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- Brundin, Peik M., et al.
(författare)
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Expression of Sex Hormone Receptor and Immune Response Genes in Peripheral Blood Mononuclear Cells During the Menstrual Cycle
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormones are known to interact with the immune system on multiple levels but information on the types of sex hormone receptors (SHR) and their expression levels in immune cells is scarce. Estrogen, testosterone and progesterone are all considered to interact with the immune system through their respective cell receptors (ERα and ERβ including the splice variant ERβ2, AR and PGR). In this study expression levels of SHR genes in peripheral blood mononuclear cells (PBMCs) and cell subsets (CD4+ and CD8+ T-cells, CD56+ NK-cells, CD14+ monocytes and CD19+ B-cells) were analyzed using standard manual qPCR or a qPCR array (TLDA). Nine healthy individuals including men (n = 2), premenopausal (Pre-MP, n = 5) and postmenopausal (post-MP, n = 2) women were sampled for PBMCs which were separated to cell subsets using FACS. Ten Pre-MP women were longitudinally sampled for total PBMCs at different phases of the menstrual cycle. We found that ERα was most abundant and, unexpectedly, that ERβ2 was the dominant ERβ variant in several FACS sorted cell subsets. In total PBMCs, SHR (ERα, ERβ1, ERβ2, and AR) expression did not fluctuate according to the phase of the menstrual cycle and PGR was not expressed. However, several immune response genes (GATA3, IFNG, IL1B, LTA, NFKB1, PDCD1, STAT3, STAT5A, TBX21, TGFB1, TNFA) were more expressed during the ovulatory and mid-luteal phases. Sex hormone levels did not correlate significantly with gene expression of SHR or immune response genes, but sex hormone-binding globulin (SHBG), a steroid hormone transporting protein, was positively correlated to expression of ERβ1 gene. This study provides new insights in the distribution of ERs in immune cells. Furthermore, expression patterns of several immune response genes differ significantly between phases of the menstrual cycle, supporting a role for sex hormones in the immune response.
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- Landgren, Valdemar, 1988, et al.
(författare)
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The ESSENCE-Questionnaire in Medical Records Screening for Neurodevelopmental Symptoms/Problems: Utility and Clinical Validity
- 2022
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Ingår i: Neuropsychiatric Disease and Treatment. - 1178-2021. ; 18, s. 2559-2574
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Determine the prevalence of symptoms of neurodevelopmental problems (NDPs) with a semi-structured review of fourth grade students' medical records, its interrater agreement and validity as compared with clinical assessment. Methods: A school-based sample of 11-year-old children provided child health care (CHC) records and school health care (SHC) records. A pediatric neurologist, child psychiatrist and an adult psychiatrist scored the records, with the "Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations-Questionnaire" (ESSENCE-Q, 12 items scored 0-2, summary score range 0-24). Agreement was measured with model-based kappa and intraclass correlation coefficient (ICC). Ratings were validated against a multidisciplinary assessment involving a physician, psychologist, teacher- and parental behavioral rating scales rendering a clinical global impression severity rating (CGI-S, range 1-7) of NDPs. Results: Out of 223 participants, medical charts were available from 201, of whom 169 were rated by all three raters. Kappa agreement was moderate/strong (similar to 0.8) for 7 of the 12 questionnaire items. Measured with the ICC, concordance in the summary score was good for agreement (similar to 0.8) and excellent (similar to 0.9) for consistency. Test-retest reliability was excellent (ICC = similar to 0.9). Area under the curve for the ESSENCE-Q in predicting clinical-level problems (CGI >= 4) was similar to 80% for all three raters, albeit with differing optimal cutoffs. Conclusion: Using the ESSENCE-Q as a template, NDPs appear to be common in medical records, are identified reliably, and predict clinical-level concern. Medical records screening may facilitate a structured review of medical records in work-ups or be applied in conjunction with other screening measures for neurodevelopmental disorders. However, differences in calibration currently preclude defining a universal cutoff for using the ESSENCE-Q for medical records screening.
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- Brundin, Peik M.A., et al.
(författare)
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Blood hormones and torque teno virus in peripheral blood mononuclear cells
- 2020
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.
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- Landgren, E., et al.
(författare)
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Patients' Perceptions of Person-Centred Care in Early RA : A Qualitative Study
- 2021
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:Suppl. 1, s. 1024-1024
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Tidskriftsartikel (refereegranskat)abstract
- Data on patients’ experience can identify strengths and weaknesses with given care, why a person-centred care will improve health care quality. In rheumatology care, most research on patient preferences for and experiences of RA care is performed in patients with established RA and less often in patients with early RA. In the early course of RA patients often struggle to manage their new life situation with a chronic disease and its treatment. Expectations and experiences of health care may change over time why it is important to understand how newly diagnosed patients perceive person-centred care.Objectives:To explore patients’ perceptions of person-centred care early in the RA disease course within the framework of person-centred care.Methods:In this qualitative study 31 patients with early RA from four rheumatology specialist outpatient clinics were interviewed. An abductive qualitative content analysis was conducted based on the framework of McCormack and McCance (2006, 2016). The four constructs; prerequisites, care environment, person-centred processes, and person-centred outcomes constituted the four categories in the deductive part of the study. An inductive analysis revealed eleven sub-categories exploring the content of person-centred care for patients with early RA.Results:For patients with early RA person-centred care was described as; 1. Prerequisites were to be treated with respect, to meet dedicated healthcare professionals, and to meet professional competence. 2. The care environment was to have access to a multidisciplinary team, to have access to health care, and a supportive organization. 3. Person-centred processes were to be listened to, to be supported, and to be involved in decision-making. 4. The person-centred outcomes were to be satisfied with received health care and to achieve optimal health.Conclusion:A true person-centred care is important to patients early in the RA disease course, supporting the relevance to implement person-centred approach at all stages in the health care system. This study contributes to information about how to further develop person-centredness in rheumatology care also early in the disease course.References:[1]McCormack, B., & McCance, T. V. (2006). Development of a framework for person-centred nursing. J Adv Nurs, 56(5), 472-479. doi:10.1111/j.1365-2648.2006.04042.x[2]McCormack, B., & McCance, T. V. (2016). Person-centred practice in nursing and health care: theory and practice (2nd edition ed.): John Wiley & Sons.Disclosure of Interests:None declared
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- Landgren, Valdemar, 1988, et al.
(författare)
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Effect of Gonadotropin-Releasing Hormone Antagonist on Risk of Committing Child Sexual Abuse in Men with Pedophilic Disorder: A Randomized Clinical Trial
- 2020
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Ingår i: JAMA Psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 77:9, s. 897-905
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Evidence-based treatments from randomized clinical trials for pedophilic disorder are lacking. Objective: To determine whether a gonadotropin-releasing hormone antagonist reduces dynamic risk factors for committing child sexual abuse. Design, Setting, and Participants: This academically initiated, double-blind, placebo-controlled, parallel-group, phase 2 randomized clinical trial was conducted at the ANOVA center in Stockholm, Sweden, from March 1, 2016, to April 30, 2019. Individuals who contacted PrevenTell, the national telephone helpline for unwanted sexuality, were recruited. Eligible participants were men seeking help aged 18 to 66 years with a pedophilic disorder diagnosis and no contraindications to the intervention. The primary end point was assessed by intent-to-treat analysis. Interventions: Randomization to receive either 2 subcutaneous injections of 120 mg of degarelix acetate or equal volume of placebo. Main Outcomes and Measures: The primary end point was the mean change between baseline and 2 weeks in the composite risk score of 5 domains of child sexual abuse ranging from 0 to 15 points; each domain could be rated from 0 to 3 points. Secondary end points included efficacy at 2 and 10 weeks as measured by the composite score, each risk domain, quality of life, self-reported effects, and adverse events. Results: A total of 52 male participants (mean [SD] age, 36 [12] years) were randomized to receive either degarelix (n = 25; with 1 withdrawal) or placebo (n = 26). At 2 weeks, the composite risk score decreased from 7.4 to 4.4 for participants in the degarelix group and from 7.8 to 6.6 for the placebo group, a mean between-group difference of -1.8 (95% CI, -3.2 to -0.5; P =.01). A decrease was seen in the composite score at 10 weeks (-2.2 [95% CI, -3.6 to -0.7]) as well as in the domains of pedophilic disorder (2 weeks: -0.7 [95% CI, -1.4 to 0.0]; 10 weeks: -1.1 [95% CI, -1.8 to -0.4]) and sexual preoccupation (2 weeks: -0.7 [95% CI, -1.2 to -0.3]; 10 weeks: -0.8 [95% CI, -1.3 to -0.3]) in the degarelix group compared with the placebo group. No difference was seen for the domains of self-rated risk (2 weeks: -0.4 [95% CI, -0.9 to 0.1]; 10 weeks: -0.5 [95% CI, -1 to 0.0]), low empathy (2 weeks: 0.2 [95% CI, -0.3 to 0.6]; 10 weeks: 0.2 [95% CI, -0.2 to 0.6]), and impaired self-regulation (2 weeks: -0.0 [95% CI, -0.7 to 0.6]; 10 weeks: 0.1 [95% CI, -0.5 to 0.8]), or quality of life (EuroQol 5 Dimensions questionnaire index score, 2 weeks: 0.06 [95% CI, -0.00 to 0.12], and 10 weeks: 0.04; 95% CI, -0.02 to 0.10; EuroQol visual analog scale, 2 weeks: 0.6 [95% CI, -9.7 to 10.9], and 10 weeks: 4.2 [95% CI, -6.0 to 14.4]). Two hospitalizations occurred from increased suicidal ideation, and more injection site reactions (degarelix: 22 of 25 [88%]; placebo: 1 of 26 [4%]) and hepatobiliary enzyme level elevations were reported by participants who received degarelix (degarelix: 11 of 25 [44%]; placebo: 2 of 26 [8%]). Among the 26 participants randomized to receive degarelix, 20 (77%) experienced positive effects (eg, improved attitude or behavior) on sexuality and 23 (89%) reported adverse effects on the body. Conclusion and Relevance: This trial found that degarelix reduced the risk score for committing child sexual abuse in men with pedophilic disorder 2 weeks after initial injection, suggesting use of the drug as a rapid-onset treatment option. Further studies are warranted into the effects and long-term adverse effects of hormone deficiency. Trial Registration: EU Clinical Trials Register Identifier: 2014-000647-32. © 2020 American Medical Association. All rights reserved.
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| 16. |
- Landgren, Valdemar, 1988, et al.
(författare)
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Pharmacological Treatment for Pedophilic Disorder and Compulsive Sexual Behavior Disorder: A Review
- 2022
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Ingår i: Drugs. - : Springer Science and Business Media LLC. - 0012-6667 .- 1179-1950. ; 82:6, s. 663-681
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines for the pharmacological treatment of paraphilic disorders have historically been based on data from forensic settings and on risk levels for sexual crime. However, emerging treatment options are being evaluated for individuals experiencing distress because of their sexual urges and preferences, targeting both paraphilic disorders such as pedophilic disorder (PeD) and the new diagnosis of compulsive sexual behavior disorder (CSBD) included in the International Classification of Diseases, 11th Revision (ICD-11). As in other mental disorders, this may enable individualized pharmacological treatment plans, taking into account components of sexuality (e.g. high libido, compulsivity, anxiety-driven/sex as coping), medical and psychiatric comorbidity, adverse effects and patient preferences. In order to expand on previous reviews, we conducted a literature search focusing on randomized controlled trials of pharmacological treatment for persons likely to have PeD or CSBD. Our search was not restricted to studies involving forensic or criminal samples. Twelve studies conducted between 1974 and 2021 were identified regardless of setting (outpatient or inpatient), with only one study conducted during the last decade. Of a total of 213 participants included in these studies, 122 (57%) were likely to have PeD, 34 (16%) were likely to have a CSBD, and the remainder had unspecified paraphilias (40, 21%) or sexual offense (17, 8%) as the treatment indication. The diagnostic procedure for PeD and/or CSBD, as well as comorbid psychiatric symptoms, has been described in seven studies. The studies provide some empirical evidence that testosterone-lowering drugs reduce sexual activity for patients with PeD or CSBD, but the body of evidence is meager. There is a need for studies using larger samples, specific criteria for inclusion, longer follow-up periods, and standardized outcome measures with adherence to international reporting guidelines.
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- Sigurbergsdottir, Adalbjorg Yr, et al.
(författare)
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Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts: results from the population-based iStopMM study
- 2023
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Ingår i: REVISTA CHILENA DE LITERATURA. - 0718-2295. ; :108, s. 3392-3398
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with re-gards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumato-logical disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.
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- Sverrisdottir, I. S., et al.
(författare)
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Comorbidities in multiple myeloma and implications on survival: A population-based study
- 2021
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 106:6, s. 774-782
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Tidskriftsartikel (refereegranskat)abstract
- High proportion of patients with multiple myeloma suffer from comorbidities which may alter clinical management. Therefore, our aims were to evaluate the prevalence of comorbidities and their impact on survival. We included patients diagnosed with multiple myeloma 1990-2013 in Sweden and all diagnoses from each patient from 1985. A total of 13 656 patients with multiple myeloma were included in the study, thereof 7404 (54%) had comorbidity at diagnosis. The risk of death was increased for those with one comorbidity at diagnosis compared to those without any comorbidity (hazard ratio = 1.19; 95% confidence interval:1.14-1.25); this risk was higher for those with two (1.38; 1.30-1.47) and three or more comorbidities (1.72; 1.62-1.83). Furthermore, the risk of death was increased in patients with prior history of cancer, arrhythmia, heart failure, diabetes mellitus, cerebrovascular disease, chronic lung disease, psychological disease, peptic ulcer, neurological disease, peripheral vascular disease, chronic kidney disease, dementia, and inflammatory bowel disease. This large study shows that over 50% of multiple myeloma patients have a comorbidity at diagnosis and survival decreased with increasing numbers of comorbidities. This emphasizes the importance of comorbidities when evaluating patients and deciding on treatment strategies for individuals with multiple myeloma.
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