregnancy is known to cause a number of severe adverse pregnancy outcomes, including second-trimester miscarriage, stillbirth, very pre-term delivery and neonatal death, in addition to congenital syphilis. A retrospective review of women with positive syphilis serology and a pregnancy outcome between 2005 and 2012 in Leeds, UK, was performed. In all, 57 cases of positive syphilis serology in pregnancy were identified: 24 with untreated syphilis treated in the current pregnancy (Group 1); seven with reported but unconfirmed prior treatment who were retreated (Group 2); and 26 adequately treated prior to pregnancy (Group 3). The rate of severe adverse pregnancy outcomes in Group 1 at 21% was significantly higher than the 0% outcome of Group 3 (p = 0.02). The severe adverse pregnancy outcomes were two second-trimester miscarriages, two pre-term births at 25 and 28 weeks and one stillbirth at 32 weeks. There were no cases of term congenital syphilis or term neonatal death, but we observed high rates of other adverse pregnancy outcomes despite treatment during pregnancy. Rapid referral for treatment is needed before 18 weeks in order to minimise adverse pregnancy outcomes. © The Author(s) 2016.

Recurrent Urinary Tract Infection Among Renal Transplant Recipients: Risk Factors and Long-Term Outcome.

PubMed

Tawab, Khaled Abdel; Gheith, Osama; Al Otaibi, Torki; Nampoory, Naryanam; Mansour, Hany; Halim, Medhat A; Nair, Prasad; Said, Tarek; Abdelmonem, Mohamed; El-Sayed, Ayman; Awadain, Waleed

2017-04-01

Urinary tract infection is the most common type of bacterial infection in kidney transplant procedures, with adverse effects on graft and patient survival. We aimed to evaluate the risk factors of recurrent urinary tract infection in renal transplant recipients and its impact on patient and graft survival. In a cohort of 1019 patients who were transplanted between 2000 and 2010 at Hamed Al-Essa Organ Transplant Center in Kuwait, 86% developed at least 1 episode of urinary tract infection, with only 6.2% of patients having recurrent infections. We compared patients with recurrent urinary tract infections (group 1) with those who had no recurrence (group 2) regarding their risk factors. Patients in group 1 were significantly younger than those in group 2 (34.9 ± 23 vs 42.8 ± 16 y; P < .001), with female preponderance (P < .001). The percentage of patients with thymoglobulin induction (21.5%) was significantly higher in group 1. Patients with pretransplant urologic problems experienced significantly more recurrent urinary tract infections (P < .001). Hepatitis C infections were significantly more prevalent among group 1 (10.8% vs 3.8%; P = .008). Long-term graft outcome (functioning and failed) were 78.5% and 21.5% in group 1 versus 85.1% and 13.9% in group 2 (P = .18). Patient outcomes (living and deceased donors) were 98.4% and 1.6% in group 1 versus 95.7% and 4.3% in group 2 (P = .187). Adult females, thymoglobulin induction, pretransplant urologic problems, and hepatitis C infection were the risk factors of recurrent urinary tract infection among our renal transplant patients. However, recurrence did not adversely affect graft or patient survival.

Nurse Practitioner Care Improves Renal Outcome in Patients with CKD

PubMed Central

van Zuilen, Arjan D.; van den Brand, Jan A.J.G.; Bots, Michiel L.; van Buren, Marjolijn; ten Dam, Marc A.G.J.; Kaasjager, Karin A.H.; Ligtenberg, Gerry; Sijpkens, Yvo W.J.; Sluiter, Henk E.; van de Ven, Peter J.G.; Vervoort, Gerald; Vleming, Louis-Jean; Blankestijn, Peter J.; Wetzels, Jack F.M.

2014-01-01

Treatment goals for patients with CKD are often unrealized for many reasons, but support by nurse practitioners may improve risk factor levels in these patients. Here, we analyzed renal endpoints of the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study after extended follow-up to determine whether strict implementation of current CKD guidelines through the aid of nurse practitioners improves renal outcome. In total, 788 patients with moderate to severe CKD were randomized to receive nurse practitioner support added to physician care (intervention group) or physician care alone (control group). Median follow-up was 5.7 years. Renal outcome was a secondary endpoint of the MASTERPLAN study. We used a composite renal endpoint of death, ESRD, and 50% increase in serum creatinine. Event rates were compared with adjustment for baseline serum creatinine concentration and changes in estimated GFR were determined. During the randomized phase, there were small but significant differences between the groups in BP, proteinuria, LDL cholesterol, and use of aspirin, statins, active vitamin D, and antihypertensive medications, in favor of the intervention group. The intervention reduced the incidence of the composite renal endpoint by 20% (hazard ratio, 0.80; 95% confidence interval, 0.66 to 0.98; P=0.03). In the intervention group, the decrease in estimated GFR was 0.45 ml/min per 1.73 m2 per year less than in the control group (P=0.01). In conclusion, additional support by nurse practitioners attenuated the decline of kidney function and improved renal outcome in patients with CKD. PMID:24158983

Novel therapies in advanced renal cell carcinoma: management of adverse events from sorafenib and sunitinib.

PubMed

Ivanyi, Philipp; Winkler, Thomas; Ganser, Arnold; Reuter, Christoph; Grünwald, Viktor

2008-03-01

Sorafenib and Sunitinib are the first tyrosine kinase inhibitors licensed for the treatment of advanced renal cell carcinoma. In contrast to conventional chemotherapy, targeted therapies have distinct and specific side effects. Selective review in Medline and the data base of the American Society of Clinical Oncology on the treatment and side effects of tyrosine kinase inhibitors in renal cell carcinoma, drawing on the authors' own experience. Tyrosine kinase inhibitors are characterized by a variety of uncommon side effects, such as lassitude, mucosal inflammation and skin changes. The detection and treatment of adverse events are critical for interdisciplinary cancer treatment in order to ensure patients' safety. This article offers an overview of the unwanted effects of drug therapy in the management of renal cell carcinoma.

Systematic review of pediatric health outcomes associated with childhood adversity.

PubMed

Oh, Debora Lee; Jerman, Petra; Silvério Marques, Sara; Koita, Kadiatou; Purewal Boparai, Sukhdip Kaur; Burke Harris, Nadine; Bucci, Monica

2018-02-23

Early detection of and intervention in childhood adversity has powerful potential to improve the health and well-being of children. A systematic review was conducted to better understand the pediatric health outcomes associated with childhood adversity. PubMed, PsycArticles, and CINAHL were searched for relevant articles. Longitudinal studies examining various adverse childhood experiences and biological health outcomes occurring prior to age 20 were selected. Mental and behavioral health outcomes were excluded, as were physical health outcomes that were a direct result of adversity (i.e. abusive head trauma). Data were extracted and risk of bias was assessed by 2 independent reviewers. After identifying 15940 records, 35 studies were included in this review. Selected studies indicated that exposure to childhood adversity was associated with delays in cognitive development, asthma, infection, somatic complaints, and sleep disruption. Studies on household dysfunction reported an effect on weight during early childhood, and studies on maltreatment reported an effect on weight during adolescence. Maternal mental health issues were associated with elevated cortisol levels, and maltreatment was associated with blunted cortisol levels in childhood. Furthermore, exposure to childhood adversity was associated with alterations of immune and inflammatory response and stress-related accelerated telomere erosion. Childhood adversity affects brain development and multiple body systems, and the physiologic manifestations can be detectable in childhood. A history of childhood adversity should be considered in the differential diagnosis of developmental delay, asthma, recurrent infections requiring hospitalization, somatic complaints, and sleep disruption. The variability in children's response to adversity suggests complex underlying mechanisms and poses a challenge in the development of uniform diagnostic guidelines. More large longitudinal studies are needed to better

.Network analytics for adverse outcome pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) organize toxicological knowledge from the molecular level up to the population level, providing evidence-based causal linkages at each step. The AOPWiki serves as a repository of AOPs. With the international adoption of the AOP framework, the AOPw...

The adverse outcome pathway knowledge base

EPA Science Inventory

The rapid advancement of the Adverse Outcome Pathway (AOP) framework has been paralleled by the development of tools to store, analyse, and explore AOPs. The AOP Knowledge Base (AOP-KB) project has brought three independently developed platforms (Effectopedia, AOP-Wiki, and AOP-X...

Adverse Outcome Pathways: From Research to Regulation ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) organizes existing knowledge on chemical mode of action, starting with a molecular initiating event such as receptor binding, continuing through key events, and ending with an adverse outcome such as reproductive impairment. AOPs can help identify knowledge gaps where more research is needed to understand the underlying mechanisms, aid in chemical hazard characterization, and guide the development of new testing approaches that use fewer or no animals. A September 2014 workshop co-sponsored by NICEATM and PCRM considered how the AOP concept could improve regulatory assessments of chemical toxicity. Scientists from 21 countries, representing industry, academia, regulatory agencies, and special interest groups, attended the workshop, titled Adverse Outcome Pathways: From Research to Regulation. Workshop plenary presentations were followed by breakout sessions that considered regulatory acceptance of AOPs and AOP-based tools, criteria for building confidence in an AOP for regulatory use, and requirements to build quantitative AOPs and AOP networks. Discussions during the closing session emphasized a need to increase transparent and inclusive collaboration, especially with disciplines outside of toxicology. Additionally, to increase impact, working groups should be established to systematically prioritize and develop AOPs. Multiple collaborative projects and follow-up activities resulted from the workshop. This manuscript provides a

Applying Aggregate Exposure Pathway and Adverse Outcome ...

EPA Pesticide Factsheets

Hazard assessment for nanomaterials often involves applying in vitro dose-response data to estimate potential health risks that arise from exposure to products that contain nanomaterials. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biological mechanisms that lead to apical adverse health outcomes in living organisms. The Adverse Outcome Pathway (AOP) framework addresses this uncertainty by acting as a scaffold onto which in vitro toxicity testing and other data can be arranged to aid in the interpretation of these results in terms of biologically-relevant responses, as an AOP connects an upstream molecular initiating event (MIE) to a downstream adverse outcome. In addition to hazard assessment, risk estimation also requires reconciling in vitro concentrations sufficient to produce bioactivity with in vivo concentrations that can trigger a MIE at the relevant biological target. Such target site exposures (TSEs) can be estimated by integrating pharmacokinetic considerations with environmental and exposure factors. Environmental and exposure data have been historically scattered in various resources, such as monitoring data for air pollutants or exposure models for specific chemicals. The Aggregate Exposure Pathway (AEP) framework is introduced to organize existing knowledge concerning biologically, chemically, and physically plausible, as well as empirically supported, links between the i

The Adverse Survival Implications of Bland Thrombus in Renal Cell Carcinoma With Venous Tumor Thrombus.

PubMed

Hutchinson, Ryan; Rew, Charles; Chen, Gong; Woldu, Solomon; Krabbe, Laura-Maria; Meissner, Matthew; Sheth, Kunj; Singla, Nirmish; Shakir, Nabeel; Master, Viraj A; Karam, Jose A; Matin, Surena F; Borregales, Leonardo D; Wood, Christopher; Masterson, Timothy; Thompson, R Houston; Boorjian, Stephen A; Leibovich, Bradley C; Abel, E Jason; Bagrodia, Aditya; Margulis, Vitaly

2018-05-01

To characterize the presence of bland (nontumor) thrombus in advanced renal cell carcinoma and assess the impact of this finding on cancer-specific survival. A multi-institutional database of patients treated with nephrectomy with caval thrombectomy for locally-advanced renal tumors was assembled from 5 tertiary care medical centers. Using clinicopathologic variables including patient age, body mass index, Eastern Cooperative Oncology Group performance status, tumor stage, grade, nodal status and histology, and nearest-neighbor and multiple-matching propensity score matched cohorts of bland thrombus vs nonbland thrombus patients were assessed. Multivariable analysis for predictors of cancer-specific survival was performed. From an initial cohort of 579 patients, 446 met inclusion criteria (174 with bland thrombus, 272 without). At baseline, patients with bland thrombus had significantly worse performance status, higher tumor stage, higher prevalence of regional nodal metastases and higher nuclear grade (P < .01 for all). In both nearest-neighbor and multiple-matching propensity score matched cohorts, the presence of bland thrombus presence was associated with inferior median cancer-specific survival (28.1 months vs 156.8 months, and 28.1 months vs 76.7 months, P < .001 for both). The presence of bland thrombus remained independently associated with an increased risk of cancer-specific mortality on multivariable analysis (hazard ratio 4.33, 95% confidence interval 2.79-6.73, P < .001). Presence of bland thrombus is associated with adverse survival outcomes in patients treated surgically for renal tumors with venous tumor thrombus. These findings may have important implications in patient counseling, selection for surgery and inclusion in clinical trials. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of a labor and delivery safety bundle on a modified adverse outcomes index.

PubMed

Tolcher, Mary Catherine; Torbenson, Vanessa E; Weaver, Amy L; McGree, Michaela E; El-Nashar, Sherif A; Nesbitt, Katharine M; Gostout, Bobbie S; Famuyide, Abimbola O

2016-03-01

The Obstetrics Adverse Outcomes Index was designed to measure the quality of perinatal care and includes 10 adverse events that may occur at or around the time of delivery. We hypothesized that adverse outcomes in the labor and delivery suite, including hypoxic ischemic encephalopathy, could be decreased with a combination of interventions, even among high-risk pregnancies. The objective of the study was to evaluate the impact of a labor and delivery care bundle on adverse obstetrics outcomes as measured by a modified Obstetrics Adverse Outcomes Index, Weighted Adverse Outcomes Index, and Severity Index. This is a retrospective cohort study including all women who delivered at our academic, tertiary care institution over a 3 year period of time, before and after the implementation of an intervention to decrease adverse outcomes. Outcome measures consisted of previously reported indices that were modified including the addition of hypoxic ischemic encephalopathy. The adverse outcomes index is a percentage of deliveries with 1 or more adverse events, the weighted adverse outcomes index is the sum of the points assigned to cases with adverse outcomes divided by the number of deliveries, and the severity index is the sum of the adverse outcome scores divided by the number of deliveries with an identified adverse outcome. A segmented regression analysis was utilized to evaluate the differences in the level and trend of each index before and after our intervention using calendar month as the unit of analysis. During the study period, 5826 deliveries met inclusion criteria. Comparing the pre- and postintervention periods, high-risk pregnancy was more common in the postintervention period (73.5% vs 79.4%, P < .001). Overall, there was a decrease in both the Modified Weighted Adverse Outcomes Index (P = .0497) and the Modified Severity Index (P = 0.01) comparing the pre- and postintervention periods; there was no difference in the Modified Adverse Outcomes Index (P = .43

Early Dialysis and Adverse Outcomes After Hurricane Sandy.

PubMed

Lurie, Nicole; Finne, Kristen; Worrall, Chris; Jauregui, Maria; Thaweethai, Tanayott; Margolis, Gregg; Kelman, Jeffrey

2015-09-01

Hemodialysis patients have historically experienced diminished access to care and increased adverse outcomes after natural disasters. Although "early dialysis" in advance of a storm is promoted as a best practice, evidence for its effectiveness as a protective measure is lacking. Building on prior work, we examined the relationship between the receipt of dialysis ahead of schedule before the storm (also known as early dialysis) and adverse outcomes of patients with end-stage renal disease in the areas most affected by Hurricane Sandy. Retrospective cohort analysis, using claims data from the Centers for Medicare & Medicaid Services Datalink Project. Patients receiving long-term hemodialysis in New York City and the state of New Jersey, the areas most affected by Hurricane Sandy. Receipt of early dialysis compared to their usual treatment pattern in the week prior to the storm. Emergency department (ED) visits, hospitalizations, and 30-day mortality following the storm. Of 13,836 study patients, 8,256 (60%) received early dialysis. In unadjusted logistic regression models, patients who received early dialysis were found to have lower odds of ED visits (OR, 0.75; 95% CI, 0.63-0.89; P=0.001) and hospitalizations (OR, 0.77; 95% CI, 0.65-0.92; P=0.004) in the week of the storm and similar odds of 30-day mortality (OR, 0.80; 95% CI, 0.58-1.09; P=0.2). In adjusted multivariable logistic regression models, receipt of early dialysis was associated with lower odds of ED visits (OR, 0.80; 95% CI, 0.67-0.96; P=0.01) and hospitalizations (OR, 0.79; 95% CI, 0.66-0.94; P=0.01) in the week of the storm and 30-day mortality (OR, 0.72; 95% CI, 0.52-0.997; P=0.048). Inability to determine which patients were offered early dialysis and declined and whether important unmeasured patient characteristics are associated with receipt of early dialysis. Patients who received early dialysis had significantly lower odds of having an ED visit and hospitalization in the week of the storm and of

Comparison of cystatin C and creatinine to determine the incidence of composite adverse outcomes in HIV-infected individuals.

PubMed

Yanagisawa, Naoki; Sasaki, Shugo; Suganuma, Akihiko; Imamura, Akifumi; Ajisawa, Atsushi; Ando, Minoru

2015-02-01

Cystatin C is an overall biomarker of pathophysiologic abnormalities that accompany chronic kidney disease (CKD). The utility of cystatin C is not fully understood in an HIV-infected population. This prospective study investigated 661 HIV-infected individuals for 4 years to determine the incidence of adverse outcomes, including all-cause mortality, cardiovascular disease, and renal dysfunction. The risk of developing the outcomes was discriminated with a 4 color-coded classification in a 3 × 6 contingency table, that combined 3 grades of dipstick proteinuria with 6 grades of estimated glomerular filtration rate (eGFR) calculated using either serum creatinine (eGFRcr) or cystatin C (eGFRcy): green, low risk; yellow, moderately increased risk; orange, high risk; and red, very high risk. The cumulative incidence of the outcomes was assessed by the Kaplan-Meier method, and the association between color-coded risk and the time to outcome was evaluated using multivariate proportional hazards analysis. Compared with eGFRcr, the use of eGFRcy reduced the prevalence of risk ≥ orange by 0.8%. The adverse outcomes were significantly more likely to occur to the patients with baseline risk category ≥orange than those with ≤ yellow, independent of risk categories based on eGFRcr or eGFRcy. However, in multivariate analysis, risk category ≥orange with eGFRcy-based classification was significantly associated with adverse outcomes, but not the one with eGFRcr. Replacing creatinine by cystatin C in the CKD color-coded risk classification may be appropriate to discriminate HIV-infected patients at increased risk of a poor prognosis. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant.

PubMed

Leem, Jong-Han; Chung, Kyu Hyuck

2016-01-01

According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs' victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD.

Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant

PubMed Central

2017-01-01

According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD. PMID:28111421

NURSE STAFFING AND RENAL ANAEMIA OUTCOMES IN HAEMODIALYSIS CARE.

PubMed

Erlingmark, Julia; Hedström, Mariann; Lindberg, Magnus

2016-09-01

Current trends in renal anaemia management place greater emphasis, and thus increased workload, on the role of the nurse in haemodialysis settings. However, there is little evidence that demonstrates the relationship between nurse staffing and patient outcomes. To describe nurse staffing in haemodialysis settings, its relationship with target levels of renal anaemia management and to describe target level achievement for different ways of organising anaemia management. Cross-sectional audit. Forty (out of 78) haemodialysis centres in Sweden reported quality assurance data. The numbers of bedside registered nurses, licensed nurse assistants and patients undergoing haemodialysis during a predefined morning shift; type of anaemia management and achieved target levels of anaemia management. The mean patient:registered nurse ratio was 2.4 and the mean patient:nurse assistant ratio was 12.8. There were no significant relationships between registered nurse staffing and target level achievement. On average, 45.6% of the patients had haemoglobin within the target levels at centres applying nurse-driven anaemia management, compared with 47.3% at physician-driven centres. These cross-sectional data suggest that renal anaemia outcomes are unrelated to the patient:registered nurse ratio. There is, however, room for improvement in renal anaemia management in the units included in this study, particularly the achievement of target levels of haemoglobin and transferrin saturation. © 2016 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Laparoscopic partial nephrectomy for hilar tumors: oncologic and renal functional outcomes.

PubMed

George, Arvin K; Herati, Amin S; Rais-Bahrami, Soroush; Waingankar, Nikhil; Kavoussi, Louis R

2014-01-01

To present our experience with laparoscopic partial nephrectomy (LPN) for hilar tumors and evaluate intermediate oncologic and renal functional outcomes. A retrospective review of LPN cases performed in 488 patients was performed. Hilar lesions were defined as renal cortical tumors in direct physical contact with the renal artery, vein, or both, as identified on preoperative imaging and confirmed intraoperatively. The clinicopathologic parameters, perioperative course, complications, and oncologic and 6-month renal functional outcomes were analyzed. A total of 488 patients underwent LPN, of which 43 were hilar. The mean tumor size for hilar and nonhilar tumors was 3.6 cm and 3.1 cm, respectively. The mean operative time was shorter for hilar as compared with nonhilar tumors (129.1 minutes vs 141.8 minutes). Mean estimated blood loss was greater in LPN for hilar tumors (311.65 mL vs 298.4 mL). There were no statistically significant differences noted in any of the perioperative parameters investigated despite a higher nephrometry complexity score in the hilar group. Change in estimated glomerular filtration rate at 6 months showed a decrease of 10.9 mL/min and 8.8 mL/min for hilar and nonhilar tumors, respectively (P = NS). There was 1 recurrence detected in the hilar group, with a median follow-up of 41.6 months. In the hands of an experienced laparoscopist, LPN can safely be performed for hilar tumors, with preservation of perioperative outcomes and durable renal functional and oncologic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

[Severe Adverse Pregnancy Outcomes in Placenta Previa and Prior Cesarean Delivery].

PubMed

Zhou, Mi; Chen, Meng; Zhang, Li; He, Guo-Lin; He, Lei; Wei, Qiang; Li, Tao; Liu, Xing-Hui

2017-09-01

To investigate the severe adverse pregnancy outcomes in pregnancies with placenta previa and prior cesarean delivery and its risk factors. This retrospective casecontrol study reviewed all pregnancies with placenta previa and prior cesarean delivery delivered by repeat cesarean section in our institution between January 2005 and June 2015,and investigated the incidence of severe adverse pregnancy outcome. A composite of severe adverse pregnancy outcomes (including transfusion of 10 units or more red blood cells,maternal ICU admission,unanticipated injuries,repeat operation,hysterectomy,and maternal death) and other maternal and neonatal outcomes were described. Univariate and multivariable logistic regression analysis were used to quantify the effects of risk factors on severe adverse pregnancy outcomes. There were 478 women with placenta previa and prior cesarean delivery in our hospital over the last decade. The average age of them was 32.5±4.8 years old,most women were beyond 30 years old,the average gravidity and parity were 4 and 1,131 cases (27.4%) had severe adverse pregnancy outcomes. Transfusion of 10 units or more red blood cells happened in 75 cases (15.7%,75/478); 44 cases (9.2%,44/478) necessitated maternal ICU admission; unanticipated bladder injury occurred in 11 cases,but non ureter or bowel injury happened; All 4 repeat operations were due to delayed hemorrhage after conservative management during cesarean delivery,and an emergent hysterectomy was performed for all of the 4 cases. Hysterectomy (107 cases,22.4%) was the most common severe adverse pregnancy outcome. Among all 311 morbidly adherent placenta cases finally confirmed by pathological or surgical findings or both,only 172 (55.3%) were suspected before delivery. Multivariable logistic regression analysis showed that the risk of severe adverse pregnancy outcomes was significantly increased by pernicious placenta previa (i.e. anterior placenta overlying the prior cesarean scar),suspicion of

Perioperative renal outcome in cardiac surgical patients with preoperative renal dysfunction: aprotinin versus epsilon aminocaproic acid.

PubMed

Maslow, Andrew D; Chaudrey, Alyas; Bert, Arthur; Schwartz, Carl; Singh, Arun

2008-02-01

patients were significantly older (75.2 v 70.2 years, p < 0.05), had lower left ventricular ejection fraction (44.4% v 49.2%, p < 0.05), a greater preoperative history of congestive heart failure (63 v 44%, p < 0.05), a greater renal risk score (5.8 v 4.9, p < 0.05), and underwent more nonisolated coronary artery bypass graft surgeries (77% v 29%, p < 0.0001). CPB time (126.0 v 96.5 minutes, p < 0.001) and AoXCl duration (100.9 v 78.0 minutes, p < 0.005) were longer in the aprotinin group. Diabetes (60.5% v 41.5%, p < 0.05) and hypertension (90.1% v 73.2%, p < 0.05) were more prevalent in the EACA group. Baseline renal function and renal outcomes were not significantly different between the aprotinin and EACA groups. Six of the 7 patients who required HD received EACA (p = 0.1). The earliest SCr recorded > or =3 months after surgery was significantly lower in the aprotinin group compared with the EACA group (1.8 v 2.2 mg/dL, p < 0.05). Acute perioperative renal dysfunction was associated with worse patient outcome and longer CPB and AoXCl times. Demographic and surgical variables indicated that the sicker patients undergoing more complex surgeries were more likely to be treated with aprotinin. Although aprotinin patients had a higher renal risk score, the administration of aprotinin did not negatively impact renal outcome.

Factors associated with adverse clinical outcomes among obstetric trainees

PubMed Central

Aiken PhD, Catherine E.; Aiken, Abigail; Park, Hannah; Brockelsby, Jeremy C.; Prentice, Andrew

2016-01-01

Objective To determine whether UK obstetric trainees transitioning from directly to indirectly-supervised practice have a higher likelihood of adverse patient outcomes from operative deliveries compared to other indirectly supervised trainees and to examine whether performing more procedures under direct supervision is associated with fewer adverse outcomes in initial indirect practice. Methods We examined all deliveries (13,861) conducted by obstetricians at a single centre over 5 years (2008-2013). Mixed-effects logistic regression models were used to compare estimated blood loss, maternal trauma, umbilical arterial pH, delayed neonatal respiration, failed instrumental delivery, and critical incidents for trainees in their first indirectly-supervised year with trainees in all other years of indirect practice. Outcomes for trainees in their first indirectly-supervised 3 months were compared to their outcomes for the remainder of the year. Linear regression was used to examine the relationship between number of procedures performed under direct supervision and initial outcomes under indirect supervision. Results Trainees in their first indirectly-supervised year had a higher likelihood of >2 litres estimated blood loss at any delivery (OR 1.32;CI(1.01-1.64) p<0.05) and of failed instrumental delivery (OR 2.33;CI(1.37-3.29) p<0.05) compared with other indirectly-supervised trainees. Other measured outcomes showed no significant differences. Within the first three months of indirect supervision, the likelihood of operative vaginal deliveries with >1litre estimated blood loss (OR 2.54;CI(1.88-3.20) p<0.05) was higher compared to the remainder of the first year. Performing more deliveries under direct supervision prior to beginning indirectly-supervised training was associated with decreased risk of >1litre estimated blood loss (p<0.05). Conclusions Obstetric trainees in their first year of indirectly-supervised practice have a higher likelihood of immediate adverse

[Long-term outcomes of children treated with continuous renal replacement therapy].

PubMed

Almarza, S; Bialobrzeska, K; Casellas, M M; Santiago, M J; López-Herce, J; Toledo, B; Carrillo, Á

2015-12-01

The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

EPA Science Inventory

INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences, including racial residential segr...

A Quantative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population Dynamics

EPA Science Inventory

A Quantitative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population DynamicsAn adverse outcome pathway (AOP) is a qualitative description linking a molecular initiating event (MIE) with measureable key events leading to an adverse outcome (AO). ...

A new pathological scoring system by the Japanese classification to predict renal outcome in diabetic nephropathy.

PubMed

Hoshino, Junichi; Furuichi, Kengo; Yamanouchi, Masayuki; Mise, Koki; Sekine, Akinari; Kawada, Masahiro; Sumida, Keiichi; Hiramatsu, Rikako; Hasegawa, Eiko; Hayami, Noriko; Suwabe, Tatsuya; Sawa, Naoki; Hara, Shigeko; Fujii, Takeshi; Ohashi, Kenichi; Kitagawa, Kiyoki; Toyama, Tadashi; Shimizu, Miho; Takaichi, Kenmei; Ubara, Yoshifumi; Wada, Takashi

2018-01-01

The impact of the newly proposed pathological classification by the Japan Renal Pathology Society (JRPS) on renal outcome is unclear. So we evaluated that impact and created a new pathological scoring to predict outcome using this classification. A multicenter cohort of 493 biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The association between each pathological factor-Tervaert' and JRPS classifications-and renal outcome (dialysis initiation or 50% eGFR decline) was estimated by adjusted Cox regression. The overall pathological risk score (J-score) was calculated, whereupon its predictive ability for 10-year risk of renal outcome was evaluated. The J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3, presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were, respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were, respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2, and 3 were 5, 5, and 4 (J-score range, 0-19). Renal survival curves, when dividing into four J-score grades (0-5, 6-10, 11-15, and 16-19), were significantly different from each other (p<0.01, log-rank test). After adjusting clinical factors, the J-score was a significant predictor of renal outcome. Ability to predict 10-year renal outcome was improved when the J-score was added to the basic model: c-statistics from 0.661 to 0.685; category-free net reclassification improvement, 0.154 (-0.040, 0.349, p = 0.12); and integrated discrimination improvement, 0.015 (0.003, 0.028, p = 0.02). Mesangiolysis, polar vasculosis, and doubling of GBM-features of the JRPS system-were significantly associated with renal outcome. Prediction of DN patients' renal outcome was better with the J-score than without it.

Adverse pregnancy outcomes in women with nausea and vomiting of pregnancy.

PubMed

Temming, Lorene; Franco, Albert; Istwan, Niki; Rhea, Debbie; Desch, Cheryl; Stanziano, Gary; Joy, Saju

2014-01-01

To examine the influence of nausea and vomiting of pregnancy (NVP) on pregnancy outcomes. Outcomes were compared for primigravidas with a current singleton gestation enrolled at <20 weeks' gestation in a maternity risk screening and education program (n = 81 486). Patient-reported maternal characteristics and pregnancy outcomes were compared for women with and without NVP and within the NVP group for those with and without poor weight gain. 6.4% of women reported NVP as a pregnancy complication. Women reporting NVP were more likely to be younger, obese, single and smoke. They had higher rates of preterm delivery, pregnancy-induced hypertension and low birth weight <2500 g. Almost one-quarter of women with NVP had lower than recommended weight gain. Poor weight gain was associated with a higher incidence of adverse outcomes. Obesity, tobacco use and poor pregnancy weight gain independently increased the odds of an adverse outcome. NVP and subsequent poor weight gain may be associated with adverse pregnancy outcomes.

Adverse Outcome Pathways: From Definition to Application

EPA Science Inventory

A challenge for both human health and ecological toxicologists is the transparent application of mechanistic (e.g., molecular, biochemical, histological) data to risk assessments. The adverse outcome pathway (AOP) is a conceptual framework designed to meet this need. Specifical...

Adverse Outcomes after Major Surgery in Patients with Pressure Ulcer: A Nationwide Population-Based Retrospective Cohort Study

PubMed Central

Chou, Chia-Lun; Lee, Woan-Ruoh; Yeh, Chun-Chieh; Shih, Chun-Chuan

2015-01-01

Background Postoperative adverse outcomes in patients with pressure ulcer are not completely understood. This study evaluated the association between preoperative pressure ulcer and adverse events after major surgeries. Methods Using reimbursement claims from Taiwan’s National Health Insurance Research Database, we conducted a nationwide retrospective cohort study of 17391 patients with preoperative pressure ulcer receiving major surgery in 2008-2010. With a propensity score matching procedure, 17391 surgical patients without pressure ulcer were selected for comparison. Eight major surgical postoperative complications and 30-day postoperative mortality were evaluated among patients with pressure ulcer of varying severity. Results Patients with preoperative pressure ulcer had significantly higher risk than controls for postoperative adverse outcomes, including septicemia, pneumonia, stroke, urinary tract infection, and acute renal failure. Surgical patients with pressure ulcer had approximately 1.83-fold risk (95% confidence interval 1.54-2.18) of 30-day postoperative mortality compared with control group. The most significant postoperative mortality was found in those with serious pressure ulcer, such as pressure ulcer with local infection, cellulitis, wound or treatment by change dressing, hospitalized care, debridement or antibiotics. Prolonged hospital or intensive care unit stay and increased medical expenditures were also associated with preoperative pressure ulcer. Conclusion This nationwide propensity score-matched retrospective cohort study showed increased postoperative complications and mortality in patients with preoperative pressure ulcer. Our findings suggest the urgency of preventing and managing preoperative pressure ulcer by a multidisciplinary medical team for this specific population. PMID:26000606

Adverse outcome pathway (AOP) development and evaluation

EPA Science Inventory

The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be mea...

Paternal education and adverse birth outcomes in Canada.

PubMed

Shapiro, Gabriel D; Bushnik, Tracey; Sheppard, Amanda J; Kramer, Michael S; Kaufman, Jay S; Yang, Seungmi

2017-01-01

Research on predictors of adverse birth outcomes has focused on maternal characteristics. Much less is known about the role of paternal factors. Paternal education is an important socioeconomic marker that may predict birth outcomes over and above maternal socioeconomic indicators. Using data from the 2006 Canadian Birth-Census Cohort, we estimated the associations between paternal education and preterm birth, small-for-gestational-age (SGA) birth, stillbirth and infant mortality in Canada, controlling for maternal characteristics. Binomial regression was used to estimate risk ratios and risk differences for adverse birth outcomes associated with paternal education, after controlling for maternal education, age, marital status, parity, ethnicity and nativity. A total of 131 285 singleton births were included in the present study. Comparing the lowest to the highest paternal education category, adjusted risk ratios (95% CIs) were 1.22 (1.10 to 1.35) for preterm birth, 1.13 (1.03 to 1.23) for SGA birth, 1.92 (1.28 to 2.86) for stillbirth and 1.67 (1.01 to 2.75) for infant mortality. Consistent patterns of associations were observed for absolute risk differences. Our study suggests that low paternal education increases the risk of adverse birth outcomes, and especially of fetal and infant mortality, independently from maternal characteristics. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Accelerating Adverse Outcome Pathway (AOP) development ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. However, the conventional process for assembly of these AOPs is time and resource intensive, and has been a rate limiting step for AOP use and development. Therefore computational approaches to accelerate the process need to be developed. We previously developed a method for generating computationally predicted AOPs (cpAOPs) by association mining and integration of data from publicly available databases. In this work, a cpAOP network of ~21,000 associations was established between 105 phenotypes from TG-GATEs rat liver data from different time points (including microarray, pathological effects and clinical chemistry data), 994 REACTOME pathways, 688 High-throughput assays from ToxCast and 194 chemicals. A second network of 128,536 associations was generated by connecting 255 biological target genes from ToxCast to 4,980 diseases from CTD using either HT screening activity from ToxCast for 286 chemicals or CTD gene expression changes in response to 2,330 chemicals. Both networks were separately evaluated through manual extraction of disease-specific cpAOPs and comparison with expert curation of the relevant literature. By employing data integration strategies that involve the weighting of n

Trends in adverse maternal outcomes during childbirth: a population-based study of severe maternal morbidity.

PubMed

Roberts, Christine L; Ford, Jane B; Algert, Charles S; Bell, Jane C; Simpson, Judy M; Morris, Jonathan M

2009-02-25

Maternal mortality is too rare in high income countries to be used as a marker of the quality of maternity care. Consequently severe maternal morbidity has been suggested as a better indicator. Using the maternal morbidity outcome indicator (MMOI) developed and validated for use in routinely collected population health data, we aimed to determine trends in severe adverse maternal outcomes during the birth admission and in particular to examine the contribution of postpartum haemorrhage (PPH). We applied the MMOI to the linked birth-hospital discharge records for all women who gave birth in New South Wales, Australia from 1999 to 2004 and determined rates of severe adverse maternal outcomes. We used frequency distributions and contingency table analyses to examine the association between adverse outcomes and maternal, pregnancy and birth characteristics, among all women and among only those with PPH. Using logistic regression, we modelled the effects of these characteristics on adverse maternal outcomes. The impact of adverse outcomes on duration of hospital admission was also examined. Of 500,603 women with linked birth and hospital records, 6242 (12.5 per 1,000) suffered an adverse outcome, including 22 who died. The rate of adverse maternal outcomes increased from 11.5 in 1999 to 13.8 per 1000 deliveries in 2004, an annual increase of 3.8% (95%CI 2.3-5.3%). This increase occurred almost entirely among women with a PPH. Changes in pregnancy and birth factors during the study period did not account for increases in adverse outcomes either overall, or among the subgroup of women with PPH. Among women with severe adverse outcomes there was a 12% decrease in hospital days over the study period, whereas women with no severe adverse outcome occupied 23% fewer hospital days in 2004 than in 1999. Severe adverse maternal outcomes associated with childbirth have increased in Australia and the increase was entirely among women who experienced a PPH. Reducing or stabilising

Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

PubMed

Park, Brian; Dargon, Phong; Binette, Christopher; Babic, Bruna; Thomas, Tina; Divinagracia, Thomas; Dahn, Michael S; Menzoian, James O

2011-10-01

Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

An Integrative data mining approach to identifying Adverse Outcome Pathway (AOP) Signatures

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or populatio...

Area-level risk factors for adverse birth outcomes: trends in urban and rural settings.

PubMed

Kent, Shia T; McClure, Leslie A; Zaitchik, Ben F; Gohlke, Julia M

2013-06-10

Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban-rural status. Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991-2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse birth outcomes elsewhere may not be reaching

Area-level risk factors for adverse birth outcomes: trends in urban and rural settings

PubMed Central

2013-01-01

Background Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban–rural status. Methods Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Results Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991–2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Conclusions Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse

Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus

PubMed Central

Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

2016-01-01

Abstract Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach. PMID:26735528

Endovascular Management of Atherosclerotic Renal Artery Stenosis: Post-Cardiovascular Outcomes in Renal Atherosclerotic Lesions Era Winner or False Alarm?

PubMed Central

Karanikola, Evridiki; Karaolanis, Georgios; Galyfos, George; Barbaressos, Emmanuel; Palla, Viktoria; Filis, Konstantinos

2017-01-01

Renal artery stenosis (RAS) is frequently associated with severe comorbidities such as reduced renal perfusion, hypertension, and end-stage renal failure. In approximately 90% of patients, renal artery atherosclerosis is the main cause for RAS, and it is associated with an increased risk for fatal and non-fatal cardiovascular and renal complications. Endovascular management of atherosclerotic RAS (ARAS) has been recently evaluated by several randomized controlled trials that failed to demonstrate benefit of stenting. Furthermore, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study did not demonstrate any benefit over the revascularization approach. In this review, we summarized the available data from retrospective, prospective and randomized trials on ARAS to provide clinicians with sufficient data in order to produce useful conclusions for everyday clinical practice. PMID:28377906

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

PubMed

Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

1975-11-01

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Adverse outcome pathways (AOPs) to enhance EDC ...

EPA Pesticide Factsheets

Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway (AOP) framework, which organizes information concerning measureable changes that link initial biological interactions with a chemical to adverse effects that are meaningful to risk assessment and management, can aid this process. This presentation outlines the ways in which the AOP framework has already been employed to support EDSP and how it may further enhance endocrine disruptor assessments in the future. Screening and testing for endocrine active chemicals was mandated under 1996 amendments to the Safe Drinking Water Act and Food Quality Protection Act. Efficiencies can be gained in the endocrine disruptor screening program by using available biological and toxicological knowledge to facilitate greater use of high throughput screening data and other data sources to inform endocrine disruptor assessments. Likewise, existing knowledge, when properly organized, can help aid interpretation of test results. The adverse outcome pathway

Application of Adverse Outcome Pathways (AOPs) in Human ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

Application of adverse outcome pathways (AOPs) in human ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making. Because many fundamental molecular and cellular pathways are conserved across taxa, data from assays that screen chemicals for their ability to interact with specific biomolecular targets can often be credibly applied to a broad range of species, even if the apical outcomes of those perturbations may differ. Information concerning the different trajectories of adversity that molecular initiating events may take in different taxa, life stages, and sexes of organisms can be captured in the form of an AOP network. As an example, AOPs documenting divergent consequences of thyroid peroxidase (TPO) and deiodinase (DIO) inhibition in mammals, amphibians, and fish have been developed. These AOPs provide the foundation for using data from common in vitro assays for TPO or DIO activity to inform both human health and ecological risk assessments. They also provide the foundation for an integrated approach to testing and assessment, where available information and biological understanding can be integrated in order to formulate plausible and testable hypotheses which can be used to target in vivo testing on the endpoints of greatest concern. Application of this AOP knowledge in several different r

Early Elevations of the Complement Activation Fragment C3a and Adverse Pregnancy Outcomes

PubMed Central

Lynch, Anne M.; Gibbs, Ronald S.; Murphy, James R.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

2016-01-01

OBJECTIVE To estimate whether elevations of complement C3a early in pregnancy are predictive of the subsequent development of adverse pregnancy outcomes. METHODS A plasma sample was obtained from each enrolled pregnant woman before 20 weeks of gestation. The cohort (n=1,002) was evaluated for the development of adverse pregnancy outcomes defined as hypertensive diseases of pregnancy (gestational hypertension or preeclampsia), preterm birth (before 37 weeks of gestation), premature rupture of the membranes, pregnancy loss (during the embryonic and fetal period), intrauterine growth restriction, and the composite outcome of any adverse outcome. RESULTS One or more adverse pregnancy outcomes occurred in 211 (21%) of the cohort. The mean levels (ng/mL) of C3a in early pregnancy were significantly (P=<.001) higher among women with one or more adverse outcomes (858±435) compared with women with an uncomplicated pregnancy (741±407). Adjusted for parity and prepregnancy body mass index, women with levels of C3a in the upper quartile in early pregnancy were three times more likely to have an adverse outcome later in pregnancy compared with women in the lowest quartile (95% confidence interval, 1.8–4.8; P<.001). The link between early elevated C3a levels and adverse pregnancy outcomes was driven primarily by individual significant (P<.05) associations of C3a with hypertensive diseases of pregnancy, preterm birth, and premature rupture of the membranes. CONCLUSION Elevated C3a as early as the first trimester of pregnancy is an independent predictive factor for adverse pregnancy outcomes, suggesting that complement-related inflammatory events in pregnancy contribute to the subsequent development of poor outcomes at later stages of pregnancy. PMID:21173647

Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

PubMed

Miyamoto, Koji; Aiba, Takeshi; Arihiro, Shoji; Watanabe, Makoto; Kokubo, Yoshihiro; Ishibashi, Kohei; Hirose, Sayako; Wada, Mitsuru; Nakajima, Ikutaro; Okamura, Hideo; Noda, Takashi; Nagatsuka, Kazuyuki; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kamakura, Shiro; Shimizu, Wataru; Miyamoto, Yoshihiro; Toyoda, Kazunori; Kusano, Kengo

2016-08-01

Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was

Disease management improves end-stage renal disease outcomes.

PubMed

Sands, Jeffrey J

2006-01-01

Renal disease management organizations have reported achieving significant decreases in mortality and hospitalization in conjunction with cost savings, improved patient satisfaction and quality of life. Disease management organizations strive to fill existing gaps in care delivery through the standardized use of risk assessment, predictive modeling, evidence-based guidelines, and process and outcomes measurement. Patient self-management education and the provision of individual nurse care managers are also key program components. As we more fully measure clinical outcomes and total healthcare costs, including payments from all insurance and government entities, pharmacy costs and out of pocket expenditures, the full implications of disease management can be better defined. The results of this analysis will have a profound influence on United States healthcare policy. At present current data suggest that the promise of disease management, improved care at reduced cost, can and is being realized in end-stage renal disease. Copyright 2006 S. Karger AG, Basel.

Etiology and outcome of acute renal failure in pregnancy.

PubMed

Hassan, Irfana; Junejo, Abdul Manan; Dawani, Manohar Lal

2009-11-01

To determine the etiology and outcome of Acute Renal Failure (ARF) in pregnancy. A case series. Nephrology Department of the Jinnah Postgraduate Medical Centre, Karachi, from August 2007 to July 2008. Pregnant women who were healthy previously and had developed ARF, diagnosed on oliguria (urine output <400 ml/day) and mounting azotemia (serum creatinine > 2 mg%) were included in the study. Percutaneous renal biopsy was performed for delayed recovery, i.e. after three weeks. Patients were followed up for a period of 6 months. Percentages were calculated for qualitative variables i.e. causes of ARF, mortality, morbidity and outcome in form of complete recovery, partial recovery, demise and non-recovery. A total of 43 patients with pregnancy-related ARF were included in the study. The puerperal group comprised 36 patients (83.7%). Haemorrhage was the etiology for ARF in 25 (58.1%), antepartum haemorrhage APH in 8 (18.6%) and postpartum haemorrhage PPH in 16 (37.2%) of patients. In 12 (27.9%), puerperal sepsis was the etiological factor, while 4 (9.3%) patients had DIC on presentation. Pre-eclampsia, eclampsia and HELLP syndrome accounted for 5 (11.6%). While 1 (2.3%) was diagnosed with hemolytic uremic syndrome and another one was diagnosed as ARF secondary to hypotension produced by hyperemesis gravidarum. Renal biopsy was performed in 31 patients showing that 10 had acute cortical necrosis and 21 had acute tubular necrosis. Maternal mortality was 16.2% (n=7). Of the 36 (83.7%) surviving patients, 18 (41.4%) had complete recovery of renal function; 12 (27.9%) had partial recovery; and 6 (13.9%) required chronic dialysis. Pregnancy-related ARF was associated with poor outcome. Antepartum and postpartum haemorrhage were the most common cause of ARF in pregnancy.

The influence of the built environment on adverse birth outcomes.

PubMed

Woods, N; Gilliland, J; Seabrook, J A

2017-01-01

Adverse birth outcomes are associated with neonatal morbidity and mortality, and higher risk for coronary heart disease, non-insulin-dependent diabetes and hypertension in adulthood. Although there has been considerable research investigating the association between maternal and environmental factors on adverse birth outcomes, one risk factor, not fully understood, is the influence of the built environment. A search of MEDLINE, Scopus, and Cochrane was conducted to find articles assessing the influence of the built environment on preterm birth (PTB), low birth weight (LBW), and small-for-gestational-age (SGA). In total, 41 studies met our inclusion criteria, and were organized into nine categories: Roadways, Greenness, Power Plants, Gas Stations/Wells, Waste Management, Power Lines, Neighborhood Conditions, Food Environment, and Industry. The most common built environmental variable was roads/traffic, encompassing 17/41 (41%) of the articles reviewed, of which 12/17 (71%) found a significant small to moderate association between high traffic exposure and adverse birth outcomes.

Outcomes of Renal Allograft Recipients With Hepatitis C.

PubMed

Carpio, R; Pamugas, G E; Danguilan, R; Que, E

2016-04-01

Studies on the effect of hepatitis C virus (HCV) infection showed decreased graft survival compared to HCV-negative matched patients. It was also identified as an independent risk factor for graft loss and mortality in kidney transplantation patients. This study was designed to evaluate the 10-year graft and patient outcomes of renal allograft recipients with HCV infection at the National Kidney and Transplant Institute. This is a retrospective study of patients who underwent renal transplantation with HCV infection and a group who were HCV-negative in the same post-transplantation period. Data were gathered from the in-patient and out-patient clinic records. Patient survival was significantly lower in the HCV-positive than in the HCV-negative group. The mean duration of patient survival was 154.95 (+4.95) months (12 years and 10 months) in HCV-negative patients compared to 141 (+6.52) months (11 years and 9 months) in the HCV-positive group (P = .05). Graft survival did not differ significantly between HCV-positive and HCV-negative recipients (P = .734). The mean duration of graft survival was 137 (+7.68) months (11 years and 5 months) in HCV-negative patients compared to 130 (+6.84) months (10 years and 10 months) in HCV-positive patients. Short- and long-term outcomes including biopsy-proven acute rejection, transplant glomerulopathy, chronic allograft nephropathy, renal function, and proteinuria were similar in both groups. Rejection, glomerulopathy, and renal function were similar in both groups. HCV progression was also observed in patients with detectable HCV-RNA 6 months before transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of reducing blood pressure on renal outcomes in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.

PubMed

Scheen, A J; Delanaye, P

2017-04-01

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function. While systemic BP reduction associated to empagliflozin therapy may have contributed to the renal benefits reported in EMPA-REG OUTCOME, other local mechanisms related to kidney homoeostasis most probably also played a role in the overall protection observed in the trial. Copyright © 2017. Published by Elsevier Masson SAS.

Renal arterial resistive index is associated with severe histological changes and poor renal outcome during chronic kidney disease

PubMed Central

2012-01-01

Background Chronic kidney disease (CKD) is a growing public health problem and end stage renal disease (ESRD) represents a large human and economic burden. It is important to identify patients at high risk of ESRD. In order to determine whether renal Doppler resistive index (RI) may discriminate those patients, we analyzed whether RI was associated with identified prognosis factors of CKD, in particular histological findings, and with renal outcome. Methods RI was measured in the 48 hours before renal biopsy in 58 CKD patients. Clinical and biological data were collected prospectively at inclusion. Arteriosclerosis, interstitial fibrosis and glomerulosclerosis were quantitatively assessed on renal biopsy in a blinded fashion. MDRD eGFR at 18 months was collected for 35 (60%) patients. Renal function decline was defined as a decrease in eGFR from baseline of at least 5 mL/min/ 1.73 m2/year or need for chronic renal replacement therapy. Pearson’s correlation, Mann–Whitney and Chi-square tests were used for analysis of quantitative and qualitative variables respectively. Kaplan Meier analysis was realized to determine renal survival according to RI value using the log-rank test. Multiple logistic regression was performed including variables with p < 0.20 in univariate analysis. Results Most patients had glomerulonephritis (82%). Median age was 46 years [21–87], eGFR 59 mL/min/ 1.73m2 [5–130], percentage of interstitial fibrosis 10% [0–90], glomerulosclerosis 13% [0–96] and RI 0.63 [0.31-1.00]. RI increased with age (r = 0.435, p = 0.0063), pulse pressure (r = 0.303, p = 0.022), renal atrophy (r = −0.275, p = 0.038) and renal dysfunction (r = −0.402, p = 0.0018). Patients with arterial intima/media ratio ≥ 1 (p = 0.032), interstitial fibrosis > 20% (p = 0.014) and renal function decline (p = 0.0023) had higher RI. Patients with baseline RI ≥ 0.65 had a poorer renal outcome than those with baseline RI < 0.65 (p = 0.0005). In multiple logistic

Sclerotherapy with tetracycline for hydroceles in renal transplant patients.

PubMed

Sankari, B R; Boullier, J A; Garvin, P J; Parra, R O

1992-10-01

A total of 17 patients with hydroceles following renal transplantation underwent sclerotherapy with tetracycline hydrochloride (10 ml. of a 5% solution of tetracycline in 1% lidocaine). A successful outcome was obtained in 15 patients (88%). Post-sclerotherapy hydrocelectomy was necessary in 2 patients (12%). No major complications (testicular loss, scrotal abscess or necrosis) occurred in any patient. Pain at injection was the only adverse effect. Tetracycline sclerotherapy for hydroceles appears to be an effective and safe procedure in the renal transplant population. We recommend this procedure as the initial treatment modality for hydroceles in patients with a renal allograft.

Adverse outcome pathway (AOP) development II: Best practices

EPA Science Inventory

Organization of existing and emerging toxicological knowledge into adverse outcome pathway (AOP) descriptions can facilitate greater application of mechanistic data, including high throughput in vitro, high content omics and imaging, and biomarkers, in risk-based decision-making....

Social capital and adverse treatment outcomes of tuberculosis: a case-control study.

PubMed

Deshmukh, P R; Mundra, A; Dawale, A

2017-08-01

'Social capital' refers to social norms, relationships, networks and values that affect the functioning and development of society. Social capital influences health positively, but its role in the treatment outcomes of tuberculosis (TB) is not known. To study the role of social capital in determining adverse TB treatment outcomes. Of 516 patients registered under the Revised National Tuberculosis Control Programme in 2014 in Wardha Tuberculosis Unit, Wardha, India, we included 88 patients with adverse treatment outcomes as cases and 187 controls from among those without adverse outcomes. Multiple logistic regression was used to compare standardised Z-scores. A greater proportion of controls than cases belonged to higher quartiles of social capital and its domains than cases, and the mean standardised Z-score was also consistently higher among controls than cases. Respectively 47% and 15% of cases and controls were in the poorest quartile of social capital, whereas respectively 10% and 33% of cases and controls were in the richest quartile. Each unit increase in Z-score of overall social capital reduced the odds of adverse treatment outcomes by 63.1%. Appropriate interventions for building social capital for TB patients and linking them with the programme would improve programme performance.

Radiofrequency ablation of renal cell carcinoma: a follow up of outcomes.

PubMed

Curry, David; Yassin, Musaab; Thwaini, Ali; Pahuja, Ajay; Alanbuki, Ammar H; Rajan, Thiagarajan Nambi; Loan, Willie

2014-02-01

To present the oncological outcomes in a series of patients with cT1a renal cell carcinoma (RCC) treated with radiofrequency ablation (RFA) and its effect on the glomerular filtration rate (GFR). Forty-five patients (48 renal units) treated at the Belfast City Hospital, over 4 years. Average age is 61.5 years (range 41-80). Eighteen patients (22 renal units) were included with American Society of Anesthesiologists (ASA) II and III. The rest were ASA I. Average tumor size was 2.63 cm (range 1.2 cm-6 cm). Renal function before and after RFA was recorded by means of the estimated glomerular filtration rate (eGFR) and the changes are presented. Oncological outcomes were established from follow up imaging. A satisfactory response was defined by disappearance or a persistence of non-enhancing lesion of smaller size at follow up. A partial response was defined by a persistent but non-enhancing similar size lesion. A failed response was defined by enlarging or persistently enhancing lesions. Mean follow up was 30.6 months (4-60 months). A good response was found in 33 (74%) patients. A partial response was found in 3 (8%) patients and failed response was identified in 8 (18%) patients. The average reduction in eGFR was 11 mL/min. Two patients had a 50% reduction in their eGFR. No patient required dialysis following treatment. RFA presents safe treatment choice for patients with RCC, particularly those that are high risk surgical candidates and those who refuse surgery. Short term results suggest good oncological outcomes and preservation of renal function.

Adverse Outcome Pathways – Organizing Toxicological ...

EPA Pesticide Factsheets

The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High throughput screening (HTS) commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP) concept has emerged as a natural framework for connecting high throughput toxicity testing (HTT) results to potential impacts on humans and wildlife populations. An AOP consists of two main components that describe the biological mechanisms driving toxicity. Key events represent biological processes essential for causing the adverse outcome that are also measurable experimentally. Key event relationships capture the biological processes connecting the key events. Evidence documented for each KER based on measurements of the KEs can provide the confidence needed for extrapolating HTT from early key events to overt toxicity represented by later key events based on the AOP. The IPCS mode of action (MOA) framework incorporates information required for making a chemical-specific toxicity determination. Given the close relationship between the AOP and MOA frameworks, it is possible to assemble an MOA by incorporating HTT results, chemical properties including absorption, distribution, metabolism, and excretion (ADME), and an AOP describing the biological basis of toxicity thereby streamlining the process. While current applications focus on the assessment of risk for environmental chemicals,

Accelerating Adverse Outcome Pathway Development via Systems Approaches

EPA Science Inventory

The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

Novel Renal Biomarkers to Assess Cardiorenal Syndrome

PubMed Central

Brisco, Meredith A.; Testani, Jeffrey M.

2014-01-01

Renal dysfunction (RD) in heart failure portends adverse outcomes and often limits aggressive medical and decongestive therapies. Despite the high prevalence in this population, not all forms of RD are prognostically or mechanistically equivalent: RD can result from irreversible nephron loss secondary to diabetic or hypertensive kidney disease or it can develop secondary to the HF itself, i.e. the cardiorenal syndrome. Furthermore, filtration is only one aspect of renal performance such that significant renal impairment secondary to cardiorenal syndrome can exist despite a normal glomerular filtration rate. Renal biomarkers have the potential to inform some of the intricacies involved in accurately assessing cardiorenal interactions. This article discusses novel biomarkers for cardiorenal syndrome and their utility in prognosis, diagnosis, and targeted treatment of heart failure-induced RD. PMID:25239434

Long-Term Outcomes of Renal Transplant in Recipients With Lower Urinary Tract Dysfunction.

PubMed

Wilson, Rebekah S; Courtney, Aisling E; Ko, Dicken S C; Maxwell, Alexander P; McDaid, James

2018-01-02

Lower urinary tract dysfunction can lead to chronic kidney disease, which, despite surgical intervention, will progress to end-stage renal disease, requiring dialysis. Urologic pathology may damage a transplanted kidney, limiting patient and graft survival. Although smaller studies have suggested that urinary tract dysfunction does not affect graft or patient survival, this is not universally accepted. Northern Ireland has historically had the highest incidence of neural tube defects in Europe, giving rich local experience in caring for patients with lower urinary tract dysfunction. Here, we analyzed outcomes of renal transplant recipients with lower urinary tract dysfunction versus control recipients. We identified 3 groups of kidney transplant recipients treated between 2001 and 2010; those in group 1 had end-stage renal disease due to lower urinary tract dysfunction with prior intervention (urologic surgery, long-term catheter, or intermittent self-catheterization), group 2 had end-stage renal disease secondary to lower urinary tract dysfunction without intervention, and group 3 had end-stage renal disease due to polycystic kidney disease (chosen as a relatively healthy control cohort without comorbid burden of other causes of end-stage renal disease such as diabetes). The primary outcome measured, graft survival, was death censored, with graft loss defined as requirement for renal replacement therapy or retransplant. Secondary outcomes included patient survival and graft function. In 150 study patients (16 patients in group 1, 64 in group 2, and 70 in group 3), 5-year death-censored graft survival was 93.75%, 90.6%, and 92.9%, respectively, with no significant differences in graft failure among groups (Cox proportional hazards model). Five-year patient survival was 100%, 100%, and 94.3%, respectively. Individuals with a history of lower urinary tract dysfunction had graft and patient survival rates similar to the control group. When appropriately treated, lower

One Year Clinical Outcomes of Renal Artery Stenting: The Results of ODORI Registry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sapoval, M., E-mail: marc.sapoval2@egp.aphp.f; Tamari, I.; Goffette, P.

2010-06-15

The safety, efficacy and long term clinical benefits of renal artery revascularization by stenting are still a matter of debate. The aim of our study was to define the safety and efficacy of renal artery stenting with the Tsunami peripheral stent (Terumo Corporation, Tokyo, Japan). The ODORI was a prospective, multicentre registry which enrolled 251 consecutive patients, (276 renal arteries) in 36 centres across Europe. The primary endpoint was acute procedural success defined as <30% residual stenosis after stent placement. Secondary endpoints included major adverse events, blood pressure control, serum creatinine level, and target lesion revascularization (TLR) at 6 andmore » 12 months. Patients were 70 {+-} 10 years old, 59% were male, 33% had diabetes, and 96% hypertension. The main indications for renal stent implantation were hypertension in 83% and renal salvage in 39%. Direct stent implantation was performed in 76% of the cases. Acute success rate was 100% with residual stenosis of 2.5 {+-} 5.4%. Systolic/diastolic blood pressure decreased from a mean of 171/89 at baseline to 142/78 mmHg at 6 months (p < 0.0001 vs. baseline), and 141/80 mmHg at 12 months (p < 0.0001 vs. baseline). Mean serum creatinine concentration did not change significantly in the total population. However, there was significant improvement in the highest tercile (from 283 {mu}mol/l at baseline to 205 and 209 {mu}mol/l at 6 and 12 months respectively). At 12-months, rates of restenosis and TLR were 6.6 and 0.8% respectively. The 12 month cumulative rate of all major clinical adverse events was 6.4% while the rate of device or procedure related events was 2.4%. In hypertensive patients with atherosclerotic renal artery stenosis Tsunami peripheral balloon-expandable stent provides a safe revascularization strategy, with a potential beneficial impact on hypertension control and renal function in the highest risk patients.« less

A thick placenta: a predictor of adverse pregnancy outcomes.

PubMed

Miwa, Ichiro; Sase, Masakatsu; Torii, Mayumi; Sanai, Hiromi; Nakamura, Yasuhiko; Ueda, Kazuyuki

2014-01-01

The aim of this study is to evaluate the efficacy of an ultrasonographic measurement of placental thickness and the correlation of a thick placenta with adverse perinatal outcome. Placental thickness was measured in single gravidas, 16 to 40 weeks of gestation, between 2005 and 2009. Placentas were considered to be thick if their measured thickness were above the 95th percentile for gestational age. The incidence of thick placentas was 4.3% (138/3,183). Perinatal morbidity and neonatal conditions were worse in cases with thick placenta rather than without thick placenta. Ultrasonographic measurement of placental thickness is a simple method to estimate placental size. Thick placenta may be a useful predictor of adverse pregnancy outcomes.

Development of an adverse outcome pathway for acetylcholinesterase inhibition leading to acute mortality

EPA Science Inventory

Adverse outcome pathways (AOPs) are designed to describe linkages of key events (KEs) within a biological pathway that result in an adverse outcome associated with chemical perturbation of a well-defined molecular initiating event (MIE). Risk assessors have traditionally relied ...

Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources

EPA Science Inventory

The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledg...

Long-term renal outcome in patients with malignant hypertension: a retrospective cohort study

PubMed Central

2012-01-01

Background Malignant hypertension is frequently complicated by renal insufficiency. Although the survival of this hypertensive emergency has improved, recent data on renal outcome and its predictors are lacking. We assessed renal outcome and its predictors in patients with malignant hypertension. Methods Retrospective analysis of patients admitted with malignant hypertension in Amsterdam, the Netherlands between August 1992–January 2010. Follow-up data on vital status, renal function and blood pressure (BP) were obtained from the outpatient department and from general practitioners. The primary composite endpoint was end-stage renal disease (ESRD) defined as the start of kidney replacement therapy (KRT) or ≥ 50% decline of estimated glomerular filtration rate (eGFR). The secondary endpoint was all cause mortality. Results A total of 120 patients admitted with malignant hypertension were included. After a median follow-up period of 67 months (IQR 28 to 108 months) the primary endpoint was reached by 37 (31%) patients, whereas 18 patients (15%) reached the secondary endpoint. Twenty-nine (24%) patients started KRT and 8 patients (7%) had an eGFR decline ≥ 50%. After the acute phase (> 3 months after admission), initial serum creatinine and follow-up BP were the main predictors of future ESRD with hazard ratios of 6.1 (95% CI, 2.2–17) for patients with initial serum creatinine ≥ 175 μmol /L and 4.3 (95% CI, 1.4–14) for patients with uncontrolled hypertension. Conclusions Progressive renal function decline leading to ESRD remains a major threat to patients with malignant hypertension. BP control during follow-up was an important modifiable predictor of renal outcome. PMID:22846257

Integrating toxicogenomics data into cancer adverse outcome pathways

EPA Science Inventory

Integrating toxicogenomics data into adverse outcome pathways for cancer.J. Christopher CortonNHEERL/ORD, EPA, Research Triangle Park, NCAs the toxicology field continues to move towards a new paradigm in toxicity testing and safety assessment, there is the expectation that model...

Associations Between Renal Duplex Parameters and Adverse Cardiovascular Events in the Elderly: A Prospective Cohort Study

PubMed Central

Pearce, Jeffrey D.; Craven, Timothy E.; Edwards, Matthew S.; Corriere, Matthew A.; Crutchley, Teresa A.; Fleming, Shawn H.; Hansen, Kimberley J.

2010-01-01

Background Atherosclerotic renovascular disease is associated with an increased risk of cardiovascular disease (CVD) events. This study examines associations between Doppler-derived parameters from the renal artery and renal parenchyma and all-cause mortality and fatal and nonfatal CVD events in a cohort of elderly Americans. Study Design Cohort study. Setting A subset of participants from the Cardiovascular Health Study (CHS). Through an ancillary study, 870 (70% recruitment) Forsyth County, NC, CHS participants consented to undergo renal duplex sonography to define the prevalence of renovascular disease in the elderly, resulting in 726 (36% men; mean age, 77 years) technically adequate complete studies included in this investigation. Predictor Renal duplex sonography–derived Doppler signals from the main renal arteries and renal parenchyma. Spectral analysis from Doppler-shifted frequencies and angle of insonation were used to estimate renal artery peak systolic and end diastolic velocity (both in meters per second). Color Doppler was used to identify the corticomedullary junction. Using a 3-mm Doppler sample, the parenchymal peak systolic and end diastolic frequency shift (both in kilohertz) were obtained. Resistive index was calculated as (1 – [end diastolic frequency shift/peak systolic frequency shift]) using Doppler samples from the hilar arteries of the left or right kidney with the higher main renal artery peak systolic velocity. Outcomes & Measurements Proportional hazard regression analysis was used to determine associations between renal duplex sonography–derived Doppler signals and CVD events and all-cause mortality adjusted for accepted cardiovascular risk factors. Index CVD outcomes were defined as coronary events (angina, myocardial infarction, and coronary artery bypass grafting/percutaneous coronary intervention), cerebrovascular events (stroke or transient ischemic attack), and any CVD event (angina, congestive heart failure, myocardial

Informatics approaches in the Biological Characterization of Adverse Outcome Pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) are a conceptual framework to characterize toxicity pathways by a series of mechanistic steps from a molecular initiating event to population outcomes. This framework helps to direct risk assessment research, for example by aiding in computational ...

From anatomy to function: diagnosis of atherosclerotic renal artery stenosis.

PubMed

Odudu, Aghogho; Vassallo, Diana; Kalra, Philip A

2015-12-01

Atherosclerotic renal artery stenosis (ARAS) affects 7% of the over 65 s and will be increasingly common with an ageing population. ARAS obstructs normal renal perfusion with adverse renal and cardiovascular consequences. Drug therapy is directed at reducing atherosclerotic risk. Two recent major trials of revascularization for ARAS showed that clinical outcomes were not improved beyond those offered by optimal drug therapy in most patients. This reflects experimental data showing that restoration of blood flow alone may not attenuate a cascade of tissue injury. A shift from anatomic to functional imaging of ARAS coupled to novel therapies might improve clinical outcomes in selected patients. This review outlines the case for separately assessing hemodynamic significance of arterial stenosis and functional reserve of renal parenchymal tissue. The authors consider current and emerging diagnostic techniques for ARAS and their potential to allow individualized and functionally directed treatments.

Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis.

PubMed

Damman, Kevin; Valente, Mattia A E; Voors, Adriaan A; O'Connor, Christopher M; van Veldhuisen, Dirk J; Hillege, Hans L

2014-02-01

Chronic kidney disease (CKD) and worsening renal function (WRF) have been associated with poor outcome in heart failure (HF). Articles were identified by literature search of MEDLINE (from inception to 1 July 2012) and Cochrane. We included studies on HF patients and mortality risk with CKD and/or WRF. In a secondary analysis, we selected studies investigating predictors of WRF. We retrieved 57 studies (1,076,104 patients) that investigated CKD and 28 studies (49,890 patients) that investigated WRF. The prevalence of CKD was 32% and associated with all-cause mortality: odds ratio (OR) 2.34, 95% confidence interval (CI) 2.20-2.50, P < 0.001). Worsening renal function was present in 23% and associated with unfavourable outcome (OR 1.81, 95% CI 1.55-2.12, P < 0.001). In multivariate analysis, moderate renal impairment: hazard ratio (HR) 1.59, 95% CI 1.49-1.69, P < 0.001, severe renal impairment, HR 2.17, 95% CI 1.95-2.40, P < 0.001, and WRF, HR 1.95, 95% CI 1.45-2.62, P < 0.001 were all independent predictors of mortality. Across studies, baseline CKD, history of hypertension and diabetes, age, and diuretic use were significant predictors for the occurrence of WRF. Across all subgroups of patients with HF, CKD, and WRF are prevalent and associated with a strongly increased mortality risk, especially CKD. Specific conditions may predict the occurrence of WRF and thereby poor prognosis.

Multiple Renal Artery Pseudoaneurysms in Patients Undergoing Renal Artery Embolization Following Partial Nephrectomy: Correlation with RENAL Nephrometry Scores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Nakul; Patel, Anish; Ensor, Joe

PurposeTo describe the incidence of multiple renal artery pseudoaneurysms (PSA) in patients referred for renal artery embolization following partial nephrectomy and to study its relationship to RENAL nephrometry scores.Materials and MethodsThe medical records of 25 patients referred for renal artery embolization after partial nephrectomy were retrospectively reviewed for the following parameters: size and number of tumors, RENAL nephrometry scores, angiographic abnormalities, technical and clinical outcomes, and estimated glomerular filtration rates (eGFRs) after embolization.ResultsTwenty-four patients had primary renal tumors, while 1 patient had a pancreatic tumor invading the kidney. Multiple tumors were resected in 4 patients. Most patients (92 %) were symptomatic,more » presenting with gross hematuria, flank pain, or both. Angiography revealed PSA with (n = 5) or without (n = 20) AV fistulae. Sixteen patients (64 %) had multiple PSA involving multiple renal vessels. Higher RENAL nephrometry scores were associated with an increasing likelihood of multiple PSA. Multiple vessels were embolized in 14 patients (56 %). Clinical success was achieved after one (n = 22) or two (n = 3) embolization sessions in all patients. Post-embolization eGFR values at different time points after embolization were not significantly different from the post-operative eGFR.ConclusionA majority of patients requiring renal artery embolization following partial nephrectomy have multiple pseudoaneurysms, often requiring selective embolization of multiple vessels. Higher RENAL nephrometry score is associated with an increasing likelihood of multiple pseudoaneurysms. We found transarterial embolization to be a safe and effective treatment option with no long-term adverse effect on renal function in all but one patient with a solitary kidney.« less

Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study.

PubMed

Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

2017-08-15

Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Retrospective cohort study. Primary care practices affiliated with 2 academic medical centers. Patients with a presumed adverse reaction to a statin between 2000 and 2011. Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College

The Associations Between Air Pollution and Adverse Pregnancy Outcomes in China.

PubMed

Tan, Yafei; Yang, Rong; Zhao, Jinzhu; Cao, Zhongqiang; Chen, Yawen; Zhang, Bin

2017-01-01

Research on the potential impact of air pollution on the human's health has increased rapidly in recent years. Several studies have suggested that exposure to air pollutants during period of pregnancy which is a crucial time point of mother-fetus development may have long-term and serious impact on adverse pregnancy outcomes. There is lack of review to evaluate the existed epidemiologic evidence on the associations between air pollutants and adverse pregnancy outcomes in China, so we conducted a review to explore the current epidemiological evidence on the effects of air pollutants to pregnancy outcomes and possible mechanisms during the pregnancy process. We used keywords to systematically search all the English and Chinese literatures on studies that were conducted in China. Exposure to air pollutants during pregnancy had shown there were harmful effects for different birth outcomes: preterm birth, low birth weight, stillbirth, birth defects, infertility, and macrosomia fetus. Results on the effects of air pollutants on adverse pregnancy outcomes are small and inconsistent because they vary in their design and methodology. The existed available evidence is compatible with either a small negative effect of air pollutants on pregnancy outcomes or with no effect; therefore, further studies are needed to confirm and quantify the possible associations and potential biologic mechanisms between air pollutants and pregnancy outcomes.

Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

PubMed

Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

2014-01-01

Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

Renal mass anatomic characteristics and perioperative outcomes of laparoscopic partial nephrectomy: a critical analysis.

PubMed

Tsivian, Matvey; Ulusoy, Said; Abern, Michael; Wandel, Ayelet; Sidi, A Ami; Tsivian, Alexander

2012-10-01

Anatomic parameters determining renal mass complexity have been used in a number of proposed scoring systems despite lack of a critical analysis of their independent contributions. We sought to assess the independent contribution of anatomic parameters on perioperative outcomes of laparoscopic partial nephrectomy (LPN). Preoperative imaging studies were reviewed for 147 consecutive patients undergoing LPN for a single renal mass. Renal mass anatomy was recorded: Size, growth pattern (endo-/meso-/exophytic), centrality (central/hilar/peripheral), anterior/posterior, lateral/medial, polar location. Multivariable models were used to determine associations of anatomic parameters with warm ischemia time (WIT), operative time (OT), estimated blood loss (EBL), intra- and postoperative complications, as well as renal function. All models were adjusted for the learning curve and relevant confounders. Median (range) tumor size was 3.3 cm (1.5-11 cm); 52% were central and 14% hilar. While 44% were exophytic, 23% and 33% were mesophytic and endophytic, respectively. Anatomic parameters did not uniformly predict perioperative outcomes. WIT was associated with tumor size (P=0.068), centrality (central, P=0.016; hilar, P=0.073), and endophytic growth pattern (P=0.017). OT was only associated with tumor size (P<0.001). No anatomic parameter predicted EBL. Tumor centrality increased the odds of overall and intraoperative complications, without reaching statistical significance. Postoperative renal function was not associated with any of the anatomic parameters considered after adjustment for baseline function and WIT. Learning curve, considered as a confounder, was independently associated with reduced WIT and OT as well as reduced odds of intraoperative complications. This study provides a detailed analysis of the independent impact of renal mass anatomic parameters on perioperative outcomes. Our findings suggest diverse independent contributions of the anatomic parameters to

Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome.

PubMed

Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

2015-07-01

Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome.

Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome

PubMed Central

Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

2015-01-01

Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsia. The factors like low socio-economic status, mother's age, race, multiple births, tobacco and drug-abuse may be found to increase risk of adverse pregnancy outcome. However, the same are less correlated with PLBW cases. Even the invasion of both aerobic and anerobic may lead to inflammation of gastrointestinal tract and vagina hence contributing to PLBW. The biological mechanism involved between PLBW and Maternal periodontitis is the translocation of chemical mediators of inflammation. Pre-eclampsia is one of the commonest cause of both maternal and fetal morbidity as it is characterized by hypertension and hyperprotenuria. Improving periodontal health before or during pregnancy may prevent or reduce the occurrences of these adverse pregnancy outcomes and, therefore, reduce the maternal and perinatal morbidity and mortality. Hence, this article is an attempt to review the relationship between periodontal condition and altered pregnancy outcome. PMID:26229389

Elevated risk of adverse obstetric outcomes in pregnant women with depression.

PubMed

Kim, Deborah R; Sockol, Laura E; Sammel, Mary D; Kelly, Caroline; Moseley, Marian; Epperson, C Neill

2013-12-01

In this study, we evaluated the association between prenatal depression symptoms adverse birth outcomes in African-American women. We conducted a retrospective cohort study of 261 pregnant African-American women who were screened with the Edinburgh Postnatal Depression Scale (EPDS) at their initial prenatal visit. Medical records were reviewed to assess pregnancy and neonatal outcomes, specifically preeclampsia, preterm birth, intrauterine growth retardation, and low birth weight. Using multivariable logistic regression models, an EPDS score ≥10 was associated with increased risk for preeclampsia, preterm birth, and low birth weight. An EPDS score ≥10 was associated with increased risk for intrauterine growth retardation, but after controlling for behavioral risk factors, this association was no longer significant. Patients who screen positive for depression symptoms during pregnancy are at increased risk for multiple adverse birth outcomes. In a positive, patient-rated depression screening at the initial obstetrics visit, depression is associated with increased risk for multiple adverse birth outcomes. Given the retrospective study design and small sample size, these findings should be confirmed in a prospective cohort study.

Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta-analysis.

PubMed

Liu, Xiaoyan; Fiocco, Marta; Swen, Jesse J; Guchelaar, Henk-Jan

2017-04-01

An increasing number of studies have reported ethnic differences in sunitinib outcome in metastatic renal cell carcinoma (mRCC) patients. However, a comprehensive analysis is still lacking. Therefore, we systematically collected available published data and performed a meta-analysis to compare sunitinib efficacy and toxicity in Asian and Caucasian mRCC patients. Data were extracted from published results from clinical trials, expanded access program and real-world clinical practice. Progression-free survival (or time to tumor progression), overall survival, objective response rate and adverse events were used as endpoints to evaluate the differences of sunitinib outcome between the two ethnicities. For adverse events, we focused the following clinically relevant side effects: diarrhea, fatigue, mucositis/stomatitis, hand-foot syndrome, hypertension, leukopenia, neutropenia and thrombocytopenia. A total of 33 publications including 9977 patients were available for meta-analysis. The efficacy of sunitinib in Asian patients was similar to that in Caucasian patients. However, Asian patients showed a higher incidence of all grades toxicity of hand-foot syndrome, > grade 2 fatigue, > grade 2 hand-foot syndrome and > grade 2 thrombocytopenia. Ethnic differences in adverse events of sunitinib in mRCC patients existed and dose adjustment in Asian patients may be considered.

Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study

PubMed Central

2012-01-01

Background Evidence is lacking to inform providers’ and patients’ decisions about many common treatment strategies for patients with end stage renal disease (ESRD). Methods/design The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003–2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006–2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. Discussion The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD

Pregnancy loss history at first parity and selected adverse pregnancy outcomes.

PubMed

Ahrens, Katherine A; Rossen, Lauren M; Branum, Amy M

2016-07-01

To evaluate the association between pregnancy loss history and adverse pregnancy outcomes. Pregnancy history was captured during a computer-assisted personal interview for 21,277 women surveyed in the National Survey of Family Growth (1995-2013). History of pregnancy loss (<20 weeks) at first parity was categorized in three ways: number of losses, maximum gestational age of loss(es), and recency of last pregnancy loss. We estimated risk ratios for a composite measure of selected adverse pregnancy outcomes (preterm, stillbirth, or low birthweight) at first parity and in any future pregnancy, separately, using predicted margins from adjusted logistic regression models. At first parity, compared with having no loss, having 3+ previous pregnancy losses (adjusted risk ratio (aRR) = 1.66 [95% CI = 1.13, 2.43]), a maximum gestational age of loss(es) at ≥10 weeks (aRR = 1.28 [1.04, 1.56]) or having experienced a loss 24+ months ago (aRR = 1.36 [1.10, 1.68]) were associated with increased risks of adverse pregnancy outcomes. For future pregnancies, only having a history of 3+ previous pregnancy losses at first parity was associated with increased risks (aRR = 1.97 [1.08, 3.60]). Number, gestational age, and recency of pregnancy loss at first parity were associated with adverse pregnancy outcomes in U.S. women. Published by Elsevier Inc.

FGF-23 as a Predictor of Renal Outcome in Diabetic Nephropathy

PubMed Central

Zatz, Roberto; Graciolli, Fabiana G.; dos Reis, Luciene M.; Barros, Rui T.; Jorgetti, Vanda; Moysés, Rosa M.A.

2011-01-01

Summary Background and objectives Fibroblast growth factor 23 (FGF-23) has emerged as a new factor in mineral metabolism in chronic kidney disease (CKD). An important regulator of phosphorus homeostasis, FGF-23 has been shown to independently predict CKD progression in nondiabetic renal disease. We analyzed the relation between FGF-23 and renal outcome in diabetic nephropathy (DN). Design, setting, participants, & measurements DN patients participating in a clinical trial (enalapril+placebo versus enalapril+losartan) had baseline data collected and were followed until June 2009 or until the primary outcome was reached. Four patients were lost to follow-up. The composite primary outcome was defined as death, doubling of serum creatinine, and/or dialysis need. Results At baseline, serum FGF-23 showed a significant association with serum creatinine, intact parathyroid hormone, proteinuria, urinary fractional excretion of phosphate, male sex, and race. Interestingly, FGF-23 was not related to calcium, phosphorus, 25OH-vitamin D, or 24-hour urinary phosphorus. Mean follow-up time was 30.7 ± 10 months. Cox regression showed that FGF-23 was an independent predictor of the primary outcome, even after adjustment for creatinine clearance and intact parathyroid hormone (10 pg/ml FGF-23 increase = hazard ratio, 1.09; 95% CI, 1.01 to 1.16, P = 0.02). Finally, Kaplan-Meier analysis showed a significantly higher risk of the primary outcome in patients with FGF-23 values of >70 pg/ml. Conclusions FGF-23 is a significant independent predictor of renal outcome in patients with macroalbuminuric DN. Further studies should clarify whether this relation is causal and whether FGF-23 should be a new therapeutic target for CKD prevention. PMID:20966122

The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function

PubMed Central

Reid, Ryan; Ezekowitz, Justin A.; Brown, Paul M.; McAlister, Finlay A.; Rowe, Brian H.; Braam, Branko

2015-01-01

Background Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed. Objectives The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function. Methods 696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR≥45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR ≥20% decline; stable [SRF]; and improving [IRF]: eGFR ≥20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7–24.9) and 32.5 months (95%CI 18.8–56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function. PMID:26380982

Characteristics and clinical outcomes of living renal donors in Hong Kong.

PubMed

Hong, Y L; Yee, C H; Leung, C B; Teoh, J Yc; Kwan, B Ch; Li, P Kt; Hou, S Sm; Ng, C F

2018-02-01

In Asia, few reports are available on the outcomes for living renal donors. We report the short- and long-term clinical outcomes of individuals following living donor nephrectomy in Hong Kong. We retrospectively reviewed the characteristics and clinical outcomes of all living renal donors who underwent surgery from January 1990 to December 2015 at a teaching hospital in Hong Kong. Information was obtained from hospital records and territory-wide electronic patient records. During the study period, 83 individuals underwent donor nephrectomy. The mean (± standard deviation) follow-up time was 12.0 ± 8.3 years, and the mean age at nephrectomy was 37.3 ± 10.0 years. A total of 44 (53.0%), four (4.8%), and 35 (42.2%) donors underwent living donor nephrectomy via an open, hand-port assisted laparoscopic, and laparoscopic approach, respectively. The overall incidence of complications was 36.6%, with most being grade 1 or 2. There were three (9.4%) grade 3a complications; all were related to open donor nephrectomy. The mean glomerular filtration rate was 96.0 ± 17.5 mL/min/1.73 m 2 at baseline and significantly lower at 66.8 ± 13.5 mL/min/1.73 m 2 at first annual follow-up (P<0.01). The latest mean glomerular filtration rate was 75.6% ± 15.1% of baseline. No donor died or developed renal failure. Of the donors, 14 (18.2%) developed hypertension, two (2.6%) had diabetes mellitus, and three (4.0%) had experienced proteinuria. The overall perioperative outcomes are good, with very few serious complications. The introduction of a laparoscopic approach has decreased perioperative blood loss and also shortened hospital stay. Long-term kidney function is satisfactory and no patients developed end-stage renal disease. The incidences of new-onset medical diseases and pregnancy-related complications were also low.

Adverse Perinatal Outcomes among Immigrant Women from Ethiopia in Israel.

PubMed

Calderon-Margalit, Ronit; Sherman, Dan; Manor, Orly; Kurzweil, Yaffa

2015-06-01

Immigration from Ethiopia to Israel started about 30 years ago. We aimed to compare birth outcomes between Israeli women of Ethiopian origin and Israeli-born, non-Ethiopian women. We hypothesized a higher frequency of adverse birth outcomes among Ethiopian women and a trend of improvement among those who were raised in Israel since early childhood. This is a descriptive study, comparing birth outcomes of Ethiopian (n = 1,319) and non-Ethiopian women (n = 27,307) who gave birth in a medical center in Central Israel in 2002 to 2009. Ethiopian women were further categorized by age at immigration. Logistic regressions were constructed to compare the incidence of adverse birth outcomes between Ethiopian and non-Ethiopian women, controlling for potential confounders. Ethiopian women had about twice the incidence of very and extremely preterm births, compared with non-Ethiopians. Ethiopian women had twice the odds for neonates who were either small for gestational age or had low 5-minute Apgar scores. Ethiopian women had about threefold increased risk of stillbirths (OR 2.9 [95% CI 1.87-4.49]). No trend of improvement was noted for women who were raised in Israel from early childhood. Ethiopian women are at increased risk of adverse birth outcomes. Future research is needed to investigate the underlying causes for the increased risks and lack of improvement among those who were raised in Israel that will lead to effective interventions. © 2015 Wiley Periodicals, Inc.

Quantitative Adverse Outcome Pathways and Their ...

EPA Pesticide Factsheets

A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course predictions that can support regulatory decision-making. Herein we describe several facets of qAOPs, including (a) motivation for development, (b) technical considerations, (c) evaluation of confidence, and (d) potential applications. The qAOP used as an illustrative example for these points describes the linkage between inhibition of cytochrome P450 19A aromatase (the MIE) and population-level decreases in the fathead minnow (FHM; Pimephales promelas). The qAOP consists of three linked computational models for the following: (a) the hypothalamic-pitutitary-gonadal axis in female FHMs, where aromatase inhibition decreases the conversion of testosterone to 17β-estradiol (E2), thereby reducing E2-dependent vitellogenin (VTG; egg yolk protein precursor) synthesis, (b) VTG-dependent egg development and spawning (fecundity), and (c) fecundity-dependent population trajectory. While development of the example qAOP was based on experiments with FHMs exposed to the aromatase inhibitor fadrozole, we also show how a toxic equivalence (TEQ) calculation allows use of the qAOP to predict effects of another, untested aromatase inhibitor, iprodione. While qAOP development can be resource-intensive, the quan

Setting the stage to advance the adverse outcome pathway (AOP) framework through horizon scanning

EPA Science Inventory

Recognizing the international interest surrounding the adverse outcome pathway framework, which captures existing information describing causal linkages between a molecular initiating event through levels of biological organization to an adverse outcome of regulatory significance...

Dental neglect and adverse birth outcomes: a validation and observational study.

PubMed

Acharya, S; Pentapati, K C; Bhat, P V

2013-05-01

The objectives of this study were to validate the Indian translation of the Dental Neglect Scale (DNS) among a sample of parturient Indian women and to investigate dental neglect as a possible risk indicator in adverse birth outcomes. Three hundred and sixteen parturient women were administered the DNS and the Modified Dental Beliefs Scale (MDBS) and were also clinically examined for oral health status. Information regarding socio-economic status, weeks of gestation and birth weight was also collected. A gestation period of less than 37 weeks was considered as preterm and a birth weight of less than 2500 gm as 'low birth weight'. The Indian version of the DNS was found to be reliable (Cronbach's Alpha = 0.72) and valid for assessing dental neglect among the women. Factor analysis of the DNS revealed a two-factor structure accounting for 56% variance. Dental neglect was higher among those with poorer oral health status, lower socio-economic and educational status. Multinomial logistic regression showed high dental neglect and negative dental beliefs and not poor oral health, as significant risk indicators for occurrence of adverse birth outcomes. The finding of an association of adverse birth outcomes with dental neglect and beliefs, but not with poor oral health could be due to the influence of other more important general factors which had a direct bearing on birth outcomes. There is a need for further research to assess the role of behavioural factors like dental neglect as risk indicators for adverse birth outcomes. © 2012 John Wiley & Sons A/S.

Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy.

PubMed

Sachs, Adam; Guglielminotti, Jean; Miller, Russell; Landau, Ruth; Smiley, Richard; Li, Guohua

2017-05-01

Identification of risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy is necessary for evidence-based risk reduction and adequate patient counseling. To identify risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy and stratify the risk of such outcomes. A cohort study was conducted using the Nationwide Inpatient Sample, a nationally representative sample of patients discharged from community hospitals in the United States, from January 1, 2003, to December 31, 2012. Multivariable analysis of risk factors for adverse obstetric outcomes was performed for 19 926 women undergoing appendectomy or cholecystectomy during pregnancy and a scoring system for such risk factors was developed. Data analysis was conducted from January 1, 2015, to July 31, 2016. A composite measure including 7 adverse obstetrical outcomes throughout pregnancy and occurring before hospital discharge. Of the 19 926 women (mean [SD] age, 26 [6] years) in the study, 1018 adverse obstetrical events were recorded in 953 pregnant women (4.8%). The 3 most frequent adverse events were preterm delivery (360 [35.4%]), preterm labor without preterm delivery (269 [26.4%]), and miscarriage (262 [25.7%]). The risk factors associated most strongly with an adverse obstetrical outcome included cervical incompetence (adjusted odds ratio, 24.29; 95% CI, 7.48-78.81), preterm labor during current pregnancy (adjusted odds ratio, 18.34; 95% CI, 4.95-67.96), vaginitis or vulvovaginitis (adjusted odds ratio, 5.17; 95% CI, 2.19-12.23), and sepsis (adjusted odds ratio, 3.39; 95% CI, 2.08-5.51). A scoring system based on statistically significant variables classified the study sample into 3 risk groups corresponding to predicted probabilities of adverse obstetrical outcomes of 2.5% (≤4 points), 8.2% (5-8 points), and 21.8% (≥9 points). Approximately 5% of women experience adverse obstetrical outcomes after appendectomy

Maternal psychological distress during pregnancy does not increase the risk for adverse birth outcomes.

PubMed

Staneva, Aleksandra A; Morawska, Alina; Bogossian, Fiona; Wittkowski, Anja

2018-01-01

Maternal psychological distress during pregnancy is a potential risk factor for various birth complications. This study aimed to explore psychological factors associated with adverse birth outcomes. Symptoms of psychological distress, individual characteristics, and medical complications were assessed at two time points antenatally in 285 women from Australia and New Zealand; birth outcomes were assessed postpartum, between January 2014 and September 2015. Hierarchical multiple regression analyses were conducted to examine the relation of psychological distress to adverse birth outcomes. Medical complications during pregnancy, such as serious infections, placental problems and preeclampsia, and antenatal cannabis use, were the factors most strongly associated with adverse birth outcomes, accounting for 22 percent of the total variance (p < .001). Symptoms of depression and/or anxiety, low social support, and low sense of coherence were not associated with birth complications. In unadjusted analyses, self-reported diagnosis of anxiety disorder during pregnancy and an orientation toward a Regulator mothering style were associated with adverse birth outcomes; however, after controlling for medical complications, these were no longer associated. Our study results indicate that antenatal depressive and/or anxiety symptoms were not independently associated with adverse birth outcomes, a reassuring finding for women who are already psychologically vulnerable during pregnancy.

Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

PubMed Central

Goetzl, Laura

2010-01-01

Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy

PubMed Central

Guglielminotti, Jean; Miller, Russell; Landau, Ruth; Smiley, Richard; Li, Guohua

2017-01-01

Importance Identification of risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy is necessary for evidence-based risk reduction and adequate patient counseling. Objectives To identify risk factors for adverse obstetrical outcomes after appendectomy and cholecystectomy during pregnancy and stratify the risk of such outcomes. Design, Setting, and Participants A cohort study was conducted using the Nationwide Inpatient Sample, a nationally representative sample of patients discharged from community hospitals in the United States, from January 1, 2003, to December 31, 2012. Multivariable analysis of risk factors for adverse obstetric outcomes was performed for 19 926 women undergoing appendectomy or cholecystectomy during pregnancy and a scoring system for such risk factors was developed. Data analysis was conducted from January 1, 2015, to July 31, 2016. Main Outcomes and Measures A composite measure including 7 adverse obstetrical outcomes throughout pregnancy and occurring before hospital discharge. Results Of the 19 926 women (mean [SD] age, 26 [6] years) in the study, 1018 adverse obstetrical events were recorded in 953 pregnant women (4.8%). The 3 most frequent adverse events were preterm delivery (360 [35.4%]), preterm labor without preterm delivery (269 [26.4%]), and miscarriage (262 [25.7%]). The risk factors associated most strongly with an adverse obstetrical outcome included cervical incompetence (adjusted odds ratio, 24.29; 95% CI, 7.48-78.81), preterm labor during current pregnancy (adjusted odds ratio, 18.34; 95% CI, 4.95-67.96), vaginitis or vulvovaginitis (adjusted odds ratio, 5.17; 95% CI, 2.19-12.23), and sepsis (adjusted odds ratio, 3.39; 95% CI, 2.08-5.51). A scoring system based on statistically significant variables classified the study sample into 3 risk groups corresponding to predicted probabilities of adverse obstetrical outcomes of 2.5% (≤4 points), 8.2% (5-8 points), and 21.8% (≥9

Do the outcomes of living donor renal allograft recipients differ with peritoneal dialysis and hemodialysis as a bridge renal replacement therapy?

PubMed

Prasad, Narayan; Vardhan, Harsh; Baburaj, Vinod P; Bhadauria, Dharmendra; Gupta, Amit; Sharma, Raj K; Kaul, Anupama

2014-11-01

This study was undertaken to compare the outcomes of living donor renal transplant recipients using peritoneal dialysis (PD) and hemodialysis (HD) as a bridge modality for renal replacement therapy till renal transplantation. The demographic profiles of the recipients and donors, the patients' native kidney disease (diabetic versus non-diabetic), duration on dialysis, requirement of anti-hypertensive drugs, number of blood transfusions, human leukocyte antigen (HLA) mismatch status, pre- and post-transplant infectious complications, and post-transplant outcomes of patients were compared between the two groups. The demographic features of the study patients were similar in the two groups. The duration of dialysis prior to transplant was significantly longer in the PD group than in the HD group of patients. The anti-hypertensive drug requirement was lower and the hemoglobin level and residual urine volume at the time of transplant were relatively better in the PD patients compared to the HD patients. The number of acute rejection episodes, delayed graft function, surgical complications, glomerular filtration rate at one month and at the last follow-up, were also similar in both groups. The short-term and long-term graft survival was similar in both groups of patients. The one-, two-, five-, and eight-year death-censored graft survival rates of the PD patients were 98, 95, 85, and 73%, respectively, and in the HD group of patients, they were 100, 93, 84, and 79%, respectively. The one-, two-, five-, and eight-year patient survival rates in the PD group were 97, 92, 77, and 66%, respectively, and in the HD group, they were 97, 92, 79, and 69%, respectively. Our study suggests that the outcomes of the living donor renal allograft recipients did not differ between the groups of patients who used PD or HD as renal replacement therapy prior to renal transplantation.

Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

PubMed

Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

2016-08-01

Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity. © The Author(s) 2015.

Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.

PubMed

Kovesdy, Csaba P; Matsushita, Kunihiro; Sang, Yingying; Brunskill, Nigel J; Carrero, Juan J; Chodick, Gabriel; Hasegawa, Takeshi; Heerspink, Hiddo L; Hirayama, Atsushi; Landman, Gijs W D; Levin, Adeera; Nitsch, Dorothea; Wheeler, David C; Coresh, Josef; Hallan, Stein I; Shalev, Varda; Grams, Morgan E

2018-05-01

Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.

Renal function following xenon anesthesia for partial nephrectomy-An explorative analysis of a randomized controlled study.

PubMed

Stevanovic, Ana; Schaefer, Patrick; Coburn, Mark; Rossaint, Rolf; Stoppe, Christian; Boor, Peter; Pfister, David; Heidenreich, Axel; Christ, Hildegard; Hellmich, Martin; Fahlenkamp, Astrid V

2017-01-01

Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies. We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients. A prospective randomized, single-blinded, controlled study. Single-center, University Hospital of Aachen, Germany between July 2013-October 2015. Forty-six patients with regular renal function undergoing partial nephrectomy. Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia. Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months. Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months. Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon. ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

THE ADVERSE OUTCOME PATHWAY (AOP) FRAMEWORK ...

EPA Pesticide Factsheets

An Adverse Outcome Pathway (AOP) represents the organization of current and newly acquired knowledge of biological pathways. These pathways contain a series of nodes (Key Events, KEs) that when sufficiently altered influence the next node on the pathway, beginning from an Molecular Initiating Event (MIE), through intermediate KEs, ending in an Adverse Outcome (AO) which may be used as a basis for decision making. A KE is a measurable biological change, and is linked with other KEs via Key Event Relationships (KERs). A given KE may be involved in several AOPs, leading to a plausible network of biological changes that are involved in an organism’s response to an external stressor. When describing an AOP, five guiding principles have been proposed [1]: 1) an AOP is not specific to a single external stressor, 2) AOPs are modular, with KEs and KERs that can be used in several AOPs, 3) a single AOP is the unit of development, 4) most biological responses will be the result of networks of AOPs, and 5) AOPs will be modified as more biological knowledge becomes available. The collaborative development of AOPs is recommended to be performed using the AOP-Wiki (https://aopwiki.org), which is an effort between the European Commission – DG Joint Research Centre (JRC) and U.S. Environmental Protection Agency (EPA). The Wiki is one part of a larger OECD-sponsored AOP Knowledgebase effort, which is a repository for all AOPs developed as part of the Organization for Economic

PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework proceeds from a general (e.g., not chemical specific) molecular mode of action, designated as a MIE, through stepwise changes in biological status, defined as key events (KEs), to a final AO that can be used in risk assessment. Because aromatase-inhibiting pharmaceuticals are widely used to treat breast cancer patients, we explored the unintended consequences that might occur in fish exposed to these chemicals through wastewater discharge into the aquatic environment. Unlike mammals, fish have two isoforms of aromatase, one that predominates in the ovary (cyp19a1a) and a second (cyp19a1b) that prevails in the brain. Aromatase activity in fish brain can be 100 to 1000 times that in mammals and is associated with reproduction. We have developed a putative AOP for inhibition of brain aromatase in fish leading to reproductive dysfunction based on review of relevant literature and reproductive experiments with the marine fish cunner (Tautogolabrus adspersus) exposed to aromatase-inhibiting pharmaceuticals in the laboratory. The first KE in this AOP is a decrease in brain aromatase activity due to exposure to an aromatase inhibitor. KEs then progress through subsequent steps including decreas

Comparison of clamping technique in robotic partial nephrectomy: does unclamped partial nephrectomy improve perioperative outcomes and renal function?

PubMed

Krane, L Spencer; Mufarrij, Patrick W; Manny, Theodore B; Hemal, Ashok K

2013-02-01

Partial nephrectomy without renal vascular occlusion has been introduced to improve outcomes in patients undergoing robotic partial nephrectomy (RPN). We prospectively evaluated unclamped RPN at our institution and compared this to other clamping techniques in a non-randomized fashion. Ninety-five consecutive patients who successfully completed RPN between June 2010 and October 2011 are included in this analysis. All RPNs were performed by a single surgeon. Clamping technique was artery and vein (AV), artery alone (AO) or unclamped (U) without hypotensive anesthesia. Clamping decision was based on surgeon preference and feasibility of minimizing ischemia. All patients had bilateral functional renal units. Eighteen (19%), 58 (61%) and 19 (20%) patients had AV, AO and U technique respectively. Preoperative characteristics including age (p = 0.43), body mass index (p = 0.40) and RENAL nephromety distribution (p = 0.10) were similar. In AV and AO, mean warm ischemia time were 19 and 17 minutes and similar between the two cohorts (p = 0.39). Mean glomerular filtration rate (GFR) and overall percentage decrease in GFR at time of at last follow up were (64, 69, 81, p = 0.12) and (6%, 6%,and 2%,p = 0.79) for AV, AO and U respectively. Median follow up for last serum creatinine was 113 days and was similar between all cohorts (p = 0.37). Complication rate (p = 0.37), positive margin rate (p = 0.84), and change in hemoglobin concentration postoperatively (p = 0.94) were similar between cohorts. Unclamped partial nephrectomy is possible in patients undergoing RPN. In this study, it does not significantly alter perioperative or postoperative renal function or change rate of complications. Minimal ischemia, irrespective of clamping technique, in patients with bilateral renal units does not appear to adversely effect intermediate term renal function in these patients.

Racial Discrimination and Adverse Birth Outcomes: An Integrative Review.

PubMed

Alhusen, Jeanne L; Bower, Kelly M; Epstein, Elizabeth; Sharps, Phyllis

2016-11-01

This article presents an integrative review of the literature examining the relationship between racial discrimination and adverse birth outcomes. Searches for research studies published from 2009 to 2015 were conducted using PubMed, CINAHL, Scopus, PsycINFO, Web of Science, and Embase. Articles were assessed for potential inclusion using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2009 framework. Fifteen studies met criteria for review. The majority of the studies found a significant relationship between racial discrimination and low birth weight, preterm birth, and small for gestational age. Each of the studies that examined more proximal variables related to birth outcomes such as entry into prenatal care, employment opportunities, neighborhood characteristics, or inflammatory markers found significant associations between the specific variables examined and racial discrimination. Participants in qualitative studies discussed experiences of institutional racism with regard to several components of prenatal care including access and quality of care. Racial discrimination is a significant risk factor for adverse birth outcomes. To best understand the mechanisms by which racial discrimination impacts birth outcomes, and to inform the development of effective interventions that eliminate its harmful effects on health, longitudinal research that incorporates comprehensive measures of racial discrimination is needed. Health care providers must fully acknowledge and address the psychosocial factors that impact health outcomes in minority racial/ethnic women. © 2016 by the American College of Nurse-Midwives.

Racial Discrimination and Adverse Birth Outcomes: An Integrative Review

PubMed Central

Alhusen, Jeanne L.; Bower, Kelly; Epstein, Elizabeth; Sharps, Phyllis

2016-01-01

Introduction This article presents an integrative review of the literature examining the relationship between racial discrimination and adverse birth outcomes. Methods Searches for research studies published from 2009 to 2015 were conducted using PubMed, CINAHL, Scopus, PsycINFO, Web of Science, and Embase. Articles were assessed for potential inclusion using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2009 framework. Results Fifteen studies met criteria for review. The majority of the studies found a significant relationship between racial discrimination and low birth weight, preterm birth, and small for gestational age. Each of the studies that examined more proximal variables related to birth outcomes such as entry into prenatal care, employment opportunities, neighborhood characteristics, or inflammatory markers found significant associations between the specific variables examined and racial discrimination. Participants in qualitative studies discussed experiences of institutional racism with regard to several components of prenatal care including access and quality of care. Discussion Racial discrimination is a significant risk factor for adverse birth outcomes. To best understand the mechanisms by which racial discrimination impacts birth outcomes, and to inform the development of effective interventions that eliminate its harmful effects on health, longitudinal research that incorporates comprehensive measures of racial discrimination is needed. Health care providers must fully acknowledge and address the psychosocial factors that impact health outcomes in minority racial/ethnic women. PMID:27737504

[Chorionicity and adverse perinatal outcome].

PubMed

Ferreira, Isabel; Laureano, Carla; Branco, Miguel; Nordeste, Ana; Fonseca, Margarida; Pinheiro, Adelaide; Silva, Maria Isabel; Almeida, Maria Céu

2005-01-01

Considering the highest rate of morbidity and mortality in diamniotic monochorionic twins, the authors evaluated and compared the adverse obstetric and perinatal outcome in twin pregnancies according to chorionicity. A retrospective study was conducted in all twin deliveries that occurred in the Obstetric Unit of Maternidade Bissaya-Barreto, for a period of tree years (from the 1st of January 1999 until the 31st of December 2001). From de 140 diamniotic twin pregnancies studied, we considered two groups according to the chorionicity: monochorionic and dichorionic. We compared multiple parameters as, epidemiologic data, adverse obstetric outcome, gestacional delivery age, type of delivery and the morbidity, the mortality and the follow-up of the newborn. The statistic tests used were the X2 and the t student. From the 140 twin pregnancies included in the study, 66% (92 cases) presented dichorionic placentation and 34% (48 cases) were monochorionic. In the group of monochorionic pregnancies, we observed highly difference related to pathology of amniotic fluid (14.5% vs 2.2%), discordant fetal growth (41.6% vs 22.8%) and rate of preterm delivery (66.6% vs 32.6%). Related to the newborn we verified that they had a lower average birth weight (1988g vs 2295g), a highly rate of weight discordancy (23% vs 15.3%), intraventricular haemorrhage (2.2% vs 0%) and IUGR (6.6% vs 1.6%), statistically significant in the monochorionic group. Also the perinatal mortality rate was significantly higher in the monochorionic pregnancies (93.7 per thousand vs 21.7 per thousand). The high rate of morbidity and mortality related to the monochorionic twin pregnancies, implies the need of a correct identification of the type of chorionicity and also a high standard of prenatal surveillance in prenatal specialised health centers.

The perioperative outcomes between renal hilar and non-hilar tumors following robotic-assisted partial nephrectomy (RAPN).

PubMed

Lu, Shih-Yen; Chung, Hsiao-Jen; Huang, Eric Yi-Hsiu; Lin, Tzu-Pin; Lin, Alex T L

2018-03-15

The aim of this study was to compare the perioperative outcomes between renal hilar tumors and non-hilar tumors after robotic-assisted partial nephrectomy (RAPN). A retrospective review of consecutive patients who underwent RAPN from December 2009 to September 2015 at our institution was recruited. Perioperative outcomes including demographic characteristics, perioperative, pathological and renal function outcomes were compared between the hilar group (n = 30) and non-hilar group (n = 170). In characteristics, hilar group was younger (52.4 vs. 58 years, p = 0.04) and had less body mass index (23.7 vs. 25.4 kg/m 2 , p = 0.018). Hilar group had larger tumor size (4.8 vs. 3.7 cm, p = 0.009), higher Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score (10.7 vs. 8.5, p < 0.001) and higher RENAL (radius, exophytic/endophytic properties of the tumor, nearness of tumor deepest portion to the collecting system or sinus, anterior/posterior description and the location relative to polar lines) score (9.0 vs. 7.4, p < 0.001). Hilar tumor was associated with longer operative time (293.6 vs. 240.5 min, p = 0.001) and warm ischemia time (39.9 vs. 21.8 min, p < 0.001). But there was no statistically difference in estimated blood loss (EBL), postoperative stay and complication rate. For pathological outcomes, there was no difference of positive margin rate and pathological T stage between these groups. For renal function outcomes, hilar tumor patients had no difference of the change of creatinine and estimated glomerular filtration rate (eGFR) at postoperative 6 and 12 month as compared with non-hilar tumor patients. For renal hilar tumor, RAPN could provide acceptable results of perioperative, pathological and renal function outcome as compared with non-hilar tumor group. Thus RAPN is a safe and effective nephron-sparing surgery technique for renal hilar tumors. Copyright © 2018. Published by Elsevier Taiwan LLC.

Atherosclerotic renal artery stenosis: epidemiology, cardiovascular outcomes, and clinical prediction rules.

PubMed

Zoccali, Carmine; Mallamaci, Francesca; Finocchiaro, Pietro

2002-11-01

Atherosclerotic renal artery stenosis is the most common primary disease of the renal arteries, and it is associated with two major clinical syndromes, ischemic renal disease and hypertension. The prevalence of this disease in the population is undefined because there is no simple and reliable test that can be applied on a large scale. Renal artery involvement in patients with coronary heart disease and/or heart failure is frequent, and it may influence cardiovascular outcomes and survival in these patients. Suspecting renal arterial stenosis in patients with recurrent episodes of pulmonary edema is justified by observations showing that about one third of elderly patients with heart failure display atherosclerotic renal disease. Whether interventions aimed at restoring arterial patency may reduce the high mortality in patients with heart failure is still unclear because, to date, no prospective study has been carried out in these patients. Increased awareness of the need for cost containment has renewed the interest in clinical cues for suspecting renovascular hypertension. In this regard, the DRASTIC study constitutes an important attempt at validating clinical prediction rules. In this study, a clinical rule was derived that predicted renal artery stenosis as efficiently as renal scintigraphy (sensitivity: clinical rule, 65% versus scintigraphy, 72%; specificity: 87% versus 92%). When tested in a systematic and quantitative manner, clinical findings can perform as accurately as more complex tests in the detection of renal artery stenosis.

Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

PubMed Central

Fejzo, Marlena S.; Magtira, Aromalyn; Schoenberg, Frederic Paik; MacGibbon, Kimber; Mullin, Patrick; Romero, Roberto; Tabsh, Khalil

2014-01-01

Objective The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors. Study design This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test. Results Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhy- dramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome. Conclusion Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy. PMID:23751910

ADVERSE PREGNANCY OUTCOMES ASSOCIATED WITH MATERNAL ENALAPRIL ANTIHYPERTENSIVE TREATMENT

EPA Science Inventory

Enalapril, one of several antihypertensive drugs that act as angiotensin-converting enzyme (ACE) inhibitors, is often used for treatment of hypertension in women of reproductive age. Adverse birth outcomes following the use of ACE inhibitors, including enalapril, during pregnanc...

Development of Quantitative Adverse Outcome Pathways Using Health-Protective Assumptions to Fill Data Gaps

EPA Science Inventory

In an adverse outcome pathway (AOP), the target site dose participates in a molecular initiating event (MIE), which in turn triggers a sequence of key events leading to an adverse outcome (AO). Quantitative AOPs (QAOP) are needed if AOP characterization is to address risk as well...

20170312 - Adverse Outcome Pathway (AOP) framework for ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Adverse Outcome Pathway (AOP) framework for embryonic ...

EPA Pesticide Factsheets

Vascular development commences with de novo assembly of a primary capillary plexus (vasculogenesis) followed by its expansion (angiogenesis) and maturation (angio-adaptation) into a hierarchical system of arteries and veins. These processes are tightly regulated by genetic signals and environmental factors linked to morphogenesis and microphysiology. Gestational exposure to some chemicals disrupts vascular development leading to adverse outcomes. To broadly assess consequences of gestational toxicant exposure on vascular development, an Adverse Outcome Pathway (AOP) framework was constructed that integrates data from ToxCast high-throughput screening (HTS) assays with pathway-level information from the literature and public databases. The AOP-based model resolved the ToxCast library (1065 compounds) into a matrix based on several dozen molecular functions critical for developmental angiogenesis. A sample of 38 ToxCast chemicals selected across the matrix tested model performance. Putative vascular disrupting chemical (pVDC) bioactivity was assessed by multiple laboratories utilizing diverse angiogenesis assays, including: transgenic zebrafish, complex human cell co-cultures, engineered microscale systems, and human-synthetic models. The ToxCast pVDC signature predicted vascular disruption in a manner that was chemical-specific and assay-dependent. An AOP for developmental vascular toxicity was constructed that focuses on inhibition of VEGF receptor (VEGFR2). Thi

Predicting adverse neonatal outcomes in fetuses with abdominal wall defects using prenatal risk factors.

PubMed

Nicholas, Sara S; Stamilio, David M; Dicke, Jeffery M; Gray, Diana L; Macones, George A; Odibo, Anthony O

2009-10-01

The aim of this study was to determine whether prenatal variables can predict adverse neonatal outcomes in fetuses with abdominal wall defects. A retrospective cohort study that used ultrasound and neonatal records for all cases of gastroschisis and omphalocele seen over a 16-year period. Cases with adverse neonatal outcomes were compared with noncases for multiple candidate predictive factors. Univariable and multivariable statistical methods were used to develop the prediction models, and effectiveness was evaluated using the area under the receiver operating characteristic curve. Of 80 fetuses with gastroschisis, 29 (36%) had the composite adverse outcome, compared with 15 of 33 (47%) live neonates with omphalocele. Intrauterine growth restriction was the only significant variable in gastroschisis, whereas exteriorized liver was the only predictor in omphalocele. The areas under the curve for the prediction models with gastroschisis and omphalocele are 0.67 and 0.74, respectively. Intrauterine growth restriction and exteriorization of the liver are significant predictors of adverse neonatal outcome with gastroschisis and omphalocele.

Does early second-trimester sonography predict adverse perinatal outcomes in monochorionic diamniotic twin pregnancies?

PubMed

Allaf, M Baraa; Campbell, Winston A; Vintzileos, Anthony M; Haeri, Sina; Javadian, Pouya; Shamshirsaz, Amir A; Ogburn, Paul; Figueroa, Reinaldo; Wax, Joseph; Markenson, Glenn; Chavez, Martin R; Ravangard, Samadh F; Ruano, Rodrigo; Sangi-Haghpeykar, Haleh; Salmanian, Bahram; Meyer, Marjorie; Johnson, Jeffery; Ozhand, Ali; Davis, Sarah; Borgida, Adam; Belfort, Michael A; Shamshirsaz, Alireza A

2014-09-01

To determine whether intertwin discordant abdominal circumference, femur length, head circumference, and estimated fetal weight sonographic measurements in early second-trimester monochorionic diamniotic twins predict adverse obstetric and neonatal outcomes. We conducted a multicenter retrospective cohort study involving 9 regional perinatal centers in the United States. We examined the records of all monochorionic diamniotic twin pregnancies with two live fetuses at the 16- to 18-week sonographic examination who had serial follow-up sonography until delivery. The intertwin discordance in abdominal circumference, femur length, head circumference, and estimated fetal weight was calculated as the difference between the two fetuses, expressed as a percentage of the larger using the 16- to 18-week sonographic measurements. An adverse composite obstetric outcome was defined as the occurrence of 1 or more of the following in either fetus: intrauterine growth restriction, twin-twin transfusion syndrome, intrauterine fetal death, abnormal growth discordance (≥20% difference), and very preterm birth at or before 28 weeks. An adverse composite neonatal outcome was defined as the occurrence of 1 or more of the following: respiratory distress syndrome, any stage of intraventricular hemorrhage, 5-minute Apgar score less than 7, necrotizing enterocolitis, culture-proven early-onset sepsis, and neonatal death. Receiver operating characteristic and logistic regression-with-generalized estimating equation analyses were constructed. Among the 177 monochorionic diamniotic twin pregnancies analyzed, intertwin abdominal circumference and estimated fetal weight discordances were only predictive of adverse composite obstetric outcomes (areas under the curve, 79% and 80%, respectively). Receiver operating characteristic curves showed that intertwin discordances in abdominal circumference, femur length, head circumference, and estimated fetal weight were not acceptable predictors of twin

Theoretical Framework to Extend Adverse Outcome Pathways to Include Pharmacokinetic Considerations

EPA Science Inventory

Adverse Outcome Pathways (AOPs) have generated intense interest for their utility in linking known population outcomes to a molecular initiating event (MIE) that can be quantified using in vitro methods. While there are tens of thousands of chemicals in commercial use, biology h...

Trainee participation is associated with adverse outcomes in emergency general surgery: an analysis of the National Surgical Quality Improvement Program database.

PubMed

Kasotakis, George; Lakha, Aliya; Sarkar, Beda; Kunitake, Hiroko; Kissane-Lee, Nicole; Dechert, Tracey; McAneny, David; Burke, Peter; Doherty, Gerard

2014-09-01

To identify whether resident involvement affects clinically relevant outcomes in emergency general surgery. Previous research has demonstrated a significant impact of trainee participation on outcomes in a broad surgical patient population. We identified 141,010 patients who underwent emergency general surgery procedures in the 2005-2010 Surgeons National Surgical Quality Improvement Program database. Because of the nonrandom assignment of complex cases to resident participation, patients were matched (1:1) on known risk factors [age, sex, inpatient status, preexisting comorbidities (obesity, diabetes, smoking, alcohol, steroid use, coronary artery disease, chronic renal failure, pulmonary disease)] and preoperatively calculated probability for morbidity and mortality. Clinically relevant outcomes were compared with a t or χ test. The impact of resident participation on outcomes was assessed with multivariable regression modeling, adjusting for risk factors and operative time. The most common procedures in the matched cohort (n = 83,790) were appendectomy (39.9%), exploratory laparotomy (8.8%), and adhesiolysis (6.6%). Trainee participation is independently associated with intra- and postoperative events, wound, pulmonary, and venous thromboembolic complications, and urinary tract infections. Trainee participation is associated with adverse outcomes in emergency general surgery procedures.

Comparison of clinical and laboratory parameters in patients with end-stage renal failure in the outcome of chronic glomerulonephritis and patients with end-stage renal failure in the outcome of other diseases.

PubMed

Popova, J A; Yadrihinskaya, V N; Krylova, M I; Sleptsovа, S S; Borisovа, N V

frequent complications of hemodialysis treatments are coagulation disorders. This is due to activation of the coagulation of blood flow in the interaction with a dialysis membrane material vascular prostheses and extracorporeal circuit trunks. In addition, in hemodialysis patients receiving heparin for years, there is depletion of stocks in endothelial cells in tissue factor inhibitor, inhibits the activity of an external blood clotting mechanism. the aim of our study was to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure. to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure and hemodialysis treatment duration conducted a study that included 100 patients observed in the department of chronic hemodialysis and nephrology hospital №1 Republican National Medical Center in the period of 2013-2016. in patients with end-stage renal failure in the outcome of chronic glomerulonephritis, a great expression of activation of blood coagulation confirm increased the mean concentration of fibrinogen, whereas in the group, which included patients with end-stage renal failure in the outcome of other diseases, such is not different from the norm, and a higher rate of hyperfibrinogenemia, identified in 2/3 patients in this group. it was revealed that the state of homeostasis in patients with end-stage renal failure in increasingly characterizes the level of fibrinogen and the activation of the hemostatic markers: soluble fibrin monomer complexes, D-dimers.

[Adverse pregnancy outcomes after Assisted Reproduction Technology in women with endometriosis].

PubMed

Carassou-Maillan, A; Pouly, J-L; Mulliez, A; Dejou-Bouillet, L; Gremeau, A-S; Brugnon, F; Janny, L; Canis, M

2014-04-01

While association between endometriosis and infertility is well established, there are few studies about the impact of endometriosis on adverse pregnancy outcomes. The aim of this study was to determine the effect of endometriosis on obstetric outcomes and whether the severity of the disease had an influence on these. We performed a retrospective study to investigate the obstetric outcomes of a population of 1204 subfertile women, including 258 with endometriosis, who obtained, thanks to assisted reproduction technology, a singleton pregnancy evolving beyond embryonic stage. Two analyzes were performed. The first compared women with endometriosis to women with other causes of infertility. The second observed adverse pregnancy outcomes according to AFS-R stages of endometriosis. The overall rate of live birth children was 95.8%. In case of endometriosis, there was a significant increase of the incidence of preterm delivery, especially before 32 weeks amenorrhea (6.2% vs 3.1% in the group "without endometriosis", P = 0.03), antenatal bleeding (5.3% vs 2.2%, P = 0.01) and placenta previa (4.9% vs 0.9%, P < 0.0001). The incidence of gestational diabetes was significantly decreased (0.4% vs 2.7%, P = 0.04). There was no correlation between endometriosis and cesarean section or preeclampsia, or between the AFS-R stage and adverse pregnancy outcomes. Endometriosis is a factor of obstetrical risk, independently of the infertility it causes. The AFS-R score does not seem to be representative of obstetric outcomes beyond first trimester of pregnancy for women with endometriosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Outcome of Renal Artery Reconstruction

PubMed Central

Darling, R. Clement; Kreienberg, Paul B.; Chang, Benjamin B.; Paty, Philip S. K.; Lloyd, William E.; Leather, Robert P.; Shah, Dhiraj M.

1999-01-01

Objective To evaluate the short- and long-term results of surgical reconstruction of the renal arteries, the authors review their experience with more than 600 reconstructions performed over a 12-year period. Summary Background Data Reconstruction of the renal arteries, whether for primary renal indications or concomitantly with aortic reconstruction, has evolved over the past 40 years. There is concern that renal artery reconstructions carry significant rates of mortality and morbidity and may fare poorly compared with less-invasive procedures. Methods From 1986 to 1998, 687 renal artery reconstructions were performed in 568 patients. Of these, 105 patients had simultaneous bilateral renal artery reconstructions. Fifty-six percent of the patients were male; 11% had diabetes; 35% admitted to smoking at the time of surgery. Mean age was 67 (range, 1 to 92). One hundred fifty-six (23%) were primary procedures and the remainder were adjunctive procedures with aortic reconstructions; 406 were abdominal aortic aneurysms and 125 were aortoiliac occlusive disease. Five hundred procedures were bypasses, 108 were endarterectomies, 72 were reimplantation, and 7 were patch angioplasties. There were 31 surgical deaths (elective and emergent) in the entire group for a mortality rate of 5.5%. Predictors of increased risk of death were patients with aortoiliac occlusive disease and patients undergoing bilateral simultaneous renal artery revascularization. Cause of death was primarily cardiac. Other nonfatal complications included bleeding (nine patients) and wound infection (three patients). There were 9 immediate occlusions (1.3%) and 10 late occlusions (1.5%). Thirty-three patients (4.8%) had temporary worsening of their renal function after surgery. Conclusion Renal artery revascularization is a safe and durable procedure. It can be performed in selected patients for primary renovascular pathology. It can also be an adjunct to aortic reconstruction with acceptable mortality

Impact of Prophylactic Versus Preemptive Valganciclovir on Long-term Renal Allograft Outcomes

PubMed Central

Spinner, Michael L.; Saab, Georges; Casabar, Ed; Bowman, Lyndsey J.; Storch, Gregory A.; Brennan, Daniel C.

2010-01-01

Background Both prophylactic and preemptive oral valganciclovir therapy are effective for management of cytomegalovirus (CMV) post renal transplantation in the short-term. The long-term effect of either strategy is less well-defined. Methods We analyzed data on 115 adult recipients previously enrolled in a prospective randomized controlled trial of prophylaxis versus preemptive therapy for CMV. The primary outcome was a composite of freedom from acute rejection, graft loss, or death. Secondary outcomes included individual primary outcomes, post-transplant cardiovascular events, new-onset diabetes mellitus after transplant (NODAT), achievement of goal blood pressure, change in body mass index (BMI), interstitial fibrosis/tubular atrophy (IF/TA) and change in renal function. The analysis period was a 48-months post-transplant or date of death/graft loss, whichever was earlier. Results The primary outcome was similar between groups (83% prophylactic versus 81% preemptive, p = 0.754). The secondary outcomes showed similarities between the prophylactic and preemptive groups. Four patients in the prophylactic group (8%) compared to none in the preemptive group (0%) died with a functioning graft, p=0.043. Conclusions Within the limitations of sample size, our data suggest that either strategy for the management of CMV immediately post-transplantation appears effective for patient and graft survival in the long-term. CMV-management is one of many therapeutic strategies incorporated into a renal transplantation protocol which often differs among institutions, and the decision as to which approach to use remains center and resource specific. The increased incidence of death in the prophylactic group requires further investigation. PMID:20555305

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

PubMed Central

Bal-Price, Anna; Lein, Pamela J.; Keil, Kimberly P.; Sethi, Sunjay; Shafer, Timothy; Barenys, Marta; Fritsche, Ellen; Sachana, Magdalini; Meek, M.E. (Bette)

2016-01-01

The Adverse Outcome Pathway (AOP) concept has recently been proposed to support a paradigm shift in regulatory toxicology testing and risk assessment. This concept is similar to the Mode of Action (MOA), in that it describes a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis for predicting effects of structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed. A variety of cellular and molecular processes are known to be critical for normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of the principles of MOA and AOPs, examples of potential or putative adverse outcome pathways specific for developmental or adult neurotoxicity are summarized and aspects of their assessment considered. Their possible application in developing mechanistically informed Integrated Approaches to Testing and Assessment (IATA) is also discussed. PMID:27212452

Opioid Analgesics and Adverse Outcomes among Hemodialysis Patients.

PubMed

Ishida, Julie H; McCulloch, Charles E; Steinman, Michael A; Grimes, Barbara A; Johansen, Kirsten L

2018-05-07

Patients on hemodialysis frequently experience pain and may be particularly vulnerable to opioid-related complications. However, data evaluating the risks of opioid use in patients on hemodialysis are limited. Using the US Renal Data System, we conducted a cohort study evaluating the association between opioid use (modeled as a time-varying exposure and expressed in standardized oral morphine equivalents) and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture among 140,899 Medicare-covered adults receiving hemodialysis in 2011. We evaluated risk according to average daily total opioid dose (>60 mg, ≤60 mg, and per 60-mg dose increment) and specific agents (per 60-mg dose increment). The median age was 61 years old, 52% were men, and 50% were white. Sixty-four percent received opioids, and 17% had an episode of altered mental status (15,658 events), fall (7646 events), or fracture (4151 events) in 2011. Opioid use was associated with risk for all outcomes in a dose-dependent manner: altered mental status (lower dose: hazard ratio, 1.28; 95% confidence interval, 1.23 to 1.34; higher dose: hazard ratio, 1.67; 95% confidence interval, 1.56 to 1.78; hazard ratio, 1.29 per 60 mg; 95% confidence interval, 1.26 to 1.33), fall (lower dose: hazard ratio, 1.28; 95% confidence interval, 1.21 to 1.36; higher dose: hazard ratio, 1.45; 95% confidence interval, 1.31 to 1.61; hazard ratio, 1.04 per 60 mg; 95% confidence interval, 1.03 to 1.05), and fracture (lower dose: hazard ratio, 1.44; 95% confidence interval, 1.33 to 1.56; higher dose: hazard ratio, 1.65; 95% confidence interval, 1.44 to 1.89; hazard ratio, 1.04 per 60 mg; 95% confidence interval, 1.04 to 1.05). All agents were associated with a significantly higher hazard of altered mental status, and several agents were associated with a significantly higher hazard of fall and fracture. Opioids were associated with adverse outcomes in patients on hemodialysis, and this risk

Outcomes of kidney transplantation in Alport syndrome compared with other forms of renal disease.

PubMed

Kelly, Yvelynne P; Patil, Anish; Wallis, Luke; Murray, Susan; Kant, Saumitra; Kaballo, Mohammed A; Casserly, Liam; Doyle, Brendan; Dorman, Anthony; O'Kelly, Patrick; Conlon, Peter J

2017-11-01

Alport syndrome is an inherited renal disease characterized by hematuria, renal failure, hearing loss and a lamellated glomerular basement membrane. Patients with Alport syndrome who undergo renal transplantation have been shown to have patient and graft survival rates similar to or better than those of patients with other renal diseases. In this national case series, based in Beaumont Hospital Dublin, we studied the cohort of patients who underwent renal transplantation over the past 33 years, recorded prospectively in the Irish Renal Transplant Registry, and categorized them according to the presence or absence of Alport syndrome. The main outcomes assessed were patient and renal allograft survival. Fifty-one patients diagnosed with Alport syndrome in Beaumont Hospital received 62 transplants between 1982 and 2014. The comparison group of non-Alport patients comprised 3430 patients for 3865 transplants. Twenty-year Alport patient survival rate was 70.2%, compared to 44.8% for patients with other renal diseases (p = .01). Factors associated with patient survival included younger age at transplantation as well as differences in recipient sex, donor age, cold ischemia time, and episodes of acute rejection. Twenty-year graft survival was 46.8% for patients with Alport syndrome compared to 30.2% for those with non-Alport disease (p = .11). Adjusting for baseline differences between the groups, patients with end-stage kidney disease (ESKD) due to Alport syndrome have similar patient and graft survival to those with other causes of ESKD. This indicates that early diagnosis and management can lead to favorable outcomes for this patient cohort.

Association of maternal periodontal health with adverse pregnancy outcome.

PubMed

Kumar, Ashok; Basra, Minu; Begum, Nargis; Rani, Vigya; Prasad, Sudha; Lamba, Arundeep Kaur; Verma, Mahesh; Agarwal, Sarita; Sharma, Shashi

2013-01-01

The present study aims to determine the association of periodontal disease (identified early in pregnancy) and adverse pregnancy outcomes in a North Indian population.   A total of 340 primigravida women, aged 20-35 years with single live pregnancy were recruited at 14-20 weeks period of gestation from the antenatal clinic. These women had undergone periodontal examination at time of recruitment. The pregnancy outcomes were recorded. Out of 340 primigravida women, 147 (43.23%) women had gingivitis and 61 (17.94%) women had periodontitis. Periodontitis was found to be significantly associated with pre-eclampsia, intrauterine growth restriction, preterm delivery, and low birthweight with odds ratios (95% confidence interval) of 7.48 (2.72-22.42), 3.35 (1.20-9.55), 2.72 (1.30-5.68) and 3.03 (1.53-5.97), respectively. The study shows a significant association between periodontitis (but not with gingivitis) and adverse pregnancy outcomes. Maternal periodontitis is associated with an increased risk of pre-eclampsia, intrauterine growth restriction, preterm delivery and low birthweight infants. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Renal, auricular, and ocular outcomes of Alport syndrome and their current management.

PubMed

Zhang, Yanqin; Ding, Jie

2017-09-01

Alport syndrome is a hereditary glomerular basement membrane disease caused by mutations in the COL4A3/4/5 genes encoding the type IV collagen alpha 3-5 chains. Most cases of Alport syndrome are inherited as X-linked dominant, and some as autosomal recessive or autosomal dominant. The primary manifestations are hematuria, proteinuria, and progressive renal failure, whereas some patients present with sensorineural hearing loss and ocular abnormalities. Renin-angiotensin-aldosterone system blockade is proven to delay the onset of renal failure by reducing proteinuria. Renal transplantation is a curative treatment for patients who have progressed to end-stage renal disease. However, only supportive measures can be used to improve hearing loss and visual loss. Although both stem cell therapy and gene therapy aim to repair the basement membrane defects, technical difficulties require more research in Alport mice before clinical studies. Here, we review the renal, auricular, and ocular manifestations and outcomes of Alport syndrome and their current management.

Maternal language and adverse birth outcomes in a statewide analysis.

PubMed

Sentell, Tetine; Chang, Ann; Ahn, Hyeong Jun; Miyamura, Jill

2016-01-01

Limited English proficiency is associated with disparities across diverse health outcomes. However, evidence regarding adverse birth outcomes across languages is limited, particularly among U.S. Asian and Pacific Islander populations. The study goal was to consider the relationship of maternal language to birth outcomes using statewide hospitalization data. Detailed discharge data from Hawaii childbirth hospitalizations from 2012 (n = 11,419) were compared by maternal language (English language or not) for adverse outcomes using descriptive and multivariable log-binomial regression models, controlling for race/ethnicity, age group, and payer. Ten percent of mothers spoke a language other than English; 93% of these spoke an Asian or Pacific Islander language. In multivariable models, compared to English speakers, non-English speakers had significantly higher risk (adjusted relative risk [ARR]: 2.02; 95% confidence interval [CI]: 1.34-3.04) of obstetric trauma in vaginal deliveries without instrumentation. Some significant variation was seen by language for other birth outcomes, including an increased rate of primary Caesarean sections and vaginal births after Caesarean, among non-English speakers. Non-English speakers had approximately two times higher risk of having an obstetric trauma during a vaginal birth when other factors, including race/ethnicity, were controlled. Non-English speakers also had higher rates of potentially high-risk deliveries.

Acute coronary syndromes in patients with renal failure.

PubMed

McCullough, Peter A

2003-07-01

As the rates of obesity and diabetes continue to rise sharply in the United States, there is a secondary epidemic of diabetic nephropathy, chronic kidney disease, and end-stage renal disease requiring renal replacement therapy. Cardiovascular disease is the leading cause of death in patients with renal disease. Many sources of information support the concept that the metabolic condition caused by renal failure is an independent cardiac risk factor with a direct relationship to the pathogenesis of atherosclerosis, acute coronary syndromes (ACS), heart failure, and arrhythmias. An estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) has consistently been shown to be the most powerful predictor of adverse outcomes in ACS. This paper focuses on ACS and highlights the major issues with respect to diagnosis and treatment in patients with underlying renal failure. Because patients with renal disease are routinely excluded from clinical trials of ACS, we draw upon a variety of clinical data sets to gather an evidenced-based approach to this important and growing population of patients.

The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: a two-year prospective study.

PubMed

Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Ko, Chih-Hung

2008-05-01

Research has revealed that a lack of insight is associated with poorer clinical outcomes in schizophrenia; however, the predictive value of insight on adverse clinical outcomes among bipolar patients is quite understudied. The aim of this prospective study was to examine the impact of insight on adverse clinical outcomes among the patients with bipolar I disorder over a 2-year period. Sixty-five remitted bipolar I disorder patients received follow-up assessments at 3, 6, 9, 12, 18, and 24 months to detect the adverse clinical outcomes defined by the incidence of bipolar-related psychiatric hospitalization, emergency room visits, violent or suicidal behavior. The Schedule of Assessment of Insight was used to provide a baseline insight score. Cox regression analysis was used to examine the predictive value of insight on the adverse clinical outcomes. Impaired insight into treatment and a greater number of previous hospitalizations significantly increased the risk of adverse clinical outcomes with bipolar disorder in the 2-year period. However, insight into recognition of the illness and re-labeling of psychotic phenomena did not have any significant effect on adverse clinical outcomes. Bipolar patients' insight into treatment is an independent predictor of adverse clinical outcomes. Improving insight into treatment might be a promising target for a better outcome.

Cytomegalovirus seroprevalence in pregnant women and association with adverse pregnancy/neonatal outcomes in Jiangsu Province, China.

PubMed

Zhang, Shu; Hu, Lingqing; Chen, Jie; Xu, Biyun; Zhou, Yi-Hua; Hu, Yali

2014-01-01

In this study, we aimed to determine the provincial population-based seroprevalence in pregnant women and to further explore the association of maternal CMV infection status and adverse pregnancy/neonatal/growth outcomes in Jiangsu, China. In this case-control study, the sera from 527 pregnant women with adverse pregnancy/neonatal outcomes and 496 mothers of healthy infants in Jiangsu Province, collected at gestation age of 15-20 weeks, were tested for anti-CMV IgG, IgM and IgG avidity. Adverse pregnancy/neonatal outcomes were identified based on pregnancy/neonatal outcomes. The overall seroprevalence of anti-CMV IgG was 98.7%, with 99.4% and 98.0% in the case and control groups, respectively (P = 0.039). The prevalence of anti-CMV IgG+/IgM+, was higher in the case group than that in the control group (3.8% vs. 1.6%, P = 0.033). Anti-CMV IgG avidity assay showed that none in the control group were primarily infected, but five (0.9%) in the case group underwent primary infection (P = 0.084); all five infants of these women presented severe adverse neonatal/growth outcomes. Exact logistic regression analysis showed that anti-CMV IgG+/IgM+ was associated with adverse pregnancy/neonatal/growth outcomes (aOR = 2.44, 95% CI 1.01-6.48, P = 0.047). Maternal low education level and prior abnormal pregnancies also were risk factors for adverse pregnancy/neonatal outcomes. In populations with very high prevalence of latent CMV infection, active maternal CMV infection during pregnancy might be a risk factor for adverse pregnancy/neonatal outcomes.

Cytomegalovirus Seroprevalence in Pregnant Women and Association with Adverse Pregnancy/Neonatal Outcomes in Jiangsu Province, China

PubMed Central

Chen, Jie; Xu, Biyun; Zhou, Yi-Hua; Hu, Yali

2014-01-01

Background In this study, we aimed to determine the provincial population-based seroprevalence in pregnant women and to further explore the association of maternal CMV infection status and adverse pregnancy/neonatal/growth outcomes in Jiangsu, China. Methods In this case-control study, the sera from 527 pregnant women with adverse pregnancy/neonatal outcomes and 496 mothers of healthy infants in Jiangsu Province, collected at gestation age of 15–20 weeks, were tested for anti-CMV IgG, IgM and IgG avidity. Adverse pregnancy/neonatal outcomes were identified based on pregnancy/neonatal outcomes. Results The overall seroprevalence of anti-CMV IgG was 98.7%, with 99.4% and 98.0% in the case and control groups, respectively (P = 0.039). The prevalence of anti-CMV IgG+/IgM+, was higher in the case group than that in the control group (3.8% vs. 1.6%, P = 0.033). Anti-CMV IgG avidity assay showed that none in the control group were primarily infected, but five (0.9%) in the case group underwent primary infection (P = 0.084); all five infants of these women presented severe adverse neonatal/growth outcomes. Exact logistic regression analysis showed that anti-CMV IgG+/IgM+ was associated with adverse pregnancy/neonatal/growth outcomes (aOR = 2.44, 95% CI 1.01–6.48, P = 0.047). Maternal low education level and prior abnormal pregnancies also were risk factors for adverse pregnancy/neonatal outcomes. Conclusions In populations with very high prevalence of latent CMV infection, active maternal CMV infection during pregnancy might be a risk factor for adverse pregnancy/neonatal outcomes. PMID:25211647

Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes

PubMed Central

Smith, Laura E.; Prendergast, Andrew J.; Turner, Paul C.; Humphrey, Jean H.; Stoltzfus, Rebecca J.

2017-01-01

Pregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight. PMID:28500823

Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes.

PubMed

Smith, Laura E; Prendergast, Andrew J; Turner, Paul C; Humphrey, Jean H; Stoltzfus, Rebecca J

2017-04-01

AbstractPregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight.

Resistant Hypertension, Time-Updated Blood Pressure Values and Renal Outcome in Type 2 Diabetes Mellitus.

PubMed

Viazzi, Francesca; Piscitelli, Pamela; Ceriello, Antonio; Fioretto, Paola; Giorda, Carlo; Guida, Pietro; Russo, Giuseppina; De Cosmo, Salvatore; Pontremoli, Roberto

2017-09-22

Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long-term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real-life clinical practice. Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4-year follow-up, were retrieved and analyzed. The association between time-updated BP control (ie, 75% of visits with BP <140/90 mm Hg) and the occurrence of estimated glomerular filtration rate <60 and/or a reduction ≥30% from baseline was assessed. At baseline, 17% of patients had aTRH. Over the 4-year follow-up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction ≥30% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; P <0.001 respectively), as compared with those with non-aTRH. No association was found between BP control and renal outcomes in non-aTRH, whereas in aTRH, BP control was associated with a 30% ( P =0.036) greater risk of developing the renal end points. ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more-favorable renal outcome in aTRH. The relationship between time-updated BP and renal function seems to be J-shaped, with optimal systolic BP values between 120 and 140 mm Hg. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Adverse Pregnancy Outcomes Among Women with Prior Spontaneous or Induced Abortions

PubMed Central

Makhlouf, Michel A; Clifton, Rebecca G.; Roberts, James M.; Myatt, Leslie; Hauth, John C.; Leveno, Kenneth J.; Varner, Michael W.; Thorp, John M.; Mercer, Brian M.; Peaceman, Alan M.; Ramin, Susan M.; Iams, Jay D.; Sciscione, Anthony; Tolosa, Jorge E.; Sorokin, Yoram

2014-01-01

OBJECTIVE To determine whether prior spontaneous (SAB) or induced (IAB) abortions, or the inter-pregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. METHODS We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared to primigravid participants. RESULTS Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (OR 1.5; 95% CI 1.1–2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (OR 2.6, 95% CI 1.7–4.0), preterm PROM (OR 2.9, 95% CI 1.6–5.3) and perinatal death (OR 2.8, 95% CI 1.5–5.3). Women with one previous IAB had higher rates of spontaneous preterm birth (OR 1.4, 95% CI 1.0–1.9) and preterm PROM (OR 2.0, 95% CI 1.4–3.0). An inter-pregnancy interval less than 6 months after SAB was not associated with adverse outcomes. CONCLUSION Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. PMID:24347257

PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON OF BRAIN AROMATASE IN FISH LEADING TO REPRODUCTIVE IMPAIRMENT

EPA Science Inventory

The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework p...

Adverse outcome pathway (AOP) development and evaluation ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be measured in high throughput toxicity testing and the organism or population-level events that are commonly relevant in defining risk. Recognizing the importance of this emerging framework, the Organisation for Economic Co-operation and Development (OECD) launched a program to support the development, documentation and consideration of AOPs by the international community in 2012 (http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). In 2014, a handbook (https://aopkb.org/common/AOP_Handbook.pdf) was developed to guide users in the documentation and evaluation of AOPs and their entry into an official knowledgebase. The handbook draws on longstanding experience in consideration of mechanistic data (e.g., mode of action analysis) to inform risk assessment. To further assist users, a training program was developed by members of the OECD Extended Advisory Group to teach users the basic principles of AOP development and the best practices as outlined in the OECD AOP handbook. Training sessions began in early 2015, and this course will provide training for interested SOT scientists. Following this course, all participants will be familiar w

Frequency, Risk Factors, and Adverse Fetomaternal Outcomes of Placenta Previa in Northern Tanzania

PubMed Central

Senkoro, Elizabeth Eliet; Mwanamsangu, Amasha H.; Chuwa, Fransisca Seraphin; Msuya, Sia Emmanuel; Mnali, Oresta Peter

2017-01-01

Background and Objective. Placenta previa (PP) is a potential risk factor for obstetric hemorrhage, which is a major cause of fetomaternal morbidity and mortality in developing countries. This study aimed to determine frequency, risk factors, and adverse fetomaternal outcomes of placenta previa in Northern Tanzania. Methodology. A retrospective cohort study was conducted using maternally-linked data from Kilimanjaro Christian Medical Centre birth registry spanning 2000 to 2015. All women who gave birth to singleton infants were studied. Adjusted odds ratios (ORs) with 95% confidence intervals for risk factors and adverse fetomaternal outcomes associated with PP were estimated in multivariable logistic regression models. Result. A total of 47,686 singleton deliveries were analyzed. Of these, the frequency of PP was 0.6%. Notable significant risk factors for PP included gynecological diseases, alcohol consumption during pregnancy, malpresentation, and gravidity ≥5. Adverse maternal outcomes were postpartum haemorrhage, antepartum haemorrhage, and Caesarean delivery. PP increased odds of fetal Malpresentation and early neonatal death. Conclusion. The prevalence of PP was comparable to that found in past research. Multiple independent risk factors were identified. PP was found to have associations with several adverse fetomaternal outcomes. Early identification of women at risk of PP may help clinicians prevent such complications. PMID:28321338

Plasma biomarkers are associated with renal outcomes in individuals with APOL1 risk variants.

PubMed

Nadkarni, Girish N; Chauhan, Kinsuk; Verghese, Divya A; Parikh, Chirag R; Do, Ron; Horowitz, Carol R; Bottinger, Erwin P; Coca, Steven G

2018-04-20

G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1 high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1 genotype. Biomarker association with a composite renal outcome of ESRD or 40% sustained decline in estimated glomerular filtration rate (eGFR) was then determined and then assessed as improvement in area under curve. Among the 498 participants, the median age was 56 years, 67.7% were female, and the baseline eGFR was 83.3 ml/min/1.73 m 2 with 80 reaching outcome over 5.9 years. TNFR1, TNFR2, and KIM1 at enrollment were independently associated with renal outcome continuously (adjusted hazard ratio 2.0 [95% confidence interval 1.3-3.1]; 1.5 [1.2-1.9]; and 1.6 [1.3-1.9] per doubling in levels, respectively) or by tertiles. The area under the curve significantly improved from 0.75 with the clinical model to 0.79 with the biomarker-enhanced model. The event rate was 40% with all 3 biomarkers elevated (adjusted odds ratio of 5.3 (2.3-12.0) vs. 17% (adjusted odds ratio 1.8 [0.9-3.6] with 1 or 2 elevated and 7% with no biomarkers elevated. Thus, plasma concentrations of TNFR1, TNFR2, and KIM1 are independently associated with renal outcome and improve discrimination or reclassification of African ancestry individuals with a high-risk APOL1 genotype and preserve renal function. Elevation of all markers had higher risk of outcome and can assist with better clinical prediction and improved clinical trial efficiency by enriching event rates. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Urinary tract infection and adverse outcome of pregnancy.

PubMed

Dimetry, Shaira R; El-Tokhy, Hanan M; Abdo, Nagla M; Ebrahim, Moustafa A; Eissa, Mohammed

2007-01-01

Urinary tract infections (UTIs) during pregnancy are among the commonest health problems world wide, specially in developing countries, including Egypt. It has several adverse outcomes not only on the mother but also on the fetus as well.. The aim of this study is to determine the incidence of UTIs during pregnancy, study the main risk factors associated with such infections and find the impact of these infections on some pregnancy outcomes namely the gestational age and birth weight. A follow-up study on 249 pregnant women attending the ante natal care clinic at Zagazig university hospital. They were recruited over a period from 1st of September to 30th of or November, 2005. The outcome could be recorded for 201 of them. Data were collected through a pretested questionnaire, repeated urine analyses and recording of outcome of pregnancy. The study revealed that the incidence of UTIs during pregnancy was 31.3%. The commonest organisms were Klebsiella and E-coli. Several socio-demographic characteristics were found significantly associated with UTIs, age being 30 years and more, illiterates and low educational level, low socio-economic level and those with unsatisfactory personal hygiene and those using underwear clothes other than cotton. Significant associations with UTIs were also found in multigravidae 4th and more, those having more than one child and those who previously suffered UTIs. The only predicting variable with UTIs was low socio-economic level. The study revealed that the probability of delivering premature infants and low birth weights was significantly higher among those who experienced UTIs during pregnancy. Multivariate analysis revealed that UTI was one of the main contributors to pre-mature deliveries. Urinary tract infections with pregnancy still constitute a big problem with high incidence. It has a great impact on pregnancy outcome mainly pre-mature labor. So, the study recommends health education about personal hygiene, repeated urine

The future trajectory of adverse outcome pathways: a commentary.

PubMed

Sewell, Fiona; Gellatly, Nichola; Beaumont, Maria; Burden, Natalie; Currie, Richard; de Haan, Lolke; Hutchinson, Thomas H; Jacobs, Miriam; Mahony, Catherine; Malcomber, Ian; Mehta, Jyotigna; Whale, Graham; Kimber, Ian

2018-04-01

The advent of adverse outcome pathways (AOPs) has provided a new lexicon for description of mechanistic toxicology, and a renewed enthusiasm for exploring modes of action resulting in adverse health and environmental effects. In addition, AOPs have been used successfully as a framework for the design and development of non-animal approaches to toxicity testing. Although the value of AOPs is widely recognised, there remain challenges and opportunities associated with their use in practise. The purpose of this article is to consider specifically how the future trajectory of AOPs may provide a basis for addressing some of those challenges and opportunities.

Early Imaging and Adverse Neurodevelopmental Outcome in Asphyxiated Newborns Treated With Hypothermia.

PubMed

Al Amrani, Fatema; Kwan, Saskia; Gilbert, Guillaume; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

2017-08-01

Brain injury can be identified as early as day two of life in asphyxiated newborns treated with hypothermia, when using diffusion magnetic resonance imaging (MRI). However, it remains unclear whether these diffusion changes can predict future neurodevelopment. This study aimed to determine whether abnormal early diffusion changes in newborns treated with hypothermia are associated with adverse neurodevelopmental outcome at age two years. Asphyxiated newborns treated with hypothermia were enrolled prospectively. They underwent magnetic resonance imaging (MRI) at specific time points over the first month of life, including diffusion-weighted imaging and diffusion-tensor imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in different regions of interest. Adverse neurodevelopmental outcome was defined as cerebral palsy, global developmental delay, and/or seizure disorder around age two years. ADC and FA values were compared between the newborns developing or not developing adverse outcome. Twenty-nine asphyxiated newborns treated with hypothermia were included. Among the newborns developing adverse outcome, ADC values were significantly decreased on days two to three of life and increased around day ten of life in the thalamus, posterior limb of the internal capsule, and the lentiform nucleus. FA values decreased in the same regions around day 30 of life. These newborns also had increased ADC around day ten of life and around day 30 of life, and decreased FA around day 30 of life in the anterior and posterior white matter. Diffusion changes that were evident as early as day two of life, when the asphyxiated newborns were still treated with hypothermia, were associated with later abnormal neurodevelopmental outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Interventions designed to prevent adverse programming outcomes resulting from exposure to maternal obesity during development

PubMed Central

Nathanielsz, PW; Ford, SP; Long, NM; Vega, CC; Reyes-Castro, LA; Zambrano, E

2013-01-01

Maternal obesity is a global epidemic affecting the developed and developing world. Human and animal studies indicate that maternal obesity programs development predisposing offspring to later-life chronic diseases. Several mechanisms act together to produce these adverse health problems. There is a need for effective interventions that prevent these outcomes and guide management in human pregnancy. We report here dietary and exercise intervention studies in both altricial and precocial species, rats and sheep, designed to prevent adverse offspring outcomes. Both interventions present exciting opportunities to at least in part prevent adverse metabolic and other outcomes in mother and offspring. PMID:24147928

Incidence and Patient Outcomes in Renal Replacement Therapy After Orthotopic Liver Transplant.

PubMed

Ayhan, Asude; Ersoy, Zeynep; Ulas, Aydin; Zeyneloglu, Pinar; Pirat, Arash; Haberal, Mehmet

2017-02-01

Our objective was to evaluate the incidence of renal replacement therapy after orthotopic liver transplant and to evaluate and analyze patient outcomes. We performed a retrospective analysis of 177 consecutive patients at a tertiary care unit who underwent orthotopic liver transplant between January 2010 and June 2016. Patients who were admitted to the intensive care unit after orthotopic liver transplant and who required renal replacement therapy were included. A total of 177 (79 adult, 98 pediatric) orthotopic liver transplants were performed during the study period. Of these, 35 patients (19%) required renal replacement therapy during the early posttransplantation period. After excluding 5 patients with previous chronic renal failure, 30 patients (17%; 20 adult [25% ], 10 pediatric [10% ]) with acute kidney injury required renal replacement therapy. The mean patient age was 31.1 ± 20.0 years, with a mean Model for End-stage Liver Disease score of 16.7 ± 12.3. Of the patients with acute kidney injury who underwent renal replacement therapy, in-hospital mortality was 23.3% (7 of 30 patients), and 40% remained on dialysis. No significant difference was seen in mortality between early versus delayed initiation of renal replacement therapy in patients with stage 3 acute kidney injury (P = .17). Of liver transplant recipients who present with acute kidney injury, 19% require renal replacement therapy, and in-hospital mortality is 20% in the early postoperative period.

Predictors of Adverse Cosmetic Outcome in the RAPID Trial: An Exploratory Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, David; Truong, Pauline T.; Parpia, Sameer

Purpose: To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial. Methods and Materials: Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assessmore » the association of risk factors for these outcomes among all patients and those treated with APBI only. Results: Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients. Conclusion: In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high

Prenatal Depression and Adverse Birth Outcomes: An Updated Systematic Review

PubMed Central

Accortt, Eynav Elgavish; Cheadle, Alyssa C. D.; Schetter, Christine Dunkel

2015-01-01

Complications related to preterm birth (PTB) and low birth weight (LBW) are leading causes of infant morbidity and mortality. Prenatal depression is a hypothesized psychosocial risk factor for both birth outcomes. The purpose of this systematic review was to examine evidence published between 1977 and 2013 on prenatal depression and risks of these primary adverse birth outcomes. A systematic search of the PUBMED and PsycINFO databases was conducted to identify studies testing the associations between prenatal depressive symptoms, or diagnoses of depression, and risk of PTB or LBW. We systematically selected 50 published reports on PTB and length of gestation, and 33 reports on LBW and BW. Results were reviewed by two independent reviewers and we evaluated the quality of the evidence with an established systematic review method, the Newcastle Ottawa Scale. We then undertook a narrative synthesis of the results following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Less than a quarter of 50 published reports found that prenatal depression was significantly associated with PTB or gestational age. In contrast, slightly more than half of the 33 reports found that prenatal depression was associated with LBW or BW. When weighing methodological features, we determined that the effects of prenatal depression on LBW are more consistent than effects on length of gestation or PTB. Although the evidence may not be strong enough to support routine depression screening for risk of adverse outcomes, screening to enable detection and timely treatment to reduce risk of postpartum depression is warranted. Further rigorous research on prenatal depression and adverse birth outcomes is needed. PMID:25452215

Adverse outcome pathway (AOP) development: Guiding principles and best practices

EPA Science Inventory

Adverse outcome pathways (AOPs) represent a conceptual framework that can support greater application of mechanistic data in regulatory decision-making. However, in order for the scientific community to collectively address the daunting challenge of describing relevant toxicologi...

The reproducibility and predictive value on outcome of renal biopsies from expanded criteria donors.

PubMed

Azancot, M Antonieta; Moreso, Francesc; Salcedo, Maite; Cantarell, Carme; Perello, Manel; Torres, Irina B; Montero, Angeles; Trilla, Enric; Sellarés, Joana; Morote, Joan; Seron, Daniel

2014-05-01

Reproducibility and predictive value on outcome are the main criteria to evaluate the utility of histological scores. Here we analyze the reproducibility of donor biopsy assessment by different on-call pathologists and the retrospective evaluation by a single renal pathologist blinded to clinical outcomes. We also evaluate the predictive value on graft outcome of both evaluations. A biopsy was performed in donors with any of the following: age≥55 years, hypertension, diabetes, creatinine>1.5 mg/dl, or stroke. Glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal thickening, and arteriolar hyalinosis evaluated according to the Banff criteria were added to obtain a chronic score. Biopsies were classified as mild (≥3), intermediate (4-5), or advanced (6-7) damage, and unacceptable (≥8) for transplantation of 127 kidneys biopsied. Weighted κ value between both readings was 0.41 (95% CI: 0.28-0.54). Evaluation of biopsies by the renal pathologist was significantly and independently associated with estimated 12-month glomerular filtration rate and a significant composite outcome variable, including death-censored graft survival and time to reach an estimated glomerular filtration rate<30 ml/min per 1.73 m2. Thus, there was no association between readings of on-call pathologists and outcome. The lack of association between histological scores obtained by the on-call pathologists and graft outcome suggests that a specific training on renal pathology is recommended to optimize the use of kidneys retrieved from expanded criteria donors.

Maternal Language and Adverse Birth Outcomes in a Statewide Analysis

PubMed Central

Sentell, Tetine; Chang, Ann; Jun Ahn, Hyeong; Miyamura, Jill

2016-01-01

Background Limited English proficiency is associated with disparities across diverse health outcomes. However, evidence regarding adverse birth outcomes across languages is limited, particularly among US Asian and Pacific Islander populations. The study goal was to consider the relationship of maternal language to birth outcomes using statewide hospitalization data. Methods Detailed discharge data from Hawai‘i childbirth hospitalizations from 2012 (n=11,419) were compared by maternal language (English language or not) for adverse outcomes using descriptive and multivariable log-binomial regression models, controlling for race/ethnicity, age group, and payer. Results Ten percent of mothers spoke a language other than English; 93% of these spoke an Asian or Pacific Islander language. In multivariable models, compared to English speakers non-English speakers had significantly higher risk (adjusted relative risk [ARR]: 2.02; 95% Confidence Interval [CI]: 1.34–3.04) of obstetric trauma in vaginal deliveries without instrumentation. Some significant variation was seen by language for other birth outcomes, including an increased rate of primary Caesarean sections and vaginal births after Caesarean among non-English speakers. Conclusions Non-English speakers had approximately two times higher risk of having an obstetric trauma during a vaginal birth when other factors, including race/ethnicity, were controlled. Non-English speakers also had higher rates of potentially high-risk deliveries. PMID:26361937

Ionotropic GABA receptor antagonism-induced adverse outcome pathways for potential neurotoxicity biomarkers.

PubMed

Gong, Ping; Hong, Huixiao; Perkins, Edward J

2015-01-01

Antagonism of ionotropic GABA receptors (iGABARs) can occur at three distinct types of receptor binding sites causing chemically induced epileptic seizures. Here we review three adverse outcome pathways, each characterized by a specific molecular initiating event where an antagonist competitively binds to active sites, negatively modulates allosteric sites or noncompetitively blocks ion channel on the iGABAR. This leads to decreased chloride conductance, followed by depolarization of affected neurons, epilepsy-related death and ultimately decreased population. Supporting evidence for causal linkages from the molecular to population levels is presented and differential sensitivity to iGABAR antagonists in different GABA receptors and organisms discussed. Adverse outcome pathways are poised to become important tools for linking mechanism-based biomarkers to regulated outcomes in next-generation risk assessment.

Adverse pregnancy outcomes among women with prior spontaneous or induced abortions.

PubMed

Makhlouf, Michel A; Clifton, Rebecca G; Roberts, James M; Myatt, Leslie; Hauth, John C; Leveno, Kenneth J; Varner, Michael W; Thorp, John M; Mercer, Brian M; Peaceman, Alan M; Ramin, Susan M; Iams, Jay D; Sciscione, Anthony; Tolosa, Jorge E; Sorokin, Yoram

2014-10-01

The aim of the article is to determine whether prior spontaneous abortion (SAB) or induced abortion (IAB), or the interpregnancy interval are associated with subsequent adverse pregnancy outcomes in nulliparous women. We performed a secondary analysis of data collected from nulliparous women enrolled in a completed trial of vitamins C and E or placebo for preeclampsia prevention. Adjusted odds ratios (ORs) for maternal and fetal outcomes were determined for nulliparous women with prior SABs and IABs as compared with primigravid participants. Compared with primigravidas, women with one prior SAB were at increased risk for perinatal death (adj. OR, 1.5; 95% CI, 1.1-2.3) in subsequent pregnancies. Two or more SABs were associated with an increased risk for spontaneous preterm birth (PTB) (adj. OR, 2.6, 95% CI, 1.7-4.0), preterm premature rupture of membranes (PROM) (adj. OR, 2.9; 95% CI, 1.6-5.3), and perinatal death (adj. OR, 2.8; 95% CI, 1.5-5.3). Women with one previous IAB had higher rates of spontaneous PTB (adj. OR, 1.4; 95% CI, 1.0-1.9) and preterm PROM (OR, 2.0; 95% CI, 1.4-3.0). An interpregnancy interval less than 6 months after SAB was not associated with adverse outcomes. Nulliparous women with a history of SAB or IAB, especially multiple SABs, are at increased risk for adverse pregnancy outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Magnitude of income-related disparities in adverse perinatal outcomes.

PubMed

Shankardass, Ketan; O'Campo, Patricia; Dodds, Linda; Fahey, John; Joseph, Ks; Morinis, Julia; Allen, Victoria M

2014-03-04

To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases.

Development of a Screening Tool for Predicting Adverse Outcomes of Gestational Diabetes Mellitus: A Retrospective Cohort Study.

PubMed

Park, Jee Soo; Kim, Deok Won; Kwon, Ja-Young; Park, Yong Won; Kim, Young Han; Cho, Hee Young

2016-01-01

Gestational diabetes mellitus (GDM) is a common disease in pregnancy causing maternal and fetal complications. To prevent these adverse outcomes, optimal screening and diagnostic criteria must be adequate, timely, and efficient. This study suggests a novel approach that is practical, efficient, and patient- and clinician-friendly in predicting adverse outcomes of GDM. The authors conducted a retrospective cohort study via medical record review of patients admitted between March 2001 and April 2013 at the Severance Hospital, Seoul, South Korea. Patients diagnosed by a conventional 2-step method were evaluated according to the presence of adverse outcomes (neonatal hypoglycemia, hyperbilirubinemia, and hyperinsulinemia; admission to the neonatal intensive care unit; large for gestational age; gestational insulin therapy; and gestational hypertension). Of 802 women who had an abnormal 50-g, 1-hour glucose challenge test, 306 were diagnosed with GDM and 496 did not have GDM (false-positive group). In the GDM group, 218 women (71.2%) had adverse outcomes. In contrast, 240 women (48.4%) in the false-positive group had adverse outcomes. Women with adverse outcomes had a significantly higher body mass index (BMI) at entry (P = 0.03) and fasting blood glucose (FBG) (P = 0.03). Our logistic regression model derived from 2 variables, BMI at entry and FBG, predicted GDM adverse outcome with an area under the curve of 0.642, accuracy of 61.3%, sensitivity of 57.2%, and specificity of 66.9% compared with the conventional 2-step method with an area under the curve of 0.610, accuracy of 59.1%, sensitivity of 47.6%, and specificity of 74.4%. Our model performed better in predicting GDM adverse outcomes than the conventional 2-step method using only BMI at entry and FBG. Moreover, our model represents a practical, inexpensive, efficient, reproducible, easy, and patient- and clinician-friendly approach.

Associations of neighborhood-level racial residential segregation with adverse pregnancy outcomes.

PubMed

Salow, Arturo D; Pool, Lindsay R; Grobman, William A; Kershaw, Kiarri N

2018-03-01

Previous analyses utilizing birth certificate data have shown environmental factors such as racial residential segregation may contribute to disparities in adverse pregnancy outcomes. However, birth certificate data are ill equipped to reliably differentiate among small for gestational age, spontaneous preterm birth, and medically indicated preterm birth. We sought to utilize data from electronic medical records to determine whether residential segregation among Black women is associated with an increased risk of adverse pregnancy outcomes. The study population was composed of 4770 non-Hispanic Black women who delivered during the years 2009 through 2013 at a single urban medical center. Addresses were geocoded at the level of census tract, and this tract was used to determine the degree of residential segregation for an individual's neighborhood. Residential segregation was measured using the Gi* statistic, a z-score that measures the extent to which the neighborhood racial composition deviates from the composition of the larger surrounding area. The Gi* statistic z-scores were categorized as follows: low (z < 0), medium (z = 0-1.96), and high (z > 1.96). Adverse pregnancy outcomes included overall preterm birth, spontaneous preterm birth, medically indicated preterm birth, and small for gestational age. Hierarchical logistic regression models accounting for clustering by census tract and repeated births among mothers were used to estimate odds ratios of adverse pregnancy outcomes associated with segregation. In high segregation areas, the prevalence of overall preterm birth was significantly higher than that in low segregation areas (15.5% vs 10.7%, respectively; P < .001). Likewise, the prevalence of spontaneous preterm birth and medically indicated preterm birth were higher in high (9.5% and 6.0%) vs low (6.2% and 4.6%) segregation neighborhoods (P < .001 and P = .046, respectively). The associations of high segregation with overall preterm birth (odds

The Association between Rural-Urban Continuum, Maternal Education and Adverse Birth Outcomes in Quebec, Canada

ERIC Educational Resources Information Center

Auger, Nathalie; Authier, Marie-Andree; Martinez, Jerome; Daniel, Mark

2009-01-01

Context: Rural relative to urban area and low socioeconomic status (SES) are associated with adverse birth outcomes. Whether a graded association of increasing magnitude is present across the urban-rural continuum, accounting for SES, is unclear. We examined the association between rural-urban continuum, SES and adverse birth outcomes. Methods:…

Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.

PubMed

Watts, Kara L; Ghosh, Propa; Stein, Solomon; Ghavamian, Reza

2017-01-01

To assess the relationship between individual nephrometry score (NS) constituents (RENAL) on perioperative outcomes and renal function of the surgical kidney in patients undergoing laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy. Two hundred forty-five patients who underwent laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each renal mass' NS was calculated from preoperative computed tomography imaging. Multivariate regression analysis was used to evaluate the effect of NS variables on perioperative outcomes and change in overall renal function (as estimated by glomerular filtration rate) from preoperative to 1-year postoperative. A cohort analysis assessed the effect of NS variables on change in split renal function of the surgical kidney from pre- to postoperative based on nuclear medicine renal scintigraphy. Tumor radius (R), endophytic nature (E), and nearness to collecting system (N) variables significantly and incrementally predicted a longer operative time and warm ischemia time. Overall renal function based on glomerular filtration rate was not affected by any NS variable. However, percent function of the surgical kidney by renal scintigraphy significantly decreased postoperatively as R and E values increased. R, E, and N were associated with significant changes in warm ischemia time and operative time. R and E were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery but not with overall renal function. R, E, and N are the NS constituents most relevant to perioperative outcomes and postoperative differential renal function after partial nephrectomy. Copyright © 2016. Published by Elsevier Inc.

Long-term outcomes of acute kidney injury.

PubMed

Coca, Steven G

2010-05-01

The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

The Association Between Learning Climate and Adverse Obstetrical Outcomes in 16 Nontertiary Obstetrics-Gynecology Departments in the Netherlands.

PubMed

Smirnova, Alina; Ravelli, Anita C J; Stalmeijer, Renée E; Arah, Onyebuchi A; Heineman, Maas Jan; van der Vleuten, Cees P M; van der Post, Joris A M; Lombarts, Kiki M J M H

2017-12-01

To investigate the association between learning climate and adverse perinatal and maternal outcomes in obstetrics-gynecology departments. The authors analyzed 23,629 births and 103 learning climate evaluations from 16 nontertiary obstetrics-gynecology departments in the Netherlands in 2013. Multilevel logistic regressions were used to calculate the odds of adverse perinatal and maternal outcomes, by learning climate score tertile, adjusting for maternal and department characteristics. Adverse perinatal outcomes included fetal or early neonatal mortality, five-minute Apgar score < 7, or neonatal intensive care unit admission for ≥ 24 hours. Adverse maternal outcomes included postpartum hemorrhage and/or transfusion, death, uterine rupture, or third- or fourth-degree perineal laceration. Bias analyses were conducted to quantify the sensitivity of the results to uncontrolled confounding and selection bias. Learning climate scores were significantly associated with increased odds of adverse perinatal outcomes (aOR 2.06, 95% CI 1.14-3.72). Compared with the lowest tertile, departments in the middle tertile had 46% greater odds of adverse perinatal outcomes (aOR 1.46, 95% CI 1.09-1.94); departments in the highest tertile had 69% greater odds (aOR 1.69, 95% CI 1.24-2.30). Learning climate was not associated with adverse maternal outcomes (middle vs. lowest tertile: OR 1.04, 95% CI 0.93-1.16; highest vs. lowest tertile: OR 0.98, 95% CI 0.88-1.10). Learning climate was associated with significantly increased odds of adverse perinatal, but not maternal, outcomes. Research in similar clinical contexts is needed to replicate these findings and explore potential mechanisms behind these associations.

Use of Putative Adverse Outcome Pathways for Chemical Hazard Identification

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework provides a knowledge infrastructure for evaluating health effects of environmental chemicals. In this work we are examining proof-of-concept issues in the development and prospective application of AOPs in chemical safety. Key outputs i...

Developing confidence in adverse outcome pathway-based ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD. An intended application of the AOP framework is to support the use of mechanistic or pathway-based data to infer or predict chemical hazards and apical adverse outcomes. As part of this work, ToxCast high throughput screening data were used to identify a chemicals’ ability to inhibit aromatase activity in vitro. Twenty-four hour in vivo exposures, focused on effects on production and circulating concentrations of 17β-estradiol (E2), key events in the AOP, were conducted to verify in vivo activity. Based on these results, imazalil was selected as a case study chemical to test an AOP-based hazard prediction. A computational model of the fish hypothalamic-pituitary-gonadal-liver axis and a statistically-based model of oocyte growth dynamics were used to predict impacts of different concentrations of imazalil on multiple key events along the AOP, assuming continuous exposure for 21 d. Results of the model simulations were used to select test concentrations and design a fathead minnow reproduction study in which fish were exposed to 20, 60, or 200 µg imazalil/L for durations of 2.5, 10, or 21d. Within 60 h of exposure, female fathead minnows showed significant reductions in ex vivo production of E2, circulating E2 concentrations, and significant increases in

Developing confidence in adverse outcome pathway-based ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) description linking inhibition of aromatase (cytochrome P450 [cyp] 19) to reproductive dysfunction was reviewed for scientific and technical quality and endorsed by the OECD (https://aopwiki.org/wiki/index.php/Aop:25). An intended application of the AOP framework is to support the use of mechanistic or pathway-based data to infer or predict chemical hazards and apical adverse outcomes. As part of this work, ToxCast high throughput screening data were used to identify a chemicals’ ability to inhibit aromatase activity in vitro. Twenty-four hour in vivo exposures, focused on effects on production and circulating concentrations of 17â-estradiol (E2), key events in the AOP, were conducted to verify in vivo activity. Based on these results, imazalil was selected as a case study chemical to test an AOP-based hazard prediction. A computational model of the fish hypothalamic-pituitary-gonadal-liver axis and a statistically-based model of oocyte growth dynamics were used to predict impacts of different concentrations of imazalil on multiple key events along the AOP, assuming continuous exposure for 21 d. Results of the model simulations were used to select test concentrations and design a fathead minnow reproduction study in which fish were exposed to 20, 60, or 200 µg imazalil/L for durations of 2.5, 10, or 21d. Within 60 h of exposure, female fathead minnows showed significant reductions in ex vivo production of E2, circulating E2 c

Practical approaches to adverse outcome pathway (AOP) ...

EPA Pesticide Factsheets

Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and depend largely on the intended use or motivation for development. Four ecological AOP case studies, which were developed for different purposes, are described herein. In each situation, creation of the AOP began in a manner determined by the initial motivation for its creation, and expanded either to include additional components of the pathway, or to address the domains of applicability in terms of chemical initiators, susceptible species, life stages, etc. From these case studies, some general strategies can be gleaned which a developer may find useful for supporting an existing AOP or creating a new one. Several web-based tools which can aid in AOP assembly, as well as evaluation of weight of evidence for scientific robustness of AOP components are highlighted. The need for AOP development and greater population of AOPs in the online knowledgebase has been widely recognized (e.g., OECD Project 1.29, Knapen et al 2015, Escher et al 2016; Groh et al 2015), but currently there are few AOP developers. To promote broader development of AOPs, and the inclusion of potential developers across various types of institutes and fields of study, this manuscript outlines strategies for initiating

Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

PubMed

Thomas, Jeremy; Hanby, Andrew; Pinder, Sarah E; Ball, Graham; Lawrence, Gill; Maxwell, Anthony; Wallis, Matthew; Evans, Andrew; Dobson, Hilary; Clements, Karen; Thompson, Alastair

2014-07-01

The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual. Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL). Inter-hospital variation was analysed by grouping hospitals into high, medium and low frequency subgroups for these two adverse outcomes. Patients with failed BCS or MFSL together accounted for 49% of all mastectomies. Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated with significant radiological under-estimation of disease extent and MFSL significant radiological over-estimation of disease extent. There was considerable and significant inter-hospital variation in failed BCS (range 3-32%) and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively. Conversely, there were no differences between the key radiological and pathological parameters in high, medium and low frequency adverse-outcome hospitals. This evidence suggests significant practice variation, not patient factors, is responsible for these adverse surgical outcomes in screen-detected DCIS. The Sloane Project provides an evidence base for future practice benchmarking. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association of Serum Bicarbonate With Risk of Renal and Cardiovascular Outcomes in CKD: A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study

PubMed Central

Dobre, Mirela; Yang, Wei; Chen, Jing; Drawz, Paul; Hamm, L. Lee; Horwitz, Edward; Hostetter, Thomas; Jaar, Bernard; Lora, Claudia M; Nessel, Lisa; Ojo, Akinlolu; Scialla, Julia; Steigerwalt, Susan; Teal, Valerie; Wolf, Myles; Rahman, Mahboob

2013-01-01

Background The purpose of this study is to evaluate serum bicarbonate as a risk factor for renal outcomes, cardiovascular events and mortality in patients with chronic kidney disease (CKD). Study Design Observational cohort study. Setting & Participants 3939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 - December 2008. Predictor Serum bicarbonate. Outcomes Renal outcomes, defined as end-stage renal disease (either initiation of dialysis or kidney transplantation) or 50% reduction in eGFR; atherosclerotic events (myocardial infarction, stroke, peripheral arterial disease); congestive heart failure events; and death. Measurements Time to event. Results The mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m2, and the median serum bicarbonate was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, and 332 experienced an atherosclerotic event and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal endpoint was 3% lower per mEq/L increase in serum bicarbonate (HR, 0.97; 95% CI, 0.94-0.99; p=0.01). The association was stronger for participants with eGFR> 45ml/min/1.73m2 (HR, 0.91; 95%CI, 0.85-0.97; p=0.004). The risk of heart failure increased by 14% (HR, 1.14; 95%CI, 1.03-1.26; p=0.02) per mEq/L increase in serum bicarbonate over 24 mEq/L. Serum bicarbonate was not independently associated with atherosclerotic events (HR, 0.99; 95%CI, 0.95-1.03; p=0.6) and all-cause mortality (HR, 0.98; 95%CI, 0.95-1.02; p=0.3). Limitations Single measurement of sodium bicarbonate. Conclusions In a cohort of participants with CKD, low serum bicarbonate was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate. There was no association between serum bicarbonate and all

Serum Lactate Predicts Adverse Outcomes in Emergency Department Patients With and Without Infection.

PubMed

Oedorf, Kimie; Day, Danielle E; Lior, Yotam; Novack, Victor; Sanchez, Leon D; Wolfe, Richard E; Kirkegaard, Hans; Shapiro, Nathan I; Henning, Daniel J

2017-02-01

Lactate levels are increasingly used to risk stratify emergency department (ED) patients with and without infection. Whether a serum lactate provides similar prognostic value across diseases is not fully elucidated. This study assesses the prognostic value of serum lactate in ED patients with and without infection to both report and compare relative predictive value across etiologies. We conducted a prospective, observational study of ED patients displaying abnormal vital signs (AVS) (heart rate ≥130 bpm, respiratory rate ≥24 bpm, shock index ≥1, and/or systolic blood pressure <90 mmHg). The primary outcome, deterioration, was a composite of acute renal failure, non-elective intubation, vasopressor administration or in-hospital mortality. Of the 1,152 patients with AVS who were screened, 488 patients met the current study criteria: 34% deteriorated and 12.5% died. The deterioration rate was 88/342 (26%, 95% CI: 21 - 30%) for lactate < 2.5 mmol/L, 47/90 (52%, 42 - 63%) for lactate 2.5 - 4.0 mmol/L, and 33/46 (72%, 59 - 85%) for lactate >4.0mmol/L. Trended stratified lactate levels were associated with deterioration for both infected (p<0.01) and non-infected (p<0.01) patients. In the logistic regression models, lactate > 4mmol/L was an independent predictor of deterioration for patients with infection (OR 4.8, 95% CI: 1.7 - 14.1) and without infection (OR 4.4, 1.7 - 11.5). Lactate levels can risk stratify patients with AVS who have increased risk of adverse outcomes regardless of infection status.

Adverse perinatal outcomes in borderline amniotic fluid index.

PubMed

Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh

2016-11-01

Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10 th percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10 th percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI.

Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis

PubMed Central

Kamb, Mary L; Newman, Lori M; Mark, Jennifer; Broutet, Nathalie; Hawkes, Sarah J

2013-01-01

Abstract Objective To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. Methods PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Findings Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0–74.1]; I2 = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8–17.2]; I2 = 95.9%; P < 0.001). Conclusion Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women. PMID:23476094

Proteomics for Adverse Outcome Pathway Discovery using Human Kidney Cells?

EPA Science Inventory

An Adverse Outcome Pathway (AOP) is a conceptual framework that applies molecular-based data for use in risk assessment and regulatory decision support. AOP development is based on effects data of chemicals on biological processes (i.e., molecular initiating events, key intermedi...

Weight-of-evidence evaluation of an adverse outcome ...

EPA Pesticide Factsheets

Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating staple food crops. Chemical and non-chemical stressors both have been implicated as possible contributors to colony failure, however, the potential role of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptor (nAChR) to eliminate target pest insects, however, mounting evidence indicates that these chemicals may adversely affect beneficial pollinators, such as the honey bee, via impacts on learning and memory thereby affecting foraging success. However, the mechanisms linking activation of the nAChR to adverse effects on learning and memory are uncertain. Additionally, clear connections between observed impacts on individual bees and colony level effects are lacking. Therefore, the objective of this work was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between the nAChR and colony level impacts. Development of these AOPs has led to the identification of research gaps which, for example, may be of high priority in understanding how perturbation of pathways involved in neurotransmission can adversely affect honey bee health, causing colony instability and further failure. From this effort, an AOP network also was developed, laying the f

Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

Volumetric Nephrogram Represents Renal Function and Complements Aortic Anatomic Severity Grade in Predicting EVAR Outcomes.

PubMed

Balceniuk, Mark D; Trakimas, Lauren; Aghaie, Claudia; Mix, Doran; Rasheed, Khurram; Seaman, Matthew; Ellis, Jennifer; Glocker, Roan; Doyle, Adam; Stoner, Michael C

2018-07-01

Chronic kidney disease (CKD) is a predictor of poor outcomes for patients undergoing endovascular aortic aneurysm repair (EVAR). Anatomic severity grade (ASG) represents a quantitative mechanism for assessing anatomical suitability for endovascular aortic repair. Anatomic severity grade has been correlated with repair outcomes and resource utilization. The purpose of this study was to identify a novel renal perfusion metric as a way to assist ASG with predicting EVAR outcomes. Retrospective review of a prospectively maintained database identified elective infrarenal aortic aneurysm repair cases. Anatomic grading was undertaken by independent reviewers. Using volumetric software, kidney volume, and a novel measure of kidney functional volume, the volumetric nephrogram (VN) was recorded. Systematic evaluation of the relationship of kidney volume and VN to CKD and ASG was undertaken using linear regression and receiver-operator statistical tools. A total of 386 cases with patient and anatomic data were identified and graded. Mean age was 72.9 ± 0.4 years. Renal volume <281 mL correlated with CKD (area under the curve [AUC] = .708; P ≤ .0001). Volumetric nephrogram <22.5 HU·L correlated with CKD (AUC = 0.764; P ≤ .0001). High (≥15) ASG scores correlated with both renal volume (AUC = .628; P ≤ .0001) and VN (AUC = .628; P ≤ .0001). Regression analysis demonstrated a strong, inverse relationship between ASG and VN ( R 2 = .95). These data demonstrate that VN is a strong predictor of CKD in a large database of patients undergoing elective aneurysm repair. We demonstrate an inverse relationship between renal function and ASG that has not been previously described in the literature. Additionally, we have shown that VN complements ASG as a model of overall cardiovascular health and atherosclerotic burden. Outcomes in patients with poor renal function may be related to anatomical issues in addition to well-described systemic ramifications.

Sirolimus Versus Tacrolimus as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

PubMed

Liu, Jin-Yu; Song, Ming; Guo, Min; Huang, Feng; Ma, Bing-Jun; Zhu, Lan; Xu, Gang; Li, Juan; You, Ru-Xu

Sirolimus and tacrolimus are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of sirolimus and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection (AR), and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and QALYs gained and incremental cost-effectiveness. Altogether, 1189 patients from 8 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of AR and patient withdrawn. Nevertheless, tacrolimus increased the risk of infection. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events after renal transplant. Tacrolimus is an effective and safe immunosuppressive agent, and it may be more cost-effective than cyclosporine for the primary prevention of AR in renal transplant recipients. However, it should be noted that such superiority was reversal when the cost of sirolimus and tacrolimus changed.

Tacrolimus Versus Cyclosporine as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

PubMed

Liu, Jin-Yu; You, Ru-Xu; Guo, Min; Zeng, Lu; Zhou, Pu; Zhu, Lan; Xu, Gang; Li, Juan; Liu, Dong

2016-01-01

Tacrolimus and cyclosporine are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of cyclosporine and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane Controlled Trials Register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection, and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and quality-adjusted life years gained and incremental cost-effectiveness. Altogether, 6137 patients from 27 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of patient mortality, graft loss, acute rejection, and hypercholesterolemia. Nevertheless, tacrolimus increased the risk of new-onset diabetes. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events following renal transplant. Tacrolimus is an effective and safe immunosuppressive agent and it may be more cost-effective than cyclosporine for the primary prevention of graft rejection in renal transplant recipients. However, new-onset diabetes should be closely monitored during the medication period.

Decreased first trimester PAPP-A is a predictor of adverse pregnancy outcome.

PubMed

Yaron, Yuval; Heifetz, Sigal; Ochshorn, Yifat; Lehavi, Ofer; Orr-Urtreger, Avi

2002-09-01

Low levels of maternal serum pregnancy associated plasma protein-A (PAPP-A) have been linked to chromosome anomalies such as trisomy 21, 13 and 18, triploidy and sex chromosome aneuploidy. Low levels of PAPP-A have also been implicated in spontaneous miscarriage. The purpose of this study was to evaluate whether low levels of first trimester PAPP-A are predictive of other adverse pregnancy outcomes. The study included patients with singleton pregnancies who underwent combined first trimester screening using nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and PAPP-A at 10-13 weeks' gestation. Patients with chromosome aberrations or fetal anomalies were excluded. Serum marker levels were expressed as gestational age-specific multiples of the median (MoMs). The incidences of various adverse pregnancy outcomes (spontaneous preterm labor, fetal growth restriction (FGR), proteinuric and non-proteinuric pregnancy induced hypertension (PIH), intrauterine fetal demise, oligohydramnios, spontaneous miscarriage and placental abruption) were evaluated, according to maternal PAPP-A MoM levels. Of the 1622 patients in the study, pregnancy complications were observed in 184 (11.3%). Patients with PAPP-A < or =0.25 MoM had significantly higher rates of FGR (RR = 3.12), proteinuric PIH (RR = 6.09), spontaneous miscarriage (RR = 8.76). No statistically significant differences were noted for other adverse outcomes evaluated Women with PAPP-A < or =0.50 MoM also had significantly higher rates of FGR (RR = 3.30) and spontaneous miscarriage (RR = 3.78). We conclude that decreased levels of first trimester maternal serum PAPP-A are predictive not only of chromosome anomalies but also of adverse pregnancy outcome. Copyright 2002 John Wiley & Sons, Ltd.

Parameters Associated with Adverse Fetal Outcomes in Parvovirus B19 Congenital Infection.

PubMed

Agra, Isabela Karine Rodrigues; Amorim Filho, Antonio Gomes; Lin, Lawrence Hsu; Biancolin, Sckarlet Ernandes; Francisco, Rossana Pulcineli Vieira; Brizot, Maria de Lourdes

2017-11-01

Objective  To investigate the clinical and sonographic parameters associated with adverse fetal outcomes in patients with congenital parvovirus B19 infection managed by intrauterine transfusion. Methods  This was a single-center retrospective study conducted from January 2005 to December 2016 that assessed patients with singleton pregnancies with fetal parvovirus infection confirmed by a polymerase chain reaction of the amniotic fluid or fetal blood samples who underwent at least one intrauterine transfusion. The maternal characteristics, sonographic findings and parameters related to intrauterine transfusion were compared between the two groups (recovery/non-recovery), who were categorized based on fetal response after in-utero transfusions. Progression to fetal death or delivery without fetal recovery after the transfusions was considered non-recovery and categorized as an adverse outcome. Results  The final analysis included ten singleton pregnancies: seven of which were categorized into the recovery group and three of which into the non-recovery group. The baseline characteristics were similar between the groups. All fetuses were hydropic at the time of diagnosis. No significant differences related to sonographic or intrauterine transfusion parameters were identified between the groups; however, the non-recovery group tended to have an increased number of sonographic markers and lower fetal hemoglobin and platelet levels before the transfusion. Conclusion  We were unable to firmly establish the clinical or sonographic parameters associated with adverse fetal outcomes in patients with parvovirus infection managed with intrauterine transfusions; however, edema, placental thickening and oligohydramnios may indicate greater fetal compromise and, subsequently, adverse outcomes. However, further studies are necessary, mainly due to the small number of cases analyzed in the present study. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Long-term outcome of patients with multiple [corrected] myeloma-related advanced renal failure following auto-SCT.

PubMed

Glavey, S V; Gertz, M A; Dispenzieri, A; Kumar, S; Buadi, F; Lacy, M; Hayman, S R; Kapoor, P; Dingli, D; McCurdy, A; Hogan, W J; Gastineau, D A; Leung, N

2013-11-01

Renal failure commonly complicates multiple myeloma (MM) and is associated with reduced survival. It is not clear whether auto-SCT results in improved renal function or attainment of independence from dialysis in patients with advanced renal impairment due to MM. We conducted a retrospective cohort study of all patients who underwent auto-SCT for MM complicated by advanced renal failure at our institution over a 10-year period (2000-2010). We aimed to assess the association between auto-SCT and renal outcome in patients with serum creatinine (SCr) over 3 mg/dL, attributable to MM, including those who were dialysis dependent. Thirty patients (2.8% of all auto-SCT patients) met inclusion criteria. Fourteen of 15 patients who were dialysis dependent before auto-SCT remained dialysis dependent in the long term despite hematological response (HR). Of the remaining 15 patients with SCr >3 mg/dL, an improvement in glomerular filtration rate (GFR) from 15 to 19.4 mL/min/1.73 m(2) was noted post auto-SCT (P=0.035); however, neither HR post auto-SCT or pre-existing renal function were independently associated with renal outcome. Auto-SCT was not associated with independence from dialysis in patients with renal failure due to MM at our institution. Although auto-SCT was associated with an improvement in GFR in patients with SCr >3 mg/dL, this improvement was not related to HR.

Magnitude of income-related disparities in adverse perinatal outcomes

PubMed Central

2014-01-01

Background To assess and compare multiple measurements of socioeconomic position (SEP) in order to determine the relationship with adverse perinatal outcomes across various contexts. Methods A birth registry, the Nova Scotia Atlee Perinatal Database, was confidentially linked to income tax and related information for the year in which delivery occurred. Multiple logistic regression was used to examine odds ratios between multiple indicators of SEP and multiple adverse perinatal outcomes in 117734 singleton births between 1988 and 2003. Models for after tax family income were also adjusted for neighborhood deprivation to gauge the relative magnitude of effects related to SEP at both levels. Effects of SEP were stratified by single- versus multiple-parent family composition, and by urban versus rural location of residence. Results The risk of small for gestational age and spontaneous preterm birth was higher across all the indicators of lower SEP, while risk for large for gestational age was lower across indicators of lower SEP. Higher risk of postneonatal death was demonstrated for several measures of lower SEP. Higher material deprivation in the neighborhood of residence was associated with increased risk for perinatal death, small for gestational age birth, and iatrogenic and spontaneous preterm birth. Family composition and urbanicity were shown to modify the association between income and some perinatal outcomes. Conclusions This study highlights the importance of understanding the definitions of SEP and the mechanisms that lead to the association between income and poor perinatal outcomes, and broadening the types of SEP measures used in some cases. PMID:24589212

Kidney disease in heart failure: the importance of novel biomarkers for type 1 cardio-renal syndrome detection.

PubMed

Palazzuoli, Alberto; McCullough, Peter A; Ronco, Claudio; Nuti, Ranuccio

2015-08-01

Chronic kidney disease (CKD) in heart failure (HF) has been recognized as an independent risk factor for adverse outcome, although the most important clinical trials tend to exclude patients with moderate and severe renal insufficiency. Despite this common association, the precise pathophysiological connection and liaison between heart and kidney is partially understood. Moreover, is it not enough considering how much cardio-renal syndrome type 1 is attributable to previous CKD, and how much to new-onset acute kidney injury (AKI). Neither development of AKI, its progression and time nor duration is related to an adverse outcome. An AKI definition is not universally recognized, and many confounding terms have been used in literature: "worsening renal function", "renal impairment", "renal dysfunction", etc., are all names that contribute to misunderstanding, and do not facilitate an universal classification. Therefore, AKI development should be the consequence of the basal clinical characteristics of patients, different primitive kidney disease and hemodynamic status. AKI could also be the mirror of several underlying associated diseases poorly controlled. Finally, it is not clear which is the optimal laboratory tool for identifying patients with an increased risk of AKI. In the current report, we review the different kidney diseases' impact in HF, and we analyze the modalities for AKI recognition during HF focusing our attention about some new biomarkers with potential application in the current setting.

Meningitis With a Negative Cerebrospinal Fluid Gram Stain in Adults: Risk Classification for an Adverse Clinical Outcome

PubMed Central

Khoury, Nabil T.; Hossain, Md Monir; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

2012-01-01

Objective To derive and validate a risk score for an adverse clinical outcome in adults with meningitis and a negative cerebrospinal fluid (CSF) Gram stain. Patients and Methods We conducted a retrospective study of 567 adults from Houston, Texas, with meningitis evaluated between January 1, 2005, and January 1, 2010. The patients were divided into derivation (N=292) and validation (N=275) cohorts. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Of the 567 patients, 62 (11%) had an adverse clinical outcome. A predictive model was created using 3 baseline variables that were independently associated with an adverse clinical outcome (P<.05): age greater than 60 years, abnormal findings on neurologic examination (altered mental status, focal neurologic deficits, or seizures), and CSF glucose level of less than 2.4975 mmol/L (to convert CSF glucose to mmol/L, multiply by 0.05551). The model classified patients into 2 categories of risk for an adverse clinical outcome—derivation sample: low risk, 0.6% and high risk, 32.8%; P<.001; and validation sample: low risk, 0.5% and high risk, 21.1%; P<.001. Conclusion Adults with meningitis and a negative CSF Gram stain can be accurately stratified for the risk of an adverse clinical outcome using clinical variables available at presentation. PMID:23218086

Risk factors for acute adverse events during ultrasound-guided central venous cannulation in the emergency department.

PubMed

Theodoro, Daniel; Krauss, Missy; Kollef, Marin; Evanoff, Bradley

2010-10-01

Ultrasound (US) greatly facilitates cannulation of the internal jugular vein. Despite the ability to visualize the needle and anatomy, adverse events still occur. The authors hypothesized that the technique has limitations among certain patients and clinical scenarios. The purpose of this study was to identify characteristics of adverse events surrounding US-guided central venous cannulation (CVC). The authors assembled a prospective observational cohort of emergency department (ED) patients undergoing consecutive internal jugular CVC with US. The primary outcome of interest was a composite of acute mechanical adverse events including hematoma, arterial cannulation, pneumothorax, and unsuccessful placement. Physicians performing the CVC recorded anatomical site, reason for insertion, and acute complications. The patients with catheters were followed until the catheters were removed based on radiographic evidence or hospital nursing records. ED charts and pharmacy records contributed variables of interest. A self-reported online survey provided physician experience information. Logistic regression was used to calculate the odds of an adverse outcome.   Physicians attempted 289 CVCs on 282 patients. An adverse outcome occurred in 57 attempts (19.7%, 95% confidence interval [CI] = 15.5 to 24.7), the most common being 31 unsuccessful placements (11%, 95% CI = 7.7 to 14.8). Patients with a history of end-stage renal disease (odds ratio [OR] = 3.54, 95% CI = 1.59 to 7.89), and central lines placed by operators with intermediate experience (OR = 2.26, 95% CI = 1.19 to 4.32), were most likely to encounter adverse events. Previously cited predictors such as body mass index (BMI), coagulopathy, and pulmonary hyperinflation were not significant in our final model. Acute adverse events occurred in approximately one-fifth of US-guided internal jugular central line attempts. The study identified both patient (history of end-stage renal disease) and physician (intermediate

[Maternal hemoglobin in Peru: regional differences and its association with adverse perinatal outcomes].

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Carrillo, Carlos

2011-01-01

To evaluate hemoglobin (Hb) levels in pregnant women from different geographical regions from Peru; to establish anemia and erythrocytocis rates and to establish the role of Hb on adverse perinatal outcomes using the Perinatal Information System (PIS) database of Peruvian Ministry of Health. Data were obtained from 379,816 births of 43 maternity care units between 2000 and 2010. Anemia and erythrocytocis rates were determined in each geographical region as well as rates of adverse perinatal outcomes. To analyze data the STATA program (versión 10.0,Texas, USA) was used. The results were considered significant at p<0.01. Mild anemia rate was higher in the coast (25.8%) and low forest (26.2%). Moderate/severe anemia rate in low forest was 2.6% and at the coast was 1.0%. In the highland, the highest rate of moderate/severe anemia was in the southern highlands (0.6%). The highest rate of erythrocytocis was found in the central highland (23.7%), 11.9% in the southern highland and 9.5% in the north highland. Severe anemia and erythrocytocis were associated with adverse perinatal outcomes. There are differences by Peruvian geographical region in anemia rates. In the central highlands were found the highest rates of erythrocytocis due to hypoxia effect in the high altitudes; however in the southern highlands, erythrocytocis was lower. Severe anemia and erythrocytosis were associated with increased adverse perinatal outcomes.

Application of the adverse outcome pathway framework - advances and challenges

EPA Science Inventory

The adverse outcome pathway (AOP) framework, while not new in concept, has gained attention in recent years as a set of organizing principles and tools that can help facilitate greater use of mechanistic or pathway-based data in risk assessment and regulatory decision-making. Reg...

Risk factors for adverse outcomes in older adults with blunt chest trauma: A systematic review.

PubMed

Sawa, Jake; Green, Robert S; Thoma, Brent; Erdogan, Mete; Davis, Philip J

2017-08-11

The objective of this study was to systematically review the published literature for risk factors associated with adverse outcomes in older adults sustaining blunt chest trauma. EMBASE and MEDLINE were searched from inception until March 2017 for prognostic factors associated with adverse outcomes in older adults sustaining blunt chest trauma using a pre-specified search strategy. References were independently screened for inclusion by two reviewers. Study quality was assessed using the Quality in Prognostic Studies tool. Where appropriate, descriptive statistics were used to evaluate study characteristics and predictors of adverse outcomes. Thirteen cohort studies representing 79,313 patients satisfied our selection criteria. Overall, 26 prognostic factors were examined across studies and were reported for morbidity (8 studies), length of stay (7 studies), mortality (6 studies), and loss of independence (1 study). No studies examined patient quality of life or emergency department recidivism. Prognostic factors associated with morbidity and mortality included age, number of rib fractures, and injury severity score. Although age and rib fractures were found to be associated with adverse outcomes in more than 3 studies, meta-analysis was not performed due to heterogeneity amongst included studies in how these variables were measured. While blunt chest wall trauma in older adults is relatively common, the literature on prognostic factors for adverse outcomes in this patient population remains inadequate due to a paucity of high quality studies and lack of consistent reporting standards.

Is polypharmacy an independent risk factor for adverse outcomes after an emergency department visit?

PubMed

Salvi, Fabio; Rossi, Lorena; Lattanzio, Fabrizia; Cherubini, Antonio

2017-03-01

This study aimed at verifying the role of polypharmacy as an independent risk factor for adverse health outcomes in older emergency department (ED) patients. This was a large (n = 2057) sample of older ED patients (≥65 years) participating in an observational cohort study. Polypharmacy and excessive polypharmacy were defined as having 6-9 drug prescriptions and 10 or more drug prescriptions in the last 3 months, respectively. The total number of medication prescriptions was also available. Outcome measures were in-hospital mortality; 30-day ED return; ED revisit, hospital admission, and mortality at 6 months. Logistic and Cox regression models as well as receiver operating characteristic curves using the Youden index and the area under the curve were calculated. Polypharmacy and excessive polypharmacy were present in 624 (30.3 %) and 367 (17.8 %) subjects, respectively. The mean number of prescriptions in the last 3 months was 5.7 (range 0-25) drugs. Polypharmacy and, particularly, excessive polypharmacy were constantly and independently associated with worse outcomes. A cut-off of 6 had the highest value of the Youden Index in predicting the majority of the adverse outcomes considered. Polypharmacy and excessive polypharmacy are independent risk factors for adverse health outcomes after an ED visit. Further studies are needed to clarify whether drug related issues (such as non-compliance, inappropriate or suboptimal prescribing, adverse drug reactions, and drug-drug or drug-disease interactions) or underlying multimorbidity and disease severity, as well as clinical complexity and frailty, are responsible for the negative outcomes associated with polypharmacy.

Further evidence for periodontal disease as a risk indicator for adverse pregnancy outcomes.

PubMed

Turton, Mervyn; Africa, Charlene W J

2017-06-01

Although there is increasing evidence to suggest an association between periodontal disease and adverse pregnancy outcomes, the issue remains controversial. This study tested the hypothesis that periodontal disease is a risk indicator for preterm delivery of low-birthweight infants. The study sample comprised 443 pregnant women with a mean (± standard deviation) age of 24.13 (±5.30) years. At first visit, maternal oral health status was assessed by the measurement of probing pocket depth and clinical attachment loss, and periodontal status was graded as absent, mild, moderate or severe. An association was sought between pregnancy outcomes and maternal periodontal status. While controlling for other factors, significant associations were found between pregnancy outcomes and maternal periodontal index scores. This study provides further evidence that periodontal disease is a risk indicator for adverse pregnancy outcomes. © 2016 FDI World Dental Federation.

The adverse outcome pathway concept: a pragmatic tool in toxicology.

PubMed

Vinken, Mathieu

2013-10-04

Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes.

PubMed

Milton, Abul H; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A; Mitchell, Kane

2017-05-23

Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low-moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations.

A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes

PubMed Central

Milton, Abul H.; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A.; Mitchell, Kane

2017-01-01

Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low–moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations. PMID:28545256

Childhood and Adolescent Adversity and Cardiometabolic Outcomes: A Scientific Statement From the American Heart Association.

PubMed

Suglia, Shakira F; Koenen, Karestan C; Boynton-Jarrett, Renée; Chan, Paul S; Clark, Cari J; Danese, Andrea; Faith, Myles S; Goldstein, Benjamin I; Hayman, Laura L; Isasi, Carmen R; Pratt, Charlotte A; Slopen, Natalie; Sumner, Jennifer A; Turer, Aslan; Turer, Christy B; Zachariah, Justin P

2018-01-30

Adverse experiences in childhood and adolescence, defined as subjectively perceived threats to the safety or security of the child's bodily integrity, family, or social structures, are known to be associated with cardiometabolic outcomes over the life course into adulthood. This American Heart Association scientific statement reviews the scientific literature on the influence of childhood adversity on cardiometabolic outcomes that constitute the greatest public health burden in the United States, including obesity, hypertension, type 2 diabetes mellitus, and cardiovascular disease. This statement also conceptually outlines pathways linking adversity to cardiometabolic health, identifies evidence gaps, and provides suggestions for future research to inform practice and policy. We note that, despite a lack of objective agreement on what subjectively qualifies as exposure to childhood adversity and a dearth of prospective studies, substantial evidence documents an association between childhood adversity and cardiometabolic outcomes across the life course. Future studies that focus on mechanisms, resiliency, and vulnerability factors would further strengthen the evidence and provide much-needed information on targets for effective interventions. Given that childhood adversities affect cardiometabolic health and multiple health domains across the life course, interventions that ameliorate these initial upstream exposures may be more appropriate than interventions remediating downstream cardiovascular disease risk factor effects later in life. © 2017 American Heart Association, Inc.

Overview of an internationally-harmonized program for adverse outcome pathway development

EPA Science Inventory

Adverse outcome pathways (AOPs) are critical frameworks for organizing knowledge concerning the scientifically-credible predictive linkages between toxicological observations made at molecular and cellular levels (e.g., via molecular screening assays, biomarker responses, or chem...

Sodium intake, RAAS-blockade and progressive renal disease.

PubMed

de Borst, Martin H; Navis, Gerjan

2016-05-01

Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) by angiotensin converting enzyme inhibitors or angiotensin receptor blockers is the current standard treatment to prevent progressive renal function loss in patients with chronic kidney disease. Yet in many patients the renal protective effect of RAAS-blockade is incomplete. Short-term clinical studies have demonstrated that dietary sodium restriction potentiates the antiproteinuric effect of RAAS-blockade. More recently, it was shown that this effect is accompanied by a lower risk of end-stage renal disease and adverse cardiovascular outcomes. The modulation of RAAS-blockade efficacy by sodium intake is likely multifactorial, and is mediated by effects of sodium on local tissue RAAS in kidney, vasculature and brain, and by effects on the immune system. Despite the evidence showing the beneficial effects of even a moderate sodium restriction (∼2.5g/d), it remains difficult to realize in clinical practice. In an analysis based on 24-h urinary sodium excretion data from more than 10,000 CKD patients and renal transplant recipients, we found that sodium intake in these patients is on average 3.8g/d, closely resembling the global general population (3.95g/d). Behavioral approaches including the use of online dietary coaching (ehealth) and feedback using data from 24-h urine collections may be useful to successfully lower dietary sodium intake, aiming to improve cardio-renal outcomes in patients with CKD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adverse Experiences in Early Childhood and Kindergarten Outcomes.

PubMed

Jimenez, Manuel E; Wade, Roy; Lin, Yong; Morrow, Lesley M; Reichman, Nancy E

2016-02-01

To examine associations between adverse childhood experiences (ACEs) in early childhood and teacher-reported academic and behavioral problems in kindergarten. We conducted a secondary analysis of data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort. Subjects with primary caregiver-reported information on ACE exposures ascertained at 5 years and teacher-reported outcomes at the end of the child's kindergarten year were included. Outcomes included teacher ratings of academic skills, emergent literacy skills, and behavior. We included 8 ACE exposures on the basis of the original Centers for Disease Control and Prevention Kaiser study and created an ACE score by summing individual adversities. We examined the associations between teacher-reported academic and behavioral outcomes and ACE scores by using logistic regression. In the study sample, 1007 children were included. Fifty-five percent had experienced 1 ACE and 12% had experienced ≥ 3. Adjusting for potential confounders, experiencing ≥ 3 ACEs was associated with below-average language and literacy skills (adjusted odds ratio [AORs]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and math skills (AOR: 1.8, 95% CI: 1.1-2.9), poor emergent literacy skills, attention problems (AOR: 3.5, 95% CI: 1.8-6.5), social problems (AOR: 2.7, 95% CI: 1.4-5.0), and aggression (AOR: 2.3, 95% CI: 1.2-4.6). In this study of urban children, experiencing ACEs in early childhood was associated with below-average, teacher-reported academic and literacy skills and behavior problems in kindergarten. These findings underscore the importance of integrated approaches that promote optimal development among vulnerable children. Copyright © 2016 by the American Academy of Pediatrics.

Women's health: periodontitis and its relation to hormonal changes, adverse pregnancy outcomes and osteoporosis.

PubMed

Krejci, Charlene B; Bissada, Nabil F

2012-01-01

To examine the literature with respect to periodontitis and issues specific to women's health, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. The literature was evaluated to review reported associations between periodontitis and genderspecific issues, namely, hormonal changes, adverse pregnancy outcomes and osteoporosis. Collectively, the literature provided a large body of evidence that supports various associations between periodontitis and hormonal changes, adverse pregnancy outcomes and osteoporosis; however, certain shortcomings were noted with respect to biases involving definitions, sample sizes and confounding variables. Specific cause and effect relationships could not be delineated at this time and neither could definitive treatment interventions. Future research must include randomised controlled trials with consistent definitions, adequate controls and sufficiently large sample sizes in order to clarify specific associations, identify cause and effect relationships, define treatment options and determine treatment interventions which will lessen the untoward effects on the at-risk populations.

Predicting adverse obstetric outcome after early pregnancy events and complications: a review.

PubMed

van Oppenraaij, R H F; Jauniaux, E; Christiansen, O B; Horcajadas, J A; Farquharson, R G; Exalto, N

2009-01-01

BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited or small uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care.

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes.

PubMed

Adachi, Kristina; Klausner, Jeffrey D; Xu, Jiahong; Ank, Bonnie; Bristow, Claire C; Morgado, Mariza G; Watts, D Heather; Weir, Fred; Persing, David; Mofenson, Lynne M; Veloso, Valdilea G; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J; Grinsztejn, Beatriz; Bastos, Francisco I; Siberry, George; Nielsen-Saines, Karin

2016-08-01

Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03-1.76). STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

PubMed Central

Adachi, Kristina; Klausner, Jeffrey D.; Xu, Jiahong; Ank, Bonnie; Bristow, Claire C.; Morgado, Mariza G.; Watts, D. Heather; Weir, Fred; Persing, David; Mofenson, Lynne M.; Veloso, Valdilea G.; Pilotto, Jose Henrique; Joao, Esau; Gray, Glenda; Theron, Gerhard; Santos, Breno; Fonseca, Rosana; Kreitchmann, Regis; Pinto, Jorge; Mussi-Pinhata, Marisa M.; Ceriotto, Mariana; Machado, Daisy Maria; Bryson, Yvonne J.; Grinsztejn, Beatriz; Bastos, Francisco I.; Siberry, George; Nielsen-Saines, Karin

2016-01-01

BACKGROUND Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. METHODOLOGY Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. RESULTS Of 1373 maternal urines, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG, and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery, death) were noted in infants of women with CT and NG (23/35, 65.7%) compared to NG (16/28, 57.1%), CT (84/214, 39.3%), and no STI (405/1096, 37%, p=0.001). Death (11.4% vs. 3%, p=0.02), low birth weight (42.9% vs. 16.9%, p=0.001), and preterm delivery (28.6% vs. 10.2%, p=0.008) were higher among infants of CT and NG co-infected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV-infected after controlling for maternal syphilis (OR 3.5, 95% CI 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (OR 1.35, 95% CI 1.03-1.76). CONCLUSION STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants. PMID:27164464

Cardiovascular recovery from psychological and physiological challenge and risk for adverse cardiovascular outcomes and all-cause mortality

PubMed Central

Panaite, Vanessa; Salomon, Kristen; Jin, Alvin; Rottenberg, Jonathan

2015-01-01

Objective Exaggerated cardiovascular (CV) reactivity to laboratory challenge has been shown to predict future CV morbidity and mortality. CV recovery, has been less studied, and has yielded inconsistent findings, possibly due to presence of moderators. Reviews on the relationship between CV recovery and CV outcomes have been limited to cross-sectional studies and have not considered methodological factors. We performed a comprehensive meta-analytic review of the prospective literature investigating CV recovery to physical and psychological challenge and adverse cardiovascular outcomes. Methods We searched PsycINFO and PubMed for prospective studies investigating the relationship between CV recovery and adverse CV outcomes. Studies were coded for variables of interest and for effect sizes (ES). We conducted a random effects weighted meta-analysis. Moderators were examined with ANOVA-analog and meta-regression analyses. Results Thirty seven studies met inclusion criteria (N=125386). Impaired recovery from challenge predicted adverse cardiovascular outcomes (summary effect, r = .17, p < .001). Physical challenge was associated with larger predictive effects than psychological challenge. Moderator analyses revealed that recovery measured at 1 minute post-exercise, passive recovery, use of mortality as an outcome measure, and older sample age were associated with larger effects. Conclusions Poor recovery from laboratory challenges predicts adverse CV outcomes, with recovery from exercise serving as a particularly strong predictor of CV outcomes. The overall ES for recovery and CV outcomes is similar to that observed for CV reactivity and suggests that the study of recovery may have incremental value for understanding adverse CV outcomes. PMID:25829236

Partner Disengagement from Pregnancy and Adverse Maternal and Infant Outcomes.

PubMed

Urquia, Marcelo L; Pulver, Ariel; Heaman, Maureen I; Ray, Joel G; Daoud, Nihaya; O'Campo, Patricia

2017-03-01

To assess whether partner disengagement from pregnancy is associated with adverse maternal and infant outcomes. We analyzed data from the 2006-2007 Canadian Maternity Experiences Survey, comprising a cross-sectional representative sample of 6,421 childbearing women. Multiple logistic regression assessed the association between adverse outcomes and three indicators of partner disengagement: (1) partner did not want the pregnancy, (2) partner argued more than usual in the year prior to the baby's birth, and (3) partner was absent at the delivery. Of all respondents, 3.8% had partners who did not want the pregnancy, 16.1% argued more than usual with their partner in the past year, and 7.6% had partners who were absent at the delivery. Women whose partner did not want the pregnancy were more likely to report intimate partner violence (IPV) (adjusted odds ratio [AOR] 3.55; 95% confidence interval [95% CI] 2.36-5.14), elevated depressive symptoms in the extended postpartum period (AOR 2.56, 95% CI 1.70-3.83), and nonroutine child healthcare visits after birth (AOR 1.54, 95% CI 1.13-2.11). Women whose partner argued more in the past year had higher odds of IPV (AOR 4.82, 95% CI 3.69-6.30), elevated depressive symptoms in the extended postpartum period (AOR 3.63; 95% CI 2.84-4.64), and nonroutine child healthcare visits (AOR 1.49, 95% CI 1.26-1.77), after adjustment for potential confounders. Partner disengagement is common and is associated with adverse maternal and infant outcomes. Affected women may benefit from special assistance during pregnancy and after delivery.

Anti-prothrombin antibodies are associated with adverse pregnancy outcome.

PubMed

Marozio, Luca; Curti, Antonella; Botta, Giovanni; Canuto, Emilie M; Salton, Loredana; Tavella, Anna Maria; Benedetto, Chiara

2011-11-01

Women with antiphospholipid antibodies (aPL) such as lupus anticoagulant, anticardiolipin antibodies, and anti-β(2) glycoprotein-1 antibodies are at high risk of late pregnancy complications, such as severe pre-eclampsia, placental insufficiency, and fetal loss. It has been observed that aPL consists of a heterogeneous group of antibodies targeting several phospholipid-binding plasma proteins, including also anti-prothrombin (anti-PT), anti-protein S (anti-PS), and anti-protein C (anti-PC) antibodies. Their potential role in late pregnancy complications is not known. The aim of this work was to investigate the association between those autoantibodies and histories for adverse pregnancy outcome. Anti-PT, anti-PS, and anti-PC antibodies were evaluated in 163 patients with previous severe pre-eclampsia, fetal death, and/or placental abruption and in as many women with previous uneventful pregnancies, negative for aPL. The prevalence of anti-PT antibodies was higher in cases than in controls (OR, 95% CI: 10.92, 4.52-26.38). The highest prevalence was observed in subjects with fetal death. Anti-PT antibodies appear to be associated with adverse pregnancy outcome, irrespectively of aPL. © 2011 John Wiley & Sons A/S.

Evaluation of Clinical Outcomes and Renal Vascular Pathology among Patients with Lupus

PubMed Central

Barber, Claire; Herzenberg, Andrew; Aghdassi, Ellie; Su, Jiandong; Lou, Wendy; Qian, Gan; Yip, Jonathan; Nasr, Samih H.; Thomas, David; Scholey, James W.; Wither, Joan; Urowitz, Murray; Gladman, Dafna; Reich, Heather

2012-01-01

Summary Background and objectives The objective of this study was to determine the clinical significance of renal vascular lesions in lupus nephritis. Design, setting, participants, & measurements Renal vascular lesions defined as thrombotic microangiopathy, lupus vasculopathy, uncomplicated vascular immune deposits, and arterial sclerosis were evaluated in relation to renal and vascular morbidity and overall mortality. Results Biopsies from 161 patients revealed thrombotic microangiopathy (13), lupus vasculopathy (5), and arterial sclerosis (93). No renal vascular lesions were found in 24.8% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older (arterial sclerosis=37.9±13.0 and lupus vasculopathy=44.4±8.9 versus controls=33.1±8.9 years, P<0.05), and the mean arterial pressure was higher in all groups compared with controls. Nephritis subtype, activity indices, and proteinuria were similar between groups, estimated GFR was lower in arterial sclerosis (70.5±33.3 versus 84.5±26.6 ml/min per 1.73 m2, P=0.03), and chronicity index (thrombotic microangiopathy=3.5, lupus vasculopathy=4.5, and arterial sclerosis=2.5) was higher in all renal vascular lesions subgroups versus controls (1.0, P<0.05). In 133 patients with similar follow-up, the association between renal vascular lesions and vascular events was significant (Fisher exact test, P=0.002) and remained so after multivariate analysis (exact conditional scores test, P=0.04), where the difference between arterial sclerosis and uncomplicated vascular immune deposits was most noticeable (odds ratio [95% confidence interval]=8.35[0.98, 83.12], P=0.05). The associations between renal vascular lesions, renal outcomes, and death were not significant, likely because of insufficient power. Conclusions Renal vascular lesions are common in SLE patients with nephritis and may be associated with arterial vascular events. PMID:22442181

Renal sympathetic denervation for resistant hypertension.

PubMed

Froeschl, Michael; Hadziomerovic, Adnan; Ruzicka, Marcel

2013-05-01

Resistant hypertension is an increasingly prevalent health problem associated with important adverse cardiovascular outcomes. The pathophysiology that underlies this condition involves increased function of both the sympathetic nervous system and the renin-angiotensin II-aldosterone system. A crucial link between these 2 systems is the web of sympathetic fibres that course within the adventitia of the renal arteries. These nerves can be targeted by applying radiofrequency energy from the lumen of the renal arteries to renal artery walls (percutaneous renal sympathetic denervation [RSD]), an approach that has attracted great interest. This paper critically reviews the evidence supporting the use of RSD. Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data. Some of these concerns are being addressed in the ongoing Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN-3) trial. The first percutaneous RSD system was approved by Health Canada in the spring of 2012. But until more and better-quality data are available, this procedure should generally be reserved for those patients whose resistant hypertension is truly uncontrolled. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II.

PubMed

Tumlin, James A; Murugan, Raghavan; Deane, Adam M; Ostermann, Marlies; Busse, Laurence W; Ham, Kealy R; Kashani, Kianoush; Szerlip, Harold M; Prowle, John R; Bihorac, Azra; Finkel, Kevin W; Zarbock, Alexander; Forni, Lui G; Lynch, Shannan J; Jensen, Jeff; Kroll, Stew; Chawla, Lakhmir S; Tidmarsh, George F; Bellomo, Rinaldo

2018-06-01

Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. ICUs. Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). IV angiotensin II or placebo. Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Employment outcomes following successful renal transplantation.

PubMed

Eng, Mary; Zhang, Jie; Cambon, Alexander; Marvin, Michael R; Gleason, John

2012-01-01

Data on employment outcomes after successful renal transplantation are few. We conducted this study to identify favorable factors for employment after transplantation. Adult patients <65 yr of age who underwent renal transplantation between January 1, 2002 and December 31, 2007 were surveyed. Patients with graft survival <1 yr were excluded. We also tested their knowledge of Medicare coverage after transplantation. Data were analyzed using chi-squared and Fisher's exact tests. p-Value <0.05 was considered statistically significant. A 55% response rate was obtained where 56% of respondents were employed after transplantation. Race, marital status, previous transplant, and complicated post-operative course did not influence employment. Favorable factors include male gender (p=0.04), younger age (<40 [p=0.0003] or <50 yr [p<0.0001]), having ≥1 dependent (p=0.04), higher education (minimum high school degree [p=0.003] or some college [p=0.002]), live donor recipient (p=0.004), wait time <2 yr (p=0.03), dialysis <2 yr (p<0.0001) or pre-dialysis (p=0.04), and pre-transplantation employment (p<0.0001). Mean time for employment was 4.9±6.3 months (median three months). Common reasons for unemployment were disability (59%) and retirement (27%). Finally, 7% correctly responded that Medicare benefits end 36 months following transplantation. Potentially modifiable factors to improve employment are earlier referral and better education regarding Medicare eligibility. © 2011 John Wiley & Sons A/S.

Adverse health outcomes in women exposed in utero to diethylstilbestrol.

PubMed

Hoover, Robert N; Hyer, Marianne; Pfeiffer, Ruth M; Adam, Ervin; Bond, Brian; Cheville, Andrea L; Colton, Theodore; Hartge, Patricia; Hatch, Elizabeth E; Herbst, Arthur L; Karlan, Beth Y; Kaufman, Raymond; Noller, Kenneth L; Palmer, Julie R; Robboy, Stanley J; Saal, Robert C; Strohsnitter, William; Titus-Ernstoff, Linda; Troisi, Rebecca

2011-10-06

Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood. We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero. Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes. In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes

Patient-Reported Disease Activity and Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

PubMed

Harris, Nathaniel; Eudy, Amanda; Clowse, Megan

2018-06-15

While increased rheumatic disease activity during pregnancy has been associated with adverse pregnancy outcomes, this activity is typically assessed by the physician. Little is known, however, about the association between patient-reported measures of disease activity and pregnancy outcomes. Univariate and multivariable regression models were used to assess the relationship between patient and physician-reported measures of disease activity and adverse pregnancy outcomes in 225 patients with lupus or rheumatoid arthritis (RA) enrolled in a prospective registry at a single academic center from 2008-2016. In women with RA, patient-reported disease activity is associated with preterm birth (OR 5.9 (1.5-23.9)), and gestational age (beta -1.5 weeks (-2.6, -0.4 weeks)). The physician assessment of disease activity also predicted preterm (OR 2.1 (1.2-3.5)), small for gestational age births (OR 1.8 (1.03-3.1), and gestational age in weeks (beta -0.6 weeks (-0.9, -0.02 weeks)). On the other hand, SLE patient-reported disease activity measures, including the HAQ, pain or global health measures, are not associated with adverse pregnancy outcomes. However, physician measures of SLE disease activity are associated with preterm birth (OR 2.9 (1.-6.3)), cesarean delivery (OR 2.3 (1.0-5.3)), and preeclampsia (OR 2.8 (1.3-6.3)). The results do not appear to be driven by lupus nephritis or antiphospholipid syndrome. For women with RA, patient-reported measures of disease activity may be useful adjuncts to physician-reported measures in identifying pregnancies at greater risk. In contrast, in SLE, no patient-reported measures were associated with adverse outcomes while physician measures of disease activity helped predict several adverse pregnancy outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

An Integrative Data Mining Approach to Identify Adverse Outcome Pathway Signatures

EPA Science Inventory

Adverse Outcome Pathways (AOPs) provide a formal framework for describing the mechanisms underlying the toxicity of chemicals in our environment. This process improves our ability to incorporate high-throughput toxicity testing (HTT) results and biomarker information on early key...

Pregnancy and renal outcomes in lupus nephritis: an update and guide to management.

PubMed

Bramham, K; Soh, M C; Nelson-Piercy, C

2012-10-01

Systemic lupus erythematosis (SLE) commonly affects women of child bearing-age, and advances in treatment have resulted in an increasing number of women with renal involvement becoming pregnant. Knowledge of the relationship of the condition with respect to fertility and pregnancy is important for all clinicians involved in the care of women with lupus nephritis because they have complicated pregnancies. Presentation of lupus nephritis can range from mild asymptomatic proteinuria to rapidly progressive renal failure and may occur before, during, or after pregnancy. The timing of diagnosis may influence pregnancy outcome. Pregnancy may also affect the course of lupus nephritis. All pregnancies in women with lupus nephritis should be planned, preferably after more than six-months of quiescent disease. Predictors of poor obstetric outcome include active disease at conception or early pregnancy, baseline poor renal function with Creatinine >100 μmol/L, proteinuria >0.5 g/24 hours, presence of concurrent antiphospholipid syndrome and hypertension. In this review the most recent studies of pregnancies in women with lupus nephritis are discussed and a practical approach to managing women prepregnancy, during pregnancy and post-partum is described.

Classification of individual well-being scores for the determination of adverse health and productivity outcomes in employee populations.

PubMed

Shi, Yuyan; Sears, Lindsay E; Coberley, Carter R; Pope, James E

2013-04-01

Adverse health and productivity outcomes have imposed a considerable economic burden on employers. To facilitate optimal worksite intervention designs tailored to differing employee risk levels, the authors established cutoff points for an Individual Well-Being Score (IWBS) based on a global measure of well-being. Cross-sectional associations between IWBS and adverse health and productivity outcomes, including high health care cost, emergency room visits, short-term disability days, absenteeism, presenteeism, low job performance ratings, and low intentions to stay with the employer, were studied in a sample of 11,702 employees from a large employer. Receiver operating characteristics curves were evaluated to detect a single optimal cutoff value of IWBS for predicting 2 or more adverse outcomes. More granular segmentation was achieved by computing relative risks of each adverse outcome from logistic regressions accounting for sociodemographic characteristics. Results showed strong and significant nonlinear associations between IWBS and health and productivity outcomes. An IWBS of 75 was found to be the optimal single cutoff point to discriminate 2 or more adverse outcomes. Logistic regression models found abrupt reductions of relative risk also clustered at IWBS cutoffs of 53, 66, and 88, in addition to 75, which segmented employees into high, high-medium, medium, low-medium, and low risk groups. To determine validity and generalizability, cutoff values were applied in a smaller employee population (N=1853) and confirmed significant differences between risk groups across health and productivity outcomes. The reported segmentation of IWBS into discrete cohorts based on risk of adverse health and productivity outcomes should facilitate well-being comparisons and worksite interventions.

Surgical Adverse Events, Risk Management, and Malpractice Outcome: Morbidity and Mortality Review Is Not Enough

PubMed Central

Morris, John A.; Carrillo, Ysela; Jenkins, Judith M.; Smith, Philip W.; Bledsoe, Sandy; Pichert, James; White, Andrew

2003-01-01

Objective To review all admissions (age > 13) to three surgical patient care centers at a single academic medical center between January 1, 1995, and December 6, 1999, for significant surgical adverse events. Summary Background Data Little data exist on the interrelationships between surgical adverse events, risk management, malpractice claims, and resulting indemnity payments to plaintiffs. The authors hypothesized that examination of this process would identify performance improvement opportunities overlooked by standard medical peer review; the risk of litigation would be constant across the three homogeneous patient care centers; and the risk management process would exceed the performance improvement process. Methods Data collected included patient demographics (age, gender, and employment status), hospital financials (hospital charges, costs, and financial class), and outcome. Outcome categories were medical (disability: <1 month, 1–6 months, permanent/death), legal (no legal action, settlement, summary judgment), financial (indemnity payments, legal fees, write-offs), and cause and effect analysis. Cause and effect analysis attempts to identify system failures contributing to adverse outcomes. This was determined by two independent analysts using the 17 Harvard criteria and subdividing these into subsystem causative factors. Results The study group consisted of 130 patients with surgical adverse events resulting in total liabilities of $8.2 million. The incidence of adverse events per 1,000 admissions across the three patient care centers was similar, but indemnity payments per 1,000 admissions varied (cardiothoracic = $30, women’s health = $90, trauma = $520). Patient demographics were not predictive of high-risk subgroups for adverse events or litigation. In terms of medical outcome, 51 patients had permanent disability or death, accounting for 98% of the indemnity payments. In terms of legal outcome, 103 patients received no indemnity payments, 15

Adverse Outcome Pathways – Organizing Toxicological Information to Improve Decision Making

EPA Science Inventory

The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High throughput screening (HTS) commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP)...

Early Childhood Adversity and Pregnancy Outcomes

PubMed Central

Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

2016-01-01

Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

Acculturation and Adverse Birth Outcomes in a Predominantly Puerto Rican Population.

PubMed

Barcelona de Mendoza, Veronica; Harville, Emily; Theall, Katherine; Buekens, Pierre; Chasan-Taber, Lisa

2016-06-01

Introduction Latinas in the United States on average have poorer birth outcomes than Whites, yet considerable heterogeneity exists within Latinas. Puerto Ricans have some of the highest rates of adverse outcomes and are understudied. The goal of this study was to determine if acculturation was associated with adverse birth outcomes in a predominantly Puerto Rican population. Methods We conducted a secondary analysis of Proyecto Buena Salud, a prospective cohort study conducted from 2006 to 2011. A convenience sample of pregnant Latina women were recruited from a tertiary care hospital in Massachusetts. Acculturation was measured in early pregnancy; directly via the Psychological Acculturation Scale, and via proxies of language preference and generation in the United States. Birth outcomes (gestational age and birthweight) were abstracted from medical records (n = 1362). Results After adjustment, psychological acculturation, language preference, and generation was not associated with odds of preterm birth. However, every unit increase in psychological acculturation score was associated with an increase in gestational age of 0.22 weeks (SE = 0.1, p = 0.04) among all births. Women who preferred to speak Spanish (β = -0.39, SE = 0.2, p = 0.02) and who were first generation in the US (β = -0.33, SE = 0.1, p = 0.02) had significantly lower gestational ages than women who preferred English or who were later generation, respectively. Similarly, women who were first generation had babies who weighed 76.11 g less (SE = 35.2, p = 0.03) than women who were later generation. Discussion We observed a small, but statistically significant adverse impact of low acculturation on gestational age and birthweight in this predominantly Puerto Rican population.

Intimate partner violence among Egyptian pregnant women: incidence, risk factors, and adverse maternal and fetal outcomes.

PubMed

Ibrahim, Z M; Sayed Ahmed, W A; El-Hamid, S A; Hagras, A M

2015-01-01

To assess incidence and risk factors of intimate partner violence (IPV) during pregnancy among a sample of women from Egypt and to evaluate its impact on maternal and fetal adverse health outcomes. After obtaining ethical approval, a total of 1,857 women aged 18 - 43 years completed the study and were investigated using an interview questionnaire. The questionnaire contains five main items: demographic characteristics of women, intimate partner characteristics, assessment of IPV during current pregnancy, and assessment of maternal as well as fetal/neonatal adverse outcomes. Women were also examined to detect signs of violence and identify injuries. Exposure to IPV during pregnancy was reported among 44.1% of the studied women. Emotional violence was the most common form. Women exposed to violence were of younger age, higher parity, and lower educational level. Their partners were older, less educated, and more likely to be addicted to drugs and alcohol. Women were also found to have significantly higher incidence of adverse pregnancy outcomes (miscarriage, preterm labor, and premature rupture of membrane), and fetal/neonatal adverse outcomes (fetal distress, fetal death, and low birth weight). A total of 297 cases had been exposed to physical violence (15.9%) vs 32.6% and 10% exposed to emotional and sexual violence, respectively. The most common form of physical violence was kicking. Violence during pregnancy is prevalent among Egyptian women. Exposure to violence was a significant risk factor for multiple adverse maternal and fetal health outcomes.

Elevated urinary neutrophil gelatinase-associated lipocalcin after acute heart failure treatment is associated with worsening renal function and adverse events

PubMed Central

Collins, Sean P.; Hart, Kimberly W.; Lindsell, Christopher J.; Fermann, Gregory J.; Weintraub, Neal L.; Miller, Karen F.; Roll, Susan N.; Sperling, Matthew I.; Sawyer, Douglas B.; Storrow, Alan B.

2012-01-01

Aims Reliable detectors of worsening renal function (WRF) in Emergency Department (ED) patients with acute heart failure (AHF) are limited. We hypothesized that initial urinary neutrophil gelatinase-associated lipocalcin (NGAL) levels, and changes in urinary NGAL levels after initial ED AHF therapy, would be associated with WRF and adverse events. Methods and results Urinary NGAL upon ED presentation and 12–24 h after ED treatment was measured in a cohort of ED patients with AHF. NGAL was corrected for urinary creatinine (uCr). WRF was defined as RIFLE stages 1, 2, or 3, or a creatinine increase of ≥0.3 mg/dL. Patients were prospectively followed for 5- and 30-day adverse cardiovascular events. The 399 patients had a median age of 63 years, 50% were Caucasian, and 62% were male. Those with WRF at 72–96 h were more likely to have a higher initial NGAL value (71 vs. 32 ng NGAL/mg uCr) (P = 0.005), and a higher NGAL level at 12–24 h after ED therapy (107 vs. 25ng NGAL/mg uCr, P < 0.001). In a multivariable model, NGAL at 12–24 h remained a significant predictor of WRF (P = 0.012). Of all variables available 12–24 h after initial therapy, the only significant predictor of 30-day events was an elevated urinary NGAL level (P = 0.02). Conclusions Urinary NGAL levels determined 12–24 h after ED therapy are significantly associated with both WRF at 72–96 h and 30-day adverse events. This suggests that early management strategies may have an impact on subsequent WRF and outcomes. If confirmed, NGAL may have a role for guiding therapeutic decisions. PMID:22733980

Using continuous renal replacement therapy to manage patients of shock and acute renal failure

PubMed Central

Soni, Sachin S; Nagarik, Amit P; Adikey, Gopal Kishan; Raman, Anuradha

2009-01-01

Background: The incidence of acute renal failure (ARF) in the hospital setting is increasing. It portends excessive morbidity and mortality and a considerable burden on hospital resources. Extracorporeal therapies show promise in the management of patients with shock and ARF. It is said that the potential of such therapy goes beyond just providing renal support. The aim of our study was to analyze the clinical setting and outcomes of critically ill ARF patients managed with continuous renal replacement therapy (CRRT). Patients and Methods: Ours was a retrospective study of 50 patients treated between January 2004 and November 2005. These 50 patients were in clinical shock and had concomitant ARF. All of these patients underwent CVVHDF (continuous veno-venous hemodiafiltration) in the intensive care unit. For the purpose of this study, shock was defined as systolic BP < 100 mm Hg in spite of administration of one or more inotropic agents. SOFA (Sequential Organ Failure Assessment) score before initiation of dialysis support was recorded in all cases. CVVHDF was performed using the Diapact® (Braun) CRRT machine. The vascular access used was as follows: femoral in 32, internal jugular in 8, arteriovenous fistula (AVF) in 4, and subclavian in 6 patients. We used 0.9% or 0.45% (half-normal) saline as a prefilter replacement, with addition of 10% calcium gluconate, magnesium sulphate, sodium bicarbonate, and potassium chloride in separate units, while maintaining careful monitoring of electrolytes. Anticoagulation of the extracorporeal circuit was achieved with systemic heparin in 26 patients; frequent saline flushes were used in the other 24 patients. Results: Of the 50 patients studied, 29 were males and 21 females (1.4:1). The average age was 52.88 years (range: 20–75 years). Causes of ARF included sepsis in 24 (48%), hemodynamically mediated renal failure (HMRF) in 18 (36%), and acute over chronic kidney disease in 8 (16%) patients. The overall mortality was 74

Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Dobre, Mirela; Yang, Wei; Chen, Jing; Drawz, Paul; Hamm, L Lee; Horwitz, Edward; Hostetter, Thomas; Jaar, Bernard; Lora, Claudia M; Nessel, Lisa; Ojo, Akinlolu; Scialla, Julia; Steigerwalt, Susan; Teal, Valerie; Wolf, Myles; Rahman, Mahboob

2013-10-01

The purpose of this study is to evaluate serum bicarbonate level as a risk factor for renal outcomes, cardiovascular events, and mortality in patients with chronic kidney disease (CKD). Observational cohort study. 3,939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and December 2008. Serum bicarbonate level. Renal outcomes, defined as end-stage renal disease (either initiation of dialysis therapy or kidney transplantation) or 50% reduction in estimated glomerular filtration rate (eGFR); atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease); congestive heart failure events; and death. Time to event. Mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m(2), and median serum bicarbonate level was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, 332 experienced an atherosclerotic event, and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal end point was 3% lower per 1-mEq/L increase in serum bicarbonate level (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01). The association was stronger for participants with eGFR >45 mL/min/1.73 m(2) (HR, 0.91; 95% CI, 0.85-0.97; P = 0.004). The risk of heart failure increased by 14% (HR, 1.14; 95% CI, 1.03-1.26; P = 0.02) per 1-mEq/L increase in serum bicarbonate level over 24 mEq/L. Serum bicarbonate level was not associated independently with atherosclerotic events (HR, 0.99; 95% CI, 0.95-1.03; P = 0.6) and all-cause mortality (HR, 0.98; 95% CI, 0.95-1.02; P = 0.3). Single measurement of sodium bicarbonate. In a cohort of participants with CKD, low serum bicarbonate level was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate levels. There was no association between serum bicarbonate level and all

Exposure and Dosimetry Considerations for Adverse Outcome Pathways (AOPs) (NIH-AOP)

EPA Science Inventory

Risk is a function of both of hazard and exposure. Toxicokinetic (TK) models can determine whether chemical exposures produce potentially hazardous tissue concentrations. Whether or not the initial molecular event (MIE) in an Adverse Outcome Pathway (AOP) occurs depends on both e...

Modeling Major Adverse Outcomes of Pediatric and Adult Patients With Congenital Heart Disease Undergoing Cardiac Catheterization: Observations From the NCDR IMPACT Registry (National Cardiovascular Data Registry Improving Pediatric and Adult Congenital Treatment).

PubMed

Jayaram, Natalie; Spertus, John A; Kennedy, Kevin F; Vincent, Robert; Martin, Gerard R; Curtis, Jeptha P; Nykanen, David; Moore, Phillip M; Bergersen, Lisa

2017-11-21

Risk standardization for adverse events after congenital cardiac catheterization is needed to equitably compare patient outcomes among different hospitals as a foundation for quality improvement. The goal of this project was to develop a risk-standardization methodology to adjust for patient characteristics when comparing major adverse outcomes in the NCDR's (National Cardiovascular Data Registry) IMPACT Registry (Improving Pediatric and Adult Congenital Treatment). Between January 2011 and March 2014, 39 725 consecutive patients within IMPACT undergoing cardiac catheterization were identified. Given the heterogeneity of interventional procedures for congenital heart disease, new procedure-type risk categories were derived with empirical data and expert opinion, as were markers of hemodynamic vulnerability. A multivariable hierarchical logistic regression model to identify patient and procedural characteristics predictive of a major adverse event or death after cardiac catheterization was derived in 70% of the cohort and validated in the remaining 30%. The rate of major adverse event or death was 7.1% and 7.2% in the derivation and validation cohorts, respectively. Six procedure-type risk categories and 6 independent indicators of hemodynamic vulnerability were identified. The final risk adjustment model included procedure-type risk category, number of hemodynamic vulnerability indicators, renal insufficiency, single-ventricle physiology, and coagulation disorder. The model had good discrimination, with a C-statistic of 0.76 and 0.75 in the derivation and validation cohorts, respectively. Model calibration in the validation cohort was excellent, with a slope of 0.97 (standard error, 0.04; P value [for difference from 1] =0.53) and an intercept of 0.007 (standard error, 0.12; P value [for difference from 0] =0.95). The creation of a validated risk-standardization model for adverse outcomes after congenital cardiac catheterization can support reporting of risk

Incidence and Predictors of Long-Term Adverse Outcomes in Patients with Rheumatic Mitral Stenosis in Sinus Rhythm.

PubMed

Nachom, Patsadee; Ratanasit, Nithima

2016-04-01

Rheumatic fever and rheumatic heart disease remain important health problems in developing countries. Mitral stenosis (MS) is the most common form of rheumatic heart disease. The aim of this study was to investigate incidence and echocardiographic predictors of long-term adverse outcomes in patients with rheumatic mitral stenosis in sinus rhythm. We retrospectively reviewed medical records of patients diagnosed with isolated rheumatic MS of any severity at Siriraj Hospital between 1996 and 2013. Demographic data, echocardiographic data, and long-term adverse outcomes were collected. Long-term adverse outcomes included all-cause mortality, hospitalization due to heart failure, new-onset atrial fibrillation, and/or embolic stroke during follow-up. One hundred eighty five patients (aged 41.9 ± 13.2 years, 81.1% female) were included during the median follow-up period of 12.6 years (95% CI: 11.2-14.0). MS was classified as mild, moderate, and severe in 8.6%, 2 7.6%, and 63.8% of patients, respectively. Average mitral valve score was 8.25 ± 1.5. Most patients (61.6%) underwent percutaneous balloon mitral valvulotomy. Incidence of long-term adverse outcome was 43.2% (95% CI: 36.0-50.7%) and included mortality in two patients (1.1%, 95% CI: 0.13-3.9%), hospitalization due to heart failure in 20 patients (10.8%, 95% CI: 6.7-16.2%), new-onset atrial fibrillation in 71 patients (38.4%, 95% CI: 31.3-45.8%), and embolic stroke in 14 patients (7.6%, 95% CI: 4.2-12.4%). Echocardiographic parameters associated with long-term adverse outcomes were left atrial dimension greater than 50 mm (HR 2.61, 95% CI: 1.08-6.30; p = 0.03) and left ventricular end-systolic dimension less than 28 mm (HR 3.06, 95% CI: 1.25-7.49; p = 0.01). Long-term adverse outcomes are common in patients with rheumatic MS in sinus rhythm. Long-term adverse outcomes were found to correlate with left atrial dimension and left ventricular end-systolic dimension.

Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.

PubMed

Shih, Yu-Hsuan; Islam, Tariqul; Hore, Samar Kumar; Sarwar, Golam; Shahriar, Mohammad Hasan; Yunus, Mohammad; Graziano, Joseph H; Harjes, Judith; Baron, John A; Parvez, Faruque; Ahsan, Habibul; Argos, Maria

2017-10-01

Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of renal and patient outcomes in anti-GBM disease: clinicopathologic analysis of a two-centre cohort.

PubMed

Alchi, Bassam; Griffiths, Meryl; Sivalingam, Murugan; Jayne, David; Farrington, Ken

2015-05-01

Patients with anti-glomerular basement membrane (GBM) disease are at increased risk of morbidity and mortality from renal failure, pulmonary haemorrhage or complications of treatment. One-third also have circulating anti-neutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine the clinicopathologic predictors of patient and renal outcomes in anti-GBM disease with or without ANCA. Retrospective review of 43 patients diagnosed with anti-GBM disease over 20 years in two centres, including nine with dual anti-GBM and ANCA positivity. Renal biopsies from 27 patients were scored for the presence of active and chronic lesions. Dual-positive patients were almost 20 years older than those with anti-GBM positivity alone (P = 0.003). The overall 1-year patient and renal survivals were 88 and 16%, respectively. Oligoanuria at diagnosis was the strongest predictor of mortality; none of the 16 patients without oligoanuria died. In a Cox regression model excluding oligoanuria, age was the only other independent predictor of survival. Pulmonary haemorrhage and dialysis dependence did not influence mortality. Thirty-five of the forty-three (81%) patients required dialysis at presentation, including all nine dual-positive patients. Of them, only two (5.7%) regained renal function at 1 year. By logistic regression, oligoanuria at diagnosis and percentage of crescents were independent predictors of dialysis independence at 3 months. However, in biopsied patients, the presence of crescents (>75%) added little to the presence of oligoanuria in predicting dialysis independence. Histological activity and chronicity indices did not predict renal outcome. Two of the nine (22%) dual-positive patients relapsed compared with none of the anti-GBM alone patients. Seven patients received kidney transplants without disease recurrence. Oligoanuria is the strongest predictor of patient and renal survival while percentage of glomerular crescents is the only pathologic

Prenatal hazardous substance use and adverse birth outcomes

PubMed Central

Quesada, Odayme; Gotman, Nathan; Howell, Heather B.; Funai, Edmund F.; Rounsaville, Bruce J.; Yonkers, Kimberly A.

2012-01-01

Objective Assess the relative effects of a variety of illicit and licit drugs on risk for adverse birth outcomes. Methods We used data from two large prospective investigations, and a novel analytic method, recursive partitioning class analysis to identify risk factors associated with preterm birth and delivering a small for gestational age infant. Results Compared to cocaine and opiate non-users, cocaine users were 3.53 times as likely (95% Cl: 1.65–7.56; p=0.001) and opiate users 2.86 times as likely (95% Cl: 1.11–7.36; p=0.03) to deliver preterm. The odds of delivering a small for gestational age infant for women who smoked more than two cigarettes daily was 3.74, (95% Cl: 2.47–5.65; p<0.0001) compared to women who smoked two or less cigarettes daily and had one previous child. Similarly, less educated, nulliparous women who smoked two or fewer cigarettes daily were 4.12 times as likely (95% Cl: 2.04–8.34; p<0.0001) to have a small for gestational age infant. Conclusions Among our covariates, prenatal cocaine and opiate use are the predominant risk factors for preterm birth; while tobacco use was the primary risk factor predicting small for gestational age at delivery. Multi-substance use did not substantially increase risk of adverse birth outcomes over these risk factors. PMID:22489543

Classification of Individual Well-Being Scores for the Determination of Adverse Health and Productivity Outcomes in Employee Populations

PubMed Central

Sears, Lindsay E.; Coberley, Carter R.; Pope, James E.

2013-01-01

Abstract Adverse health and productivity outcomes have imposed a considerable economic burden on employers. To facilitate optimal worksite intervention designs tailored to differing employee risk levels, the authors established cutoff points for an Individual Well-Being Score (IWBS) based on a global measure of well-being. Cross-sectional associations between IWBS and adverse health and productivity outcomes, including high health care cost, emergency room visits, short-term disability days, absenteeism, presenteeism, low job performance ratings, and low intentions to stay with the employer, were studied in a sample of 11,702 employees from a large employer. Receiver operating characteristics curves were evaluated to detect a single optimal cutoff value of IWBS for predicting 2 or more adverse outcomes. More granular segmentation was achieved by computing relative risks of each adverse outcome from logistic regressions accounting for sociodemographic characteristics. Results showed strong and significant nonlinear associations between IWBS and health and productivity outcomes. An IWBS of 75 was found to be the optimal single cutoff point to discriminate 2 or more adverse outcomes. Logistic regression models found abrupt reductions of relative risk also clustered at IWBS cutoffs of 53, 66, and 88, in addition to 75, which segmented employees into high, high-medium, medium, low-medium, and low risk groups. To determine validity and generalizability, cutoff values were applied in a smaller employee population (N=1853) and confirmed significant differences between risk groups across health and productivity outcomes. The reported segmentation of IWBS into discrete cohorts based on risk of adverse health and productivity outcomes should facilitate well-being comparisons and worksite interventions. (Population Health Management 2013;16:90–98) PMID:23013034

Renal function and acute heart failure outcome.

PubMed

Llauger, Lluís; Jacob, Javier; Miró, Òscar

2018-06-05

The interaction between acute heart failure (AHF) and renal dysfunction is complex. Several studies have evaluated the prognostic value of this syndrome. The aim of this systematic review, which includes non-selected samples, was to investigate the impact of different renal function variables on the AHF prognosis. The categories included in the studies reviewed included: creatinine, blood urea nitrogen (BUN), the BUN/creatinine quotient, chronic kidney disease, the formula to estimate the glomerular filtration rate, criteria of acute renal injury and new biomarkers of renal damage such as neutrophil gelatinase-associated lipocalin (NGAL and cystatin c). The basal alterations of the renal function, as well as the acute alterations, transient or not, are related to a worse prognosis in AHF, it is therefore necessary to always have baseline, acute and evolutive renal function parameters. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Influence of median surgeon operative duration on adverse outcomes in bariatric surgery.

PubMed

Reames, Bradley N; Bacal, Daniel; Krell, Robert W; Birkmeyer, John D; Birkmeyer, Nancy J O; Finks, Jonathan F

2015-01-01

Evidence suggests that prolonged operative time adversely affects surgical outcomes. However, whether faster surgeons have better outcomes is unclear, as a surgeon׳s speed could reflect skill and efficiency, but may alternatively reflect haste. This study evaluates whether median surgeon operative time is associated with adverse surgical outcomes after laparoscopic Roux-en-Y gastric bypass. We performed a retrospective cohort study using statewide clinical registry data from the years 2006 to 2012. Surgeons were ranked by their median operative time and grouped into terciles. Multivariable logistic regression with robust standard errors was used to evaluate the influence of median surgeon operative time on 30-day surgical outcomes, adjusting for patient and surgeon characteristics, trainee involvement, concurrent procedures, and the complex interaction between these variables. A total of 16,344 patients underwent surgery during the study period. Compared to surgeons in the fastest tercile, slow surgeons required 53 additional minutes to complete a gastric bypass procedure (median [interquartile range] 139 [133-150] versus 86 [69-91], P<.001). After adjustment for patient characteristic only, slow surgeons had significantly higher adjusted rates of any complication, prolonged length of stay, emergency department visits or readmissions, and venous thromboembolism (VTE). After further adjustment for surgeon characteristics, resident involvement, and the interaction between these variables, slow surgeons had higher rates of any complication (10.5% versus 7.1%, P=.039), prolonged length of stay (14.0% versus 4.4%, P=.002), and VTE (0.39% versus .22%, P<.001). Median surgeon operative duration is independently associated with adjusted rates of certain adverse outcomes after laparoscopic Roux-en-Y gastric bypass. Improving surgeon efficiency while operating may reduce operative time and improve the safety of bariatric surgery. Copyright © 2015 American Society for

Creating a Structured Adverse Outcome Pathway Knowledgebase via Ontology-Based Annotations

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly used to integrate data based on traditional and emerging toxicity testing paradigms. As the number of AOP descriptions has increased, so has the need to define the AOP in computable terms. Herein, we present a comprehens...

Integrating publicly-available data to generate computationally-predicted adverse outcome pathways for hepatic steatosis

EPA Science Inventory

The adverse outcome pathway (AOP) framework provides a way of organizing knowledge related to the key biological events that result in a particular health outcome. For the majority of environmental chemicals, the availability of curated pathways characterizing potential toxicity ...

Adverse outcome pathway networks II: Network analytics.

PubMed

Villeneuve, Daniel L; Angrish, Michelle M; Fortin, Marie C; Katsiadaki, Ioanna; Leonard, Marc; Margiotta-Casaluci, Luigi; Munn, Sharon; O'Brien, Jason M; Pollesch, Nathan L; Smith, L Cody; Zhang, Xiaowei; Knapen, Dries

2018-06-01

Toxicological responses to stressors are more complex than the simple one-biological-perturbation to one-adverse-outcome model portrayed by individual adverse outcome pathways (AOPs). Consequently, the AOP framework was designed to facilitate de facto development of AOP networks that can aid in the understanding and prediction of pleiotropic and interactive effects more common to environmentally realistic, complex exposure scenarios. The present study introduces nascent concepts related to the qualitative analysis of AOP networks. First, graph theory-based approaches for identifying important topological features are illustrated using 2 example AOP networks derived from existing AOP descriptions. Second, considerations for identifying the most significant path(s) through an AOP network from either a biological or risk assessment perspective are described. Finally, approaches for identifying interactions among AOPs that may result in additive, synergistic, or antagonistic responses (or previously undefined emergent patterns of response) are introduced. Along with a companion article (part I), these concepts set the stage for the development of tools and case studies that will facilitate more rigorous analysis of AOP networks, and the utility of AOP network-based predictions, for use in research and regulatory decision-making. The present study addresses one of the major themes identified through a Society of Environmental Toxicology and Chemistry Horizon Scanning effort focused on advancing the AOP framework. Environ Toxicol Chem 2018;37:1734-1748. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. © 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the

Practical approaches to adverse outcome pathway development and weight‐of‐evidence evaluation as illustrated by ecotoxicological case studies

EPA Science Inventory

Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and dep...

Frameworks for organizing exposure and toxicity data - the Aggregate Exposure Pathway (AEP) and the Adverse Outcome Pathway (AOP)

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework organizes existing knowledge regarding a series of biological events, starting with a molecular initiating event (MIE) and ending at an adverse outcome. The AOP framework provides a biological context to interpret in vitro toxicity dat...

Impact of Continuous Administration of Tolvaptan on Preventing Medium-Term Worsening Renal Function and Long-Term Adverse Events in Heart Failure Patients with Chronic Kidney Disease.

PubMed

Nakano, Yusuke; Mizuno, Tomofumi; Niwa, Toru; Mukai, Kentaro; Wakabayashi, Hirokazu; Watanabe, Atsushi; Ando, Hirohiko; Takashima, Hiroaki; Murotani, Kenta; Waseda, Katsuhisa; Amano, Tetsuya

2018-01-27

Tolvaptan (TLV) has an inhibiting effect for worsening renal function (WRF) in acute decompensated heart failure (HF) patients. However, there are limited data regarding the effect of continuous TLV administration on medium-term WRF.This was a retrospective observational study in hospitalized HF patients with chronic kidney disease (CKD). TLV was administered to those patients with fluid retention despite standard HF therapy. We compared 34 patients treated with TLV (TLV group) to 33 patients treated with conventional HF therapy with high-dose loop diuretics (furosemide ≥ 40 mg) (Loop group). Clinical outcomes, including the incidence of medium-term WRF, defined as increase of serum creatinine > 0.3 mg/dL, at 6 months after discharge and adverse events rate, were evaluated.Baseline patient characteristics were not different between the TLV and Loop group. The TLV group consisted of less frequent use of loop diuretics and carperitide compared with the Loop group. The incidence of medium-term WRF was significantly lower in the TLV group than in the Loop group (3.2% versus 31.0%, P = 0.002). Multivariate logistic analysis showed that the TLV non-user was an independent predictor of medium-term WRF. Kaplan-Meier analysis revealed that the long-term event-free survival was significantly higher in the TLV group (log-rank P = 0.01).Continuous administration of TLV may reduce the risk of medium-term WRF, resulting possibility in improvement of long-term adverse outcomes in HF patients with CKD.

Prevalence of abortion and adverse pregnancy outcomes among working women in Korea: A cross-sectional study

PubMed Central

Park, Chulyong; Kang, Mo-Yeol; Kim, Dohyung; Park, Jaechan; Eom, Huisu

2017-01-01

Objectives To investigate incidence and distribution of major adverse reproductive health problems related to various kinds of industries in Korea and to compare risks for major reproductive outcomes to assess maternal health in working and non-working women. Methods We requested claim data from the Korean National Health Insurance. We defined reference groups as (1) non-working women and (2) workers in the education field. Women working in each industry were compared with reference groups regarding rates of miscarriage, threatened abortion, preterm labor, and intrauterine growth restriction. Logistic regression was used for multivariate analysis, and age and income adjustment was performed. Results The percentages of all adverse obstetric outcomes were higher in working women than in non-working women. Working women had higher and statistically significant adjusted odds ratios (ORs) for miscarriage in 18 of the 21 industries. The age and income-adjusted OR for miscarriage for all working women was 1.26 (95% confidence interval, 1.23–1.28). Business facilities management and business support services, manufacturing, human health and social work activities, wholesale and retail trade, and professional, scientific, and technical activities were major industries with higher adjusted ORs for adverse obstetric outcomes. Conclusions We confirmed that compared to non-working women, working women have a higher risk for adverse pregnancy outcomes. Thus, adverse pregnancy outcomes such as threatened abortion, preterm labor, and intrauterine growth restriction may be associated with working status. This exploratory study identified several industries where in-depth studies are required in future to improve occupational safety in women of reproductive age. PMID:28850585

Prevalence of abortion and adverse pregnancy outcomes among working women in Korea: A cross-sectional study.

PubMed

Park, Chulyong; Kang, Mo-Yeol; Kim, Dohyung; Park, Jaechan; Eom, Huisu; Kim, Eun-A

2017-01-01

To investigate incidence and distribution of major adverse reproductive health problems related to various kinds of industries in Korea and to compare risks for major reproductive outcomes to assess maternal health in working and non-working women. We requested claim data from the Korean National Health Insurance. We defined reference groups as (1) non-working women and (2) workers in the education field. Women working in each industry were compared with reference groups regarding rates of miscarriage, threatened abortion, preterm labor, and intrauterine growth restriction. Logistic regression was used for multivariate analysis, and age and income adjustment was performed. The percentages of all adverse obstetric outcomes were higher in working women than in non-working women. Working women had higher and statistically significant adjusted odds ratios (ORs) for miscarriage in 18 of the 21 industries. The age and income-adjusted OR for miscarriage for all working women was 1.26 (95% confidence interval, 1.23-1.28). Business facilities management and business support services, manufacturing, human health and social work activities, wholesale and retail trade, and professional, scientific, and technical activities were major industries with higher adjusted ORs for adverse obstetric outcomes. We confirmed that compared to non-working women, working women have a higher risk for adverse pregnancy outcomes. Thus, adverse pregnancy outcomes such as threatened abortion, preterm labor, and intrauterine growth restriction may be associated with working status. This exploratory study identified several industries where in-depth studies are required in future to improve occupational safety in women of reproductive age.

Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus Nephritis cohort.

PubMed

Dall'Era, Maria; Cisternas, Miriam G; Smilek, Dawn E; Straub, Laura; Houssiau, Frédéric A; Cervera, Ricard; Rovin, Brad H; Mackay, Meggan

2015-05-01

There is a need to determine which response measures in lupus nephritis trials are most predictive of good long-term renal function. We used data from the Euro-Lupus Nephritis Trial to evaluate the performance of proteinuria, serum creatinine (Cr), and urinary red blood cells (RBCs) as predictors of good long-term renal outcome. Patients from the Euro-Lupus Nephritis Trial with proteinuria, serum Cr, and urinary RBC measurements at 3, 6, or 12 months and with a minimum of 7 years of followup were included (n = 76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long-term renal outcome (defined as a serum Cr value ≤1.0 mg/dl) at 7 years. Receiver operating characteristic curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters. Sensitivity and specificity were calculated for the parameters alone and in combination. A proteinuria value of <0.8 gm/day at 12 months after randomization was the single best predictor of good long-term renal function (sensitivity 81% and specificity 78%). The addition of serum Cr to proteinuria as a composite predictor did not improve the performance of the outcome measure; addition of urinary RBCs as a predictor significantly decreased the sensitivity to 47%. This study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long-term renal outcome in patients with lupus nephritis. Inclusion of urinary RBCs as part of a composite outcome measure actually undermined the predictive value of the trial data. We therefore suggest that urinary RBCs should not be included as a component of clinical trial response criteria in lupus nephritis. © 2015, American College of Rheumatology.

The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease.

PubMed

Oh, Yun Jung; Kim, Sun Moon; Shin, Byung Chul; Kim, Hyun Lee; Chung, Jong Hoon; Kim, Ae Jin; Ro, Han; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Lee, Chungsik; Jung, Ji Yong

2017-01-01

Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071-1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123-1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016-1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996-1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

Effect of conservative treatment on the renal outcome of children with primary hyperoxaluria type 1.

PubMed

Fargue, Sonia; Harambat, Jérôme; Gagnadoux, Marie-France; Tsimaratos, Michel; Janssen, Françoise; Llanas, Brigitte; Berthélémé, Jean-Pierre; Boudailliez, Bernard; Champion, Gérard; Guyot, Claude; Macher, Marie-Alice; Nivet, Hubert; Ranchin, Bruno; Salomon, Rémi; Taque, Sophie; Rolland, Marie-Odile; Cochat, Pierre

2009-10-01

Primary hyperoxaluria type 1 results from alanine:glyoxylate aminotransferase deficiency. Due to genotype/phenotype heterogeneity in this autosomal recessive disorder, the renal outcome is difficult to predict in these patients and the long-term impact of conservative management in children is unknown. We report here a multicenter retrospective study on the renal outcome in 27 affected children whose biological diagnosis was based on either decreased enzyme activity or identification of mutations in the patient or his siblings. The median age at first symptoms was 2.4 years while that at initiation of conservative treatment was 4.1 years; 6 children were diagnosed upon family screening. The median follow-up was 8.7 years. At diagnosis, 15 patients had an estimated glomerular filtration rate (eGFR) below 90, and 7 children already had stage 2-3 chronic kidney disease. The median baseline eGFR was 74, which rose to 114 with management in the 22 patients who did not require renal replacement therapy. Overall, 20 patients had a stable eGFR, however, 7 exhibited a decline in eGFR of over 20 during the study period. In a Cox regression model, the only variable significantly associated with deterioration of renal function was therapeutic delay with a relative risk of 1.7 per year. Our study strongly suggests that early and aggressive conservative management may preserve renal function of compliant children with this disorder, thereby avoiding dialysis and postponing transplantation.

Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function: Data from the CANVAS Program.

PubMed

Neuen, Brendon L; Ohkuma, Toshiaki; Neal, Bruce; Matthews, David R; de Zeeuw, Dick; Mahaffey, Kenneth W; Fulcher, Greg; Desai, Mehul; Li, Qiang; Deng, Hsiaowei; Rosenthal, Norm; Jardine, Meg J; Bakris, George; Perkovic, Vlado

2018-06-25

Background : Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease (CKD), including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m 2 in whom the drug is not currently approved for use. Methods : The CANagliflozin cardioVascular Assessment Study Program (CANVAS) randomized 10,142 participants with type 2 diabetes and eGFR greater than 30 mL/min/1.73 m 2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without CKD, defined as eGFR <60 and ≥60 mL/min/1.73 m 2 , and according to baseline kidney function (eGFR <45, 45-<60, 60-<90, and ≥90 mL/min/1.73 m 2 ). Results : At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m 2 , of whom 71.6% had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with CKD (HR 0.70, 95% CI 0.55-0.90) and those with preserved kidney function (HR 0.92, 95% CI 0.79-1.07, P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. Conclusions : The effect of canagliflozin on cardiovascular and renal outcomes was not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m 2 Reassessing current limitations on the use of canagliflozin in CKD may allow additional individuals to benefit from this therapy. Clinical Trial Registration : URL: https

OS104. Are preeclampsia and adverse obstetrical outcomes predictors for longterm cardiovascular disease?

PubMed

Sia, W W; Tsuyuki, R; Pertman, S; Hui, W

2012-07-01

Epidemiologic studies suggest that pregnancy complications such as preeclampsia, gestational diabetes, preterm delivery and low birth weight independently increase maternal risk for future development of cardiovascular disease. To further investigate whether preeclampsia, gestational diabetes, and adverse obstetrical outcomes such as placental abruption, intrauterine growth restriction and preterm delivery, are independent risk factors for longterm cardiovascular disease. This was a case-control study where 252 parous women (cases) with coronary artery disease were matched with a parous woman within 5 years of age with no known coronary artery disease (controls). Participants were recruited from the Royal Alexandra Hospital in cardiac catheterization lab recovery room in Edmonton, Canada. Women with significant angiographic coronary artery stenosis were eligible as cases and those without were eligible as controls. Participants were interviewed on their pregnancy histories and traditional cardiovascular risk factors, such as hypertension, diabetes etc. Descriptive statistics, chi-square tests and conditional regression analysis were performed. We recruited 244 cases and 246 controls. The average age was 66.3 and 65.8 respectively. Cases were more likely obese, had more pregnancies as well as traditional cardiovascular risk factors than controls. Adverse pregnancy outcomes were similar between the two groups except gestational hypertension. However, it was not statistically significant in the conditional logistic regression model. Independent risk factors for future cardiovascular diseases were: dyslipidemia (OR 12.8), hypertension (3.0), and being a current (OR 7.4) or former smoker (1.8). Adverse pregnancy outcomes In this study, adverse pregnancy outcomes were not independently associated with cardiovascular disorders. Our study was limited by recall bias, and ascertainment of diagnosis.Our study supports that dyslipidemia, hypertensiion and smoking increase

Can a brief period of double J stenting improve the outcome of extracorporeal shock wave lithotripsy for renal calculi sized 1 to 2 cm?

PubMed

Sharma, Rakesh; Choudhary, Arpan; Das, Ranjit Kumar; Basu, Supriya; Dey, Ranjan Kumar; Gupta, Rupesh; Deb, Partha Pratim

2017-03-01

Extracorporeal shock wave lithotripsy (ESWL) is an established modality for renal calculi. Its role for large stones is being questioned. A novel model of temporary double J (DJ) stenting followed by ESWL was devised and outcomes were assessed. The study included 95 patients with renal calculi sized 1 to 2 cm. Patients were randomized into 3 groups. Group 1 received ESWL only, whereas group 2 underwent stenting followed by ESWL. In group 3, a distinct model was applied in which the stent was kept for 1 week and then removed, followed by ESWL. Procedural details, analgesic requirements, and outcome were analyzed. Eighty-eight patients (male, 47; female, 41) were available for analysis. The patients' mean age was 37.9±10.9 years. Stone profile was similar among groups. Group 3 received fewer shocks (mean, 3,155) than did group 1 (mean, 3,859; p=0.05) or group 2 (mean, 3,872; p=0.04). The fragmentation rate was similar in group 3 (96.7%) and groups 1 (81.5%, p=0.12) and 2 (87.1%, p=0.16). Overall clearance in group 3 was significantly improved (83.3%) compared with that in groups 1 (63.0%, p=0.02) and 2 (64.5%, p=0.02) and was maintained even in lower pole stones. The percentage successful outcome in groups 1, 2, and 3 was 66.7%, 64.5%, and 83.3%, respectively (p=0.21). The analgesic requirement in group 2 was higher than in the other groups (p=0.00). Group 2 patients also had more grade IIIa (2/3) and IIIB (1/2) complications. Stenting adversely affects stone clearance and also makes the later course uncomfortable. Our model of brief stenting followed by ESWL provided better clearance, comfort, and a modest improvement in outcome with fewer sittings and steinstrasse in selected patients with large renal calculi.

Early warning score independently predicts adverse outcome and mortality in patients with acute pancreatitis.

PubMed

Jones, Michael J; Neal, Christopher P; Ngu, Wee Sing; Dennison, Ashley R; Garcea, Giuseppe

2017-08-01

The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

Adverse effects of methotrexate in three psoriatic arthritis patients.

PubMed

Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei

2014-04-01

Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.

Adverse nurse outcomes: correlation to nurses' workload, staffing, and shift rotation in Kuwaiti hospitals.

PubMed

Al-Kandari, Fatimah; Thomas, Deepa

2008-08-01

This study was conducted to identify adverse outcomes to nurses in relation to their daily patient load, nursing care activities, staffing, and shift rotation. A structured questionnaire was used to collect data from medical and surgical nurses (N = 784). Skipping tea/coffee breaks (95%), feeling responsible for more patients than they could safely care for (87%), inadequate help available (86%), inadequate time to document care (80%), verbal abuse by a patient or a visitor (77%), and concern about quality of care (71%) were the major reported adverse outcomes related to short staffing, increased patient load, and increased nursing care activities.

Association of assisted reproductive technology with adverse pregnancy outcomes

PubMed Central

Jie, Zhang; Yiling, Ding; Ling, Yu

2015-01-01

Background: More and more infertile patients have accepted the assisted reproductive technique (ART) therapy. Concerns have been raised over an increased risk of adverse maternal outcomes in ART populations as compared with natural conception (NC). Objective: The aim was to improve the ART in clinicial work and to reduce the incidence of pregnancy complications in ART group according to analyzing the reasons of high incidence of pregnancy complications in ART group, comparing the incidence of pregnancy complications in different controlled ovarian hyperstimulation (COH) programs and evaluating the effects of ART which attribute to adverse pregnancy outcomes. Materials and Methods: In this prospective population-based cohort study,3216 pregnant women with gestational age ≤12 weeks, regular antenatal examination,and ultrasound identification of intrauterine pregnancy were enrolled from January 2010 to June 2013. According to having ART history, the participantswere divided into two groups: ART group (contains fresh embryo transfer group or frozen-thawed embryo transfer group) and NC group. We compared the incidence of pregnancy complications between different groups and evaluated the factors which could affect the occurrence of these complications. Results: When compared to NC group, significantly increased rates of gestational diabetes mellitus (GDM) (p<0.01), preeclampsia (PE) (p<0.01) and intrahepatic cholestasis of pregnancy (ICP) (p˂0.01) were observed in ART group. There was no significant difference in the incidence of birth defect between the two groups (p=0.07). Multiple pregnancies and Gonadotropin (Gn) were risk factors in GDM, PE, and ICP. The exogenous progesterone treatment had no effect on GDM, PE or ICP. Conclusion: ART increases the risk of adverse maternal complications such as GDM, PE and ICP. The dosages of Gn should be reduced to an extent and the number of embryo implantation should be controlled. Exogenous progesterone treatment is safe

Interpregnancy interval following miscarriage and adverse pregnancy outcomes: systematic review and meta-analysis.

PubMed

Kangatharan, Chrishny; Labram, Saffi; Bhattacharya, Sohinee

2017-03-01

A short interpregnancy interval (IPI) following a delivery is believed to be associated with adverse outcomes in the next pregnancy. The optimum IPI following miscarriage is controversial. Based on a single large-scale study in Latin and South America, the World Health Organization recommends delaying pregnancy for 6 months after a miscarriage to achieve optimal outcomes in the next pregnancy. Our aim was to determine if a short IPI (<6 months) following miscarriage is associated with adverse outcomes in the next pregnancy. Studies were retrieved from MEDLINE, Embase and Pubmed, with no time and language restrictions. The search strategy used a combination of Medical Subject Headings terms for miscarriage, IPI and adverse outcomes. Bibliographies of the retrieved articles were also searched by hand. All studies including women with at least one miscarriage, comparing subsequent adverse pregnancy outcomes for IPIs of less than and more than 6 months were included. Two independent reviewers screened titles and abstracts for inclusion. Characteristics of the studies were extracted and quality assessed using Critical Appraisal Skills Programme criteria. A systematic review and meta-analysis were conducted to compare short (<6 months) versus long (>6 months) IPI following miscarriage in terms of risk of further miscarriage, preterm birth, stillbirth, pre-eclampsia and low birthweight babies in the subsequent pregnancy. Review Manager 5.3 was used for conducting meta-analyses. Sixteen studies including 1 043 840 women were included in the systematic review and data from 10 of these were included in one or more meta-analyses (977 972 women). With an IPI of less than 6 months, the overall risk of further miscarriage (Risk ratio (RR) 0.82 95% CI 0.78, 0.86) and preterm delivery (RR 0.79 95% CI 0.75, 0.83) were significantly reduced. The pooled risks of stillbirth (RR 0.88 95% CI 0.76, 1.02); low birthweight (RR 1.05 95% CI 0.48, 2.29) and pre-eclampsia (RR 0.95 95% CI 0

Metastatic renal cell carcinoma complicated with diffuse alveolar hemorrhage: a rare adverse effect of sunitinib.

PubMed

Yamada, Tadaaki; Ohtsubo, Koushiro; Izumi, Kouji; Takeuchi, Shinji; Mouri, Hisatsugu; Yamashita, Kaname; Yasumoto, Kazuo; Ghenev, Peter; Kitagawa, Satoshi; Yano, Seiji

2010-12-01

We report the case of a 67-year-old man with metastatic papillary renal cell carcinoma (RCC) who developed bloody sputum after the administration of sunitinib. Chest computed tomography revealed diffuse ground-glass opacity lesions, and bloody bronchoalveolar lavage fluid was obtained by flexible bronchoscopy. The abnormal shadows promptly regressed after withdrawal of sunitinib. In four cycles of sunitinib treatment, he suffered from controllable diffuse alveolar hemorrhage. Finally, he died of respiratory failure 8 months after onset. This is the first case report of diffuse alveolar hemorrhage as an adverse effect of sunitinib in metastatic papillary RCC. Care should be taken with pulmonary hemorrhage in the use of anti-angiogenesis agents in not only squamous cell lung cancer, but also metastatic lung tumors.

Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta-analysis.

PubMed

Wang, J; Moore, D; Subramanian, A; Cheng, K K; Toulis, K A; Qiu, X; Saravanan, P; Price, M J; Nirantharakumar, K

2018-05-21

Low and high birthweight is known to increase the risk of acute and longer-term adverse outcomes, such as stillbirth, infant mortality, obesity, type 2 diabetes and cardiovascular diseases. Gestational dyslipidaemia is associated with a numbers of adverse birth outcomes, but evidence regarding birthweight is still inconsistent to reliably inform clinical practice and treatment recommendations. The aim of this study was to explore the relationship between maternal gestational dyslipidaemia and neonatal health outcomes, namely, birthweight, metabolic factors and inflammatory parameters. We searched systematically Embase, MEDLINE, PubMed, CINAHL Plus and Cochrane Library up to 1 August 2016 (with an updated search in MEDLINE at the end of July 2017) for longitudinal studies that assessed the association of maternal lipid levels during pregnancy with neonatal birthweight, or metabolic and inflammatory parameters up to 3 years old. Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high-density-lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight, higher risk of large for gestational age and macrosomia and lower risk of small-for-gestational age. The findings were consistent across the studied populations, but stronger associations were observed in women who were overweight or obese prior to pregnancy. This meta-analysis suggested that the potential under-recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials. © 2018 World Obesity Federation.

Development & Use of Adverse Outcome Pathways for 21st Century Decision Support

EPA Science Inventory

The Adverse Outcome Pathway has emerged as an internationally harmonized mechanism for organizing biological information in a chemical agnostic manner. This construct is valuable for interpreting the results from high-throughput toxicity (HTT) assessment by providing a mechanisti...

The Japanese Histologic Classification and T-score in the Oxford Classification system could predict renal outcome in Japanese IgA nephropathy patients.

PubMed

Kaihan, Ahmad Baseer; Yasuda, Yoshinari; Katsuno, Takayuki; Kato, Sawako; Imaizumi, Takahiro; Ozeki, Takaya; Hishida, Manabu; Nagata, Takanobu; Ando, Masahiko; Tsuboi, Naotake; Maruyama, Shoichi

2017-12-01

The Oxford Classification is utilized globally, but has not been fully validated. In this study, we conducted a comparative analysis between the Oxford Classification and Japanese Histologic Classification (JHC) to predict renal outcome in Japanese patients with IgA nephropathy (IgAN). A retrospective cohort study including 86 adult IgAN patients was conducted. The Oxford Classification and the JHC were evaluated by 7 independent specialists. The JHC, MEST score in the Oxford Classification, and crescents were analyzed in association with renal outcome, defined as a 50% increase in serum creatinine. In multivariate analysis without the JHC, only the T score was significantly associated with renal outcome. While, a significant association was revealed only in the JHC on multivariate analysis with JHC. The JHC and T score in the Oxford Classification were associated with renal outcome among Japanese patients with IgAN. Superiority of the JHC as a predictive index should be validated with larger study population and cohort studies in different ethnicities.

Effects of Hyperbaric Oxygen Treatment on Renal System.

PubMed

Tezcan, Orhan; Caliskan, Ahmet; Demirtas, Sinan; Yavuz, Celal; Kuyumcu, Mahir; Nergiz, Yusuf; Guzel, Abdulmenap; Karahan, Oguz; Ari, Seyhmus; Soker, Sevda; Yalinkilic, Ibrahim; Turkdogan, Kenan Ahmet

2017-01-01

Hyperbaric oxygen (HBO) treatment is steadily increasing as a therapeutic modality for various types of diseases. Although good clinical outcomes were reported with HBO treatment for various diseases, the multisystemic effects of this modality are still unclear. This study aimed to investigate the renal effects of HBO experimentally. Fourteen New Zealand White rabbits were divided into 2 groups randomly as the control group and the study group. The study group received HBO treatment for 28 days (100% oxygen at 2.5 atmospheres for 90 minutes daily) and the control group was used to obtain normal renal tissue of the animal genus. After the intervention period, venous blood samples were obtained, and renal tissue samples were harvested for comparisons. Normal histological morphology was determined with Masson trichrome staining and periodic acid-Schiff staining in the control group. Atrophic glomerular structures, vacuolated tubule cells, and degeneration were detected in the renal samples of the study group with Masson trichrome staining. Additionally, flattening was observed on the brush borders of the proximal tubules, and tubular dilatation was visualized with periodic acid-Schiff staining. The histopathologic disruption of renal morphology was verified with detection of significantly elevated kidney function laboratory biomarkers in the study group. Our findings suggests that HBO has adverse effects on renal glomerulus and proximal tubules. However, the functional effects of this alteration should be investigated with further studies.

An “ADME Module” in the Adverse Outcome Pathway ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway (AOP) framework has generated intense interest for its utility to organize knowledge on the toxicity mechanisms, starting from a molecular initiating event (MIE) to an adverse outcome across various levels of biological organization. While the AOP framework is designed to be chemical agnostic, it is widely recognized that considering chemicals’ absorption, distribution, metabolism, and excretion (ADME) behaviors is critical in applying the AOP framework in chemical-specific risk assessment. Currently, information being generated as part of the Organisation for Economic Co-operation and Development (OECD) AOP Development Programme is being consolidated into an AOP Knowledgebase (http://aopwiki.org). To enhance the use of this Knowledgebase in risk assessment, an ADME Module has been developed to contain the ADME information needed to connect MIEs and other key events in an AOP for specific chemicals. The conceptual structure of this module characterizes the potential of a chemical to reach the target MIE based on either its structure-based features or relative rates of ADME. The key features of this module include (1) a framework for connecting biology-based AOP to biochemical-based ADME and chemical/human activity-based exposure pathways; (2) links to qualitative tools (e.g., structure-based cheminformatic model) that screen for chemicals that could potentially reach the target MIE; (3) links to quantitative tools (e.g., dose-r

Advancing the adverse outcome pathway framework - An international horizon scanning approach (presentation)

EPA Science Inventory

In preparation for a Society of Environmental Toxicology and Chemistry Pellston Workshop titled “Advancing the Adverse Outcome Pathway (AOP) Concept: An International Horizon Scanning Approach,” a horizon scanning effort was undertaken to gather input from the global ...

Establishing Adverse Outcome Pathways of Thyroid Hormone Disruption in an Amphibian Model

EPA Science Inventory

The Adverse Outcome Pathway (AOP) provides a framework for understanding the relevance of toxicology data in ecotoxicological hazard assessments. The AOP concept can be applied to many toxicological pathways including thyroid hormone disruption. Thyroid hormones play a critical r...

Accelerating Adverse Outcome Pathway Development Using ...

EPA Pesticide Factsheets

The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledgebase, however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally-predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of twenty-first century toxicity testing strategies. This review article describes how effective knowledge management and automated approaches to AOP development can enhance and accelerate the development and use of AOPs. As the principles documented in this review are put into practice, we anticipate that the quality and quantity of AOPs available will increase substantially. This, in turn, will aid in the interpretation of ToxCast and other high-throughput tox

Morbidity, mortality and economic burden of renal impairment in cardiac intensive care.

PubMed

Chew, D P; Astley, C; Molloy, D; Vaile, J; De Pasquale, C G; Aylward, P

2006-03-01

Moderate to severe impairment of renal function has emerged as a potent risk factor for adverse short- and long-term outcomes among patients presenting with cardiac disease. We sought to define the clinical, late mortality and economic burden of this risk factor among patients presenting to cardiac intensive care. A clinical audit of patients presenting to cardiac intensive care was undertaken between July 2002 and June 2003. All patients presenting with cardiac diagnoses were included in the study. Baseline creatinine levels were assessed in all patients. Late mortality was assessed by the interrogation of the National Death Register. Renal impairment was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2, as calculated by the Modified Diet in Renal Disease formula. In-hospital and late outcomes were compared by Cox proportional hazards modelling, adjusting for known confounders. A matched analysis and attributable risk calculation were undertaken to assess the proportion of late mortality accounted for by impairment of renal function and other known negative prognostic factors. The in-hospital total cost associated with renal impairment was assessed by linear regression. Glomerular filtration rate <60 mL/min per 1.73 m2 was evident in 33.0% of this population. Among these patients, in-hospital and late mortality were substantially increased: risk ratio 13.2; 95% CI 3.0-58.1; P < 0.001 and hazard ratio 6.2; 95% CI 3.6-10.7; P < 0.001, respectively. In matched analysis, renal impairment to this level was associated with 42.1% of all the late deaths observed. Paradoxically, patients with renal impairment were more conservatively managed, but their hospitalizations were associated with an excess adjusted in-hospital cost of $A1676. Impaired renal function is associated with a striking clinical and economic burden among patients presenting to cardiac intensive care. As a marker for future risk, renal function accounts for a substantial proportion

AOP-DB Frontend: A user interface for the Adverse Outcome Pathways Database.

EPA Science Inventory

The EPA Adverse Outcome Pathway Database (AOP-DB) is a database resource that aggregates association relationships between AOPs, genes, chemicals, diseases, pathways, species orthology information, ontologies. The AOP-DB frontend is a simple yet powerful AOP-DB user interface in...

AOP-DB Frontend: A user interface for the Adverse Outcome Pathways Database

EPA Science Inventory

The EPA Adverse Outcome Pathway Database (AOP-DB) is a database resource that aggregates association relationships between AOPs, genes, chemicals, diseases, pathways, species orthology information, ontologies. The AOP-DB frontend is a simple yet powerful user interface in the for...

The adverse outcome pathway: A multifaceted framework supporting 21st century toxicology

EPA Science Inventory

The adverse outcome pathway (AOP) framework serves as a knowledge assembly, interpretation, and communication tool designed to support the translation of pathway-specific mechanistic data into responses relevant to assessing and managing risks of chemicals to human health and the...

Frailty in community-dwelling older adults: association with adverse outcomes

PubMed Central

Sánchez-García, Sergio; García-Peña, Carmen; Salvà, Antoni; Sánchez-Arenas, Rosalinda; Granados-García, Víctor; Cuadros-Moreno, Juan; Velázquez-Olmedo, Laura Bárbara; Cárdenas-Bahena, Ángel

2017-01-01

Background The study of frailty is important to identify the additional needs of medical long-term care and prevent adverse outcomes in community dwelling older adults. This study aimed to determine the prevalence of frailty and its association with adverse outcomes in community dwelling older adults. Methods A cross-sectional study was carried out from April to September 2014. The population sample was 1,252 older adults (≥60 years) who were beneficiaries of the Mexican Institute of Social Security (IMSS) in Mexico City. Data were derived from the database of the “Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults” (COSFOMA). Operationalization of the phenotype of frailty was performed using the criteria of Fried et al (weight loss, self-report of exhaustion, low physical activity, slow gait, and weakness). Adverse outcomes studied were limitation in basic activities of daily living (ADLs), falls and admission to emergency services in the previous year, and low quality of life (WHOQOL-OLD). Results Frailty was identified in 20.6% (n=258), pre-frailty in 57.6% (n=721), and not frail in 21.8% (n=273). The association between frailty and limitations in ADL was odds ratio (OR) =2.3 (95% confidence interval [CI] 1.7–3.2) and adjusted OR =1.7 (95% CI 1.2–2.4); falls OR =1.6 (95% CI 1.2–2.1) and adjusted OR =1.4 (95% CI 1.0–1.9); admission to emergency services OR =1.9 (95% CI 1.1–3.1) and adjusted OR =1.9 (95% CI 1.1–3.4); low quality of life OR =3.4 (95% CI 2.6–4.6) and adjusted OR =2.1 (95% CI 1.5–2.9). Conclusion Approximately 2 out of 10 older adults demonstrate frailty. This is associated with limitations in ADL, falls, and admission to emergency rooms during the previous year as well as low quality of life. PMID:28721028

Risk factors for adverse driving outcomes in Dutch adults with ADHD and controls.

PubMed

Bron, Tannetje I; Bijlenga, Denise; Breuk, Minda; Michielsen, Marieke; Beekman, Aartjan T F; Kooij, J J Sandra

2018-02-01

To identify risk factors for adverse driving outcomes and unsafe driving among adults with and without ADHD in a Dutch sample. In this cross-sectional study, validated self-report questionnaires were used to compare driving history and current driving behavior between 330 adults diagnosed with ADHD and 330 controls. Adults with ADHD had significantly more adverse driving outcomes when compared to controls. Having an ADHD diagnosis significantly increased the odds for having had 3 or more vehicular crashes (OR = 2.72; p = .001). Driving frequency, male gender, age, high anxiety levels, high hostility levels, and alcohol use all significantly influenced the odds for unsafe driving behavior, for having had 12 or more traffic citations, and/or for having had 3 or more vehicular crashes. Alcohol use, and high levels of anxiety and hostility are highly prevalent among adults with ADHD, and they mediate the risk for negative driving outcomes in this group. Copyright © 2017 Elsevier Ltd. All rights reserved.

Waste incineration and adverse birth and neonatal outcomes: a systematic review.

PubMed

Ashworth, Danielle C; Elliott, Paul; Toledano, Mireille B

2014-08-01

Public concern about potential health risks associated with incineration has prompted studies to investigate the relationship between incineration and risk of cancer, and more recently, birth outcomes. We conducted a systematic review of epidemiologic studies evaluating the relationship between waste incineration and the risk of adverse birth and neonatal outcomes. Literature searches were performed within the MEDLINE database, through PubMed and Ovid interfaces, for the search terms; incineration, birth, reproduction, neonatal, congenital anomalies and all related terms. Here we discuss and critically evaluate the findings of these studies. A comprehensive literature search yielded fourteen studies, encompassing a range of outcomes (including congenital anomalies, birth weight, twinning, stillbirths, sex ratio and infant death), exposure assessment methods and study designs. For congenital anomalies most studies reported no association with proximity to or emissions from waste incinerators and "all anomalies", but weak associations for neural tube and heart defects and stronger associations with facial clefts and urinary tract defects. There is limited evidence for an association between incineration and twinning and no evidence of an association with birth weight, stillbirths or sex ratio, but this may reflect the sparsity of studies exploring these outcomes. The current evidence-base is inconclusive and often limited by problems of exposure assessment, possible residual confounding, lack of statistical power with variability in study design and outcomes. However, we identified a number of higher quality studies reporting significant positive relationships with broad groups of congenital anomalies, warranting further investigation. Future studies should address the identified limitations in order to help improve our understanding of any potential adverse birth outcomes associated with incineration, particularly focussing on broad groups of anomalies, to inform

Pleiotropic effects of type 2 diabetes management strategies on renal risk factors.

PubMed

Muskiet, Marcel H A; Tonneijck, Lennart; Smits, Mark M; Kramer, Mark H H; Heerspink, Hiddo J Lambers; van Raalte, Daniël H

2015-05-01

In parallel with the type 2 diabetes pandemic, diabetic kidney disease has become the leading cause of end-stage renal disease worldwide, and is associated with high cardiovascular morbidity and mortality. As established in landmark randomised trials and recommended in clinical guidelines, prevention and treatment of diabetic kidney disease focuses on control of the two main renal risk factors, hyperglycaemia and systemic hypertension. Treatment of systemic hypertension with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers is advocated because these drugs seem to exert specific renoprotective effects beyond blood pressure lowering. Emerging evidence shows that obesity, glomerular hyperfiltration, albuminuria, and dyslipidaemia might also adversely affect the kidney in diabetes. Control of these risk factors could have additional benefits on renal outcome in patients with type 2 diabetes. However, despite multifactorial treatment approaches, residual risk for the development and progression of diabetic kidney disease in patients with type 2 diabetes remains, and novel strategies or therapies to treat the disease are urgently needed. Several drugs used in the treatment of type 2 diabetes are associated with pleiotropic effects that could favourably or unfavourably change patients' renal risk profile. We review the risk factors and treatment of diabetic kidney disease, and describe the pleiotropic effects of widely used drugs in type 2 diabetes management on renal outcomes, with special emphasis on antihyperglycaemic drugs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Agricultural pesticide use and adverse birth outcomes in the San Joaquin Valley of California.

PubMed

Larsen, Ashley E; Gaines, Steven D; Deschênes, Olivier

2017-08-29

Virtually all agricultural communities worldwide are exposed to agricultural pesticides. Yet, the health consequences of such exposure are poorly understood, and the scientific literature remains ambiguous. Using individual birth and demographic characteristics for over 500 000 birth observations between 1997-2011 in the agriculturally dominated San Joaquin Valley, California, we statistically investigate if residential agricultural pesticide exposure during gestation, by trimester, and by toxicity influences birth weight, gestational length, or birth abnormalities. Overall, our analysis indicates that agricultural pesticide exposure increases adverse birth outcomes by 5-9%, but only among the population exposed to very high quantities of pesticides (e.g., top 5th percentile, i.e., ~4200 kg applied over gestation). Thus, policies and interventions targeting the extreme right tail of the pesticide distribution near human habitation could largely eliminate the adverse birth outcomes associated with agricultural pesticide exposure documented in this study.The health consequences of exposure to pesticides are uncertain and subject to much debate. Here, the effect of exposure during pregnancy is investigated in an agriculturally dominated residential area, showing that an increase in adverse birth outcomes is observed with very high levels of pesticide exposure.

Sunitinib Possible Sex-Divergent Therapeutic Outcomes.

PubMed

Segarra, Ignacio; Modamio, Pilar; Fernández, Cecilia; Mariño, Eduardo L

2016-10-01

Sunitinib is a tyrosine kinase inhibitor used for the treatment of renal cell carcinoma and metastatic brain tumors. Preclinical pharmacokinetic studies have shown higher sunitinib hepatic and brain exposure in female mice and higher sunitinib kidney concentrations in male mice. We explored whether sex-divergent tissue pharmacokinetics may anticipate sex-divergent therapeutic and toxicology responses in male and female patients. The review of the available scientific literature identified case reports, case series reports, clinical trials, and other studies associating sex with sunitinib outcomes. The results suggest male patients may respond better to renal cell carcinoma treatment and female patients may have better brain tumor treatment outcomes but a higher incidence of adverse events. Although more high-quality evidence is needed, these results, as anticipated by the preclinical data, may indicate possible sunitinib sex-divergent therapeutic outcomes in patients. In addition, we propose the systematic analysis of sex-based outcomes in clinical trial reports and their inclusion and review in the ethics committees and review boards to prevent, amongst others, patient burden in upcoming clinical trials.

Can Erythrocytes Transmit Oxidative Stress Beyond the Lungs? An Adverse Outcome Pathway for the Cardiovascular Effects of Air Pollution.

EPA Science Inventory

Adverse outcome pathways (AOPs) are systems biology roadmaps with potential utility in xenobiotic exposure risk assessment. AOPs connect molecular initiating events (MIEs) to population-level adverse outcomes (AOs) via cellular, organ, and organism key events (KE) and KE relatio...

Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data.

PubMed

Newman, Lori; Kamb, Mary; Hawkes, Sarah; Gomez, Gabriela; Say, Lale; Seuc, Armando; Broutet, Nathalie

2013-01-01

The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥ 90% of pregnant women to be tested for syphilis and ≥ 90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was "probable active," and for testing and treatment coverage. Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that could be prevented by early testing and treatment

Prostate cancer outcomes in France: treatments, adverse effects and two-year mortality

PubMed Central

2014-01-01

Background This very large population-based study investigated outcomes after a diagnosis of prostate cancer (PCa) in terms of mortality rates, treatments and adverse effects. Methods Among the 11 million men aged 40 years and over covered by the general national health insurance scheme, those with newly managed PCa in 2009 were followed for two years based on data from the national health insurance information system (SNIIRAM). Patients were identified using hospitalisation diagnoses and specific refunds related to PCa and PCa treatments. Adverse effects of PCa treatments were identified by using hospital diagnoses, specific procedures and drug refunds. Results The age-standardised two-year all-cause mortality rate among the 43,460 men included in the study was 8.4%, twice that of all men aged 40 years and over. Among the 36,734 two-year survivors, 38% had undergone prostatectomy, 36% had been treated by hormone therapy, 29% by radiotherapy, 3% by brachytherapy and 20% were not treated. The frequency of treatment-related adverse effects varied according to age and type of treatment. Among men between 50 and 69 years of age treated by prostatectomy alone, 61% were treated for erectile dysfunction and 24% were treated for urinary disorders. The frequency of treatment for these disorders decreased during the second year compared to the first year (erectile dysfunction: 41% vs 53%, urinary disorders: 9% vs 20%). The frequencies of these treatments among men treated by external beam radiotherapy alone were 7% and 14%, respectively. Among men between 50 and 69 years with treated PCa, 46% received treatments for erectile dysfunction and 22% for urinary disorders. For controls without PCa but treated surgically for benign prostatic hyperplasia, these frequencies were 1.5% and 6.0%, respectively. Conclusions We report high survival rates two years after a diagnosis of PCa, but a high frequency of PCa treatment-related adverse effects. These frequencies remain

Adverse obstetric and perinatal outcomes in subfertile women conceiving without assisted reproductive technologies.

PubMed

Jaques, Alice M; Amor, David J; Baker, H W Gordon; Healy, David L; Ukoumunne, Obioha C; Breheny, Sue; Garrett, Claire; Halliday, Jane L

2010-12-01

To determine whether adverse perinatal outcomes are increased in subfertile women. Cohort study. Two tertiary assisted reproductive technologies (ART) centers; Victorian births register. Records of women who registered with the clinics (1991-2000), but did not have an infant using ART, were linked to the birth register (1991-2004) to identify singleton non-ART births within 5 years of registration (N = 2171). Controls, matched by maternal age and year of infant's birth, were selected randomly from birth records (N = 4363). None. Adverse obstetric and perinatal outcomes. After adjusting for confounders, compared with controls, subfertile women had increased odds of hypertension or preeclampsia (adjusted odds ratio [OR] 1.29, 1.02-1.61), antepartum hemorrhage (adjusted OR 1.41, 1.05-1.89), perinatal death (adjusted OR 2.19, 1.10-4.36), low birth weight (adjusted OR 1.44, 1.11-1.85), preterm birth <37 weeks (adjusted OR 1.32, 1.05-1.67) or <31 weeks (adjusted OR 2.37, 1.35-4.13), and cesarean delivery (adjusted OR 1.56, 1.37-1.77). There was weak evidence for increased birth defects (adjusted OR 1.30, 0.98-1.72) and gestational diabetes (adjusted OR 1.25, 0.96-1.63). No increased risk was found for prelabor rupture of membranes, small for gestational age, or postpartum hemorrhage. Subfertile women with singleton births are at increased risk of several adverse outcomes. These risks should be considered during their antenatal care and when analyzing adverse effects of ART. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Safety and Clinical Outcome of the Delivery of Radiofrequency Nerve Ablation Therapy in a Renal Artery of Unusual Anatomy.

PubMed

de Leon-Martinez, Enrique Ponce; Garza, Javier A; Azpiri-Lopez, Jose R; Dillon, Krista N; Salazar, Leonel Olivas; Canepa-Campos, Francisco; Rousselle, Serge D; Tellez, Armando

2015-12-01

Catheter-based renal sympathetic denervation is an emerging therapy for resistant hypertension (RHTN) patients, resulting in a significant blood pressure reduction. The presence of accessory renal arteries and anomalous branching patterns are reported in approximately 20-27 % of patients. However, accessory renal arteries, when smaller than 4 mm in diameter, they are out of the inclusion criteria for renal denervation therapy. For this reason patients with evidence of accessory renal arteries have been excluded in previous clinical trials. Recent data suggest that accessory renal arteries may play an important role in non-response therapy when they do not receive renal denervation treatment. In this report, we present the outcome of a patient with resistant hypertension and an anomalous right renal artery, having undergone denervation of both principal and accessory renal arteries. The renal ablation by radiofrequency energy of a distant accessory renal artery resulted in a safe procedure with no clinical complications. Consistent with literature the RDN of all, main and accessory renal arteries, was effective in decreasing patient blood pressure while decreasing the need for antihypertensive medication.

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations of maternal A1C and glucose with pregnancy outcomes.

PubMed

Lowe, Lynn P; Metzger, Boyd E; Dyer, Alan R; Lowe, Julia; McCance, David R; Lappin, Terence R J; Trimble, Elisabeth R; Coustan, Donald R; Hadden, David R; Hod, Moshe; Oats, Jeremy J N; Persson, Bengt

2012-03-01

To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. Eligible pregnant women underwent a 75-g OGTT at 24-32 weeks' gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women.

Prediction of adverse pregnancy outcome in monochorionic- diamniotic twin pregnancies complicated by selective fetal growth restriction.

PubMed

Monaghan, Caitriona; Kalafat, Erkan; Binder, Julia; Thilaganathan, Baskaran; Khalil, Asma

2018-04-28

To identify key factors implicated in adverse perinatal outcome in monochorionic twin pregnancies complicated by selective fetal growth restriction. This is a retrospective cohort study conducted in a single tertiary referral centre included all monochorionic diamniotic (MCDA) twin pregnancies complicated by selective fetal growth restriction (sFGR). The presence of co-existing twin to twin transfusion syndrome (TTTS) was noted. Fetal biometry and Doppler indices, including the umbilical artery (UA) and ductus venosus (DV), were recorded at the time of diagnosis. The type of sFGR was diagnosed according to the pattern of end-diastolic flow (EDF) in the UA of the smaller twin. DV pulsatility indices were converted to z-scores and estimated fetal weight (EFW) values to centiles, to correct for gestational age (GA). Cox proportional hazards model was used to examine for independent predictors of adverse perinatal outcome. Adverse perinatal outcome was defined according to survival and included both intra-uterine fetal demise and neonatal death of the FGR twin. We analysed 104 pregnancies complicated by sFGR. Sixty-six (63.5%) were diagnosed with type I and 38 (36.5%) with type II at initial presentation. Pregnancies complicated by type II sFGR were diagnosed (median GA 19.6 weeks' vs 21.5 weeks, p=0.012) and delivered (median GA 30.4 weeks' vs 32.57 weeks; p=0.055) earlier and are associated with increased risk of adverse perinatal outcomes (intrauterine demise of the smaller twin 19.7% vs 10.6%, p=0.001), when compared to type I sFGR. Twin pregnancies complicated by sFGR, whether type I or II, resulting in intrauterine demise have a significantly earlier onset of diagnosis (p<0.001), earlier GA at delivery (p<0.05), higher DV pulsatility index (p<0.05), and lower birth weight (BW) centile of the smaller twin (p<0.01) when compared to pregnancies resulting in livebirth. Co-existing TTTS had no significant impact on the perinatal outcome of pregnancies diagnosed with

Concomitant use of low-dose methotrexate and NSAIDs and the risk of serious adverse events among patients with rheumatoid arthritis.

PubMed

Svanström, Henrik; Lund, Marie; Melbye, Mads; Pasternak, Björn

2018-05-24

Case reports and pharmacokinetic studies have suggested that concomitant use of low-dose methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with increased risk of methotrexate toxicity. This study aimed to investigate the risk of serious adverse events associated with concomitant use of low-dose methotrexate and NSAIDs, compared with use of methotrexate alone, among patients with rheumatoid arthritis. The study was conducted as a register-based cohort study in Denmark, 2004 to 2015, including episodes of concomitant use of methotrexate and NSAIDs (n = 21 536) and control episodes of use of methotrexate alone (n = 21 725). The primary outcome was the composite end point any serious adverse event, including liver toxicity, acute renal failure, and cytopenia. Secondary outcomes were the individual outcome components. Analyses were conducted using proportional-hazards regression, with adjustment using inverse-probability-of-treatment weighting based on propensity scores. During follow-up, 110 cases of the primary outcome occurred during concomitant use of methotrexate and NSAIDs (unadjusted incidence rate 12.1 per 1000 person-years) and 129 during control episodes (11.0 per 1000 person-years). Concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of any serious adverse event (weighted hazard ratio 1.40; 95% CI, 1.07-1.82). In secondary analyses, concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of acute renal failure and cytopenia. Concomitant use of low-dose methotrexate and NSAIDs was associated with a significantly increased risk of serious adverse events, expanding on the evidence base for current regulatory recommendations that advocate caution when low-dose methotrexate and NSAID are coprescribed. Copyright © 2018 John Wiley & Sons, Ltd.

Adverse Outcome Pathways for Embryonic Vascular Disruption and Alternative Methods to Identify Chemical Vascular Disruptor

EPA Science Inventory

Chemically induced vascular toxicity during embryonic development can result in a wide range of adverse prenatal outcomes. We used information from genetic mouse models linked to phenotypic outcomes and a vascular toxicity knowledge base to construct an embryonic vascular disrupt...

Studying Biology to Understand Risk: Dosimetry Models and Quantitative Adverse Outcome Pathways

EPA Science Inventory

Confidence in the quantitative prediction of risk is increased when the prediction is based to as great an extent as possible on the relevant biological factors that constitute the pathway from exposure to adverse outcome. With the first examples now over 40 years old, physiologi...

Intestinal Microbiota-Dependent Phosphatidylcholine Metabolites, Diastolic Dysfunction and Adverse Clinical Outcomes in Chronic Systolic Heart Failure

PubMed Central

Wilson Tang, W. H.; Wang, Zeneng; Shrestha, Kevin; Borowski, Allen G; Wu, Yuping; Troughton, Richard W; Klein, Allan L; Hazen, Stanley L

2014-01-01

Background Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aim to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF). Methods and Results In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median TMAO levels, choline, and betaine levels were 5.8 [3.6, 12.1] μM, 10.9 [8.4, 14.0] μM, 43.8 [37.1, 53.0] μM, respectively, and were correlated with each other (all p<0.0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9, 13.2] vs 4.8 [3.4, 9.8] μM, p=0.005) and in subjects with New York Heart Association (NYHA) class III or greater (7.0 [4.7, 14.8] vs 4.7 [3.4, 11.3] μM, p=0.02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma NT-proBNP levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (Hazard ratio (HR) 1.64 [95% CI: 1.22 2.20], p=0.001), betaine (HR 1.51 [1.10–2.08], p=0.01), and TMAO (HR 1.48 [1.10–1.96], p=0.01) predicted increased risk for 5-year adverse clinical events (death/transplant). Only higher TMAO levels predicted incident adverse clinical events independent of age, eGFR, mitral E/septal Ea, and NT-proBNP levels (HR 1.46 [1.03 2.14], p=0.03). Conclusion Elevated plasma TMAO, choline and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO levels was associated with poor prognosis after adjustment for cardio-renal indices. PMID:25459686

Long-Term Outcomes in Idiopathic Membranous Nephropathy Using a Restrictive Treatment Strategy

PubMed Central

van Dijk, Peter R.; Hofstra, Julia M.; Wetzels, Jack F.M.

2014-01-01

Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend limiting the use of immunosuppressive drugs in idiopathic membranous nephropathy to patients at the highest risk of kidney failure. However, recommendations are based on natural history rather than direct assessment of a restrictive treatment strategy. Here, we describe the long-term outcomes of treating a large cohort of patients with idiopathic membranous nephropathy according to a restrictive treatment policy. We analyzed data for 254 patients who visited our outpatient clinic between 1995 and 2009. All patients were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Immunosuppressive therapy was recommended in cases of deteriorating renal function or untreatable nephrotic syndrome. Primary outcomes for the present study were renal replacement therapy and death. Secondary outcomes included adverse events during follow-up and remission of proteinuria. In total, 124 patients (49%) received immunosuppressive therapy, which predominantly consisted of cyclophosphamide combined with steroids. Ten-year cumulative incidence rates were 3% for renal replacement therapy and 10% for death. Partial remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively; complete remission rates were 5%, 24%, and 38% at 1, 3, and 5 years, respectively. A serious adverse event occurred in 23% of all patients. The most notable complications were infections (17%), leukopenia (18%), cardiovascular events (13%), and malignancies (8%). In conclusion, the use of a restrictive treatment strategy in this cohort of patients with idiopathic membranous nephropathy yielded favorable outcomes while limiting the number of patients exposed to toxic drugs. These results support current KDIGO guidelines. PMID:24029426

Biomarkers for Adverse Pregnancy Outcomes in Rheumatic Diseases.

PubMed

Soh, May Ching; Nelson-Piercy, Catherine

2017-05-01

Pregnancy is a delicate balance of angiogenic factors. Adverse pregnancy outcomes in the form of placental insufficiency occur when antiangiogenic factors predominate, which manifests as maternal-placental syndrome (MPS). Women with rheumatic disease are at increased risk of MPS. Endothelial damage from circulating antiangiogenic factors and other inflammatory molecules in combination with preexisting maternal vascular risk factors is the likely underlying pathophysiological process for MPS. It is likely that these changes persist, and additional "insults" from ongoing inflammation, medications, and disease damage contribute to the development of accelerated cardiovascular disease seen in young women with rheumatic disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of the FDA adverse event report system database.

PubMed

Perlman, A; Heyman, S N; Matok, I; Stokar, J; Muszkat, M; Szalat, A

2017-12-01

Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database. We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016. ARF cases were identified using a structured medical query. Medications were identified using both brand and generic names. During the period evaluated, 18,915 reports (out of a total of 3,832,015 registered in FAERS) involved the use of SGLT2-inhibitors. SGLT2-inhibitors were reportedly associated with ARF in 1224 of these cases (6.4%), and were defined as the "primary" or "secondary" cause of the adverse event in 96.8% of these cases. The proportion of reports with ARF among reports with SGLT2 inhibitor was almost three-fold higher compared to reports without these drugs (ROR 2.88, 95% CI 2.71-3.05, p < 0.001). The proportion of ARF reports among cases with SGLT2-inhibitors was significantly greater than the proportion of ARF among cases with T2DM without SGLT2-inhibitors (ROR 1.68, 95% CI 1.57-1.8, p < 0.001). Among the SGLT2-inhibitors, canagliflozin was associated with a higher proportion of reports of renal failure (7.3%), compared to empagliflozin and dapagliflozin (4.7% and 4.8% respectively, p < 0.001). SGLT2-inhibitors are associated with an increase in the proportion of reports of ARF compared to other medications. SGLT2-inhibitor agents may differ from one another in their respective risk for ARF. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

The adverse outcome pathway for skin sensitisation: Moving closer to replacing animal testing.

PubMed

Schultz, Terry W; Dimitrova, Gergana; Dimitrov, Sabcho; Mekenyan, Ovanes G

2016-10-01

This article outlines the work of the Organisation for Economic Co-operation and Development (OECD) that led to being jointly awarded the 2015 Lush Black Box Prize. The award-winning work centred on the development of 'The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins'. This Adverse Outcome Pathway (AOP) has provided the mechanistic basis for the integration of skin sensitisation-related information. Recent developments in integrated approaches to testing and assessment, based on the AOP, are summarised. The impact of the AOP on regulatory policy and on the Three Rs are discussed. An overview of the next generation of the skin sensitisation AOP module in the OECD QSAR Toolbox, based on more-recent work at the Laboratory of Mathematical Chemistry, is also presented. 2016 FRAME.

Travel time from home to hospital and adverse perinatal outcomes in women at term in the Netherlands.

PubMed

Ravelli, A C J; Jager, K J; de Groot, M H; Erwich, J J H M; Rijninks-van Driel, G C; Tromp, M; Eskes, M; Abu-Hanna, A; Mol, B W J

2011-03-01

To study the effect of travel time, at the start or during labour, from home to hospital on mortality and adverse outcomes in pregnant women at term in primary and secondary care. Population-based cohort study from 2000 up to and including 2006. The Netherlands Perinatal Registry. A total of 751,926 singleton term hospital births. We assessed the impact of travel time by car, calculated from the postal code of the woman's residence to the 99 maternity units, on neonatal outcome. Logistic regression modelling with adjustments for gestational age, maternal age, parity, ethnicity, socio-economic status, urbanisation, tertiary care centres and volume of the hospital was used. Mortality (intrapartum, and early and late neonatal mortality) and adverse neonatal outcomes (mortality, Apgar <4 and/or admission to a neonatal intensive care unit). The mortality was 1.5 per 1000 births, and adverse outcomes occurred in 6.0 per 1000 births. There was a positive relationship between longer travel time (≥20 minutes) and total mortality (OR 1.17, 95% CI 1.002-1.36), neonatal mortality within 24 hours (OR 1.51, 95% CI 1.13-2.02) and with adverse outcomes (OR 1.27, 95% CI 1.17-1.38). In addition to travel time, both delivery at 37 weeks of gestation (OR 2.23, 95% CI 1.81-2.73) or 41 weeks of gestation (OR 1.52, 95% CI 1.29-1.80) increased the risk of mortality. A travel time from home to hospital of 20 minutes or more by car is associated with an increased risk of mortality and adverse outcomes in women at term in the Netherlands. These findings should be considered in plans for the centralisation of obstetric care. © 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.

Fetal sex modifies effects of prenatal stress exposure and adverse birth outcomes.

PubMed

Wainstock, Tamar; Shoham-Vardi, Ilana; Glasser, Saralee; Anteby, Eyal; Lerner-Geva, Liat

2015-01-01

Prenatal maternal stress is associated with pregnancy complications, poor fetal development and poor birth outcomes. Fetal sex has also been shown to affect the course of pregnancy and its outcomes. The aim of this study was to evaluate whether fetal sex modifies the association between continuous exposure to life-threatening rocket attack alarms and adverse pregnancy outcomes. A retrospective cohort study was conducted in which the exposed group was comprised of 1846 women exposed to rocket-attack alarms before and during pregnancy. The unexposed group, with similar sociodemographic characteristics, delivered during the same period of time at the same medical center, but resided out of rocket-attack range. Multivariable models for each gender separately, controlling for possible confounders, evaluated the risk associated with exposure for preterm births (PTB), low birthweight (LBW), small for gestational age and small head circumference (HC). In both univariable and multivariable analyses exposure status was a significant risk factor in female fetuses only: PTB (adj. OR = 1.43; 1.04-1.96), LBW (adj. OR = 1.41; 1.02-1.95) and HC < 31 cm (adj. OR = 1.78; 1.11-2.88). In addition, regarding all adverse outcomes, the male-to-female ratio was higher in the exposed group than in the unexposed group. The findings support the hypothesis that male and female fetuses respond differentially to chronic maternal stress.

Peritumoral Artery Scoring System: a Novel Scoring System to Predict Renal Function Outcome after Laparoscopic Partial Nephrectomy.

PubMed

Zhang, Ruiyun; Wu, Guangyu; Huang, Jiwei; Shi, Oumin; Kong, Wen; Chen, Yonghui; Xu, Jianrong; Xue, Wei; Zhang, Jin; Huang, Yiran

2017-06-06

The present study aimed to assess the impact of peritumoral artery characteristics on renal function outcome prediction using a novel Peritumoral Artery Scoring System based on computed tomography arteriography. Peritumoral artery characteristics and renal function were evaluated in 220 patients who underwent laparoscopic partial nephrectomy and then validate in 51 patients with split and total glomerular filtration rate (GFR). In particular, peritumoral artery classification and diameter were measured to assign arteries into low, moderate, and high Peritumoral Artery Scoring System risk categories. Univariable and multivariable logistic regression analyses were then used to determine risk factors for major renal functional decline. The Peritumoral Artery Scoring System and four other nephrometry systems were compared using receiver operating characteristic curve analysis. The Peritumoral Artery Scoring System was significantly superior to the other systems for predicting postoperative renal function decline (p < 0.001). In receiver operating characteristic analysis, our category system was a superior independent predictor of estimated glomerular filtration rate (eGFR) decline (area-under-the-curve = 0.865, p < 0.001) and total GFR decline (area-under-the-curve = 0.796, p < 0.001), and split GFR decline (area-under-the-curve = 0.841, p < 0.001). Peritumoral artery characteristics were independent predictors of renal function outcome after laparoscopic partial nephrectomy.

Use of Adverse Outcome Pathways for Assessing Effects of the Fungicide Propiconazole on Fish Reproduction

EPA Science Inventory

Adverse outcome pathways (AOP) are used to describe the linkage of biological events from a molecular initiating point, to individual-level-endpoints relevant to risk assessment. This study was done to assess toxicity outcomes for the conazole fungicide propiconazole based on a p...

End-Stage Renal Disease Models in the Americas: Optimizing Resources to Achieve Better Health Outcomes.

PubMed

Gilardino, Ramiro E; González-Pier, Eduardo; Brabata, Claudia

2018-05-21

End-stage renal disease, the last and most severe stage of chronic kidney disease, represents a major and rising concern for countries in Latin America, driven in large part by aging populations and the near-epidemic rises in diabetes, obesity, and hypertension. This places a great clinical, economic, and social burden on the region's health systems. During the ISPOR 6th Latin America Conference held in Sao Paulo, Brazil, in September 2017, an educational forum debated on value-based decision making in the treatment of end-stage renal disease in Latin America. We summarize the current state and how to build strategies and implement actions to move to a more patient-centered, outcomes-based approach for renal care in the region, taken from the discussions in the conference and also from a literature review. Models of renal care used in Ontario (Canada), Colombia, and a Chilean hospital stress the importance of empowering and supporting patients and their families, allowing for a better coordination between primary care providers and specialists, providing financial incentives to health units, and establishing an entity that holds insurers and providers accountable for health outcomes and costs of treatment. The study uses the framework of value-based health care for the evaluation of different dialysis options-peritoneal dialysis, hemodialysis, home dialysis, and so forth-and calls for the countries to adopt an integrated care model. We emphasize that countries in Latin America need to recognize the chronic kidney disease challenge and develop health systems and efficient renal care models to be able to reduce the burden of the disease. Copyright © 2018. Published by Elsevier Inc.

Serious fall injury history and adverse health outcomes after initiating hemodialysis among older U.S. adults.

PubMed

Bowling, C Barrett; Hall, Rasheeda; Khakharia, Anjali; Franch, Harold A; Plantinga, Laura C

2018-01-16

Although older adults with pre-dialysis chronic kidney disease (CKD) are at higher risk for falls, the prognostic significance of a serious fall injury prior to dialysis initiation has not been well described in the end-stage renal disease population. We examined the association between a serious fall injury in the year prior to starting hemodialysis and adverse health outcomes in the year following dialysis initiation using a retrospective cohort study of U.S. Medicare beneficiaries ≥ 67 years old who initiated dialysis in 2010-2012. Serious fall injuries were defined using diagnostic codes for falls plus an injury (fracture, joint dislocation, or head injury). Health outcomes, defined as time-to-event variables within the first year of dialysis, included four outcomes: a subsequent serious fall injury, hospital admission, post-acute skilled nursing facility (SNF) utilization, and mortality. Among this cohort of 81,653 initiating hemodialysis, 2,958 (3.6%) patients had a serious fall injury in the year prior to hemodialysis initiation. In the first year of dialysis, 7.6% had a subsequent serious fall injury, 67.6% a hospitalization, 30.7% a SNF claim and 26.1% died. Those with vs. without a serious fall injury in the year prior to hemodialysis initiation were at higher risk (hazard ratio, 95% confidence interval) for a subsequent serious fall injury (2.65, 2.41-2.91), hospitalization (1.11, 1.06-1.16), SNF claim (1.40, 1.30-1.50), and death (1.14, 1.06-1.22). For older adults initiating dialysis, a history of a serious fall injury may provide prognostic information to support decision-making and establish expectations for life after dialysis initiation. Published by Oxford University Press on behalf of The Gerontological Society of America 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Intersections of poverty, race/ethnicity, and sex: Alcohol consumption and adverse outcomes in the United States

PubMed Central

Glass, Joseph E.; Rathouz, Paul J.; Gattis, Maurice; Joo, Young Sun; Nelson, Jennifer C.; Williams, Emily C.

2017-01-01

We examine whether intersectionality theory—which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic —can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the U.S. Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption. PMID:28349171

Intersections of poverty, race/ethnicity, and sex: alcohol consumption and adverse outcomes in the United States.

PubMed

Glass, Joseph E; Rathouz, Paul J; Gattis, Maurice; Joo, Young Sun; Nelson, Jennifer C; Williams, Emily C

2017-05-01

We examine whether intersectionality theory-which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic-can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the US Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption.

Impact of Renal Disease on Patients with Hepatitis C: A Retrospective Analysis of Disease Burden, Clinical Outcomes, and Health Care Utilization and Cost.

PubMed

Solid, Craig A; Peter, Senaka A; Natwick, Tanya; Guo, Haifeng; Collins, Allan J; Arduino, Jean Marie

2017-01-01

Few studies explore the magnitude of the disease burden and health care utilization imposed by renal disease among patients with hepatitis C virus (HCV). We aimed to describe the characteristics, outcomes, and health care utilization and costs of patients with HCV with and without renal impairment. This retrospective analysis used 2 administrative claims databases: the US commercially insured population in Truven Health MarketScan® data (aged 20-64 years), and the US Medicare fee-for-service population in the Medicare 20% sample (aged ≥65 years). Baseline characteristics and comorbid conditions were identified from claims during 2011; patients were followed for up to 1 year (beginning January 1, 2012) to identify health outcomes of interest and health care utilization and costs. In the MarketScan and Medicare databases, 35,965 and 10,608 patients with HCV were identified, 8.5 and 26.5% with evidence of renal disease (chronic kidney disease [CKD] or end-stage renal disease [ESRD]). Most comorbid conditions and unadjusted outcome rates increased across groups from patients with no evidence of renal disease to non-ESRD CKD to ESRD. Health care utilization followed a similar pattern, as did the costs. Our findings suggest that HCV patients with concurrent renal disease have significantly more comorbidity, a higher likelihood of negative health outcomes, and higher health care utilization and costs. © 2017 S. Karger AG, Basel.

Adverse Outcome Pathways and Extrapolation Tools to Advance the Three Rs in Ecotoxicology

EPA Science Inventory

Adverse outcome pathways (AOPs) are conceptual frameworks for identifying and organizing predictive and causal linkages between cellular-level responses and endpoints conventionally considered in ecological risk assessment (e.g., effects on survival, growth/development, and repro...

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

PubMed

Faisal, Nabiha; Bilodeau, Marc; Aljudaibi, Bandar; Hirch, Geri; Yoshida, Eric M; Hussaini, Trana; Ghali, Maged P; Congly, Stephen E; Ma, Mang M; Lilly, Leslie B

2018-04-04

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal

Image-guided percutaneous microwave ablation of small renal tumours: short- and mid-term outcomes.

PubMed

Genson, Pierre-Yves; Mourey, Eric; Moulin, Morgan; Favelier, Sylvain; Di Marco, Lucy; Chevallier, Olivier; Cercueil, Jean-Pierre; Krausé, Denis; Cormier, Luc; Loffroy, Romaric

2015-10-01

The purpose is to assess the short- and mid-term outcomes of microwave ablation (MWA) of small renal tumours in selected patients. From August 2012 to February 2015, 29 renal tumours in 23 patients (17 male, 6 female, mean age 75 years) were treated by percutaneous MWA under imaging guidance. The tumours were 1-4.7 cm in diameter (mean size, 2.7 cm). Therapeutic effects were assessed at follow-up with magnetic resonance imaging (MRI). All patients were followed up for 2-25 months (mean, 12.2 months) to observe the therapeutic effects and complications. Changes in renal function at day 1 after treatment were statistically analyzed using the Student paired t-test or the paired Wilcoxon test. Technical success was achieved in all cases. One severe bleeding complication post-procedure occurred leading to death. No other unexpected side effects were observed after the MWA procedures. Clinical effectiveness was 100%. None of the patients showed recurrence on MRI imaging follow-up. No significant changes in renal function were noted after treatment (P=0.57). Our preliminary study demonstrates that the use of MWA for the treatment of small renal tumours can be applied as safely and efficiently as other ablative techniques in selected patients not eligible for surgery.

Allostatic load: A theoretical model for understanding the relationship between maternal posttraumatic stress disorder and adverse birth outcomes.

PubMed

Li, Yang; Rosemberg, Marie-Anne Sanon; Seng, Julia S

2018-07-01

Adverse birth outcomes such as preterm birth and low birth weight are significant public health concerns and contribute to neonatal morbidity and mortality. Studies have increasingly been exploring the predictive effects of maternal posttraumatic stress disorder (PTSD) on adverse birth outcomes. However, the biological mechanisms by which maternal PTSD affects birth outcomes are not well understood. Allostatic load refers to the cumulative dysregulations of the multiple physiological systems as a response to multiple social-ecological levels of chronic stress. Allostatic load has been well documented in relation to both chronic stress and adverse health outcomes in non-pregnant populations. However, the mediating role of allostatic load is less understood when it comes to maternal PTSD and adverse birth outcomes. To propose a theoretical model that depicts how allostatic load could mediate the impact of maternal PTSD on birth outcomes. We followed the procedures for theory synthesis approach described by Walker and Avant (2011), including specifying focal concepts, identifying related factors and relationships, and constructing an integrated representation. We first present a theoretical overview of the allostatic load theory and the other 4 relevant theoretical models. Then we provide a brief narrative review of literature that empirically supports the propositions of the integrated model. Finally, we describe our theoretical model. The theoretical model synthesized has the potential to advance perinatal research by delineating multiple biomarkers to be used in future. After it is well validated, it could be utilized as the theoretical basis for health care professionals to identify high-risk women by evaluating their experiences of psychosocial and traumatic stress and to develop and evaluate service delivery and clinical interventions that might modify maternal perceptions or experiences of stress and eliminate their impacts on adverse birth outcomes. Copyright

Adverse obstetric outcomes during delivery hospitalizations complicated by suicidal behavior among US pregnant women.

PubMed

Zhong, Qiu-Yue; Gelaye, Bizu; Smoller, Jordan W; Avillach, Paul; Cai, Tianxi; Williams, Michelle A

2018-01-01

The effects of suicidal behavior on obstetric outcomes remain dangerously unquantified. We sought to report on the risk of adverse obstetric outcomes for US women with suicidal behavior at the time of delivery. We performed a cross-sectional analysis of delivery hospitalizations from 2007-2012 National (Nationwide) Inpatient Sample. From the same hospitalization record, International Classification of Diseases codes were used to identify suicidal behavior and adverse obstetric outcomes. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were obtained using logistic regression. Of the 23,507,597 delivery hospitalizations, 2,180 were complicated by suicidal behavior. Women with suicidal behavior were at a heightened risk for outcomes including antepartum hemorrhage (aOR = 2.34; 95% CI: 1.47-3.74), placental abruption (aOR = 2.07; 95% CI: 1.17-3.66), postpartum hemorrhage (aOR = 2.33; 95% CI: 1.61-3.37), premature delivery (aOR = 3.08; 95% CI: 2.43-3.90), stillbirth (aOR = 10.73; 95% CI: 7.41-15.56), poor fetal growth (aOR = 1.70; 95% CI: 1.10-2.62), and fetal anomalies (aOR = 3.72; 95% CI: 2.57-5.40). No significant association was observed for maternal suicidal behavior with cesarean delivery, induction of labor, premature rupture of membranes, excessive fetal growth, and fetal distress. The mean length of stay was longer for women with suicidal behavior. During delivery hospitalization, women with suicidal behavior are at increased risk for many adverse obstetric outcomes, highlighting the importance of screening for and providing appropriate clinical care for women with suicidal behavior during pregnancy.

Four trace elements in pregnant women and their relationships with adverse pregnancy outcomes.

PubMed

Shen, P-J; Gong, B; Xu, F-Y; Luo, Y

2015-12-01

Lack of trace elements during pregnancy is detrimental to maternal and fetal health. Our aim is to study the changes in trace element levels in Chinese pregnant women and their association with adverse pregnancy outcomes. 1568 cases of Chinese pregnant women in remote areas were collected for a prospective cohort study. Serum copper, zinc, calcium and iron levels were measured at pre-pregnancy, 1st trimester (7w-12w), 2nd trimester (24w-28w) and 3rd trimester (35w-40w). (1) Serum copper levels was significantly higher after pregnancy than before, calcium and iron levels decreased, but zinc levels did not change significantly. (2) Copper and zinc deficiency in pregnant women was not a common finding, but lack of iron and calcium was frequently encountered; iron deficiency was especially common in the 3rd trimester (42.27%). (3) Serum zinc and iron levels in patients who either had a miscarriage or a preterm delivery were significantly lower than in the control group (p < 0.05). In patients with premature rupture of membranes, serum zinc levels were significantly lower (p < 0.05). In patients with intrauterine growth restriction (IUGR), serum copper, zinc, calcium and iron were significantly lower (p < 0.05). Trace elements is closely associated with fetal growth and development during pregnancy. Deficiency can lead to adverse pregnancy outcomes. Therefore, we should have a reasonable diet, replenish trace elements, therefore reducing the occurrence of adverse pregnancy outcomes.

EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES

EPA Science Inventory

Embryonic vascular disruption is an important adverse outcome pathway (AOP) given the knowledge that chemical disruption of early cardiovascular system development leads to broad prenatal defects. High throughput screening (HTS) assays provide potential building blocks for AOP d...

VIOLENT CRIME EXPOSURE CLASSIFICATION AND ADVERSE BIRTH OUTCOMES: A GEOGRAPHICALLY-DEFINED COHORT STUDY

EPA Science Inventory

Background

Area-level socioeconomic disparities have long been associated with adverse pregnancy outcomes. Crime is an important element of the neighborhood environment inadequately investigated in the public health literature. Using geocoded linked birth, crime and cens...

Global Estimates of Syphilis in Pregnancy and Associated Adverse Outcomes: Analysis of Multinational Antenatal Surveillance Data

PubMed Central

Newman, Lori; Kamb, Mary; Hawkes, Sarah; Gomez, Gabriela; Say, Lale; Seuc, Armando; Broutet, Nathalie

2013-01-01

Background The World Health Organization initiative to eliminate mother-to-child transmission of syphilis aims for ≥90% of pregnant women to be tested for syphilis and ≥90% to receive treatment by 2015. We calculated global and regional estimates of syphilis in pregnancy and associated adverse outcomes for 2008, as well as antenatal care (ANC) coverage for women with syphilis. Methods and Findings Estimates were based upon a health service delivery model. National syphilis seropositivity data from 97 of 193 countries and ANC coverage from 147 countries were obtained from World Health Organization databases. Proportions of adverse outcomes and effectiveness of screening and treatment were from published literature. Regional estimates of ANC syphilis testing and treatment were examined through sensitivity analysis. In 2008, approximately 1.36 million (range: 1.16 to 1.56 million) pregnant women globally were estimated to have probable active syphilis; of these, 80% had attended ANC. Globally, 520,905 (best case: 425,847; worst case: 615,963) adverse outcomes were estimated to be caused by maternal syphilis, including approximately 212,327 (174,938; 249,716) stillbirths (>28 wk) or early fetal deaths (22 to 28 wk), 91,764 (76,141; 107,397) neonatal deaths, 65,267 (56,929; 73,605) preterm or low birth weight infants, and 151,547 (117,848; 185,245) infected newborns. Approximately 66% of adverse outcomes occurred in ANC attendees who were not tested or were not treated for syphilis. In 2008, based on the middle case scenario, clinical services likely averted 26% of all adverse outcomes. Limitations include missing syphilis seropositivity data for many countries in Europe, the Mediterranean, and North America, and use of estimates for the proportion of syphilis that was “probable active,” and for testing and treatment coverage. Conclusions Syphilis continues to affect large numbers of pregnant women, causing substantial perinatal morbidity and mortality that

Effect of ionized serum calcium on outcomes in acute kidney injury needing renal replacement therapy: Secondary analysis of the Acute Renal Failure Trial Network Study

PubMed Central

Afshinnia, Farsad; Belanger, Karen; Palevsky, Paul M.; Young, Eric W.

2014-01-01

Background Hypocalcemia is very common in critically ill patients. While the effect of ionized calcium (iCa) on outcome is not well understood, manipulation of iCa in critically ill patients is a common practice. We analyzed all-cause mortality and several secondary outcomes in patients with acute kidney injury (AKI) by categories of serum iCa among participants in the Acute Renal Failure Trial Network (ATN) Study. Methods This is a post hoc secondary analysis of the ATN Study which was not preplanned in the original trial. Risk of mortality and renal recovery by categories of iCa were compared using multiple fixed and adjusted time-varying Cox regression models. Multiple linear regression models were used to explore the impact of baseline iCa on days free from ICU and hospital. Results A total of 685 patients were included in the analysis. Mean age was 60 (SD=15) years. There were 502 male patients (73.3%). Sixty-day all-cause mortality was 57.0%, 54.8%, and 54.4%, in patients with an iCa <1, 1–1.14, and ≥1.15 mmol/L, respectively (P=0.87). Mean of days free from ICU or hospital in all patients and the 28-day renal recovery in survivors to day 28 were not significantly different by categories of iCa. The hazard for death in a fully adjusted time-varying Cox regression survival model was 1.7 (95% CI: 1.3–2.4) comparing iCa <1 to iCa ≥1.15 mmol/L. No outcome was different for levels of iCa >1 mmol/L. Conclusion Severe hypocalcemia with iCa <1 mmol/L independently predicted mortality in patients with AKI needing renal replacement therapy. PMID:23992422

Patient-specific evolution of renal function in chronic heart failure patients dynamically predicts clinical outcome in the Bio-SHiFT study.

PubMed

Brankovic, Milos; Akkerhuis, K Martijn; van Boven, Nick; Anroedh, Sharda; Constantinescu, Alina; Caliskan, Kadir; Manintveld, Olivier; Cornel, Jan Hein; Baart, Sara; Rizopoulos, Dimitris; Hillege, Hans; Boersma, Eric; Umans, Victor; Kardys, Isabella

2018-04-01

Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18[1.07-1.31], CysC: 2.41[1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76[1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF. Copyright © 2017

Use of an Adverse Outcome Pathway for Hepatic Steatosis to Build Chemical Groups

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework systematically documents the mechanisms underlying effects of chemicals starting with the initial interaction of chemicals with the biological system, i.e. the molecular initiating event (MIE). Chemical activity in assays designed to mo...

Efficacy and safety of sorafenib for advanced renal cell carcinoma: real-world data of patients with renal impairment.

PubMed

Tatsugami, Katsunori; Oya, Mototsugu; Kabu, Koki; Akaza, Hideyuki

2018-04-10

We retrospectively analysed the efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with renal impairment. Patients were divided into two groups by an estimated glomerular filtration rate (eGFR) cut-off of 45 mL/min/1.73 m 2 . Background factors considered to affect prognosis were well balanced by propensity score matching between the groups. Demographics, dose modification, adverse events, tumour response, progression-free survival, and renal function (eGFR) were evaluated. Among 935 and 2008 patients with an eGFR of <45 and ≥45, respectively, 613 pairs were matched. The mean starting dose was significantly lower in patients with an eGFR of <45; however, the mean daily dose, median treatment duration, progression-free survival, and tumour response were similar between the groups. In terms of safety, no significant differences were found in serious adverse events, although cytopaenia (16.6% vs 10.6%) and renal dysfunction (4.4% vs 0.7%) were higher in patients with an eGFR of <45 than ≥45 in all adverse events. There were also no differences in dose modification, including dose reduction, dose interruption, and treatment discontinuation. Throughout the 12-month observation period, sorafenib in patients with an eGFR of <45 and ≥45 showed similar safety and efficacy, and treatment was continued without affecting renal function.

Computationally predicted Adverse Outcome Pathway networks for liver-related diseases using publicly available data sources: Case studies and lessons learned

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework summarizes key information about mechanistic events leading to an adverse health or ecological outcome. In recent years computationally predicted AOPs (cpAOP) making use of publicly available data have been proposed as a means of accele...

Development of a Novel Quantitative Adverse Outcome Pathway Predictive Model for Lung Cancer

EPA Science Inventory

Traditional methods for carcinogenicity testing are resource-intensive, retrospective, and time consuming. An increasing testing burden has generated interest in the adverse outcome pathway (AOP) concept as a tool to evaluate chemical safety in a more efficient, rapid and effecti...

Use of Adverse Outcome Pathways to Inform Decisions on Chemical Innovation, Regulation & Stewardship

EPA Science Inventory

An invited group of scientists participated in a SETAC Pellston WorkshopTM, “Advancing the Adverse Outcome Pathway (AOP) Concept – An International Horizon Scanning Approach,” in April 2017. The workshop addressed key challenges or limitations of AOP constructs...

Constructing Adverse Outcome Pathways: a Demonstration of an Ontology-based Semantics Mapping Approach

EPA Science Inventory

Adverse outcome pathway (AOP) provides a conceptual framework to evaluate and integrate chemical toxicity and its effects across the levels of biological organization. As such, it is essential to develop a resource-efficient and effective approach to extend molecular initiating ...

Adverse perinatal outcomes associated with moderate or severe maternal anaemia based on parity in Finland during 2006-10.

PubMed

Räisänen, Sari; Kancherla, Vijaya; Gissler, Mika; Kramer, Michael R; Heinonen, Seppo

2014-09-01

Anaemia during pregnancy is an important public health problem. We investigated whether the association between maternal anaemia during pregnancy and adverse perinatal outcomes differed between nulliparous and multiparous women. A retrospective population-based cohort study was conducted using data on all singleton births (n = 290 662) recorded in the Finnish Medical Birth Register during 2006-10. Maternal anaemia was defined as a maternal haemoglobin level of <100 g/L). Adverse perinatal outcomes that were examined included preterm delivery (<37 weeks), small-for-gestational age (SGA, <2 standard deviation), admission to neonatal intensive care, stillbirth, early neonatal death, and major congenital anomalies. An association between anaemia and adverse outcomes was assessed by logistic regression analysis. The prevalence of anaemia during pregnancy was 2.5% among nulliparous women and 2.3% among multiparous women. Among nulliparous women, anaemia was not associated with adverse perinatal outcomes. Among multiparous women, anaemia was associated with preterm delivery (adjusted odds ratio [aOR] 1.32, [95% CI 1.14, 1.53]), SGA (aOR 1.27, [95% CI 1.04, 1.55]), and admission to neonatal intensive care (aOR 1.23, [95% CI 1.10, 1.38]); there was a trend towards increased odds of major congenital anomalies (aOR 1.15, [95% CI 0.99, 1.34]). These data underscore that maternal anaemia is associated with several adverse perinatal outcomes. This association was, however, confined to multiparous women. Future research should explore in detail the timing of anaemia in these associations. © 2014 John Wiley & Sons Ltd.

Effects of statin therapy on cerebrovascular and renal outcomes in patients with predialysis advanced chronic kidney disease and dyslipidemia.

PubMed

Chung, Chang-Min; Lin, Ming-Shyan; Hsu, Jen-Te; Hsiao, Ju-Feng; Chang, Shih-Tai; Pan, Kuo-Li; Lin, Chun-Liang; Lin, Yu-Sheng

Treatment with statin may be beneficial for patients with chronic kidney disease (CKD). However, the debate over the clinical importance of statin in patients with predialysis advanced CKD remains unresolved. The objective of the article was to evaluate the effect of statin on mortality, cerebrovascular, and renal outcomes in patients with predialysis advanced CKD and dyslipidemia. Data on predialysis advanced CKD patients were retrieved from the National Health Insurance Research Database based on the guidelines for prescribing regular erythropoietin-stimulating agent in CKD patients. Patients with dyslipidemia were further selected and divided into 2 groups by their statin use after the prescribed erythropoietin-stimulating agent. All-cause mortality and cerebrovascular and renal outcomes were analyzed after propensity score matching. There were 2016 and 14,412 patients in the statin and nonstatin groups. Their average follow-up periods were 3.7 and 3.0 years, respectively. After 1:2 propensity score matching, the annual all-cause mortality rate was higher in the nonstatin than in the statin group (143.99 vs 109.50 per 1000 person-years; P < .001; hazard ratio: 0.73; 95% confidence interval: 0.68-080). The annual risk of ischemic stroke (P = .186) and intracranial hemorrhage (P = .322) were not significantly different between the 2 groups. The nonstatin group had a higher risk of dialysis than the statin group (1269.45 vs 1095.00 per 1000 person-years; P = .002). Adverse events were not significant between the 2 groups. Statins may reduce the all-cause mortality and reduced the risk of dialysis in patients with predialysis advanced CKD and dyslipidemia. However, statins have no impact on ischemic-hemorrhage stroke. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[Frequency, etiology, and outcomes of acute renal failure (data of Kaunas University of Medicine Hospital in 1995-2006)].

PubMed

Skarupskiene, Inga; Kuzminskis, Vytautas; Ziginskiene, Edita

2007-01-01

The aim of this study was to determine the frequency, etiology, and outcomes of acute renal failure. We retrospectively collected data on all patients (n=1653) who received renal replacement therapy for acute renal failure at the Kaunas University of Medicine Hospital during 1995-2006. The number of patients with acute renal failure increased nine times during the 11-year period. The mean age of patients was 59.76+/-17.52 years and increased from 44.97+/-17.1 years in 1995 to 62.84+/-16.49 years in 2006. The most common causes of acute renal failure were renal (n=646, 39%), prerenal (n=380, 23%), and obstructive (n=145, 9%). The renal replacement therapy was discontinued because of recovery of renal function in 49.9% of cases. The overall hospital mortality rate was 45.1%. Renal function did not recover in 6.7% of patients. The mortality rate over the 11-year period varied from 37.8 to 57.5%. The highest mortality rate was in the neurosurgical (62.3%) and cardiac surgical (61.8%) intensive care units. High mortality rate (more than 50%) was in the groups of patients with acute renal failure that was caused by hepatorenal syndrome, shock, sepsis, and reduced cardiac output.

Epidemiology and Outcome of Acute Kidney Injury According to Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes Criteria in Critically Ill Children-A Prospective Study.

PubMed

Volpon, Leila C; Sugo, Edward K; Consulin, Julio C; Tavares, Tabata L G; Aragon, Davi C; Carlotti, Ana P C P

2016-05-01

We aimed to investigate the epidemiology, risk factors, and short- and medium-term outcome of acute kidney injury classified according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease, and Kidney Disease: Improving Global Outcomes criteria in critically ill children. Prospective observational cohort study. Two eight-bed PICUs of a tertiary-care university hospital. A heterogeneous population of critically ill children. None. Demographic, clinical, laboratory, and outcome data were collected on all patients admitted to the PICUs from August 2011 to January 2012, with at least 24 hours of PICU stay. Of the 214 consecutive admissions, 160 were analyzed. The prevalence of acute kidney injury according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was 49.4% vs. 46.2%, respectively. A larger proportion of acute kidney injury episodes was categorized as Kidney Disease: Improving Global Outcomes stage 3 (50%) compared with pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease F (39.2%). Inotropic score greater than 10 was a risk factor for acute kidney injury severity. About 35% of patients with acute kidney injury who survived were discharged from the PICU with an estimated creatinine clearance less than 75 mL/min/1.73 m and one persisted with altered renal function 6 months after PICU discharge. Age 12 months old or younger was a risk factor for estimated creatinine clearance less than 75 mL/min/1.73 m at PICU discharge. Acute kidney injury and its severity were associated with increased PICU length of stay and longer duration of mechanical ventilation. Eleven patients died; nine had acute kidney injury (p < 0.05). The only risk factor associated with death after multivariate adjustment was Pediatric Risk of Mortality score greater than or equal to 10. Acute kidney injury defined by both pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease

Iodinated contrast media and the role of renal replacement therapy.

PubMed

Weisbord, Steven D; Palevsky, Paul M

2011-05-01

Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.

Preventable health and cost burden of adverse birth outcomes associated with pregestational diabetes in the United States.

PubMed

Peterson, Cora; Grosse, Scott D; Li, Rui; Sharma, Andrea J; Razzaghi, Hilda; Herman, William H; Gilboa, Suzanne M

2015-01-01

Preconception care for women with diabetes can reduce the occurrence of adverse birth outcomes. We aimed to estimate the preconception care (PCC)-preventable health and cost burden of adverse birth outcomes associated with diagnosed and undiagnosed pregestational diabetes mellitus (PGDM) in the United States. Among women of reproductive age (15-44 years), we estimated age- and race/ethnicity-specific prevalence of diagnosed and undiagnosed diabetes. We applied age and race/ethnicity-specific pregnancy rates, estimates of the risk reduction from PCC for 3 adverse birth outcomes (preterm birth, major birth defects, and perinatal mortality), and lifetime medical and lost productivity costs for children with those outcomes. Using a probabilistic model, we estimated the reduction in adverse birth outcomes and costs associated with universal PCC compared with no PCC among women with PGDM. We did not assess maternal outcomes and associated costs. We estimated 2.2% of US births are to women with PGDM. Among women with diagnosed diabetes, universal PCC might avert 8397 (90% prediction interval [PI], 5252-11,449) preterm deliveries, 3725 (90% PI, 3259-4126) birth defects, and 1872 (90% PI, 1239-2415) perinatal deaths annually. Associated discounted lifetime costs averted for the affected cohort of children could be as high as $4.3 billion (90% PI, 3.4-5.1 billion) (2012 US dollars). PCC among women with undiagnosed diabetes could yield an additional $1.2 billion (90% PI, 951 million-1.4 billion) in averted cost. Results suggest a substantial health and cost burden associated with PGDM that could be prevented by universal PCC, which might offset the cost of providing such care. Published by Elsevier Inc.

Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy.

PubMed

Young, Sera; Murray, Katherine; Mwesigwa, Julia; Natureeba, Paul; Osterbauer, Beth; Achan, Jane; Arinaitwe, Emmanuel; Clark, Tamara; Ades, Veronica; Plenty, Albert; Charlebois, Edwin; Ruel, Theodore; Kamya, Moses; Havlir, Diane; Cohan, Deborah

2012-01-01

Maternal nutritional status is an important predictor of birth outcomes, yet little is known about the nutritional status of HIV-infected pregnant women treated with combination antiretroviral therapy (cART). We therefore examined the relationship between maternal BMI at study enrollment, gestational weight gain (GWG), and hemoglobin concentration (Hb) among 166 women initiating cART in rural Uganda. Prospective cohort. HIV-infected, ART-naïve pregnant women were enrolled between 12 and 28 weeks gestation and treated with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination regimen. Nutritional status was assessed monthly. Neonatal anthropometry was examined at birth. Outcomes were evaluated using multivariate analysis. Mean GWG was 0.17 kg/week, 14.6% of women experienced weight loss during pregnancy, and 44.9% were anemic. Adverse fetal outcomes included low birth weight (LBW) (19.6%), preterm delivery (17.7%), fetal death (3.9%), stunting (21.1%), small-for-gestational age (15.1%), and head-sparing growth restriction (26%). No infants were HIV-infected. Gaining <0.1 kg/week was associated with LBW, preterm delivery, and a composite adverse obstetric/fetal outcome. Maternal weight at 7 months gestation predicted LBW. For each g/dL higher mean Hb, the odds of small-for-gestational age decreased by 52%. In our cohort of HIV-infected women initiating cART during pregnancy, grossly inadequate GWG was common. Infants whose mothers gained <0.1 kg/week were at increased risk for LBW, preterm delivery, and composite adverse birth outcomes. cART by itself may not be sufficient for decreasing the burden of adverse birth outcomes among HIV-infected women. Clinicaltrials.gov NCT00993031.

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed Central

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

Defining Adverse Outcome Pathways for Effects of the Fungicide Propiconazole of Fish Reproduction

EPA Science Inventory

Adverse outcome pathways (AOPs) are used to describe the linkage of chemical interactions in terms of molecular initiating events to whole organism responses suitable for risk assessment. This study was conducted to develop AOPs for the model fungicide propiconazole relative to r...

AOP-DB: A database resource for the exploration of Adverse Outcome Pathways through integrated association networks.

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework describes the progression of a toxicity pathway from molecular perturbation to population-level outcome in a series of measurable, mechanistic responses. The controlled, computer-readable vocabulary that defines an AOP has the ability t...

Use of Erythropoietin-Stimulating Agents (ESA) in Patients With End-Stage Renal Failure Decided to Forego Dialysis: Palliative Perspective.

PubMed

Cheng, Hon Wai Benjamin; Chan, Kwok Ying; Lau, Hoi To; Man, Ching Wah; Cheng, Suk Ching; Lam, Carman

2017-05-01

Normochromic normocytic anemia is a common complication in chronic kidney disease (CKD) and is associated with many adverse clinical consequences. Erythropoiesis-stimulating agents (ESAs) act to replace endogenous erythropoietin for patients with end-stage renal disease having anemia. Today, ESAs remain the main tool for treating anemia associated with CKD. In current practice, the use of ESA is not limited to the patients on renal replacement therapy but has extended to nondialysis patients under palliative care (PC). Current evidence on ESA usage in patients with CKD decided to forego dialysis often have to take reference from studies conducted in other groups of patients with CKD, including pre-dialysis patients and those on renal replacement therapy. There is paucity of studies targeting use of ESAs in renal PC patients. Small-scale retrospective study in renal PC patients had suggested clinical advantage of ESAs in terms of hemoglobin improvement, reduction in fatigue, and hospitalization rate. With the expected growth in elderly patients with CKD decided to forego dialysis and manage conservatively, there remains an urgent need to call for large-scale prospective trial in exploring efficacy of ESAs in this population, targeting on quality of life and symptoms improvement outcome. This article also reviews the mechanism of action, pharmacology, adverse effects, and clinical trial evidence for ESA in patients with CKD under renal PC.

Systematic review of adverse outcomes of external cephalic version and persisting breech presentation at term.

PubMed

Nassar, Natasha; Roberts, Christine L; Barratt, Alexandra; Bell, Jane C; Olive, Emily C; Peat, Brian

2006-03-01

The aim of this study was to determine the frequency of adverse maternal and fetal outcomes of both external cephalic version (ECV) and persisting breech presentation at term. We conducted a systematic review of the literature using Medline, Embase and All Evidence Based Medicine (EBM) Reviews databases. Data were extracted from studies that compared women who had an ECV from 36 weeks' gestation with a similar control group of women enrolled at the same gestational age, eligible for, but who did not have an ECV. Eleven studies with a total of 2503 women were included. Adverse outcomes related to ECV were rarely reported and in most studies there was no evidence that relevant outcomes were ascertained among similar women who did not have an ECV. There was no increased risk of antepartum fetal death associated with ECV, but numbers were small. There were no reported cases of uterine rupture, placental abruption, prelabour rupture of membranes or cord prolapse, but these outcomes were not examined among controls. Onset of labour within 24 h and nuchal cord was non-significantly higher among women who had an ECV compared with those with a persisting breech. Despite limited reporting and small numbers, the results of our review suggest that adverse maternal and fetal outcomes of both ECV and persisting breech presentation are rare. Only with improved reporting and collection of safety data on ECV and persisting breech presentation can we provide high-quality information to assist informed decision making by pregnant women with a breech presentation at term.

Adverse Childhood Experiences and Young Adult Health Outcomes among Youth Aging Out of Foster Care.

PubMed

Rebbe, Rebecca; Nurius, Paula S; Courtney, Mark E; Ahrens, Kym R

2018-04-27

Former youth in foster care (YFC) are at greater risk of chronic health conditions than their peers. Although research in general population samples has demonstrated a dose-response relationship between adverse childhood experiences (ACEs) and adult health outcomes, few studies have conducted similar analyses in highly stress-exposed populations such as YFC. This paper uses person-centered latent class analysis (LCA) methods to examine the relationship between different profiles of ACE exposures and divergent health trajectories amongst this high-risk population. Data are from longitudinal research that followed transition-age YFC from age 17-26 (N =732). Using three subgroups previously identified by their ACEs histories, Complex, Environmental, and Lower Adversity groups, we applied group mean statistics to test for differences between the groups for physical and sexual health outcomes in young adulthood. In contrast to prior research demonstrating that the Environmental group was at the highest risk of criminal behavior outcomes, for most of the physical and sexual health risk outcomes evaluated in this paper, the Complex Adversity group had the highest risk. This study demonstrates that there are subgroups of YFC which each have a distinct profile of risk in young adulthood, with the Complex group being at highest risk of the physical and sexual health risk outcomes evaluated. Findings strongly suggest the need for targeted strategies to promote screening for ACEs and chronic health conditions, linkage to adult healthcare, and continuity of care for adolescents and young adults in foster care to offset these trajectories. Copyright © 2018. Published by Elsevier Inc.

Adverse obstetric outcomes during delivery hospitalizations complicated by suicidal behavior among US pregnant women

PubMed Central

Gelaye, Bizu; Smoller, Jordan W.; Avillach, Paul; Cai, Tianxi; Williams, Michelle A.

2018-01-01

Objective The effects of suicidal behavior on obstetric outcomes remain dangerously unquantified. We sought to report on the risk of adverse obstetric outcomes for US women with suicidal behavior at the time of delivery. Methods We performed a cross-sectional analysis of delivery hospitalizations from 2007–2012 National (Nationwide) Inpatient Sample. From the same hospitalization record, International Classification of Diseases codes were used to identify suicidal behavior and adverse obstetric outcomes. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were obtained using logistic regression. Results Of the 23,507,597 delivery hospitalizations, 2,180 were complicated by suicidal behavior. Women with suicidal behavior were at a heightened risk for outcomes including antepartum hemorrhage (aOR = 2.34; 95% CI: 1.47–3.74), placental abruption (aOR = 2.07; 95% CI: 1.17–3.66), postpartum hemorrhage (aOR = 2.33; 95% CI: 1.61–3.37), premature delivery (aOR = 3.08; 95% CI: 2.43–3.90), stillbirth (aOR = 10.73; 95% CI: 7.41–15.56), poor fetal growth (aOR = 1.70; 95% CI: 1.10–2.62), and fetal anomalies (aOR = 3.72; 95% CI: 2.57–5.40). No significant association was observed for maternal suicidal behavior with cesarean delivery, induction of labor, premature rupture of membranes, excessive fetal growth, and fetal distress. The mean length of stay was longer for women with suicidal behavior. Conclusion During delivery hospitalization, women with suicidal behavior are at increased risk for many adverse obstetric outcomes, highlighting the importance of screening for and providing appropriate clinical care for women with suicidal behavior during pregnancy. PMID:29447245

Fluid Overload and Renal Angina Index at Admission Are Associated With Worse Outcomes in Critically Ill Children.

PubMed

Sethi, Sidharth K; Raghunathan, Veena; Shah, Shilpi; Dhaliwal, Maninder; Jha, Pranaw; Kumar, Maneesh; Paluri, Sravanthi; Bansal, Shyam; Mhanna, Maroun J; Raina, Rupesh

2018-01-01

Objectives: We investigated the association of fluid overload and oxygenation in critically sick children, and their correlation with various outcomes (duration of ventilation, ICU stay, and mortality). We also assessed whether renal angina index (RAI) at admission can predict mortality or acute kidney injury (AKI) on day 3 after admission. Design and setting: Prospective study, pediatric intensive care in a tertiary hospital. Duration: June 2013-June 2014. Patients: Patients were included if they needed invasive mechanical ventilation for >24 h and had an indwelling arterial catheter. Patients with congenital heart disease or those who received renal replacement therapy (RRT) were excluded. Methods: Oxygenation index, fluid overload percent (daily, cumulative), RAI at admission and pediatric logistic organ dysfunction (PELOD) score were obtained in all critically ill children. KDIGO classification was used to define AKI, using both creatinine and urine output criteria. Admission data for determination of RAI included the use of vasopressors, invasive mechanical ventilation, percent fluid overload, and change in kidney function (estimated creatinine clearance). Univariable and multivariable approaches were used to assess the relations between fluid overload, oxygenation index and clinical outcomes. An RAI cutoff >8 was used to predict AKI on day 3 of admission and mortality. Results: One hundred and two patients were recruited. Fluid overload predicted oxygenation index in all patients, independent of age, gender and PELOD score ( p < 0.05). Fluid overload was associated with longer duration of ventilation ( p < 0.05), controlled for age, gender, and PELOD score. Day-3 AKI rates were higher in patients with a RAI of 8 or more, and higher areas under the RAI curve had better prediction rates for Day-3 AKI. An RAI <8 had high negative predictive values (80-95%) for Day-3 AKI. RAI was better than traditional markers of pediatric severity of illness (PELOD) score for

Fluid Overload and Renal Angina Index at Admission Are Associated With Worse Outcomes in Critically Ill Children

PubMed Central

Sethi, Sidharth K.; Raghunathan, Veena; Shah, Shilpi; Dhaliwal, Maninder; Jha, Pranaw; Kumar, Maneesh; Paluri, Sravanthi; Bansal, Shyam; Mhanna, Maroun J.; Raina, Rupesh

2018-01-01

Objectives: We investigated the association of fluid overload and oxygenation in critically sick children, and their correlation with various outcomes (duration of ventilation, ICU stay, and mortality). We also assessed whether renal angina index (RAI) at admission can predict mortality or acute kidney injury (AKI) on day 3 after admission. Design and setting: Prospective study, pediatric intensive care in a tertiary hospital. Duration: June 2013-June 2014. Patients: Patients were included if they needed invasive mechanical ventilation for >24 h and had an indwelling arterial catheter. Patients with congenital heart disease or those who received renal replacement therapy (RRT) were excluded. Methods: Oxygenation index, fluid overload percent (daily, cumulative), RAI at admission and pediatric logistic organ dysfunction (PELOD) score were obtained in all critically ill children. KDIGO classification was used to define AKI, using both creatinine and urine output criteria. Admission data for determination of RAI included the use of vasopressors, invasive mechanical ventilation, percent fluid overload, and change in kidney function (estimated creatinine clearance). Univariable and multivariable approaches were used to assess the relations between fluid overload, oxygenation index and clinical outcomes. An RAI cutoff >8 was used to predict AKI on day 3 of admission and mortality. Results: One hundred and two patients were recruited. Fluid overload predicted oxygenation index in all patients, independent of age, gender and PELOD score (p < 0.05). Fluid overload was associated with longer duration of ventilation (p < 0.05), controlled for age, gender, and PELOD score. Day-3 AKI rates were higher in patients with a RAI of 8 or more, and higher areas under the RAI curve had better prediction rates for Day-3 AKI. An RAI <8 had high negative predictive values (80–95%) for Day-3 AKI. RAI was better than traditional markers of pediatric severity of illness (PELOD) score for

Long-term outcome of pediatric renal transplantation: a single center study in Japan.

PubMed

Yamada, Akio; Tashiro, Atsushi; Hiraiwa, Tomoko; Komatsu, Tomonori; Kinukawa, Tsuneo; Ueda, Norishi

2014-08-01

Little is known about the risk factors for long-term poor outcome in pediatric renal transplantation. Between 1973 and 2010, 111 renal transplants (92 living donations) were performed in 104 children (56 males, mean age, 12.5 yr) at the Social Insurance Chukyo Hospital, and followed-up for a mean period of 13.6 yr. The patient survival at 1, 5, 10, 15, 20 (living- and deceased-donor transplants), and 30 yr (living-donor transplants only) was 98.1%, 92.8%, 87.8%, 84.9%, 82.6%, and 79.3%. The graft survival at 1, 5, 10, 15, 20, and 30 yr was 92.0%, 77.3%, 58.4%, 50.8%, 38.5%, and 33.3%. The most common cause of graft loss was CAI, AR, death with functioning, recurrent primary disease, ATN, and malignancy. Donor gender, ATN, malignancy/cardiovascular events, and eras affected patient survival. AR and CAI were the risk factors for graft loss. The evolved immunosuppression protocols improved the outcome by reducing AR episodes and ATN but not CAI, suggesting CAI as the major risk factor for graft loss. CAI was correlated with AR episodes, CMV infection, and post-transplant hypertension. Strategies for preventing the risk factors for malignancy/cardiovascular events and CAI, including hypertension/infection, are crucial for better outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cigarette smoking and adverse health outcomes among adults receiving federal housing assistance☆

PubMed Central

Helms, Veronica E.; King, Brian A.; Ashley, Peter J.

2017-01-01

Cigarette smoking is higher among low-income adults and individuals who reside in federally assisted housing are particularly susceptible to the adverse effects of smoking and secondhand smoke exposure. This study assessed smoking-related behaviors and health outcomes among U.S. adults who received federal housing assistance during 2006–2012. National Health Interview Survey data linked with administrative data from the U.S. Department of Housing and Urban Development were analyzed; 5218 HUD-assisted adults were assessed. Demographic characteristics associated with smoking, including frequency and consumption, were assessed among adult cigarette smokers. Fourteen adverse health outcomes were examined among cigarette smoking and nonsmoking adults. One-third (33.6%) of HUD-assisted adults were current cigarette smokers. Smoking prevalence was highest among adults aged 25–44 (42.5%), non-Hispanic whites (39.5%), and adults who resided in households with children (37.5%). Half attempted to quit in the past year; 82.1% were daily smokers; and, 35.8% of daily smokers reported smoking 20+ cigarettes a day. Multivariable analyses revealed that compared to nonsmokers, cigarette smokers had increased likelihood of reporting fair or poor health (95% CI: 1.04–1.52), chronic obstructive pulmonary disease (CI: 1.87–3.06), disability (CI: 1.25–1.83), asthma (CI: 1.02–1.55), serious psychological distress (CI: 1.39–2.52), >1 emergency room visit in the past year (CI: 1.09–1.56), and ≥10 work loss days in the past year (CI: 1.15–3.06). Adults who receive housing assistance represent an at-risk population for adverse health outcomes associated with smoking and secondhand smoke. Housing assistance programs provide a valuable platform for the implementation of evidence-based tobacco prevention and control measures, including smokefree policies. PMID:28192095

Cellulitis in Obesity: Adverse Outcomes Affected by Increases in Body Mass Index.

PubMed

Theofiles, Meghan; Maxson, Julie; Herges, Lori; Marcelin, Alberto; Angstman, Kurt B

2015-10-01

Cellulitis in obese patients is associated with increased rates of treatment failure compared to those with normal body mass index (BMI); however, patients have not been extensively studied in the outpatient environment or stratified based on range of obesity and associated risk factors. This study looked at antibiotic dosing and treatment failure in the obese population from the primary care perspective and accounts for BMI range, weight, comorbid diabetes, and tobacco use. This study was a retrospective chart review of 637 adult primary care patients designed to evaluate rates of treatment failure of outpatient cellulitis among patients of varying BMI. Treatment failure was defined as (a) hospital admission for intravenous antibiotics, (b) prolonged antibiotic course, or (c) requiring a different antibiotic after initial course. Adverse outcomes were not statistically significant between normal BMI and those with BMI ≥40 kg/m(2). A subset of patients with a BMI ≥50 kg/m(2) was noted to have approximately twice the rate of adverse outcomes as the normal BMI group. While controlling for age, gender, race, diagnosis of diabetes mellitus, and tobacco use, a BMI of ≥50 kg/m(2) and a weight ≥120 kg was associated with adverse outcomes with an odds ratio of 2.440 (95% CI, 1.260-4.724; P = .008) and 2.246 (95% CI, 1.154-4.369; P = .017), respectively. Patients with cellulitis weighing >120kg or with a BMI ≥50 kg/m(2) were at greatest risk for treatment failure in the outpatient setting, even when controlling for comorbid diabetes and tobacco use. As morbid obesity continues to become more prevalent, it becomes imperative that primary care physicians have better antibiotic dosing guidelines to account for the physiologic effects of obesity to minimize the risk of increased morbidity, health care costs, and antibiotic resistance. © The Author(s) 2015.

Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers.

PubMed

Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A; Andress, Dennis; Brennan, John J; Coll, Blai; Correa-Rotter, Ricardo; Hou, Fan Fan; Kohan, Donald; Kitzman, Dalane W; Makino, Hirofumi; Parving, Hans-Henrik; Perkovic, Vlado; Remuzzi, Giuseppe; Tobe, Sheldon; Toto, Robert; Hoekman, Jarno; Lambers Heerspink, Hiddo J

2016-05-01

A recent phase II clinical trial (Reducing Residual Albuminuria in Subjects with Diabetes and Nephropathy with AtRasentan trial and an identical trial in Japan (RADAR/JAPAN)) showed that the endothelin A receptor antagonist atrasentan lowers albuminuria, blood pressure, cholesterol, hemoglobin, and increases body weight in patients with type 2 diabetes and nephropathy. We previously developed an algorithm, the Parameter Response Efficacy (PRE) score, which translates short-term drug effects into predictions of long-term effects on clinical outcomes. We used the PRE score on data from the RADAR/JAPAN study to predict the effect of atrasentan on renal and heart failure outcomes. We performed a post-hoc analysis of the RADAR/JAPAN randomized clinical trials in which 211 patients with type-2 diabetes and nephropathy were randomly assigned to atrasentan 0.75 mg/day, 1.25 mg/day, or placebo. A PRE score was developed in a background set of completed clinical trials using multivariate Cox models. The score was applied to baseline and week-12 risk marker levels of RADAR/JAPAN participants, to predict atrasentan effects on clinical outcomes. Outcomes were defined as doubling serum creatinine or end-stage renal disease and hospitalization for heart failure. The PRE score predicted renal risk changes of -23% and -30% for atrasentan 0.75 and 1.25 mg/day, respectively. PRE scores also predicted a small non-significant increase in heart failure risk for atrasentan 0.75 and 1.25 mg/day (+2% vs. +7%). Selecting patients with >30% albuminuria reduction from baseline (responders) improved renal outcome to almost 50% risk reduction, whereas non-responders showed no renal benefit. Based on the RADAR/JAPAN study, with short-term changes in risk markers, atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit

Rifampicin-Induced Concomitant Renal Injury and Hepatitis

PubMed Central

Chogtu, Bharti; Surendra, Vyshak Uddur; Acharya, Preetam Rajgopal; Yerrapragada, Devesh Bhaskar

2016-01-01

Adverse drug reactions are not unusual during Anti-Tubercular Therapy (ATT). One of the common complications of anti-tubercular treatment is drug induced hepatitis and renal insufficiency has also been reported. Renal failure and/or hepatitis encountered during treatment of tuberculosis can have varied aetiologies: drug induced, concomitant viral infection, pre-existing co-morbidities or a combination of these. Since, hepatitis and/or renal insufficiency can be life threatening a prompt diagnosis is warranted, where drugs should be kept as one of the important cause. Identifying the drug helps in treating hepatitis and/or renal insufficiency along with helping the physician to change the combination of ATT regimen. Rifampicin is one of the most important first line drugs in the treatment of tuberculosis. Hepatitis, epigastric distress, anaemia, thrombocytopenia, and interstitial nephritis are reported adverse drug reactions to rifampicin. As per literature rifampicin induced renal toxicity is usually seen on rifampicin re-exposure, or rifampicin administration on alternate days, both being present in this case. Here we are reporting a case of ATT induced renal failure with concomitant hepatitis where rifampicin was suspected to be the cause. PMID:27790502

Tiered Approaches to Incorporate the Adverse Outcome Pathway Framework into Chemical-Specific Risk-Based Decision Making

EPA Science Inventory

The concept of Adverse Outcome Pathways (AOPs) arose as a means of addressing the challenges associated with establishing relationships between high-throughout (HT) in vitro dose response data and in vivo biological outcomes. However, AOP development has also been met with challe...

The household food insecurity gradient and potential reductions in adverse population mental health outcomes in Canadian adults.

PubMed

Jessiman-Perreault, Geneviève; McIntyre, Lynn

2017-12-01

Household food insecurity is related to poor mental health. This study examines whether the level of household food insecurity is associated with a gradient in the risk of reporting six adverse mental health outcomes. This study further quantifies the mental health impact if severe food insecurity, the extreme of the risk continuum, were eliminated in Canada. Using a pooled sample of the Canadian Community Health Survey (N = 302,683), we examined the relationship between level of food insecurity, in adults 18-64 years, and reporting six adverse mental health outcomes. We conducted a probit analysis adjusted for multi-variable models, to calculate the reduction in the odds of reporting mental health outcomes that might accrue from the elimination of severe food insecurity. Controlling for various demographic and socioeconomic covariates, a food insecurity gradient was found in six mental health outcomes. We calculated that a decrease between 8.1% and 16.0% in the reporting of these mental health outcomes would accrue if those who are currently severely food insecure became food secure, after controlling for covariates. Household food insecurity has a pervasive graded negative effect on a variety of mental health outcomes, in which significantly higher levels of food insecurity are associated with a higher risk of adverse mental health outcomes. Reduction of food insecurity, particularly at the severe level, is a public health concern and a modifiable structural determinant of health worthy of macro-level policy intervention.

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

EPA Science Inventory

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecula...

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

PubMed

Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

2017-03-01

Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1

Predictors and Outcomes of Postcontrast Acute Kidney Injury after Endovascular Renal Artery Intervention.

PubMed

Takahashi, Edwin A; Kallmes, David F; Fleming, Chad J; McDonald, Robert J; McKusick, Michael A; Bjarnason, Haraldur; Harmsen, William S; Misra, Sanjay

2017-12-01

To determine incidence, predictors, and clinical outcomes of postcontrast acute kidney injury (PC-AKI) following renal artery stent placement for atherosclerotic renal artery stenosis. This retrospective study reviewed 1,052 patients who underwent renal artery stent placement for atherosclerotic renal artery stenosis; 437 patients with follow-up data were included. Mean age was 73.6 years ± 8.3. PC-AKI was defined as absolute serum creatinine increase ≥ 0.3 mg/dL or percentage increase in serum creatinine ≥ 50% within 48 hours of intervention. Logistic regression analysis was performed to identify risk factors for PC-AKI. The cumulative proportion of patients who died or went on to hemodialysis was determined using Kaplan-Meier survival analysis. Mean follow-up was 71.1 months ± 68.4. PC-AKI developed in 26 patients (5.9%). Patients with PC-AKI had significantly higher levels of baseline proteinuria compared with patients without PC-AKI (odds ratio = 1.38; 95% confidence interval, 1.11-1.72; P = .004). Hydration before intervention, chronic kidney disease stage, baseline glomerular filtration rate, statin medications, contrast volume, and iodine load were not associated with higher rates of PC-AKI. Dialysis-free survival and mortality rates were not significantly different between patients with and without PC-AKI (P = .50 and P = .17, respectively). Elevated baseline proteinuria was the only predictor for PC-AKI in patients undergoing renal artery stent placement. Patients who developed PC-AKI were not at greater risk for hemodialysis or death. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Management and Outcomes of ST-Segment Elevation Myocardial Infarction in US Renal Transplant Recipients.

PubMed

Gupta, Tanush; Kolte, Dhaval; Khera, Sahil; Goel, Kashish; Aronow, Wilbert S; Cooper, Howard A; Jain, Diwakar; Rihal, Charanjit S; Fonarow, Gregg C; Panza, Julio A; Bhatt, Deepak L

2017-03-01

Renal transplantation is associated with reduction in the risk for myocardial infarction (MI) in patients with chronic kidney disease requiring long-term dialysis (stage 5D CKD). Whether outcomes of MI differ among renal transplant recipients vs patients with stage 5D CKD or those without CKD has not been well examined. To compare in-hospital reperfusion rates and outcomes of ST-segment elevation MI (STEMI) in renal transplant recipients vs the stage 5D CKD group or the non-CKD group. The National Inpatient Sample database was queried to identify patients 18 years or older who were hospitalized with the principal diagnosis of STEMI. All hospitalizations for STEMI in the United States from January 1, 2003, to December 31, 2013, were included. Codes from International Classification of Diseases, Ninth Revision, Clinical Modification, were used to identify patients in the non-CKD, stage 5D CKD, or prior renal transplant groups. Data were analyzed from March to May 2016. In-hospital mortality. From 2003 to 2013, 2 319 002 patients in the non-CKD group (34.7% women; 65.3% men; mean [SD] age, 64.2 [14.4] years), 30 072 patients in the stage 5D CKD group (45.0% women; 55.0% men; mean [SD] age, 66.9 [12.5] years), and 2980 patients in the renal transplant group (27.3% women; 72.7% men; mean [SD] age, 57.5 [11.1] years) were identified who were hospitalized with STEMI. Of these, 68.9% of the patients in the non-CKD group, 39.5% in the stage 5D CKD group, and 65.2% in the renal transplant group received in-hospital reperfusion for STEMI. The renal transplant group was more likely to receive reperfusion compared with the stage 5D CKD group (adjusted odds ratio [AOR], 1.83; 95% CI, 1.67-2.01; P < .001) but less likely compared with the non-CKD group (AOR, 0.75; 95% CI, 0.68-0.83; P < .001). Risk-adjusted in-hospital mortality among the renal transplant group with STEMI was markedly lower compared with the stage 5D CKD group (AOR, 0.37; 95% CI, 0.33-0.43; P�

Conceptualizing adverse outcome pathways for ...

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