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  • Lumbers, R. T., et al. (författare)
  • The genomics of heart failure: design and rationale of the HERMES consortium
  • 2021
  • Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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  • Madsen, C. L., et al. (författare)
  • The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk
  • 2023
  • Ingår i: American Heart Journal. - 0002-8703. ; 264, s. 133-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Current recommendations regarding the use of surgical left atrial appendage (IAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant IAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA 2 DS 2 -VASc score. Methods This protocol describes a randomized multicenter trial. Consecutive participants & GE;18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA 2 DS 2 -VASc score. Patients already planned for ablation or IAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant IAA closure or standard care (ie, open IAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). Conclusions The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. Trial registration: NCT03724318. (Am HeartJ 2023;264:133-142.)
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  • Patel, Riyaz S., et al. (författare)
  • Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
  • 2019
  • Ingår i: Circulation. - 2574-8300. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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  • Conzelmann, A., et al. (författare)
  • Internet-based psychotherapy in children with obsessive-compulsive disorder (OCD): protocol of a randomized controlled trial
  • 2022
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1
  • Tidskriftsartikel (refereegranskat)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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  • Glinge, Charlotte, et al. (författare)
  • Seasonality of ventricular fibrillation at first myocardial infarction and association with viral exposure
  • 2020
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To investigate seasonality and association of increased enterovirus and influenza activity in the community with ventricular fibrillation (VF) risk during first ST-elevation myocardial infarction (STEMI). Methods This study comprised all consecutive patients with first STEMI (n = 4,659; aged 18–80 years) admitted to the invasive catheterization laboratory between 2010–2016, at Copenhagen University Hospital, Rigshospitalet, covering eastern Denmark (2.6 million inhabitants, 45% of the Danish population). Hospital admission, prescription, and vital status data were assessed using Danish nationwide registries. We utilized monthly/weekly surveillance data for enterovirus and influenza from the Danish National Microbiology Database (2010–2016) that receives copies of laboratory tests from all Danish departments of clinical microbiology. Results Of the 4,659 consecutively enrolled STEMI patients, 581 (12%) had VF before primary percutaneous coronary intervention. In a subset (n = 807), we found that VF patients experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with the patients without VF (OR 3.39, 95% CI 1.76–6.54). During the study period, 2,704 individuals were diagnosed with enterovirus and 19,742 with influenza. No significant association between enterovirus and VF (OR 1.00, 95% CI 0.99–1.02), influenza and VF (OR 1.00, 95% CI 1.00–1.00), or week number and VF (p-value 0.94 for enterovirus and 0.89 for influenza) was found. Conclusion We found no clear seasonality of VF during first STEMI. Even though VF patients had experienced more generalized fatigue and flu-like symptoms within 7 days before STEMI compared with patients without VF, no relationship was found between enterovirus or influenza exposure and occurrence of VF.
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  • Shah, S, et al. (författare)
  • Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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  • Angelison, Leif, et al. (författare)
  • Long-term outcome of infliximab treatment in chronic active ulcerative colitis : a Swedish multicentre study of 250 patients
  • 2017
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell Publishing Inc.. - 0269-2813 .- 1365-2036. ; 45:4, s. 519-532
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited.Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined.Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant.Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy.Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.
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  • Christiansen, M. N., et al. (författare)
  • Preheart failure comorbidities and impact on prognosis in heart failure patients : a nationwide study
  • 2020
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:6, s. 698-710
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. Objectives: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. Methods: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities antedating the HF-diagnosis in the Danish nationwide registries. HF patients were matched with up to five controls. One-year all-cause mortality rates and population attributable risk (PAR) were estimated for three separate age groups (≤50, 51–74 and >74 years). Results: Totally 280 002 patients with HF and 1 166 773 controls were included. Cardiovascular comorbidities, for example, cerebrovascular disease and ischaemic heart disease were more frequent in the oldest (17.9% and 29.7% in HF vs. 9.8% and 10.7% in controls) compared to the youngest age group (3.9% and 15.2% in HF vs. 0.7% and 0.9% in controls). Amongst patients with HF, 1-year mortality rates (per 100 person-years) were highest amongst those with >1 noncardiovascular comorbidity: ≤50 years (10.4; 9.64–11.3), 51–74 years (23.3; 22.9–23.7), >74 years (58.5; 57.9–59.0); hazard ratios 245.18 (141.45–424.76), 45.85 (42.77–49.15) and 24.5 (23.64–25.68) for those ≤50, 51–74 and >74 years, respectively. For HF patients ≤50 years, PAR was greatest for hypertension (17.8%), cancer (14.1%) and alcohol abuse (8.5%). For those aged >74 years, PAR was greatest for hypertension (23.6%), cerebrovascular disease (6.2%) and cancer (7.2%). Conclusions: Heart failure patients had a higher burden of pre-existing comorbidities, compared to controls, which adversely impacted prognosis, especially in the young.
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  • Connolly, Stuart J, et al. (författare)
  • Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.
  • 2018
  • Ingår i: Lancet (London, England). - 1474-547X. ; 391:10117, s. 205-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.Between March 12, 2013, and May 10, 2016, 27395 patients were enrolled to the COMPASS trial, of whom 24824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012).In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.Bayer AG.
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  • Glinge, Charlotte, et al. (författare)
  • Sibling history is associated with heart failure after a first myocardial infarction
  • 2020
  • Ingår i: Open Heart. - : BMJ. - 2398-595X .- 2053-3624. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Morbidity and mortality due to heart failure (HF) as a complication of myocardial infarction (MI) is high, and remains among the leading causes of death and hospitalisation. This study investigated the association between family history of MI with or without HF, and the risk of developing HF after first MI. Methods: Through nationwide registries, we identified all individuals aged 18-50 years hospitalised with first MI from 1997 to 2016 in Denmark. We identified 13 810 patients with MI, and the cohort was followed until HF diagnosis, second MI, 3 years after index MI, emigration, death or the end of 2016, whichever occurred first. HRs were estimated by Cox hazard regression models adjusted for sex, age, calendar year and comorbidities (reference: patients with no family history of MI). Results: After adjustment, we observed an increased risk of MI-induced HF for those having a sibling with MI with HF (HR 2.05, 95% CI 1.02 to 4.12). Those having a sibling with MI without HF also had a significant, but lower increased risk of HF (HR 1.39, 95% CI 1.05 to 1.84). Parental history of MI with or without HF was not associated with HF. Conclusion: In this nationwide cohort, sibling history of MI with or without HF was associated with increased risk of HF after first MI, while a parental family history was not, suggesting that shared environmental factors may predominate in the determination of risk for developing HF.
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  • Gustafsson, I., et al. (författare)
  • [Metabolic control by means of insulin in patients with type 2 diabetes and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity--secondary publication]
  • 2006
  • Ingår i: Ugeskr Laeger. - : Almindelige danske Lægeforening. - 1603-6824 .- 0041-5782. ; 168:6, s. 581-4
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with diabetes have an unfavourable prognosis after an acute myocardial infarction. The DIGAMI 2 study investigated the effect of various metabolic treatment strategies in type 2 diabetic patients with acute myocardial infarction: acutely introduced, long-term insulin treatment did not improve survival when compared with conventional management at similar levels of glucose control. However, good glucose control seems important since the glucose level was found to be a strong predictor of long-term mortality in this patient category.
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  • Hollmann, K., et al. (författare)
  • Internet-based cognitive behavioral therapy in children and adolescents with obsessive compulsive disorder: a feasibility study
  • 2021
  • Ingår i: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 128, s. 1445-1459
  • Tidskriftsartikel (refereegranskat)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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  • Højgaard, Davíð R M A, et al. (författare)
  • Do Autistic Traits Predict Outcome of Cognitive Behavioral Therapy in Pediatric Obsessive-Compulsive Disorder?
  • 2023
  • Ingår i: Research on child and adolescent psychopathology. - 2730-7174. ; 51:8, s. 1083-1095
  • Tidskriftsartikel (refereegranskat)abstract
    • The first aim of this study was to explore whether children with obsessive compulsive disorder (OCD) and subclinical autistic traits can be differentiated from children with OCD without these traits based on clinical OCD-related characteristics, distinct OCD symptom patterns, and type of comorbidity. The second aim was to investigate whether autistic traits predict immediate and long-term outcome of exposure-based cognitive behavioral therapy (CBT) in pediatric OCD.The participants in this study were a total of 257 children and adolescents aged 7-17 years, recruited from Denmark, Norway, and Sweden as a part of the Nordic long-term OCD treatment study (NordLOTS). Inclusion criteria were an OCD diagnosis based on DSM-IV criteria and a Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) total severity score of 16 or higher. No children with a diagnosis on the autism spectrum were included. An Autism Spectrum Screening Questionnaire (ASSQ) cut-off score of ≥ 17 was used to define the group of OCD patients with autistic traits and all participants were treated with 14 weekly sessions of manualized CBT.Comorbid attention-deficit/hyperactivity disorder and tic disorders, subclinical internalizing and externalizing symptoms, lower insight into OCD symptoms, more indecisiveness and pervasive slowness, and ordering/arranging OCD symptoms were found to be significantly associated with having OCD with autistic traits. No difference was found between the groups on treatment outcomes.Results suggest that children and adolescents with OCD and autistic traits portray a different clinical profile than those without these traits, but that CBT is equally effective for those with and without autistic traits.
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  • Ivarsson, Tord, 1946, et al. (författare)
  • Remission and Relapse Across Three Years in Pediatric Obsessive-Compulsive Disorder Following Evidence-Based Treatments
  • 2024
  • Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - 0890-8567 .- 1527-5418. ; 63:5, s. 519-527
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine relapse rates following remission in a 3-year follow-up study in pediatric patients with obsessive-compulsive disorder (OCD) treated with cognitive–behavioral therapy (CBT) in a first step, and either continued CBT or sertraline (randomized selection) in a second step. Method: Participants (N = 269) fulfilled DSM-IV OCD criteria with a mean severity on the Children's Yale–Brown Obsessive Compulsive Scale (CY-BOCS) of 24.6 (SD = 5.1) and were included in analyses according to intent-to-treat principles. CBT used manualized exposure and response prevention (ERP) during both steps 1 and 2, and step 2 sertraline medication used flexible dosing. The follow-up schedules were timed to 6, 12, 24, and 36 months following step 1 CBT. Remission was defined as a CY-BOCS score ≤10 and relapse as an elevated CY-BOCS score ≥16 in those who had remitted. Results: A good third of our patients were in stable and full remission at all examinations (n = 98, 36.4%). Further, some in remission following treatment (n = 36, 13.4%) had mild OCD at some examinations. Relapses during follow-up were not uncommon (n = 28, 10.4%), but in many patients these improved again (n = 10, 3.7%) and were in remission at the final 3-year follow-up. Furthermore, a considerable proportion (n = 50, 18.6%) of the patients were initial non-remitters to the treatment but achieved remission at some point during the follow-up. In addition, 11.5% (n = 31) had persistent OCD but reached remission by the last follow-up. Finally, a smaller segment of our sample (9.7%, n = 26), did not attain remission at any point during the study. Conclusion: Our outcome paints a more promising picture of pediatric OCD long-term outcome than previous studies have done. However, both relapse rates and the presence of initial non-remitters and persistent OCD show that treatments need improvement, particularly for those who respond slowly, partially, or not at all. The lack of a general psychiatric interview at follow-up is a marked limitation. Clinical trial registration information: Nordic Long-term Obsessive compulsive disorder (OCD) Treatment Study; https://www.isrctn.com; ISRCTN66385119
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24.
  • Jakola, Asgeir Store, et al. (författare)
  • Surgical resection versus watchful waiting in low-grade gliomas.
  • 2017
  • Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 28:8, s. 1942-1948
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared to watchful waiting in light of recently established molecular markers. Material and methods: Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18 years or older. Follow-up ended 1st January 2016. Making regional comparisons, the primary end-point was overall survival. Results 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared to 75 (86%) patients in region B. Overall survival was 5.8 years (95% CI 4.5–7.2) in region A compared to 14.4 years (95% CI 10.4–18.5) in region B (P<0.01). The effect of surgical strategy remained after adjustment for molecular markers (P=0.001). Conclusion In parallel population based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.
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25.
  • Jensen, S., et al. (författare)
  • Distinct trajectories of long-term symptom severity in pediatric obsessive-compulsive disorder during and after stepped-care treatment
  • 2020
  • Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 61:9, s. 969-978
  • Tidskriftsartikel (refereegranskat)abstract
    • Background First-line treatments for pediatric obsessive-compulsive disorder (OCD) include exposure-based cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). No studies have thus far identified distinct classes and associated predictors of long-term symptom severity during and after treatment. Yet, these could form the basis for more personalized treatment in pediatric OCD. Method The study included 269 OCD patients aged 7-17 years from the Nordic Long-term OCD Treatment Study (NordLOTS). All participants received stepped-care treatment starting with 14 weekly sessions of manualized CBT. Nonresponders were randomized to either prolonged CBT or SSRIs. Symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale at seven time points from pre- to post-treatment and over a three-year follow-up. Latent class growth analysis (LCGA) was performed to identify latent classes of symptom severity trajectories. Univariate and multivariate analyses were used to detect differences between classes and identify predictors of trajectory class membership including several clinical and demographic variables. Trial registry: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; ; ISRCTN66385119. Results Three LCGA classes were identified: (a) acute, sustained responders (54.6%); (b) slow, continued responders (23.4%); and (c) limited long-term responders (21.9%). Class membership was predicted by distinct baseline characteristics pertaining to age, gender, symptom presentation, insight, avoidance, and comorbidity. Conclusions The LCGA suggests three distinct trajectory classes of long-term symptom severity during and after treatment in pediatric OCD with different clinical profiles at pretreatment. The results point to required clinical attention for adolescent patients with contamination/cleaning symptoms and reduced insight who do not show convincing responses to first-line treatment even though they may have reached the established cutoff for treatment response.
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26.
  • Jensen, S., et al. (författare)
  • Long- term remission status in pediatric obsessive-compulsive disorder: Evaluating the predictive value of symptom severity after treatment
  • 2022
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781. ; 317
  • Tidskriftsartikel (refereegranskat)abstract
    • It is unknown if long-term remission for pediatric obsessive-compulsive disorder (OCD) patients is associated with post-treatment OCD symptom severity. The aim of the present study was to evaluate if post-treatment symptom severity cut-offs can discriminate remitters from non-remitters in pediatric OCD patients during three years of follow-up. All participants (N = 269) from the Nordic Long-term OCD Treatment Study (Nor-dLOTS) undergoing stepped-care treatment were included. Patients were rated with the Clinical Global Impression - Severity Scale (CGI-S) one (n = 186), two (n = 167), and three years (n = 166) after first-line cognitive-behavioral therapy. Post-treatment symptom severity scores as well as percentage reductions during treatment evaluated with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) were analyzed using receiver operating characteristics according to the CGI-S remission scores (< 2) at follow-up. Post-treatment CY-BOCS severity scores acceptably discriminated remitters from non-remitters at one-year follow-up, but poorly for the two-and three-year follow-up. Severity percentage reduction during treatment did not discriminate remis-sion status acceptably at any follow-up point. Post-treatment OCD symptom severity status seems to have little discriminative value for long-term remission status in pediatric patients. Further research is warranted to detect post-treatment factors of prognostic value.
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27.
  • Jensen, Sanne, et al. (författare)
  • The Children's Yale-Brown Obsessive-Compulsive Scale's auxiliary items: Long-term outcome
  • 2020
  • Ingår i: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier BV. - 2211-3649 .- 2211-3657. ; 27
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2020 Elsevier Inc. Objective: Standard assessment of pediatric obsessive-compulsive disorder (OCD) patients includes ratings of insight, avoidance, indecisiveness, sense of responsibility, pervasive slowness, pathological doubting, and obsession-free intervals. The present study aims to identify pre-treatment associations of these clinical features to symptom severity and symptom dimensions as well as to describe and analyze the long-term levels and distribution in different treatment responder groups. Method: Severity ratings as well as clinical feature ratings were evaluated in 268 pediatric OCD patients using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) at seven time points before, during, and up to three years after first-line cognitive-behavioral therapy. The CY-BOCS auxiliary items were evaluated on the basis of three symptom severity trajectory classes: acute, slow, and limited responders. Results: Insight, avoidance, pervasive slowness, and obsession-free intervals were positively associated with pre-treatment symptom severity. Symptom dimensions were associated with different auxiliary items. At three-year follow-up, the limited responder class had higher scores than the acute and slow responder classes on all items except for responsibility. Conclusion: The CY-BOCS auxiliary items are closely related to symptom dimensions and partly to symptom severity. The features appear to be dynamic concepts prone to change, yet, less so in patients showing limited long-term treatment response.
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28.
  • Kragh, Kristin, et al. (författare)
  • Convergent and divergent validity of the schedule for affective disorders and schizophrenia for school-age children - present and lifetime version diagnoses in a sample of children and adolescents with obsessive-compulsive disorder.
  • 2019
  • Ingår i: Nordic journal of psychiatry. - : Informa UK Limited. - 1502-4725 .- 0803-9488. ; 73:2, s. 111-117
  • Tidskriftsartikel (refereegranskat)abstract
    • The presence of comorbid conditions associated with paediatric obsessive-compulsive disorder (OCD) is reported to range from 50 to 80% and to have an impact on treatment outcome. Accurate identification of comorbid psychiatric disorders is necessary in order to provide personalised care. Reliable and valid diagnostic interviews are essential in the process of establishing the correct diagnoses. The objective of this study was to evaluate the convergent and divergent validity of four diagnose categories generated by the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL). The diagnose categories were: anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). The K-SADS-PL was applied in a clinical sample of youth aged 7-17 years (N=269), who were participants in the Nordic long-term OCD-treatment study (NordLOTS). Youth and parents completed measures to evaluate symptoms of anxiety, depression, ADHD, and ODD. Convergent and divergent validity of K-SADS-PL anxiety diagnosis was supported based on both anxiety self- and parent-reports. Similarly, support was found for convergent and divergent validity of ADHD and ODD diagnoses. For depressive disorder, support for convergent validity was found based on the depression self-report. Support for divergent validity of depression was found based on both the depression self- and parent-reports. Results of the present study suggest that the K-SADS-PL generates valid diagnoses of comorbid anxiety disorders, depression disorders, ODD, and ADHD in children and adolescents with OCD.
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29.
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30.
  • Martinsen, TC, et al. (författare)
  • Spontaneous ECL cell carcinomas in cotton rats: natural course and prevention by a gastrin receptor antagonist
  • 2003
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 24:12, s. 1887-1896
  • Tidskriftsartikel (refereegranskat)abstract
    • In our inbred strain of cotton rats (Sigmodon hispidus) 50% of the females develop spontaneous ECL cell-derived tumors in the acid-producing part of the stomach due to hypergastrinemia secondary to gastric hypoacidity. Although the mechanism behind the hypoacidity is unknown, the female cotton rat is an excellent model for studying ECL cell-related tumorigenesis. In this study we wanted to explore the malignancy potential of these tumors and the ability of a gastrin receptor antagonist (YF476) to prevent their development. First, nine hypergastrinemic female cotton rats (10 months of age) were diagnosed by laparotomy as having gastric tumors. They were killed 6 months later. Second, 18 female cotton rats (2 months of age) were dosed monthly for 6 months with YF476 (500 mumol/kg body wt) by s.c. injection, while 21 age-matched animals received vehicle. Samples from each stomach were collected for histology, immunohistochemistry and northern blot analysis. The gastric tumors harbored cells with immunohistochemical features of ECL cells. The tumors were found at times to invade and penetrate the stomach wall and to metastasize to perigastric sites. ECL-derived tumor cells were discovered in peritoneal fluid. At death only 1 out of 18 animals given YF476 displayed carcinomas (invasive growth), compared with 7 out of 21 in the vehicle dosed control group (P = 0.048). The spontaneous gastric tumors in cotton rats derived from ECL cells. The tumors were able to penetrate the stomach wall and to metastasize by intracavital seeding. Gastrin receptor blockade lowered the incidence of such tumors. We propose that the tumors are ECL cell carcinomas and that gastrin is the driving force behind the transformation from normal to malignant ECL cells.
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31.
  • Melin, Karin, 1964, et al. (författare)
  • Treatment Gains Are Sustainable in Pediatric Obsessive-Compulsive Disorder: Three-Year Follow-Up From the NordLOTS
  • 2020
  • Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - Amsterdam : Elsevier BV. - 0890-8567 .- 1527-5418. ; 59:2, s. 244-253
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019 American Academy of Child and Adolescent Psychiatry Objective: This study evaluated the long-term outcomes of a stepped care treatment for pediatric obsessive-compulsive disorder (OCD) and investigated whether response to first-step cognitive-behavioral therapy (CBT) is an important indicator of 3-year outcomes. Method: This study is a part of the Nordic Long-term OCD Treatment Study (NordLOTS), in which 269 children and adolescents were treated with CBT. Nonresponders to CBT were randomized to extended treatment with continued CBT or pharmacotherapy with sertraline. Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores no higher than 15 and no higher than 10 were defined as treatment response and remission, respectively. Participants were assessed 2 and 3 years after first-step CBT. Linear mixed-effects models were used to analyze the outcomes. Results: Intent-to-treat analyses showed a significant decrease in CY-BOCS total score from baseline (24.6) to 3-year follow-up (5.0; p = .001), with a mean decrease of 5.9 from after treatment to 3-year follow-up. Three years after treatment, 90% (n = 242) of participants were rated as responders and 73% were in clinical remission. The duration of treatment did not influence the symptom level at 3-year follow-up (p = .998) and no significant difference was found (p = .169) between the extended treatment conditions. Conclusion: The results suggest that evidence-based treatment for pediatric OCD has long-term positive effects, whether a first step of manual-based CBT or extended treatment with CBT or sertraline. The improvements were maintained, and the symptoms decreased further during follow-up and were, after 3 years, similarly independent of treatment duration and form of extended treatment. Clinical trial registration information: Nordic Long-term Obsessive-Compulsive Disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119.
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32.
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33.
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34.
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35.
  • Pingel, Jessica, et al. (författare)
  • Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection. Additionally, there was clear evidence of microstructural changes on the tissue level by as evidenced by 3D imaging of the muscles by Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM). Both the fibrillar and the non-fibrillar tissues were affected. The volume fraction of fibrillary tissue was reduced significantly and the non-fibrillar tissue increased. This was accompanied by a loss of the linear structure of the muscle tissue. Furthermore, gene expression analysis showed a significant upregulation of COL1A1, MMP-2, TGF-b1, IL-6, MHCIIA and MHCIIx in the BoNT/A injected leg, while MHVIIB was significantly downregulated. In conclusion: The present study reveals that high dose intramuscular BoNT/A injections cause microstructural damage of the muscle tissue, which contributes to impaired gait.
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36.
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37.
  • Smárason, Orri, et al. (författare)
  • Long-term functional impairment in pediatric OCD after and during treatment: An analysis of distinct trajectories.
  • 2023
  • Ingår i: Psychiatry research. - 1872-7123. ; 324
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study aimed to: (a) identify latent class trajectories of OCD-related functional impairment, before, during and over three years after stepped-care treatment in children and adolescents with OCD; (b) describe these classes according to pretreatment characteristics; (c) identify predictors of trajectory class membership and (d) examine the relationship of functional impairment trajectory classes with OCD symptom severity trajectory classes. The sample consisted of 266 children and adolescents (aged 7-17 years) with OCD, participating in the Nordic long-term OCD treatment study. Latent class growth analysis was conducted using Child Obsessive-Compulsive Impact Scale-Revised (COIS-R) data from children and parents on seven assessment points over a three-year period. A 3-class solution was identified. The largest class (70.7%) initiated treatment with lower functional impairment and obtained moderate reduction which was maintained over time. The second class (24.4%) initiated with higher functional impairment which rapidly diminished over time. The third and smallest class (4.9%), initiated with moderate functional impairment which remained stable over time. The classes differed on measures of OCD severity and comorbid symptoms. Most participants improved with treatment and maintained low levels of impairment. However, a subgroup distinguished by higher levels of ADHD symptoms, remained at pretreatment levels of impairment throughout.
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38.
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39.
  • Torp, N. C., et al. (författare)
  • Is it time to rethink standard dosage of exposure-based cognitive behavioral therapy for pediatric obsessive-compulsive disorder?
  • 2019
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781. ; 281
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Identifying factors associated with early treatment response is important, because it can help allocate limited resources in psychiatric care more appropriately. This study examined baseline characteristics of participants with early response to exposure-based cognitive behavior therapy (CBT) for pediatric obsessive-compulsive disorder (OCD). Method: 269 participants with OCD, aged 7-17 years, were enrolled in a 14-weeks CBT program. We identified participants with early response to treatment, (CY-BOCS total score of <= 15), by the seventh session. Results: At week 7, 248 (92.2%) participants were assessed, 38.3% (95% CI 32.4-44.5%, n = 95) were identified as treatment responders. Univariate analyses showed that six baseline characteristics were significantly associated with early treatment response: young age, lower levels of symptom severity, functional impairment, internalizing- and externalizing problems, depressive symptoms, and family accommodation. Conclusions: These results suggested that treatment plans for younger children with moderate OCD symptoms and no major comorbid disorder should include briefer and less resource demanding treatment formats than the commonly recommended and applied standard doses of 15 CBT sessions.
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40.
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41.
  • Vamos, Mate, et al. (författare)
  • Efficacy and safety of dronedarone in patients with a prior ablation for atrial fibrillation/flutter : Insights from the ATHENA study
  • 2020
  • Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 43:3, s. 291-297
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The role of antiarrhythmic drugs for atrial fibrillation/atrial flutter (AF/AFL) after catheter ablation is not well established. Hypothesis: We hypothesized that changing the myocardial substrate by ablation may alter the responsiveness to dronedarone. Methods: We assessed the efficacy and safety of dronedarone in the treatment of paroxysmal/persistent atrial fibrillation/atrial flutter (AF/AFL) post-ablation, based on a post hoc analysis of the ATHENA study. A total of 196 patients (dronedarone 90, placebo 106) had an ablation for AF/AFL before study entry. In these patients, the effect of treatment on the first hospitalization because of cardiovascular (CV) events/all-cause death was assessed, as was AF/AFL recurrence in individuals with sinus rhythm at baseline. The safety of dronedarone vs placebo was also determined. Results: In patients with prior ablation, dronedarone reduced the risk of AF/AFL recurrence (hazard ratio [HR]: 0.65 [95% confidence interval [CI]: 0.42, 1.00]; P <.05) as well as the median time to first AF/AFL recurrence (561 vs 180 days) compared with placebo. The HR for first CV hospitalization/all-cause death with dronedarone vs placebo was 0.98 (95% CI: 0.62, 1.53; P =.91). Rates of treatment-emergent adverse events were 83.1% vs 75.5% and rates of serious TEAEs were 27.0% vs 18.9% in the dronedarone and placebo groups, respectively. One death occurred with dronedarone (not treatment-emergent) and five occurred with placebo. Conclusion: In patients with prior ablation for AF/AFL, dronedarone reduced the risk of AF/AFL recurrence compared with placebo, but not the risk of first CV hospitalization/all-cause death. Safety outcomes were consistent with those of the overall ATHENA study.
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42.
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43.
  • Weidle, Bernhard, et al. (författare)
  • Sexual obsessions in children and adolescents: Prevalence, clinical correlates, response to cognitive-behavior therapy and long-term follow up
  • 2022
  • Ingår i: Journal of Obsessive-Compulsive and Related Disorders. - : Elsevier BV. - 2211-3649 .- 2211-3657. ; 32
  • Tidskriftsartikel (refereegranskat)abstract
    • Sexual obsessions occur in pediatric and adult OCD including thoughts about sexual acts with family members, sexually inappropriate behavior, or homosexual orientation. They may remain undiagnosed because of embarrassment to report thoughts that are perceived as unacceptable. Prevalence studies of sexual obsessions in pediatric populations are rare. The present study investigated prevalence of sexual obsessions and treatment outcome compared to youth with OCD without sexual obsessions in a large sample. Sexual obsessions and OCD severity were assessed with the Children's Yale-Brown Obsessive- Compulsive Scale in all 269 participants of the Nordic Longterm OCD Treatment study (mean age 12.8 years, 48.7% boys) at baseline, after treatment and three years follow-up. Treatment consisted in individual manualized CBT with exposure and response prevention. Patients with and without sexual obsessions were compared on clinical characteristics and treatment outcomes. Sexual obsessions were reported by 18%, those with sexual obsessions were slightly older (13.5 versus 12.7 years). Both groups had no difference in treatment outcome, suggesting that if addressed, the response to CBT is similar in sexual, as in other obsessions. Clinicians need to be aware that children may need help to disclose and to identify these thoughts as obsessions to address them in treatment.
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44.
  • Yang, Wen-Yi, et al. (författare)
  • Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes
  • 2019
  • Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 322:5, s. 409-420
  • Tidskriftsartikel (refereegranskat)abstract
    • ImportanceBlood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. ObjectiveTo evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and ParticipantsLongitudinal population-based cohort study of 11135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). ExposuresBlood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and MeasuresMultivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). ResultsAmong 11135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P<.001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and RelevanceIn this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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