Publications by authors named "Cathrine Brunborg"

116 Publications

Maternal education has significant influence on progression in multiple sclerosis.

Mult Scler Relat Disord 2021 May 30;53:103052. Epub 2021 May 30.

Institute of Clinical Medicine, University of Oslo, Norway; Department of Neurology, Oslo University Hospital, Norway.

Objective: The identification of potential risk factors for disease severity is of great importance in the treatment of multiple sclerosis. The influence of socioeconomic status on progression in multiple sclerosis (MS) is sparsely investigated. Our aim was to investigate how socioeconomic status in adolescence influences disease progression in later life.

Methods: A total of 1598 patients with multiple sclerosis from a well-defined population in Norway were included. Detailed information on disease progression, measured by expanded disability status scale (EDSS) and multiple sclerosis severity score (MSSS), were combined with data on socioeconomic factors. We used residency and parental level of education at patients' age 16 and exposure to second-hand smoking as a measure of socioeconomic status in adolescence, adjusting for the same variables as well as use of disease modifying treatments at prevalence date 01.01.18.

Results: High maternal level of education at patients' age 16 was significantly associated with less pronounced disease progression measured by MSSS (β-coefficient -0.58, p = 0.015), younger age and lower EDSS at disease onset, and shorter time from onset to diagnosis. No significant associations were found for paternal education level and MSSS. The use of any disease modifying treatment before prevalence date was significantly associated with disease progression (β-coefficient -0.49, p=0.004), while residence, current and second-hand smoking were not.

Conclusion: This study on a population-based, real-world cohort shows that the parental level of education has a significant impact on a timely diagnosis of MS. In addition to disease modifying treatment, maternal level of education also had an impact on disease progression in later life.
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http://dx.doi.org/10.1016/j.msard.2021.103052DOI Listing
May 2021

Cost Analysis of Open Surgical Bedside Tracheostomy in Intensive Care Unit Patients.

Ear Nose Throat J 2021 May 19:1455613211018578. Epub 2021 May 19.

Division of Emergencies and Critical Care, Department of Anesthesiology, Oslo University Hospital Ullevål, Oslo, Norway.

Objectives: Open surgical tracheostomy (OST) is a common procedure performed on intensive care unit (ICU) patients. The procedure can be performed bedside in the ICU (bedside open surgical tracheostomy, BeOST) or in the operating room (operating room open surgical tracheostomy, OROST), with comparable safety and long-term complication rates. We aimed to perform a cost analysis and evaluate the use of human resources and the total time used for both BeOSTs and OROSTs.

Methods: All OSTs performed in 2017 at 5 different ICUs at Oslo University Hospital Ullevål were retrospectively evaluated. The salaries of the personnel involved in the 2 procedures were obtained from the hospital's finance department. The time taken and the number of procedures performed were extracted from annual reports and from the electronic patient record system, and the annual expenditures were calculated.

Results: Altogether, 142 OSTs were performed, of which 122 (86%) and 20 (14%) were BeOSTs and OROSTs, respectively. A BeOST cost 343 EUR (95% CI: 241.4-444.6) less than an OROST. Bedside open surgical tracheostomies resulted in an annual cost efficiency of 41.818 EUR. In addition, BeOSTs freed 279 hours of operating room occupancy during the study year. Choosing BeOST instead of OROST made 1 nurse, 2 surgical nurses, and 1 anesthetic nurse redundant.

Conclusion: Bedside open surgical tracheostomy appears to be cost-, time-, and resource-effective than OROST. In the absence of contraindications, BeOSTs should be performed in ICU patients whenever possible.
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http://dx.doi.org/10.1177/01455613211018578DOI Listing
May 2021

Cognitive and vocational rehabilitation after mild-to-moderate traumatic brain injury: a randomised controlled trial.

Ann Phys Rehabil Med 2021 May 3:101538. Epub 2021 May 3.

Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.

Background: Returning to work is often a primary rehabilitation goal after traumatic brain injury (TBI). However, the evidence base for treatment options regarding return to work (RTW) and stable work maintenance remains scarce.

Objective: This study aimed to examine the effect of a combined cognitive and vocational intervention on work-related outcomes after mild-to-moderate TBI.

Methods: In this study, we compared 6 months of a combined compensatory cognitive training and supported employment (CCT-SE) intervention with 6 months of treatment as usual (TAU) in a randomised controlled trial to examine the effect on time to RTW, work percentage, hours worked per week and work stability. Eligible patients were those with mild-to-moderate TBI who were employed ≥ 50% at the time of injury, 18 to 60 years old and sick-listed ≥ 50% at 8 to 12 weeks after injury due to post-concussion symptoms, assessed by the Rivermead Post Concussion Symptoms Questionnaire. Both treatments were provided at the outpatient TBI department at Oslo University Hospital, and follow-ups were conducted at 3, 6 and 12 months after inclusion.

Results: We included 116 individuals, 60 randomised to CCT-SE and 56 to TAU. The groups did not differ in characteristics at the 12-month follow-up. Overall, a high proportion had returned to work at 12 months (CCT-SE, 90%; TAU, 84%, P = 0.40), and all except 3 were stably employed after the RTW. However, a significantly higher proportion of participants in the CCT-SE than TAU group had returned to stable employment at 3 months (81% vs 60%, P = 0.02).

Conclusion: These results suggest that the CCT-SE intervention might help patients with mild-to-moderate TBI who are still sick-listed 8 to 12 weeks after injury in an earlier return to stable employment. However, the results should be replicated and a cost-benefit analysis performed before concluding.
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http://dx.doi.org/10.1016/j.rehab.2021.101538DOI Listing
May 2021

Thymectomy in Juvenile Myasthenia Gravis Is Safe Regarding Long Term Immunological Effects.

Front Neurol 2021 25;12:596859. Epub 2021 Feb 25.

Department of Neurology, Oslo University Hospital, Oslo, Norway.

Thymectomy is an established treatment in adult MG and also recommended for the treatment of post-pubertal onset juvenile MG. Whether the youngest children should be thymectomized is still debated. Signs of premature aging of the immune system have been shown in studies on early perioperative thymectomy in children with congenital heart defect. In this retrospective cohort study the objective was to investigate the long-term effects of treatment related thymectomy on T cell subsets and T cell receptor rearrangement excision circles (TRECs) in peripheral blood of juvenile myasthenia gravis (MG) patients, as well as clinical occurrence of autoimmune disorders, malignancies and infectious diseases. Forty-seven patients with onset of myasthenia gravis before the age of 19 years were included; 32 (68.1%) had been thymectomized and 15 (31.8%) had not. They were studied at varying times after thymectomy (7-26 years). We found a significant lower number of naïve helper T cells (CD4+CD45RA+) with an increased proportion of memory helper T cells (CD4+CD45RO+), and a significant lower number of naïve cytotoxic T cells (CD8+CD27+CD28+) in the thymectomized patients. In addition they showed a significant reduction in the number of TRECs and proportion of recent thymic emigrants (RTE) compared to non-thymectomized patients. In none of them an increased frequency of malignancies or infections was found. Our findings indicate a premature aging of the immune system after thymectomy in juvenile MG, but associated clinical consequences could not be verified.
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http://dx.doi.org/10.3389/fneur.2021.596859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947605PMC
February 2021

Preoperative CTC-Detection by CellSearch Is Associated with Early Distant Metastasis and Impaired Survival in Resected Pancreatic Cancer.

Cancers (Basel) 2021 Jan 27;13(3). Epub 2021 Jan 27.

Department of Gastrointestinal Surgery, Oslo University Hospital, 0424 Oslo, Norway.

In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5-10 years of follow-up. Preoperative samples were analysed by the CellSearch system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future.
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http://dx.doi.org/10.3390/cancers13030485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865868PMC
January 2021

Association of Lymphangiogenic Factors With Pulmonary Arterial Hypertension in Systemic Sclerosis.

Arthritis Rheumatol 2021 Jan 26. Epub 2021 Jan 26.

Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Objective: Pulmonary arterial hypertension (PAH) is a major complication in systemic sclerosis (SSc), a disease marked by vascular and lymphatic vessel abnormalities. This study was undertaken to assess the role of the lymphangiogenic factors vascular endothelial growth factor C (VEGF-C) and angiopoietin 2 (Ang-2) and the soluble forms of their respective cognate receptors, soluble VEGF receptor 3 (sVEGFR-3) and soluble TIE-2, in patients with SSc, and to evaluate their predictive ability as markers for PAH development in SSc.

Methods: In this cohort study, we used multiplex bead assays to assess serum levels of lymphangiogenic factors in 2 well-characterized SSc cohorts: an unselected identification cohort of SSc patients from Oslo University Hospital (n = 371), and a PAH-enriched validation cohort of SSc patients from Zurich University Hospital and Oslo University Hospital (n = 149). As controls for the identification and validation cohorts, we obtained serum samples from 100 healthy individuals and 68 healthy individuals, respectively. Patients in whom SSc-related PAH was identified by right-sided heart catheterization (RHC) in both cohorts were studied in prediction analyses. PAH was defined according to the European Society of Cardiology/European Respiratory Society 2015 guidelines for the diagnosis and treatment of PAH. Associations of serum levels of lymphangiogenic factors with the risk of PAH development were assessed in logistic regression and Cox regression analyses. Associations in Cox regression analyses were expressed as the hazard ratio (HR) with 95% confidence interval (95% CI).

Results: In the identification cohort, SSc patients had lower mean serum levels of VEGF-C and higher mean serum levels of Ang-2 compared to healthy controls (for VEGF-C, mean ± SD 2.1 ± 0.5 ng/ml in patients versus 2.5 ± 0.4 ng/ml in controls; for Ang-2, mean ± SD 6.1 ± 7.6 ng/ml in patients versus 2.8 ± 1.8 ng/ml in controls; each P < 0.001); these same trends were observed in SSc patients with PAH compared to those without PAH. The association of serum VEGF-C levels with SSc-PAH was confirmed in the PAH-enriched RHC validation cohort. For prediction analyses, we assembled all 251 cases of SSc-PAH identified by RHC from the identification and validation cohorts. In multivariable Cox regression analyses adjusted for age and sex, the mean serum levels of VEGF-C and sVEGFR-3 were predictive of PAH development in patients with SSc (for VEGF-C, HR 0.53 [95% CI 0.29-0.97], P = 0.04; for sVEGFR-3, HR 1.21 [95% CI 1.01-1.45], P = 0.042).

Conclusion: These findings support the notion that lymphangiogenesis is deregulated during PAH development in SSc, and indicate that VEGF-C could be a promising marker for early PAH detection in patients with SSc.
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http://dx.doi.org/10.1002/art.41665DOI Listing
January 2021

Visual, Verbal and Everyday Memory 2 Years After Bariatric Surgery: Poorer Memory Performance at 1-Year Follow-Up.

Front Psychol 2020 8;11:607834. Epub 2021 Jan 8.

Regional Department for Eating Disorders, Oslo University Hospital, Oslo, Norway.

Severe obesity has been associated with reduced performance on tests of verbal memory in bariatric surgery candidates. There is also some evidence that bariatric surgery leads to improved verbal memory, yet these findings need further elucidation. Little is known regarding postoperative memory changes in the visual domain and how patients subjectively experience their everyday memory after surgery. The aim of the current study was to repeat and extend prior findings on postoperative memory by investigating visual, verbal, and self-reported everyday memory following surgery, and to examine whether weight loss and somatic comorbidity predict memory performance. The study was a prospective, observational study in which participants ( = 48) underwent cognitive testing at baseline, 1 and 2 years after bariatric surgery. Repeated measures analyses of variance revealed significantly poorer visual and verbal memory performance at the 1-year follow-up, with performance subsequently returning to baseline levels after 2 years. Verbal learning and self-reported everyday memory did not show significant postoperative changes. Memory performance at 1 year was not significantly predicted by weight loss, changes in C-reactive protein levels or postoperative somatic comorbidity (Type 2 diabetes, sleep apnea, and hypertension). The study demonstrated poorer visual and verbal memory performance at 1-year follow-up that returned to baseline levels after 2 years. These findings are in contrast to most previous studies and require further replication, however, the results indicate that postoperative memory improvements following bariatric surgery are not universal. Findings suggest that treatment providers should also be aware of patients potentially having poorer memory at 1 year following surgery.
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http://dx.doi.org/10.3389/fpsyg.2020.607834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820680PMC
January 2021

Associations between Macular OCT Angiography and Nonproliferative Diabetic Retinopathy in Young Patients with Type 1 Diabetes Mellitus.

J Diabetes Res 2020 30;2020:8849116. Epub 2020 Nov 30.

Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, 0407 Oslo, Norway.

Methods: OCTA of both eyes was performed in a cross-sectional study of 14 to 30-year-old individuals with at least 10-year duration of T1D and controls recruited from the Norwegian Atherosclerosis and Childhood Diabetes (ACD) study. Vessel density (VD) and foveal avascular zone (FAZ) area in the superficial and deep capillary plexus (SCP and DCP), total retinal volume (TRV), and central macular thickness (CMT) were calculated using automated software. Univariate and multivariate ordered logistic regression (OLR) models were used accordingly.

Results: We included 168 control eyes and 315 T1D eyes. Lower VD in DCP (OR 0.65, 95% CI 0.51-0.83), longer diabetes duration (OR 1.51, 95% CI 1.22-1.87), and higher waist circumference (OR 1.08, 95% CI 1.02-1.14) were significantly associated with progression of NPDR. VD in SCP and DCP were significantly lower in T1D patients without diabetic retinopathy than in controls.

Conclusions: Sparser VD in DCP is significantly associated with severity of NPDR, supporting that OCTA might detect the earliest signs of NPDR before it is visible by ophthalmoscopy.
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http://dx.doi.org/10.1155/2020/8849116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721511PMC
November 2020

Health-related quality of life in Marfan syndrome: a 10-year follow-up.

Health Qual Life Outcomes 2020 Dec 1;18(1):376. Epub 2020 Dec 1.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Background: Marfan syndrome, a rare hereditary connective tissue disorder caused by mutations in fibrillin-1, can affect many organ systems, especially the cardiovascular system. Previous research has paid less attention to health-related quality of life and prospective studies on this topic are needed. The aim of this study was to assess changes in health-related quality of life after 10 years in a Norwegian Marfan syndrome cohort.

Methods: Forty-seven Marfan syndrome patients ≥ 18 years were investigated for all organ manifestations in the 1996 Ghent nosology and completed the self-reported questionnaire, Short-Form-36 Health Survey, at baseline in 2003-2004 and at follow-up in 2014-2015. Paired sample t tests were performed to compare means and multiple regression analyses were performed with age, sex, new cardiovascular and new non-cardiovascular pathology as predictors.

Results: At 10-year follow-up: a significant decline was found in the physical domain. The mental domain was unchanged. Older age predicted a larger decline in physical health-related quality of life. None of the chosen Marfan-related variables predicted changes in any of the subscales of the Short-Form 36 Health Survey or in the physical or the mental domain.

Conclusion: Knowledge of decline in the physical domain, not related to organ affections, may be important in the follow-up of Marfan syndrome patients.
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http://dx.doi.org/10.1186/s12955-020-01633-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706277PMC
December 2020

Care transitions in the first 6 months following traumatic brain injury: Lessons from the CENTER-TBI study.

Ann Phys Rehabil Med 2020 Nov 24. Epub 2020 Nov 24.

Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Health and Society, Research Centre for Habilitation and Rehabilitation Models and Services (CHARM), University of Oslo, Oslo, Norway.

Background: No large international studies have investigated care transitions during or after acute hospitalisations for traumatic brain injury (TBI).

Objectives: To characterise various TBI-care pathways and the number of associated transitions during the first 6 months after TBI and to assess the impact of these on functional TBI outcome controlled for demographic and injury-related factors.

Methods: This was a cohort study of patients with TBI admitted to various trauma centres enrolled in the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study. Number of transitions and specific care pathways were identified. Multiple logistic regression analyses were used to assess the impact of number of transitions and care pathways on functional outcome at 6 months post-injury as assessed by the Glasgow Outcome Scale-Extended (GOSE).

Results: In total, 3133 patients survived the acute TBI-care pathway and had at least one documented in-hospital transition at 6-month follow-up. The median number of transitions was 3 (interquartile range 2-3). The number of transitions did not predict functional outcome at 6 months (odds ratio 1.08, 95% confidence interval 1.09-1.18; p = 0.063). A total of 378 different care pathways were identified; 8 were identical for at least 100 patients and characterized as "common pathways". Five of these common care pathways predicted better functional outcomes at 6 months, and the remaining 3 pathways were unrelated to outcome. In both models, increased age, violence as the cause of injury, pre-injury presence of systemic disease, both intracranial and overall injury severity, and regions of Southern/Eastern Europe were associated with unfavourable functional outcomes at 6 months.

Conclusions: A high number of different and complex care pathways was found for patients with TBI, particularly those with severe injuries. This high number and variety of care pathway possibilities indicates a need for standardisation and development of "common data elements for TBI care pathways" for future studies.

Study Registration: ClinicalTrials.gov NCT02210221.
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http://dx.doi.org/10.1016/j.rehab.2020.10.009DOI Listing
November 2020

Effectiveness of Combining Compensatory Cognitive Training and Vocational Intervention vs. Treatment as Usual on Return to Work Following Mild-to-Moderate Traumatic Brain Injury: Interim Analysis at 3 and 6 Month Follow-Up.

Front Neurol 2020 10;11:561400. Epub 2020 Nov 10.

Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway.

Knowledge regarding the most effective return to work (RTW) approaches after traumatic brain injury (TBI) is lacking. This trial aimed to compare the effectiveness of a combined cognitive and vocational intervention to treatment as usual (TAU) on RTW and work stability after TBI. We performed a parallel-group randomized controlled trial (RCT) at a TBI outpatient clinic at Oslo University Hospital (OUH), Norway. Patients with a history of mild-to-moderate TBI ( = 116) aged 18-60 were randomized (1:1) by an independent investigator to receive group-based compensatory cognitive training (CCT) and supported employment (SE) ( = 60) or TAU consisting of individualized multidisciplinary treatment ( = 56). Participants were enrolled 2-3 months post-injury. The nature of the intervention prevented blinding of patients and therapists, however, outcome assessors were blinded to group allocation. The primary outcome measure was RTW at 3 and 6 months following study inclusion. Secondary outcomes were work percentage, stability, and productivity. The present study provides results from an interim analysis from the first two planned follow ups, while subsequent publications will present results up to 12 months following study inclusion. Mixed effects models showed no between-group differences in the RTW proportion, work percentage, and hours worked between CCT-SE and TAU from baseline to 6 months. A significantly higher proportion of participants in CCT-SE had returned to work at 3 months when adjusting for baseline differences. The majority of participants who were employed at 3 and 6 months were stably employed. There was a statistically significant within-group improvement on RTW proportion, hours worked and work percentage in both groups. The results revealed no difference between CCT-SE and TAU on work-related outcomes from baseline to 6 months. However, there was a higher RTW proportion in the CCT-SE group compared to TAU at 3 months. Future publications will assess the effectiveness of CCT-SE vs. TAU up to 12 months. US National Institutes of Health ClinicalTrials.gov, identifier #NCT03092713.
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http://dx.doi.org/10.3389/fneur.2020.561400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683428PMC
November 2020

Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information.

BMC Cancer 2020 Nov 16;20(1):1107. Epub 2020 Nov 16.

Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway.

Background: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC).

Methods: Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis.

Results: Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC).

Conclusions: The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed.

Trial Registration: clinicaltrials.gov ( NCT01919151 ).
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http://dx.doi.org/10.1186/s12885-020-07510-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667773PMC
November 2020

Preoperative inhibitory control predicts weight loss 1 year after bariatric surgery.

Eur Eat Disord Rev 2021 Jan 30;29(1):123-132. Epub 2020 Oct 30.

Regional Department for Eating Disorders, Oslo University Hospital, Oslo, Norway.

Objective: Executive function (EF) and, in particular, inhibitory control have been associated with weight loss (WL) in behavioural WL treatment for obesity. Few studies have focused on the relationship between preoperative inhibitory control and post-operative WL following bariatric surgery, and the potential mediating role of maladaptive eating behaviours is unclear. The aim of this study was to investigate preoperative executive function as a predictor of WL at 1 year following bariatric surgery. Additionally, we aimed to explore the mediating role of postoperative compulsive grazing in the relationship between inhibitory control and WL.

Method: A prospective observational study in which participants completed neuropsychological testing 30 days before and 1 year following surgery (n = 61/80; 76% follow-up). Participants were 80% female, with an average age of 41 years. Approximately 54% underwent gastric bypass, 26% gastric sleeve and 20% had one anastomosis gastric bypass. Regression analyses were employed to examine the relationship between preoperative EF and percentage total weight loss (%TWL), and structural equation modelling was used to examine compulsive grazing as a mediator.

Results: After adjusting for control variables, preoperative inhibitory control explained 8% of the variance in %TWL (p ≤ 0.05). Preoperative working memory was not significantly associated with %TWL. Postoperative compulsive grazing was significantly associated with %TWL (p ≤ 0.05), but did not mediate the association between preoperative inhibitory control and %TWL.

Conclusion: The results suggest that preoperative inhibitory control performance is a relevant predictor of postoperative WL and that compulsive grazing is a maladaptive eating behaviour that warrants clinical attention after surgery.
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http://dx.doi.org/10.1002/erv.2801DOI Listing
January 2021

The course of multiple sclerosis rewritten: a Norwegian population-based study on disease demographics and progression.

J Neurol 2021 Apr 22;268(4):1330-1341. Epub 2020 Oct 22.

Department of Neurology, Oslo University Hospital, Oslo, Norway.

Objectives: Over the past few decades, there has been an improvement in the rate of disability progression in multiple sclerosis (MS) patients, and most studies relate this evolvement to the introduction of disease-modifying therapies. However, several other factors have changed over this period, including access to MRI and newer diagnostic criteria. The aim of this study is to investigate changes in the natural course of MS over time in a near-complete and geographically well-defined population from the south-east of Norway.

Methods: We examined disease progression and demographics over two decades and assessed the effect of disease-modifying therapies using linear mixed-effect models.

Results: In a cohort of 2097 patients, we found a significant improvement in disability as measured by the Expanded Disability Status Scale (EDSS) stratified by age, and the improvement remained significant after adjusting for time on disease-modifying medications, gender and progressive MS at onset. The time from disease onset to EDSS 6 in the total cohort was 29.8 years (95% CI 28.5-31.1) and was significantly longer in patients diagnosed after 2006 compared to patients diagnosed before. There are significant differences between patient demographics, as well as time to EDSS 6, in the near-complete, geographically well-defined population compared to an additional cohort from the capital Oslo and its suburbs.

Conclusion: The natural course of MS is improving, but the improvement seen in disease progression has multifaceted explanations. Our study underlines the importance of completeness of data, relevant timeframes and demographics when comparing different MS populations. Studies on incomplete populations should be interpreted with caution.
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http://dx.doi.org/10.1007/s00415-020-10279-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990804PMC
April 2021

Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database.

Ann Rheum Dis 2021 02 28;80(2):219-227. Epub 2020 Sep 28.

Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland

Objectives: To identify overall disease course, progression patterns and risk factors predictive for progressive interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD (SSc-ILD), using data from the European Scleroderma Trials And Research (EUSTAR) database over long-term follow-up.

Methods: Eligible patients with SSc-ILD were registered in the EUSTAR database and had measurements of forced vital capacity (FVC) at baseline and after 12±3 months. Long-term progressive ILD and progression patterns were assessed in patients with multiple FVC measurements. Potential predictors of ILD progression were analysed using multivariable mixed-effect models.

Results: 826 patients with SSc-ILD were included. Over 12±3 months, 219 (27%) showed progressive ILD: either moderate (FVC decline 5% to 10%) or significant (FVC decline >10%). A total of 535 (65%) patients had multiple FVC measurements available over mean 5-year follow-up. In each 12-month period, 23% to 27% of SSc-ILD patients showed progressive ILD, but only a minority of patients showed progression in consecutive periods. Most patients with progressive ILD (58%) had a pattern of slow lung function decline, with more periods of stability/improvement than decline, whereas only 8% showed rapid, continuously declining FVC; 178 (33%) experienced no episode of FVC decline. The strongest predictive factors for FVC decline over 5 years were male sex, higher modified Rodnan skin score and reflux/dysphagia symptoms.

Conclusion: SSc-ILD shows a heterogeneous and variable disease course, and thus monitoring all patients closely is important. Novel treatment concepts, with treatment initiation before FVC decline occurs, should aim for prevention of progression to avoid irreversible organ damage.
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http://dx.doi.org/10.1136/annrheumdis-2020-217455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815627PMC
February 2021

Changes in prevalence of mental disorders among internally displaced persons in central Sudan: a 1-year follow-up study.

Glob Ment Health (Camb) 2020 7;7:e24. Epub 2020 Sep 7.

Department of Health and Social Sciences, Innlandet University College, P.O. Box 400, 2418 Elverum, Norway.

Background: Sudan has one of the largest numbers of internally displaced persons (IDPs) in the world, estimated at five million. The main cause of displacement was the civil war. Attention to the health and in particular the mental health of IDPs has been lacking. That includes limited population longitudinal data describing the "natural" fluctuations of mental morbidity among these groups. The aim of this study is to investigate the level and stability of mental disorders among IDPs over a 1-year period.

Method: In this 1-year follow-up of IDPs in two settlement areas in central Sudan, 1549 persons 18 years or older were interviewed twice using the MINI International Neuropsychiatric Interview. Trained psychologists collected the data in a random household survey in the selected IDP areas.

Results: We found overall high stability among those having and those free of mental disorders in this 1-year follow-up study. There were, however, discernible and statistically significant increases in overall new cases of mental disorders from T1 to T2 as major depression increased by 1.4%, generalized anxiety by 2.8% and social phobia by 1.4%.

Conclusion: The study revealed continued high levels and increases of mental disorders over time, although with a pattern of substantial persistence among those initially ill and limited recovery. This might be due to a complex set of factors such as unavailability of mental health services, poverty, low educational level and social exclusion.
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http://dx.doi.org/10.1017/gmh.2020.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490769PMC
September 2020

Bipolar offspring and mothers: interactional challenges at infant age 3 and 12 months-a developmental pathway to enhanced risk?

Int J Bipolar Disord 2020 Aug 31;8(1):27. Epub 2020 Aug 31.

Division of Mental Health and Addiction, Vestre Viken Hospital Trust, 3004, Drammen, Norway.

Background: Bipolar offspring are considered a high-risk group for developing mental disorders. Developmental outcomes result from additive and interactive effects of biological vulnerability and environmental influences. Mother-infant interactions represent important early environmental influences that may modify infants' risk of mental disorders. The aim of the current prospective study was to investigate the patterns and development of mother-infant interactions in the first year of life in dyads in which the mothers have bipolar disorder (BD).

Methods: Twenty-six dyads in which the mothers had BD and 28 dyads in which the mothers had no mental disorder were video-taped in a free play interaction. The Parent-Child Early Relational Assessment (PCERA) was used to assess the quality of the interactions on three domains (maternal behaviour, infant behaviour and dyadic coordination) at 3 and 12 months of infant age. First, we compared the mother-infant interaction patterns between the two groups at 12 months. Second, we investigated how the patterns developed within and between the groups from infant ages 3 to 12 months.

Results: BD dyads demonstrated significantly more challenges in all three interaction domains at infant age 12 months compared to the healthy dyads. This observation was in line with the findings at infant age 3 months. Subdued expression of positive affect and mutual underinvolvement represented core challenges in maternal and infant behaviours in the BD dyads. Continuous difficulties with dyadic coordination and reciprocity were the most concerning interaction behaviours at 3 and 12 months. On the positive side, there was little expression of negative affect or tension in maternal, infant and dyadic behaviour, and some positive changes in infant behaviour from 3 to 12 months.

Conclusions: The current results suggest that challenges in mother-infant interaction patterns in the first year of life may enhance the developmental risk for bipolar offspring. Clinical interventions should address both the BD mothers' needs in relation to postpartum mood deviations and mother-infant interactions. We suggest interaction interventions to promote dyadic coordination and reciprocity, such as helping mothers being more sensitive to their infant's cues and to provide attuned contingent responses.
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http://dx.doi.org/10.1186/s40345-020-00192-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459000PMC
August 2020

Prevalence and predictors of fatigue after aneurysmal subarachnoid hemorrhage.

Acta Neurochir (Wien) 2020 12 18;162(12):3107-3116. Epub 2020 Aug 18.

Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway.

Background: Fatigue is a common and disabling sequel after aneurysmal subarachnoid hemorrhage (aSAH). At present, prevalence estimates of post-aSAH fatigue in the chronic phase are scarce and vary greatly. Factors from the acute phase of aSAH have hitherto barely been associated with post-aSAH fatigue in the chronic phase.

Methods: Prospective study assessing prevalence of fatigue using the Fatigue Severity Scale (FSS) in patients who were living independently 1 to 7 years after aSAH. We compared demographic, medical, and radiological variables from the acute phase of aSAH between patients with and without fatigue (FSS ≥ 4 versus < 4) and searched for predictors of fatigue among these variables applying univariable and multivariable regression analyses.

Results: Of 726 patients treated for aSAH in the period between January 2012 and December 2017, 356 patients completed the assessment. The mean FSS score was 4.7 ± 1.7, and fatigue was present in 69.7%. The frequency of patients with fatigue did not decline significantly over time. Univariable analysis identified nicotine use, loss of consciousness at ictus (LOCi), rebleed prior to aneurysm repair, reduced consciousness to Glasgow Coma Scale (GCS) < 14, large amounts of subarachnoid blood, the presence of acute hydrocephalus, and severe vasospasm as factors that were significantly associated with fatigue. In multivariable analysis, nicotine use, reduced GCS, and severe vasospasm were independent predictors that all more than doubled the risk to develop post-aSAH fatigue.

Conclusions: Fatigue is a frequent sequel persisting several years after aSAH. Nicotine use, reduced consciousness at admission, and severe vasospasm are independent predictors of fatigue from the acute phase of aSAH. We propose inflammatory cytokines causing dopamine imbalance to be a common denominator for post-aSAH fatigue and the presently identified predictors.
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http://dx.doi.org/10.1007/s00701-020-04538-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593293PMC
December 2020

Frequency of fatigue and its changes in the first 6 months after traumatic brain injury: results from the CENTER-TBI study.

J Neurol 2021 Jan 16;268(1):61-73. Epub 2020 Jul 16.

Institute of Medical Psychology and Medical Sociology, University Medical Center, Göttingen, Germany.

Background: Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities.

Methods: Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported.

Results: Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue.

Conclusion: A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.
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http://dx.doi.org/10.1007/s00415-020-10022-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815577PMC
January 2021

Fecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial.

PLoS One 2020 21;15(5):e0232739. Epub 2020 May 21.

Department of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.

Objectives: Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc.

Methods: Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing.

Results: ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo.

Conclusions: FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232739PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241803PMC
July 2020

Venular oxygen saturation is increased in young patients with type 1 diabetes and mild nonproliferative diabetic retinopathy.

Acta Ophthalmol 2020 Dec 15;98(8):800-807. Epub 2020 May 15.

Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway.

Purpose: To clarify how early in the development of diabetic retinopathy (DR) can oxygen (O ) saturation changes be detected.

Methods: Retinal oximetry was performed in a cross-sectional study, involving 14- to 30-year-old individuals: 185 with type 1 diabetes (T1D) and 94 controls. The subjects were divided into four groups according to the grade of DR. One-way ANOVA and post hoc tests were used to test for differences in the mean O saturations between the groups.

Results: Fifty-eight (31 %) of the T1D patients had nonproliferative DR. There was no significant difference in O saturations between controls and T1D patients with no DR. Arteriolar and venular O saturations in T1D patients were significantly higher in moderate/severe DR than in no DR (p = 0.009 and p > 0.001), while venular O saturation was significantly higher in mild DR than in no DR (p = 0.013).

Conclusion: Increase in venular O saturation could not be detected before mild retinopathy had developed, and the retinal O saturation increase was measurable on the venular side first. Our results suggest that the increase in O saturation is likely a consequence of DR.
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http://dx.doi.org/10.1111/aos.14462DOI Listing
December 2020

Multidimensional tracking of phenotypes and organ involvement in a complete nationwide systemic sclerosis cohort.

Rheumatology (Oxford) 2020 10;59(10):2920-2929

Department of Rheumatology, Oslo University Hospital - Rikshospitalet, Oslo, Norway.

Objective: SSc is a severe, heterogeneous multi-organ disease where population-based estimates on phenotypic spectrum, overall disease burden and societal impact are largely missing. Here the objective was to provide the first-ever complete national-level data on phenotype and major organ afflictions in SSc.

Methods: A stepwise strategy was applied to find and characterize every SSc patient resident in Norway from 2000 to 2012. First we identified every case in the country registered with an International Classification of Diseases, Tenth Revision code for SSc (M34). Next we manually reviewed all cases coded as M34 to determine whether they met the 1980 ACR and/or 2013 ACR/EULAR classification criteria for SSc and could be included in the Norwegian SSc cohort (Nor-SSc). Finally, all disease features from SSc onset to study end were reviewed.

Results: The Nor-SSc cohort included 815 SSc patients. The mean age at diagnosis was 53 years, with 84% females and 77% limited cutaneous SSc. The estimated incidence increased from 4 per million in 2000 to 13 per million in 2012. We identified high cumulative frequencies of internal organ involvement, coexistence of multiple organ afflictions across disease subsets and autoantibody status and stable frequencies of pulmonary arterial hypertension across haemodynamic definitions, but indications of referral-related differences in pulmonary hypertension detection rates across the study area.

Conclusion: This nationwide cohort study provides new, unbiased evidence for a high disease burden in SSc patients of Caucasian descent and indicates the existence of hurdles preventing equality of assessment across the SSc population.
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http://dx.doi.org/10.1093/rheumatology/keaa026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516103PMC
October 2020

Development and validation of a questionnaire to assess young patients' experiences with diabetes care and transition.

Acta Paediatr 2020 10 13;109(10):2057-2066. Epub 2020 Feb 13.

Division of Paediatric and Adolescence Medicine, Oslo University Hospital, Oslo, Norway.

Aim: To describe the development and validation of a questionnaire in a national Norwegian population-based cohort study designed to assess the experiences of young people with type 1 diabetes who had made the transition from paediatric to adult diabetes care.

Methods: The questionnaire was developed by the authors based on literature searches, focus group interviews, discussions with experts and cognitive interviews. We included 776 individuals with type 1 diabetes who were last registered in the Norwegian Childhood Diabetes Registry between 2009 and 2012 and had been receiving adult health care for at least 2 years. The data quality was analysed, factor analysis was performed, and the internal reliability, test-retest reliability and construct validity were determined.

Results: The response rate was 321 patients (41.4%); 57.6% were female, and the average age at recruitment was 22.9 ± 1.2 years. Seven factors were identified. Satisfactory evidence was provided for the internal consistency, reliability and construct validity of the questionnaire. All scales met the criterion of Cronbach's alpha above 0.4. The test-retest correlations ranged from 0.64 to 0.92.

Conclusion: The thorough validation of the questionnaire proved satisfactory and indicated that it may be of value for further studies measuring patients' experiences with diabetes care and transition.
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http://dx.doi.org/10.1111/apa.15205DOI Listing
October 2020

Irritable bowel syndrome-like symptoms and health related quality of life two years after Roux-en-Y gastric bypass - a prospective cohort study.

BMC Gastroenterol 2019 Dec 2;19(1):204. Epub 2019 Dec 2.

Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.

Background: Irritable bowel syndrome (IBS) is prevalent in patients with morbid obesity. After Roux-en-Y gastric bypass (RYGB) chronic abdominal pain is common, however the etiology is largely unknown. We aimed to study the change in the prevalence of IBS-like symptoms 2 years after RYGB and possible preoperative predictors of such symptoms. Secondly, to evaluate changes in symptoms of constipation and diarrhea, and Health related quality of life (HRQoL).

Methods: Patients with morbid obesity were included at two obesity centers in South-Eastern Norway. IBS was diagnosed according to the Rome III criteria. Predictors were evaluated in a multivariable logistic regression analysis.

Results: Of 307 participants operated with RYGB, 233 (76%) completed the study questionnaires. Preoperatively 27/233 participants (12%) had IBS, 2 years after RYGB 61/233 (26%) had IBS-like symptoms (p < 0.001). Eleven participants with IBS preoperatively (41%) did not report such symptoms after RYGB. New onset IBS-like symptoms was identified in 45/206 (22%) after RYGB. Fibromyalgia, low LDL levels, high vitamin B levels and IBS before RYGB were independent preoperative predictors of IBS-like symptoms at the follow-up visit. Symptom scores for constipation preoperatively and 2 year after RYGB were 1.5 (0.9) and 1.8 (1.2), and for diarrhea 1.4 (0.9) and 1.8 (1.1), respectively (p < 0.001). We observed a significant improvement in the physical component score for all participants. However, participants with new onset IBS-like symptoms had a significant worsening of the mental component score.

Conclusions: The prevalence of IBS-like symptoms doubled 2 years after RYGB, and these symptoms were associated with reduced HRQoL. Preoperative IBS and fibromyalgia were strong predictors of postoperative IBS-like symptoms.
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http://dx.doi.org/10.1186/s12876-019-1103-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889730PMC
December 2019

Mothers with and without bipolar disorder and their infants: group differences in mother-infant interaction patterns at three months postpartum.

BMC Psychiatry 2019 09 18;19(1):292. Epub 2019 Sep 18.

Vestre Viken Hospital Trust Division of Mental Health and Addiction, Drammen, Norway.

Background: Women with bipolar disorder (BD) have a high risk of illness relapse postpartum. The risk coincides with the period when mother-infant interactions are evolving. We compared mother-infant interactions in dyads where the mothers have BD with dyads where the mothers have no mental disorder. The association between concurrent affective symptoms of BD mothers and interaction quality was investigated.

Methods: Twenty-six women with BD and 30 comparison women with infants were included. The Parent-Child Early Relational Assessment (PCERA) was used to assess maternal behaviour, infant behaviour and dyadic coordination in interactions at 3 months postpartum. The Inventory of Depressive Symptomatology and Young Mania Rating Scale were used to assess affective symptoms of BD mothers at the time of interaction.

Results: There were significant group differences with medium to large effect sizes (0.73-1.32) on five of six subscales within the three interactional domains. Most interactional concerns were identified in dyadic coordination. No significant associations were found between maternal symptom load and interaction quality within the BD sample. Forty-six percent of the BD mothers experienced a mood episode within 0-3 months postpartum.

Conclusions: The present study identified challenges for mothers with BD and their infants in "finding" each other in interaction at 3 months postpartum. If sustained, this interaction pattern may have a long-term impact on children's development. We suggest interventions specifically focusing on sensitising and supporting mothers to read infants' cues on a micro-level. This may help them to respond contingently and improve dyadic coordination and synchronicity.
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http://dx.doi.org/10.1186/s12888-019-2275-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751750PMC
September 2019

Bone metabolism, bone mineral density and low-energy fractures 10 years after Roux-en-Y gastric bypass.

Bone 2019 10 16;127:436-445. Epub 2019 Jul 16.

Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway; Department of Gastrointestinal and Pediatric Surgery, Oslo University, Norway.

Background: Roux-en-Y gastric bypass (RYGB) is a common surgical procedure for treatment of morbid obesity. RYGB induces considerable and sustained weight loss, and remission of obesity related-comorbidities. While studies have suggested negative effects of RYGB on bone health, long-term data are lacking. We aimed to evaluate the prevalence of aBMD below the expected range for age, osteopenia, osteoporosis and low-energy fractures in a defined patient cohort 10 years after RYGB. Secondly, we wanted to identify factors associated with increased risk of aBMD z-score or t-score of -1.1 or lower 10 years after RYGB.

Methods: Patients undergoing RYGB surgery from June 2004 to December 2006 at the Department of Morbid Obesity and Bariatric Surgery, Oslo University Hospital, a tertiary referral centre for treatment of morbid obesity, were invited to a 10 year follow-up. Follow-up visits included morning fasting blood samples, clinical examination, anthropometric measures and dual energy X-ray absorptiometry (DXA).

Results: Out of 194 patients eligible for the study, 124 attended the 10 year follow-up and 122 (63%) were examined with DXA. Mean (SD) age was 50.3 (9.0) years, 118 (97%) were of Caucasian ethnicity, 94 were females (77%), of whom 41 (44%) were postmenopausal. Secondary hyperparathyroidism (SHPT) was noted in 37 participants (31%) and vitamin D deficiency (value below 50 nmol/L) and insufficiency (value below 75 nmol/L) in 40 (33%) and 91 (75%), respectively. Among the 63 participants who were premenopausal females or males 49 years or younger the prevalence of areal bone mineral density (aBMD) in the lower range of normal (z-score -1.1- to -1.9) was 30% (n = 19) and aBMD below the expected range for age (z-score ≤ -2.0) was noted in 8% (n = 5). Among the 59 participants who were postmenopausal females or males 50 years or older, the prevalence of osteopenia (t-score -1.1 to -2.4) was 51% (n = 30) and osteoporosis (t-score ≤ -2.5) was 27% (n = 16). The bone resorption markers CTX-1 and PINP were higher in participants with aBMD z-score or t-score of -1.1 or lower compared to participants with aBMD z-score or t-score of -1.0 or higher. Preoperative hypothyroidism, or higher age, postmenopausal status, BMI < 35 kg/m, SHPT or higher PINP levels at 10 year follow-up were independently associated with aBMD z-score or t-score of -1.1 or lower 10 years after RYGB. Eighteen participants (15%) reported a clinical low-energy fracture after RYGB. In addition, vertebral fracture assessment by DXA revealed that 10 participants (8%) had experienced at least one moderate to severe morphometric vertebral fracture.

Conclusion: Ten years after RYGB 27% of postmenopausal females and males 50 years or older were osteoporotic, and 8% of premenopausal females and males 49 years or younger exhibited aBMD below the expected range for age. The prevalence of fragility fractures was high. SHPT, higher age, postmenopausal status or higher PINP levels at 10 years and preoperative hypothyroidism were all independent risk factors for aBMD z-score or t-score of -1.1 or lower 10 years after RYGB.
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http://dx.doi.org/10.1016/j.bone.2019.07.014DOI Listing
October 2019

Post-fracture Risk Assessment: Target the Centrally Sited Fractures First! A Substudy of NoFRACT.

J Bone Miner Res 2019 11 16;34(11):2036-2044. Epub 2019 Aug 16.

Department of Clinical Medicine, University of Oslo, Oslo, Norway.

The location of osteoporotic fragility fractures adds crucial information to post-fracture risk estimation. Triaging patients according to fracture site for secondary fracture prevention can therefore be of interest to prioritize patients considering the high imminent fracture risk. The objectives of this cross-sectional study were therefore to explore potential differences between central (vertebral, hip, proximal humerus, pelvis) and peripheral (forearm, ankle, other) fractures. This substudy of the Norwegian Capture the Fracture Initiative (NoFRACT) included 495 women and 119 men ≥50 years with fragility fractures. They had bone mineral density (BMD) of the femoral neck, total hip, and lumbar spine assessed using dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS) calculated, concomitantly vertebral fracture assessment (VFA) with semiquantitative grading of vertebral fractures (SQ1-SQ3), and a questionnaire concerning risk factors for fractures was answered. Patients with central fractures exhibited lower BMD of the femoral neck (765 versus 827 mg/cm ), total hip (800 versus 876 mg/cm ), and lumbar spine (1024 versus 1062 mg/cm ); lower mean TBS (1.24 versus 1.28); and a higher proportion of SQ1-SQ3 fractures (52.0% versus 27.7%), SQ2-SQ3 fractures (36.8% versus 13.4%), and SQ3 fractures (21.5% versus 2.2%) than patients with peripheral fractures (all p < 0.05). All analyses were adjusted for sex, age, and body mass index (BMI); and the analyses of TBS and SQ1-SQ3 fracture prevalence was additionally adjusted for BMD). In conclusion, patients with central fragility fractures revealed lower femoral neck BMD, lower TBS, and higher prevalence of vertebral fractures on VFA than the patients with peripheral fractures. This suggests that patients with central fragility fractures exhibit more severe deterioration of bone structure, translating into a higher risk of subsequent fragility fractures and therefore they should get the highest priority in secondary fracture prevention, although attention to peripheral fractures should still not be diminished. © 2019 American Society for Bone and Mineral Research. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3827DOI Listing
November 2019

Tracking Impact of Interstitial Lung Disease in Systemic Sclerosis in a Complete Nationwide Cohort.

Am J Respir Crit Care Med 2019 11;200(10):1258-1266

Department of Rheumatology.

Interstitial lung disease (ILD) represents a major challenge in systemic sclerosis (SSc), but there are no precise, population-based data on its overall impact, limiting opportunities for screening and management strategies. Evaluate impact of ILD in a unique, nationwide, population-based SSc cohort. ILD was assessed prospectively in the Norwegian SSc (Nor-SSc) cohort, including all 815 patients with SSc resident in the country from 2000 to 2012. Lung high-resolution computed tomography (HRCT) scans were available for fibrosis quantification at baseline ( = 650, 80%) and follow-up. Pulmonary function tests were assessed at baseline ( = 703, 86%) and follow-up. Vital status and standardized mortality ratios (SMRs) were estimated at study end (2018) in the 630 incident Nor-SSc cases and 15 individually matched control subjects. Cumulative survival rates were computed. At baseline, 50% of the subjects with SSc ( = 324) had ILD by HRCT and 46% displayed pulmonary function declines consistent with ILD progression. Mortality correlated with extent of lung fibrosis as SMR increased from 2.2 with no fibrosis to 8.0 with greater than 25% fibrosis. SMR was inversely related to baseline FVC% and increased at all FVC levels below 100%. In patients with normal-range baseline FVC (80-100%), the 5- and 10-year survival rates correlated with presence or absence of lung fibrosis, being 83% and 80%, respectively, with no fibrosis and 69% and 56%, respectively, with lung fibrosis ( = 0.03). The mere presence of ILD at baseline appears to affect outcome in SSc, suggesting that all patients with SSc should undergo a baseline pulmonary function test and lung HRCT screening to diagnose ILD early and tailor further management.
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http://dx.doi.org/10.1164/rccm.201903-0486OCDOI Listing
November 2019

Changes in Bone Marrow Adipose Tissue One Year After Roux-en-Y Gastric Bypass: A Prospective Cohort Study.

J Bone Miner Res 2019 10 7;34(10):1815-1823. Epub 2019 Aug 7.

Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.

Bone marrow adipose tissue (BMAT) has been postulated to mediate skeletal fragility in type 2 diabetes (T2D) and obesity. Roux-en-Y gastric bypass (RYGB) induces a substantial weight loss and resolution of comorbidities. However, the procedure induces increased bone turnover and fracture rates. No previous study has evaluated biopsy-measured BMAT fraction preoperatively and after RYGB. In this study, we aimed to investigate BMAT fraction of the hip in participants with and without T2D preoperatively and 1 year after RYGB and explore factors associated with BMAT change. Patients with morbid obesity scheduled for RYGB were examined preoperatively and 1 year after RYGB. Forty-four participants were included and preoperative examinations were possible in 35. Of these, 33 (94%) met for follow-up, 2 were excluded, and BMAT estimation was not possible in 1. Eighteen (60%) of the participants were females and 11 (37%) had T2D. Preoperative BMAT fraction was positively associated with glycosylated hemoglobin and negatively associated with areal bone mineral density (aBMD). After RYGB, BMAT fraction decreased from 40.4 ± 1.7% to 35.6 ± 12.8%, p = 0.042, or with mean percent change of 10.7% of preoperative BMAT fraction. Change in BMAT fraction was positively associated with change in body mass index (BMI) and total body fat. In females, we observed a mean percent reduction of 22.4 ± 19.6%, whereas in males BMAT increased with a mean percent of 6.8 ± 37.5%, p = 0.009. For males, changes in estradiol were associated with BMAT change; this was not observed for females. In participants with and without T2D, the mean percent BMAT reduction was 5.8 ± 36.9% and 13.5 ± 28.0%, respectively, p = 0.52. We conclude that a high BMAT seems to be associated with lower aBMD and poorer glycemic control in obese subjects. After RYGB, we observed a significant decrease in BMAT. The reduction in BMAT did not differ between participants with and without T2D, but appeared sex specific. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jbmr.3814DOI Listing
October 2019