| 1. |
- Dahle, Dag Olav, et al.
(författare)
-
Uric acid and clinical correlates of endothelial function in kidney transplant recipients
- 2014
-
Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 28:10, s. 1167-1176
-
Tidskriftsartikel (refereegranskat)abstract
- Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores.METHODS: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models.RESULTS: Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05).CONCLUSIONS: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores.
|
|
| 2. |
- Boenink, Rianne, et al.
(författare)
-
Trends in kidney transplantation rate across Europe : a study from the ERA Registry
- 2023
-
Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 38:6, s. 1528-1539
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The aim of this study was to identify trends in total, deceased donor (DD) and living donor (LD) kidney transplantation (KT) rates in European countries. Methods. The European Renal Association (ERA) Registry and the Global Observatory on Donation and Transplantation (GODT) databases were used to obtain the number of KTs in individual European countries between 2010 and 2018. General population counts were obtained from Eurostat or the national bureaus of statistics. The KT rate per million population (p.m.p.) and the average annual percentage change (APC) were calculated. Results. The total KT rate in the 40 participating countries increased with 1.9% annually [95% confidence interval (CI) 1.5, 2.2] from 29.6 p.m.p. in 2010 to 34.7 p.m.p. in 2018, reflecting an increase of 3.4 p.m.p. in the DD-KT rate (from 21.6 p.m.p. to 25.0 p.m.p.; APC 1.9%; 95% CI 1.3, 2.4) and of 1.5 p.m.p. in the LD-KT rate (from 8.1 p.m.p. to 9.6 p.m.p.; APC 1.6%; 95% CI 1.0, 2.3). The trends in KT rate varied widely across European countries. An East-West gradient was observed for DD-KT rate, with Western European countries performing more KTs. In addition, most countries performed fewer LD-KTs. In 2018, Spain had the highest DD-KT rate (64.6 p.m.p.) and Turkey the highest LD-KT rate (37.0 p.m.p.). Conclusions. The total KT rate increased due to a rise in the KT rate from DDs and to a lesser extent from LDs, with large differences between individual European countries.
|
|
| 3. |
- Ejeby, Kersti, et al.
(författare)
-
Randomized controlled trial of transdiagnostic group treatments for primary care patients with common mental disorders
- 2014
-
Ingår i: Family Practice. - : Oxford University Press (OUP). - 0263-2136 .- 1460-2229. ; 31:3, s. 273-280
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The purpose was to test the effectiveness of two transdiagnostic group interventions compared to care as usual (CAU) for patients with anxiety, depressive or stress-related disorders within a primary health care context. Objectives. To compare the effects of cognitive-based-behavioural therapy (CBT) and multimodal intervention (MMI) on the quality of life and relief of psychological symptoms of patients with common mental disorders or problems attending primary health care centre. Methods. Patients (n = 278), aged 18-65 years, were referred to the study by the GPs and 245 were randomized to CAU or one of two group interventions in addition to CAU: (i) group CBT administered by psychologists and (ii) group MMI administered by assistant nurses. The primary outcome measure was the Mental Component Summary score of short form 36. Secondary outcome measures were Perceived Stress Scale and Self-Rating Scale for Affective Syndromes. The data were analysed using intention-to-treat with a linear mixed model. Results. On the primary outcome measure, the mean improvement based on mixed model analyses across post-and follow-up assessment was significantly larger for the MMI group than for the CBT (4.0; P = 0.020) and CAU (7.5; P = .001) groups. Participants receiving CBT were significantly more improved than those in the CAU group. On four of the secondary outcome measures, the MMI group was significantly more improved than the CBT and CAU groups. The course of improvement did not differ between the CBT group and the CAU group on these measures. Conclusions. Transdiagnostic group treatment can be effective for patients with common mental disorders when delivered in a primary care setting. The group format and transdiagnostic approach fit well with the requirements of primary care.
|
|
| 4. |
- Ejeby, Kersti, et al.
(författare)
-
Symptom reduction due to psychosocial interventions is not accompanied by a reduction in sick leave : Results from a randomized controlled trial in primary care
- 2014
-
Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 32:2, s. 67-72
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate whether interventions that have positive effects on psychological symptoms and quality of life compared with usual care would also reduce days on sick leave. Design. A randomized controlled trial. Setting. A large primary health care centre in Stockholm, Sweden. Intervention. Patients with common mental disorders were recruited by their GPs and randomized into one of two group interventions that took place in addition to usual care. These group interventions were: (a) group cognitive behavioural therapy (CBT), and (b) group multimodal intervention (MMI). Both types of intervention had previously shown significant effects on quality of life, and MMI had also shown significant effects on psychological symptoms. Patients. Of the 245 randomized patients, 164 were employed and had taken sick leave periods of at least two weeks in length during the study period of two years. They comprised the study group. Main outcome measures. The odds, compared with usual care, for being sick-listed at different times relative to the date of randomization. Results. The mean number of days on sick leave increased steadily in the two years before randomization and decreased in the two years afterwards, showing the same pattern for all three groups. The CBT and MMI interventions did not show the expected lower odds for sick-listing compared with usual care during the two-year follow-up. Conclusion. Reduction in psychological symptoms and increased well-being did not seem to be enough to reduce sickness absence for patients with common mental problems in primary care. The possibility of adding workplace-oriented interventions is discussed.
|
|
| 5. |
- Hajjari, Parisa, et al.
(författare)
-
Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) and intravenous immunoglobulin (IVIG): comprehensive open-label trial in ten children
- 2022
-
Ingår i: Bmc Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Treatment with intravenous immunoglobulin (IVIG) in children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) has for many years been used on clinical indications, but the research evidence for its efficacy is insufficient. Methods Open-label prospective in-depth trial including ten children (median age 10.3 years) with PANS, who received IVIG treatment 2 g/kg monthly for three months. Primary outcomes were changes in symptom severity and impairment from baseline to first and second follow-up visits one month after first and one month after third treatment, using three investigator-rated scales: Paediatric Acute Neuropsychiatric Symptom (PANS) scale, Clinical Global Impression - Severity and Improvement (CGI-S and CGI-I) scales. Secondary outcomes reported here were changes in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores, and side effects. Results All ten children received three treatments at one-month intervals according to study plan. From baseline to second follow-up marked reductions were seen in mean total PANS scale scores (p = .005), and CGI-S scores (p = .004). CGI-I ratings showed much to very much global improvement (mean CGI-I 1.8). Nine children had clinical response defined as > 30% reduction in PANS Scale scores. Improvements were also noted for CY-BOCS scores (p = .005), and in school attendance. Three children suffered moderate to severe temporary side effects after the first treatment, and the remaining seven had mild to moderate side effects. Side effects were much less severe after second and third treatments. Conclusions Considerable and pervasive improvements in symptoms and clinical impairments were seen in these ten children after three monthly IVIG treatments. Moderate to severe transient side effects occurred in three cases.
|
|
| 6. |
|
|
| 7. |
- Jesper, Kristiansen, et al.
(författare)
-
The Danish version of the Karolinska Exhaustion Disorder Scale (KEDS)
- 2016
-
Konferensbidrag (refereegranskat)abstract
- Jesper Kristiansen1, Maria Kristine Friborg1, Lars Brandt2, Nanna Eller3, David Glasscock4, Anders Daldorph Nielsen2, Roger Persson5, Aniella Besèr6, Marie Åsberg6
|
|
| 8. |
-
Psykiatri
- 2009
-
Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)
|
|
| 9. |
- Tulstrup, Morten, et al.
(författare)
-
Parents' and Adolescents' Preferences for Intensified or Reduced Treatment in Randomized Lymphoblastic Leukemia Trials.
- 2016
-
Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 63:5, s. 865-871
-
Tidskriftsartikel (refereegranskat)abstract
- When offered participation in clinical trials, families of children with cancer face a delicate balance between cure and toxicity. Since parents and children may perceive this balance differently, this paper explores whether adolescent patients have different enrollment patterns compared to younger children in trials with different toxicity profiles.
|
|
| 10. |
- Wegler, Christine, et al.
(författare)
-
Drug Disposition Protein Quantification in Matched Human Jejunum and Liver From Donors With Obesity
- 2022
-
Ingår i: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 111:5, s. 1142-1154
-
Tidskriftsartikel (refereegranskat)abstract
- Mathematical models, such as physiologically-based pharmacokinetic models, are used to predict, for example, drug disposition and toxicity. However, populations differ in the abundance of proteins involved in these processes. To improve the building and refinement of such models, they must take into account these interindividual variabilities. In this study, we used global proteomics to characterize the protein composition of jejunum and liver from 37 donors with obesity enrolled in the COCKTAIL study. Liver protein levels from the 37 donors were further compared with those from donors without obesity. We quantified thousands of proteins and could present the expression of several drug-metabolizing enzymes, for the first time, in jejunum, many of which belong to the cytochrome P450 (CYP) (e.g., CYP2U1) and the amine oxidase (flavin-containing) (e.g., monoamine oxidase A (MAOA)) families. Although we show that many metabolizing enzymes had greater expression in liver, others had higher expression in jejunum (such as, MAOA and CES2), indicating the role of the small intestine in extrahepatic drug metabolism. We further show that proteins involved in drug disposition are not correlated in the two donor-matched tissues. These proteins also do not correlate with physiological factors such as body mass index, age, and inflammation status in either tissue. Furthermore, the majority of these proteins are not differently expressed in donors with or without obesity. Nonetheless, interindividual differences were considerable, with implications for personalized prediction models and systems pharmacology.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Wegler, Christine, et al.
(författare)
-
Global variability analysis of mRNA and protein concentrations across and within human tissues
- 2020
-
Ingår i: NAR Genomics and Bioinformatics. - : Oxford University Press (OUP). - 2631-9268. ; 2:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genes and proteins show variable expression patterns throughout the human body. However, it is not clear whether relative differences in mRNA concentrations are retained on the protein level. Furthermore, inter-individual protein concentration variability within single tissue types has not been comprehensively explored. Here, we used the Gini index for in-depth concentration variability analysis of publicly available transcriptomics and proteomics data, and of an in-house proteomics dataset of human liver and jejunum from 38 donors. We found that the transfer of concentration variability from mRNA to protein is limited, that established ‘reference genes’ for data normalization vary markedly at the protein level, that protein concentrations cover a wide variability spectrum within single tissue types, and that concentration variability analysis can be a convenient starting point for identifying disease-associated proteins and novel biomarkers. Our results emphasize the importance of considering individual concentration levels, as opposed to population averages, for personalized systems biology analysis.
|
|
| 14. |
- Wegler, Christine, et al.
(författare)
-
Proteomics‐Informed Prediction of Rosuvastatin Plasma Profiles in Patients with a Wide Range of Body Weight
- 2021
-
Ingår i: Clinical Pharmacology and Therapeutics. - : John Wiley & Sons. - 0009-9236 .- 1532-6535. ; 109:3, s. 762-771
-
Tidskriftsartikel (refereegranskat)abstract
- Rosuvastatin is a frequently used probe to study transporter-mediated hepatic uptake. Pharmacokinetic models have therefore been developed to predict transporter impact on rosuvastatin disposition in vivo. However, the interindividual differences in transporter concentrations were not considered in these models, and the predicted transporter impact was compared with historical in vivo data. In this study, we investigated the influence of interindividual transporter concentrations on the hepatic uptake clearance of rosuvastatin in 54 patients covering a wide range of body weight. The 54 patients were given an oral dose of rosuvastatin the day before undergoing gastric bypass or cholecystectomy, and pharmacokinetic (PK) parameters were established from each patient’s individual time-concentration profiles. Liver biopsies were sampled from each patient and their individual hepatic transporter concentrations were quantified. We combined the transporter concentrations with in vitro uptake kinetics determined in HEK293-transfected cells, and developed a semimechanistic model with a bottom-up approach to predict the plasma concentration profiles of the single dose of rosuvastatin in each patient. The predicted PK parameters were evaluated against the measured in vivo plasma PKs from the same 54 patients. The developed model predicted the rosuvastatin PKs within two-fold error for rosuvastatin area under the plasma concentration versus time curve (AUC; 78% of the patients; average fold error (AFE): 0.96), peak plasma concentration (Cmax; 76%; AFE: 1.05), and terminal half-life (t1/2; 98%; AFE: 0.89), and captured differences in the rosuvastatin PKs in patients with the OATP1B1 521T
|
|
| 15. |
- Åsberg, Dennis, 1988-, et al.
(författare)
-
A quality control method enhancement concept : Continual improvement of regulatory approved QC methods
- 2016
-
Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 129, s. 273-281
-
Tidskriftsartikel (refereegranskat)abstract
- Quality Control methods (QC-methods) play an important role in the overall control strategy for drug manufacturing. However, efficient life-cycle management and continual improvement are hindered due to a variety of post-approval variation legislations across territories and a lack of harmonization of the requirements. As a result, many QC-methods fall behind the technical development. Developing the QC-method in accordance with the Quality by Design guidelines gives the possibility to do continual improvements inside the original Method Operable Design Region (MODR). However, often it is necessary to do changes outside the MODR, e.g. to incorporate new technology that was not available at the time the original method was development. Here, we present a method enhancement concept which allows minor adjustments, within the same measuring principle, outside the original MODR without interaction with regulatory agencies. The feasibility of the concept is illustrated by a case study of a QC-method based on HPLC, assumed to be developed before the introduction of UHPLC, where the switch from HPLC to UHPLC is necessary as a continual improvement strategy. The concept relies on the assumption that the System Suitability Test (SST) and failure modes are relevant for other conditions outside the MODR as well when the same measuring principle is used. It follows that it should be possible to move outside the MODR as long as the SST has passed. All minor modifications of the original, approved QC-method must be re-validated according to a template given in the original submission and a statistical equivalence should be shown between the original and modified QC-methods. To summarize, revalidation is handled within the pharmaceutical quality control system according to internal change control procedures, but without interaction with regulating agencies.
|
|
| 16. |
- Åsberg, Dennis, et al.
(författare)
-
Analytical method development in the quality by design framework
- 2014
-
Ingår i: American Laboratory. - : AMERICAN LABORATORY-LABCOMPARE. - 0044-7749. ; 46:9, s. 12-15
-
Tidskriftsartikel (refereegranskat)abstract
- The development of analytical methods in the Quality by Design (QbD) framework is currently gaining great momentum in the pharmaceutical industry. Presented here is a case study in which a pharmaceutical Quality Control (QC) method was developed using HPLC. The possibilities of continuous improvements during the method’s lifetime are demonstrated by switching to ultrahigh performance liquid chromatography (UHPLC).
|
|
| 17. |
- Åsberg, Dennis, 1988-, et al.
(författare)
-
Combining Chemometric Models with Adsorption Isotherm Measurements to Study Omeprazole in RP-LC
- 2016
-
Ingår i: Chromatographia. - : Springer Berlin/Heidelberg. - 0009-5893 .- 1612-1112. ; 79:19, s. 1283-1291
-
Tidskriftsartikel (refereegranskat)abstract
- The adsorption of the proton-pump inhibitor omeprazole was investigated using RP-LC with chemometric models combined with adsorption isotherm modelling to study the effect of pH and type of organic modifier (i.e., acetonitrile or methanol). The chemometric approach revealed that omeprazole was tailing with methanol and fronting with acetonitrile along with increased fronting at higher pH. The increased fronting with higher pH for acetonitrile was explored using a pH-dependent adsorption isotherm model that was determined using the inverse method and it agreed well with the experimental data. The model indicated that the peaks exhibit more fronting at high pH due to a larger fraction of charged omeprazole molecules. This model could accurately predict the shape of elution profiles at arbitrary pH levels in the studied interval. Using a two-layer adsorption isotherm model, the difference between acetonitrile and methanol was studied at the lowest pH at which almost all omeprazole molecules are neutral. Omeprazole had adsorbate–adsorbate interactions that were similar in strength for the acetonitrile and methanol mobile phases, while the solute–adsorbent interactions were almost twice as strong with methanol. The difference in the relative strengths of these two interactions likely explains the different peak asymmetries (i.e., tailing/fronting) in methanol and acetonitrile. In conclusion, thermodynamic modelling can complement chemometric modeling in HPLC method development and increase the understanding of the separation.
|
|
