An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

2021 ◽  
Author(s):  
Jose de Leon ◽  
Georgios Schoretsanitis ◽  
Robert L. Smith ◽  
Espen Molden ◽  
Anssi Solismaa ◽  
...  
Keyword(s):  
Reference Range ◽  
Asian Population ◽  
The United States ◽  
Serum Concentrations ◽  
Poor Metabolizer ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Asian Ancestry ◽  
Toxic Drug ◽  
The Us

AbstractThis international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

C-REACTIVE PROTEIN SERUM CONCENTRATIONS IN WELL-TRAINED ATHLETES

1982 ◽  
Vol 14 (2) ◽  
pp. 172
Author(s):  
B. Dufaux ◽  
U. Order ◽  
H. Geyer ◽  
W. Hollmann
Keyword(s):  
Serum Concentrations ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Protein Serum

scholarly journals MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN: DIAGNOSTIC MARKERS AND FEATURES OF PHARMACOTHERAPY

2021 ◽  
Vol 17 (1) ◽  
pp. 24-28
Author(s):  
M.V. Кhaitovych ◽  
L.M. Voroniuk ◽  
G.Yu. Borisova ◽  
N.V. Diudenko ◽  
N.M. Miagka
Keyword(s):  
Distress Syndrome ◽  
The United States ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Laboratory Markers ◽  
Mucous Membranes ◽  
Coronavirus Infection ◽  
Polymerase Chain ◽  
Inflammatory Syndrome

Relevance. In 2020, children were hospitalized with fever and multisystem inflammation throughout the world during the COVID-19 pandemic. In the United States, this condition is called MIS-C (Multisystem Inflammatory Syndrome in Children). This syndrome is thought to be similar to the severe course of COVID-19 in adults (cytokine storm). The objective of the work is to evaluate the features of the course and pharmacotherapy of multisystem inflammatory syndrome in children. Materials and methods. The study included 17 children (10 boys and 7 girls) aged 3-16 years (on average – 9.5±3.4 years). Diagnosis of coronavirus infection was performed by polymerase chain reaction with real-time detection, determined the level of immunoglobulins M and G before coronavirus infection. Results. The duration of fever in patients was 5-21 days (average 8.1±4.0 days), the duration of inpatient treatment – 7-35 days (average 15.7±7.0 days). Blood albumin levels were reduced in 53.8% of children; the level of fibrinogen was increased in 88.2% of children, the level of C-reactive protein, ferritin, and D-dimer – in all patients. 15 (88.2%) children had pathology of the digestive system, 13 (76.5%) – cardiovascular system (7 children were diagnosed with carditis, 2 – dilation of coronary arteries, 7 – cardiac arrhythmia). Acute respiratory distress -syndrome was found in a 13-year-old girl, shock - in an 11-year-old boy, 11 children (64.7%) were diagnosed with the pathology of the respiratory system (pleurisy, pneumonia), skin and mucous membranes, and 4 children (23.5%) there were manifestations of central nervous system disorders (meningism, decreased reflexes, ataxia), in 2 (11.8%) – renal failure. On average, each patient had lesions of 3.9 ±1.2 systems. Conclusions. MIS-C was manifested by prolonged fever, high levels of laboratory markers of inflammation, hypoalbuminemia, hypercoagulation, often – pathological manifestations of the cardiovascular, digestive, respiratory systems, skin, and mucous membranes. The treatment included intravenous immunoglobulin, steroids, anticoagulant, and antibacterial therapy and was effective.

scholarly journals Multimorbidity, inflammation, and disability: a longitudinal mediational analysis

2018 ◽  
Vol 10 ◽  
pp. 204062231880684 ◽  
Author(s):  
Elliot M. Friedman ◽  
Daniel K. Mroczek ◽  
Sharon L. Christ
Keyword(s):  
Chronic Conditions ◽  
Structural Equation ◽  
Structural Equation Models ◽  
Functional Limitations ◽  
The United States ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Mediational Analysis

Background: Using longitudinal data from the Survey of Mid-Life Development in the United States, this study examined the role of systemic inflammation in mediating the link between multimorbidity and increases in and onset of functional limitations over a 17–19 year follow-up period. Methods: Participants completed questionnaire assessments of chronic conditions and functional limitations. Interleukin-6, C-reactive protein, and fibrinogen were assayed in serum. Structural equation models were used to predict increases in and onset of functional limitations associated with baseline multimorbidity status; mediation by inflammation was also determined. Results: Multimorbidity ( versus 0–1 conditions) predicted more functional limitations and greater odds of onset of limitations over time. Significant indirect effects showed that inflammation partially mediated the link between multimorbidity and changes in, but not onset of, limitations. Discussion: These results show that inflammation, a nonspecific marker of multiple disease conditions, explains in part the degree to which multimorbidity is disabling.

scholarly journals Alterations of pancreatic functions and lipid profiles in dairy cows with left displacement of the abomasum

2019 ◽  
Vol 64 (No. 5) ◽  
pp. 204-208
Author(s):  
Z Ismail ◽  
AM Al-Majali ◽  
O Al-Rawashdeh ◽  
M Daradka ◽  
M Mohaffel
Keyword(s):  
High Density Lipoprotein ◽  
Dairy Cows ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Low Density ◽  
Serum Concentrations ◽  
C Reactive Protein ◽  
Reactive Protein

The objectives of this study were to determine the serum activities of the pancreatic enzymes amylase, lipase, trypsinogen 1 and trypsinogen 2, serum concentrations of total cholesterol, high density lipoprotein, low-density lipoprotein and triglycerides and serum inflammatory indicators, namely C-reactive protein and procalcitonin, in Holstein-Friesian dairy cows with left displacement of the abomasum (LDA). A total of 60 cows (30 LDA-affected and 30 healthy) were included in the study. Laboratory analyses were performed using commercially available ELISA kits and chemical reagents according to the manufacturers’ recommendations. There was a significant increase (P ≤ 0.05) in the activities of lipase, trypsinogen 1 and trypsinogen 2 in LDA-affected cows compared to healthy cows. Amylase concentrations, however, remained unchanged. The serum concentrations of total cholesterol and high-density lipoprotein were significantly (P ≤ 0.05) increased in LDA-affected cows while the concentrations of low-density lipoprotein and triglycerides were significantly (P ≤ 0.05) decreased compared to healthy cows. Procalcitonin and C-reactive protein concentrations were significantly (P ≤ 0.05) increased in LDA-affected cows compared to healthy cows. This study indicates that displacement of the abomasum may be associated with significant pathological effects in the pancreas that may affect cows in the post-operative period.

scholarly journals Serum Calprotectin and Chemerin Concentrations as Markers of Low-Grade Inflammation in Prepubertal Children with Obesity

2020 ◽  
Vol 17 (20) ◽  
pp. 7575 ◽  
Author(s):  
Grażyna Rowicka ◽  
Hanna Dyląg ◽  
Magdalena Chełchowska ◽  
Halina Weker ◽  
Jadwiga Ambroszkiewicz
Keyword(s):  
Low Grade ◽  
Serum Concentrations ◽  
C Reactive Protein ◽  
Prepubertal Children ◽  
Reactive Protein ◽  
Study Population ◽  
Normal Body Weight ◽  
Wbc Count ◽  
Low Grade Inflammation

In adults, obesity is associated with chronic low-grade inflammation, which may cause long-term adverse health consequences. We evaluated whether obesity in prepubertal children also generates this kind of inflammation and whether calprotectin and chemerin may be useful markers for early detection of such inflammation in this group of children. The study population included 83 children aged 2 to 10 years; 62 with obesity and without components of metabolic syndrome and 21 healthy controls with normal body weight. White blood cell (WBC) count, concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), calprotectin, and chemerin were determined in peripheral blood. Our study showed that in the group with obesity, serum concentrations of calprotectin and chemerin, as well as CRP were significantly higher as compared with the controls. We found a significant positive correlation between serum chemerin concentrations and BMI z-score (r = 0.33, p < 0.01) in children with obesity. Chemerin concentration was also positively correlated with CRP level (r = 0.36, p < 0.01) in the whole group of children. These findings suggest that obesity may generate chronic low-grade inflammation as early as in the prepubertal period which can be indicated by significantly higher serum concentrations of calprotectin and chemerin. Calprotectin and especially chemerin seem to be promising indicators of this type of inflammation in children with obesity, but the correlation between these markers requires further research.

5947Predictive role of C-reactive protein levels in patients with ST-segment elevation acute myocardial infarction for heart failure related events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B Van Tassell ◽  
C R Trankle ◽  
D Kadariya ◽  
J M Canada ◽  
S Carbone ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Multivariate Analysis ◽  
Inflammatory Response ◽  
Composite Endpoint ◽  
The United States ◽  
C Reactive Protein ◽  
St Segment Elevation ◽  
Reactive Protein ◽  
St Segment

Abstract Background ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). C-reactive protein (CRP) is the inflammatory biomarker most commonly used for risk stratification in patients with cardiovascular diseases. CRP levels are known to rise and fall during STEMI in response to myocardial injury. In this study, we analyzed whether admission CRP or delayed CRP (measured at 72 hours after admission) held a greater predictive value for adverse HF events in patients with STEMI. Methods We analyzed data from the VCUART3 clinical trial enrolling 99 patients with STEMI within 12 hours of presentation at 3 sites in the United States of America treated with anakinra or placebo. CRP levels were measured with a high-sensitivity assay at time of admission and again at 72 hours later. A dedicated committee composed of individuals not involved in the conduct of the trial adjudicated HF events including a composite endpoint of death from any reason or incidence of HF defined as new-onset HF requiring hospital admission or a new prescription for a loop diuretic (D+HF) and a composite endpoint of death and HF hospitalization (D+HHF) at 1 year. We used a time-dependent Cox-regression analysis to determine the association of CRP at admission or at 72 hours with the outcomes of interest in univariate and multivariate analysis. Data are presented as median and interquartile range. (ClinicalTrials NCT01950299) Results CRP levels from admission and 72 hours were available in 90 and 87 subjects respectively and they increased from 4.6 [2.8–8.5] mg/L to 11.6 [4.6–24.5] mg/L (P<0.001). Both admission CRP (CRP0) and CRP at 72 hours (CRP72) were associated with the risk of D+HF (P=0.011 and <0.001, respectively) and of D+HHF (P=0.010 and P<0.001, respectively); however at multivariate analysis, only CRP72 remained significantly associated with the risk of D+HF (P=0.001) and D+HHF (P=0.004) while CRP0 was not. CRP72 significantly correlated with NTproBNP levels at 72 hours (NTproBNP72, Spearman rho R=+0.37, P=0.001). NTproBNP72 predicted D+HF (P=0.030) but not independently of CRP72 (P=0.096 for NTproBNP72 and P=0.007 for CRP72 at multivariate analysis including the 2 variables). NTproBNP72 did not predict D-HHF. Conclusions Among contemporary patients with STEMI, the levels of CRP at 72 hours after admission was superior to admission CRP levels for predicting the incidence of HF events, and independent of NTproBNP levels. Our results indicate the importance of the inflammatory response during STEMI, supporting the concept of inhibiting the inflammatory response as a therapeutic strategy. Acknowledgement/Funding Funded by NHLBI 1R34HL121402; Drug supply from Swedish Orphan Biovitrum

scholarly journals Kinetic simulation method of C-reactive protein in beagle dogs during acute inflammation

2017 ◽  
Vol 15 (2) ◽  
pp. 120-123
Author(s):  
Takashi Kuribayashi
Keyword(s):  
Rate Constant ◽  
Inflammatory Responses ◽  
Elimination Rate ◽  
Simulation Method ◽  
Elimination Rate Constant ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Concentrations ◽  
Beagle Dogs ◽  
C Reactive Protein ◽  
Reactive Protein

The half-life ( t1/2) of C-reactive protein (CRP) and its ability to stimulate weak inflammatory responses were investigated in beagle dogs. Four beagle dogs were administered 20 mg/kg indomethacin and blood was collected from the cephalic vein pre-dosing and at 24, 48, 72, 96, 144, 192, 240, 312, and 360 h post-administration. The serum concentrations of CRP were measured by enzyme-linked immunosorbent assay. The serum t1/2 was calculated using the equation 0.693/elimination rate constant. The serum concentration of CRP beyond 192 h post-administration declined to levels in the normal range. The t1/2 was 148.3 h, which is considered to be the essential t1/2 of CRP. The simulation of CRP serum concentrations at arbitrary times using the elimination rate constant obtained in this study became possible.

Sign in / Sign up

Export Citation Format

Share Document