| 1. |
- Af Winklerfelt Hammarberg, Sandra, et al.
(författare)
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Outcomes of psychiatric interviews and self-rated symptom scales in people on sick leave for common mental disorders: an observational study.
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the correspondence between diagnoses on sick leave certificates and diagnoses made in structured psychiatric interviews. Secondary aims were to investigate length of sick leave by diagnoses on sick leave certificates, diagnoses made in structured interviews and symptom severity.Observational study consisting of a secondary analysis of data from a randomised controlled trial and an observational study.The regions of Stockholm and Västra Götaland, Sweden.480 people on sick leave for common mental disorders.Participants were examined with structured psychiatric interviews and self-rated symptom severity scales.(1) Sick leave certificate diagnoses, (2) diagnoses from the Mini International Neuropsychiatric Interview and the Self-rated Stress-Induced Exhaustion Disorder (SED) Instrument (s-ED), (3) symptom severity (Montgomery-Asberg Depression Rating Scale-self-rating version and the Karolinska Exhaustion Disorder Scale) and (4) number of sick leave days.There was little correspondence between diagnoses on sick leave certificates and diagnoses made in structured psychiatric interviews. Many participants on sick leave for SED, anxiety disorder or depression fulfilled criteria for other mental disorders. Most on sick leave for SED (76%) and anxiety disorder (67%) had depression (p=0.041). Length of sick leave did not differ by certificate diagnoses. Participants with SED (s-ED) had longer sick leave than participants without SED (144 vs 84 days; 1.72 (1.37-2.16); p<0.001). More severe symptoms were associated with longer sick leave.Diagnoses on sick leave certificates did not reflect the complex and overlapping nature of the diagnoses found in the structured psychiatric interviews. This finding is relevant to the interpretation of information from health data registers, including studies and guidelines based on these data. A result of clinical interest was that more severe symptoms predicted long-term sick leave better than actual diagnoses.
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| 2. |
- Hedenstedt, Anna, et al.
(författare)
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B cell polygenic risk scores associate with anti-dsDNA antibodies and nephritis in systemic lupus erythematosus.
- 2023
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Ingår i: Lupus science & medicine. - : BMJ Publishing Group Ltd. - 2053-8790. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- B cell function and autoantibodies are important in SLE pathogenesis. In this work, we aimed to investigate the impact of cumulative SLE B cell genetics on SLE subphenotype and autoantibody profile.Female patients with SLE (n=1248) and healthy controls (n=400) were genotyped using Illumina's Global Screening Array. Two polygenic risk scores (PRSs), one representing B cell genes and the other B cell activation genes, were calculated for each individual using risk loci for SLE in genes assigned to B cell-related pathways according to the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Reactome Databases.Double-stranded DNA (dsDNA) antibodies were more prevalent among patients with a high compared with a low SLE B cell PRS (OR 1.47 (1.07 to 2.01), p=0.018), and effect sizes were augmented in patients with human leucocyte antigen (HLA) risk haplotypes HLA-DRB1*03:01 and HLA-DRB1*15:01 (DRB1*03/15 -/- (OR 0.99 (0.56 to 1.77), p=0.98; DRB1*03/15 +/- or -/+ (OR 1.64 (1.06 to 2.54), p=0.028; and DRB1*03/15 +/+ (OR 4.47 (1.21 to 16.47), p=0.024). Further, a high compared with a low B cell PRS was associated with low complement levels in DRB1*03/15 +/+ patients (OR 3.92 (1.22 to 12.64), p=0.022). The prevalence of lupus nephritis (LN) was higher in patients with a B cell activation PRS above the third quartile compared with patients below (OR 1.32 (1.00 to 1.74), p=0.048).High genetic burden related to B cell function is associated with dsDNA antibody development and LN. Assessing B cell PRSs may be important in order to determine immunological pathways influencing SLE and to predict clinical phenotype.
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| 3. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 4. |
- Skoglund, Charlotte, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder With Teenage Birth Among Women and Girls in Sweden
- 2019
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) is associated with a plethora of adverse health outcomes throughout life. While Swedish specialized youth clinics have carefully and successfully targeted risk of unplanned pregnancies in adolescents, important risk groups, such as women and girls with ADHD, might not be identified or appropriately assisted by these interventions. OBJECTIVES To determine whether women and girls with ADHD are associated with increased risk of teenage birth compared with their unaffected peers and to examine the association of ADHD with risk factors for adverse obstetric and perinatal outcomes, such as smoking, underweight or overweight, and substance use disorder. DESIGN, SETTING, AND PARTICIPANTS This nationwide cohort study included data from 6 national longitudinal population-based registries in Sweden. All nulliparous women and girls who gave birth in Sweden between January 1, 2007, and December 31, 2014, were included. Data analyses were conducted from October 7, 2018, to February 8, 2019. EXPOSURES Women and girls treated with stimulant or nonstimulant medication for ADHD (Anatomic Therapeutic Chemical classification code N06BA) in the Swedish Prescribed Drug Register between July 1, 2005, and December 31, 2014. MAIN OUTCOMES AND MEASURES Maternal age at birth. Secondary outcome measures were body mass index, smoking habits, and psychiatric comorbidities. RESULTS Among 384 103 nulliparous women and girls aged 12 to 50 years who gave birth between 2007 and 2014 included in the study, 6410 (1.7%) (mean [SD] age, 25.0 [5.5] years) were identified as having ADHD. The remaining 377 693 women and girls without ADHD (mean [SD] age, 28.5 [5.1] years) served as the control group. Teenage deliveries were more common among women and girls with ADHD than among women and girls without ADHD (15.3% vs 2.8%; odds ratio [OR], 6.23 [95% CI, 5.80-6.68]). Compared with women and girls without ADHD, those with ADHD were more likely to present with risk factors for adverse obstetric and perinatal outcomes, including smoking during the third trimester (OR, 6.88 [95% CI, 6.45-7.34]), body mass index less than 18.50 (OR, 1.29 [95% CI, 1.12-1.49]), body mass index more than 40.00 (OR, 2.01 [95% CI, 1.60-2.52]), and alcohol and substance use disorder (OR, 20.25 [95% CI, 18.74-21.88]). CONCLUSIONS AND RELEVANCE This study found that women and girls with ADHD were associated with an increased risk of giving birth as teenagers compared with their unaffected peers. The results suggest that standard of care for women and girls with ADHD should include active efforts to prevent teenage pregnancies.
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| 5. |
- Skoglund, Karin, et al.
(författare)
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In vivo CYP3A activity and pharmacokinetics of imatinib in relation to therapeutic outcome in chronic myeloid leukemia patients
- 2016
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Ingår i: Therapeutic Drug Monitoring. - 0163-4356 .- 1536-3694. ; 38:2, s. 230-238
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: CYP3A metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in chronic myeloid leukemia (CML) patients. The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in CML patients.METHODS: Forty-three CML patients were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry.RESULTS: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to non-optimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P=0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity.CONCLUSIONS: CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that even though imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.
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| 6. |
- Skoglund, Karin, et al.
(författare)
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In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia
- 2016
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Ingår i: Therapeutic Drug Monitoring. - : LIPPINCOTT WILLIAMS & WILKINS. - 0163-4356 .- 1536-3694. ; 38:2, s. 230-238
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytochrome P450 3A (CYP3A) isoenzyme metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML). The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in patients with CML. Methods: Forty-three patients with CML were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. Results: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to nonoptimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P = 0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. Conclusions: The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.
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| 7. |
- Wester, Tomas, et al.
(författare)
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Attention deficit hyperactivity and autism spectrum disorders in patients with anorectal malformations
- 2021
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 110:11, s. 3131-3136
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Tidskriftsartikel (refereegranskat)abstract
- AimTo assess the risk of neurodevelopmental disorders in patients with anorectal malformations compared to controls.MethodsThis was a population-based cohort study including all patients born in Sweden 1997–2012 with anorectal malformation in the Swedish National Patient Register and five matched controls per patient. Anorectal malformation was the exposure. All individuals were evaluated for the outcomes, attention deficit hyperactivity disorder or autism spectrum disorder in the National Patient Register. Data on drugs for attention deficit hyperactivity disorder were retrieved from the Swedish Prescribed Drug Register and used as proxy for attention deficit hyperactivity disorder. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Analyses were adjusted for confounders.ResultsFive hundred and fifteen patients with anorectal malformations and 2560 controls were included. Patients with anorectal malformation had a higher risk of attention deficit hyperactivity disorder (OR 3.01 (95% CI, 1.83–4.95)) and autism spectrum disorders (OR 3.07 (95% CI, 1.62–5.79)) compared to the controls. Significantly more patients with anorectal malformation had been prescribed medication for attention deficit hyperactivity disorder compared to controls (OR 2.26 (95% CI 1.33–3.85)).ConclusionPatients with anorectal malformations have a higher risk of attention deficit hyperactivity disorder and autism spectrum disorders than controls.
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| 8. |
- Wikman, Anna, et al.
(författare)
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Factors associated with re-initiation of antidepressant treatment following discontinuation during pregnancy : a register-based cohort study.
- 2020
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Ingår i: Archives of Women's Mental Health. - : Springer Science and Business Media LLC. - 1434-1816 .- 1435-1102. ; 23:5, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Antidepressant treatment when facing a pregnancy is an important issue for many women and their physicians. We hypothesized that women with a greater burden of pre-pregnancy psychiatric illness would be more likely to re-initiate antidepressants following discontinuation of treatment during pregnancy. A register-based cohort study was carried out including 38,595 women who gave birth between the 1st of January 2007 and the 31st of December 2014, who had filled a prescription for an antidepressant medication in the year prior to conception. Logistic regressions were used to explore associations between maternal characteristics and antidepressant treatment discontinuation or re-initiation during pregnancy. Most women discontinued antidepressant treatment during pregnancy (n = 29,095, 75.4%), of whom nearly 12% (n = 3434, 11.8%) re-initiated treatment during pregnancy. In adjusted analyses, parous women (aOR 1.22, 95% CI 1.12-1.33), with high educational level (aOR 1.21, 95% CI 1.08-1.36); born within the EU (excluding Nordic countries, aOR 1.41, 95% CI 1.03-1.92) or a Nordic country (aOR 1.42, 95% CI 1.22-1.65); who more often reported prior hospitalizations due to psychiatric disorders (aOR 1.50, 95% CI 1.10-2.03, for three or more episodes); and had longer duration of pre-pregnancy antidepressant use (aOR 6.10, 95% CI 5.48-6.77, for >2 years antidepressant use), were more likely to re-initiate antidepressants than were women who remained off treatment. Women with a greater burden of pre-pregnancy psychiatric illness were more likely to re-initiate antidepressants. Thus, pre-pregnancy psychiatric history may be particularly important for weighing the risks and benefits of discontinuing antidepressants during pregnancy.
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| 9. |
- Ahrén, Maria, et al.
(författare)
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Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
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Tidskriftsartikel (refereegranskat)abstract
- Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
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| 10. |
- Albán Reyes, Diana Carolina, et al.
(författare)
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The influence of different parameters on the mercerisation of cellulose for viscose production
- 2016
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Ingår i: Cellulose. - : Springer Netherlands. - 0969-0239 .- 1572-882X. ; 23:2, s. 1061-1072
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Tidskriftsartikel (refereegranskat)abstract
- A quantitative analysis of degree of transformation from a softwood sulphite dissolving pulp to alkalised material and the yield of this transformation as a function of the simultaneous variation of the NaOH concentration, denoted [NaOH], reaction time and temperature was performed. Samples were analysed with Raman spectroscopy in combination with multivariate data analysis and these results were confirmed by X-ray diffraction. Gravimetry was used to measure the yield. The resulting data were related to the processing conditions in a Partial Least Square regression model, which made it possible to explore the relevance of the three studied variables on the responses. The detailed predictions for the interactive effects of the measured parameters made it possible to determine optimal conditions for both yield and degree of transformation in viscose manufacturing. The yield was positively correlated to the temperature from room temperature up to 45 A degrees C, after which the relation was negative. Temperature was found to be important for the degree of transformation and yield. The time to reach a certain degree of transformation (i.e. mercerisation) depended on both temperature and [NaOH]. At low temperatures and high [NaOH], mercerisation was instantaneous. It was concluded that the size of fibre particles (mesh range 0.25-1 mm) had no influence on degree of transformation in viscose processing conditions, apparently due to the quick reaction with the excess of NaOH.
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