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Abstract Background Traumatic injuries, defined as physical injuries with sudden onset, are a major cause of distress and disability, with far-reaching societal consequences. A significant proportion of trauma survivors report persistent symptoms and difficulties after the injury, and studies show unmet health care needs. Self-management programs delivered in the sub-acute phase after traumatic injuries are scarcely evaluated. The aim of the present study is to evaluate the effectiveness of a self-management program (SEMPO), delivered 3–4 months after moderate-to-severe traumatic injury. Methods This study protocol describes a pragmatic randomized controlled trial (RCT) with two classical RCT arms (intervention and control) and an explorative self-selection arm. 220 patients will be recruited from Oslo University Hospital, the largest Trauma Referral Centre in Norway. Patients aged 18–72 years residing in the south-east region of Norway, admitted to the Trauma Centre directly or within 72 h after having sustained a moderate to severe traumatic injury, defined as a New Injury Severity Score > 9, having at least 2 days hospital stay, and reporting injury-related symptoms and impairment at discharge from the acute hospital will be included. Patients will be randomly assigned to either a classical RCT randomization arm (intervention or control arm) or to a self-selection arm. In the randomization arm, participants are further randomized into intervention or control group. Participants allocated to the self-selection arm will choose to partake either in the intervention or control arm. The primary outcome is the level of self-efficacy in trauma coping assessed 6 months after completion of the intervention, with a similar time point for the control group. Secondary outcomes include symptom burden, physical functioning and disability, return to work and health care utilization, health-related quality of life, and communication competency. In addition, patients will be asked to nominate one domain-related measurement as their preferred outcome measure. Discussion This RCT will determine the effect of a self-management program tailored to patients with moderate to severe physical trauma, and the self-selection arm incorporates the potential influence of patient treatment preferences on intervention results. If the intervention proves effective, cost-effectiveness and cost-utility analyses will be performed and thereby provide important information for clinicians and policy makers. Trial registration The study is registered in Clinical Trials with the identifier: NCT06305819. Registered on March 05, 2004.

Abstract Background Family members are often affected by the long-term consequences of traumatic brain injury, but are rarely involved in rehabilitation programs in the chronic phase. We thus do not know what family members´ main concerns are in the chronic phase, what factors are associated with perceived caregiver burden, and whether family members´ health and functioning improves due to rehabilitation efforts received by the patients. This study explored family-members` functioning, predictors of caregiver burden and effect for family members of a goal-oriented intervention in the chronic phase of traumatic brain injury. Methods Family members self-reported data measuring their caregiver burden, depression, general health, loneliness, and their evaluation of patient competency in everyday life, patient awareness levels, main problem areas (target outcomes) for the patient related to the brain injury, and demographic data were collected. Regression models were used to explore predictors of caregiver burden, and mixed models analysis was used to explore treatment effects. Results In total, 73 family members were included, 39 in the intervention group and 34 in the control group. Moderate to high caregiver burden was reported by 40% of family members, and 16% experienced clinical levels of depression. Family member loneliness and their evaluation of the patient`s level of functional competency explained 57% of the variability in caregiver burden. There were no treatment-related changes in caregiver burden, family member depression or general health. At T2 there was however a significant reduction in how family members rated severity of target outcomes that the family members had nominated at baseline (-0.38, 95% CI, -0.75 to -0.02, p = 0.04), but not for the target outcomes the patients had nominated. Conclusions A significant proportion of family members to patients in the chronic phase of TBI continue to experience challenging caregiver burden and emotional symptoms. Both family member-related and patient factors contribute to caregiver burden. Interventions targeting patient complaints do not automatically alleviate family members´ burden. It is important to address social support for family members early after injury, and there is a need for more interventions specifically targeting family members´ needs. Trial registration The trial was registered at ClinicalTrials.gov, NCT03545594 on the 4th of June 2018.

Introduction: The selection of endovascular thrombectomy (EVT) for acute ischemic stroke in the elderly remains challenging due to the underrepresentation of these patients in landmark randomized trials. The aim of this study was to assess the association between age and the pre-stroke modified Rankin scale score with functional outcomes after EVT in elderly patients aged ≥80 years. Methods: We prospectively collected data from consecutive elderly patients who underwent EVT of the anterior or posterior circulation at our institution between 2007 and 2022. Clinical and radiological parameters were analyzed using a fair outcome (mRS ≤3 or retained pre-stroke mRS score of 4) as the primary outcome. Results: In total, 307 elderly patients were included in the analysis. Fair functional outcomes were achieved in 162 (53%) patients. Eighty-four (27.4%) patients were deceased at 3-month follow-up and the mortality rate increased to 37.1% (114 deceased) at 1-year follow-up. The likelihood of achieving a fair functional outcome decreased by 8% for every 1-year age increase (OR 0.81, 95% CI 0.73–0.90). Lower National Institutes of Health Stroke Scale (OR 0.89, 95% CI 0.85–0.93, p < 0.001) and pre-stroke mRS (OR 0.67, 95% CI 0.53–0.84, p < 0.001) were associated with fair outcomes. Conclusions: EVT in elderly patients with stroke is beneficial in selected cases. Increasing age was associated with an increased risk of an mRS change to 4 or worse and death within 1 year. The pre-stroke mRS may aid clinicians in the selection of elderly patients for EVT.

Abstract Background Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury. Methods A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors. Results A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury. Conclusions Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache. Trial registration ClinicalTrials.gov NCT02210221.

Objectives To compare the sensitivity of 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria against 1997 ACR criteria for systemic lupus erythematosus (SLE), for incident SLE cases in the presumably complete population-based Nor-SLE cohort from Southeast Norway (2.9 million inhabitants).Methods All cases International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coded as SLE during 2000–2017 were individually reviewed. Those with a confirmed SLE diagnosis by expert clinical assessment were included in the Nor-SLE cohort. Core clinical data were recorded, and the cases were classified according to 2019 EULAR/ACR and 1997 ACR criteria. Juvenile SLE was defined as

BackgroundMeningioma is the most common primary brain tumor, with a clear preponderance in women. Obesity is considered a risk factor for the development of meningioma. Obesity is also the clinical hallmark of metabolic syndrome, characterized by glucose intolerance, dyslipidemia, and hypertension. Lifestyle and metabolic factors directly impact overweight and obesity and are therefore potential risk factors for meningioma development. The aim of this study is to assess lifestyle and metabolic factors for meningioma risk in women.MethodsThe Cohort of Norway (CONOR) is a nationwide health survey, conducted between 1994 and 2003, including anthropometric measures, blood tests, and health questionnaires. Linkage to the National Cancer Registry enabled the identification of intracranial meningioma during follow-up until December 2018.ResultsA total of 81,652 women were followed for a combined total of 1.5 million years, and 238 intracranial meningiomas were identified. Increasing levels of physical activity (HR 0.81; 95% CI 0.68–0.96; p trend

Abstract Aims Currently, no incident heart failure (HF) risk score that is in regular use in a general population is available. We aimed to develop this and compare with existing HF risk scores. Methods and results Participants in the third wave (2006–08) of the population‐based Trøndelag Health Study 3 (HUNT3) were included if they reported no previous HF. Any hospital diagnoses captured during follow‐up (until the end of 2018) of HF, cardiomyopathy, or hypertensive heart disease were assessed by an experienced cardiologist. Valid HF events were defined as symptoms/signs of HF and objective evidence of structural/functional abnormality of the heart at rest. The model was compared with slightly modified HF risk scores (the Health Aging and Body Composition HF risk score, the Framingham HF risk score, the Pooled Cohort equations to Prevent HF risk score, and NORRISK 2). Among 36 511 participants (mean ± SD age of 57.9 ± 13.3 years, 55.4% female), with a mean follow‐up of 10.2 ± 1.3 years, 1366 developed HF (incidence rate of 3.66 per 1000 participant years). Out of the 38 relevant clinical variables assessed, we identified 12 (atrial fibrillation being the strongest) that independently predicted an HF event. The final model demonstrated good discrimination (C statistics = 0.904) and calibration, was stable in internal validation, and performed well compared with existing risk scores. The model identified that, at enrolment, 31 391 (86%), 2386 (7%), 1246 (3%), and 1488 (4%) had low, low‐intermediate, high‐intermediate, and high 10‐year HF risk, respectively. Conclusions Twelve clinical variables independently predicted 10‐year HF risk. The model may serve well as the foundation of a practical, online risk score for HF in general practice. Trial Registration: ClinicalTrials.gov Identifier: NCT04648852.

Background Mechanical insufflation–exsufflation (MI-E) is used to augment cough in children with neurodisability. We aimed to determine the user comfort and cough flows during three MI-E strategies, and to predict factors associated with improved comfort and cough flows. Methods This multicentre, crossover trial was done at four regional hospitals in Norway. Children with neurodisability using MI-E long term via mask were enrolled. In randomised order, they tested three MI-E setting strategies (in-/exsufflation pressure (cmH2O)/in (In)- versus exsufflation (Ex) time): 1) “A-symmetric” (±50/In=Ex); 2) “B-asymmetric” (+25– +30)/−40, In>Ex); and 3) “C-personalised”, as set by their therapist. The primary outcomes were user-reported comfort on a visual analogue scale (VAS) (0=maximum comfort) and peak cough flows (PCF) (L·min−1) measured by a pneumotachograph in the MI-E circuit. Results We recruited 74 children median (IQR) age 8.1 (4.4–13.8) years, range 0.6–17.9, and analysed 218 MI-E sequences. The mean±sd VAS comfort scores were 4.7±2.96, 2.9±2.44 and 3.2±2.46 for strategies A, B and C, respectively (A versus B and C, p

Abstract Background Previous studies have demonstrated that the trauma population has needs for rehabilitation services that are best provided in a continuous and coordinated way. The discharge destination after acute care is the second step to ensuring quality of care. There is a lack of knowledge regarding the factors associated with the discharge destination for the overall trauma population. This paper aims to identify sociodemographic, geographical, and injury-related factors associated with discharge destination following acute care at trauma centers for patients with moderate-to-severe traumatic injuries. Methods A multicenter, population-based, prospective study was conducted with patients of all ages with traumatic injury [New Injury Severity Score (NISS) > 9] admitted within 72 h after the injury to regional trauma centers in southeastern and northern Norway over a 1-year period (2020). Results In total, 601 patients were included; a majority (76%) sustained severe injuries, and 22% were discharged directly to specialized rehabilitation. Children were primarily discharged home, and most of the patients ≥ 65 years to their local hospital. Depending on the centrality of their residence [Norwegian Centrality Index (NCI) 1–6, where 1 is most central], we found that patients residing in NCI 3–4 and 5–6 areas sustained more severe injuries than patients residing in NCI 1–2 areas. An increase in the NISS, number of injuries, or a spinal injury with an Abbreviated Injury Scale (AIS) ≥ 3 was associated with discharge to local hospitals and specialized rehabilitation than to home. Patients with an AIS ≥ 3 head injury (RRR 6.1, 95% Confidence interval 2.80–13.38) were significantly more likely to be discharged to specialized rehabilitation than patients with a less severe head injury. Age

AbstractAim The aim of this study was to compare the prevalence of daytime contacts and consultations, and pain as a reason for encounter (RFE) with a general practitioner (GP), in children with cerebral palsy (CP) (cases) to that of the general paediatric population (controls).Methods The study linked the Norwegian Directorate of Health’s database for the control and reimbursement of health expenses, and the Norwegian Quality and Surveillance Registry for Cerebral Palsy, including children born from 1996 to 2012 in the period 2006 to 2018. All daytime contacts were included. International Classification for Primary Care was applied for RFE.Results Cases accounted for 0.46% of all daytime contacts and 0.27% of all daytime consultations, the latter corresponding with the estimated national prevalence of CP. GPs registered more administrative contact and coded pain as an RFE less frequently in consultations with cases (6%) than with controls (12%).Interpretation Children with CP did not consult GPs more than the general paediatric population did. In consultations, GPs should ask for pain even if the child with CP or parent does not address pain. The local multidisciplinary team should encourage the family to consider consulting a GP if the child is in pain.KEY MESSAGESPrevalence of GP consultations in children with CP is similar to that of children in the general population.GPs perform more administrative work for children with CP than for their other paediatric patients.GPs code pain as an RFE less frequently in consultations with children with CP than in consultations with children in the general population.

Goal Management Training (GMT) improved self-reported executive functioning in a recent randomized, controlled trial in early intervention for psychosis participants. Little is known about the mechanism for this benefit, so this study investigates objectively measured executive function, the difference between subjective and objective executive function, independent living and employment status as potential moderators of efficacy of GMT.Baseline scores from 81 participants (GMT n = 39 vs Treatment-as-usual; TAU n = 42) were analyzed in a linear mixed model analysis for repeated measures as predictors of improvement on the self-reported Behavior Rating Inventory of Executive Function–Adult version (BRIEF-A) immediately and 30 weeks after GMT. Potential moderators were scores from objective measures of executive functioning, discrepancy between subjective and objective measures, independent living and employment status. Discrepancy was assessed by comparing four clusters of participants with differing patterns of scores.The effect of GMT remained significant regardless of initial objective executive functioning at baseline. Those with higher subjective complaints at baseline in two clusters with (i) both objective and subjective executive dysfunction, and (ii) mostly subjective executive dysfunction experienced greater change after treatment. Living arrangements or participation in education or work did not significantly moderate the effects of GMT.Poor performance on neuropsychological tasks is not an obstacle to making use of GMT, but further knowledge is needed about the benefits of strategy training for individuals with a combination of poor performance with few subjective complaints.

Abstract Primary cardiac involvement is one of the leading causes of mortality in systemic sclerosis (SSc), but little is known regarding circulating biomarkers for cardiac SSc. Here, we aimed to investigate potential associations between cardiac SSc and candidate serum markers. Serum samples from patients of the Oslo University SSc cohort and 100 healthy controls were screened against two custom-made candidate marker panels containing molecules deemed relevant for cardiopulmonary and/or fibrotic diseases. Left (LV) and right ventricular (RV) dysfunction was assessed by protocol echocardiography, performed within three years from serum sampling. Patients suspected of pulmonary hypertension underwent right heart catheterization. Vital status at study end was available for all patients. Descriptive analyses, logistic and Cox regressions were conducted to assess associations between cardiac SSc and candidate serum markers. The 371 patients presented an average age of 57.2 (± 13.9) years. Female sex (84%) and limited cutaneous SSc (73%) were predominant. Association between LV diastolic dysfunction and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (OR 0.41, 95% CI 0.21–0.78, p = 0.007) was identified. LV systolic dysfunction defined by global longitudinal strain was associated with angiopoietin 2 (ANGPT2) (OR 3.42, 95% CI 1.52–7.71, p = 0.003) and osteopontin (OPN) (OR 1.95, 95% CI 1.08–3.52, p = 0.026). RV systolic dysfunction, measured by tricuspid annular plane systolic excursion, was associated to markers of LV dysfunction (ANGPT2, OPN, and TRAIL) (OR 1.67, 95% CI 1.11–2.50, p = 0.014, OR 1.86, 95% CI 1.25–2.77, p = 0.002, OR 0.32, 95% CI 0.15–0.66, p = 0.002, respectively) and endostatin (OR 1.86, 95% CI 1.22–2.84, p = 0.004). In conclusion, ANGPT2, OPN and TRAIL seem to be circulating biomarkers associated with both LV and RV dysfunction in SSc.

Abstract Background Pediatric acquired brain injury (pABI) is associated with long-term cognitive, behavioral, social, and emotional problems, which may affect the quality of life, school, and family functioning. Yet, there is a lack of evidence-based community-centered rehabilitation programs for chronic pABI and these children do not systematically receive comprehensive rehabilitation. The Child In Context Intervention (CICI) study is a pragmatic randomized controlled trial (RCT) for children with chronic pABI, which aims to evaluate the effectiveness of an individualized and goal-oriented intervention targeting everyday functioning of the child and family. Methods Children aged 6–16 years with MRI/CT-verified intracranial abnormalities will be included in the CICI study if they have persistent self- or parent-reported cognitive, emotional, and/or behavioral challenges 1 year or more after insult and attend school regularly. A total of 70 families will be randomized 1:1 to an intervention or a control group. The intervention consists of seven family sessions, one parent seminar, and four school sessions delivered over approximately 6 months. The parent seminar will be held in person, and the other sessions will mainly be video based. The children’s and families’ self-reported major challenges in everyday life will be targeted using SMART goals. Evidence-based strategies, when available, will be applied to achieve the goals, combined with psychoeducation. Goal attainment scaling (GAS) will be used to evaluate goal attainment. Data is collected at baseline and after approximately 6 and 9 months. External assessors are blinded to group allocation. Primary outcomes are parent-reported brain injury symptoms in children and parenting self-efficacy at 9 months of follow-up. Secondary outcomes include child-reported brain injury symptoms, quality of life, executive functioning in daily life, parent emotional symptoms, family functioning, and unmet family health care needs. A process evaluation will be conducted. Discussion The current study provides an innovative approach to rehabilitation for children in the chronic phase of ABI and their families. This complex intervention may contribute to the development of evidence-based, high-quality rehabilitation for a large patient group, which is underrepresented in clinical research. It may also improve collaboration between specialized rehabilitation facilities, schools, and local health care services. Inclusion for the trial started in April 2021. Trial registration ClinicalTrials.gov NCT04798859 . Registered on March 15, 2021

IntroductionNo evidence of disease activity with three components (NEDA-3) is achieved if the person with MS (pwMS) has no new MRI lesions, no new relapses and no change in Expanded disability status scale (EDSS) over 1 year. Whether NEDA-3 is a good tool in measuring disease activity is up for discussion, but it is superior to the individual parameters separately and user-friendly. There is disagreement on whether NEDA-3 is a good predictor of long-term disability.MethodsThis is a retrospective cohort study using real-world data with limited selection bias from the complete MS population at two hospitals in the southeast of Norway. We included pwMS diagnosed between 2006 and 2017 who had enough information to determine time to failure of NEDA-3 after diagnosis.ResultsOf 536 pwMS, only 38% achieved NEDA 1 year after diagnosis. PwMS achieving NEDA were more likely to be started on a high efficacy drug as the initial drug, but there were no demographic differences. Mean time to NEDA failure was 3.3 (95% CI 2.9–3.7) years. Starting a high efficiacy therapy was associated with an increased risk of sustaining NEDA as compared to those receiving moderate efficacy therapy. PwMS who achieved NEDA at year one had a mean time to EDSS 6 of 33.8 (95% CI 30.9–36.8) years vs. 30.8 (95% CI 25.0–36.6) years in pwMS who did not achieve NEDA, p < 0.001. When rebaselining NEDA 1 year after diagnosis, 52.2% achieved NEDA in the 1st year after rebaseline, mean time to NEDA failure was 3.4 (95% CI 3.0–3.7) years and mean time to EDSS 6 was 44.5 (95% CI 40.4–48.5) years in pwMS achieving NEDA vs. 29.6 (95% CI 24.2–35.0) years in pwMS not achieving NEDA, p < 0.001. After rebaseline, pwMS with a high efficacy therapy as the initial drug had a mean time from diagnosis to NEDA fail of 4.8 years (95% CI 3.9–5.8) vs. 3.1 years (95% CI 2.7–3.5) in pwMS started on a moderate efficacy therapy, p < 0.001. In pwMS with NEDA failure at year one, 70% failed one, 28% failed two and 2% failed three components. New MRI lesions were the most common cause of NEDA failure (63%), followed by new relapses (50%) and EDSS change (25%).ConclusionNEDA-3 from rebaseline after 1 year, once treatment is stabilized, can predict the long-term disease course in MS. Starting a high efficacy DMT is associated with longer time to NEDA failure than moderate therapies. Finally, most pwMS only fail one component and new MRI lesions are the most likely cause of NEDA failure.

Objective: To quantify potential changes in direct referral to early specialized rehabilitation during the COVID-19 pandemic and the injury pattern of patients hospitalized with traumatic brain injury (TBI) at a level 1 trauma centre. Methods: In this registry-based study, data were retrieved from the Oslo TBI Registry-Neurosurgery and included adult patients with injury-related intracranial findings admitted to Oslo University Hospital (OUH). The study focused on a period of time when OUH was in any level of preparedness because of the COVID-19 pandemic; March 2020 to August 2021. For comparison, the study used patients hospitalized for TBI in 2018 and 2019. Results: A total of 1,310 hospitalized patients with TBI were divided into 2 groups; pre-pandemic and pandemic. Direct referral to early rehabilitation was maintained. Patient volume remained stable, and there were no differences between the groups regarding patient characteristics and acute management, although there was a significantly higher proportion of TBIs secondary to electric scooter accidents in the pandemic group. Results from univariable and multivariable logistic regression showed a multifaceted reality, but younger age, none or mild preinjury comorbidity and severe disability due to TBI at discharge from acute care remained stable strong predictors of direct referral to rehabilitation. Conclusion: For patients with moderate-severe TBI, the direct pathway to early specialized rehabilitation was maintained during 2020–21. However, the pandemic continued and the long-term impact for rehabilitation services is not yet known. LAY ABSTRACT After traumatic brain injury, early rehabilitation is important in order to achieve optimal functional outcome. The COVID-19 pandemic has put the health services under pressure, and hospitals in Norway were reorganized to be able to treat a large number of patients with COVID-19. Therefore, this study investigated to what extent the transfer to early rehabilitation has been affected and whether there have been changes in volume and characteristics of patients admitted to hospital with traumatic brain injury. In conclusion, the direct pathway to early rehabilitation was maintained during the pandemic years 2020 and 2021. Moreover, there was no change in the number of hospital admissions or patient characteristics, and acute management was maintained. However, the true long-term consequences for rehabilitation are not yet known.

IntroductionSystemic sclerosis (SSc) is a heterogenous disorder that appears to result from interplay between vascular pathologies, tissue fibrosis and immune processes, with evidence for deregulation of chemokines, which normally control immune trafficking. We recently identified altered levels of chemokine CCL21 in SSc associated pulmonary arterial hypertension (PAH). Here, we aimed to define target organ expression and biomarker characteristics of CCL21.Materials and methodsTo investigate target organ expression of CCL21, we performed immunohistochemistry (IHC) on explanted lung tissues from SSc-PAH patients. We assessed serum levels of CCL21 by ELISA and Luminex in two well-characterized SSc cohorts from Oslo (OUH, n=552) and Zurich (n=93) University hospitals and in 168 healthy controls. For detection of anti-CCl21 antibodies, we performed protein array analysis applying serum samples from SSc patients (n=300) and healthy controls. To characterize circulating CCL21 in SSc, we applied immunoprecipitation (IP) with antibodies detecting both full length and tailless and a custom-made antibody detecting only the C-terminal of CCL21. IP products were analyzed by SDS-PAGE/western blot and Mass spectrometry (MS).ResultsBy IHC, we found that CCL21 was mainly expressed in the airway epithelial cells of SSc patients with PAH. In the analysis of serum levels of CCL21 we found weak correlation between Luminex and ELISA (r=0.515, p

Purpose: to gain insight into the baseline parameters of a population with diabetes mellitus (DM) included in a pilot diabetic retinopathy (DR) screening program at Oslo University Hospital (OUH), Norway. Methods: This was a cross-sectional study of a cohort of adult patients (≥18 years) with type 1 or 2 DM (T1D and T2D). We measured the best-corrected visual acuity (BCVA), blood pressure (BP), heart rate (HR), intraocular pressure (IOP), height and weight. We also collected HbA1c, total serum cholesterol and urine-albumin, -creatinine and -albumin-to-creatinine ratio (ACR), as well as socio-demographic parameters, medications and previous screening history. We obtained color fundus photographs, which were graded by two experienced ophthalmologists according to the International Clinical Disease Severity Scale for DR. Results: The study included 180 eyes of 90 patients: 12 patients (13.3%) had T1D and 78 (86.7%) had T2D. In the T1D group, 5 patients (41.7%) had no DR, and 7 (58.3%) had some degree of DR. In the T2D group, 60 patients (76.9%) had no DR, and 18 (23.1%) had some degree of DR. None of the patients had proliferative DR. Of the 43 patients not newly diagnosed (time of diagnosis > 5 years for T1D and >1 years for T2D), 37.5% of the T1D patients and 5.7% of the T2D patients had previously undergone regular screening. Univariate analyses found for the whole cohort significant associations between DR and age, HbA1c, urine albumin-to-creatinine ratio, body mass index (BMI) and duration of DM. For the T2D group alone, there were significant associations between DR and HbA1c, BMI, urine creatinine, urine albumin-to-creatinine ratio and duration of DM. The analysis also showed three times higher odds for DR in the T1D group than the T2D group. Conclusions: This study underscores the need for implementing a systematic DR screening program in the Oslo region, Norway, to better reach out to patients with DM and improve their screening adherence. Timely and proper treatment can prevent or mitigate vision loss and improve the prognosis. A considerable number of patients were referred from general practitioners for not being followed by an ophthalmologist.Among patients not newly diagnosed with DM, 62.8% had never had an eye exam, and the duration of DM for these patients was up to 18 years (median: 8 years).

Abstract 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.

Abstract 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 ).

Abstract 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.

Background Limited population‐based data on the (sex‐specific) link between subclinical measures of peripheral atherosclerosis and new‐onset atrial fibrillation (AF) exist. Methods and Results Subclinical measures of peripheral atherosclerosis including carotid intima‐media thickness (cIMT), carotid plaque, and ankle‐brachial index (ABI) were assessed at baseline and follow‐up examinations. A total of 12 840 participants free of AF at baseline from the population‐based Rotterdam Study were included. Cox proportional hazards models and joint models, adjusted for cardiovascular risk factors, were used to determine the associations between baseline and longitudinal measures of cIMT, carotid plaque, and ABI with new‐onset AF. During a median follow‐up of 9.2 years, 1360 incident AF cases occurred among 12 840 participants (mean age 65.2 years, 58.3% women). Higher baseline cIMT (fully‐adjusted hazard ratio [HR], 95% CI, 1.81, 1.21–2.71; P=0.0042), presence of carotid plaque (fully‐adjusted HR, 95% CI, 1.19, 1.04–1.35; P=0.0089), lower ABI (fully‐adjusted HR, 95% CI, 1.57, 1.14–2.18; P=0.0061) and longitudinal measures of higher cIMT (fully‐adjusted HR, 95% CI, 2.14, 1.38–3.29; P=0.0021), presence of carotid plaque (fully‐adjusted HR, 95% CI, 1.61, 1.12–2.43; P=0.0112), and lower ABI (fully‐adjusted HR, 95% CI, 4.43, 1.83–10.49; P=0.0007) showed significant associations with new‐onset AF in the general population. Sex‐stratified analyses showed that the associations for cIMT, carotid plaque, and ABI were mostly prominent among women. Conclusions Baseline and longitudinal subclinical measures of peripheral atherosclerosis (carotid atherosclerosis, and lower extremity peripheral atherosclerosis) were significantly associated with an increased risk of new‐onset AF, especially among women. Registration URL: https://www.trialregister.nl, https://www.apps.who.int/trialsearch/; Unique identifier: NL6645/NTR6831.

Abstract 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

Rationale & Objective: Assessing the optimal therapy for older patients (aged ≥65 years) with end-stage kidney disease requires knowledge of longevity and health-related quality of life (HRQoL) outcomes. Kidney transplantation prolongs survival but its long-term impact on HRQoL in older recipients is not well defined. We aimed to prospectively evaluate HRQoL changes from enlisting until 3 years posttransplantation and examine pretransplantation predictors of posttransplantation outcomes. Study Design: Prospective cohort study. Setting & Participants: Patients 65 years and older enlisted at the Norwegian National Transplant Center between January 2013 and November 2016. Predictors: Kidney transplantation, dialysis vintage, and pretransplantation comorbidity assessed using the Liu Comorbidity Index. Outcomes: HRQoL, assessed using the Kidney Disease Quality of Life Short Form, version 1.3. Analytical Approach: HRQoL scores obtained at 3 years posttransplantation were compared with those obtained pretransplantation and after 1 year using a paired-sample t test. Multivariable linear mixed-effect models were used to identify possible predictors of HRQoL changes over time. Results: Among 289 patients included, 220 (mean age, 71.5 years) had undergone transplantation and 136 had completed the 3-year HRQoL follow-up by October 2020. Posttransplant HRQoL, both generic and kidney specific, substantially improved and the benefit persisted for 3 years. For wait-listed candidates remaining on dialysis, HRQoL gradually deteriorated, and recipients who died within 3 years posttransplantation experienced no improvement during the first year. Moderately elevated pretransplantation comorbidity scores and prolonged dialysis vintage independently predicted poor HRQoL outcomes posttransplantation. Recipients receiving dialysis for 1 year or longer with pretransplantation comorbidity scores ≥ 7 experienced a marked and sustained physical deterioration after transplantation. Limitations: Homogenous and highly selected population. Conclusions: Transplantation is associated with a sustained HRQoL improvement and should be the preferred treatment for selected older patients. The value of a pretransplant comorbidity score to predict posttransplantation outcomes warrants further evaluation and may improve the selection process.

During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1–2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.

Background: Moderate and high efficacy disease modifying therapies (DMTs) have a profound effect on disease activity. The current treatment guidelines only recommend high efficacy DMTs for patients with highly active MS. The objective was to examine the impact of initial treatment choice in achieving no evidence of disease activity (NEDA) at year 1 and 2.Methods: Using a real-world population-based registry with limited selection bias from the southeast of Norway, we determined how many patients achieved NEDA on moderate and high efficacy DMTs.Results: 68.0% of patients who started a high efficacy DMT as the first drug achieved NEDA at year 1 and 52.4% at year 2 as compared to 36.0 and 19.4% of patients who started a moderate efficacy DMT as a first drug. The odds ratio (OR) of achieving NEDA on high efficacy drugs compared to moderate efficacy drugs as a first drug at year 1 was 3.9 (95% CI 2.4–6.1, p < 0.001). The OR for high efficacy DMT as the second drug was 2.5 (95% CI 1.7–3.9, p < 0.001), and was not significant for the third drug. Patients with a medium or high risk of disease activity were significantly more likely to achieve NEDA on a high efficacy therapy as a first drug compared to moderate efficacy therapy as a first drug.Conclusions: Achieving NEDA at year 1 and 2 is significantly more likely in patients on high-efficacy disease modifying therapies than on moderate efficacy therapies, and the first choice of treatment is the most important. The immunomodulatory treatment guidelines should be updated to ensure early, high efficacy therapy for the majority of patients diagnosed with MS.

Abstract 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.

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.

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 (n = 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.

Aims: 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.Methods: 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 (n = 116) aged 18–60 were randomized (1:1) by an independent investigator to receive group-based compensatory cognitive training (CCT) and supported employment (SE) (n = 60) or TAU consisting of individualized multidisciplinary treatment (n = 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.Results: 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.Conclusion: 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.Clinical Trial Registration: US National Institutes of Health ClinicalTrials.gov, identifier #NCT03092713.

AbstractBackgroundSudan 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.MethodIn 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.ResultsWe 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%.ConclusionThe 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.

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.

Background/Objective. Optical coherence tomography angiography (OCTA) is increasingly used to supplement ophthalmoscopy in the diagnosis and follow-up of diabetic retinopathy. Our objective was to confirm if OCTA parameters can predict the development of nonproliferative diabetic retinopathy (NPDR) and to clarify if any single OCTA parameter is associated with NPDR independently of well-known risk factors in young type 1 diabetes (T1D) patients. 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.

Abstract Background Patients with type 1 diabetes (T1D) are at increased risk of cardiovascular disease (CVD). Measures of high-density lipoprotein (HDL) function provide a better risk estimate for future CVD events than serum levels of HDL cholesterol. The objective of this study was to evaluate HDL function in T1D patients shortly after disease onset compared with healthy control subjects. Methods Participants in the atherosclerosis and childhood diabetes study were examined at baseline and after 5 years. At baseline, the cohort included 293 T1D patients with a mean age of 13.7 years and mean HbA1c of 8.4%, along with 111 healthy control subjects. Their HDL function, quantified by HDL-apoA-I exchange (HAE), was assessed at both time points. HAE is a measure of HDL’s dynamic property, specifically its ability to release lipid-poor apolipoprotein A-I (apoA-I), an essential step in reverse cholesterol transport. Results The HAE-apoA-I ratio, reflecting the HDL function per concentration unit apoA-I, was significantly lower in the diabetes group both at baseline, 0.33 (SD = 0.06) versus 0.36 (SD = 0.06) %HAE/mg/dL, p

Abstract Background Reduced diastolic function is an early sign of diabetes cardiomyopathy in adults and is associated with elevated levels of HbA1c and advanced glycation end products (AGEs). Objective To assess the associations between early reduced diastolic function and elevated levels of HbA1c and AGEs in children and adolescents with type 1 diabetes (T1D). Methods One hundred fourty six T1D patients (age 8–18 years) without known diabetic complications were examined with tissue Doppler imaging and stratified into two groups according to diastolic function. A clinical examination and ultrasound of the common carotid arteries were performed. Methylglyoxal-derived hydroimidazolone-1 (MG-H1) was measured by immunoassay. Results At inclusion, 36 (25%) participants were stratified into a low diastolic function group (E’/A’-ratio

Purpose. Acute kidney injury (AKI) is a common complication after out-of-hospital cardiac arrest (OHCA), leading to increased mortality and challenging prognostication. Our aim was to examine if urine biomarkers could early predict postarrest AKI and patient outcome. Methods. A prospective observational study of resuscitated, comatose OHCA patients admitted to Oslo University Hospital in Norway. Urine samples were collected at admission and day three postarrest and analysed for β-2-microglobulin (β2M), osteopontin, and trefoil factor 3 (TFF3). Outcome variables were AKI within three days according to the Kidney Disease Improving Global Outcome criteria, in addition to six-month mortality and poor neurological outcome (PNO) (cerebral performance category 3–5). Results. Among 195 included patients (85% males, mean age 60 years), 88 (45%) developed AKI, 88 (45%) died, and 96 (49%) had PNO. In univariate analyses, increased urine β2M, osteopontin, and TFF3 levels sampled at admission and day three were independent risk factors for AKI, mortality, and PNO. Exceptions were that β2M measured at day three did not predict any of the outcomes, and TFF3 at admission did not predict AKI. In multivariate analyses, combining clinical parameters and biomarker levels, the area under the receiver operating characteristics curves (95% CI) were 0.729 (0.658–0.800), 0.797 (0.733–0.861), and 0.812 (CI 0.750–0.874) for AKI, mortality, and PNO, respectively. Conclusions. Urine levels of β2M, osteopontin, and TFF3 at admission and day three were associated with increased risk for AKI, mortality, and PNO in comatose OHCA patients. This trail is registered with NCT01239420.

Background. We aimed to evaluate changes in health-related quality of life (HRQoL) in patients 65 years or older from time of kidney transplantation (KTx) until 1 year postengraftment. Methods. A single-center prospective study was conducted. HRQoL was measured pre-KTx and at 2, 6, and 12 months postengraftment using self-reported Kidney Disease and Quality of Life short-form version 1.3. Intraindividual scores before and after KTx were evaluated. Liu Comorbidity Index was registered at enlisting. short-form-36 scores were additionally compared with scores from an age-matched population. Results. From January 1, 2013, until November 30, 2016, a total of 289 waitlisted patients were included. By September 1, 2017, 134 had reached 1 year postengraftment, and valid questionnaires were available in 120 (90%) patients. Mean age at KTx was 71.6 years (±4.3 years), 71% were male. Living donor was used in 21%, and preemptive KTx was performed in 30% of the recipients. Median waiting time for KTx from deceased donor was 16 months (range, 0.6-50.5 months). A total of 79 (66%) recipients had a Liu Comorbidity Index score of 3 or less. All HRQoL scores except the domain social function improved at 2 months postengraftment and remained stable or continued to improve at 1 year. HRQoL scores 12 months postengraftment were similar to those described in an age-matched general population except for the domain social function which remained at a significantly lower level. Time in dialysis was the most important variable associated with impaired HRQoL postengraftment. Conclusions. HRQoL scores showed clinically significant improvement in older KTx recipients 1 year posttransplant.

BACKGROUND AND AIM:Endothelial dysfunction is involved in the pathogenesis of atherosclerosis and is typically present in older adults with type 1 diabetes (T1D). In young adults, we aimed to assess the impact of T1D on endothelial function as detected by digital peripheral arterial tonometry (PAT) and its relationship with cardiovascular risk factors and long term glycemic control. MATERIALS AND METHODS:Reactive hyperemia index (RHI) as a measure of endothelial function was assessed by PAT in 46 T1D patients and 32 healthy controls. All were participants in the "Atherosclerosis and Childhood Diabetes" study, with baseline values registered five years previously. Annual measurements of HbA1c for assessment of glycemic burden were provided by the Norwegian Childhood Diabetes Registry. RESULTS:The diabetes patients had a mean age of 20.8 years, a median duration of diabetes of 10.0 years and a mean HbA1c of 8.7%. RHI was not significantly decreased in the diabetes group, mean 2.00 (SD = 0.59) vs. 2.21 (SD = 0.56), p = .116. There was no gender difference or any associations with traditional risk factors. Furthermore, there was no significant association between RHI and either HbA1c or long term glycemic burden. CONCLUSIONS:RHI as a measure of endothelial function was preserved in young adults with T1D compared with healthy controls.

BackgroundTreatment decisions for aortic valve replacement (AVR) should be sensitive to patient preferences. However, we lack knowledge of patient preferences and how to obtain them. Methods and ResultsWe assessed the mortality risk patients were willing to accept when undergoing AVR by using the Standard Gamble method and aimed to show how this risk willingness was affected by level of disease burden. We report findings from 439 patients, aged >18 years with severe aortic stenosis who were referred for evaluation of AVR to our institution. The vast majority of patients accepted a mortality risk regarded as high or prohibitive according to current guidelines. Of the 439 patients, 51% patients were willing to forego surgery with high mortality risk (8–50%) and 19% were willing accept a prohibitive mortality risk (>50%) as defined in current guidelines. However, the risk willingness varied considerably. Acceptance of prohibitive risk willingness (>50%) was associated with reporting of 3 to 5 different restricting symptoms, with an odds ratio of 4.07 (95% CI 1.56–10.59) opposed by increasing score on EuroQol–Visual Analog Scale, with an odds ratio of 0.99 (95% CI 0.97–1.00). The poor ability to predict risk willingness based on available clinical variables and health status suggests that other factors may be important advocating the need for tools for soliciting patient's preferences individually. ConclusionWhen undergoing AVR, patients were willing to accept considerably higher perioperative risk than what is considered acceptable in current guidelines and practice. Patient preferences varied considerably, and they should be directly assessed and taken into account in decision‐making and guidelines. Clinical Trial RegistrationURL: https://clinicaltrials.gov/. Unique identifier: NCT01794832.

Low vitamin D status has been associated with short-term (30-day) mortality in hospitalized adults with community-acquired pneumonia (CAP). Data on its prevalence in these patients are scarce, and impact on long-term prognosis is unknown. We examined the prevalence of vitamin D deficiency and inadequacy and their effect on long-term mortality in hospitalized adults with CAP.Secondary follow-up analysis of data from a prospectively recruited (January 2008-January 2011) well-defined cohort of 241 hospital survivors of CAP (Norway, latitude 60°N). Serum 25-hydroxyvitamin D levels, demographic, clinical, and laboratory data were measured within 48 hours of admission. The etiology of CAP was established in 63% of patients through extensive microbiological investigations. Mortality data were obtained from the national Cause of Death Registry. Explanatory strategy and Cox regression models were used to explore the association between vitamin D status and all-cause mortality.Median age was 66 years. Eighty-seven (36%) patients were vitamin D deficient (

Contributors to long-term mortality in patients with community-acquired pneumonia (CAP) remain unclear, with little attention paid to pneumonia etiology. We examined long-term survival, causes of death, and risk factors for long-term mortality in adult patients who had been hospitalized for CAP, with emphasis on demographic, clinical, laboratory, and microbiological characteristics.Two hundred and sixty-seven consecutive patients admitted in 2008-2011 to a general hospital with CAP were prospectively recruited and followed up. Patients who died during hospital stay were excluded. Demographic, clinical, and laboratory data were collected within 48 hours of admission. Extensive microbiological work-up was performed to establish the etiology of CAP in 63% of patients. Mortality data were obtained from the Norwegian Cause of Death Registry. Cox regression models were used to identify independent risk factors for all-cause mortality.Of 259 hospital survivors of CAP (median age 66 years), 79 (30.5%) died over a median of 1,804 days (range 1-2,520 days). Cumulative 5-year survival rate was 72.9% (95% CI 67.4-78.4%). Standardized mortality ratio was 2.90 for men and 2.05 for women. The main causes of death were chronic obstructive pulmonary disease (COPD), vascular diseases, and malignancy. Independent risk factors for death were the following (hazard ratio, 95% CI): age (1.83 per decade, 1.47-2.28), cardiovascular disease (2.63, 1.61-4.32), COPD (2.09, 1.27-3.45), immunocompromization (1.98, 1.17-3.37), and low serum albumin level at admission (0.75 per 5 g/L higher, 0.58-0.96), whereas active smoking was protective (0.32, 0.14-0.74); active smokers were younger than non-smokers (P < 0.001). Microbial etiology did not predict mortality.Results largely confirm substantial comorbidity-related 5-year mortality after hospitalization for CAP and the impact of several well-known risk factors for death, and extend previous findings on the prognostic value of serum albumin level at hospital admission. Pneumonia etiology had no prognostic value, but this remains to be substantiated by further studies using extensive diagnostic microbiological methods in the identification of causative agents of CAP.

Community-acquired urinary tract infection (CA-UTI) is the most common infection caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, but the clinical epidemiology of these infections in low prevalence countries is largely unknown. A population based case-control study was conducted to assess risk factors for CA-UTI caused by ESBL-producing E. coli or K. pneumoniae. The study was carried out in a source population in Eastern Norway, a country with a low prevalence of infections caused by ESBL-producing Enterobacteriaceae. The study population comprised 100 cases and 190 controls with CA-UTI caused by ESBL-producing and non-ESBL-producing E. coli or K. pneumoniae, respectively. The following independent risk factors of ESBL-positive UTIs were identified: Travel to Asia, The Middle East or Africa either during the past six weeks (Odds ratio (OR) = 21; 95% confidence interval (CI): 4.5-97) or during the past 6 weeks to 24 months (OR = 2.3; 95% CI: 1.1-4.4), recent use of fluoroquinolones (OR = 16; 95% CI: 3.2-80) and β-lactams (except mecillinam) (OR = 5.0; 95% CI: 2.1-12), diabetes mellitus (OR = 3.2; 95% CI: 1.0-11) and recreational freshwater swimming the past year (OR = 2.1; 95% CI: 1.0-4.0). Factors associated with decreased risk were increasing number of fish meals per week (OR = 0.68 per fish meal; 95% CI: 0.51-0.90) and age (OR = 0.89 per 5 year increase; 95% CI: 0.82-0.97). In conclusion, we have identified risk factors that elucidate mechanisms and routes for dissemination of ESBL-producing Enterobacteriaceae in a low prevalence country, which can be used to guide appropriate treatment of CA-UTI and targeted infection control measures.