Inotroopsete ravimite farmakokineetika ja farmakodünaamika vastsündinutel

Väitekirja elektrooniline versioon ei sisalda publikatsiooneSuurt osa vastsündinutel kasutatavatest ravimitest ei ole sellel populatsioonil põhjalikult uuritud. Sageli on ravimi doseerimise ja oodatava efekti osas võetud aluseks täiskasvanutel või suurematel lastel läbi viidud uuringute tulemused. Esimestel elutundidel, -päevadel ja -nädalatel aset leidvad füsioloogilised muutused mõjutavad ravimite jaotumist, toimet ja eliminatsiooni viisil, mida ei ole võimalik ennustada täiskasvanute või laste uuringutes kogutud andmete pealt. Käesoleva uurimistöös kogusime ja analüüsisime kahe vastsündinutel sageli kasutatava südant ja vereringet mõjutava ravimi – dobutamiini ja milrinooni – doseerimise, plasmakontsentratsiooni ja toimete vahelisi seoseid. Analüüsiks kasutasime mittelineaarseid segamõjudega mudeleid, mis lisaks kehas ravimiga (farmakokineetika) ja ravimi toimel toimuvatele (farmakodünaamika) protsessidele kirjeldavad ka indiviidide vahelisi variatsioone nendes protsessides ning juhusliku vea suurust, mis tekib ravimi manustamisel ja mõõtmiste teostamisel. Leidsime, et vereringe sünnijärgse ümberkohanemise ajal ilmneb dobutamiini toime südamesagedusele ja vererõhule juba suhteliselt madalatel kontsentratsioonidel ning on küllastuv, südame minutimahtu tõstev toime on uuritud doosi- ja kontsentratsioonivahemikus aga lineaarne või küllastub kõrgematel kontsentratsioonidel. Milrinooni farmakokineetika andmete alusel soovitame ravimi doseerimisskeemi, mis tagab avatud arterioosjuha ligeerimise järgselt ravi vajavatel vastsündinutel kõige suurema tõenäosusega ravimi kontsentratsiooni toimivas vahemikus. Käesolev töö lisab olulist uut teadmist ravimite kasutamiseks vastsündinutel kahes kriitilises olukorras, kus oodatava toime saavutamine, vältides samal ajal kõrvaltoimeid, on eluliselt tähtis.A lot of medications used in neonates are insufficiently studied in this vulnerable population. Often the dosing schemes and expected effects are extrapolated from adult or paediatric studies. Physiological changes within hours, days and weeks after birth affect the distribution, elimination and effect of medications in ways not predictable from adult and paediatric data. The present research analysed dosing, concentration and effect relationships of two cardiovascular medications – dobutamine and milrinone – in neonates in clinical situations where they are frequently used. Nonlinear mixed-effects modelling was used to describe the pharmacokinetic and pharmacodynamic processes with evaluation of interindividual variability and residual variability occurring during treatment and data collection. The effects of dobutamine on heart rate and blood pressure occur with relatively low concentrations and are saturable, contrarily the effect on cardiac output is linear throughout the studied dose- and concentration range or is saturable at higher concentrations. Based on the pharmacokinetic data, milrinone dosing regimen was suggested for preterm neonates undergoing patent arterial duct closure operation and at risk of postoperative respiratory and cardiac function deterioration. Additional to developmental changes the pharmacokinetics and pharmacodynamics of medications in neonates may be affected by the critical illness and intensive care, thereby the most valuable pharmacological data comes from the studies conducted in the particular situations where the effects are expected.https://www.ester.ee/record=b534663

The Balkans Peace Park (B3P) Project Development and Peacebuilding from Ground Up

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Ampitsilliini farmakokineetika enneaegsetel ja ajalistel vastsündinutel esimesel elunädalal

Eesti Arst 2022; 101(2):12

Perceived Stress During the First Wave of COVID-19 Outbreak: Results From Nationwide Cross-Sectional Study in Estonia

Objective: To study the population-level mental health responses during the first wave of coronavirus disease 2019 (COVID-19) outbreak in Estonia and analyze its socio-demographic, behavioral, and health-related variations among general population.Methods: This study used nationally representative data on 4,606 individuals, aged 18–79 years from a rapid-response cross-sectional survey conducted in April 2020. Point prevalence and mutually adjusted prevalence rate ratios for perceived stress from log-binomial regression analysis were presented for socio-demographic, behavioral, and health-related variables.Results: This study found that 52.2% of population aged 18–79 reported elevated stress levels in relation to COVID-19 outbreak. Higher levels of perceived stress were found in women, in younger age groups, in Estonians, and in those with higher self-perceived infection risk, presence of respiratory symptoms, and less than optimal health, according to self-reports.Conclusion: Although, the potential long-term health effects of the current crisis are yet unknown, the alarmingly high stress levels among people indicate that the COVID-19 pandemic might have had a widespread effect on people's mental health

Co-Creation and Enhanced Youth Participation in Local Decision-Making: The Perception of Public Sector Readiness

The reverted demographic pyramid makes youth a decreasing percentage of our increasingly ageing population, leaving youth groups with less power and chances to influence the future of public policies and services through established participation channels. There is a potential risk of losing the interests of broader, including less heard, youth groups in democratic decision-making and implementation. Research evidence shows that we need to broaden knowledge and accountability towards these groups by including them more in co-creation to secure their trust and meaningful policy impact. One major way to improve trust in the public sector is by enhancing the abilities of professionals, managers, politicians and NGOs to co-create public and individual values with youth groups for better services and solutions instead of acting and making decisions on their behalf. Also, cross-sector collaboration among institutional units or stakeholders from different sectors on a local scale is often required to enhance the value of services or local community decisions. This paper explores from a comparative perspective the readiness of the local governments for enhanced democratic participation and co-creation of public services and public value with youth. Based on document studies, interviews and cross-sectoral learning dialogues between engaged researchers, public sector and NGO representatives conducted in three countries – Sweden, Finland, and Estonia – the paper illustrates the current perceptions of public professionals and managers regarding their approach to co-creation with youth and the public