Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations

Nonadherence to drugs is a challenge in hypertension treatment. We aimed to assess the prevalence of nonadherence by serum drug concentrations compared with 2 indirect methods and relate to the prescribed drug regimens in a nationwide multicenter study. Five hundred fifty patients with hypertension using ≥2 antihypertensive agents participated. We measured concentrations of 23 antihypertensive drugs using ultra high performance liquid chromatography tandem mass-spectrometry and compared with patients’ self-reports and investigators’ assessment based on structured interview. We identified 40 nonadherent patients (7.3%) using serum drug concentrations. They had higher office diastolic blood pressure (90 versus 83 mm Hg, P<0.01) and daytime diastolic blood pressure (85 versus 80 mm Hg, P<0.01) though systolic blood pressures did not differ significantly. They had more prescribed daily antihypertensive pills (2.5 versus 2.1 pills, P<0.01) and total daily pills (5.5 versus 4.4 pills, P=0.03). Prescription of fixed-dose combination pills were lower among the nonadherent patients identified by serum concentrations (45.0 versus 67.1%, P<0.01). Fifty-three patients self-reported nonadherence, while the investigators suspected 69 nonadherent patients. These groups showed no or few differences in drug regimens, respectively. In summary, we detected 7.3% prevalence of nonadherence by serum drug measurements in patients using ≥2 antihypertensive agents in a nationwide study; they had higher office and ambulatory diastolic blood pressures, higher number of prescribed daily pills, more daily antihypertensive pills, and less frequent prescriptions of fixed-dose combination pills. Indirect methods showed poor overlap with serum drugs concentrations and no or minimal medication differences. Thus, serum measurements of drugs were useful in detection and characterization of nonadherence to antihypertensive treatment.acceptedVersio

DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development.

BACKGROUND AND AIMS: Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cell (VSMC) phenotype. The DNA glycosylase NEIL3 has previously been shown to have a role in atherogenesis, though whether this is due to its ability to repair DNA damage or to other non-canonical functions is not yet clear. Hereby, we investigate the role of NEIL3 in atherogenesis, specifically in VSMC phenotypic modulation, which is critical in plaque formation and stability. METHODS: Chow diet-fed atherosclerosis-prone Apoe-/- mice deficient in Neil3, and NEIL3-abrogated human primary aortic VSMCs were characterized by qPCR, and immunohistochemical and enzymatic-based assays; moreover, single-cell RNA sequencing, mRNA sequencing, and proteomics were used to map the molecular effects of Neil3/NEIL3 deficiency in the aortic VSMC phenotype. Furthermore, BrdU-based proliferation assays and Western blot were performed to elucidate the involvement of the Akt signaling pathway in the transdifferentiation of aortic VSMCs lacking Neil3/NEIL3. RESULTS: We show that Neil3 deficiency increases atherosclerotic plaque development without affecting systemic lipids. This observation was associated with a shift in VSMC phenotype towards a proliferating, lipid-accumulating and secretory macrophage-like cell phenotype, without changes in DNA damage. VSMC transdifferentiation in Neil3-deficient mice encompassed increased activity of the Akt signaling pathway, supported by cell experiments showing Akt-dependent proliferation in NEIL3-abrogated human primary aortic VSMCs. CONCLUSIONS: Our findings show that Neil3 deficiency promotes atherosclerosis development through non-canonical mechanisms affecting VSMC phenotype involving activation of the Akt signaling pathway

Lærere i kombinasjonsstillinger : - praksisnær teori og teorinær praksis?

Høsten 2018 ble det innledet et forsøk med å opprette stillinger for lærere i kombinasjonsstillinger knyttet til grunnskolelærerutdanningen ved Universitetet i Sørøst-Norge (USN). De som ble tilsatt, arbeider til daglig i grunnskolen og har i de fleste tilfellene erfaring som praksislærere. Prosjektet er ett av flere tiltak som er knyttet til en utviklingsavtale mellom USN og Kunnskapsdepartementet1, som har som formål å videreutvikle og styrke samarbeidet mellom universitetet og praksisfeltet innenfor universitetets profesjonsutdanninger. For å koordinere og lede dette arbeidet ble det opprettet en prosjektorganisasjon kalt USN Profesjon2. USN Profesjon ledes av Kristin Barstad, og ordningen med kombinasjonsstillinger er ett av fire hovedsatsingsområder som omfatter både lærerutdanningene og helse- og sosialfagutdanningene ved USN. Denne rapporten tar for seg ordningen med kombinasjonsstillinger slik den har blitt gjennomført i den femårige grunnskolelærerutdanningen ved USN. Arbeidet er gjennomført i samråd med Arild Hovland, som er dekan ved Fakultet for humaniora, idrett og lærerutdanning, og Anne Fængsrud, som er visedekan for lærerutdanningen. Det empiriske grunnlaget for rapporten består i hovedsak av fokusgruppeintervjuer med lærere som er tilsatt i kombinasjonsstillinger ved hvert de fire studiestedene ved USN som tilbyr grunnskolelærerutdanning, og programkoordinatorene ved de aktuelle studiestedene. Vi retter en stor takk til alle de som på ulike måter har gjort arbeidet med denne rapporten mulig, og håper den vil stimulere til videre drøfting og kvalitetsutvikling av den femårige grunnskolelærerutdanningen ved USN

Mentoring and Induction in the Nordic Countries : Some Introductory Remarks

peerReviewe

Routine pelvic MRI using phased-array coil for detection of extraprostatic tumour extension: accuracy and clinical significance

Objectives To determine the accuracy and assess the clinical significance of surface-coil 1.5-T magnetic resonance imaging (MRI) for the detection of locally advanced prostate cancer (PCa). Methods Between December 2007 and January 2010, we examined 209 PCa patients (mean age = 62.5 years) who were consecutively treated with robot-assisted laparoscopic prostatectomy and prospectively staged by MRI. One hundred and thirty-five patients (64.6 %) had locally advanced disease. Conventional clinical tumour stage and MRI-assessed tumour stage were compared with histopathological tumour stage (pT). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy (OA) were calculated using pT as the “gold standard”. Overstaged and understaged cases at MRI were reviewed. Results Sensitivity, specificity, PPV, NPV and OA for the detection of locally advanced disease were 25.9, 95.9, 92.1, 41.2 and 50.5 % and 56.3, 82.2, 85.4, 50.4 and 65.4 % for clinical staging and MRI, respectively. Among patients understaged at MRI, the resection margins were free in 64.4 % of the cases (38/59). Conclusions Although the accuracy was limited, the detection of locally advanced disease improved substantially when MRI was added to routine clinical staging. The majority of the understaged patients nevertheless achieved free margins. When assessing the clinical significance of MRI staging the extent of extraprostatic extension has to be considered. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited

Lærerstudenters forventninger til arbeidet som profesjonelle lærere i skolen: Resultater fra en spørreundersøkelse i regi av NFR-prosjektet STEP: Partnerskap for bærekraftig overgang fra lærerutdanning til yrke

Formålet med undersøkelsen var å kartlegge hvilke forventninger det første kullet i den femårige integrerte masterutdanningen for grunnskolelærere har til arbeidet som profesjonelle lærere i skolen. Det empiriske grunnlaget for rapporten består av svar fra studenter som nettopp hadde startet i det siste året i grunnskolelærerutdanningen. Spørreskjemaet omfattet i hovedsak spørsmål med faste svaralternativer, men med anledning for respondentene til å kommentere sine svar. Datainnsamlingen ble gjennomført høsten 2021, i en periode preget av Covid19-pandemien med nedstengning og utstrakt nettbasert undervisning som erstatning for planlagt undervisning på campus. Det er også verdt å merke seg at undersøkelsen ble gjennomført før studentene hadde startet arbeidet med masteroppgaven, og deres vurderinger av utdanningen og betydningen av masteroppgaven må forstås i lys av det. Resultatene viser at studentene generelt sett ser fram til yrkesstarten med forventning og spenning. De føler seg godt forberedt til å undervise i fagene de har fordypning i fra utdanningen. Samtidig viser kommentarene at mange er usikre på om de i tilstrekkelig grad er rustet for bredden og kompleksiteten i utfordringene de forventer å møte i skolen. Denne usikkerheten handler i første rekke om to forhold: For det første er de urolige med tanke på eventuelt å undervise i fag de ikke har fordypning i. Videre indikerer svar og kommentarer at de mener de er lite forberedt til å håndtere en del av de oppgavene som understøtter møtet med elevene i klasserommet. Det gjelder i første rekke samarbeid med foresatte, kontaktlærerrollen, samarbeid med skolens hjelpetjenester og tilrettelegging for elever med særskilte behov. Studentene forventer at overgangen fra utdanning til arbeidet i skolen blir krevende. De har en offensiv og læringsorientert holdning til møtet med disse utfordringene. Når det gjelder deres eget behov for tilrettelegging og lærings-støttende tiltak, peker de i første rekke på forventninger om samarbeid med erfarne kolleger, tilpasning fra ledelsen i form av arbeids- og undervisningsplaner som de kan mestre og deltakelse i en kvalitetssikret veiledningsordning i tråd med de nasjonale prinsippene for veiledning av nyutdannede lærere. På spørsmål om hva studentene mener de vil kunne tilføre det profesjonelle fellesskapet i skolen, peker de på entusiasme og glød for elevenes læring og skolemiljø og vilje til å stimulere til elevmedvirkning og demokratiforståelse. Studentene gir også uttrykk for at de tror de kan bidra med en kritisk-analytisk og utforskende tilnærming til undervisning og læring. Både svar og kommentarer viser at svært mange av studentene primært oppfatter arbeidet med masteroppgaven som en ytterligere fordypning og spesialisering i fag

Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations

Nonadherence to drugs is a challenge in hypertension treatment. We aimed to assess the prevalence of nonadherence by serum drug concentrations compared with 2 indirect methods and relate to the prescribed drug regimens in a nationwide multicenter study. Five hundred fifty patients with hypertension using ≥2 antihypertensive agents participated. We measured concentrations of 23 antihypertensive drugs using ultra high performance liquid chromatography tandem mass-spectrometry and compared with patients’ self-reports and investigators’ assessment based on structured interview. We identified 40 nonadherent patients (7.3%) using serum drug concentrations. They had higher office diastolic blood pressure (90 versus 83 mm Hg, P<0.01) and daytime diastolic blood pressure (85 versus 80 mm Hg, P<0.01) though systolic blood pressures did not differ significantly. They had more prescribed daily antihypertensive pills (2.5 versus 2.1 pills, P<0.01) and total daily pills (5.5 versus 4.4 pills, P=0.03). Prescription of fixed-dose combination pills were lower among the nonadherent patients identified by serum concentrations (45.0 versus 67.1%, P<0.01). Fifty-three patients self-reported nonadherence, while the investigators suspected 69 nonadherent patients. These groups showed no or few differences in drug regimens, respectively. In summary, we detected 7.3% prevalence of nonadherence by serum drug measurements in patients using ≥2 antihypertensive agents in a nationwide study; they had higher office and ambulatory diastolic blood pressures, higher number of prescribed daily pills, more daily antihypertensive pills, and less frequent prescriptions of fixed-dose combination pills. Indirect methods showed poor overlap with serum drugs concentrations and no or minimal medication differences. Thus, serum measurements of drugs were useful in detection and characterization of nonadherence to antihypertensive treatment

DNA glycosylase Neil3 regulates vascular smooth muscle cell biology during atherosclerosis development

Background and aims Atherogenesis involves a complex interaction between immune cells and lipids, processes greatly influenced by the vascular smooth muscle cell (VSMC) phenotype. The DNA glycosylase NEIL3 has previously been shown to have a role in atherogenesis, though whether this is due to its ability to repair DNA damage or to other non-canonical functions is not yet clear. Hereby, we investigate the role of NEIL3 in atherogenesis, specifically in VSMC phenotypic modulation, which is critical in plaque formation and stability. Methods Chow diet-fed atherosclerosis-prone Apoe−/− mice deficient in Neil3, and NEIL3-abrogated human primary aortic VSMCs were characterized by qPCR, and immunohistochemical and enzymatic-based assays; moreover, single-cell RNA sequencing, mRNA sequencing, and proteomics were used to map the molecular effects of Neil3/NEIL3 deficiency in the aortic VSMC phenotype. Furthermore, BrdU-based proliferation assays and Western blot were performed to elucidate the involvement of the Akt signaling pathway in the transdifferentiation of aortic VSMCs lacking Neil3/NEIL3. Results We show that Neil3 deficiency increases atherosclerotic plaque development without affecting systemic lipids. This observation was associated with a shift in VSMC phenotype towards a proliferating, lipid-accumulating and secretory macrophage-like cell phenotype, without changes in DNA damage. VSMC transdifferentiation in Neil3-deficient mice encompassed increased activity of the Akt signaling pathway, supported by cell experiments showing Akt-dependent proliferation in NEIL3-abrogated human primary aortic VSMCs. Conclusions Our findings show that Neil3 deficiency promotes atherosclerosis development through non-canonical mechanisms affecting VSMC phenotype involving activation of the Akt signaling pathway