24 results on '"Åsberg, Anders"'
Search Results
2. Optimization of Ganciclovir and Valganciclovir Starting Dose in Children by Machine Learning.
- Author
-
Ponthier, Laure, Autmizguine, Julie, Franck, Benedicte, Åsberg, Anders, Ovetchkine, Philippe, Destere, Alexandre, Marquet, Pierre, Labriffe, Marc, and Woillard, Jean-Baptiste
- Subjects
RANDOM forest algorithms ,VALGANCICLOVIR ,GANCICLOVIR ,MONTE Carlo method ,ACHIEVEMENT tests ,DEMOGRAPHIC characteristics ,MACHINE learning ,IMAGING phantoms - Abstract
Background and Objectives: Ganciclovir (GCV) and valganciclovir (VGCV) show large interindividual pharmacokinetic variability, particularly in children. The objectives of this study were (1) to develop machine learning (ML) algorithms trained on simulated pharmacokinetics profiles obtained by Monte Carlo simulations to estimate the best ganciclovir or valganciclovir starting dose in children and (2) to compare its performances on real-world profiles to previously published equation derived from literature population pharmacokinetic (POPPK) models achieving about 20% of profiles within the target. Materials and Methods: The pharmacokinetic parameters of four literature POPPK models in addition to the World Health Organization (WHO) growth curve for children were used in the mrgsolve R package to simulate 10,800 pharmacokinetic profiles. ML algorithms were developed and benchmarked to predict the probability to reach the steady-state, area-under-the-curve target (AUC
0–24 within 40–60 mg × h/L) based on demographic characteristics only. The best ML algorithm was then used to calculate the starting dose maximizing the target attainment. Performances were evaluated for ML and literature formula in a test set and in an external set of 32 and 31 actual patients (GCV and VGCV, respectively). Results: A combination of Xgboost, neural network, and random forest algorithms yielded the best performances and highest target attainment in the test set (36.8% for GCV and 35.3% for the VGCV). In actual patients, the best GCV ML starting dose yielded the highest target attainment rate (25.8%) and performed equally for VGCV with the Franck model formula (35.3% for both). Conclusion: The ML algorithms exhibit good performances in comparison with previously validated models and should be evaluated prospectively. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
3. Digoxin Pharmacokinetics in Patients with Obesity Before and After a Gastric Bypass or a Strict Diet Compared with Normal Weight Individuals.
- Author
-
Kvitne, Kine Eide, Hovd, Markus, Johnson, Line Kristin, Wegler, Christine, Karlsson, Cecilia, Artursson, Per, Andersson, Shalini, Sandbu, Rune, Hjelmesæth, Jøran, Skovlund, Eva, Jansson-Löfmark, Rasmus, Christensen, Hege, Åsberg, Anders, and Robertsen, Ida
- Subjects
MORBID obesity ,GASTRIC bypass ,DIGOXIN ,DIET ,PHARMACOKINETICS ,WEIGHT loss ,GALLBLADDER - Abstract
Background and Objective: Several drugs on the market are substrates for P-glycoprotein (P-gp), an efflux transporter highly expressed in barrier tissues such as the intestine. Body weight, weight loss, and a Roux-en-Y gastric bypass (RYGB) may influence P-gp expression and activity, leading to variability in the drug response. The objective of this study was therefore to investigate digoxin pharmacokinetics as a measure of the P-gp phenotype in patients with obesity before and after weight loss induced by an RYGB or a strict diet and in normal weight individuals. Methods: This study included patients with severe obesity preparing for an RYGB (n = 40) or diet-induced weight loss (n = 40) and mainly normal weight individuals scheduled for a cholecystectomy (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day) followed by an additional 6 weeks of <800 kcal/day induced by an RYGB (performed at week 3) or a very-low-energy diet. Follow-up time was 2 years, with four digoxin pharmacokinetic investigations at weeks 0, 3, and 9, and year 2. Hepatic and jejunal P-gp levels were determined in biopsies obtained from the patients undergoing surgery. Results: The RYGB group and the diet group had a comparable weight loss in the first 9 weeks (13 ± 2.3% and 11 ± 3.6%, respectively). During this period, we observed a minor increase (16%) in the digoxin area under the concentration–time curve from zero to infinity in both groups: RYGB: 2.7 µg h/L [95% confidence interval (CI) 0.67, 4.7], diet: 2.5 µg h/L [95% CI 0.49, 4.4]. In the RYGB group, we also observed that the time to reach maximum concentration decreased after surgery: from 1.0 ± 0.33 hours at week 3 to 0.77 ± 0.08 hours at week 9 (−0.26 hours [95% CI −0.47, −0.05]), corresponding to a 25% reduction. Area under the concentration–time curve from zero to infinity did not change long term (week 0 to year 2) in either the RYGB (1.1 µg h/L [−0.94, 3.2]) or the diet group (0.94 µg h/L [−1.2, 3.0]), despite a considerable difference in weight loss from baseline (RYGB: 30 ± 7%, diet: 3 ± 6%). At baseline, the area under the concentration–time curve from zero to infinity was −5.5 µg h/L [95% CI −8.5, −2.5] (−26%) lower in patients with obesity (RYGB plus diet) than in normal weight individuals scheduled for a cholecystectomy. Further, patients undergoing an RYGB had a 0.05 fmol/µg [95% CI 0.00, 0.10] (29%) higher hepatic P-gp level than the normal weight individuals. Conclusions: Changes in digoxin pharmacokinetics following weight loss induced by a pre-operative low-energy diet and an RYGB or a strict diet (a low-energy diet plus a very-low-energy diet) were minor and unlikely to be clinically relevant. The lower systemic exposure of digoxin in patients with obesity suggests that these patients may have increased biliary excretion of digoxin possibly owing to a higher expression of P-gp in the liver. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Intraindividual Variability in Absolute Bioavailability and Clearance of Midazolam in Healthy Individuals.
- Author
-
Kvitne, Kine Eide, Drevland, Ole Martin, Haugli, Nora, Skadberg, Eline, Zaré, Hasse Khiabani, Åsberg, Anders, and Robertsen, Ida
- Subjects
BIOAVAILABILITY ,MIDAZOLAM ,WEIGHT loss ,BODY mass index ,GASTRIC bypass - Abstract
Background and Objective: Midazolam is the preferred clinical probe drug for assessing CYP3A activity. We have previously shown substantial intraindividual variability in midazolam absolute bioavailability and clearance in patients with obesity before and after weight loss induced by gastric bypass or a strict diet. The objective was to describe intraindividual variability in absolute bioavailability and clearance of midazolam in healthy individuals without obesity. Methods: This study included 33 healthy volunteers [28 ± 8 years, 21% males, body mass index (BMI) 23 ± 2.5 kg/m
2 ] subjected to four pharmacokinetic investigations over a 2-month period (weeks 0, 2, 4, and 8). Semi-simultaneous oral (0 h) and intravenous (2 h later) midazolam dosing was used to assess absolute bioavailability and clearance of midazolam. Results: At baseline, mean absolute bioavailability and clearance were 46 ± 18% and 31 ± 10 L/h, respectively. The mean coefficient of variation (CV, %) for absolute bioavailability and clearance of midazolam was 26 ± 15% and 20 ± 10%, respectively. Approximately one-third had a CV > 30% for absolute bioavailability, while 13% had a CV > 30% for clearance. Conclusions: On average, intraindividual variability in absolute bioavailability and clearance of midazolam was low to moderate; however, especially absolute bioavailability showed considerable variability in a relatively large proportion of the individuals. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
5. Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance.
- Author
-
Hovd, Markus, Robertsen, Ida, Johnson, Line Kristin, Krogstad, Veronica, Wegler, Christine, Kvitne, Kine Eide, Kringen, Marianne Kristiansen, Skovlund, Eva, Karlsson, Cecilia, Andersson, Shalini, Artursson, Per, Sandbu, Rune, Hjelmesæth, Jøran, Åsberg, Anders, Jansson-Löfmark, Rasmus, and Christensen, Hege
- Subjects
GASTRIC bypass ,ROSUVASTATIN ,WEIGHT loss ,BODY weight - Abstract
Introduction: Rosuvastatin pharmacokinetics is mainly dependent on the activity of hepatic uptake transporter OATP1B1. In this study, we aimed to investigate and disentangle the effect of Roux-en-Y gastric bypass (RYGB) and weight loss on oral clearance (CL/F) of rosuvastatin as a measure of OATP1B1-activity. Methods: Patients with severe obesity preparing for RYGB (n = 40) or diet-induced weight loss (n = 40) were included and followed for 2 years, with four 24-hour pharmacokinetic investigations. Both groups underwent a 3-week low-energy diet (LED; < 1200 kcal/day), followed by RYGB or a 6-week very-low-energy diet (VLED; < 800 kcal/day). Results: A total of 80 patients were included in the RYGB group (40 patients) and diet-group (40 patients). The weight loss was similar between the groups following LED and RYGB. The LED induced a similar (mean [95% CI]) decrease in CL/F in both intervention groups (RYGB: 16% [0, 31], diet: 23% [8, 38]), but neither induced VLED resulted in any further changes in CL/F. At Year 2, CL/F had increased by 21% from baseline in the RYGB group, while it was unaltered in the diet group. Patients expressing the reduced function SLCO1B1 variants (c.521TC/CC) showed similar changes in CL/F over time compared with patients expressing the wild-type variant. Conclusions: Neither body weight, weight loss nor RYGB per se seem to affect OATP1B1 activity to a clinically relevant degree. Overall, the observed changes in rosuvastatin pharmacokinetics were minor, and unlikely to be of clinical relevance. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Kidney biopsy diagnosis in childhood in the Norwegian Kidney Biopsy Registry and the long-term risk of kidney replacement therapy: a 25-year follow-up.
- Author
-
Gjerstad, Ann Christin, Skrunes, Rannveig, Tøndel, Camilla, Åsberg, Anders, Leh, Sabine, Klingenberg, Claus, Døllner, Henrik, Hammarstrøm, Clara, and Bjerre, Anna Kristina
- Subjects
KIDNEY disease diagnosis ,CHRONIC kidney failure complications ,THERAPEUTICS ,PATIENT aftercare ,REPORTING of diseases ,BIOPSY ,NEPHRITIS ,RENAL replacement therapy ,RETROSPECTIVE studies ,RISK assessment ,DESCRIPTIVE statistics ,RESEARCH funding ,GLOMERULONEPHRITIS ,CYSTIC kidney disease ,LONGITUDINAL method ,SECONDARY analysis ,FOCAL segmental glomerulosclerosis ,URINARY calculi ,DISEASE complications ,CHILDREN - Abstract
Background: There is scarce information on biopsy-verified kidney disease in childhood and its progression to chronic kidney disease stage 5 (CKD 5). This study aims to review biopsy findings in children, and to investigate risk of kidney replacement therapy (KRT). Methods: We conducted a retrospective long-term follow-up study of children included in the Norwegian Kidney Biopsy Registry (NKBR) and in the Norwegian Renal Registry (NRR) from 1988 to 2021. Results: In total, 575 children with a median (interquartile range, IQR) age of 10.7 (6.1 to 14.1) years were included, and median follow-up time (IQR) after kidney biopsy was 14.3 (range 8.9 to 21.6) years. The most common biopsy diagnoses were minimal change disease (MCD; n = 92), IgA vasculitis nephritis (IgAVN; n = 76), IgA nephropathy (n = 63), and focal and segmental glomerulosclerosis (FSGS; n = 47). In total, 118 (20.5%) of the biopsied children reached CKD 5, median (IQR) time to KRT 2.3 years (7 months to 8.4 years). Most frequently, nephronophthisis (NPHP; n = 16), FSGS (n = 30), IgA nephropathy (n = 9), and membranoproliferative glomerulonephritis (MPGN; n = 9) led to KRT. Conclusions: The risk of KRT after a kidney biopsy diagnosis is highly dependent on the diagnosis. None of the children with MCD commenced KRT, while 63.8% with FSGS and 100% with NPHP reached KRT. Combining data from kidney biopsy registries with registries on KRT allows for detailed information concerning the risk for later CKD 5 after biopsy-verified kidney disease in childhood. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants.
- Author
-
Tran, Trung The, Vaage, Eline Benno, Mehta, Adi, Chopra, Adity, Tietze, Lisa, Kolderup, Anette, Anthi, Aina, König, Marton, Nygaard, Gro, Lind, Andreas, Müller, Fredrik, Nissen-Meyer, Lise Sofie, Magnus, Per, Trogstad, Lill, Mjaaland, Siri, Søraas, Arne, Midtvedt, Karsten, Åsberg, Anders, Barratt-Due, Andreas, and Medhus, Asle W.
- Subjects
ANTIBODY titer ,IMMUNOGLOBULINS ,SARS-CoV-2 Omicron variant ,SARS-CoV-2 ,PROTEIN domains ,COVID-19 vaccines - Abstract
Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
8. Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.
- Author
-
Eide Kvitne, Kine, Hole, Kristine, Krogstad, Veronica, Wollmann, Birgit Malene, Wegler, Christine, Johnson, Line K., Hertel, Jens K., Artursson, Per, Karlsson, Cecilia, Andersson, Shalini, Andersson, Tommy B., Sandbu, Rune, Hjelmesæth, Jøran, Skovlund, Eva, Christensen, Hege, Jansson-Löfmark, Rasmus, Åsberg, Anders, Molden, Espen, and Robertsen, Ida
- Subjects
BIOMARKERS ,OBESITY ,CYTOCHROME P-450 ,JEJUNUM ,BODY weight ,IN vivo studies ,BIOPSY ,INTRAVENOUS therapy ,LIVER ,BLOOD plasma ,BIOAVAILABILITY ,ORAL drug administration ,CELL physiology ,OXYSTEROLS ,GENE expression ,CHOLECYSTECTOMY ,PROTEOMICS ,MIDAZOLAM ,GASTRIC bypass ,INTESTINES ,PHENOTYPES - Abstract
Purpose: Variability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4β-hydroxycholesterol (4βOHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4βOHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range. Methods: The patients (n = 96; 78 with obesity and 18 normal or overweight individuals) were included from the COCKTAIL-study (NCT02386917). Plasma samples for analysis of 4βOHC and midazolam concentrations, and liver (n = 56) and jejunal (n = 38) biopsies were obtained. The biopsies for determination of CYP3A4 protein concentration and microsomal activity were obtained during gastric bypass or cholecystectomy. In vivo CYP3A4 phenotyping was performed using semi-simultaneous oral (1.5 mg) and intravenous (1.0 mg) midazolam. Results: 4βOHC concentrations were positively correlated with hepatic microsomal CYP3A4 activity (ρ = 0.53, p < 0.001), and hepatic CYP3A4 concentrations (ρ = 0.30, p = 0.027), but not with intestinal CYP3A4 concentrations (ρ = 0.18, p = 0.28) or intestinal microsomal CYP3A4 activity (ρ = 0.15, p = 0.53). 4βOHC concentrations correlated weakly with midazolam absolute bioavailability (ρ = − 0.23, p = 0.027) and apparent oral clearance (ρ = 0.28, p = 0.008), but not with systemic clearance (ρ = − 0.03, p = 0.81). Conclusion: These findings suggest that 4βOHC concentrations reflect hepatic, but not intestinal, CYP3A4 activity. Further studies should investigate the potential value of 4βOHC as an endogenous biomarker for individual dose requirements of intravenously administered CYP3A4 substrate drugs. Trial registration: Clinical.Trials.gov identifier: NCT02386917. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
9. A Hybrid Model Associating Population Pharmacokinetics with Machine Learning: A Case Study with Iohexol Clearance Estimation.
- Author
-
Destere, Alexandre, Marquet, Pierre, Gandonnière, Charlotte Salmon, Åsberg, Anders, Loustaud-Ratti, Véronique, Carrier, Paul, Ehrmann, Stephan, Guellec, Chantal Barin-Le, Premaud, Aurélie, and Woillard, Jean-Baptiste
- Abstract
Background: Maximum a posteriori Bayesian estimation (MAP-BE) based on a limited sampling strategy and a population pharmacokinetic model is frequently used to estimate pharmacokinetic parameters in individuals, however with some uncertainty (bias). Recent works have shown that the performance in individual estimation or pharmacokinetic parameters can be improved by combining population pharmacokinetic and machine learning algorithms. Objective: The objective of this work was to investigate the use of a hybrid machine learning/population pharmacokinetic approach to improve individual iohexol clearance estimation. Methods: The reference iohexol clearance values were derived from 500 simulated profiles (samples collected between 0.1 and 24.7 h) using a population pharmacokinetic model we recently developed in Monolix and obtained using all the concentration timepoints available. Xgboost and glmnet algorithms able to predict the error of MAP-BE clearance estimates based on a limited sampling strategy (0.1 h, 1 h, and 9 h) versus reference values were developed in a training subset (75%) and were evaluated in a testing subset (25%) and in 36 real patients. Results: The MAP-BE limited sampling strategy estimated clearance was corrected by the machine learning predicted error leading to a decrease in root mean squared error by 29% and 24%, and in the percentage of profiles with the mean prediction error out of the ± 20% bias by 60% and 40% in the external validation dataset for the glmnet and Xgboost machine learning algorithms, respectively. These results were attributable to a decrease in the eta-shrinkage (shrinkage for a MAP-BE limited sampling strategy = 32.4%, glmnet = 18.2%, and Xgboost = 19.4% in the external dataset). Conclusions: In conclusion, this hybrid algorithm represents a significant improvement in comparison to MAP-BE estimation alone. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. Thoroughly Validated Bayesian Estimator and Limited Sampling Strategy for Dose Individualization of Ganciclovir and Valganciclovir in Pediatric Transplant Recipients.
- Author
-
Franck, Bénédicte, Autmizguine, Julie, Åsberg, Anders, Théorêt, Yves, Marquet, Pierre, Ovetchkine, Philippe, and Woillard, Jean-Baptiste
- Subjects
DRUG monitoring ,STANDARD deviations ,BASILIXIMAB ,VALGANCICLOVIR ,LIVER transplantation ,GANCICLOVIR ,TRANSPLANTATION of organs, tissues, etc. - Abstract
Background and Objective: Given a high pharmacokinetic inter-individual variability and a low exposure target achievement, ganciclovir (GCV) therapeutic drug monitoring is sometimes used in children. We aimed to develop and validate Bayesian estimators based on limited sampling strategies for the estimation of GCV area under the concentration–time curve from 0 to 24 h in pediatric transplant recipients treated with valganciclovir (VGCV) or GCV. Methods: Solid organ transplant or stem-cell transplant recipients who received GCV or VGCV and had available GCV concentrations per standard of care were retrospectively included in this study for pharmacokinetic modeling and development of Bayesian estimators using the iterative two-stage Bayesian method. Validation datasets included additional child recipients of a solid organ transplant or stem-cell transplant, and child recipients of a kidney or liver transplant enrolled in a previous study. Various combinations of three or two sampling times, applicable in clinical practice, were assessed based on the relative mean bias, standard deviation, and the root mean square error in a development dataset and three independent validation datasets. Results: In the development dataset, the mean bias/standard deviation/root mean square error for the 1 h/2 h/3 h and 1 h/3 h limited sampling strategies were − 1.4%/9.3%/9.1% and − 3.5%/12.2%/12.3%, respectively for GCV, while for VGCV, the mean bias/standard deviation/root mean square error for the 1 h/2 h/6 h and 1 h/6 h limited sampling strategies were 0.7%/13.5%/13.3% and − 0.1%/12.1%/11.8%, respectively. In the independent validation datasets, seven (13%) and five (14%) children would have had misclassifications of their exposure using these Bayesian estimators and limited sampling strategies for VGCV and GCV, respectively. Conclusions: Three plasma samples collected at 1 h/2 h/3 h and 1 h/2 h/6 h post-dose for GCV and VGCV respectively, are sufficient to accurately determine GCV area under the concentration–time curve from 0 to 24 h for pharmacokinetic-enhanced therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
11. A Limited Sampling Strategy to Estimate Exposure of Everolimus in Whole Blood and Peripheral Blood Mononuclear Cells in Renal Transplant Recipients Using Population Pharmacokinetic Modeling and Bayesian Estimators.
- Author
-
Robertsen, Ida, Debord, Jean, Åsberg, Anders, Marquet, Pierre, and Woillard, Jean-Baptiste
- Subjects
EVEROLIMUS ,ANTINEOPLASTIC agents ,IMMUNOSUPPRESSIVE agents ,PHARMACOKINETICS ,KIDNEY transplant patients - Abstract
Background and Objective: Intracellular exposure of everolimus may be a better marker of therapeutic effect than trough whole blood concentrations. We aimed to develop pharmacokinetic population models and Bayesian estimators based on a limited sampling strategy for estimation of dose interval exposures of everolimus in whole blood and peripheral blood mononuclear cells (PBMCs) in renal transplant recipients.Methods: Full whole blood and PBMC concentration-time profiles of everolimus were obtained from 12 stable renal transplant recipients on two different occasions, 4 weeks apart. The dataset was treated as 24 individual profiles and split into a development dataset (n = 20) and a validation dataset (n = 4). The pharmacokinetic model was developed using non-parametric modeling and its performances and those of the derived Bayesian estimator were evaluated in the validation set.Results: A structural two-compartment model with first-order elimination and two absorption phases described by a sum of two gamma distributions were developed. None of the tested covariates (age, sex, albumin, hematocrit, fat-free mass and genetic variants such as CYP3A5*1, ABCB1 haplotype, PPARA*42, PPARA*48, and POR*28) were retained in the final model. A limited sampling schedule of two whole blood samples at 0 and 1.5 h and one PBMC sample at 1.5 h post dose provided accurate estimates of the area under the plasma concentration-time curve (AUC) in comparison with the trapezoidal reference AUC (relative bias ± standard deviation = - 3.9 ± 10.6 and 4.1 ± 12.3% for whole blood and PBMC concentrations, respectively).Conclusion: The developed model allows simultaneous and accurate prediction of everolimus exposure in whole blood and PBMCs, and supplies a base for a feasible exploration of the relationships between intracellular exposure and therapeutic effects in prospective trials. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
12. Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants.
- Author
-
Tran, Trung The, Vaage, Eline Benno, Mehta, Adi, Chopra, Adity, Tietze, Lisa, Kolderup, Anette, Anthi, Aina, König, Marton, Nygaard, Gro, Lind, Andreas, Müller, Fredrik, Nissen-Meyer, Lise Sofie, Magnus, Per, Trogstad, Lill, Mjaaland, Siri, Søraas, Arne, Midtvedt, Karsten, Åsberg, Anders, Barratt-Due, Andreas, and Medhus, Asle W.
- Subjects
ANTIBODY titer ,SARS-CoV-2 ,MONOCLONAL antibodies - Abstract
Correction to: I npj Vaccines i https://doi.org/10.1038/s41541-022-00586-7, published online 30 December 2022 In this article the author name Marte Lie Høivik was incorrectly written as Marte Lie Høivk. The original article can be found online at https://doi.org/10.1038/s41541-022-00586-7. [Extracted from the article]
- Published
- 2023
- Full Text
- View/download PDF
13. The influence of CYP3A, PPARA, and POR genetic variants on the pharmacokinetics of tacrolimus and cyclosporine in renal transplant recipients.
- Author
-
Lunde, Ingrid, Bremer, Sara, Midtvedt, Karsten, Mohebi, Beata, Dahl, Miriam, Bergan, Stein, Åsberg, Anders, and Christensen, Hege
- Subjects
ACADEMIC medical centers ,ANALYSIS of variance ,CHI-squared test ,CYCLOSPORINE ,FISHER exact test ,TACROLIMUS ,GENES ,IMMUNOSUPPRESSION ,KIDNEY transplantation ,OXIDOREDUCTASES ,POLYMERASE chain reaction ,STATISTICS ,DATA analysis ,RETROSPECTIVE studies ,DATA analysis software ,DESCRIPTIVE statistics - Abstract
Purpose: Tacrolimus (Tac) and cyclosporine (CsA) are mainly metabolized by CYP3A4 and CYP3A5. Several studies have demonstrated an association between the CYP3A5 genotype and Tac dose requirements. Recently, CYP3A4, PPARA, and POR gene variants have been shown to influence CYP3A metabolism. The present study investigated potential associations between CYP3A5*3, CYP3A4*22, PPARA c.209-1003G>A and c.208 + 3819A>G, and POR*28 alleles and dose-adjusted concentrations (C/D) of Tac and CsA in 177 renal transplant patients early post-transplant. Methods: All patients ( n = 177) were genotyped for CYP3A4*22, CYP3A5*3, POR*28, PPARA c.209-1003G>A, and PPARA c.208 + 3819A>G using real-time polymerase chain reaction (PCR) and melting curve analysis with allele-specific hybridization probes or PCR restriction fragment length polymorphisms (RFLP) methods. Drug concentrations and administered doses were retrospectively collected from patient charts at Oslo University Hospital, Rikshospitalet, Norway. One steady-state concentration was collected for each patient. Results: We confirmed a significant impact of the CYP3A5*3 allele on Tac exposure. Patients with POR*28 and PPARA variant alleles demonstrated 15 % lower ( P = 0.04) and 19 % higher ( P = 0.01) Tac C/D respectively. CsA C/D was 53 % higher among CYP3A4*22 carriers ( P = 0.03). Conclusion: The results support the use of pre-transplant CYP3A5 genotyping to improve initial dosing of Tac, and suggest that Tac dosing may be further individualized by additional POR and PPARA genotyping. Furthermore, initial CsA dosing may be improved by pre-transplant CYP3A4*22 determination. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
14. Importance of hematocrit for a tacrolimus target concentration strategy.
- Author
-
Størset, Elisabet, Holford, Nick, Midtvedt, Karsten, Bremer, Sara, Bergan, Stein, and Åsberg, Anders
- Subjects
AGE distribution ,BIOAVAILABILITY ,CONFIDENCE intervals ,TACROLIMUS ,GENES ,HEMATOCRIT ,KIDNEY transplantation ,OXIDOREDUCTASES ,REGRESSION analysis ,RESEARCH funding ,T-test (Statistics) ,DATA analysis software ,STATISTICAL models ,DESCRIPTIVE statistics - Abstract
Purpose: To identify patient characteristics that influence tacrolimus individual dose requirement in kidney transplant recipients. Methods: Data on forty-four 12-h pharmacokinetic profiles from 29 patients and trough concentrations in 44 patients measured during the first 70 days after transplantation (1,546 tacrolimus whole blood concentrations) were analyzed. Population pharmacokinetic modeling was performed using NONMEM 7.2®. Results: Standardization of tacrolimus whole blood concentrations to a hematocrit value of 45 % improved the model fit significantly ( p < 0.001). Fat-free mass was the best body size metric to predict tacrolimus clearance and volume of distribution. Bioavailability was 49 % lower in expressers of cytochrome P450 3A5 (CYP3A5) than in CYP3A5 nonexpressers. Younger females (<40 years) showed a 35 % lower bioavailability than younger males. Bioavailability increased with age for both males and females towards a common value at age >55 years that was 47 % higher than the male value at age <40 years. Bioavailability was highest immediately after transplantation, decreasing steeply thereafter to reach its nadir at day 5, following which it increased during the next 55 days towards an asymptotic value that was 28 % higher than that on day 5. Conclusions: Hematocrit predicts variability in tacrolimus whole blood concentrations but is not expected to influence unbound (therapeutically active) concentrations. Fat-free mass, CYP3A5 genotype, sex, age and time after transplant influence the tacrolimus individual dose requirement. Because hematocrit is highly variable in kidney transplant patients and increases substantially after kidney transplantation, hematocrit is a key factor in the interpretation of tacrolimus whole blood concentrations. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
15. UGT1A1*28 is Associated with Decreased Systemic Exposure of Atorvastatin Lactone.
- Author
-
Stormo, Camilla, Bogsrud, Martin, Hermann, Monica, Åsberg, Anders, Piehler, Armin, Retterstøl, Kjetil, and Kringen, Marianne
- Subjects
LACTONES ,ATORVASTATIN ,BLOOD cholesterol ,GLUCURONIDATION ,URIDINE diphosphate ,MUSCLE diseases - Abstract
Background: Atorvastatin is commonly used to reduce cholesterol. Atorvastatin acid is converted to its corresponding lactone form spontaneously or via glucuronidation mediated by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A3. Atorvastatin lactone is pharmacologically inactive, but is suspected to be muscle toxic and cause statin-induced myopathy (SIM). A several fold increase in systemic exposure of atorvastatin lactone has previously been observed in patients with SIM compared with healthy control subjects. In this study we aimed to investigate the association between polymorphisms in the UGT1A gene locus and plasma atorvastatin lactone levels. Methods: DNA was extracted from whole blood obtained from a previous pharmacokinetic study of patients carefully diagnosed as having true SIM ( n = 13) and healthy control subjects ( n = 15). The UGT1A1*28(TA), UGT1A3*2, UGT1A3*3, and UGT1A3*6 polymorphisms were detected by pyrosequencing. Results: Carriers of the low-expression allele UGT1A1*28(TA) tended to have lower levels of atorvastatin lactone ( p < 0.05) than carriers with the normal-activity allele (TA). Conclusion: The low-expression UGT1A1*28(TA) allele seems to be associated with decreased systemic exposure of the suspected muscle-toxic metabolite atorvastatin lactone. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
16. Long-term effects of gastric bypass and duodenal switch on systemic exposure of atorvastatin.
- Author
-
Jakobsen, Gunn, Skottheim, Ine, Sandbu, Rune, Christensen, Hege, Røislien, Jo, Åsberg, Anders, and Hjelmesæth, Jøran
- Subjects
GASTRIC bypass ,DUODENAL diseases ,ATORVASTATIN ,PANCREATIC duct ,BODY mass index ,COMPARATIVE studies - Abstract
Background: A previous study of 22 patients undergoing either gastric bypass or duodenal switch showed increased systemic exposure of atorvastatin acid 3-8 weeks after surgery in the majority of patients. This study aimed to investigate the long-term effects on systemic exposure of atorvastatin acid in the same group of patients. Methods: An 8-h pharmacokinetic investigation was performed a median of 27 months (range 21-45 months) after surgery. Systemic exposure was measured as the area under the plasma concentration versus the time curve from 0 to 8 h postdose (AUC). Linear mixed models with AUC as the dependent variable were implemented to assess the effect of time, surgical procedure, and body mass index (BMI) as explanatory variables. Results: The study enrolled 20 patients. The systemic exposure of atorvastatin acid changed significantly over time ( p = 0.001), albeit there was substantial variation between subjects. The effect of time was attenuated but remained significant after adjustment for surgical procedure and BMI ( p = 0.048). The initial AUC increase seen in the majority of patients 3-8 weeks after surgery was normalized long term, with 7 of the 12 gastric bypass patients and 6 of the 8 duodenal switch patients showing decreased AUC compared with preoperative values. Conclusions: The systemic exposure of atorvastatin showed a significant change over time after bariatric surgery, albeit with large inter- and intraindividual variations. The findings indicate that patients using atorvastatin or drugs with similar pharmacokinetic properties should be monitored closely for both therapeutic effects and adverse events the first years after gastric bypass and duodenal switch. ClinicalTrial NCT00331565. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
17. Atorvastatin Metabolite Measurements as a Diagnostic Tool for Statin-Induced Myopathy.
- Author
-
Skottheim, Ine B., Bogsrud, Martin P., Hermann, Monica, Retterstøl, Kjetil, and Åsberg, Anders
- Subjects
ATORVASTATIN ,DIAGNOSIS of muscle diseases ,RHABDOMYOLYSIS ,LACTONES ,PATIENTS ,METABOLITES - Abstract
Background: Myopathic complaints are common in the general population and are more frequent with increasing age. When myopathic symptoms arise in a patient treated with a HMG-CoA reductase inhibitor (statin), it is always a question of whether the symptoms are due to statin-induced myopathy (SIM) or not (non-SIM). Diagnosis of SIM is not as straightforward as previously thought, because the most commonly used biomarker, serum creatine kinase, shows low specificity and selectivity, except in serious cases of rhabdomyolysis. There is a definite need for a novel biomarker for SIM. Objective: Based on a previous study reporting an altered metabolic profile with increased systemic exposure to the suspected muscle-toxic metabolite atorvastatin lactone in patients with SIM compared with healthy controls, this study aimed to explore the use of atorvastatin metabolite measurements to diagnose muscular complaints during statin treatment as being either SIM or non-SIM. Patients, Setting, and Study Design: Fifty-three patients with self-reported myopathic symptoms during atorvastatin treatment were recruited from our outpatient clinic. The symptoms were clinically evaluated as being SIM or non-SIM, on the basis of atorvastatin re-challenge testing. Atorvastatin and its metabolites were measured at steady state in all patients and compared with the clinical evaluation to see if this could predict the outcome and hence be suitable as a diagnostic tool for SIM. Main Outcome Measure: This was an exploratory study to investigate the proportion of patients correctly diagnosed by different metabolite cut-off ratios. Results: With a cut-off ratio set at 1.1 for the atorvastatin lactone to atorvastatin acid ratio, 15 of 28 SIM patients (sensitivity of 54%) and 20 of 24 non-SIM patients (specificity of 83%) were correctly diagnosed. This corresponds to a positive predictive value of 79% and a negative predictive value of 61% (p = 0.006). Conclusion: The present study confirms an altered metabolic pattern of atorvastatin in patients with SIM and substantiates a central role of the lactone forms of statins in future investigations of statin myotoxicity. The atorvastatin lactone to acid ratio seems to be a valuable supportive diagnostic tool with high specificity and moderate sensitivity, adding to ordinary clinical evaluations when diagnosing SIM. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
18. A Population Pharmacokinetic Model of Ciclosporin Applicable for Assisting Dose Management of Kidney Transplant Recipients.
- Author
-
Falck, Pål, Midtvedt, Karsten, vân Lé, Thanh Trúc, Storehagen, Live, Holdaas, Hallvard, Hartmann, Anders, and Åsberg, Anders
- Subjects
PHARMACOKINETICS ,KIDNEY diseases ,TRANSPLANTATION of organs, tissues, etc. ,PATIENT monitoring ,GENETIC polymorphisms ,GENETIC research - Abstract
Background and Objective: The pharmacokinetic disposition of ciclosporin shows great intra- and interpatient variability, and that combined with a narrow therapeutic window makes therapeutic drug monitoring of ciclosporin necessary. The nonlinear mixed-effects population pharmacokinetic program NONMEM® predicts individual pharmacokinetic parameters based not only on individual patient observations but also on population characteristics and the patient's covariates. The aim of this model development is to potentially use it in the clinical setting to optimize ciclosporin dosing in renal transplant recipients. Methods: A population pharmacokinetic model of ciclosporin has been developed with NONMEM® using full 12-hour pharmacokinetic profiles from 29 renal transplant recipients, 3 months of daily follow-up data from an additional 11 recipients, and both 3 months of follow-up data and full 12-hour pharmacokinetic profiles from nine patients. The internal validation of the model was based on data splitting and jack-knife methods. In addition, the model was validated for its clinical applicability on standard trough and 2-hour post-dose concentration data from 12 additional patients with 3 months of follow-up. Results: The model that best described the ciclosporin data was a two-compartment model with first-order absorption process with lagged time. The population pharmacokinetic parameters were oral clearance (CL/F) = 26.9L/h; central volume of distribution after oral administration (V
1 /F) = 24.4 L; absorption rate constant (ka ) = 0.544 h-1 ; lag time = 0.460 h; peripheral volume of distribution = 1119L and intercompartmental clearance after oral administration (Q/F) = 19.6L/h. Three covariates had significant effect on a total of six pharmacokinetic parameters. These were bodyweight onV1 /Fand ka , time after transplantation on ka , and age on CL/F, ka and V1 /F. Cytochrome P450 3A5 genotype was also a significant covariate but was not included in the final model since such information is not available in clinical practice. The external validation showed that the model was able to predict ciclosporin concentrations in the 12 new patients with an average predictive error of 17.4 ± 14% when the standard sample concentrations from the previous week were given. Conclusion: A NONMEM® pharmacokinetic model for ciclosporin in renal transplant recipients was successfully developed and validated for the first 3 months post-transplantation. The model showed good predictability in a new patient cohort. After further clinical validation, the model may be applicable as a clinical tool for optimizing ciclosporin dosing in renal transplant recipients in the early post-transplant period. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
19. Atorvastatin does not affect the pharmacokinetics of cyclosporine in renal transplant recipients.
- Author
-
Hermann, Monica, Åsberg, Anders, Christensen, Hege, Reubsaet, Jan Leo Egge, Holdaas, Hallvard, and Hartmann, Anders
- Subjects
- *
CYCLOSPORINE , *CYCLIC peptides , *IMMUNOSUPPRESSIVE agents , *PATIENTS , *KIDNEY transplantation , *PHARMACOKINETICS , *PHARMACOLOGY - Abstract
The aim of the present study was to evaluate the possible influence of atorvastatin on the pharmacokinetics of cyclosporine (INN ciclosporin) and its main metabolites, AM1 and AM9, in renal transplant recipients. Whole blood samples from 18 renal transplanted patients on cyclosporine-based immunosuppressive therapy were collected prior to and after 4 weeks of treatment with atorvastatin (10 mg/day) and analysed with regard to both cyclosporine and its main metabolites, AM1 and AM9, using a specific chromatographic method with ultraviolet detection. On average, AUC0-12 [area under the whole blood concentration versus time curve in the dosing interval (0-12 h)] of cyclosporine was 5% (16, 5) (90% confidence interval) lower upon co-administration with atorvastatin. No statistically significant changes in any of the calculated pharmacokinetic variables [AUC0-12, maximum whole blood concentration (Cmax), whole blood concentration 12 h post dose (C12), time to Cmax (tmax), terminal half-life (t1/2)] for cyclosporine or the two metabolites, AM1 and AM9, upon atorvastatin treatment were observed. On average, atorvastatin did not affect the ratio between the CYP3A4-mediated metabolite AM9 and cyclosporine, suggesting that atorvastatin does not affect the CYP3A4 metabolism of cyclosporine to any significant extent. However, the influence of atorvastatin on the ratio between AM9 and cyclosporine showed large interindividual variability. The results of this study indicate that atorvastatin does not, on average, affect cyclosporine pharmacokinetics in renal transplant recipients. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
20. Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers.
- Author
-
Christensen, Hege, &Åsberg, Anders, Holmboe, Aase-Britt, and Berg, Knut
- Subjects
GRAPEFRUIT juice ,PHARMACOKINETICS ,PHARMACOLOGY ,DIHYDROPYRIDINE ,VERAPAMIL ,DRUGS ,BIOAVAILABILITY - Abstract
Objectives. Grapefruit juice has been reported to increase the bioavailability of several calcium-channel antagonists, i.e. the dihydropyridines and verapamil, which are cytochrome P
450 3A4 (CYP3A4) substrates. The objective of the present study was to investigate the effect of grapefruit juice on the pharmacokinetics of diltiazem and the metabolites N-demethyl-diltiazem (MA) and desacetyl-diltiazem (M1). Methods. Ten healthy male volunteers were included in a randomised, open, crossover study, comparing the effect of a single oral dose of non-retard formulated diltiazem (120 mg) administered with 250 ml grapefruit juice or water. The study was performed on two investigation days separated by 13–38 days (median 28 days). Plasma samples were collected for measurement of diltiazem and the metabolites MA and M1. Blood pressure and heart rate were monitored throughout the study. Results. Grapefruit juice intake resulted in a statistically significant average individual increase in the area under the plasma diltiazem concentration–time curve (AUC0–24 ) of 20±25% (P=0.02) compared with water. The average individual increase in peak plasma concentration (Cmax ) of diltiazem after grapefruit juice administration was 22±37%, but this effect was not statistically significant (P=0.14). The time to Cmax (tmax ) or terminal half-life was not affected by grapefruit juice. Considerable interindividual variability in the interaction was observed. There were no statistically significant differences in blood pressure and heart rate between the two treatments. Conclusion. The present study demonstrated that a single intake of grapefruit juice (250 ml) caused a slight but statistically significant increase in the systemic exposure of diltiazem. Inhibition of intestinal metabolism and/or P-glycoprotein efflux transport may be responsible for this effect. [ABSTRACT FROM AUTHOR]- Published
- 2002
- Full Text
- View/download PDF
21. Early intervention with a potent endothelin-A/endothelin-B receptor antagonist aggravates left ventricular remodeling after myocardial infarction in rats.
- Author
-
Øie, Erik, Yndestad, Arne, Robins, Simon P., Bjørnerheim, Reidar, Åsberg, Anders, and Attramadal, Håvard
- Subjects
LEFT heart ventricle ,MYOCARDIAL infarction ,ENDOTHELINS ,CARDIAC research ,CORONARY disease ,HEART ventricles - Abstract
Intervention with selective endothelin (ET)A receptor antagonists within 24 h after myocardial infarction (MI) in rats has been reported to aggravate left ventricular (LV) remodeling. In contrast, beneficial effects are reported when initiation of treatment is delayed 7 days or more after MI. However, bosentan, a mixed ET
A /ETB receptor antagonist with low affinity for the ET receptors, has been shown to exert beneficial effects independent of the time point of initiation of treatment after MI. The aim of the present study was to investigate to what extent early intervention with a mixed ETA /ETB receptor antagonist with higher affinity at the ET receptors (SB 209670) would also exert beneficial effects on postinfarction LV remodeling. After ligation of the left coronary artery, rats were randomized to treatment with SB 209670 (6.25 mg·kg-1 SC b.i.d., n = 10) or vehicle (n = 12) for 26 days, starting 48 h after MI. Treatment with SB 209670 adversely affected the postinfarction remodeling process causing further dilatation of the LV (LV end-diastolic diameter: 10.4 ± 0.5 vs 9.1 ± 0.2 mm; LV end-systolic diameter: 8.5 ± 0.4 vs 7.2 ± 0.2 mm, P < 0.05). However, SB 209670 did not significantly affect infarct size, compensatory cardiac hypertrophy, nor the myocardial mRNA levels of procollagen type I and III, and prolyl 4-hydroxylase and lysyl oxidase, 2 important enzymes affecting collagen secretion, stability and functionality. In addition, SB 209670 had no significant effects on LV collagen cross-linking or extent of fibrosis. Thus, our data demonstrate that early intervention with a potent, mixed ETA /ETB receptor antagonist after MI may promote dilatation of the LV without significant alterations of infarct size and extracellular matrix composition. Our data support the notion that the timing of initiation of ET receptor antagonism after MI is critical and that potent ET receptor antagonists may be harmful during the first few days after MI. [ABSTRACT FROM AUTHOR]- Published
- 2002
- Full Text
- View/download PDF
22. CYP2D6 is involved in O-demethylation of diltiazem: An in vitro study with transfected human liver cells.
- Author
-
Molden, Espen, Åsberg, Anders, and Christensen, Hege
- Subjects
CELL culture ,METABOLISM ,BIOCHEMISTRY ,ERYTHROMYCIN ,ANTIBACTERIAL agents ,MACROLIDE antibiotics - Abstract
Objective: In a previous study of diltiazem (DTZ) pharmacokinetics in renal transplant patients, we speculated that a polymorphic enzyme could be involved in O-demethylation of diltiazem. The aim of this in vitro study was to investigate whether O-demethylation of DTZ is mediated by cytochrome P
450 -2D6 (CYP2D6). Methods: DTZ was incubated with transfected human liver epithelial (THLE) cells expressing CYP2D6 (T5-2D6 clone). Metabolism of DTZ was studied over a concentration range of 12.5–400 µM and in the presence of quinidine (a CYP2D6 inhibitor) or erythromycin (a CYP3A4 inhibitor). THLE cells lacking CYP2D6 activity (T5-neo clone) were used as control. The culture medium of the cells, in which DTZ was dissolved, was analysed for DTZ and metabolites prior to and after 8 h of incubation using high-performance liquid chromatography (HPLC, UV detection). Authentic O-demethyl-DTZ (Mx) was not available, and this metabolite was therefore not identifiable. Results: Desacetyl-O-demethyl-DTZ (M4) was exclusively produced during incubations of DTZ with THLE cells expressing CYP2D6. The rate of M4 formation was described using Michaelis Menten kinetics in the concentration range of DTZ used. Production of M4 was inhibited by quinidine, but not erythromycin. An unidentified chromatographic peak, which was interpreted to be Mx, showed the same pattern of formation as M4 both in absence and presence of inhibitors. N-demethylated metabolites, formed by CYP3A4, were not observed in any of the cell lines. Conclusion: Evidence was provided in vitro that O-demethylation of DTZ is mediated by the polymorphic isoenzyme CYP2D6. Involvement of CYP2D6 in the metabolism of DTZ may have clinical implications regarding pharmacokinetic variability and interactions. [ABSTRACT FROM AUTHOR]- Published
- 2000
- Full Text
- View/download PDF
23. The HUNT4 study: the validity of questionnaire-based diagnoses.
- Author
-
Hagen, Knut, Åsberg, Anders Nikolai, Uhlig, Benjamin L., Tronvik, Erling, Brenner, Eiliv, and Sand, Trond
- Subjects
- *
HEADACHE diagnosis , *MIGRAINE diagnosis , *CONFIDENCE intervals , *INTERVIEWING , *QUESTIONNAIRES , *SELF-evaluation , *STATISTICS - Abstract
Background: Questionnaire-based headache diagnoses should be validated against diagnoses made by the gold standard, which is personal interview by a headache expert. The diagnostic algorithm with the best diagnostic accuracy should be used when later analysing the data. Methods: The Nord-Trøndelag Health Study (HUNT4) was performed between 2017 and 2019. Among HUNT4 participants, a total of 232 (19.3%) out of 1201 randomly invited were interviewed by a headache expert to assess the sensitivity, specificity and kappa value of the questionnaire-based headache diagnoses. Results: The median interval between answering the headache questions and the validation interview was 60 days (95% CI 56–62 days). The best agreements were found for self-reported lifetime migraine (sensitivity of 59%, specificity of 99%, and a kappa statistic of 0.65, 95% CI 0.55–0.75), self-reported active migraine (sensitivity of 50%, specificity of 97%, and a kappa statistic of 0.55, 95% 0.39–0.71), liberal criteria of migraine (sensitivity of 64%, specificity of 93%, and a kappa statistic of 0.58, 95% CI 0.43–0.73) and ICDH3-based migraine ≥1 days/month (sensitivity of 50%, specificity of 94%, and a kappa statistic of 0.49, 95% CI 0.30–0.68). For headache suffering ≥1 days/month a sensitivity of 90%, specificity 80%, and a kappa statistic of 0.55, 95% CI 0.41–0-69 were found. For tension-type headache (TTH) ≥ 1 days/month the agreement was 0.33 (95% CI 0.17–0.49). Conclusion: The HUNT4 questionnaire is a valid tool for identifying persons with lifetime migraine, self-reported active migraine and active migraine applying liberal modified criteria. The agreement for TTH was fair. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
24. The epidemiology of headache disorders: a face-to-face interview of participants in HUNT4.
- Author
-
Hagen, Knut, Åsberg, Anders Nikolai, Uhlig, Benjamin L., Tronvik, Erling, Brenner, Eiliv, Stjern, Marit, Helde, Grethe, Gravdahl, Gøril Bruvik, and Sand, Trond
- Subjects
- *
MIGRAINE diagnosis , *TENSION headache , *CONFIDENCE intervals , *HEADACHE , *INTERVIEWING , *SLEEP disorders , *DISEASE prevalence , *CROSS-sectional method , *DATA analysis software , *DIAGNOSIS - Abstract
Background: The primary aim of this cross-sectional population-based study was to evaluate the 1-year prevalence of common headache disorders by a face-to-face interview.Methods: The fourth wave of Nord-Trøndelag Health Survey (HUNT4) started in September 2017. The study was undertaken as part of a project mainly focusing on sleep disorders, where a total of 232 (19.3%) out of 1200 invited HUNT4 participants underwent a face-to-face headache interview.Results: The mean age of the 232 participants was 58.4 years (range 22-89). There were 71.6% (95% CI 65.7-77.4) who reported headache during the last year, and 18.5% (95% CI 13.5-23.6) had suffered from headache in the same period. The 1-year prevalence of tension-type headache (TTH) was 43.1% (95% CI 36.7-49.5), of idiopathic stabbing headache 34.1% (27.9-40.2), and of definite migraine 18.1% (95% CI 13.1-23.1). A total of 7.6% (95% CI 4.0-10.7%) had migraine with coexisting TTH. Lifetime prevalence of migraine was 32.8% (95% CI 26.7-38.8). Headache yesterday was reported by 12.1% (95% CI 7.9-16.3), and 5.6% (95% CI 2.6-8.6) had headache during the interview.Conclusion: In this population-based cross-sectional headache study performed by a face-to-face interview, the 1-year prevalence of TTH was 43.1% and of idiopathic stabbing headache 34.1%. A total of 18.1% had active migraine (18.1%), whereas the lifetime prevalence of migraine was 32.8%. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.