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Objectives: Anal incontinence (AI) is a distressing condition with grave impact on many aspects of life, including quality of life (QoL), social life and sexual activities. This study explored how AI and bowel symptoms impact QoL in a Norwegian population by (1) describing the psychosocial and sexual consequences of AI, and (2) investigating factors most often associated with AI-specific QoL., Materials and Methods: A cross-sectional study among patients with AI referred to hospital outpatient clinics was conducted. A Norwegian version of ICIQ-B was used to measure bowel control, bowel symptoms, sexual impact, and impact on QoL., Results: A total of 208 persons with AI completed the questionnaire. The results demonstrated that these patients are overall embarrassed, make plans according to the bowels, ensure the presence of a nearby toilet, and many abstain from sexual activities. After adjusting for other variables included in a multivariable model, we found that having bowel accidents on one's mind had the greatest relative impact on QoL, followed by lower bowel control, using more medications to stop bowels, having more pain/soreness around the back passage, lower age, and more straining to open the bowels., Conclusions: AI has substantial consequences for the psychosocial function and sexual activities of persons with AI. This study indicates that worrying about potential faecal accidents and the social stigma associated with this have greater impact on QoL than actual bowel leakages. Future studies should therefore focus on the emotional burden, patient coping, and health education related to bowel function and AI.

Aim: To assess the effect of single botulinum neurotoxin A (BoNT-A) injections into the calf muscles on the gross energy cost of walking in children with cerebral palsy (CP) and to evaluate the effect of BoNT-A on walking capacity, physical activity, perceived changes in mobility, and pain., Method: This was an industry-independent, randomized, quadruple-blind, placebo-controlled, multicentre trial (ClinicalTrials.gov registration: NCT02546999). Sixty-one children (33 male, median age [range] = 8 years [4-16 years]) with spastic CP and classified in Gross Motor Function Classification System (GMFCS) levels I and II allocated to single injections of either BoNT-A or 0.9% saline into the calf muscles. The main outcome was gross energy cost (J/kg/m); secondary outcomes were walking capacity, habitual physical activity, perceived change in mobility tasks, and calf pain at baseline, 4 weeks (P1), 12 weeks (P2), and 24 weeks (P3) after the injection., Results: The mean change in energy cost did not differ significantly between groups at the primary time point P2 (-0.27 J/kg/m, 95% confidence interval - 0.91 to 0.36, p = 0.404), nor at P1 or P3. Regarding the secondary outcomes, there was some evidence of a larger reduction in pain intensity in the group given BoNT-A (p = 0.043)., Interpretation: One treatment with BoNT-A was not superior to placebo in making walking easier in children with CP classified in GMFCS levels I and II, at least in the short term. BoNT-A may have a pain-reducing effect., (© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Objectives: We analysed magnetic resonance imaging (MRI) findings after traumatic brain injury (TBI) aiming to improve the grading of traumatic axonal injury (TAI) to better reflect the outcome., Methods: Four-hundred sixty-three patients (8-70 years) with mild (n = 158), moderate (n = 129), or severe (n = 176) TBI and early MRI were prospectively included. TAI presence, numbers, and volumes at predefined locations were registered on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging, and presence and numbers on T2*GRE/SWI. Presence and volumes of contusions were registered on FLAIR. We assessed the outcome with the Glasgow Outcome Scale Extended. Multivariable logistic and elastic-net regression analyses were performed., Results: The presence of TAI differed between mild (6%), moderate (70%), and severe TBI (95%). In severe TBI, bilateral TAI in mesencephalon or thalami and bilateral TAI in pons predicted worse outcomes and were defined as the worst grades (4 and 5, respectively) in the Trondheim TAI-MRI grading. The Trondheim TAI-MRI grading performed better than the standard TAI grading in severe TBI (pseudo-R 2 0.19 vs. 0.16). In moderate-severe TBI, quantitative models including both FLAIR volume of TAI and contusions performed best (pseudo-R 2 0.19-0.21). In patients with mild TBI or Glasgow Coma Scale (GCS) score 13, models with the volume of contusions performed best (pseudo-R 2 0.25-0.26)., Conclusions: We propose the Trondheim TAI-MRI grading (grades 1-5) with bilateral TAI in mesencephalon or thalami, and bilateral TAI in pons as the worst grades. The predictive value was highest for the quantitative models including FLAIR volume of TAI and contusions (GCS score <13) or FLAIR volume of contusions (GCS score ≥ 13), which emphasise artificial intelligence as a potentially important future tool., Clinical Relevance Statement: The Trondheim TAI-MRI grading reflects patient outcomes better in severe TBI than today's standard TAI grading and can be implemented after external validation. The prognostic importance of volumetric models is promising for future use of artificial intelligence technologies., Key Points: Traumatic axonal injury (TAI) is an important injury type in all TBI severities. Studies demonstrating which MRI findings that can serve as future biomarkers are highly warranted. This study proposes the most optimal MRI models for predicting patient outcome at 6 months after TBI; one updated pragmatic model and a volumetric model. The Trondheim TAI-MRI grading, in severe TBI, reflects patient outcome better than today's standard grading of TAI and the prognostic importance of volumetric models in all severities of TBI is promising for future use of AI., (© 2024. The Author(s).)

Background: Identifying individuals with intracranial injuries following mild traumatic brain injury (mTBI), i.e. complicated mTBI cases, is important for follow-up and prognostication. The main aims of our study were (1) to assess the temporal evolution of blood biomarkers of CNS injury and inflammation in individuals with complicated mTBI determined on computer tomography (CT) and magnetic resonance imaging (MRI); (2) to assess the corresponding discriminability of both single- and multi-biomarker panels, from acute to chronic phases after injury., Methods: Patients with mTBI (n = 207), defined as Glasgow Coma Scale score between 13 and 15, loss of consciousness < 30 min and post-traumatic amnesia < 24 h, were included. Complicated mTBI - i.e., presence of any traumatic intracranial injury on neuroimaging - was present in 8% (n = 16) on CT (CT+) and 12% (n = 25) on MRI (MRI+). Blood biomarkers were sampled at four timepoints following injury: admission (within 72 h), 2 weeks (± 3 days), 3 months (± 2 weeks) and 12 months (± 1 month). CNS biomarkers included were glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and tau, along with 12 inflammation markers., Results: The most discriminative single biomarkers of traumatic intracranial injury were GFAP at admission (CT+: AUC = 0.78; MRI+: AUC = 0.82), and NFL at 2 weeks (CT+: AUC = 0.81; MRI+: AUC = 0.89) and 3 months (MRI+: AUC = 0.86). MIP-1β and IP-10 concentrations were significantly lower across follow-up period in individuals who were CT+ and MRI+. Eotaxin and IL-9 were significantly lower in individuals who were MRI+ only. FGF-basic concentrations increased over time in MRI- individuals and were significantly higher than MRI+ individuals at 3 and 12 months. Multi-biomarker panels improved discriminability over single biomarkers at all timepoints (AUCs > 0.85 for admission and 2-week models classifying CT+ and AUC ≈ 0.90 for admission, 2-week and 3-month models classifying MRI+)., Conclusions: The CNS biomarkers GFAP and NFL were useful single diagnostic biomarkers of complicated mTBI, especially in acute and subacute phases after mTBI. Several inflammation markers were suppressed in patients with complicated versus uncomplicated mTBI and remained so even after 12 months. Multi-biomarker panels improved diagnostic accuracy at all timepoints, though at acute and 2-week timepoints, the single biomarkers GFAP and NFL, respectively, displayed similar accuracy compared to multi-biomarker panels., (© 2024. The Author(s).)

The aim of our study was to investigate the biological underpinnings of persistent post-concussion symptoms (PPCS) at 3 months following mild traumatic brain injury (mTBI). Patients ( n  = 192, age 16-60 years) with mTBI, defined as Glasgow Coma Scale (GCS) score between 13 and 15, loss of consciousness (LOC) <30 min, and post-traumatic amnesia (PTA) <24 h were included. Blood samples were collected at admission (within 72 h), 2 weeks, and 3 months. Concentrations of blood biomarkers associated with central nervous system (CNS) damage (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], and tau) and inflammation (interferon gamma [IFNγ], interleukin [IL]-8, eotaxin, macrophage inflammatory protein-1-beta [MIP]-1β, monocyte chemoattractant protein [MCP]-1, interferon-gamma-inducible protein [IP]-10, IL-17A, IL-9, tumor necrosis factor [TNF], basic fibroblast growth factor [FGF]-basic platelet-derived growth factor [PDGF], and IL-1 receptor antagonist [IL-1ra]) were obtained. Demographic and injury-related factors investigated were age, sex, GCS score, LOC, PTA duration, traumatic intracranial finding on magnetic resonance imaging (MRI; within 72 h), and extracranial injuries. Delta values, that is, time-point differences in biomarker concentrations between 2 weeks minus admission and 3 months minus admission, were also calculated. PPCS was assessed with the British Columbia Post-Concussion Symptom Inventory (BC-PSI). In single variable analyses, longer PTA duration and a higher proportion of intracranial findings on MRI were found in the PPCS group, but no single biomarker differentiated those with PPCS from those without. In multi-variable models, female sex, longer PTA duration, MRI findings, and lower GCS scores were associated with increased risk of PPCS. Inflammation markers, but not GFAP, NFL, or tau, were associated with PPCS. At admission, higher concentrations of IL-8 and IL-9 and lower concentrations of TNF, IL-17a, and MCP-1 were associated with greater likelihood of PPCS; at 2 weeks, higher IL-8 and lower IFNγ were associated with PPCS; at 3 months, higher PDGF was associated with PPCS. Higher delta values of PDGF, IL-17A, and FGF-basic at 2 weeks compared with admission, MCP-1 at 3 months compared with admission, and TNF at 2 weeks and 3 months compared with admission were associated with greater likelihood of PPCS. Higher IL-9 delta values at both time-point comparisons were negatively associated with PPCS. Discriminability of individual CNS-injury and inflammation biomarkers for PPCS was around chance level, whereas the optimal combination of biomarkers yielded areas under the curve (AUCs) between 0.62 and 0.73. We demonstrate a role of biological factors on PPCS, including both positive and negative effects of inflammation biomarkers that differed based on sampling time-point after mTBI. PPCS was associated more with acute inflammatory processes, rather than ongoing inflammation or CNS-injury biomarkers. However, the modest discriminative ability of the models suggests other factors are more important in the development of PPCS.

Background: Referrals to specialised mental health care (such as community mental health centres; CMHC) have increased over the last two decades. Patients often have multifaceted problems, which cannot only be solved by such care. Resources are limited, and triaging is challenging. A novel method which approaches patients early and individually upon referral to a CMHC-possibly with a brief intervention-is an Early assessment Team (EaT). In an EaT, two therapists meet the patient early in the process and seek to solve the present problem, often involving community services, primary health care, etc.; attention is paid to symptoms and functional strife, rather than diagnoses. This is in contrast to treatment as usual (TAU), where the patient (after being on a waiting list) meets one therapist, who focuses on history and situation to assign a diagnosis and eventually start a longitudinal treatment. The aim of this study is to describe and compare EaT and TAU regarding such outcomes as work and social adjustment, mental health, quality of life, use of health services, and patient satisfaction. The primary outcome is a change in perceived function from baseline to 12-month follow-up, measured by the Work and Social Adjustment Scale., Method: Patients (18 years and above; n = 588) referred to outpatient health care at a CMHC are randomised to EaT or TAU. Measures (patient self-reports and clinician reports, patients' records, and register data) are collected at baseline, after the first and last meeting, and at 2, 4, 8, 12, and 24 months after inclusion. Some participants will be invited to participate in qualitative interviews., Trial Design: The study is a single-centre, non-blinded, RCT with two conditions involving a longitudinal and mixed design (quantitative and qualitative data)., Discussion: This study will examine an intervention designed to determine early on which patients will benefit from parallel or other measures than assessment and treatment in CMHC and whether these will facilitate their recovery. Findings may potentially contribute to the development of the organisation of mental health services., Trial Registration: ClinicalTrials.gov NCT05087446. Registered on 21 October 2021., (© 2024. The Author(s).)

The aims of this study were (1) to report outcome and change in outcome in patients with moderate and severe traumatic brain injury (mo/sTBI) between 6 and 12 months post-injury as measured by the Glasgow Outcome Scale Extended (GOSE), (2) to explore if demographic/injury-related variables can predict improvement in GOSE score, and (3) to investigate rate of improvement in Disability Rating Scale (DRS) score, in patients with a stable GOSE. All surviving patients ≥16 years of age who were admitted with mo/sTBI (Glasgow Coma Scale [GCS] score ≤13) to the regional trauma center in Central Norway between 2004 and 2019 were prospectively included ( n  = 439 out of 503 eligible). GOSE and DRS were used to assess outcome. Twelve-months post-injury, 13% with moTBI had severe disability (GOSE 2-4) versus 27% in sTBI, 26% had moderate disability (GOSE 5-6) versus 41% in sTBI and 62% had good recovery (GOSE 7-8) versus 31% in sTBI. From 6 to 12 months post-injury, 27% with moTBI and 32% with sTBI had an improvement, whereas 6% with moTBI and 6% with sTBI had a deterioration in GOSE score. Younger age and higher GCS score were associated with improved GOSE score. Improvement was least frequent for patients with a GOSE score of 3 at 6 months. In patients with a stable GOSE score of 3, an improvement in DRS score was observed in 22 (46%) patients. In conclusion, two thirds and one third of patients with mo/sTBI, respectively, had a good recovery. Importantly, change, mostly improvement, in GOSE score between 6 and 12 months was frequent and argues against the use of 6 months outcome as a time end-point in research. The GOSE does, however, not seem to be sensitive to actual change in function in the lower categories and a combination of outcome measures may be needed to describe the consequences after TBI., Competing Interests: No competing financial interests exist., (© Rabea Iris Pantelatos et al., 2024; Published by Mary Ann Liebert, Inc.)

Background: It is estimated that more than 57 million people have dementia worldwide, and it is one of the leading causes of care dependency in old age. Relatives and other informal caregivers are the most important support for individuals with dementia, but caring for a loved one with dementia may burden the caregiver. Caregiver burden may have adverse outcomes for both the informal caregiver and the care recipient, including decreased quality of life. Caregiver burden is associated with several factors concerning the informal caregiver, the care recipient, and relational and other contextual factors. The aim of this study was to explore which factors are associated with informal caregivers' subjective burden when caring for individuals living at home with dementia., Methods: This study was a cross-sectional survey among informal caregivers of home-dwelling individuals with dementia in all five geographical regions of Norway. There were 540 informal caregivers who participated, 415 of whom were included in the regression analyses. Caregivers' subjective burden was assessed with the Relatives' Stress Scale. Covariates included were classified into four levels: individual (twofold: informal caregiver and person with dementia), relational, community, and time. Linear multivariable regression analyses were used to identify associations between subjective burden and included factors., Results: Several covariates were statistically significantly associated with subjective burden at the four levels. These covariates included self-rated health, mental distress, age, coping through resignation and denial, emotional and instrumental support, substance use, and humor at the informal caregiver level; behavioral and psychological symptoms of dementia, dementia severity, and degree of disability at the care recipient level; the extent of care, being the primary caregiver, and previous relationship satisfaction at the relational context level; and informal caregivers spending time with friends, leisure activities, social restriction, and knowledge of available health services at the community context level., Conclusions: Informal caregivers' mental distress and care recipients' neuropsychiatric symptoms were the factors with the strongest association with subjective burden., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Gestational diabetes mellitus (GDM) is associated with increased risk for type 2 diabetes in the mother and cardiometabolic diseases in the child. The preconception period is an optimal window to adapt the lifestyle for improved outcomes for both mother and child. Our aim is to determine the effect of a lifestyle intervention, initiated before and continued throughout pregnancy, on maternal glucose tolerance and other maternal and infant cardiometabolic outcomes., Methods and Analysis: This ongoing randomised controlled trial has included 167 females aged 18-39 years old at increased risk for GDM who are contemplating pregnancy. The participants were randomly allocated 1:1 to an intervention or control group. The intervention consists of exercise (volume is set by a heart rate-based app and corresponds to ≥ 1 hour of weekly exercise at ≥ 80% of individual heart rate maximum), and time-restricted eating (≤ 10 hours/day window of energy intake). The primary outcome measure is glucose tolerance in gestational week 28. Maternal and offspring outcomes are measured before and during pregnancy, at delivery, and at 6-8 weeks post partum. Primary and secondary continuous outcome measures will be compared between groups based on the 'intention to treat' principle using linear mixed models., Ethics and Dissemination: The Regional Committees for Medical and Health Research Ethics in Norway has approved the study (REK 143756). The anonymised results will be submitted for publication and posted in a publicly accessible database of clinical study results., Trial Registration Number: Clinical trial gov NCT04585581., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Systemic lupus erythematosus (SLE) pregnancies are considered high-risk due to risk of disease flare and pregnancy complications. A more in-depth understanding of the immunological alterations in SLE patients during pregnancy and identification of predictive biomarkers may help to achieve stable disease and to avoid pregnancy complications. Lipocalin-2 (LCN2) has been implicated as a potential biomarker for rheumatic diseases and preeclampsia, but remains unexplored in SLE pregnancies., Methods: We measured LCN2 levels in serum samples from SLE pregnancies (n=25) at seven different time points. Samples were taken preconception, in each trimester, at 6 weeks, 6 months and 12 months postpartum. Serum LCN2 levels were compared to samples from rheumatoid arthritis (RA) (n=27) and healthy (n=18) pregnancies at each time point using t-test, and for all time points using a linear mixed effects model. In addition, we investigated the association between LCN2 levels and disease activity, CRP, kidney function, BMI, treatment regimen and adverse pregnancy outcome for SLE and RA patients., Results: We found significantly lower serum LCN2 levels throughout pregnancy in SLE patients with quiescent disease compared to RA and healthy pregnancies. We did not find an association between serum LCN2 and disease activity or adverse pregnancy outcome in SLE pregnancies., Conclusions: In a population of SLE women with low disease activity we have not found evidence that serum LCN2 levels predict disease activity or adverse pregnancy outcomes. Further studies are needed to elucidate a possible biological role of low LCN2 levels in SLE pregnancies.

Background: There are various methods of respiratory support available to optimize respiratory function in preterm infants. Respiratory scoring tools might provide information on which method to choose and the level and duration of support needed. Before implementing a respiratory scoring tool in our clinical practice, we aimed to test the inter- and intra-rater reliability of the Silverman and Andersen index (SA index) among neonatologists and nurses when applied to preterm infants on respiratory support. We also examined the association between the SA index and the electrical activity of the diaphragm (Edi signals)., Methods: This was a multicenter study including three newborn intensive care units in Norway. Four neonatologists and 10 nurses applied the SA index when assessing 80 videos of 44 preterm infants on High Flow Nasal Cannula, Continuous Positive Airway Pressure and Neurally Adjusted Ventilatory Assist. The inter- and intra-rater reliability for the sum scores were measured by the intra-class correlation coefficient (ICC), and Kendall's W was used to assess the degree of agreement for each item. We quantified the association between the Edi signals and the SA index scores by the Spearman's correlation coefficient., Results: We found poor inter-rater reliability with an ICC for absolute agreement of 0.34 (95% CI: 0.20 to 0.53). There was fair agreement measuring each item separately for upper chest movements (Kendall's W 0.30), and moderate for lower chest movements (0.43) and xiphoid retractions (0.44). Expiratory grunting showed substantial agreement (0.67). The intra-rater reliability was good (ICC for absolute agreement 0.77; 95% CI: 0.68 to 0.84). We found a moderate positive correlation (r = 0.468, p = 0.028) between the maximum inspiratory diaphragm activity (Edi peak) and the mean inspiratory SA index scores., Conclusion: Our study showed poor inter-rater and good intra-rater reliability of the SA index when nurses and neonatologists assessed videos of preterm infants on various types of respiratory support. Edi peak and SA index had a moderate positive correlation. Formal training might be essential to improve the inter-rater reliability., Trial Registration: Registered 26th June 2017, ClinicalTrials.gov Identifier: NCT03199898., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Brenne et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: General anaesthesia is associated with neurocognitive deficits in infants after noncardiac surgery. Disturbances in cerebral perfusion as a result of systemic hypotension and impaired autoregulation may be a potential cause. Our aim was to study cerebral blood flow (CBF) velocity continuously during general anaesthesia in infants undergoing noncardiac surgery and compare variations in CBF velocity with simultaneously measured near-infrared spectroscopy (NIRS), blood pressure, and heart rate., Methods: NeoDoppler, a recently developed ultrasound system, was used to monitor CBF velocity via the anterior fontanelle during induction and maintenance of general anaesthesia until the start of surgery, and during recovery. NIRS, blood pressure, and heart rate were monitored simultaneously and synchronised with the NeoDoppler measurements., Results: Thirty infants, with a median postmenstrual age at surgery of 37.6 weeks (range 28.6-60.0) were included. Compared with baseline, the trend curves showed a decrease in CBF velocity during induction and maintenance of anaesthesia and returned to baseline values during recovery. End-diastolic velocity decreased in all infants during anaesthesia, on average by 59%, whereas peak systolic- and time-averaged velocities decreased by 26% and 45%, respectively. In comparison, the reduction in mean arterial pressure was only 20%. NIRS values were high and remained stable. When adjusting for mean arterial pressure, the significant decrease in end-diastolic velocity persisted, whereas there was only a small reduction in peak systolic velocity., Conclusions: Continuous monitoring of CBF velocity using NeoDoppler during anaesthesia is feasible and may provide valuable information about cerebral perfusion contributing to a more targeted haemodynamic management in anaesthetised infants., (© 2023 The Author(s).)

Lipid-rich coronary atherosclerotic plaques often cause myocardial infarction (MI), and circulating biomarkers that reflect lipid content may predict risk of MI. We investigated the association between circulating microRNAs (miRs) are lipid-rich coronary plaques in 47 statin-treated patients (44 males) with stable coronary artery disease undergoing percutaneous coronary intervention. We assessed lipid content in non-culprit coronary artery lesions with near-infrared spectroscopy and selected the 4 mm segment with the highest measured lipid core burden index (maxLCBI 4mm ). Lipid-rich plaques were predefined as a lesion with maxLCBI 4mm  ≥ 324.7. We analyzed 177 circulating miRs with quantitative polymerase chain reaction in plasma samples. The associations between miRs and lipid-rich plaques were analyzed with elastic net. miR-133b was the miR most strongly associated with lipid-rich coronary plaques, with an estimated 18% increase in odds of lipid-rich plaques per unit increase in miR-133b. Assessing the uncertainty by bootstrapping, miR-133b was present in 82.6% of the resampled dataset. Inclusion of established cardiovascular risk factors did not attenuate the association. No evidence was found for an association between the other analyzed miRs and lipid-rich coronary plaques. Even though the evidence for an association was modest, miR-133b could be a potential biomarker of vulnerable coronary plaques and risk of future MI. However, the prognostic value and clinical relevance of miR-133b needs to be assessed in larger cohorts., (© 2023. The Author(s).)

Background: Lipid content in coronary atheromatous plaques, measured by near-infrared spectroscopy (NIRS), can predict the risk of future coronary events. Biomarkers that reflect lipid content in coronary plaques may therefore improve coronary artery disease (CAD) risk assessment., Purpose: We aimed to investigate the association between circulating lipoprotein subfractions and lipid content in coronary atheromatous plaques in statin-treated patients with stable CAD undergoing percutaneous coronary intervention., Methods: 56 patients with stable CAD underwent three-vessel imaging with NIRS when feasible. The coronary artery segment with the highest lipid content, defined as the maximum lipid core burden index within any 4 mm length across the entire lesion (maxLCBI 4mm ), was defined as target segment. Lipoprotein subfractions and Lipoprotein a (Lp(a)) were analyzed in fasting serum samples by nuclear magnetic resonance spectroscopy and by standard in-hospital procedures, respectively. Penalized linear regression analyses were used to identify the best predictors of maxLCBI 4mm . The uncertainty of the lasso estimates was assessed as the percentage presence of a variable in resampled datasets by bootstrapping., Results: Only modest evidence was found for an association between lipoprotein subfractions and maxLCBI 4mm . The lipoprotein subfractions with strongest potential as predictors according to the percentage presence in resampled datasets were Lp(a) (78.1 % presence) and free cholesterol in the smallest high-density lipoprotein (HDL) subfractions (74.3 % presence). When including established cardiovascular disease (CVD) risk factors in the regression model, none of the lipoprotein subfractions were considered potential predictors of maxLCBI 4mm ., Conclusion: In this study, serum levels of Lp(a) and free cholesterol in the smallest HDL subfractions showed the strongest potential as predictors for lipid content in coronary atheromatous plaques. Although the evidence is modest, our study suggests that measurement of lipoprotein subfractions may provide additional information with respect to coronary plaque composition compared to traditional lipid measurements, but not in addition to established risk factors. Further and larger studies are needed to assess the potential of circulating lipoprotein subfractions as meaningful biomarkers both for lipid content in coronary atheromatous plaques and as CVD risk markers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: To determine the impact of cognitive function on physical activity (PA), physical function and health-related quality of life (HRQoL) in older adults within the first year after hip fracture (HF) surgery., Methods: We included 397 home-dwelling individuals aged 70 years or older with the ability to walk 10 m before the fracture. Cognitive function was measured at 1 month and other outcomes were assessed at 1, 4 and 12 months postoperatively. Mini-Mental State Examination was used to assess cognitive function, accelerometer-based body-worn sensors to register PA, Short Physical Performance Battery to test physical function and EuroQol-5-dimension-3-level to estimate the HRQoL. Data were analysed by linear mixed-effects models with interactions and ordinal logistic regression models., Results: Cognitive function, adjusted for the pre-fracture ability to perform activities of daily living, comorbidity, age and gender, had an impact on PA [b = 3.64, 95% confidence interval (CI): 2.20-5.23, P < 0.001] and physical function (b = 0.08, 95% CI: 0.04-0.11, P < 0.001; b = 0.12, 95% CI: 0.09-0.15, P < 0.001; and b = 0.14, 95% CI: 0.10-0.18, P < 0.001 at 1, 4 and 12 months, respectively). The cognitive function did not have a considerable impact on HRQoL., Conclusions: For older adults with HFs, cognitive function 1 month postoperatively had a significant impact on PA and physical function in the first postoperative year. For the HRQoL, little or no evidence of such an effect was found., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Coronary atheroma volume is associated with risk of coronary events in coronary artery disease (CAD). Exercise training is a cornerstone in primary and secondary prevention of CAD, but the effect of exercise on coronary atheromatous plaques is largely unknown. We assessed the effect of 6 months supervised high-intensity interval training (HIIT) on coronary plaque geometry using intravascular ultrasound in patients with stable CAD following percutaneous coronary intervention (PCI)., Methods and Results: Sixty patients were randomized to two sessions of weekly supervised HIIT at 85-95% of peak heart rate (n = 30) or to follow contemporary preventive guidelines (control group, n = 30). The study endpoints were change in percent atheroma volume (PAV) and total atheroma volume (TAV) normalized for segment length (TAVnorm) at 6-month follow-up. The change in average PAV for matched coronary segments from baseline to follow-up showed a significant between-group difference (-1.4, 95% CI: -2.7 to -0.1, P = 0.036). There was a significant reduction in the HIIT group (-1.2, 95% CI: -2.1 to -0.2, P = 0.017) while not in the control group (0.2, 95% CI: -0.7 to 1.1, P = 0.616). TAVnorm was reduced (-9 mm3, 95% CI: -14.7 to -3.4, P = 0.002) after HIIT, with a significant between-group difference (-12.0 mm3, 95% CI: -19.9 to -4.2, P = 0.003)., Conclusion: In patients with established CAD, a regression of atheroma volume was observed in those undergoing 6 months of supervised HIIT compared with patients following contemporary preventive guidelines. Our study indicates that HIIT counteracts atherosclerotic coronary disease progression and reduces atheroma volume in residual coronary atheromatous plaques following PCI., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Anti-vascular endothelial growth factor is a medicine administered intravitreally by an injection to maintain visual acuity in patients with a variety of retinal diseases. The demand for this treatment has grown considerably in the westernized world the last two decades and will continue to increase due to an aging population. Because of the high volume, injections seize enormous resources and represent high costs for both hospitals and society. Task-shifting of injections from physicians to nurses may be a means to reduce such costs, however the magnitude of possible savings has been poorly investigated. To this end we investigated changes in the hospital costs per injection, six-year cost projections of physician- versus nurse-administered injections for a Norwegian tertiary hospital and we compared the societal costs per patient per year., Methods: Patients (n = 318) were randomized to either physician- or nurse administered injections, and data were prospectively collected. Hospital costs per injection were calculated as the sum of training costs, personnel time and running expenses. The number of injections for the years 2014 - 21 from a Norwegian tertiary hospital was combined with age group specific injection prevalence and population projections to calculate cost projections for 2022 - 27. Societal costs per patient were calculated as the sum of hospital costs, transport costs for patients, caregivers' use of time, costs of ophthalmology consultations and community-based homecare., Results: The hospital costs per injection were 5.5 € higher for physicians compared to nurses (281.6 € versus 276.1 €). Cost projections estimated an annual hospital saving of task-shifting of 48 921 € for 2022 - 27. Societal costs per patient did not differ significantly between the two groups (mean 4988 € vs 5418 €, p = 0.398)., Conclusion: Task-shifting of injections from physicians to nurses can reduce hospital costs and increase the flexibility of physician resources. The annual savings are modest, but increased demand for injections might increase future cost savings. To achieve future savings for society, organizing ophthalmology consultations and injections on the same day to reduce the number of visits might be a solution., Trial Registration: ClinicalTrials.gov NCT02359149 (09/02/2015)., (© 2023. The Author(s).)

One in six community-dwelling older adults experience elder abuse yearly, and persons with dementia are especially at risk. Although many risk factors for elder abuse have been identified, there are still knowledge gaps concerning risk and protective factors. This cross-sectional survey among Norwegian informal caregivers (ICGs) aimed to find individual, relational, and community factors associated with psychological and physical abuse of home-dwelling persons with dementia. This study involved 540 ICGs and was conducted from May to December 2021. Statistical analysis using penalized logistic regression with lasso was performed to find covariates associated with psychological and physical elder abuse. The most prominent risk factor for both subtypes of abuse was the caregiver being a spouse. In addition, risk factors for psychological abuse were having a higher caregiver burden, experiencing psychological aggression from the person with dementia, and the person with dementia being followed up by their general practitioner. For physical abuse, the protective factors were the ICG being female and having an assigned personal municipal health service contact, while the risk factors were the ICG attending a caregiver training program and experiencing physical aggression from the person with dementia and the person with dementia having a higher degree of disability. These findings add to the existing knowledge of risk and protective factors in elder abuse among home-dwelling persons with dementia. This study provides relevant knowledge for healthcare personnel working with persons with dementia and their caregivers and for the development of interventions to prevent elder abuse.

Rationale: To describe cardiopulmonary function during exercise 12 months after hospital discharge for coronavirus disease 2019 (COVID-19), assess the change from 3 to 12 months, and compare the results with matched controls without COVID-19., Methods: In this prospective, longitudinal, multicentre cohort study, hospitalised COVID-19 patients were examined using a cardiopulmonary exercise test (CPET) 3 and 12 months after discharge. At 3 months, 180 performed a successful CPET, and 177 did so at 12 months (mean age 59.3 years, 85 females). The COVID-19 patients were compared with controls without COVID-19 matched for age, sex, body mass index and comorbidity. Main outcome was peak oxygen uptake ( V ' O 2  peak )., Results: Exercise intolerance ( V ' O 2  peak <80% predicted) was observed in 23% of patients at 12 months, related to circulatory (28%), ventilatory (17%) and other limitations including deconditioning and dysfunctional breathing (55%). Estimated mean difference between 3 and 12 months showed significant increases in V ' O 2  peak % pred (5.0 percentage points (pp), 95% CI 3.1-6.9 pp; p<0.001), V ' O 2  peak ·kg -1 % pred (3.4 pp, 95% CI 1.6-5.1 pp; p<0.001) and oxygen pulse % pred (4.6 pp, 95% CI 2.5-6.8 pp; p<0.001). V ' O 2  peak was 2440 mL·min -1 in COVID-19 patients compared to 2972 mL·min -1 in matched controls., Conclusions: 1 year after hospital discharge for COVID-19, the majority (77%), had normal exercise capacity. Only every fourth had exercise intolerance and in these circulatory limiting factors were more common than ventilator factors. Deconditioning was common. V ' O 2  peak and oxygen pulse improved significantly from 3 months., Competing Interests: Conflict of interest: C.B. Ingul has received lecture fees from Bayer AS, unrelated to the current study. I. Skjørten has provided lectures for doctors’ education paid by Norwegian Directorate of Health and Norwegian Medical Association. G. Einvik has received research grants from AstraZeneca to perform the current study. A. Edvardsen has received payment or honoraria for lectures, presentations or educational events from GlaxoSmithKline and Chiesi. K. Stavem has received consulting fees from UCB Pharma and MSD, unrelated to the present study. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: A cerebroprotective effect of low frequency oscillations (LFO) in cerebral blood flow (CBF) has been suggested in adults, but its significance in neonates is not known. This observational study evaluates normal arterial and venous cerebral blood flow in healthy neonates using NeoDoppler, a novel Doppler ultrasound system which can measure cerebral hemodynamics continuously., Method: Ultrasound Doppler data was collected for 2 h on the first and second day of life in 36 healthy term born neonates. LFO (0.04-0.15 Hz) were extracted from the velocity curve by a bandpass filter. An angle independent LFO index was calculated as the coefficient of variation of the filtered curve. Separate analyses were done for arterial and venous signals, and results were related to postnatal age and behavioral state (asleep or awake)., Results: The paper describes normal physiologic variations of arterial and venous cerebral hemodynamics. Mean (SD) arterial and venous LFO indices (%) were 6.52 (2.55) and 3.91 (2.54) on day one, and 5.60 (1.86) and 3.32 (2.03) on day two. After adjusting for possible confounding factors, the arterial LFO index was estimated to decrease by 0.92 percent points per postnatal day ( p  < 0.001). The venous LFO index did not change significantly with postnatal age ( p  = 0.539). Arterial and venous LFO were not notably influenced by behavioral state., Conclusion: The results indicate that arterial LFO decrease during the first 2 days of life in healthy neonates. This decrease most likely represents normal physiological changes related to the transitional period. A similar decrease for venous LFO was not found., Competing Interests: NTNU and St. Olavs Hospital may benefit financially from a commercialization of the US equipment through future possible intellectual properties; this may include financial benefits to authors of this article. HT, RS and SN are co-inventors of NeoDoppler. HT and SN have a part time position in CIMON medical, the company that is responsible for commercialization of NeoDoppler. HT and SN are among the shareholders and SN is board member in CIMON medical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Ødegård, Torp, Follestad, Leth-Olsen, Støen and Nyrnes.)

Background The effect of physical exercise on lipid content of coronary artery plaques is unknown. With near infrared spectroscopy we measured the effect of high intensity interval training (HIIT) on lipid content in coronary plaques in patients with stable coronary artery disease following percutaneous coronary intervention. Methods and Results In CENIT (Impact of Cardiac Exercise Training on Lipid Content in Coronary Atheromatous Plaques Evaluated by Near-Infrared Spectroscopy) 60 patients were randomized to 6 months supervised HIIT or to a control group. The primary end point was change in lipid content measured as maximum lipid core burden index at 4 mm (maxLCBI 4mm ). A predefined cutoff of maxLCBI 4mm >100 was required for inclusion in the analysis. Forty-nine patients (HIIT=20, usual care=29) had maxLCBI 4mm >100 at baseline. Change in maxLCBI 4mm did not differ between groups (-1.2, 95% CI, -65.8 to 63.4, P =0.97). The estimated reduction in maxLCBI 4mm was -47.7 (95% CI, -100.3 to 5.0, P =0.075) and -46.5 (95% CI, -87.5 to -5.4, P =0.027) after HIIT and in controls, respectively. A negative correlation was observed between change in peak oxygen uptake (VO 2peak ) and change in lipid content (Spearman's correlation -0.44, P =0.009). With an increase in VO 2peak above 1 metabolic equivalent task, maxLCBI 4mm was on average reduced by 142 (-8 to -262), whereas the change was -3.2 (154 to -255) with increased VO 2peak below 1 metabolic equivalent task. Conclusions Six months of HIIT following percutaneous coronary intervention did not reduce lipid content in coronary plaques compared with usual care. A moderate negative correlation between increase in VO 2peak and change in lipid content generates the hypothesis that exercise with a subsequent increase in fitness may reduce lipid content in coronary atheromatous plaques. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02494947.

Background The extent of cardiac dysfunction post-COVID-19 varies, and there is a lack of data on arrhythmic burden. Methods and Results This was a combined multicenter prospective cohort study and cross-sectional case-control study. Cardiac function assessed by echocardiography in patients with COVID-19 3 to 4 months after hospital discharge was compared with matched controls. The 24-hour ECGs were recorded in patients with COVID-19. A total of 204 patients with COVID-19 consented to participate (mean age, 58.5 years; 44% women), and 204 controls were included (mean age, 58.4 years; 44% women). Patients with COVID-19 had worse right ventricle free wall longitudinal strain (adjusted estimated mean difference, 1.5 percentage points; 95% CI, -2.6 to -0.5; P =0.005) and lower tricuspid annular plane systolic excursion (-0.10 cm; 95% CI, -0.14 to -0.05; P <0.001) and cardiac index (-0.26 L/min per m 2 ; 95% CI, -0.40 to -0.12; P <0.001), but slightly better left ventricle global strain (-0.8 percentage points; 95% CI, 0.2-1.3; P =0.008) compared with controls. Reduced diastolic function was twice as common compared with controls (60 [30%] versus 29 [15%], respectively; odds ratio, 2.4; P =0.001). Having dyspnea or fatigue were not associated with cardiac function. Right ventricle free wall longitudinal strain was worse after intensive care treatment. Arrhythmias were found in 27% of the patients, mainly premature ventricular contractions and nonsustained ventricular tachycardia (18% and 5%, respectively). Conclusions At 3 months after hospital discharge with COVID-19, right ventricular function was mildly impaired, and diastolic dysfunction was twice as common compared with controls. There was little evidence for an association between cardiac function and intensive care treatment, dyspnea, or fatigue. Ventricular arrhythmias were common, but the clinical importance is unknown. Registration URL: http://clinicaltrials.gov. Unique Identifier: NCT04535154.

Objective: The primary aim of this study was to evaluate the global outcome longitudinally over 5 years in children and adolescents surviving moderate to severe traumatic brain injury (msTBI) to investigate changes in outcome over time. The secondary aim was to explore how age at the time of injury affected outcome., Methods: All children and adolescents (aged 0-17 years; subdivided into children aged 0-10 years and adolescents aged 11-17 years) with moderate (Glasgow Coma Scale [GCS] score 9-13) or severe (GCS score ≤ 8) TBI who were admitted to a level I trauma center in Norway over a 10-year period (2004-2014) were prospectively included. In addition, young adults (aged 18-24 years) with msTBI were included for comparison. Outcome was assessed with the Glasgow Outcome Scale-Extended (GOS-E) at 6 months, 12 months, and 5 years after injury. The effect of time since injury and age at injury on the probability of good outcome was estimated by the method of generalized estimating equations., Results: A total of 30 children, 39 adolescents, and 97 young adults were included, among which 24 children, 38 adolescents, and 76 young adults survived and were planned for follow-up. In-hospital mortality from TBI was 7% for children, 3% for adolescents, and 18% for young adults. In surviving patients at the 5-year follow-up, good recovery (GOS-E score 7 or 8) was observed in 87% of children and all adolescents with moderate TBI, as well as in 44% of children and 59% of adolescents with severe TBI. No patient remained in a persistent vegetative state. For all patients, the odds for good recovery increased from 6 to 12 months (OR 1.79, 95% CI 1.15-2.80; p = 0.010), although not from 12 months to 5 years (OR 0.98, 95% CI 0.62-1.55; p = 0.940). Children/adolescents (aged 0-17 years) had higher odds for good recovery than young adults (OR 2.86, 95% CI 1.26-6.48; p = 0.012)., Conclusions: In this population-based study of pediatric msTBI, surprisingly high rates of good recovery over 5 years were found, including good recovery for a large majority of children and all adolescents with moderate TBI. Less than half of the children and more than half of the adolescents with severe TBI had good outcomes. The odds for good recovery increased from 6 to 12 months and were higher in children/adolescents (aged 0-17 years) than in young adults.

Some people experience persistent post-concussion symptoms (PPCS) after mild traumatic brain injury (mTBI). A meaningful clinical classification and scientific progress are hampered by a lack of consensus regarding the phenomenology, assessment, and operationalization of PPCS. Here we demonstrate and evaluate how the methodology used to assess and define persistent symptoms after mTBI influences PPCS as a binary outcome. We present empirical data from 15 classification methods reflecting procedures found in the literature and clinical practice. In total, 221 patients with mTBI, 73 patients with orthopedic injuries, and 77 community controls were included in the study. The prevalence rate of PPCS in the mTBI group varied between 10% and 47%, depending on the method used to assess and define unfavorable outcome. There was generally low positive agreement between the different methods; even the two methods yielding the most similar prevalence rates (89.2% overall proportion agreement) agreed on less than half (45.5% positive agreement) of the PPCS cases. Using a liberal but not uncommon threshold for symptom severity, there was a considerable misclassification rate of PPCS in both comparison groups. Our results highlight the importance for researchers to be aware of the limitations of using binary approaches for classification of PPCS. The poor agreement between methods should be considered when (1) interpreting the heterogeneity in the existing PPCS literature and (2) developing new improved methods. An empirically informed consensus regarding classification of PPCS should be a priority for the research community., Competing Interests: Grant Iverson serves as a scientific advisor for NanoDx™, Sway Operations, LLC, and Highmark, Inc. He has a clinical and consulting practice in forensic neuropsychology, including expert testimony, involving individuals who have sustained mTBIs. He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs, and Psychological Assessment Resources (PAR, Inc.). He has received research funding as a principal investigator from the National Football League, and salary support as a collaborator from the Harvard Integrated Program to Protect and Improve the Health of National Football League Players Association Members. He acknowledges unrestricted philanthropic support from ImPACT Applications, Inc., the Mooney-Reed Charitable Foundation, the National Rugby League, and the Spaulding Research Institute. Alexander Olsen is an owner and medical advisor for Nordic Brain Tech AS. For the remaining authors, no competing financial interests exist., (© Migle Karaliute et al., 2021; Published by Mary Ann Liebert, Inc.)

Background: The research on associations between gait, physical function, physical activity (PA), and cognitive function is growing. Still, clinical assessments of cognitive function and motor function is often kept separate. In this study, we aimed to look at a broad range of measures of gait, physical function, and PA in three groups of home-dwelling older adults with no or questionable dementia, mild dementia, and moderate/severe dementia., Methods: This cross-sectional study included 100 home-dwelling older adults, recruited from an outpatient geriatric memory clinic. Severity of dementia was categorised using the clinical dementia rating scale (CDR), with no or questionable dementia (CDR score 0 and 0.5), mild dementia (CDR score 1) and moderate/severe dementia (CDR score 2 and 3). We used thigh worn accelerometers to measure daily PA, the Short Physical Performance Battery (SPPB) to measure physical function, and an electronic gait mat to evaluate gait characteristics. Associations between severity of dementia and measures of PA, physical function, and gait characteristics were assessed by linear regression., Results: Participants' (mean age 78.9 (SD 6.7) years, 57% women) average gait speed was 0.93 m/sec, and average upright time was 301 min/day. Statistically significant associations were found for the severity of dementia and gait speed (p=0.002), step time (p=0.001), physical function (SPPB, p=0.007), and PA (upright time, p=0.031), after adjusting for age. Overall, having no or questionable dementia was associated with faster gait speed (mean difference 0.163 (95% CI: 0.053 to 0.273)), shorter step time (-0.043 (-0.082 to -0.005)), better SPPB score (1.7 (0.5 to 2.8)), and longer upright time (78.9 (18.9 to 139.0)), compared to those with mild dementia. Furthermore, having no or questionable dementia was also associated with faster gait speed and better SPPB scores, as compared to those with moderate to severe dementia. No evidence of any differences was found between the participants with the mild dementia versus the moderate to severe dementia., Conclusions: After adjusting for age, we found that the no or questionable dementia group to be associated with better gait and physical function, and more PA, as compared with the two groups with mild or moderate/severe dementia. Evaluation of gait, physical function, and PA can add clinically important information of everyday functioning in memory clinics meeting geriatric patients, but investigations on how to use these results to guide interventions are still needed., (© 2021. The Author(s).)

Background: Roux-en-Y gastric bypass (RYGBP) and laparoscopic sleeve gastrectomy (LSG) are efficient methods for weight loss (WL) and WL maintenance in severe obesity. However, the knowledge of gastrointestinal (GI) symptoms after surgery is limited. This study aimed to compare the severity of GI symptoms, pain, and self-rated health 2 to 4 years after RYGBP and LSG surgery., Methods: In this cross-sectional study, RYGBP and LSG patients answered a questionnaire including the Gastrointestinal Symptom Rating Scale (GSRS), questions from the Brief Pain Inventory (BPI), and self-rated health (SRH)., Results: A total of 172/303 (57%) responded, RYGBP (n=73) and LSG (n=99). The mean age was 45.3 (SD 11.1) years (74% females). There was no evidence of a difference in total GSRS scores between the surgical methods (p=0.638). There were higher scores of reflux symptoms in LSG vs. RYGBP (both median 1, 75-percentile 2.5 vs. 1.0, p <0.001) and higher consumption of acid-reducing medication after LSG (32% vs. 12%, p <0.001). Pain scores were low in both groups; however, average abdominal pain was higher for RYGBP, median 2 (IQR 0-4) vs. median 1 (IQR 0-3) for LSG (p = 0.025). There was no significant difference in SRH., Conclusions: Patients undergoing RYGBP and LSG surgery reported similar total GSRS scores and low pain scores 2 to 4 years after surgery. However, reflux symptoms and use of acid-reducing medication occurred more frequently after LSG surgery, while abdominal pain was more frequent in RYGBP surgery. These findings are important for surgical decision-making and follow-up., (© 2021. The Author(s).)

Objective: To test the hypothesis that poor sleep quality has a stronger negative effect on cognitive control function and psychological health after mild traumatic brain injury (mTBI) than after orthopedic injury., Method: Patients with mTBI ( n = 197) and trauma controls with orthopedic injuries ( n = 82) were included in this prospective longitudinal study. The participants (age 16-60) completed three computerized neurocognitive tests assessing response speed and accuracy at 2 weeks and 3 months after injury, as well as questionnaires and interviews assessing sleep quality and psychological distress at 2 weeks, 3 months, and 12 months after injury. Separate Linear Mixed Models (LMMs) for each of the outcome measures (response speed, response accuracy, psychological distress) were performed., Results: We observed a significant interaction effect between poor sleep quality and group (mTBI vs. trauma controls) in the response speed ( p = .028) and psychological distress ( p = .001) models, driven by a greater negative impact of poor sleep quality on response speed and psychological distress in the mTBI group. We found no such interaction effect for response accuracy ( p = .825), and poor sleep quality was associated with worse accuracy to a similar extent for both groups., Conclusions: Our findings show that poor sleep quality has a more negative impact on cognitive control function and psychological outcome in patients with mTBI, compared to trauma controls. This indicates an increased vulnerability to poor sleep quality in patients who have suffered an mTBI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Cardiorespiratory fitness is often impaired following stroke, and peak oxygen consumption (VO2peak) is an important prognostic value of all-cause mortality. The primary objective was to investigate whether functional walk tests assessed in the subacute phase after stroke added value in predicting VO2peak in chronic stroke, in addition to age, sex and functional dependency. Secondary objectives were to investigate associations between daily physical activity and functional walk tests, and with VO2peak in chronic stroke., Methods: This prospective cohort study included eligible participants originally included in the randomized controlled trial Life After Stroke. Functional walk tests, i.e., six-minute walk test (6MWT) and maximal gait speed, were assessed at inclusion and 18 months later. VO2peak [ml/kg/min] was assessed by a cardiopulmonary exercise test on a treadmill 20 months after inclusion. Daily physical activity was measured by a uniaxial accelerometer (activPAL) at 18-month follow-up., Results: Ninety-two community-dwelling individuals, with a mean (SD) age of 69.2 (10.6) years and 33 (35.9%) women, were included 3 months after stroke onset. Eighty-three (90.2%) participants had a modified Rankin Scale (mRS) score of 1 or 2, indicating functional independence. An overall assessment of four prediction models indicated the combination of age, sex, mRS and 6MWT as predictors to be the best fitted model in predicting VO2peak (adjusted R2 = 0.612). Secondary results showed statistically significant, but not clinically significant, associations between daily physical activity and functional walk tests, and with VO2peak., Conclusions: 6MWT add significant value to the prediction of mean VO2peak in the chronic phase in mild strokes, in combination with age, sex and functional dependency. This prediction model may facilitate clinical decisions and rehabilitation strategies for mildly affected stroke survivors in risk of low levels of VO2peak. Future studies should validate the model in various stages after stroke and in patients moderately and severely affected., Competing Interests: The authors have declared that no competing interests exist.

Background: In general anaesthesia practice a fresh gas flow (FGF) of ≥0.5 L/min is usually applied. Automated gas delivery devices are developed to reduce volatile anaesthetic consumption by limiting gas flow. This study aimed to compare desflurane consumption between automated gas control devices compared to conventional low flow anaesthesia in the Flow-I and Aisys anaesthesia machines, and to compare desflurane consumption between the two automated gas delivery devices. We hypothesised that desflurane consumption would be lower with automated gas delivery compared to conventional low flow anaesthesia, and that desflurane consumption could differ between the different gas delivery devices., Methods: We allocated 160 patients undergoing robot-assisted laparoscopic surgery into four groups, Flow-I with automated gas control, Flow-i with conventional low-flow (1 L/min), Aisys with end tidal gas control and Aisys with conventional low flow. Patients were maintained at minimum alveolar concentration (MAC) 0.7-0.8. Desflurane consumption was recorded after 9, 30 and 60 minutes of anaesthesia., Results: After 60 minutes, compared to conventional low flow anaesthesia, automated gas delivery systems reduced desflurane consumption from 25.8 to 15.2 mL for the Aisys machine (P < .001) and from 22.1 to 16.8 mL for the Flow-I (P < .001). Time to MAC 0.7 and stable FGF was shorter with Aisys endtidal control compared to Flow-I automated gas control., Conclusion: Under clinical conditions, we found a reduction in desflurane consumption when using automated gas delivery devices compared to conventional low flow anaesthesia. Both devices were reliable in use., (© 2021 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Objective: To describe personal factors in patients with mild traumatic brain injury (MTBI) and 2 control groups and to explore how such factors were associated with postconcussion symptoms (PCSs)., Design: Prospective cohort study., Setting: Level 1 trauma center and outpatient clinic., Participants: Participants (N=541) included patients with MTBI (n=378), trauma controls (n=82), and community controls (n=81)., Main Outcome Measures: Data on preinjury health and work status, personality, resilience, attention deficit/hyperactivity, and substance use. Computed tomography (CT) findings and posttraumatic amnesia were recorded. Symptoms were assessed at 3 months with the British Columbia Postconcussion Symptom Inventory and labeled as PCS+ if ≥3 symptoms were reported or the total score was ≥13. Predictive models were fitted with penalized logistic regression using the least absolute shrinkage and selection operator (lasso) in the MTBI group, and model fit was assessed with optimism-corrected area under the curve (AUC) of the receiver operating characteristic curve., Results: There were few differences in personal factors between the MTBI group and the 2 control groups without MTBI. Rates of PCS+ were 20.8% for the MTBI group, 8.0% for trauma controls, and 1.3% for community controls. In the MTBI group, there were differences between the PCS+ and PCS- group on most personal factors and injury-related variables in univariable comparisons. In the lasso models, the optimism-corrected AUC for the full model was 0.79, 0.73 for the model only including personal factors, and 0.63 for the model only including injury variables. Working less than full time before injury, having preinjury pain and poor sleep quality, and being female were among the selected predictors, but also resilience and some personality traits contributed in the model. Intracranial abnormalities on CT were also a risk factor for PCS., Conclusions: Personal factors convey important prognostic information in patients with MTBI. A vulnerable work status and preinjury health problems might indicate a need for follow-up and targeted interventions., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the efficacy of biosimilar infliximab compared to that of the originator infliximab for the treatment of chronic non-infectious uveitis., Design: Before-and-after study., Methods: All patients in the Central Norway Health Region between 2007 and 2018 were included. They were switched from originator to biosimilar infliximab therapy from 2014 to 2017. The primary outcome was quiescence of uveitis before and after the switch. All patients were seen every 1-3 months. Visits were binned into 3-month long periods for each patient takingboth medications. Poisson regression analysis was used to estimate the incidence rate ratio (IRR) of quiescence between the 2 treatments., Results: Twenty-nine patients were treated with infliximab. Twenty-three of those patients were switched from originator to biosimilar infliximab. The majority were white (87%), female (92%), and had chronic anterior uveitis (65%). For patients taking the originator and biosimilar drugs, the median treatment duration was38 months (range: 8-131 months) and 15 months (range: 5-55 months), respectively. Concomitant immunosuppressive medications and topical and oral steroids were used similarly during treatment with both originator and biosimilar infliximab. The IRR for quiescence was 0.91 (95% confidence intervals [CI]: 0.7-1.1; P = 0.38), which indicated no statistically significant differences in achieving quiescence after the switch. Also, there were no differences in the incidence rate of flare events with the switch (IRR: 1.04; 95% CI: 0.36-2.98; P = 0.95). IRR adjusted for intraocular surgery was 0.90 (95% CI: 0.7-1.1; P = 0.37)., Conclusions: No evidence of differences in effectiveness were found in comparing biosimilar to originator infliximab in patients with chronic non-infectious uveitis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To explore the changes over time and regional differences in the incidence of retinopathy of prematurity (ROP) in a national cohort of infants born <28 weeks' gestational age (GA)., Methods: A population-based study of infants with GA <28 weeks in Norway from 2009 to 2017. Prospectively collected data on clinical variables and outcomes were obtained from the Norwegian Neonatal Network., Results: Of 1499 live-born infants transferred to a neonatal intensive care unit, 1156 were discharged alive. Four-hundred and fifty-eight infants (39.6%) had ROP, 152 (13.1%) had severe ROP, and 110 (9.5%) were treated for ROP. Eleven hundred infants (95.2%) had complete data sets. In a model comprising region of primary care, GA [odds ratios (OR): 0.65; 95% CI: 0.55-0.77], growth velocity (OR: 1.10; 95% CI: 1.00-2.00), medically treated patent ductus arteriosus (OR: 1.80; 95% CI: 1.19-2.72), weeks of supplemental oxygen (OR: 1.07; 95% CI: 1.03 to 1.11) and region of primary care (OR: 4.95; 95% CI: 3.05-8.04 for the pair of regions with the highest estimated OR) were significantly associated with severe ROP. Additionally, institutional differences for severe ROP were found, with ORs from 0.41 (95% CI: 0.05-3.23) to 5.36 (95% CI: 3.05-9.43) using the largest institution as reference. Incidences were stable over time after adjusting for GA. A larger proportion was treated with anti-vascular endothelial growth factor after 2011., Conclusions: The incidence of severe ROP was stable between 2009 and 2017 in Norway. Regional and institutional differences need to be explored in future studies., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objective/Background : Insomnia and depression are disorders that affect many perinatal women and that often are interrelated. The present study aimed to examine concurrent and prospective associations between mid-pregnancy insomnia and depression during mid-pregnancy and 8 weeks postpartum. Furthermore, differences in depression and in the sleep-related characteristics insomnia, chronotype, and sleep efficiency were explored between the two time points (mid-pregnancy versus 8 weeks postpartum), and between primiparous and multiparous participants. Participants/Methods : The study was part of the Norwegian population-based Depression and Anxiety in the Perinatal Period (DAPP) prospective cohort study. Among 539 women that were recruited for participation when receiving a routine ultrasound examination, we analyzed data from hospital birth records and questionnaire responses from pregnancy week 17 and postpartum week 8. We used the Edinburgh Postnatal Depression Scale to measure depression. The Bergen Insomnia Scale, the reduced Horne-Östberg Morningness-Eveningness Questionnaire, and three questions from the Pittsburgh Sleep Quality Index were used to measure the sleep-related characteristics. Results : Mid-pregnancy insomnia was significantly associated with concurrent depression ( p < .001), but not with postpartum depression ( p = .288), in a linear mixed model with adjustment for several reproductive and psychosocial variables. Sleep efficiency was reduced from mid-pregnancy to postpartum (from 88% to 77%), and primiparous women reported less efficient sleep than multiparous women after childbirth. Conclusions : The results indicate that mid-pregnancy insomnia may be a marker for concurrent depression but not a predictor of postpartum depression. Future research should examine the extent to which treatment of insomnia from mid-pregnancy on reduces both perinatal insomnia and depression.

Objective: To investigate the longitudinal evolution of three blood biomarkers: neurofilament light (NFL), glial fibrillary acidic protein (GFAP) and tau, in out-patients and hospitalized patients with mild traumatic brain injury (mTBI) compared to controls, along with their associations-in patients-with clinical injury characteristics and demographic variables, and ability to discriminate patients with mTBI from controls. Methods: A longitudinal observation study including 207 patients with mTBI, 84 age and sex-matched community controls (CCs) and 52 trauma controls (TCs). Blood samples were collected at 5 timepoints: acute (<24 h), 72 h (24-72 h post-injury), 2 weeks, 3 and 12 months. Injury-related, clinical and demographic variables were obtained at inclusion and brain MRI within 72 h. Results: Plasma GFAP and tau were most elevated acutely and NFL at 2 weeks and 3 months. The group of patients with mTBI and concurrent other somatic injuries (mTBI+) had the highest elevation in all biomarkers across time points, and were more likely to be victims of traffic accidents and violence. All biomarkers were positively associated with traumatic intracranial findings on MRI obtained within 72 h. Glial fibrillary acidic protein and NFL levels were associated with Glasgow Coma Scale (GCS) score and presence of other somatic injuries. Acute GFAP concentrations showed the highest discriminability between patients and controls with an Area Under the Curve (AUC) of 0.92. Acute tau and 2-week NFL concentrations showed moderate discriminability (AUC = 0.70 and AUC = 0.75, respectively). Tau showed high discriminability between mTBI+ and TCs (AUC = 0.80). Conclusions: The association of plasma NFL with traumatic intracranial MRI findings, together with its later peak, could reflect ongoing secondary injury or repair mechanisms, allowing for a protracted diagnostic time window. Patients experiencing both mTBI and other injuries appear to be a subgroup with greater neural injury, differing from both the mTBI without other injuries and from both control groups. Acute GFAP concentrations showed the highest discriminability between patients and controls, were highly associated with intracranial traumatic injury, and showed the largest elevations compared to controls at the acute timepoint, suggesting it to be the most clinically useful plasma biomarker of primary CNS injury in mTBI., Competing Interests: HZ is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712) and Swedish State Support for Clinical Research (#ALFGBG-720931). KB holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences, and was supported by the Swedish Research Council (#2017-00915), the Swedish Alzheimer Foundation (#AF651 742881), Hjärnfonden, Sweden (#FO2017-0243), and a grant (#ALFGBG-715986) from the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement. KB has served as a consultant or at advisory boards for Alzheon, CogRx, Biogen, Lilly, Novartis and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Clarke, Skandsen, Zetterberg, Einarsen, Feyling, Follestad, Vik, Blennow and Håberg.)

In this prospective, longitudinal study, we aimed to determine the prevalence and stability of sleep-wake disturbance (SWD) and fatigue in a large representative sample of patients (Trondheim mild traumatic brain injury [mTBI] follow-up study). We included 378 patients with mTBI (age 16-60), 82 matched trauma controls with orthopedic injuries, and 83 matched community controls. Increased sleep need, poor sleep quality, excessive daytime sleepiness, and fatigue were assessed at 2 weeks, 3 months, and 12 months after injury. Mixed logistic regression models were used to evaluate clinically relevant group differences longitudinally. Prevalence of increased sleep need, poor sleep quality, and fatigue was significantly higher in patients with mTBI than in both trauma controls and community controls at all time points. More patients with mTBI reported problems with excessive daytime sleepiness compared to trauma controls, but not community controls, at all time points. Patients with complicated mTBI (intracranial findings on computed tomography or magnetic resonance imaging) had more fatigue problems compared to those with uncomplicated mTBI, at all three time points. In patients with mTBI who experienced SWDs and fatigue 2 weeks after injury, around half still had problems at 3 months and approximately one third at 12 months. Interestingly, we observed limited overlap between the different symptom measures; a large number of patients reported one specific problem with SWD or fatigue rather than several problems. In conclusion, our results provide strong evidence that mTBI contributes significantly to the development and maintenance of SWDs and fatigue.

Objective: The aim in this study was to investigate if MRI findings of traumatic axonal injury (TAI) after traumatic brain injury (TBI) are related to the admission Glasgow Coma Scale (GCS) score and prolonged duration of posttraumatic amnesia (PTA)., Methods: A total of 490 patients with mild to severe TBI underwent brain MRI within 6 weeks of injury (mild TBI: median 2 days; moderate to severe TBI: median 8 days). The location of TAI lesions and measures of total TAI lesion burden (number and volume of lesions on FLAIR and diffusion-weighted imaging and number of lesions on T2*-weighted gradient echo or susceptibility-weighted imaging) were quantified in a blinded manner for clinical information. The volume of contusions on FLAIR was likewise recorded. Associations between GCS score and the location and burden of TAI lesions were examined with multiple linear regression, adjusted for age, Marshall CT score (which includes compression of basal cisterns, midline shift, and mass lesions), and alcohol intoxication. The predictive value of TAI lesion location and burden for duration of PTA > 28 days was analyzed with multiple logistic regression, adjusted for age and Marshall CT score. Complete-case analyses of patients with TAI were used for the regression analyses of GCS scores (n = 268) and PTA (n = 252)., Results: TAI lesions were observed in 58% of patients: in 7% of mild, 69% of moderate, and 93% of severe TBI cases. The TAI lesion location associated with the lowest GCS scores were bilateral lesions in the brainstem (mean difference in GCS score -2.5), followed by lesions bilaterally in the thalamus, unilaterally in the brainstem, and lesions in the splenium. The volume of TAI on FLAIR was the measure of total lesion burden most strongly associated with the GCS score. Bilateral TAI lesions in the thalamus had the largest predictive value for PTA > 28 days (OR 16.2, 95% CI 3.9-87.4). Of the measures of total TAI lesion burden, the FLAIR volume of TAI predicted PTA > 28 days the best., Conclusions: Bilateral TAI lesions in the brainstem and thalamus, as well as the total volume of TAI lesions on FLAIR, had the strongest association with the GCS score and prolonged PTA. The current study proposes a first step toward a modified classification of TAI, with grades ranked according to their relation to these two measures of clinical TBI severity.

Background: Behavioral change is the key to alter individuals' lifestyle from sedentary to active. The aim was to assess the feasibility of delivering a Lifestyle-integrated Functional Exercise programme and evaluate the delivery of the intervention by use of digital technology (eLiFE) to prevent functional decline in 61-70 year-old adults. Methods: This multicentre, feasibility randomized controlled trial was run in three countries (Norway, Germany, and the Netherlands). Out of 7,500 potential participants, 926 seniors (12%) were screened and 180 participants randomized to eLiFE ( n = 61), aLiFE ( n = 59), and control group ( n = 60). eLiFE participants used an application on smartphones and smartwatches while aLiFE participants used traditional paper-based versions of the same lifestyle-integrated exercise intervention. Participants were followed for 12 months, with assessments at baseline, after a 6 month active trainer-supported intervention, and after a further 6 months of unsupervised continuation of the programme. Results: At 6 months, 87% of participants completed post-test , and 77% completed the final assessment at 12 months. Participants were willing to be part of the programme, with compliance and reported adherence relatively high. Despite small errors during start-up in the technological component, intervention delivery by use of technology appeared acceptable. No serious adverse events were related to the interventions. All groups improved regarding clinical outcomes over time, and complexity metrics show potential as outcome measure in young seniors. Conclusion: This feasibility RCT provides evidence that an ICT-based lifestyle-integrated exercise intervention, focusing on behavioral change, is feasible and safe for young seniors. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03065088. Registered on 14 February 2017., (Copyright © 2020 Taraldsen, Mikolaizak, Maier, Mellone, Boulton, Aminian, Becker, Chiari, Follestad, Gannon, Paraschiv-Ionescu, Pijnappels, Saltvedt, Schwenk, Todd, Yang, Zacchi, van Ancum, Vereijken and Helbostad.)