Digital teknologi i matematikkundervisningen : En kvalitativ studie om hvordan digital teknologi integreres i matematikkundervisningen på 1.-7. trinn

Master's thesis in Mathematics education (MA502

Forekomsten av REDs hos unge mannlige toppidrettsutøvere og en kontrollgruppe

Bakgrunn: REDs er et multifaktorielt syndrom som påvirker utøvere i alle aldre og blant begge kjønn. Det er gjort betydelig mindre forskning av dette fenomenet på menn og enda mindre blant unge utøvere. Hensikt: Hensikten med denne studien var å undersøke forekomsten av REDs-indikatorer blant unge mannlige toppidrettsutøvere og hos en kontrollgruppe som ikke konkurrerer. Metode: Totalt 29 deltakere fordelt på utholdenhetsutøvere (n=13), ballspillutøvere (n=8) og kontrollgruppe (n=8) deltok i studien. Forekomsten av REDs-indikatorer ble undersøkt med objektive målinger og selvrapportering i form av spørreskjemaer. De objektive målingene av REDs- indikatorer var måling av kroppssammensetning (målt med dobbel røntgen absorpsjonsmetri) og hvilemetabolisme med indirekte kalorimetri. Spørreskjemaene som ble brukt var BEDA-Q (Brief Eating Disorder in Athletes Questionnaire), EDE-Q (Eating Disorder Examination Questionnaire), EAI-Y (Exercise Addiction Inventory for Youth) og DLS (Drive for Leanness Scale). Resultater Det var høyest forekomst av REDs-indikatorer blant kontrollgruppen, hvorav 100% av gruppen viste minst én indikator. Utholdenhetsutøverne viste den nest høyeste forekomsten, da 69% av utøverne viste minst én indikator. Ballspillutøverne hadde den minste forekomsten av REDs-indikatorer, hvor 50% viste én indikator og de resterende hadde ingen. Konklusjon 72% av deltakerne i dette masterprosjektet viste tegn til minst én REDs-indikator noe som kan antyde av unge utøvere er i risikogruppen for utvikling av REDs. Det er begrenset forskning på denne gruppen, spesielt longitudinelle studier. Videre studier bør undersøke forekomsten av REDs-indikatorer blant denne gruppen, spesielt ved bruk av primær- og sekundærindikatorer

Significantly lower CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine metabolic ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients

Aims CYP2D6*9, CYP2D6*10 and CYP2D6*41 are the most frequent reduced-function CYP2D6 alleles in Caucasians. Despite lacking in vivo evidence, they are collectively classified with an enzyme activity score of 0.5. Thus, the aim of this study was to compare the functional impact of CYP2D6*9, CYP2D6*10 and CYP2D6*41 on CYP2D6 metabolism in a large patient population. Methods A total of 1003 patients (mainly Caucasians) with data on CYP2D6 genotype and serum concentrations of venlafaxine and metabolites were included from a therapeutic drug monitoring service in Oslo, Norway. The O-desmethyl-to-N-desmethyl-venlafaxine metabolic ratio (MR) was applied as CYP2D6 biomarker and compared (Mann-Whitney) between carriers of CYP2D6*9-10 (merged) and CYP2D6*41, either combined with CYP2D6*1 or non-coding (null) alleles. MR subgroup estimates were obtained by multiple linear regression for calculations of CYP2D6*9-10 and CYP2D6*41 activity scores. Results MR was significantly lower in carriers of CYP2D6*41 than CYP2D6*9-10 (P lt 0.002). The majority of CYP2D6*41/null carriers (86.7%) had MR in the observed range of CYP2D6null/null carriers compared with the minority of CYP2D6*9-10/null carriers (17.4%). CYP2D6 genotype explained 60.7% of MR variability in the multivariate analysis providing subgroup estimates of 9.54 (95% CI; 7.45-12.20), 3.55 (2.06-6.10), 1.33 (0.87-2.05) and 0.47 (0.35-0.61) in carriers of CYP2D6*1/null (n = 269), CYP2D6*9-10/null (n = 17), CYP2D6*41/null (n = 30) and CYP2D6null/null (n = 95), respectively. Based on these estimates, the calculated activity score of CYP2D6*41 was 0.095 compared to 0.34 for CYP2D6*9-10. Conclusions CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Thus, these alleles should be differentiated when classifying CYP2D6 phenotype from genotype

Genotyping av pasienter behandlet med selektive serotoninreopptakshemmere

BAKGRUNN - Selektive serotoninreopptakshemmere (SSRI) brukes av over 180 000 mennesker i Norge. Enzymene CYP2D6 og CYP2C19 er sentrale i metabolismen av SSRI-antidepressiver. Serotonintransportøren kodet av SLC6A4 kan ha betydning for effekten av medikamentene. MATERIALE OG METODE - Alle pasienter som hadde blitt genotypet for CYP2D6, CYP2C19 og SLC6A4 ved Senter for psykofarmakologi i 2020, uavhengig av indikasjon, ble inkludert. Hos de pasientene der data var tilgjengelige, ble CYP2C19-genotype koblet til serumkonsentrasjonsmåling av escitalopram, som er det mest brukte SSRI-preparatet. RESULTATER - 432 av 3 492 pasienter (12,4 %) hadde en kombinasjon av genotyper av CYP2D6, CYP2C19 og SLC6A4 som anses å gi mest gunstig metabolisme og effekt av SSRI-antidepressiver. Pasienter med manglende CYP2C19-metabolisme hadde mer enn halvert dosebehov for å oppnå samme konsentrasjon av escitalopram som pasienter med normal metabolisme. FORTOLKNING - Våre funn viser lav forekomst av den gunstigste genotypekombinasjonen for respons av SSRI-preparater. Genotypekombinasjoner bidrar sannsynligvis til den store individuelle variasjonen i effekt av disse medikamentene og til at behandlingen ikke gir ønsket utfall hos mange pasienter

Pharmacokinetic Variability of Olanzapine : A Study Based on Therapeutic Drug Monitoring Data

Olanzapine is one of the most commonly used antipsychotic drugs in treatment of schizophrenia and bipolar disorder. The interindividual variability in pharmacokinetics of olanzapine is extensive, with a 10-20-fold difference in serum concentration despite equivalent dosing. The aim of this thesis was to identify and evaluate factors that influence the pharmacokinetics of olanzapine, and thereby provide knowledge that can be applied in order to individualize treatment with olanzapine. Therapeutic drug monitoring samples from patients treated with olanzapine were used as data material in all four studies of the thesis. The serum concentration of olanzapine and metabolites were quantified with liquid chromatography-mass spectrometry (LC-MS) analyses. Overall, cigarette smoking, age and gender were shown to be significant determinants of olanzapine variability. Non-smokers generally obtained a two-fold higher dose-adjusted serum concentration (C/D ratio) compared to smokers. Age and gender were also shown to be significant determinants of olanzapine C/D ratio, but the numerical effects of these factors were less than those mentioned above. Furthermore, it was shown that comedication with the antiepileptic drugs valproic acid and carbamazepine substantially affected C/D ratio of olanzapine. The estimated reductions were approximately 30% and 50%, respectively. Concurrent use of ethinyl-estradiol containing contraceptives and a mutation in the gene encoding uridine diphosphate glycosyl transferase 1A4 (UGT1A4) did not affect serum concentration of olanzapine significantly, but both were shown to have significant impact on metabolic pathways of olanzapine. In conclusion, the present thesis reveals that cigarette smoking, age, gender and comedication with valproic acid or carbamazepine are significant factors which contribute to the variability in pharmacokinetics of olanzapine. Summarized, a female, non-smoking patient ≥60 years receiving olanzapine monotherapy, would on average obtain a more than 3-fold higher C/D ratio compared to a male, smoking patient <60 years comedicated with valproic acid or carbamazepine. To improve the therapeutic effect and reduce the risk of side effects, these factors should be considered as a basis for individualized dosing of olanzapine in clinical practice

Relationship between cytochrome P450 polymorphisms and prescribed medication in elderly haemodialysis patients

Background Elderly patients on haemodialysis have a high prevalence of polypharmacy and are at risk of drug-related complications. More than 80 % of all prescribed drugs are metabolized by the cytochrome P450 (CYP) enzyme system. The aims of this study were to describe the prevalence of polymorphism in three CYP isoenzymes and the relationship between CYP polymorphism and prescribed drugs. Methods Fifty-one elderly haemodialysis patients aged ≥65 years were included. CYP-genotyping was carried out in whole blood by a real-time PCR method for detecting common variant alleles in CYP2C9, CYP2C19 and CYP2D6. The allele frequencies were calculated using the Hardy–Weinberg equation. Results The overall prevalence of CYP polymorphisms (heterozygous and homozygous) was 77 %. The prevalence of heterozygous carriers of variant alleles coding for defective CYP2D6, CYP2C9 and CYP2C19 was 64, 22 and 55 %, respectively; the prevalence of homozygous carriers was 6 % for each of the CYP2D6, CYP2C9 and CYP2C19 enzymes. The prevalence of the CYP2D6*6, CYP2D6*9 and CYP2D6*41 variant alleles did not differ (p = 0.31) from that in a European Caucasian reference population. Twenty-three patients (45 %) had at least one CYP mutation and used drugs that are metabolized by the CYP isoenzymes. Metoprolol and proton-pump inhibitors were the most commonly used drugs that could be affected by a heterozygous or homozygous mutation. Conclusions Polymorphisms of CYP2C9, CYP2C19 and CYP2D6 are common in elderly haemodialysis patients. Many of these patients have a phenotype with altered CYP enzyme activity and could benefit from close drug monitoring or a drug switch

Pharmacotherapy of patients with schizophrenia living in nursing homes : -Impact of genetic and environmental factors

Schizophrenia is characterized by early onset and chronic lapse in most of the patients. The suffering associated with schizophrenia is enormous – for patients, families, and in society at large. Pharmacotherapy is the mainstay of treatment, without which most psychosocial treatment would not be possible. However, substantial variety in efficacy as well as frequently reported side effects are problems often encountered with current antipsychotic treatment. Cytochrome P450 (CYP) enzymes are involved in the metabolism of most psychotropic drugs and characterized as the most important factor for individual variation to drug response. This study investigated pharmacotherapy of schizophrenic inpatients in seven different nursing homes receiving long-term antipsychotic treatment. Impact of environmental- and genetic factors on serum concentration of antipsychotics was studied. CYP-genotyping of isoenzymes CYP2C9, CYP2C19 and CYP2D6 were performed for both a patient group (n=109) and a control group (n=136). Clinical data were collected from records and medicine cards. Serum concentrations (trough) were obtained for all antipsychotics used by the patients. The patients were on average treated with 1.5 antipsychotics and 2.7 concomitant drugs. Our patient group received a total of 2.2 defined daily doses (DDD) of antipsychotics compared to an average of 1.2 DDD reported in a study of psychiatric hospital inpatients. The measured genotypes were not significantly different between the patient- and control group. Only one of the patients had been genotyped prior to the project. Patients being poor metabolizers had higher serum concentrations and patients being ultra rapid metabolizers had decreased serum concentrations from a given dose. CYP2D6 intermediate-metabolizer genotype appeared to be important in some patients, especially when other factors (e.g. environmental, polypharmacy) were present. Low doses of CYP2D6 inhibitors appeared to be of minor importance as long as it was the only factor influencing CYP activity. Use of CYP inducers led to decreased serum concentrations. Smoking did significantly decrease serum concentrations of CYP1A2 substrates and the induction seemed to be similar in heavy compared to light smokers. Pharmacotherapy in patients suffering from chronic schizophrenia is characterized by polypharmacy and somewhat high doses of antipsychotics. Both genetic and environmental factors appear to influence the serum concentration. CYP-genotyping combined with therapeutic drug monitoring can be an important tool in individualization of drug regimes. Reassessing the pharmacotherapy of some of these patients might lead to an improvement of their current treatment

Digital teknologi i matematikkundervisningen : En kvalitativ studie om hvordan digital teknologi integreres i matematikkundervisningen på 1.-7. trinn

Master's thesis in Mathematics education (MA502