Argatroban pharmacokinetics and pharmacodynamics in critically ill cardiac surgical patients with suspected heparin-induced thrombocytopenia

2016 ◽  
Vol 115 (06) ◽  
pp. 1081-1089 ◽  
Author(s):  
Emanuel Zimmer ◽  
Martin Bek ◽  
Michael Wiessner ◽  
Cornelius Keyl ◽  
Dietmar Trenk
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Serum Albumin ◽  
Critically Ill ◽  
Half Life ◽  
Linear Regression Analysis ◽  
Surgical Patients ◽  
Target Range ◽  
Albumin Concentration ◽  
Plasma Half Life

SummaryOnly limited data are available on the pharmacokinetic and pharmacodynamic properties of argatroban in critically ill patients under clinical conditions. We determined plasma concentrations of argatroban, and its main metabolite M1, within a time period of 48 hours in 25 critically ill cardiac surgical patients, who were suspected of heparininduced thrombocytopenia and had the clinical need for anticoagulation. Argatroban infusion was started at 0.5 µg/kg/minute, and adjusted in 0.1–0.25 µg/kg/minute increments when the activated partial thromboplastin time (aPTT) was not within the target range. Median argatroban plasma half-life was 2.7 hours (interquartile range 1.8 to 7.3). Linear regression analysis revealed that argatroban half-life was significantly related to the total bilirubin concentration (R2 = 0.66, p< 0.001), as well as to the metabolism of argatroban, which was assessed by the ratio of the areas under the concentration time curves (AUC) of argatroban and M1 (R2 = 0.60, p< 0.001). Continuous veno-venous haemodialysis did not significantly affect argatroban plasma half-life. The predictive property of argatroban plasma levels for aPTT was low (R2 = 0.28, p< 0.001). Multiple linear regression analysis revealed significant contributions of age and serum albumin levels to the effect of argatroban on aPTT, expressed as the AUC ratio argatroban/aPTT (R2 = 0.67, adjusted R2 = 0.65, p< 0.001). In conclusion, argatroban plasma half-life is markedly increased in critically ill cardiac surgical patients, and further prolonged by hepatic dysfunction due to impaired metabolism. Patient age and serum albumin concentration significantly contribute to the variability in the anticoagulant activity of argatroban.

Clinical factors affecting cerebral oxygenation in patients undergoing peritoneal dialysis

2021 ◽  
pp. 039139882110200
Author(s):  
Taisuke Kitano ◽  
Kiyonori Ito ◽  
Susumu Ookawara ◽  
Taro Hoshino ◽  
Hideyuki Hayasaka ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Peritoneal Dialysis ◽  
Linear Regression ◽  
Serum Albumin ◽  
Cerebral Oxygenation ◽  
Linear Regression Analysis ◽  
Albumin Concentration ◽  
Healthy Controls ◽  
Serum Albumin Concentration ◽  
Factors Affecting

Background: Although cerebral regional oxygen saturation (rSO2) is significantly lower in hemodialysis (HD) patients than that in healthy controls, investigations on cerebral oxygenation in peritoneal dialysis (PD) patients are limited. We aimed to confirm the cerebral oxygenation status and identify the factors affecting cerebral rSO2 in PD patients. Methods: Thirty-six PD patients (21 men and 15 women; mean age, 62.8 ± 12.7 years) were recruited. In addition, 27 healthy volunteers (17 men and 10 women; mean age, 43.5 ± 18.8 years) were recruited as a control group. Cerebral rSO2 was monitored at the forehead using an INVOS 5100c oxygen saturation monitor. Results: Cerebral rSO2 was significantly lower in PD patients than that in healthy controls (57.0 ± 7.3% vs 68.9 ± 8.6%, p < 0.001); moreover, cerebral rSO2 was significantly correlated with natural logarithm (Ln)-PD duration ( r = −0.389, p = 0.019) and serum albumin concentration ( r = 0.370, p = 0.026) in a simple linear regression analysis. Multivariable linear regression analysis was performed using variables that showed a significant correlation and p < 0.20 (serum creatinine, serum sodium, Ln-C-reactive protein, and dosage of erythropoiesis-stimulating agent) with the cerebral rSO2. Cerebral rSO2 was independently associated with Ln-PD duration (standardized coefficient: −0.339) and serum albumin concentration (standardized coefficient: 0.316). Conclusions: Cerebral rSO2 was significantly affected by the PD duration and serum albumin concentration. Further prospective studies are needed to clarify whether preventing a decrease in serum albumin concentration leads to the maintenance of cerebral oxygenation in patients undergoing PD.

Relationships between magnesium and protein concentrations in serum.

1985 ◽  
Vol 31 (2) ◽  
pp. 244-246 ◽  
Author(s):  
M H Kroll ◽  
R J Elin
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Serum Albumin ◽  
Total Protein ◽  
Serum Magnesium ◽  
Linear Regression Analysis ◽  
Reference Interval ◽  
Magnesium Concentration ◽  
Total Serum ◽  
Albumin Concentration

Abstract We determined concentrations of magnesium, total protein, albumin, and globulin in more than 74 000 serum specimens from patients and noted a direct linear relationship between the concentration of magnesium in serum and the concentrations of total protein, albumin, and globulin in serum. Albumin and magnesium concentrations are linearly related at high and low albumin concentrations; within the reference interval, however, the magnesium concentration is independent of the albumin concentration. Linear regression analysis suggests that 25% of the total serum magnesium is bound to albumin and 8% to globulins.

Elevated Nuclease Activity Correlates With Clinical Spectrum Of Plasma Cell Dyscrasias

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4885-4885
Author(s):  
Jaymin M. Patel ◽  
Ankit V Vahia ◽  
Puru Nanjappa ◽  
Ashun Bajwa ◽  
Sima Shah ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Genomic Instability ◽  
Cell Lines ◽  
Plasma Cell ◽  
Half Life ◽  
Linear Regression Analysis ◽  
Nuclease Activity ◽  
Plasma Cell Dyscrasia ◽  
Plasma Cell Dyscrasias

Abstract Over the last decade, there has been increasing interest in mechanisms that underlie genomic instability which is implicated in tumor progression, development of drug resistance and possibly even oncogenesis. We have observed that dysregulated homologous recombination (HR) is an important contributor to genomic instability. In this study, we aim to broaden our understanding of HR by exploring alternate pathways that may affect genomic instability such as nuclease activity. Methods We have developed an assay to measure total cellular nuclease activity and compare activity levels across a spectrum of plasma cell dyscrasias. Total nuclease activity in cell lines and patient samples was assessed using a novel plasmid degradation assay. Briefly, multiple myeloma (MM) cell lines and primary MM patient cells were lysed at equal cell concentration. The lysates were mixed with plasmid DNA in triplicate/quadruplicate and incubated at 37°C for fixed time points ranging from 0 to 30 minutes. Following forced cessation of enzymatic activity, samples were fractionated on agarose gel and resultant image analyzed for band intensity by Kodak 1D Image analysis software. The ratio of degraded plasmid over time was analyzed via nonlinear regression to calculate a half-life and k-constant. Results Non-linear regression analysis of data derived from assays involving 6 MM cell lines (RPMI, OPM1, H292, U266, INA6 & MM1S) with three pellets each of equal size taken from non-confluent cell culture with > 85% viability showed statistically significant reproducibility of best fit curve with an average R-squared of 0.93. Similar regression analysis could not be performed on data derived from normal PBMC pellets because they showed minimal degradation with linear regression slope of (-0.62). Lastly, non-linear regression analysis on 22 patient samples with a plasma cell dyscrasia diagnosis, revealed a broader range of activity by half-life. Further differentiation of plasma cell dyscrasia patients into 2 groups revealed a significantly higher half-life in MGUS & smouldering (9499.8 minutes) versus newly diagnosed and refractory or relapsed multiple myeloma patients (9.4,19.3 minutes respectively). Conclusions In conclusion, we show that nuclease activity, implicated in elevated recombination and genomic instability, can be measured in a statistically reproducible fashion by our in vitro assay and may be used to differentiate plasma cell dyscrasias across a clinical spectrum. Further analysis of nuclease activity in clinically annotated samples for correlation with clinical features, genomic data and survival outcomes is ongoing. Disclosures: Anderson: celgene: Consultancy; onyx: Consultancy; gilead: Consultancy; sanofi aventis: Consultancy; oncopep: Equity Ownership; acetylon: Equity Ownership.

scholarly journals Association of Serum Albumin Concentration and Mortality Risk in Critically Ill Patients

2002 ◽  
Vol 30 (2) ◽  
pp. 202-207 ◽  
Author(s):  
F. H. Y. Yap ◽  
G. M. Joynt ◽  
T. A. Buckley ◽  
E. L. Y. Wong
Keyword(s):  
Serum Albumin ◽  
Critically Ill ◽  
Mortality Risk ◽  
Critically Ill Patients ◽  
Roc Curves ◽  
Apache Ii ◽  
Surgical Patients ◽  
Apache Ii Score ◽  
Albumin Concentration ◽  
Serum Albumin Concentration

In this study we aimed to examine the association between serum albumin concentration and mortality risk in critically ill patients. We retrospectively studied 1003 patients admitted to our Intensive Care Unit (ICU) over an 18-month period. Serial albumin measurements over 72 hours were compared between survivors and non-survivors, and medical and surgical patients were also compared. Our results showed that serum albumin decreased after ICU admission, most rapidly in the first 24 hours, in both survivors and non-survivors. Serum albumin was lower in non-survivors than in survivors, but albumin concentrations poorly differentiated the two groups. Medical patients had higher admission albumin levels than surgical patients, but both subgroups showed a similar albumin profile over 72 hours. We evaluated the prognostic value of serum albumin using receiver operator characteristic (ROC) curves. We constructed ROC curves for APACHE II score, admission albumin, albumin at 24 and 48 hours. We also combined APACHE II with albumin values and constructed the corresponding ROC curves. Our data showed that serum albumin had low sensitivity and specificity for predicting hospital mortality. Combining APACHE II score with serum albumin concentrations did not improve the accuracy of outcome prediction over that of APACHE II alone.

scholarly journals Influence of transfusions, hemodialysis and extracorporeal life support on hyperferritinemia in critically ill patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254345
Author(s):  
Cornelia Knaak ◽  
Friederike S. Schuster ◽  
Peter Nyvlt ◽  
Patrick Heeren ◽  
Claudia Spies ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Critically Ill ◽  
Sofa Score ◽  
Critically Ill Patients ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Linear Regression Analysis ◽  
Iron Storage ◽  
Multivariable Linear Regression Analysis

Background Ferritin is the major iron storage protein and an acute phase reactant. Hyperferritinemia is frequently seen in the critically ill where it has been hypothesized that not only underlying conditions but also factors such as transfusions, hemodialysis and extracorporeal life support (ECLS) lead to hyperferritinemia. This study aims to investigate the influence of transfusions, hemodialysis, and ECLS on hyperferritinemia in a multidisciplinary ICU cohort. Methods This is a post-hoc analysis of a retrospective observational study including patients aged ≥ 18 years who were admitted to at least one adult ICU between January 2006 and August 2018 with hyperferritinemia ≥ 500 μg/L and of ≥ 14 days between two ICU ferritin measurements. Patients with hemophagocytic lymphohistiocytosis (HLH) were excluded. To identify the influence of transfusions, hemodialysis, and ECLS on ferritin change, multivariable linear regression analysis with ferritin change between two measurements as dependent variable was performed. Results A total of 268 patients was analyzed. Median duration between measurements was 36 days (22–57). Over all patients, ferritin significantly increased between the first and last measurement (p = 0.006). Multivariable linear regression analysis showed no effect of transfusions, hemodialysis, or ECLS on ferritin change. Changes in aspartate aminotransferase (ASAT) and sequential organ failure assessment (SOFA) score were identified as influencing factors on ferritin change [unstandardized regression coefficient (B) = 2.6; (95% confidence interval (CI) 1.9, 3.3); p < 0.001 and B = 376.5; (95% CI 113.8, 639.1); p = 0.005, respectively]. Using the same model for subgroups of SOFA score, we found SOFA platelet count to be associated with ferritin change [B = 1729.3; (95% CI 466.8, 2991.9); p = 0.007]. No association of ferritin change and in-hospital mortality was seen in multivariable analysis. Conclusions The present study demonstrates that transfusions, hemodialysis, and ECLS had no influence on ferritin increases in critically ill patients. Hyperferritinemia appears to be less the result of iatrogenic influences in the ICU thereby underscoring its unskewed diagnostic value. Trial registration The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

Cerebral oxygenation improvement is associated with hemoglobin increase after hemodialysis initiation

2020 ◽  
Vol 43 (11) ◽  
pp. 695-700
Author(s):  
Kiyonori Ito ◽  
Susumu Ookawara ◽  
Yuichiro Ueda ◽  
Haruhisa Miyazawa ◽  
Takayuki Uchida ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Serum Albumin ◽  
Near Infrared ◽  
Cerebral Oxygenation ◽  
Linear Regression Analysis ◽  
Albumin Level ◽  
Hemoglobin Level ◽  
Multivariate Linear Regression Analysis ◽  
Clinical Parameters

Introduction: Near-infrared spectroscopy has been used to measure the regional oxygen saturation (rSO2) of the brain, and decreases in cerebral rSO2 have been reported to lead to cognitive impairment in patients undergoing hemodialysis. However, reports about the association between changes in cerebral oxygenation and clinical parameters at hemodialysis initiation, including hemoglobin level, are lacking. Methods: This study included 33 patients at the hemodialysis initiation phase. Cerebral rSO2 was monitored using an INVOS 5100C. Included patients were assessed twice (at hemodialysis initiation and 42.7 ± 20.8 days after the first measurement), and changes in cerebral rSO2 were compared with changes in clinical parameters. Results: Cerebral rSO2 at the second measurement significantly increased compared with that at hemodialysis initiation (57.2 ± 6.8% vs 54.4 ± 8.8%, p < 0.05). Changes in cerebral rSO2 represented a significant correlation with changes in hemoglobin level, pulse rate, and serum albumin level. Multivariate linear regression analysis was performed using significant factors in simple linear regression analysis. Changes in hemoglobin (standardized coefficient: 0.37) and serum albumin (standardized coefficient: 0.45) levels were identified as independent factors influencing the changes in cerebral rSO2. Conclusion: Cerebral rSO2 was low in the presence of low hemoglobin levels at hemodialysis initiation and improved in response to hemoglobin increase in addition to changes in serum albumin levels. Attention should be paid to changes in hemoglobin levels even at hemodialysis initiation to prevent the deterioration of cerebral oxygenation, and this might contribute to the maintenance of cognitive function in patients undergoing hemodialysis.

scholarly journals Evaluation of APACHE II system among intensive care patients at a teaching hospital

2003 ◽  
Vol 121 (2) ◽  
pp. 53-57 ◽  
Author(s):  
Paulo Antonio Chiavone ◽  
Yvoty Alves dos Santos Sens
Keyword(s):  
Intensive Care Unit ◽  
Regression Analysis ◽  
Intensive Care ◽  
Linear Regression ◽  
Death Rate ◽  
Elective Surgery ◽  
Linear Regression Analysis ◽  
Apache Ii ◽  
Surgical Patients ◽  
Apache Ii Score

CONTEXT: The high-complexity features of intensive care unit services and the clinical situation of patients themselves render correct prognosis fundamentally important not only for patients, their families and physicians, but also for hospital administrators, fund-providers and controllers. Prognostic indices have been developed for estimating hospital mortality rates for hospitalized patients, based on demographic, physiological and clinical data. OBJECTIVE: The APACHE II system was applied within an intensive care unit to evaluate its ability to predict patient outcome; to compare illness severity with outcomes for clinical and surgical patients; and to compare the recorded result with the predicted death rate. DESIGN: Diagnostic test. SETTING: Clinical and surgical intensive care unit in a tertiary-care teaching hospital. PARTICIPANTS: The study involved 521 consecutive patients admitted to the intensive care unit from July 1998 to June 1999. MAIN MEASUREMENTS: APACHE II score, in-hospital mortality, receiver operating characteristic curve, decision matrices and linear regression analysis. RESULTS: The patients' mean age was 50 ± 19 years and the APACHE II score was 16.7 ± 7.3. There were 166 clinical patients (32%), 173 (33%) post-elective surgery patients (33%), and 182 post-emergency surgery patients (35%), thus producing statistically similar proportions. The APACHE II scores for clinical patients (18.5 ± 7.8) were similar to those for non-elective surgery patients (18.6 ± 6.5) and both were greater than for elective surgery patients (13.0 ± 6.3) (p < 0.05). The higher this score was, the higher the mortality rate was (p < 0.05). The predicted death rate was 25.6% and the recorded death rate was 35.5%. Through the use of receiver operating curve analysis, good discrimination was found (area under the curve = 0.80). From the 2 x 2 decision matrix, 72.2% of patients were correctly classified (sensitivity = 35.1%; specificity = 92.6%). Linear regression analysis was equivalent to r² = 0.92. CONCLUSIONS: APACHE II was useful for stratifying these patients. The illness severity and death rate among clinical patients were higher than those recorded for surgical patients. Despite the stratification ability of the APACHE II system, it lacked accuracy in predicting death rates. The recorded death rate was higher than the predicted rate.

scholarly journals Association between hepatic oxygenation on near-infrared spectroscopy and clinical factors in patients undergoing hemodialysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0259064
Author(s):  
Yuichiro Ueda ◽  
Susumu Ookawara ◽  
Kiyonori Ito ◽  
Yusuke Sasabuchi ◽  
Hideyuki Hayasaka ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Regression Analysis ◽  
Serum Albumin ◽  
Oxygen Saturation ◽  
Linear Regression Analysis ◽  
Splanchnic Circulation ◽  
Control Group ◽  
Albumin Concentration ◽  
Serum Albumin Concentration ◽  
History Of

The hepato-splanchnic circulation directly influences oxygenation of the abdominal organs and plays an important role in compensating for the blood volume reduction that occurs in the central circulation during hemodialysis (HD) with ultrafiltration. However, the hepato-splanchnic circulation and oxygenation cannot be easily evaluated in the clinical setting of HD therapy. We included 185 HD patients and 15 healthy volunteers as the control group in this study. Before HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting the hepato-splanchnic circulation and oxygenation, was monitored using an INVOS 5100c oxygen saturation monitor. Hepatic rSO2 was significantly lower in patients undergoing HD than in healthy controls (56.4 ± 14.9% vs. 76.2 ± 9.6%, p < 0.001). Multivariable regression analysis showed that hepatic rSO2 was independently associated with body mass index (BMI; standardized coefficient: 0.294), hemoglobin (Hb) level (standardized coefficient: 0.294), a history of cardiovascular disease (standardized coefficient: -0.157), mean blood pressure (BP; standardized coefficient: 0.154), and serum albumin concentration (standardized coefficient: 0.150) in Model 1 via a simple linear regression analysis. In Model 2 using the colloid osmotic pressure (COP) in place of serum albumin concentration, the COP (standardized coefficient: 0.134) was also identified as affecting hepatic rSO2. Basal hepatic oxygenation before HD might be affected by BMI, Hb levels, a history of cardiovascular disease, mean BP, serum albumin concentration, and the COP. Further prospective studies are needed to clarify whether changes in these parameters, including during HD, affect the hepato-splanchnic circulation and oxygenation in HD patients.

ANALISIS PENGARUH INFLASI, KURS DAN IHSG TERHADAP RETURN REKSA DANA SAHAM PT NIKKO SECURITIES INDONESIA PERIODE 2014-2017

2019 ◽  
Vol 2 (2) ◽  
pp. 103
Author(s):  
Muhammad Rois Rois ◽  
Manarotul Fatati Fatati ◽  
Winda Ihda Magfiroh
Keyword(s):  
Regression Analysis ◽  
Exchange Rate ◽  
Linear Regression ◽  
Multiple Linear Regression ◽  
Stock Price ◽  
Price Index ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Equity Fund ◽  
Stock Price Index

This study aims to determine the effect of Inflation, Exchange Rate and Composite Stock Price Index (IHSG) to Return of PT Nikko Securities Indonesia Stock Fund period 2014-2017. The study used secondary data obtained through documentation in the form of PT Nikko Securities Indonesia Monthly Net Asset (NAB) report. Data analysis is used with quantitative analysis, multiple linear regression analysis using eviews 9. Population and sample in this research are PT Nikko Securities Indonesia. The result of multiple linear regression analysis was the coefficient of determination (R2) showed the result of 0.123819 or 12%. This means that the Inflation, Exchange Rate and Composite Stock Price Index (IHSG) variables can influence the return of PT Nikko Securities Indonesia's equity fund of 12% and 88% is influenced by other variables. Based on the result of the research, the variables of inflation and exchange rate have a negative and significant effect toward the return of PT Nikko Securities Indonesia's equity fund. While the variable of Composite Stock Price Index (IHSG) has a negative but not significant effect toward Return of Equity Fund of PT Nikko Securities Indonesia

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