| 1. |
- Aspvall, K., et al.
(författare)
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Stepped Care Internet-Delivered vs Face-to-Face Cognitive-Behavior Therapy for Pediatric Obsessive-Compulsive Disorder A Trial Protocol for a Randomized Noninferiority Trial
- 2019
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Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Internet-delivered cognitive behavior therapy is an effective treatment for children and adolescents with obsessive-compulsive disorder and has the potential to markedly increase access to treatment for patients while being cost-effective for health care organizations. OBJECTIVE To investigate whether internet-delivered cognitive behavior therapy implemented within a stepped care model is noninferior to, and cost-effective compared with, the gold standard of face-to-face cognitive behavior therapy for pediatric obsessive-compulsive disorder. DESIGN, SETTING, AND PARTICIPANTS Multicenter, single-blind, randomized clinical noninferiority trial implemented at 2 specialist pediatric obsessive-compulsive disorder clinics in Stockholm and Gothenburg, Sweden. Participants are 152 children and adolescents aged 7 to 17 years with obsessive compulsive disorder, recruited through the 2 clinics and online self-referral. Patients will be randomized 1:1 to the stepped care intervention or face-to-face therapy. Blind evaluations will be conducted after treatment and at 3-month and 6-month follow-ups. At the 6-month follow-up (primary end point), noninferiority will be tested and resource use will be compared between the 2 treatment groups. Data will be analyzed according to intention-to-treat principles. INTERVENTION Patients randomized to stepped care will first receive internet-delivered cognitive behavior therapy for 16 weeks; patients who are classified as nonresponders 3 months after treatment completion will receive additional face-to-face therapy. The control group will receive 16 weeks of face-to-face cognitive behavior therapy immediately following randomization and nonresponders at the 3-month follow-up will, as in the stepped care group, receive additional face-to-face therapy. MAIN OUTCOMES AND MEASURES Noninferiority is defined as a 4-point difference on the primary outcome measure (Children's Yale-Brown Obsessive Compulsive Scale). DISCUSSION Recruitment started October 6, 2017, and was completed May 24, 2019. Results from the primary end point will be available by May 2020. The naturalistic follow-ups (1, 2, and 5 years after the end of treatment) will continue to 2025. There are no interim analyses planned or stopping rules for the trial.
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| 2. |
- Bergman, Peter, et al.
(författare)
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Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
- 2021
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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| 3. |
- Lauri, Klara Olofsdotter, et al.
(författare)
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Long-term effect of stepped-care vs in-person cognitive behavioral therapy for pediatric obsessive-compulsive disorder
- 2023
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Ingår i: Internet Interventions. - : Elsevier BV. - 2214-7829. ; 32
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Tidskriftsartikel (refereegranskat)abstract
- Long-term follow-up data from trials of digital mental health interventions are rare. This study reports 2-year follow-up data from a non-inferiority trial (N = 152) comparing stepped-care (internet-delivered cognitive behavioral therapy [CBT] followed by traditional in-person CBT if needed) vs in-person CBT for pediatric obsessive-compulsive disorder. Both treatment groups had comparable long-term effects, with the majority of participants being responders (stepped-care 66 %; in-person CBT 71 %) 2 years after the end of treatment.
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| 4. |
- Pettersson, Hanna, et al.
(författare)
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CYP7B1-mediated metabolism of dehydroepiandrosterone and 5alpha-androstane-3beta,17beta-diol--potential role(s) for estrogen signaling
- 2008
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 275:8, s. 1778-1789
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Tidskriftsartikel (refereegranskat)abstract
- CYP7B1, a cytochrome P450 enzyme, metabolizes several steroids involved in hormonal signaling including 5 alpha-androstane-3 beta,17 beta-diol (3 beta-Adiol), an estrogen receptor agonist, and dehydroepiandrosterone, a precursor for sex hormones. Previous studies have suggested that CYP7B1-dependent metabolism involving dehydroepiandrosterone or 3 beta-Adiol may play an important role for estrogen receptor beta-mediated signaling. However, conflicting data are reported regarding the influence of different CYP7B1-related steroids on estrogen receptor beta activation. In the present study, we investigated CYP7B1-mediated conversions of dehydroepiandrosterone and 3 beta-Adiol in porcine microsomes and human kidney cells. As part of these studies, we compared the effects of 3 beta-Adiol (a CYP7B1 substrate) and 7 alpha-hydroxy-dehydroepiandrosterone (a CYP7B1 product) on estrogen receptor beta activation. The data obtained indicated that 3 beta-Adiol is a more efficient activator, thus lending support to the notion that CYP7B1 catalysis may decrease estrogen receptor beta activation. Our data on metabolism indicate that the efficiencies of CYP7B1-mediated hydroxylations of dehydroepiandrosterone and 3 beta-Adiol are very similar. The enzyme catalyzed both reactions at a similar rate and the K-cat/K-m values were in the same order of magnitude. A high dehydroepiandrosterone/3 beta-Adiol ratio in the incubation mixtures, similar to the ratio of these steroids in many human tissues, strongly suppressed CYP7B1-mediated 3 beta-Adiol metabolism. As the efficiencies of CYP7B1-mediated hydroxylation of dehydroepiandrosterone and 3 beta-Adiol are similar, we propose that varying steroid concentrations may be the most important factor determining the rate of CYP7B1-mediated metabolism of dehydroepiandrosterone or 3 beta-Adiol. Consequently, tissue-specific steroid concentrations may have a strong impact on CYP7B1-dependent catalysis and thus on the levels of different CYP7B1-related steroids that can influence estrogen receptor beta signaling.
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