This 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.
Background Alcohol drinking is an increasingly recognized risk factor for cardiovascular disease. However, there are few studies of the impact of harmful and hazardous drinking on biomarkers of myocardial health. We conducted a study in Russia to investigate the impact of heavy drinking on biomarkers of cardiac damage and inflammation. Methods and Results The Know Your Heart study recruited a random sample of 2479 participants from the population of northwest Russia (general population) plus 278 patients (narcology clinic subsample) with alcohol problems. The general population sample was categorized into harmful drinkers, hazardous drinkers, nonproblem drinkers, and nondrinkers, according to self‐reported level of alcohol consumption, whereas the narcology clinic sample was treated as the separate group in the analysis. Measurements were made of the following: (1) high‐sensitivity cardiac troponin T, (2) NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), and (3) hsCRP (high‐sensitivity C‐reactive protein). The narcology clinic subsample had the most extreme drinking pattern and the highest levels of all 3 biomarkers relative to nonproblem drinkers in the general population: high‐sensitivity cardiac troponin T was elevated by 10.3% (95% CI , 3.7%–17.4%), NT ‐pro BNP by 46.7% (95% CI , 26.8%–69.8%), and hsCRP by 69.2% (95% CI , 43%–100%). In the general population sample, NT ‐pro BNP was 31.5% (95% CI , 3.4%–67.2%) higher among harmful drinkers compared with nonproblem drinkers. Overall, NT ‐pro BNP and hsCRP increased with increasing intensity of alcohol exposure (test of trend P <0.001). Conclusions These results support the hypothesis that heavy alcohol drinking has an adverse effect on cardiac structure and function that may not be driven by atherosclerosis.
Purpose of investigation: to reveal the combined influence of hypo (Zn, Fe) and hyper (Cd, Pb) microelementosis on functional status of the cardiovascular, endocrine systems and anxiety level of adolescents (13 years of age) living in a chemically contaminated area in Stavropol region. The level of microelements (Cd, Pb, Fe, Zn, Cu) in hair and nails was determined by atomic absorption spectrophotometry method, cortisol in saliva - by ELISA method. The state of the cardiovascular system and its regulatory mechanisms was determined by indicators of variational pulsometry. To assess anxiety level of adolescents test method "Anxiety scale" was used. The analysis of microelement composition of hair and nails in adolescents, living in conditions of chemical environmental pollution with Cd and Pb subliminal doses, revealed the presence of hypo- (Zn, Fe) and hyper- (Cd, Pb) microelementosis. At the same time, increased levels of cortisol in saliva more evident in boys, increased heart rate and mode amplitude, peassure of the central mechanisms of the heart function regulation have been discovered. Change of anxiety level was stated. It has been proved that the determination of the microelement composition of hair and nails can serve as a marker of environmental contamination and complex negative changes, including the imbalance of microelements in hair and nails, functional changes in leading adaptive systems - the hypothalamic-pituitary-adrenocortical axis, cardio-vascular, changes of anxiety level can be used as a marker of dysaptation and predictor of psychosomatic problems.
Men with a burdened alcohol anamnesis, convicted for repeated crimes, commit unlawful acts in penal institutions under the influence of frustration. Aim of this study is to give an assessment to the burdened alcohol anamnesis as a factor associated with commission by convicted of crime repetition wrongful acts connected with a willful behavior misconduct while serving a sentence in penal institutions. Methods: we performed a sociological survey (the author's questionnaire was used) in a strict regime correctional colony (penal institution) in a group of 433 men - prisoners who have committed high intentional crimes in virulent crimes repetition. Results: We found every second convicted person (43.4 %) regularly consumed alcohol (3-4 times a week) before committing a repeated crime, every second convicted person (40.6 %) was drunk at the moment of committing a repeated crime; every eighth convicted person (15.2 %) had signs of harmful alcohol consumption / alcohol dependence according to the Alcohol use disorders identification test's (AUDIT) results. Every third convicted person (35.6 %) intentionally violated the order of serving punishment in penal institutions (attack on other prisoners, escort, etc.). Every additional point in the AUDIT was associated with an increased probability of order violation by a convicted person in 1.061 times (p < 0,001). Conclusions: Alcohol consumption is a factor associated with a repeated crime comission. Burdened alcohol anamnesis predisposes convicted for repeated crime to commit wrongful acts in penal institutions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.