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Therapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA).
We analyzed the time course over 8h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence d TDM.
The qualitative results of SARS-CoV-2 specific real-time reverse transcription (RT) PCR are used for initial diagnosis and follow-up of Covid-19 patients and asymptomatic virus carriers. However, clinical decision-making and health management policies often are based additionally on cycle threshold (C
) values (i.e., quantitative results) to guide patient care, segregation and discharge management of individuals testing positive. Therefore, an analysis of inter-protocol variability is needed to assess the comparability of the quantitative results.
C
values reported in a SARS-CoV-2 virus genome detection external quality assessment challenge were analyzed. Three positive and two negative samples were distributed to participating test laboratories. FTY720 Qualitative results (positive/negative) and quantitative results (C
values) were assessed.
A total of 66 laboratories participated, contributing results from 101 distinct test systems and reporting C
values for a total of 92 different protocols. In all tt standardization is necessary in the reporting of Ct values with respect to the target gene.
Venous blood gas (VBG) analysis is becoming a popular alternative to arterial blood gas (ABG) analysis due to reduced risk of complications at phlebotomy and ease of draw. In lack of published data, this study aimed to establish reference intervals (RI) for correct interpretation of VBG results.
One hundred and 51 adult volunteers (101 females, 50 males, 18-70years) were enrolled after completion of a health questionnaire. Venous blood was drawn into
PICO syringes and analysed on ABL827 blood gas analyser (Radiometer Pacific Pty. Ltd.). A non-parametric approach was used to directly establish the VBG RI which was compared to a calculated VBG RI based on a meta-analysis of differences between ABG and VBG.
After exclusions, 134 results were used to derive VBG RI pH 7.30-7.43, partial pressure of carbon dioxide (pCO
) 38-58mmHg, partial pressure of oxygen (pO
) 19-65mmHg, bicarbonate (HCO
-) 22-30mmol/L, sodium 135-143mmol/L, potassium 3.6-4.5mmol/L, chloride 101-110mmol/L, ionised calcium 1.14-1.29mmol/L, lactate 0.4-2.2mmol/L, base excess (BE)-1.9-4.5mmol/L, saturated oxygen (sO
) 23-93%, carboxyhaemoglobin 0.4-1.4% and methaemoglobin 0.3-0.9%. The meta-analysis revealed differences between ABG and VBG for pH, HCO
-, pCO
and pO
of 0.032,-1.0mmol/L,-4.2 and 39.9mmHg, respectively. Using this data along with established ABG RI, calculated VBG RI of pH 7.32-7.42, HCO
- 23- 27mmol/L, pCO
36-49mmHg (female), pCO
39-52mmHg (male) and pO
43-68mmHg were formulated and compared to the VBG RI of this study.
An adult reference interval has been established to assist interpretation of VBG results.
An adult reference interval has been established to assist interpretation of VBG results.
Midregional pro-adrenomedullin (MR-proADM) is a vasoactive peptide with key roles in reducing vascular hyperpermeability and thereby improving endothelial stability during infection. While MR-proADM is useful for risk stratification in patients with sepsis, clinical data about prediction accuracy in patients with severe acute respiratory syndrome coronavirus 2 disease (COVID-19) is currently missing.
We included consecutively adult patients hospitalized for confirmed COVID-19 at a tertiary care center in Switzerland between February and April 2020. We investigated the association of MR-proADM levels with in-hospital mortality in logistic regression and discrimination analyses.
Of 89 included COVID-19 patients, 19% (n=17) died while in the hospital. Median admission MR-proADM levels (nmol/L) were increased almost 1.5-fold increased in non-survivors compared to survivors (1.3 [interquartile range IQR 1.1-2.3]) vs. 0.8 [IQR 0.7-1.1]) and showed good discrimination (area under the curve 0.78). An increase of 1nmol/L of admission MR-proADM was independently associated with a more than fivefold increase in in-hospital mortality (adjusted odds ratio of 5.5, 95% confidence interval 1.4-21.4, p=0.015). An admission MR-proADM threshold of 0.93nmol/L showed the best prognostic accuracy for in-hospital mortality with a sensitivity of 93%, aspecificity of 60% and a negative predictive value of 97%. Kinetics of follow-up MR-proADM provided further prognostic information for in-hospital treatment.
Increased levels of MR-proADM on admission and during hospital stay were independently associated with in-hospital mortality and may allow a better risk stratification, and particularly rule-out of fatal outcome, in COVID-19 patients.
Increased levels of MR-proADM on admission and during hospital stay were independently associated with in-hospital mortality and may allow a better risk stratification, and particularly rule-out of fatal outcome, in COVID-19 patients.
Novel treatment options for some carbapenem-resistant Gram-negative pathogens have been identified by the World Health Organization as being of the highest priority. Ceftolozane-tazobactam is a novel cephalosporin-beta-lactamase inhibitor combination antibiotic with potent bactericidal activity against the most difficult-to-treat multi-drug resistant and extensively drug resistant Gram-negative pathogens. This study aimed to develop and validate a liquid chromatography- tandem mass spectrometry method for the simultaneous quantification of ceftolozane and tazobactam in plasma (total and unbound), renal replacement therapy effluent (RRTE), cerebrospinal fluid (CSF) and urine.
Analytes were separated using mixed-mode chromatography with an intrinsically base-deactivated C18 column and a gradient mobile phase consisting of 0.1% formic acid, 10mM ammonium formate and acetonitrile. The analytes and internal standards were detected using rapid ionisation switching between positive and negative modes with simultaneous selected reaction monitoring.
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