Tilrettelegging for lek og aktivitet ute om vinteren: En bacheloroppgave som omhandler personalet som tilretteleggere ute om vinteren.

Problemstilling: Hvordan legger personalet i barnehagen til rette for lek og fysisk aktivitet for 2-åringene ute om vinteren?publishedVersio

Pro-arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients – a study based on a cohort of 19,742 patients

Background - For a decade, patients have been advised against using high citalopram- and escitalopram-doses due to risk for ventricular arrhythmia and cardiac arrest. Still, these drugs are widely used to treat depression and anxiety especially in older patients. It is unclear why they are cardiotoxic and at what serum concentrations patients are at risk for arrhythmias. Thus, how many patients that are at risk for iatrogenic cardiac arrest is unknown. Methods - We studied the arrhythmogenic effects of citalopram, escitalopram and their metabolites on human cardiomyocytes. Concentrations showing pro-arrhythmic activity were compared with observed drug and metabolite serum concentrations in a cohort of 19,742 patients (age 12–105 years) using escitalopram or citalopram in Norway (2010–2019). As arrhythmia-risk is related to maximum serum concentration, this was simulated for different age-groups from the escitalopram patient material. Findings - Therapeutic concentrations of both citalopram and escitalopram but not their metabolites showed pro-arrhythmic changes in the human cardiac action potential. Due to age-dependent reduction of drug clearance, the proportion of patients above threshold for arrhythmia-risk increased with age. 20% of patients >65 years were predicted to reach potentially pro-arrhythmic concentrations, following intake of 10 mg escitalopram. Interpretation - All patients that are using escitalopram or citalopram and have genetic disposition for acquired long-QT syndrome, are >65 years, are using additional pro-arrhythmic drugs or have predisposition for arrhythmias, should be monitored with therapeutic drug monitoring (TDM) to avoid exposure to potentially cardiotoxic concentrations. Serum concentrations should be kept below 100 nM, to reduce arrhythmia-risk

Vapor-liquid equilibrium data for the carbon dioxide and nitrogen (CO2+N2) system at the temperatures 223, 270, 298 and 303 K and pressures up to 18 MPa

A new setup for the measurement of vapor-liquid phase equilibria of CO2-rich mixtures relevant for carbon capture and storage (CCS) transport conditions is presented. An isothermal analytical method with a variable volume cell is used. The apparatus is capable of highly accurate measurements in terms of pressure, temperature and composition, also in the critical region. Vapor-liquid equilibrium (VLE) measurements for the binary system CO2+N2 are reported at 223, 270, 298 and 303 K, with estimated standard uncertainties of maximum 0.006 K in the temperature, maximum 0.003 MPa in the pressure, and maximum 0.0004 in the mole fractions of the phases. These measurements are verified against existing data. Although some data exists, there is little trustworthy data around critical conditions, and our data indicate a need to revise the parameters of existing models. A fit made against our data of the vapor-liquid equilibrium prediction of GERG-2008/EOS-CG for CO2+N2 is presented. At 223 and 298 K, the critical region of the isotherm are fitted using a scaling law, and high accuracy estimates for the critical composition and pressure are found

Dopamine agonist serum concentrations and impulse control disorders in Parkinson's disease

Background and purpose: Impulse control disorders (ICDs) are common among Parkinson's disease patients using dopamine agonists. We wanted to determine whether ICD patients have higher dopamine agonist serum concentrations than those without any sign of ICD. Methods: Patients who used either pramipexole or ropinirole depot once daily were screened for ICDs using the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease–Rating Scale. Those who scored above the cut-off for one or more of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping, and binge-eating) were compared in a case–control study to patients who scored zero points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily dose, and then 6 and 12 h later. Results: Forty-six patients were included: 19 ICD-positive and 27 controls. Ropinirole serum concentrations 6 h after daily intake (Cmax) were higher in the case group compared to the control group, as was the daily ropinirole dosage. No differences were observed in serum concentrations, dosage or total drug exposure for pramipexole. Disease duration and length of dopamine agonist treatment was significantly longer among ICD patients for ropinirole, but not for pramipexole. Conclusions: The use of pramipexole may in itself confer high ICD risk, whereas ICDs among ropinirole users depend more on serum concentration and drug exposure. The pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD

Profiting from CCS Innovations: A Study to Measure Potential Value Creation from CCS Research and Development

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Population pharmacokinetics of tacrolimus in kidney transplant recipients - A model for individual dosing

Background: Population pharmacokinetics is the study of pharmacokinetic variability in the population. One goal of such studies is to improve individual drug treatment by identifying relationships between pharmacokinetic parameters and patient characteristics. Tacrolimus is an immunosuppressive drug used in kidney transplantation. Tacrolimus has a narrow therapeutic window and large pharmacokinetic variability both between and within patients. In addition, dose-normalized whole blood concentrations tend to increase during the first months after kidney transplantation. Therefore, individual dosing of tacrolimus is a major clinical challenge. The objective of this study was to develop a population pharmacokinetic model for tacrolimus to aid in prediction of initial dose and individual dose requirements during the first ten weeks after kidney transplantation. Methods: Twenty-nine kidney transplant recipients contributed full pharmacokinetic profiles of tacrolimus at 44 dosing occasions, and 44 patients contributed trough concentrations from the first ten weeks after kidney transplantation. A total of 1546 blood samples were analyzed. Demographic, clinical and pharmacogenetic patient characteristics were evaluated as covariates. Population pharmacokinetic modeling was performed in NONMEM 7.2®. Results: A two compartment model with first order absorption and lag time adequately described the data. Relative bioavailability was 24 % lower in females than in males and 49 % lower in CYP3A5 expressers than in CYP3A5 nonexpressers. Fat free mass was the most predictive body size metric. Whole blood concentrations of tacrolimus increased linearly with increasing hematocrit. An underlying increase in hematocrit with time after kidney transplantation largely explained the apparent time-varying pharmacokinetics of tacrolimus. In addition, relative bioavailability was 122 % higher than its lowest value immediately after transplantation, decreased to its lowest value during the first four days and subsequently increased by 31 % with an asymptote at day 60. Conclusions: Initial dose of tacrolimus should be predicted from sex, CYP3A5 genotype, fat free mass and hematocrit. Hematocrit is an important factor to predict changes in tacrolimus whole blood concentrations over time. The model may potentially aid in individual dosing of tacrolimus. Its predictive performance must be evaluated before application in clinical practice