Shaw A.D.,Duke University |
Bagshaw S.M.,University of Alberta |
Goldstein S.L.,Cincinnati Childrens Hospital |
Scherer L.A.,University of California at Davis |
And 3 more authors.
Annals of Surgery | Year: 2012
Objective: To assess the association of 0.9% saline use versus a calcium-free physiologically balanced crystalloid solution with major morbidity and clinical resource use after abdominal surgery. Background: 0.9% saline, which results in a hyperchloremic acidosis after infusion, is frequently used to replace volume losses after major surgery. Methods: An observational study using the Premier Perspective Comparative Database was performed to evaluate adult patients undergoing major open abdominal surgery who received either 0.9% saline (30,994 patients) or a balanced crystalloid solution (926 patients) on the day of surgery. The primary outcome was major morbidity and secondary outcomes included minor complications and acidosis-related interventions. Outcomes were evaluated using multivariable logistic regression and propensity scoring models. RESULTS:: For the entire cohort, the in-hospital mortality was 5.6% in the saline group and 2.9% in the balanced group (P < 0.001). One or more major complications occurred in 33.7% of the saline group and 23% of the balanced group (P < 0.001). In the 3:1 propensity-matched sample, treatment with balanced fluid was associated with fewer complications (odds ratio 0.79; 95% confidence interval 0.66-0.97). Postoperative infection (P = 0.006), renal failure requiring dialysis (P < 0.001), blood transfusion (P < 0.001), electrolyte disturbance (P = 0.046), acidosis investigation (P < 0.001), and intervention (P = 0.02) were all more frequent in patients receiving 0.9% saline. Conclusions: Among hospitals in the Premier Perspective Database, the use of a calcium-free balanced crystalloid for replacement of fluid losses on the day of major surgery was associated with less postoperative morbidity than 0.9% saline. © 2012 by Lippincott Williams & Wilkins.
Marik P.E.,Thomas Jefferson University |
Zaloga G.P.,Baxter Healthcare
Journal of Parenteral and Enteral Nutrition | Year: 2010
Background: Immunomodulating diets (IMDs) have been demonstrated to improve immune function and modulate inflammation. However, the clinical benefit of these diets in patients undergoing elective surgery is controversial. The goal of this meta-analysis was to determine the impact of IMDs on the clinical outcomes of high-risk patients undergoing elective surgery. Methods: The review included prospective, controlled, clinical trials that compared the clinical outcome of elective surgical patients who were randomized to receive an IMD or a control enteral diet. Studies were stratified according to the type of IMD and the timing of the initiation of the IMD. Data were abstracted on study design, study size, patient population, and IMD used. The outcomes of interest were the acquisition of new infections, wound complications, length of hospital stay (LOS), and mortality. Meta-analytic techniques were used to analyze the data. Results: Twenty-one relevant studies were identified, which included a total of 1918 patients. Immunonutrition significantly reduced the risk of acquired infections, wound complications, and LOS. The mortality rate was 1% in both groups. The treatment effect was similar regardless of the timing of the commencement of the IMD. The benefits of immunonutrition required both arginine and fish oil. Conclusions: An immunomodulating enteral diet containing increased amounts of both arginine and fish oil should be considered in all high-risk patients undergoing major surgery. Although the optimal timing cannot be determined from this study, it is suggested that immunonutrition be initiated preoperatively when feasible.
Mehrotra R.,University of California at Los Angeles |
Story K.,Baxter Healthcare |
Guest S.,Baxter Healthcare |
Fedunyszyn M.,University of California at Los Angeles
Peritoneal Dialysis International | Year: 2012
Background: The adjusted 5-year survival for dialysis patients in the United States is 33%-35%, and patients treated with peritoneal dialysis (PD) have a high risk of transfer to hemodialysis (HD). No data are available on the effect of neighborhood characteristics or regional differences on the outcomes of PD patients in the United States. Methods: We analyzed the relationships of selected patient demographics, socio-economic characteristics of the dialysis unit's neighborhood, "rurality," and geographic location with transfer to HD and with a composite outcome of transfer to HD or death, for all PD patients in the United States who, between 2004 and 2009, used supplies manufactured by Baxter Healthcare (n = 58700). Results: Over a median follow-up of 18.7 months, 29% of patients transferred to HD (median time to HD transfer: 49 months), and 54% reached the composite outcome. More than 20% of the events occurred within the first 90 days of PD start. The risk for each of the study outcomes was higher for patients who had received any previous treatment with HD, for those treated in units located in areas with a higher proportion of black residents, and for those living in remote rural areas. Furthermore, the risk for reaching either of the study outcomes was consistently lower for patients treated in units located in California, Alaska, Hawaii, Guam, the Mariana Islands, and American Samoa. Conclusions: We observed significant regional differences in the outcomes of PD patients in the United States that have not previously been reported. Understanding the differences in clinical practice that underlie these regional differences might help to further improve PD outcomes. © 2012 International Society for Peritoneal Dialysis.
Baxter International and Baxter Healthcare | Date: 2011-07-07
A liquid or liquid-frozen composition comprising: a modified vaccinia Ankara (MVA) virus or variant or derivative thereof and mannitol, wherein mannitol is the sole stabilization agent of the composition. The mannitol may provide a stabilizing effect at 0 to +10 C. or in a liquid-frozen composition, for example between 10 C. and 30 C. or between 20 C. and 23.5 C. The MVA may be used as a vaccine or for use in gene therapy, virotherapy, immunotherapy, or cancer therapy in a mammal, preferably a human.
Kreymann G.,Baxter Healthcare SA Europe |
DeLegge M.H.,Baxter Healthcare |
Luft G.,Baxter Healthcare SA Europe |
Hise M.E.,Baxter Healthcare |
Zaloga G.P.,Baxter Healthcare
Clinical Nutrition | Year: 2012
Background & aims: The ratio of energy expenditure to nitrogen loss respectively of energy to nitrogen provision (E/N) is considered a valuable tool in the creation of an enteral or parenteral formulation. Specific E/N ratios for parenteral nutrition (PN) have not yet been clearly defined. To determine the range of energy expenditure, nitrogen (protein) losses, and E/N ratios for various patient groups, we performed a systematic review of the literature. Methods: Medline 1950-2011 was searched for all studies on patients or healthy controls reporting energy expenditure and nitrogen loss at the same time. Results: We identified 53 studies with 91 cohorts which comprised 1107 subjects. Mean TEE ± standard deviation (SD) was 31.2 ± 7.2 kcal/kg BW/day in patients (n = 881) and 35.6 ± 4.3 kcal/kg BW/day in healthy controls (n = 266). Mean total protein loss (TPL) was 1.50 ± 0.57 g/kg BW/day in patients and 0.94 ± 0.24 g/kg BW/day in healthy controls. A non-linear significant correlation was found between TPL and the E/N ratio. Conclusion: The E/N ratio is not a constant value but decreases continuously with increasing protein loss. These variations should be considered in the nutritional support of patients. © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.
Fadini G.P.,Venetian Institute of Molecular Medicine |
Losordo D.,Northwestern University |
Losordo D.,Baxter Healthcare |
Dimmeler S.,Frankfurt University
Circulation Research | Year: 2012
Diverse subsets of endothelial progenitor cells (EPCs) are used for the treatment of ischemic diseases in clinical trials, and circulating EPCs levels are considered as biomarkers for coronary and peripheral artery disease. However, despite significant steps forward in defining their potential for both therapeutic and diagnostic purposes, further progress has been mired by unresolved questions around the definition and the mechanism of action of EPCs. Diverse culturing methods and detection of various combinations of different surface antigens were used to enrich and identify EPCs. These attempts were particularly challenged by the close relationship and overlapping markers of the endothelial and hematopoietic lineages. This article will critically review the most commonly used protocols to define EPCs by culture assays or by fluorescence-activated cell sorter in the context of their therapeutic or diagnostic use. We also delineate new research avenues to move forward our knowledge on EPC biology. © 2012 American Heart Association, Inc.
Cannon J.P.,Hines Veterans Administration Hospital |
Cannon J.P.,Janssen Scientific Affairs LLC |
Lee T.A.,University of Illinois at Chicago |
Clark N.M.,Loyola University Chicago |
And 3 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014
Objectives: A consensus exists among clinicians that imipenem/cilastatin is the most epileptogenic carbapenem, despite inconsistencies in the literature. Methods: We conducted a meta-analysis of all randomized controlled trials comparing carbapenems with each other or with non-carbapenem antibiotics to assess the risk of seizures for imipenem, meropenem, ertapenem and doripenem. Results: In the risk difference (RD) analysis, there were increased patients with seizure (2 per 1000 persons, 95% CI 0.001, 0.004) among recipients of carbapenems versus non-carbapenem antibiotics. This difference was largely attributed to imipenem as its use was associated with an additional 4 patients per 1000 with seizure (95% CI 0.002, 0.007) compared with non-carbapenem antibiotics, whereas none of the other carbapenems was associated with increased seizure. Similarly, in the pooled OR analysis, carbapenems were associated with a significant increase in the risk of seizures relative to non-carbapenem comparator antibiotics (OR 1.87, 95% CI 1.35, 2.59). The ORs for risk of seizures from imipenem, meropenem, ertapenem and doripenem compared with other antibiotics were 3.50 (95% CI 2.23, 5.49), 1.04 (95% CI 0.61, 1.77), 1.32 (95% CI 0.22, 7.74) and 0.44 (95% CI 0.13, 1.53), respectively. In studies directly comparing imipenem and meropenem, there was no difference in epileptogenicity in either RD or pooled OR analyses. Conclusions: The absolute risk of seizures with carbapenems was low, albeit higher than with non-carbapenem antibiotics. Although imipenem was more epileptogenic than non-carbapenem antibiotics, there was no statistically significant difference in the imipenem versus meropenem head-to-head comparison. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Riser B.L.,Baxter Healthcare
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2011
The high rate of cardiovascular mortality in patients with end-stage renal disease (ESRD) is a significant barrier to improved life expectancy. Unique in this population is the marked development and aggressive worsening of vascular calcification (VC). Pyrophosphate (PPi), an endogenous molecule, appears to naturally inhibit soft tissue calcification, but may be depressed in chronic kidney disease (CKD) and ESRD. Although once thought to be a promising therapeutic, PPi's very short half-life in circulation curtailed earlier studies. We tested the possibility that a slow, continuous entry of PPi into the circulation and prevention of VC might be achieved by daily peritoneal dialysis (PD). Pharmacokinetic studies were first carried out in rats with renal impairment resulting from a 5/6 nephrectomy. Efficacy studies were then performed in the apolipoprotein E gene knockout mouse model overlaid with CKD. PPi was delivered by means of a permanent peritoneal catheter in a solution simulating PD, but without the timed removal of spent dialysate. von Kossa's staining followed by semiquantitative morphological image processing, with separation of inside (intimal) and outside (presumed medial) lesions, was used to determine aortic root calcification. In comparison to an intravenous bolus, delivery of PPi in a PD solution resulted in a slower, extended delivery over >4 h. Next, the efficacy studies showed that a 6-day/week PD-simulated administration of PPi resulted in a dose-dependent inhibition of aortic calcification in both intimal and medial lesions. A dose-response effect on total aortic calcification was also documented, with a full inhibition seen at the highest dose. A limited peritoneal catheter-related inflammation was observed, as expected, and included the placebo-treated control groups. This inflammatory response could have masked a lower level PPi-specific adverse effect, but none was observed. Our findings suggest potential for PPi, administered during PD, to prevent the development of VC and to potentially extend the life of ESRD patients.
Gramer M.J.,Baxter Healthcare
Advances in biochemical engineering/biotechnology | Year: 2014
The manufacturing of a biologic drug from mammalian cells results in not a single substance, but an array of product isoforms, also known as variants. These isoforms arise due to intracellular or extracellular events as a result of biological or chemical modification. The most common examples related to biomanufacturing include amino acid modifications (glycosylation, isomerization, oxidation, adduct formation, pyroglutamate formation, phosphorylation, sulfation, amidation), amino acid sequence variants (genetic mutations, amino acid misincorporation, N- and C-terminal heterogeneity, clipping), and higher-order structure modifications (misfolding, aggregation, disulfide pairing). Process-related impurities (HCP, DNA, media components, viral particles) are also important quality attributes related to product safety. The observed ranges associated with each quality attribute define the product quality profile. A biologic drug must have a correct and consistent quality profile throughout clinical development and scale-up to commercial production to ensure product safety and efficacy. In general, the upstream process (cell culture) defines the quality of product-related substances, whereas the downstream process (purification) defines the residual level of process- and product-related impurities. The purpose of this chapter is to review the impact of the cell culture process on product quality. Emphasis is placed on studies with industrial significance and where the direct mechanism of product quality impact was determined. Where possible, recommendations for maintaining consistent or improved quality are provided.
Yao Q.,Baxter Healthcare |
Zhou G.,Baxter Healthcare
Peritoneal Dialysis International | Year: 2014
Improving the quality of peritoneal dialysis (PD) in areas with a rapid increase in PD patient numbers constitutes the most significant PD challenge in China. Here, we share our experience of implementing a quality improvement program in 8 PD centers, with guidance from matched experienced centers. © 2014 International Society for Peritoneal Dialysis.