Publications by authors named "John Schomberg"

14 Publications

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Novel use of a midline catheter for therapeutic and donor apheresis in children and adults.

J Clin Apher 2021 Jul 5. Epub 2021 Jul 5.

CHOC Children's, Orange, California, USA.

Background: Apheresis procedures require adequate vascular access to achieve optimal inlet flow rates. While central lines provide such access, their placement and use are associated with risks; some of these risks are minimized if peripheral intravenous access can be established. However, peripheral intravenous access is associated with challenges in the pediatric setting. Research indicates that midline catheters reduce the use of CVADs and their associated risks. The use of midline catheters for apheresis has been reported recently in adults, but no studies have been published on their use in children. Thus, the purpose of this study was to evaluate the use of midline catheters for apheresis in the pediatric setting.

Methods: A retrospective observational study was conducted to evaluate the safety and efficacy of midline catheters in subjects who underwent apheresis at a pediatric hospital from April 2018 to August 2020. Demographic data, clinical data (diagnosis, procedure, catheter size, body mass), and outcome data (inlet flow rate, total blood volume [TBV] processed, procedure time, and cell counts) were collected.

Results: Eighteen subjects received a total of 100 midline catheters for 73 apheresis procedures. Inlet flow rates ranged from 45 to 80 mL/min, TBV ranged from 2872 to 20 000 mL, and procedure time ranged from 1.25 to 7 hours. Inlet flow rates met or exceeded the recommended inlet flow rates for apheresis in children and adults (P < .0001). No adverse events occurred.

Conclusion: Midline catheters provide safe and effective vascular access for apheresis. Future research should include younger patients with lower body mass.
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http://dx.doi.org/10.1002/jca.21919DOI Listing
July 2021

Analysis of Unintentional Falls in Pediatric Population and Predictors of Morbidity.

J Surg Res 2021 Jun 12;267:48-55. Epub 2021 Jun 12.

Division of Pediatric Surgery, Children's Hospital of Orange County, Orange, California.

Introduction: Unintentional falls are a leading cause of pediatric traumatic injury. This study evaluates clinical outcomes of fall-related injuries in children under the age of 10.

Methods: The National Trauma Database was queried for children who experienced an unintentional fall. Patients were stratified by age in two groups: 1-5 and 6-10 years old. The primary outcome was post discharge extension of care, defined as transfer to skilled nursing facility or rehabilitation center after discharge from the hospital. Descriptive statistics and a multivariable logistic regression analysis were used to compare the two groups.

Results: From 2009 to 2016, a total of 8,277 pediatric patients experienced an unintentional fall, with 93.6% of patients being discharged home. Falls were more common in younger children, with greater odds of post discharge extension of care. Predictors of increased associated risk of extended medical care included intracranial hemorrhage (OR 1.05, 95% CI 1.03-1.06) and thoracic injuries (OR 1.03, 95% CI 1.00-1.1.05) (P< 0.05). Mortality in pediatric patients suffering unintentional falls was a rare event occurring in 0.7% of cases in children 1-5 years old and 0.4% of children 6-10 years old.

Conclusion: The majority of children experiencing an unintentional fall are discharged home, with mortality being very rare. However, younger age is prone to more severe and serious injury patterns. Intracranial hemorrhage and thoracic injury were a predictor of need for extended medical care.
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http://dx.doi.org/10.1016/j.jss.2021.04.036DOI Listing
June 2021

Provider Antibody Serology Study of Virus in the Emergency Room (PASSOVER) Study: Special Population COVID-19 Seroprevalence.

West J Emerg Med 2021 Apr 9;22(3):565-571. Epub 2021 Apr 9.

Children's Hospital of Orange County, Research Institute, Orange, California.

Introduction: Limited data on the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among healthcare workers (HCW) are publicly available. In this study we sought to determine the seroprevalence of SARS-CoV-2 in a population of HCWs in a pediatric emergency department (ED).

Methods: We conducted this observational cohort study from April 14-May 13, 2020 in a pediatric ED in Orange County, CA. Asymptomatic HCW ≥18 years of age were included in the study. Blood samples were obtained by fingerstick at the start of each shift. The inter-sampling interval was ≤96 hours. The primary outcome was positive seroprevalence of SARS-CoV-2 as determined with an antibody fast detection kit (Colloidal Gold, Superbio, Timisoara, Romania) for the SARS-CoV-2 immunoglobulin M/immunoglobulin G (IgM/IgG) antibody.

Results: A total of 143 HCWs participated in the study. Overall SARS-CoV-2 seroprevalence was 10.5% (n = 15). Positive seroprevalence was classified as IgG only (4.9%), IgM+IgG (3.5%), or IgM only (2.1%). SARS-CoV-2 was detected by reverse transcription polymerase chain reaction RT-PCR in 0.7% of the overall study population (n = 1). Samples obtained on Day 1 indicated seropositivity in 4.2% of the study population (n = 6). Subsequent seroconversion occurred in 6.3% of participants (n = 9). The rate of seroconversion was linear with a rate of approximately one new case every two days, starting at Day 9 of the study.

Conclusion: We observed a linear rate of seroconversion to SARS-CoV-2-positive status among asymptomatic HCWs who underwent daily symptom surveys and temperature screens in an environment with universal source control. Rapid antibody testing may be useful for screening for SARS-CoV-2 seropositivity in high-risk populations, such as HCWs in the ED.
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http://dx.doi.org/10.5811/westjem.2021.1.50058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203005PMC
April 2021

COVID-19: Differences in sentinel injury and child abuse reporting during a pandemic.

Child Abuse Negl 2021 06 8;116(Pt 2):104990. Epub 2021 Mar 8.

Children's Health of Orange County, Orange, CA, United States; Emergency Department, University of California, Irvine, United States. Electronic address:

Background And Objectives: There is widespread concern that the COVID-19 pandemic has increased the incidence of child maltreatment. However, reports in the scientific literature documenting rates of child maltreatment during this period are scarce. This study was designed to explore whether the incidence of child maltreatment among patients presenting to a pediatric emergency department has increased during the COVID-19 pandemic.

Methods: We conducted a retrospective review of patients of all ages presenting to a pediatric Emergency Department trauma center, who also had a child abuse report filing or a sentinel injury diagnosis related to their index visit. All such patients who presented to this institution from March through July of 2017 through 2020 were included in the study.

Results: Analysis demonstrated an increase in the incidence of child maltreatment in May and June of 2020 and that there was an overall shift in distribution of types of child maltreatment during the COVID-19 pandemic. There was a significant increase in the proportion of emotional/psychological abuse (2.52 % before the pandemic to 7.00 % during the pandemic, p ≤ 0.0001) and non-medical neglect (31.5%-40.0%, p ≤ 0.0001).

Conclusions: We observed an increase in specific types of child maltreatment during the COVID-19 pandemic. These findings highlight the need for increased attention to children at risk for child abuse and neglect.
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http://dx.doi.org/10.1016/j.chiabu.2021.104990DOI Listing
June 2021

Risk Factors for Hemolysis During Extracorporeal Life Support for Congenital Diaphragmatic Hernia.

J Surg Res 2021 Jul 20;263:14-23. Epub 2021 Feb 20.

Department of Medicine, Irvine School of Medicine, University of California, Irvine, California.

Background: Neonates receiving extracorporeal life support (ECLS) for congenital diaphragmatic hernia (CDH) require prolonged support compared with neonates with other forms of respiratory failure. Hemolysis is a complication that can be seen during ECLS and can lead to renal failure and potentially to worse outcomes. The purpose of this study was to identify risk factors for the development of hemolysis in CDH patients treated with ECLS.

Methods: The Extracorporeal Life Support Organization database was used to identify infants with CDH (2000-2015). The primary outcome was hemolysis (plasma-free hemoglobin >50 mg/dL). Potentially associated variables were identified in the data set. Descriptive statistics and a series of nested multivariable logistic regression models were used to identify associations between hemolysis and demographic, pre-ECLS, and on-ECLS factors.

Results: There were 4576 infants with a mortality of 52.5%. The overall mean rate of hemolysis was 10.5% during the study period. In earlier years (2000-2005), the hemolysis rates were 6.3% and 52.7% for roller versus centrifugal pumps, whereas in later years (2010-2015), they were 2.9% and 26.5%, respectively. The fully adjusted model demonstrated that the use of centrifugal pumps was a strong predictor of hemolysis (odds ratio: 6.67, 95% confidence interval: 5.14-8.67). In addition, other risk factors for hemolysis included low 5-min Apgar score, on-ECLS complications (renal, metabolic, and cardiovascular), and duration of ECLS.

Conclusions: In our cohort of CDH patients receiving ECLS over 15 y, the use of centrifugal pumps increased over time, along with the rate of hemolysis. Patient- and treatment-level risk factors were identified contributing to the development of hemolysis.
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http://dx.doi.org/10.1016/j.jss.2021.01.007DOI Listing
July 2021

Are routine chest X-rays following chest tube removal necessary in asymptomatic pediatric patients?

Pediatr Surg Int 2021 May 1;37(5):631-637. Epub 2021 Jan 1.

Department of Clinical Education and Professional Development, CHOC Children's Hospital of Orange County, 1201 W. La Veta Avenue, Orange, CA, 92868, USA.

Purpose: The purpose of this study was to determine if routine chest X-rays (CXRs) performed after chest tube (CT) removal in pediatric patients provide additional benefit for clinical management compared to observation of symptoms alone.

Methods: A single-center retrospective study was conducted of inpatients, 18 years or younger, who had a CT managed by the pediatric surgery team between July 2017 and May 2019. The study compared two groups: (1) patients who received a post-pull CXR and (2) those who did not. The primary outcome of the study was the need for intervention after CT removal.

Results: 102 patients had 116 CTs and met inclusion criteria; 79 post-pull CXRs were performed; the remaining 37 CT pulls did not have a follow-up CXR. No patients required CT replacement or surgery in the absence of symptoms. Three patients exhibited clinical symptoms that would have prompted intervention regardless of post-pull CXR results. One patient had an intervention guided by post-pull CXR results alone. Meanwhile, another patient had delayed onset of symptoms and intervention. No patients required an intervention in the group that did not have a post-pull CXR.

Conclusion: Chest X-ray after CT removal had a very low yield for changing clinical management of asymptomatic patients. Clinical symptoms predict the need for an intervention.
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http://dx.doi.org/10.1007/s00383-020-04809-7DOI Listing
May 2021

Prolonged hospital length of stay in pediatric trauma: a model for targeted interventions.

Pediatr Res 2020 Nov 12. Epub 2020 Nov 12.

CHOC Children's Hospital, Orange, CA, USA.

Background: In this study, trauma-specific risk factors of prolonged length of stay (LOS) in pediatric trauma were examined. Statistical and machine learning models were used to proffer ways to improve the quality of care of patients at risk of prolonged length of stay and reduce cost.

Methods: Data from 27 hospitals were retrieved on 81,929 hospitalizations of pediatric patients with a primary diagnosis of trauma, and for which the LOS was >24 h. Nested mixed effects model was used for simplified statistical inference, while a stochastic gradient boosting model, considering high-order statistical interactions, was built for prediction.

Results: Over 18.7% of the encounters had LOS >1 week. Burns and corrosion and suspected and confirmed child abuse are the strongest drivers of prolonged LOS. Several other trauma-specific and general pediatric clinical variables were also predictors of prolonged LOS. The stochastic gradient model obtained an area under the receiver operator characteristic curve of 0.912 (0.907, 0.917).

Conclusions: The high performance of the machine learning model coupled with statistical inference from the mixed effects model provide an opportunity for targeted interventions to improve quality of care of trauma patients likely to require long length of stay.

Impact: Targeted interventions on high-risk patients would improve the quality of care of pediatric trauma patients and reduce the length of stay. This comprehensive study includes data from multiple hospitals analyzed with advanced statistical and machine learning models. The statistical and machine learning models provide opportunities for targeted interventions and reduction in prolonged length of stay reducing the burden of hospitalization on families.
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http://dx.doi.org/10.1038/s41390-020-01237-0DOI Listing
November 2020

Luteolin inhibits melanoma growth in vitro and in vivo via regulating ECM and oncogenic pathways but not ROS.

Biochem Pharmacol 2020 07 13;177:114025. Epub 2020 May 13.

Department of Medicine, University of California Irvine, Irvine, CA 92697, United States; Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA 92697, United States; Department of Epidemiology, University of California Irvine, Irvine, CA 92697, United States. Electronic address:

Luteolin inhibited growth of several cancer cells in vitro in previous studies, with limited in vivo studies, and no comprehensive understanding of molecular mechanisms at genomics level. This study identified luteolin as an effective agent to inhibit melanoma cell growth in vitro and in vivo. Molecular studies and genomic profiling were used to identify the mechanism of action of luteolin in melanoma cells. As a ROS (reactive oxygen species) scavenger, luteolin unexpectedly induced ROS; but co-treatment with antioxidants NAC or mito-TEMPO did not rescue cell growth inhibition, although the levels of ROS levels were reduced. Next, we profiled luteolin-induced differentially expressed genes (DEGs) in 4 melanoma cell lines using RNA-Seq, and performed pathway analysis using a combination of bioinformatics software including PharmetRx which was especially effective in discovering pharmacological pathways for potential drugs. Our results show that luteolin induces changes in three main aspects: the cell-cell interacting pathway (extracellular matrix, ECM), the oncogenic pathway and the immune response signaling pathway. Based on these results, we further validated that luteolin was especially effective in inhibiting cell proliferation when cells were seeded at low density, concomitantly with down-regulation of fibronectin accumulation. In conclusion, through extensive DEG profiling in a total of 4 melanoma cell lines, we found that luteolin-mediated growth inhibition in melanoma cells was perhaps not through ROS induction, but likely through simultaneously acting on multiple pathways including the ECM (extracellular matrix) pathway, the oncogenic signaling and the immune response pathways. Further investigations on the mechanisms of this promising compound are warranted and likely result in application to cancer patients as its safety pharmacology has been validated in autism patients.
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http://dx.doi.org/10.1016/j.bcp.2020.114025DOI Listing
July 2020

Identification of Targetable Pathways in Oral Cancer Patients via Random Forest and Chemical Informatics.

Authors:
John Schomberg

Cancer Inform 2019 28;18:1176935119889911. Epub 2019 Nov 28.

CHOC Children's, Orange, CA, USA.

Treatment of head and neck cancer has been slow to change with epidermal growth factor receptor (EGFR) inhibitors, PD1 inhibitors, and taxane-/plant-alkaloid-derived chemotherapies being the only therapies approved by the U.S. Food and Drug Administration (FDA) in the last 10 years for the treatment of head and neck cancers. Head and neck cancer is a relatively rare cancer compared to breast or lung cancers. However, it is possible that existing therapies for more common solid tumors or for the treatment of other diseases could also prove effective against oral cancers. Many therapies have molecular targets that could be appropriate in oral cancer as well as the cancer in which the drug gained initial FDA approval. Also, there may be targets in oral cancer for which existing FDA-approved drugs could be applied. This study describes informatics methods that use machine learning to identify influential gene targets in patients receiving platinum-based chemotherapy, non-platinum-based chemotherapy, and genes influential in both groups of patients. This analysis yielded 6 small molecules that had a high Tanimoto similarity (>50%) to ligands binding genes shown to be highly influential in determining treatment response in oral cancer patients. In addition to influencing treatment response, these genes were also found to act as gene hubs connected to more than 100 other genes in pathways enriched with genes determined to be influential in treatment response by a random forest classifier with 20 000 trees trying 320 variables at each tree node. This analysis validates the use of multiple informatics methods to identify small molecules that have a greater likelihood of efficacy in a given cancer of interest.
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http://dx.doi.org/10.1177/1176935119889911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883365PMC
November 2019

Identification of a gene expression signature predicting survival in oral cavity squamous cell carcinoma using Monte Carlo cross validation.

Oral Oncol 2018 03 20;78:72-79. Epub 2018 Feb 20.

Department of Epidemiology School of Medicine, University of California, Irvine, Irvine, CA 92617, United States.

Objectives: This study aims to identify a robust signature that performs well in predicting overall survival across tumor phenotypes and treatment strata, and validates the application of Monte Carlo cross validation (MCCV) as a means of identifying molecular signatures when utilizing small and highly heterogeneous datasets.

Materials And Methods: RNA sequence gene expression data for 264 patient tumors were acquired from The Cancer Genome Atlas (TCGA). 100 iterations of Monte Carlo cross validation were applied to differential expression and Cox model validation. The association between the gene signature risk score and overall survival was measured using Kaplan-Meier survival curves, univariate, and multivariable Cox regression analyses.

Results: Pathway analysis findings indicate that ligand-gated ion channel pathways are the most significantly enriched with the genes in the aggregated signature. The aggregated signature described in this study is predictive of overall survival in oral cancer patients across demographic and treatment strata.

Conclusion: This study reinforces previous findings supporting the role of ion channel gating, interleukin, calcitonin receptor, and keratinization pathways in tumor progression and treatment response in oral cancer. These results strengthen the argument that differential expression of genes within these pathways reduces tumor susceptibility to treatment. Conducting differential gene expression (DGE) with Monte Carlo cross validation, as this study describes, offers a potential solution to decreasing the variability in DGE results across future studies that are reliant upon highly heterogeneous datasets. This improves the ability of studies reliant upon similarly structured datasets to reach results that are reproducible.
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http://dx.doi.org/10.1016/j.oraloncology.2018.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853240PMC
March 2018

Successful Conversion From Parenteral Paricalcitol to Pulse Oral Calcitriol for the Management of Secondary Hyperparathyroidism in Hemodialysis Patients.

J Ren Nutr 2016 07 30;26(4):265-9. Epub 2016 Mar 30.

Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, California. Electronic address:

Objective: The management of hyperparathyroidism in hemodialysis patients involves the administration of phosphate binders, vitamin D receptor activators, and calcimimetics. Intravenous paricalcitol has been preferred over oral calcitriol as it may cause less hypercalcemia and hyperphosphatemia. However, there is little data looking at the efficacy and tolerability of oral calcitriol in the calcimimetic era particularly in a real practice-based experience. The University of California, Irvine free-standing dialysis center converted from routine intravenous paricalcitol to oral calcitriol due to pharmacy purchasing preferences. We report the efficacy, safety, and cost of such a change.

Subjects: Ninety-three preconversion intravenous paricalcitol and 91 postconversion oral calcitriol.

Intervention: Conversion to in-center, pulse, oral calcitriol (0.25 mcg = 1 mcg paricalcitol) 3 times a week from intravenous paricalcitol. Additional dose adjustments were made by the nephrologists based on clinical indications.

Main Outcome Measure: Five-month average serum calcium, phosphorous, and intact parathyroid hormone levels and cardiovascular events pretransition and posttransition.

Results: There were 93 patients on intravenous paricalcitol between April 2013 and August 2013, of which 74 converted to oral calcitriol and were included in the postconversion group evaluated between October 2013 and February 2014. An additional 17 new patients had initiated calcitriol such that 91 patients were on oral therapy in the postconversion period. Sevelamer use increased from 41 (44.1%) patients preconversion to 48 (52.7%) postconversion, whereas calcium acetate use significantly dropped from 62 (66.7%) to 46 (50.5%) (P = .026). Cinacalcet use dropped slightly from 37 (39.7%) patients preconversion to 35 (38.4%) postconversion. Average serum calcium, phosphorus, and intact parathyroid hormone levels remained unchanged after conversion. Percent of values within Kidney Disease Outcome Quality Initiative guidelines were similarly maintained. Estimated vitamin D cost savings were $564 per person/year. No increase in the incidence of cardiovascular events was observed.

Conclusions: We conclude that in-center distributed pulse oral calcitriol may be an effective, safe, and economical treatment option for the management of hyperparathyroidism in hemodialysis patients.
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http://dx.doi.org/10.1053/j.jrn.2016.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912884PMC
July 2016

Supplementing Public Health Inspection via Social Media.

PLoS One 2016 29;11(3):e0152117. Epub 2016 Mar 29.

Department of Epidemiology School of Medicine, University of California Irvine, Irvine, CA, United States of America.

Foodborne illness is prevented by inspection and surveillance conducted by health departments across America. Appropriate restaurant behavior is enforced and monitored via public health inspections. However, surveillance coverage provided by state and local health departments is insufficient in preventing the rising number of foodborne illness outbreaks. To address this need for improved surveillance coverage we conducted a supplementary form of public health surveillance using social media data: Yelp.com restaurant reviews in the city of San Francisco. Yelp is a social media site where users post reviews and rate restaurants they have personally visited. Presence of keywords related to health code regulations and foodborne illness symptoms, number of restaurant reviews, number of Yelp stars, and restaurant price range were included in a model predicting a restaurant's likelihood of health code violation measured by the assigned San Francisco public health code rating. For a list of major health code violations see (S1 Table). We built the predictive model using 71,360 Yelp reviews of restaurants in the San Francisco Bay Area. The predictive model was able to predict health code violations in 78% of the restaurants receiving serious citations in our pilot study of 440 restaurants. Training and validation data sets each pulled data from 220 restaurants in San Francisco. Keyword analysis of free text within Yelp not only improved detection of high-risk restaurants, but it also served to identify specific risk factors related to health code violation. To further validate our model we applied the model generated in our pilot study to Yelp data from 1,542 restaurants in San Francisco. The model achieved 91% sensitivity 74% specificity, area under the receiver operator curve of 98%, and positive predictive value of 29% (given a substandard health code rating prevalence of 10%). When our model was applied to restaurant reviews in New York City we achieved 74% sensitivity, 54% specificity, area under the receiver operator curve of 77%, and positive predictive value of 25% (given a prevalence of 12%). Model accuracy improved when reviews ranked highest by Yelp were utilized. Our results indicate that public health surveillance can be improved by using social media data to identify restaurants at high risk for health code violation. Additionally, using highly ranked Yelp reviews improves predictive power and limits the number of reviews needed to generate prediction. Use of this approach as an adjunct to current risk ranking of restaurants prior to inspection may enhance detection of those restaurants participating in high risk practices that may have gone previously undetected. This model represents a step forward in the integration of social media into meaningful public health interventions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152117PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811425PMC
August 2016

Sevelamer carbonate increases serum bicarbonate in pediatric dialysis patients.

Pediatr Nephrol 2010 Feb 30;25(2):373-5. Epub 2009 Oct 30.

Division of Pediatric Nephrology, Department of Pediatrics, Mattel Children's Hospital at UCLA, Box 951752, Los Angeles, CA 90095-1752, USA.

Sevelamer hydrochloride (HCl), a calcium-free phosphate binder, is increasingly used due to concerns related to calcium exposure and the development of vascular calcifications. However, a common side effect of sevelamer HCl, metabolic acidosis, is particularly concerning in children, as it can contribute to poor growth. Sevelamer carbonate is now available and has been shown to increase serum bicarbonate in adult patients. We conducted a prospective single-center study of pediatric dialysis patients comparing serum bicarbonate before and 3 months after a switch from sevelamer HCl to sevelamer carbonate. Inclusion criteria were a minimum of 3 months of dialysis therapy and either a serum bicarbonate <20 mmol/L or the need for sodium bicarbonate supplementation. Ten hemodialysis and 14 peritoneal dialysis patients, aged 16 +/- 3 years, were enrolled. Whereas serum calcium and phosphorus remained unchanged, serum bicarbonate increased from 20 (17.2-22.0) to 24.5 (20.75-26) mmol/L (p < 0.001) after 3 months of sevelamer carbonate therapy. Sodium bicarbonate supplementation was stopped in all patients (n = 10), reducing the mean daily sodium intake by an average of 2.3 g per patient. These results demonstrate that sevelamer carbonate is an effective phosphate binder that improves acid-base status in pediatric dialysis patients.
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http://dx.doi.org/10.1007/s00467-009-1328-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811522PMC
February 2010