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- Conzelmann, A., et al.
(author)
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Internet-based psychotherapy in children with obsessive-compulsive disorder (OCD): protocol of a randomized controlled trial
- 2022
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1
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Journal article (peer-reviewed)abstract
- Background: Obsessive-compulsive disorder (OCD) in children can lead to a huge burden on the concerned patients and their family members. While successful state-of-the art cognitive behavioral interventions exist, there is still a lack of available experts for treatment at home, where most symptoms manifest. Internet-based cognitive behavioral therapy (iCBT) could overcome these restrictions; however, studies about iCBT in children with OCD are rare and mostly target computerized self-help resources and only email contact with the therapist. Therefore, we intended to build up and to evaluate an iCBT approach for children with OCD, replacing successful elements of traditional in-office face-to-face CBT, with face-to-face teleconferences, online materials, and apps. Methods: With the help of a pilot feasibility study, we developed the iCBT consisting of 14 teleconference sessions with the child and parents. The sessions are supported by an app assessing daily and weekly symptoms and treatment course completed by children and parents. Additionally, we obtain heart rate and activity scores from the child via wristbands during several days and exposure sessions. Using a waiting list randomized control trial design, we aim to treat and analyze 20 children with OCD immediately after a diagnostic session whereas the control group of another set of 20 OCD patients will be treated after waiting period of 16 weeks. We will recruit 30 patients in each group to take account for potential dropouts. Outcomes for the treatment group are evaluated before randomization (baseline, t0), 16 weeks (end of treatment, t1), 32 weeks (follow-up 1, t2), and 48 weeks after randomization (follow-up 2, t3). For the waiting list group, outcomes are measured before the first randomization (baseline), at 16 weeks (waiting list period), 32 weeks (end of treatment), 48 weeks after the first randomization (follow-up I), and 64 weeks after the first randomization (follow-up II). Discussion: Based on our experience of feasibility during the pilot study, we were able to develop the iCBT approach and the current study will investigate treatment effectiveness. Building up an iCBT approach, resembling traditional in-office face-to-face therapy, may ensure the achievement of well-known therapy effect factors, the acceptance in both patients and clinicians, and the wide distribution within the health system.
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- Bybrant, M. C., et al.
(author)
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Celiac disease can be predicted by high levels of tissue transglutaminase antibodies in children and adolescents with type 1 diabetes
- 2021
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In: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 417-424
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Journal article (peer-reviewed)abstract
- Objectives Children with type 1 diabetes (T1D) are not included in guidelines regarding diagnosis criteria for celiac disease (CD) without a diagnostic biopsy, due to lack of data. We explored whether tissue transglutaminase antibodies (anti-tTG) that were >= 10 times the upper limit of normal (10x ULN) predicted CD in T1D. Methods Data from the Swedish prospective Better Diabetes Diagnosis study was used, and 2035 children and adolescents with T1D diagnosed between 2005-2010 were included. Of these, 32 had been diagnosed with CD before T1D. The children without CD were repeatedly screened for CD using anti-tTG antibodies of immunoglobulin type A. In addition, their human leukocyte antigen (HLA) were genotyped. All children with positive anti-tTG were advised to undergo biopsy. Biopsies were performed on 119 children and graded using the Marsh-Oberhuber classification. Results All of the 60 children with anti-tTG >= 10x ULN had CD verified by biopsies. The degree of mucosal damage correlated with anti-tTG levels. Among 2003 screened children, 6.9% had positive anti-tTG and 5.6% were confirmed CD. The overall CD prevalence, when including the 32 children with CD before T1D, was 7.0% (145/2035). All but one of the children diagnosed with CD had HLA-DQ2 and/or DQ8. Conclusions As all screened children and adolescents with T1D with tissue transglutaminase antibodies above 10 times the positive value 10x ULN had CD, we propose that the guidelines for diagnosing CD in screened children, when biopsies can be omitted, should also apply to children and adolescents with T1D as a noninvasive method.
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- Hollmann, K., et al.
(author)
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Internet-based cognitive behavioral therapy in children and adolescents with obsessive compulsive disorder: a feasibility study
- 2021
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In: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 128, s. 1445-1459
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Journal article (peer-reviewed)abstract
- Cognitive behavioral therapy (CBT) is the first choice of treatment of obsessive-compulsive disorder (OCD) in children and adolescents. However, there is often a lack of access to appropriate treatment close to the home of the patients. An internet-based CBT via videoconferencing could facilitate access to state-of-the-art treatment even in remote areas. The aim of this study was to investigate feasibility and acceptability of this telemedical approach. A total of nine children received 14 sessions of CBT. The first session took place face-to-face, the remaining 13 sessions via videoconference. OCD symptoms were recorded with a smartphone app and therapy materials were made accessible in a data cloud. We assessed diagnostic data before and after treatment and obtained measures to feasibility, treatment satisfaction and acceptability. Outcomes showed high acceptance and satisfaction on the part of patients with online treatment (89%) and that face-to-face therapy was not preferred over an internet-based approach (67%). The majority of patients and their parents classified the quality of treatment as high. They emphasized the usefulness of exposures with response prevention (E/RP) in triggering situations at home. The app itself was rated as easy to operate and useful. In addition to feasibility, a significant decrease in obsessive-compulsive symptoms was also achieved. Internet-based CBT for pediatric OCD is feasible and well received by the patients and their parents. Furthermore, obsessive-compulsive symptomatology decreased in all patients. The results of this study are encouraging and suggest the significance of further research regarding this technology-supported approach, with a specific focus on efficacy. Trial registration number: Clinical trials AZ53-5400.1-004/44.
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- Selles, R. R., et al.
(author)
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Avoidance, Insight, Impairment Recognition Concordance, and Cognitive-Behavioral Therapy Outcomes in Pediatric Obsessive-Compulsive Disorder
- 2020
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In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 59:5
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Journal article (peer-reviewed)abstract
- Objective: Insight and avoidance are commonly discussed factors in obsessive-compulsive disorder (OCD) that have demonstrated associations with increased severity as well as reduced treatment response in adults, but these factors have not been sufficiently examined in pediatric OCD. This study examined the impacts of avoidance, insight, and impairment recognition concordance on cognitive-behavioral therapy (CBT) outcomes as well as impacts of CBT on insight and avoidance in a large sample of youths affected by OCD. Method: Data from 573 OCD-affected youths enrolled in CBT trials were aggregated. Children's Yale-Brown Obsessive-Compulsive Scale items measured treatment response, insight, and avoidance. Standardized differences between child and parent ratings of impairment were used to calculate impairment recognition concordance. Binary logistic regression was used to identify variables associated with treatment response. Results: Greater avoidance, limited child recognition of impairment, older age, and lower baseline severity predicted reduced likelihood of treatment response, but insight did not. Both insight and avoidance improved significantly following CBT. Response rates were lower when posttreatment insight and avoidance were worse. Conclusion: Contrasting with prevailing belief, poor insight does not appear to limit CBT response potential in pediatric OCD. Avoidance and impairment recognition are understudied CBT response predictors and warrant further consideration in pediatric OCD. Clinicians should attend to these factors to optimize outcomes for children affected by this common, debilitating illness.
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- Western, Benedikte, et al.
(author)
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Dropout from exercise trials among cancer survivors—An individual patient data meta-analysis from the POLARIS study
- 2024
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In: Scandinavian Journal of Medicine and Science in Sports. - Chichester, West Sussex : Wiley-Blackwell Publishing Inc.. - 0905-7188 .- 1600-0838. ; 34:2, s. 1-10
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Journal article (peer-reviewed)abstract
- Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. Results: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2, performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. Conclusions: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects. © 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
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- Jensen, S., et al.
(author)
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Quality of life in pediatric patients with obsessive-compulsive disorder during and 3 years after stepped-care treatment
- 2022
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In: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 31:9, s. 1377-1389
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Journal article (peer-reviewed)abstract
- The present study aimed to investigate the long-term quality of life (QoL) in a large sample of pediatric obsessive-compulsive disorder (OCD) patients. The study included 220 pediatric OCD patients from the Nordic Long-term OCD Treatment Study (NordLOTS) who were evaluated at seven time points before, during, and after stepped-care treatment over a 3-year follow-up period. Data from three symptom severity trajectory classes formed the basis of the QoL evaluation: acute (n = 127, N = 147), slow (n = 46, N = 63), and limited responders (n = 47, N = 59). Patients' QoL was assessed using parent and child ratings of the revised Questionnaire for Measuring Health-related Quality of Life in Children and Adolescents (KINDL-R). QoL was analyzed by trajectory class using a random mixed effects model. The association between pre-treatment factors and long-term QoL was investigated across classes in a multivariate model. Three years after treatment, the acute responder class had reached QoL levels from a general population, whereas the limited responder class had not. The slow responder class reached norm levels for the child-rated QoL only. Higher levels of co-occurring externalizing symptoms before treatment were associated with lower parent-rated QoL during follow-up, while adolescence and higher levels of co-occurring internalizing symptoms were associated with lower child-rated QoL during follow-up. For some patients, residual OCD symptoms in the years after treatment, even at levels below assumed clinical significance, are associated with compromised QoL. Co-occurring symptoms could be part of the explanation. Assessing QoL after OCD treatment, beyond the clinician-rated symptom severity, could detect patients in need of further treatment and/or assessment. Trial registry: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; ; ISRCTN66385119.
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- Strunz, B., et al.
(author)
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Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy
- 2021
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In: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 6:56
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Journal article (peer-reviewed)abstract
- Immune cell differentiation is critical for adequate tissue-specific immune responses to occur. Here, we studied differentiation of human uterine natural killer cells (uNK cells). These cells reside in a tissue undergoing constant regeneration and represent the major leukocyte population at the maternal-fetal interface. However, their physiological response during the menstrual cycle and in pregnancy remains elusive. By surface proteome and transcriptome analysis as well as using humanized mice, we identify a differentiation pathway of uNK cells in vitro and in vivo with sequential acquisition of killer cell immunoglobulin-like receptors and CD39. uNK cell differentiation occurred continuously in response to the endometrial regeneration and was driven by interleukin-15. Differentiated uNK cells displayed reduced proliferative capacity and immunomodulatory function including enhanced angiogenic capacity. By studying human uterus transplantation and monozygotic twins, we found that the uNK cell niche could be replenished from circulation and that it was under genetic control. Together, our study uncovers a continuous differentiation pathway of human NK cells in the uterus that is coupled to profound functional changes in response to local tissue regeneration and pregnancy.
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- Trkulja, C. L., et al.
(author)
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Rational antibody design for undruggable targets using kinetically controlled biomolecular probes
- 2021
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:16
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Journal article (peer-reviewed)abstract
- Several important drug targets, e.g., ion channels and G protein-coupled receptors, are extremely difficult to approach with current antibody technologies. To address these targets classes, we explored kinetically controlled proteases as structural dynamics-sensitive druggability probes in native-state and disease-relevant proteins. By using low-Reynolds number flows, such that a single or a few protease incisions are made, we could identify antibody binding sites (epitopes) that were translated into short-sequence antigens for antibody production. We obtained molecular-level information of the epitope-paratope region and could produce high-affinity antibodies with programmed pharmacological function against difficult-to-drug targets. We demonstrate the first stimulus-selective monoclonal antibodies targeting the transient receptor potential vanilloid 1 (TRPV1) channel, a clinically validated pain target widely considered undruggable with antibodies, and apoptosis-inducing antibodies selectively mediating cytotoxicity in KRAS-mutated cells. It is our hope that this platform will widen the scope of antibody therapeutics for the benefit of patients.
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