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.

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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.

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Relevance. Internal Affairs employees during the anti-epidemic measures of COVID-19 period protected public order and the safety of citizens in crowded places. During the pandemic, according to departmental statistics, morbidity rates in police officers were 6.6 times higher than in general population and close to the healthcare professionals. Due to police officers' professional activities, the COVID-19 pandemic was associated not only with high contamination risks, but also with certain emotional stress and destabilization.Intention. To identify mental traumatization features in police officers who serve to protect public order and citizens safety during the COVID-19 pandemic.Methodology. 371 male employees of the Internal Affairs Headquarters in Moscow were surveyed. Three groups were identified: Group I - 127 police officers (average age 33.3 ± 1.1 years, service experience 6.1 ± 1.3 years) with positive test results and COVID-19 clinical manifestations (mild and moderate severity, inpatient and outpatient treatment) over the period from 10.04.2020 to 9.06.2020 (the restrictive measures and self-isolation period announced by the decree of the Russian Chief State Sanitary Doctor on 30.03.2020 N 9 “On additional measures to prevent the COVID-2019 spread in connection with the COVID-19 pandemic”); Group II - 118 healthy police officers (average age 30.9 ± 1.5 years, service experience 5.6 ± 1.9 years), without COVID-19 clinical manifestations but released from their duties as contacts; Group III - 126 healthy police officers (average age 32.4 ± 1.5 years, service experience 7.1 ± 1.9 years) not released from their duties during the COVID-19 pandemic, who protected public order in crowded places (patrolling streets, metro duty, etc.). Our questionnaire was intended for self-assessing mental state, and experimental psychological examination was also included. To meet the anti-epidemic requirements, respondents were surveyed online using electronic digital resources.Results and Discussion. Based on self-assessment results, police officers in all groups showed high levels of well-being, mood, performance and emotional stability on duty during the COVID-19 pandemic.Mental traumatization in police officers of the Group 1 was associated with increased personal anxiety and responses to everyday situations tended to be maladaptive, with physical and verbal aggression, irritation. In Group 2 employees, mental trauma included emotional stress and situational anxiety associated with the COVID-19 risk. Healthy police officers who were not released from their duties during the COVID-19 pandemic and continued to serve as law enforcement officers in crowded areas were prone to non-constructive responses to stress in the form of feelings of guilt, hostility, and irritability. In all respondents, constructive business relationships with direct managers and additional financial incentives helped prevent psychological trauma during the COVID-19 pandemic.Conclusion. The study results justify developing an algorithm for psycho-prevention in police officers during medical and biological emergencies, including psychological support, social support and a positive social environment in service teams. This will help prevent the psychological trauma and borderline mental disorders in police officers and, accordingly, increase their personal reliability and reduce damage to the Department image.