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Lars Christian Haugli Bråten,1 Elisabeth Gjefsen,1,2 Kristina Gervin,1 Are Hugo Pripp,3 Jan Sture Skouen,4 Elina Schistad,5 Linda Margareth Pedersen,1 Monica Wigemyr,1 Kaja Kristine Selmer,1 Hans Christian Dalsbotten Aass,6 Guro Goll,7 Jens Ivar Brox,5 Ansgar Espeland,8,9 Lars Grøvle,10 John-Anker Zwart,1,2 Kjersti Storheim1,11 On behalf of The AIM-study group1Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital HF, Oslo, Norway; 2Faculty of Medicine, University of Oslo, Oslo, Norway; 3Oslo Centre of Biostatistics and Epidemiology Research Support Services, Oslo University Hospital Ulleval, Oslo, Norway; 4Department of Physical Medicine and Rehabilitation, Haukeland University Hospital, Bergen, Norway; 5Department of Physical Medicine and Rehabilitation, Oslo University Hospital HF, Oslo, Norway; 6Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway; 7Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway; 8Department of Radiology, Haukeland University Hospital, Bergen, Norway; 9Department of Clinical Medicine, University of Bergen, Bergen, Norway; 10Department of Rheumatology, Østfold Hospital Trust, Grålum, Norway; 11Oslo Metropolitan University, Department of Physiotherapy, Oslo, NorwayCorrespondence: Lars Christian Haugli Bråten, Tel +4722117769, Email l.c.h.braten@studmed.uio.noObjective: Randomized trials testing the effect of antibiotics for chronic low back pain (LBP) with vertebral bone marrow changes on MRI (Modic changes) report inconsistent results. A proposed explanation is subgroups with low grade discitis where antibiotics are effective, but there is currently no method to identify such subgroups. The objective of the present study was to evaluate whether distinct patterns of serum cytokine levels predict any treatment effect of oral amoxicillin at one-year follow-up in patients with chronic low back pain and Modic changes at the level of a previous lumbar disc herniation.Design: We used data from an overpowered, randomized, placebo-controlled trial (the AIM study) that tested 100 days of oral 750 mg amoxicillin vs placebo three times daily in hospital outpatients with chronic (> 6 months) LBP with pain intensity ≥ 5 on a 0– 10 numerical rating scale and Modic changes type 1 (oedema type) or 2 (fatty type). We measured serum levels of 40 inflammatory cytokines at baseline and analysed six predefined potential predictors of treatment effect based on cytokine patterns in 78 randomized patients; three analyses with recursive partitioning, one based on cluster analysis and two based on principal component analyses. The primary outcome was the Roland–Morris Disability Questionnaire score at one-year follow-up in the intention to treat population. The methodology and overall results of the AIM study were published previously.Results: The 78 patients were 25– 62 years old and 47 (60%) were women. None of the three recursive partitioning analyses resulted in any suggested subgroups. Of all main analyses, the largest effect estimate (mean difference between antibiotic and placebo groups) was seen in a subgroup not predefined as of main interest (Cluster category 3+4; − 2.0, 95% CI: − 5.2– 1.3, RMDQ points; p-value for interaction 0.54).Conclusion: Patterns of inflammatory serum cytokine levels did not predict treatment effect of amoxicillin in patients with chronic LBP and Modic changes.Clinical Trial Registration Number: ClinicalTrials.gov (identifier: NCT02323412).Keywords: low back pain, Modic changes, infection, cytokines, inflammation

Objective: To examine the effect of a prenatal lifestyle intervention on postpartum weight retention (PPWR).Design: Randomised controlled trial.Setting: Healthcare clinics in southern Norway.Population: Healthy, nulliparous women with body mass index ≥19 kg/m2 , age ≥18 years, and singleton pregnancy of ≤20 gestational weeks.Methods: Women were randomised to intervention (dietary counselling twice by phone and access to twice-weekly exercise groups during pregnancy) or control group (standard prenatal care). Intervention compliance was defined post-factum as attending dietary counselling and ≥14 exercise classes.Main Outcome Measures: PPWR (weight measured postpartum minus self-reported pre-pregnancy weight) and the proportion of women returning to pre-pregnancy weight.Results: Of 606 women randomised, 591 were included in an intention-to-treat analysis of pregnancy outcomes and 391 (64.5%) were analysed 12 months postpartum. Mean PPWR was not significantly different between groups (0.66 kg for intervention versus 1.42 kg for control group, mean difference -0.77 kg, 95% CI -1.81, 0.28; P = 0.149). An increased proportion of intervention participants achieved pre-pregnancy weight (53% versus 43%, OR 1.50, 95% CI 1.003, 1.471; P = 0.045). However, the difference was not statistically significant when we adjusted for missing data (adjusted odds ratio (OR) 2.23, P = 0.067) using logistic mixed-effects models analysis. Women compliant with intervention had significantly lower PPWR than control participants, also after adjusting for potential confounders (adjusted mean diff -1.54 kg, 95% CI -3.02, -0.05; P = 0.039).Conclusions: The Norwegian Fit for Delivery intervention had little effect on PPWR, although women who were compliant with the intervention demonstrated significantly lower PPWR at 12 months.Tweetable Abstract: Norwegian Fit for Delivery RCT: little effect of lifestyle intervention on weight retention 1 year postpartum. [ABSTRACT FROM AUTHOR]

Objectives: To establish the prevalence of protrusio acetabuli (PA) in adults fulfilling the Ghent criteria for Marfan syndrome (MFS), and in a normal adult population.Methods: 105 adults with probable MFS and 107 controls were included. CT of the hips was obtained. A qualitative assessment of PA was performed. A new method for estimating the degree of PA was introduced with measurement of the parameter CWD (circle-wall distance). Results were compared to an alternative method based on MRI [1].Results: 87 of the study group fulfilled the Ghent criteria of MFS (Ghent positives), and 18 did not (Ghent negatives). PA was diagnosed qualitatively in 74.7% of Ghent positive persons, in 27.8% of Ghent negative persons, and in 3.7% of the controls. CWD was significantly different between the three groups (p < 0.001). A slight but significant gender difference was found in Ghent positive persons only. The alternative method did not differentiate between the groups with respect to PA, but showed a significant difference between genders.Conclusions: PA was found significantly more often in MFS persons than in controls. Our method was found to be robust and highly reproducible, giving a direct measurement of pelvic protrusion irrespective of pelvic shape. [ABSTRACT FROM AUTHOR]

Background: The treatment of primary traumatic anterior shoulder dislocation varies widely from no immobilization, to two or three weeks of immobilization in internal rotation with the arm in a sling, to treatment with a brace in external rotation. The aim of the present clinical trial was to compare immobilization in internal and external rotation after anterior shoulder dislocation.Methods: One hundred and eighty-eight patients with a primary anterior traumatic dislocation of the shoulder were randomly assigned to treatment with immobilization in either internal rotation (ninety-five patients) or external rotation (ninety-three patients) for three weeks. The primary outcome measure was a recurrent dislocation within twenty-four months of follow-up.Results: The follow-up rate after a minimum period of two years was 97.9% (ninety-three of ninety-five) in the internal rotation group and 97.8% (ninety-one of ninety-three) in the external rotation group. The compliance rate with the immobilization was 47.4% (forty-five of ninety-five) in the internal rotation group and 67.7% (sixty-three of ninety-three) in the external rotation group. The intention-to-treat analyses showed that the recurrence rate was 24.7% (twenty-three of ninety-three) in the internal rotation group and 30.8% (twenty-eight of ninety-one) in the external rotation group (p = 0.36).Conclusions: Immobilization in external rotation does not reduce the rate of recurrence for patients with first-time traumatic anterior shoulder dislocation. [ABSTRACT FROM AUTHOR]

Aims: Short-term treatment with calcium channel blockers lowers levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and reduces rhythm-related symptoms compared to treatment with beta-blockers. The aim of this study was to compare the effects of metoprolol and diltiazem for rate control in patients with permanent atrial fibrillation (AF) after 6 months., Methods and Results: Men and women with permanent AF and preserved left ventricular systolic function were randomized to receive either diltiazem 360 mg or metoprolol 100 mg once daily. The primary endpoint was the level of NT-proBNP after a 6-month treatment period. Secondary endpoints included heart rate, rhythm-related symptoms and exercise capacity. A total of 93 patients (mean age 71 ± 7 years, 28 women) were randomized. After 6-months' treatment, mean levels of NT-proBNP decreased in the diltiazem group and increased in the metoprolol group, with a significant between-group difference (409.8 pg/mL, 95% CI: 230.6-589.1, P < 0.001). Treatment with diltiazem significantly reduced rhythm-related symptoms compared to baseline, but no change was observed in the metoprolol group. Diltiazem and metoprolol had similar effects on heart rate and exercise capacity., Conclusion: Diltiazem reduced NT-proBNP levels and improved rhythm-related symptoms. Metoprolol increased peptide levels but had no impact on symptoms despite similar heart rate reduction. Non-dihydropyridine calcium channel blockers should be considered more often for rate control in permanent AF., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Atrial fibrillation (AF) is a common arrhythmia, and many cases of AF may be undiagnosed. Whether screening for AF and subsequent treatment if AF is detected can improve long-term outcome remains an unsettled question. The primary aim of the NORwegian atrial fibrillation self-SCREENing (NORSCREEN) trial is to assess whether self-screening for AF with continuous electrocardiogram (ECG) for 3-7 days in individuals aged 65 years or older with at least one additional risk factor for stroke, and initiation of guideline-recommended therapy in patients with detected AF, will reduce the occurrence of stroke., Methods and Results: This study is a nationwide open, siteless, randomized, controlled trial. Individuals ≥65 years of age are randomly identified from the National Population Register of Norway and are invited to take a digital inclusion/exclusion test. Individuals passing the inclusion/exclusion test are randomized to either the intervention group or the control group. A total of 35 000 participants will be enrolled. In the intervention group, self-screening is performed continuously over 3-7 days at home with a patch ECG device (ECG247) at inclusion and after 12-18 months. If AF is detected, guideline-recommended therapy will be initiated. Patients will be followed up for 5 years through national health registries. The primary outcome is time to a first stroke (ischaemic or haemorrhagic stroke). The first participant in the NORSCREEN trial was enrolled on 1 September 2023., Conclusion: The results from the NORSCREEN trial will provide new insights regarding the efficacy of digital siteless self-screening for AF with respect to stroke prevention in individuals at an increased risk of stroke., Trial Registration: Clinical trials: NCT05914883., Competing Interests: Conflict of interest: M.B. has received consultant fees from Pfizer. J.J. has received consultant or lecture fees from Amarin, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Novartis, Pfizer, and Sanofi. He is a shareholder in Appsens AS and is partly employed in the company. T.B. has received consultant or lecture fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Pfizer. J.E. has received consultant or lecture fees from Roche Diagnostics, Pfizer, Bristol Myers Squibb, Organon, Piotrode, and Philips and research grants from the Swedish Research Council, the Swedish Heart and Lung Foundation, the Swedish Innovation Agency, and the Stockholm Region. M.-L.L. has received lecture fees from Bayer, Bristol Myers Squibb, Pfizer, and Sanofi. P.S. has received lecture fees from Johnson & Johnson. E.L.S. has received consultant or lecture fees from AstraZeneca and Pfizer. J.G. has received consultant or lecture fees from Bayer, Boehringer Ingelheim, Novartis, and Sanofi and fees for participating in an expert panel from Sanofi, unrelated to this work. D.A. has received consultant or lecture fees from Amarin, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Merck & Co., Novartis, Pfizer, Pharmacosmos, Sanofi, and Vifor, as well as research funding to his institution from Bristol Myers Squibb, Pfizer, Medtronic, and Roche Diagnostics. B.L.G. has received consultant or lecture fees from Bristol Myers Squibb, Pfizer, Novartis, Astra Zeneca, Boehringer Ingelheim, and Bayer. S.H. has received consultant or lecture fees from Astra Zeneca, Bristol Myers Squibb, Novartis, Pfizer, and Sanofi. All other authors have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Diagnostic assessment of ADHD is challenging due to comorbid psychopathologies and symptoms overlapping with other psychiatric disorders. In this study, we investigate if a distinct pattern of neuromuscular dysregulation previously reported in ADHD, can help identifying ADHD in psychiatric patients with diverse and complex symptoms., Method: We explored the impact of neuromuscular dysregulation, as measured by The Motor Function Neurologic Assessment (MFNU), on the likelihood of being diagnosed with ADHD, affective disorder, anxiety disorder, or personality disorder among adults ( n  = 115) referred to a psychiatric outpatient clinic., Results: Logistic regression revealed that neuromuscular dysregulation was significantly associated with ADHD diagnosis only ( OR 1.15, p  < .01), and not with affective-, anxiety-, or personality disorders. Sensitivity and specificity for ADHD at different MFNU scores is provided., Conclusions: A test of neuromuscular dysregulation may promote diagnostic accuracy in differentiating ADHD from other psychiatric disorders in patients with an overlapping symptom picture. This may have important implications for clinical practice. More studies are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The MFNU manual is edited by LLS and TS. The other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To evaluate the longitudinal impact of introducing a national, direct access physiotherapy model of care on the rates of primary and secondary care consultations for musculoskeletal (MSK) conditions., Design: Interrupted time series analysis using segmented linear regression., Setting: Norway primary care PARTICIPANTS: A cohort of 82 072 participants was derived from 3 population-based health surveys conducted across separate geographical regions in Norway. All participants surveyed were eligible for inclusion as a national representative sample of the Norwegian population. Registered MSK consultations were linked to the Norwegian Control and Payment of Health Reimbursement database and the Norwegian Patient Register using the International Classification of Primary Care diagnostic medical codes L-chapter for MSK conditions and spine related International Classification of Diseases, 10th Revision, codes., Intervention: Direct access to physiotherapy model of care introduced nationally in Norway in 2018. This model allowed Norwegians to consult directly with qualified physiotherapists for MSK conditions (eg, back pain, knee osteoarthritis) without the need for a medical referral in order to claim a social security reimbursement., Main Outcomes Measured: Rates of primary care consultations per 10 000 population (general practitioner (GP) and physiotherapist consultations) and secondary care (specialist consultations and surgical procedures) measured from 2014 to 2021., Results: The introduction of the direct access physiotherapy model was associated with an immediate stepped reduction of 391 general practice consultations per 10 000 population, (95% CI: -564 to -216), without an associated change in physiotherapy consultations. Subgroup analyses suggested there was an associated reduction in physiotherapy consultations for those in the lowest education group of 150 consultations per quarter (95% CI:-203 to -97), 70 consultations per quarter in the intermediate education group (95% CI:-115 to -27) and a stepped reduction of 2 spinal surgical procedures per 10 000 population, for those aged between 40 and 60 years (95% CI: -3 to -1) following the introduction of the direct access physiotherapy model., Conclusion: The national introduction of a direct access to physiotherapy model of care was associated with a reduction in the workload of GPs for the management of MSK conditions. The use of physiotherapists in direct contact roles is a potential strategic model to reduce the burden on the GP workforce in primary care worldwide., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Perinatal asphyxia initiates cytokine release and complement activation with risk of brain damage. We assessed the effect of nicotine on innate immunity and hypothesized that nicotine infusion in a newborn piglet model of asphyxia would decrease the immune response and be neuroprotective., Methods: Newborn piglets (n = 41) were randomized to one of three groups after hypoxia: two groups receiving nicotine, (1) 18 µg/kg/h (n = 17), (2) 46 µg/kg/h (n = 15), and (3) control group receiving saline (n = 9). C3a, IL-6, TNF, and IL-10 were measured in plasma and IL-6 and IL-8 in microdialysis fluid from cerebral periventricular white matter, using immuno-assays., Results: Plasma C3a and IL-6 increased significantly from start to end hypoxia (mean 4.4 ± 0.55 to 5.6 ± 0.71 ng/mL and 1.66 ± 1.04 to 2.68 ± 0.71 pg/mL, respectively), while IL-10 and TNF increased significantly after 4 h (mean 1.4 ± 1.08 to 2.9 ± 1.87 and 3.3 ± 0.67 to 4.0 ± 0.58 pg/mL, respectively) (p &lt; 0.001 for all). IL-6 increased significantly (p &lt; 0.001) in microdialysis samples from end hypoxia to end experiment (mean 0.65 ± 0.88 to 2.78 ± 1.84 ng/mL). No significant differences were observed between the nicotine groups and the control group neither in plasma nor in microdialysis samples., Conclusion: Hypoxia leads to rapid release of cytokines in plasma and cerebral microdialysis fluid, and complement activation measured on C3a. However, low-dose nicotine administration did not affect the immune response., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: Funding for this study was received from Sophies Minde Ortopedi AS, The South-East Health Authority Norway, and The Research Council of Norway. The funding sources did not play a role in the investigation. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I188)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Objectives: A high incidence of attention-deficit hyperactivity disorder (ADHD) has been reported in chronic pain (ChP) patients. Furthermore, an association between ChP and muscular dysregulation has been reported in adults with ADHD. The present study investigated whether ADHD was more prevalent among psychiatric outpatients with ChP than those without ChP, and if there was an association between ChP, muscular dysregulation and characteristics of pain in patients with ADHD., Methods: One-hundred and twenty-one individuals remitted to an outpatient psychiatry unit took part in this naturalistic epidemiological cross-sectional study. They were assessed with a pain self-report form (localization, intensity, and onset) and a test of muscle dysregulation (the Motor Function Neurological Assessment). Prevalence of ADHD among patients with ChP, as well as the qualitative characteristics of ChP within the ADHDgroup are reported. Both ChP and pain intensity correlated with muscular dysregulation through Spearman's rho analysis. Additionally, the relationship between various diagnostic categories (ADHD, affective disorders, anxiety, or personality disorders) and incidence of axial pain was evaluated in logistic regression., Results: ADHD was significantly more prevalent in patients with ChP, than in patients without ChP. In the ADHD group, ChP and pain intensity was associated with muscular dysregulation, particularly with high muscle tone. ChP was more axial and widespread, than for the patients without ADHD, and started at an early age. ADHD diagnosis predicted axial pain, whereas affective-, anxiety-, or personality disorders did not., Conclusions: The study suggests that ChP in ADHD is associated with muscular dysregulation and is qualitatively different from ChP in psychiatric patients without ADHD. These findings may lead to further understanding of potential mechanisms involved in ADHD and ChP, and in turn to new treatment strategies for both disorders., (© 2024 the author(s), published by De Gruyter.)

Objective: The relationship between the surgical approach used for hemiarthroplasty and periprosthetic bone mineral density (BMD) is not well understood. We have previously described a decrease in BMD 1 year postoperatively. Here, we assessed the medium-term changes in periprosthetic BMD., Methods: We performed a follow-up study of patients with femoral neck fracture (FNF) who underwent uncemented hemiarthoplasty using a direct lateral or anterolateral approach. Dual-energy X-ray absorptiometry (DXA) was used to evaluate the changes in BMD in 23 patients over 5 years., Results: A mean 6% loss of total BMD occurred over 1 year, but between 1 and 5 years, BMD was restored to the baseline value. The mean total BMD in the anterolateral group had decreased by 2% after 3 months and 3% after 12 months, and increased by 2% after 5 years, vs . decreases of 7%, 8%, and 3% for the direct lateral group. Between 1 and 5 years, BMD increased in Gruen zones 2, 3, 4, 5, and 6 in both groups. There was a significantly larger increase in zone 4 in the lateral group (4%) than the anterolateral group., Conclusion: The surgical approach affects periprosthetic BMD in patients with FNF. Furthermore, BMD is restored to the baseline value 5 years postoperatively. ClinicalTrials.gov registration number: NCT03753100., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Maternal anxiety and depression during pregnancy and early childhood have been associated with child anxiety and attention-deficit/hyperactivity disorder (ADHD). However, previous studies are limited by their short follow-up, few assessments of maternal symptoms, and by not including maternal and child ADHD. The present study aimed to fill these gaps by investigating whether maternal anxiety and depressive symptoms from pregnancy to child age 5 years increase the risk of child anxiety disorders at age 8 years. This study is part of the population-based Norwegian Mother, Father, and Child Cohort Study. Maternal anxiety and depressive symptoms were assessed by the Hopkins Symptom Checklist (SCL) six times from pregnancy through early childhood, and ADHD symptoms by the Adult Self-Report Scale (ASRS). At age 8 years (n = 781), symptoms of anxiety disorders and ADHD were assessed, and disorders classified by the Child Symptom Inventory-4. Logistic regression models estimated the risk of child anxiety depending on maternal symptoms. The mothers of children classified with an anxiety disorder (n = 91) scored significantly higher on the SCL (at all time points) and ASRS compared with the other mothers. In univariable analyses, maternal anxiety and/or depression and ADHD were associated with increased risk of child anxiety (odds ratios = 2.99 and 3.64, respectively), remaining significant in the multivariable analysis adjusted for covariates. Our findings link maternal anxiety, depression, and ADHD during pregnancy and early childhood to child anxiety at age 8 years., (© 2024. The Author(s).)

Objective: To describe intrapartum fetal monitoring methods used in all births in Norway in 2019-2020, assess adherence to national guidelines, investigate variation by women's risk status, and explore associations influencing monitoring practices., Methods: A nationwide population-based study. We collected data about all pregnancies with a gestational age ≥ 22 weeks during 2019-2020 from the Medical Birth Registry of Norway. We used descriptive analyses, stratified for risk status, to examine fetal monitoring methods used in all deliveries. Univariable and multivariable logistic regression models were used to determine factors associated with monitoring with cardiotocography (CTG) in low-risk, straightforward births., Results: In total, 14 285 (14%) deliveries were monitored with only intermittent auscultation (IA), 46214 (46%) with only CTG, and 33417 (34%) with IA and CTG combined. Four percent (2 067/50 533) of women with risk factors were monitored with IA only. Half (10589/21 282) of the low-risk women with straightforward births were monitored with CTG. Maternal and fetal characteristics, size of the birth unit and regional practices influenced use of CTG monitoring in this group., Conclusions: Most births are monitored with CTG only, or combined with IA. Half the women with low-risk pregnancies and straightforward births were monitored with CTG although national guidelines recommending IA., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: We aim to compare drug effectiveness and persistence between the reference etanercept (ETN) and ETN biosimilar SB4 in patients with psoriatic arthritis (PsA) naive to ETN and to investigate drug effectiveness and persistence in those undergoing a mandatory nonmedical switch from ETN to SB4., Methods: We used a retrospective comparative database study including 1,138 patients with PsA treated with ETN or SB4 (years 1999-2021) in Norway. Disease activity score in 28 joints (DAS28) and drug persistence were compared between unmatched ETN (n = 644) and SB4 (n = 252) cohorts and in matched analyses (n = 144, both cohorts) at baseline using a propensity score (PS) to adjust for confounders. Drug persistence was analyzed with the Kaplan-Meier method., Results: In unmatched analyses, difference in change from baseline between ETN (n = 140) and SB4 (n = 132) for DAS28 at one year was mean 0.67 (95% confidence interval [CI] 0.38-0.96) in favor of ETN. In PS-matched analyses, the difference in change from baseline between ETN (n = 54) and SB4 (n = 54) was mean 0.09 (95% CI -0.33 to 0.50), and the mean difference assessed with an analysis of covariance model was 0.01 (95% CI -0.38 to 0.40), both within predefined equivalence margin (±0.6). Drug persistence at one year was mean 0.75 (95% CI 0.71-0.78) for ETN, mean 0.58 (95% CI 0.51-0.63) for SB4, hazard ratio (HR) 2.45 (95% CI 2.02-2.97) in unmatched analysis, and mean 0.55 (95% CI 0.46-0.63) for ETN, mean 0.60 (95% CI 0.51-0.67) for SB4, HR 1.29 (95%CI 0.94-1.76) in PS-matched cohorts., Conclusion: At one year, outcomes for PsA disease activity and drug persistence were comparable for patients treated with either ETN or SB4. In patients undergoing a mandatory nonmedical switch from ETN to SB4, drug effectiveness was maintained during a two-year period., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Abstract: The optimal treatment for small-to-medium-sized rotator cuff tears remains a topic of debate. While both tendon repair and physiotherapy have shown comparable short-term results, there are concerns about the long-term effectiveness of physiotherapy. In 2 previous reports presenting the 5 and 10-year results of this trial, significant and increasing differences were observed in favor of tendon repair. Further investigation of the unexplored time interval after 10 years is essential to fully understand the implications of our treatment approaches. A total of 103 patients with a full-thickness rotator cuff tear not exceeding 3 cm were randomly allocated to tendon repair or physiotherapy with optional secondary repair. Measurements of shoulder function were performed by a blinded assessor at 6 months and 1, 2, 5, 10, and 15 years. The outcome of primary interest was the 15-year result for the Constant score. Secondary outcome measures included the self-report section of the American Shoulder and Elbow Surgeons (ASES) score; the Short Form-36 (SF-36) Health Survey; assessments of pain, motion, and strength; and patient satisfaction. Tear-size increase in unrepaired tears was assessed by sonography. Statistical analysis was by mixed-model analysis for repeated measurements and by intention to treat. Eighty-three (81%) of 103 patients attended the 15-year follow-up. Fifteen of 51 patients in the physiotherapy group had crossed over to secondary surgery. Results from primary tendon repair were superior by a mean difference of 11.8 points for the Constant score (p = 0.001), 13.9 points for the ASES score (p < 0.001), 1.8 cm on a 10-cm visual analog scale for pain (p < 0.001), and 16.2° and 22.4°, respectively, for pain-free abduction and flexion (p = 0.04 and 0.001). On the SF-36, differences did not reach significance for any of the scoring scales. In 26 tears treated by physiotherapy only, the mean tear size had increased from 16.2 to 31.6 mm in the anterior-posterior direction. Long-term outcomes from primary tendon repair remained superior to physiotherapy up to 15 years of follow-up, supporting its use as the primary treatment for small-to-medium-sized rotator cuff tears., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I154)., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Access to valid and reliable instruments is essential in the field of implementation science, where the measurement of factors associated with healthcare professionals' uptake of EBP is central. The Norwegian version of the Evidence-based practice profile questionnaire (EBP 2 -N) measures EBP constructs, such as EBP knowledge, confidence, attitudes, and behavior. Despite its potential utility, the EBP 2 -N requires further validation before being used in a cross-sectional survey targeting different healthcare professionals in Norwegian primary healthcare. This study assessed the content validity, construct validity, and internal consistency of the EBP 2 -N among Norwegian primary healthcare professionals., Methods: To evaluate the content validity of the EBP 2 -N, we conducted qualitative individual interviews with eight healthcare professionals in primary healthcare from different disciplines. Qualitative data was analyzed using the "text summary" model, followed by panel group discussions, minor linguistic changes, and a pilot test of the revised version. To evaluate construct validity (structural validity) and internal consistency, we used data from a web-based cross-sectional survey among nurses, assistant nurses, physical therapists, occupational therapists, medical doctors, and other professionals (n = 313). Structural validity was tested using a confirmatory factor analysis (CFA) on the original five-factor structure, and Cronbach's alpha was calculated to assess internal consistency., Results: The qualitative interviews with primary healthcare professionals indicated that the content of the EBP 2 -N was perceived to reflect the constructs intended to be measured by the instrument. However, interviews revealed concerns regarding the formulation of some items, leading to minor linguistic revisions. In addition, several participants expressed that some of the most specific research terms in the terminology domain felt less relevant to them in clinical practice. CFA results exposed partial alignment with the original five-factor model, with the following model fit indices: CFI = 0.749, RMSEA = 0.074, and SRMR = 0.075. Cronbach's alphas ranged between 0.82 and 0.95 for all domains except for the Sympathy domain (0.69), indicating good internal consistency in four out of five domains., Conclusion: The EBP 2 -N is a suitable instrument for measuring Norwegian primary healthcare professionals' EBP knowledge, attitudes, confidence, and behavior. Although EBP 2 -N seems to be an adequate instrument in its current form, we recommend that future research focuses on further assessing the factor structure, evaluating the relevance of the items, and the number of items needed., Registration: Retrospectively registered (prior to data analysis) in OSF Preregistration. Registration DOI: https://doi.org/10.17605/OSF.IO/428RP ., (© 2024. The Author(s).)

Objective: To document the impact of early follow-up by specialized cleft nurses (SCNs) to families of infants with cleft lip and/or cleft palate (CL/P)., Design: Prospective inclusion of a control group, which received standard care alone, followed by an intervention group, which in addition received early SCN follow-up., Setting: The cleft lip and palate team at a University hospital., Participants: 70 families (69 mothers and 57 fathers); control group (n = 38); intervention group (n = 32)., Intervention: SCNs offered a consultation at the maternity ward and follow-ups by phone or face-to-face at one, three, eight weeks and six months after birth., Outcome Measures: Use of Internet-Questionnaire, Quality of discharge teaching scale (QDTS), Post discharge coping difficulty scale (PDCDS), Response on follow-up by health professionals., Results: Infants in the intervention group were admitted less frequently to a Neonatal Intensive Care unit (NICU); 21.9% vs 51.4%, P  = .012. Parents in the intervention group used internet for cleft-related reasons less frequently (74.6% vs 85.9%), P  = .112 and the mothers benefitted less from cleft-related activity on the internet ( P  = .013). The intervention group reported higher mean score for satisfaction with total cleft care ( P  = .001). There were no significant group differences regarding mean total score for discharge teaching ( P  = .315) and coping difficulties ( P  = .919)., Conclusion: Early follow-up by a SCN with expertise in cleft care is highly valued by parents. Closer cooperation between the cleft team and health professionals at birth hospitals and Child health centers is necessary for optimal follow-up., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Randomized controlled trials are considered the gold standard in study methodology. However, due to their study design and inclusion criteria, these studies may not capture the heterogeneity of real-world patient populations. In contrast, the lack of randomization and the presence of both measured and unmeasured confounding factors could bias the estimated treatment effect when using observational data. While causal inference methods allow for the estimation of treatment effects, their mathematical complexity may hinder their application in clinical research., Methods: We present a practical, nontechnical guide using a common statistical package (Stata) and a motivational simulated dataset that mirrors real-world observational data from patients with rheumatic diseases. We demonstrate regression analysis, regression adjustment, inverse-probability weighting, propensity score (PS) matching and two robust estimation methods., Results: Although the methods applied to control for confounding factors produced similar results, the commonly used one-to-one PS matching method could yield biased results if not thoroughly assessed., Conclusion: The guide we propose aims to facilitate the use of readily available methods in a common statistical package. It may contribute to robust and transparent epidemiological and statistical methods, thereby enhancing effectiveness research using observational data in rheumatology., (© 2024. The Author(s).)

Background & Aims: Refeeding syndrome (RFS) lacks both a global definition and diagnostic criteria. Different diagnostic criteria are used; serum phosphate (traditional criterion (TC)), the Friedli consensus recommendations, and the ASPEN. We investigated the incidence of RFS in older hospitalized patients and the mortality rates in patients with or without RFS using these three different diagnostic criteria., Methods: This is a longitudinal study with data originating from a randomized controlled trial conducted between March 2017 and August 2019. A total of 85 malnourished hospitalized patients at risk of RFS according to the National Institute for Health and Clinical Excellence tool for detecting patients at risk of RFS, were included. All patients were provided with enteral tube feeding, and electrolytes were measured daily during the intervention period. Friedli and ASPEN included phosphate, magnesium, and potassium in their definitions, but used different cut-off values. Incidences were recorded, and Kaplan-Meier estimates were used to determine whether mortality was more prevalent in patients with RFS. Regression analysis was used to test for confounders regarding the association between RFS and death, and Kappa was used to test for agreement between the three diagnostic criteria., Results: The mean (SD) age of the patients was 79.8 (7.4) years, and the mean (SD) BMI was 18.5 (3.4) kg/m 2 . The mean (SD) kcal/kg/day was 19 (11) on day one and 26 (15) on day seven. The incidences of RFS differed with the criteria used; 12.9% (TC), 31.8% (Friedli), and 65.9% (ASPEN). Mortality was high, with 36.5% (n = 31) and 56.5% (n = 48) of patients dead at three-month and one-year follow-up, respectively. In the TC, 8/11 (72.7%) with RFS vs. 40/74 (54.1%) without RFS died within one-year, in Friedli 15/27 (55.5%) with RFS vs. 33/58 (56.9%) without RFS died, and in ASPEN 32/56 (65.9%) with RFS, vs. 16/29 (55.2%) without RFS died within one-year. There was no statistically significant difference in mortality between patients with or without RFS regardless of which criteria were used. Age was the only variable associated with death at one-year. The Kappa analysis showed very low agreement between the categories., Conclusion: Our results show that using different diagnostic criteria significantly impacts incidence rates. However, regardless of criteria used, the mortality was not significantly higher in the group of patients with RFS compared to the patients without RFS. Furthermore, none of the criteria showed a significant association with death at one-year. This supports the need for a global unified diagnostic criterion for RFS. This study was registered in ClinicalTrials.gov (identifier NCT03141489)., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Preschool screening of attention-deficit/hyperactivity disorder (ADHD) has been found too inaccurate to be clinically useful. This may be due to the known instability of ADHD symptoms from preschool onwards, and the use of a single screening only. We hypothesized that by identifying a group of children with persistent ADHD from preschool to school age and repeating the screening, the clinical usefulness of screening would increase. This study is part of the prospective longitudinal, population-based Norwegian Mother, Father and Child Cohort Study, with a diagnostic parent interview at 3.5 years and follow-up with parent questionnaires at ages 5 and 8 years (n = 707). We identified a group classified with ADHD at all three time points (persistent ADHD). We then used the Child Behavior Checklist ADHD DSM-oriented scale at ages 3.5 and 5 years to investigate the accuracies of single- and two-stage screening at different thresholds to identify children with persistent ADHD. About 30% of the children were classified with ADHD at least once across time (at ages 3.5, 5, and/or 8 years), but only 4% (n = 30) had persistent ADHD. At all thresholds, the two-stage screening identified children with persistent ADHD more accurately than single screening, mainly due to a substantial reduction in false positives. Only a small group of children were classified with persistent ADHD from preschool to school age, underlining that future screening studies should distinguish this group from those with fluctuating symptoms when estimating screening accuracies. We recommend a two-stage screening process to reduce false positives., (© 2023. The Author(s).)

Objective: To validate self-reported hysterectomy and bilateral oophorectomy., Design: Validation study., Setting: Large population-based cohort study in Norway: The Trøndelag Health Study (HUNT)., Population: The Trøndelag Health Study 2 and 3 (HUNT2 and HUNT3) included questions on gynaecological history. Women who answered questions regarding hysterectomy and/or oophorectomy were included. In total, 30 263 women were included from HUNT2 (1995-1997) and 23 138 from HUNT3 (2006-2008), of which 16 261 attended both HUNT2 and HUNT3., Methods: We compared self-reported hysterectomy and bilateral oophorectomy with electronic hospital procedure codes., Main Outcome Measures: Sensitivity, specificity, positive predictive value and negative predictive value of self-reported hysterectomy and bilateral oophorectomy, by comparing with hospital procedure codes., Results: Self-reported hysterectomy and bilateral oophorectomy in HUNT2 and/or HUNT3 both had specificity and negative predictive value above 99%. Self-reported hysterectomy had a sensitivity of 95.9%, and for bilateral oophorectomy sensitivity was 91.2%. Positive predictive value of self-reported hysterectomy was 85.8%, but for self-reported bilateral oophorectomy it was 65.4%., Conclusions: Self-reported hysterectomy corresponded quite well with hospital data and can be used in epidemiological studies. Self-reported bilateral oophorectomy, on the other hand, had low positive predictive value, and results based on such data should be interpreted with caution. Women who report no previous hysterectomy or bilateral oophorectomy can safely be classified as unexposed to these surgeries., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objectives: The objective was to identify modifiable prognostic factors of high societal costs among people on sick leave due to musculoskeletal disorders, and to identify modifiable prognostic factors of high costs related to separately healthcare utilisation and productivity loss., Design: A prospective cohort study with a 1-year follow-up., Participants and Setting: A total of 549 participants (aged 18-67 years) on sick leave (≥ 4 weeks) due to musculoskeletal disorders in Norway were included., Outcome Measures and Method: The primary outcome was societal costs aggregated for 1 year of follow-up and dichotomised as high or low, defined by the top 25th percentile. Secondary outcomes were high costs related to separately healthcare utilisation and productivity loss aggregated for 1 year of follow-up. Healthcare utilisation was collected from public records and included primary, secondary and tertiary healthcare use. Productivity loss was collected from public records and included absenteeism, work assessment allowance and disability pension. Nine modifiable prognostic factors were selected based on previous literature. Univariable and multivariable binary logistic regression analyses were performed to identify associations (crude and adjusted for selected covariates) between each modifiable prognostic factor and having high costs., Results: Adjusted for selected covariates, six modifiable prognostic factors associated with high societal costs were identified: pain severity, disability, self-perceived health, sleep quality, return to work expectation and long-lasting disorder expectation. Depressive symptoms, work satisfaction and health literacy showed no prognostic value. More or less similar results were observed when high costs were related to separately healthcare utilisation and productivity loss., Conclusion: Factors identified in this study are potential target areas for interventions which could reduce high societal costs among people on sick leave due to musculoskeletal disorders. However, future research aimed at replicating these findings is warranted., Trial Registration Number: NCT04196634, 12 December 2019., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To document the impact of early follow-up by specialized cleft nurses (SCNs) provided to families affected by cleft lip and/or palate (CL/P) and the status of parental stress, infant feeding and well-being., Design: Prospective inclusion of a control group, which only received standard care, followed by an intervention group that also received early SCN follow-up., Setting: The cleft lip and palate team at Oslo University Hospital, Norway., Participants: Seventy families (69 mothers and 57 fathers) distributed into an intervention group (n = 32) and a control group (n = 38)., Intervention: SCNs provided a consultation at the maternity ward and a follow-up conversation by phone or face-to-face at scheduled times for six months., Outcome Measures: Parental Stress Index (PSI), Perceived Stress Scale (PSS-14), feeding questionnaire, survey of infant diets, weight percentiles., Results: The mothers reported higher stress scores than the fathers, but in the control group only in the PSI parent domain at T2 and T3 ( P  = .007, P  = .018). Infants in the intervention group used pacifiers less frequently than in the control group (55.2% vs. 81.1%, P  = .023). Otherwise, no significant differences were found between the groups. Overall, the infants received less breast milk than norms., Conclusion: Contextual strategies for early follow-up of families affected by clefts need to be developed, with an emphasis on involving fathers and those parents reporting elevated stress and/or feeding difficulties. There is a need for diagnosis-specific guidelines about the use of pacifiers as well as collaboration between the health professionals involved to increase breastmilk feeding., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To test the hypothesis that long-chain polyunsaturated fatty acid (LC-PUFA) supplementation improves lung function at 3 months corrected age (CA) compared with standard treatment in very preterm infants. We also aimed to investigate the association between bronchopulmonary dysplasia (BPD), longitudinal growth, and lung function at 3 months CA., Methods: A secondary analysis from the ImNuT trial, in which 121 infants with gestational age <29 weeks were randomized to a daily supplement with arachidonic acid (ARA) and docosahexaenoic acid (DHA) (ARA:DHA group) or MCT-oil (control group) from birth up to 36 weeks postmenstrual age (PMA). Lung function was assessed at 3 months CA by tidal flow volume loops and the outcomes were the ratio of time to peak tidal expiratory flow to expiratory time (t PTEF /t E ) and tidal volume (V T ) per body weight (mL/kg)., Results: Thirty-nine infants in the ARA:DHA group versus 51 in the control group had a successful lung function test. There was no mean difference (MD) in t PTEF /t E ratio (MD: 0.01, 95% confidence interval [CI]: -0.04 to 0.05; p = .77) or V T (MD: 0.09 mL/kg, 95% CI: -0.79 to 0.62; p = .81) between the study groups. The multivariable regression model showed that BPD was associated with t PTEF /t E ratio ≤ 0.25 (p = .03) and that an increase in z score for length after 36 weeks PMA correlated positively with V T (mL/kg) (p = .03)., Conclusion: Neonatal LC-PUFA supplementation did not improve lung function at 3 months CA in very preterm infants. BPD was independently associated with reduced lung function, while improved linear growth correlated with higher tidal volumes., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Despite substantial research evidence indicating the effectiveness of a range of interventions to prevent falls, uptake into routine clinical practice has been limited by several implementation challenges. The complexity of fall prevention in municipality health care underlines the importance of flexible implementation strategies tailored both to general determinants of fall prevention and to local contexts. This cluster-randomised trial (RCT) investigates the effectiveness of a tailored intervention to implement national recommendations on fall prevention among older home-dwelling adults compared to usual practice on adherence to the recommendations in health professionals., Methods: Twenty-five municipalities from four regions in Norway will be randomised to intervention or control arms. Each municipality cluster will recruit up to 30 health professionals to participate in the study as responders. The tailored implementation intervention comprises four components: (1) identifying local structures for implementation, (2) establishing a resource team from different professions and levels, (3) promoting knowledge on implementation and fall prevention and (4) supporting the implementation process. Each of these components includes several implementation activities. The Consolidated Framework for Implementation Research (CFIR) will be used to categorise determinants of the implementation process and the Expert Recommendations for Implementing Change (ERIC) will guide the matching of barriers to implementation strategies. The primary outcome measure for the study will be health professionals' adherence to the national recommendations on fall prevention measured by a questionnaire. Secondary outcomes include injurious falls, the feasibility of the intervention, the experiences of the implementation process and intervention costs. Measurements will be carried out at baseline in August 2023, post-intervention in May 2024 and at a follow-up in November 2024., Discussion: This study will provide evidence on the effectiveness, intervention costs and underlying processes of change of tailored implementation of evidence-based fall prevention recommendations., Trial Registration: The trial is registered in the Open Science Registry: https://doi.org/10.17605/OSF.IO/JQ9T5 . Registered: March 03, 2023., (© 2024. The Author(s).)

Aims: Despite limited clinical scientific backing, an additional trochanteric stabilizing plate (TSP) has been advocated when treating unstable trochanteric fractures with a sliding hip screw (SHS). We aimed to explore whether the TSP would result in less post operative fracture motion, compared to SHS alone., Methods: Overall, 31 patients with AO/OTA 31-A2 trochanteric fractures were randomized to either a SHS alone or a SHS with an additional TSP. To compare postoperative fracture motion, radiostereometric analysis (RSA) was performed before and after weightbearing, and then at four, eight, 12, 26, and 52 weeks. With the "after weightbearing" images as baseline, we calculated translations and rotations, including shortening and medialization of the femoral shaft., Results: Similar migration profiles were observed in all directions during the course of healing. At one year, eight patients in the SHS group and 12 patients in the TSP group were available for analysis, finding a clinically non-relevant, and statistically non-significant, difference in total translation of 1 mm (95% confidence interval -4.7 to 2.9) in favour of the TSP group. In line with the migration data, no significant differences in clinical outcomes were found., Conclusion: The TSP did not influence the course of healing or postoperative fracture motion compared to SHS alone. Based on our results, routine use of the TSP in AO/OTA 31-A2 trochanteric fractures cannot be recommended. The TSP has been shown, in biomechanical studies, to increase stability in sliding hip screw constructs in both unstable and intermediate stable trochanteric fractures, but the clinical evidence is limited. This study showed no advantage of the TSP in unstable (AO 31-A2) fractures in elderly patients when fracture movement was evaluated with radiostereometric analysis., Competing Interests: The following authors have disclosures, all of which are unrelated to this paper: C. E. Alm and J. E. Madsen report payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Smith & Nephew and AO Foundation. F. Frihagen declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Smith & Nephew, and receipt of educational materials from Depuy Synthes. L. Nordsletten discloses payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Ortomedic. S. M. Röhrl reports payment for lectures from Tecres and Link, and being an advisory board member for the Norwegian Arthroplasty Registry and vice-president for the international Radiostereometric Society., (© 2024 Frihagen et al.)

Background: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important structural components of neural cellular membranes and possess anti-inflammatory properties. Very preterm infants are deprived of the enhanced placental supply of these fatty acids, but the benefit of postnatal supplementation on brain development is uncertain. The aim of this study was to test the hypothesis that early enteral supplementation with ARA and DHA in preterm infants improves white matter (WM) microstructure assessed by diffusion-weighted MRI at term equivalent age., Methods: In this double-blind, randomized controlled trial, infants born before 29 weeks gestational age were allocated to either 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) or medium chain triglycerides (control). Supplements were started on the second day of life and provided until 36 weeks postmenstrual age. The primary outcome was brain maturation assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS) analysis., Results: We included 120 infants (60 per group) in the trial; mean (range) gestational age was 26 +3 (22 +6 - 28 +6 ) weeks and postmenstrual age at scan was 41 +3 (39 +1 - 47+ 0 ) weeks. Ninety-two infants underwent MRI imaging, and of these, 90 had successful T1/T2 weighted MR images and 74 had DTI data of acceptable quality. TBSS did not show significant differences in mean or axial diffusivity between the groups, but demonstrated significantly higher fractional anisotropy in several large WM tracts in the ARA:DHA group, including corpus callosum, the anterior and posterior limb of the internal capsula, inferior occipitofrontal fasciculus, uncinate fasciculus, and the inferior longitudinal fasciculus. Radial diffusivity was also significantly lower in several of the same WM tracts in the ARA:DHA group., Conclusion: This study suggests that supplementation with ARA and DHA at doses matching estimated fetal accretion rates improves WM maturation compared to control treatment, but further studies are needed to ascertain any functional benefit., Clinical Trial Registration: www., Clinicaltrials: gov; ID:NCT03555019., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The aims of this nationwide retrospective cohort study were to determine the time and causes of detection of severe congenital heart defects (CHDs) in live-born infants in Norway between 2017 and 2020., Methods: Information regarding live-born infants with severe CHDs was retrieved from national registries and medical records., Results: A total of 219 776 infants were born in Norway from 01.01.2017 to 31.12.2020. Severe CHDs were diagnosed in 442 (0.2%) infants. Of these, 376 (85%) infants were diagnosed either prenatally (n = 203, 46%) or before discharge from hospital after birth (n = 173, 39%). A total of 56 (13%) infants were discharged with undetected CHDs. Time of detection was unknown in 10 cases (2%). The most frequent undetected CHDs at discharge were coarctation of the aorta/aortic arch hypoplasia (n = 24), atrioventricular septal defect (n = 13), anomalous pulmonary venous connection (n = 5) and coronary artery anomalies (n = 4). Seven (13%) children with undetected CHD experienced circulatory collapse out of hospital., Conclusion: Most infants with severe CHDs in Norway were identified prior to hospital discharge. However, some infants were discharged undiagnosed. Awareness of undetected CHDs and immediate cardiac assessment in infants with signs of circulatory failure early in life are still important., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Acute sleep deprivation has been shown to affect cerebrospinal fluid and plasma concentrations of biomarkers associated with neurodegeneration, though the mechanistic underpinnings remain unknown. This study compared individuals who, for one night, were either subject to total sleep deprivation or free sleep, (i) examining plasma concentrations of neurodegeneration biomarkers the morning after sleep deprivation or free sleep and (ii) determining how overnight changes in biomarkers plasma concentrations correlate with indices of meningeal lymphatic and glymphatic clearance functions. Plasma concentrations of amyloid-β 40 and 42, phosphorylated tau peptide 181, glial fibrillary acid protein and neurofilament light were measured longitudinally in subjects who from Day 1 to Day 2 either underwent total sleep deprivation ( n = 7) or were allowed free sleep ( n = 21). The magnetic resonance imaging contrast agent gadobutrol was injected intrathecally, serving as a cerebrospinal fluid tracer. Population pharmacokinetic model parameters of gadobutrol cerebrospinal fluid-to-blood clearance were utilized as a proxy of meningeal lymphatic clearance capacity and intrathecal contrast-enhanced magnetic resonance imaging as a proxy of glymphatic function. After one night of acute sleep deprivation, the plasma concentrations of amyloid-β 40 and 42 were reduced, but not the ratio, and concentrations of the other biomarkers were unchanged. The overnight change in amyloid-β 40 and 42 plasma concentrations in the sleep group correlated significantly with indices of meningeal lymphatic clearance capacity, while this was not seen for the other neurodegeneration biomarkers. However, overnight change in plasma concentrations of amyloid-β 40 and 42 did not correlate with the glymphatic marker. On the other hand, the overnight change in plasma concentration of phosphorylated tau peptide 181 correlated significantly with the marker of glymphatic function in the sleep deprivation group but not in the sleep group. The present data add to the evidence of the role of sleep and sleep deprivation on plasma neurodegeneration concentrations; however, the various neurodegeneration biomarkers respond differently with different mechanisms behind sleep-induced alterations in amyloid-β and tau plasma concentrations. Clearance capacity of meningeal lymphatics seems more important for sleep-induced changes in amyloid-β 40 and 42 plasma concentrations, while glymphatic function seems most important for change in plasma concentration of phosphorylated tau peptide 181 during sleep deprivation. Altogether, the present data highlight diverse mechanisms behind sleep-induced effects on concentrations of plasma neurodegeneration biomarkers., Competing Interests: P.K.E. and G.R. are shareholders in BrainWide Solutions AS, Oslo, Norway, which is a holder of patent US 11 272 841. K.B. has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics and Siemens Healthineers and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. H.Z. has served at scientific advisory boards and/or as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZpath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, NervGen, Novo Nordisk, OptoCeutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

BACKGROUNDIntrathecal injection is an attractive route through which drugs can be administered and directed to the spinal cord, restricted by the blood-spinal cord barrier. However, in vivo data on the distribution of cerebrospinal fluid (CSF) substances in the human spinal cord are lacking. We conducted this study to assess the enrichment of a CSF tracer in the upper cervical spinal cord and the brain stem.METHODSAfter lumbar intrathecal injection of a magnetic resonance imaging (MRI) contrast agent, gadobutrol, repeated blood samples and MRI of the upper cervical spinal cord, brain stem, and adjacent subarachnoid spaces (SAS) were obtained through 48 hours. The MRI scans were then analyzed for tracer distribution in the different regions and correlated to age, disease, and amounts of tracer in the blood to determine CSF-to-blood clearance.RESULTSThe study included 26 reference individuals and 35 patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH). The tracer enriched all analyzed regions. Moreover, tracer enrichment in parenchyma was associated with tracer enrichment in the adjacent SAS and with CSF-to-blood clearance. Clearance from the CSF was delayed in patients with iNPH compared with younger reference patients.CONCLUSIONA CSF tracer substance administered to the lumbar thecal sac can access the parenchyma of the upper cervical spinal cord and brain stem. Since CSF-to-blood clearance is highly individual and is associated with tracer level in CSF, clearance assessment may be used to tailor intrathecal treatment regimes.FUNDINGSouth-Eastern Norway Regional Health and Østfold Hospital Trust supported the research and publication of this work.

Background & Aims: A balanced supply of arachidonic acid (ARA) and docosahexaenoic acid (DHA) may be crucial for quality of growth in preterm infants. This secondary analysis of a randomized controlled trial aimed to determine the effect of enhanced ARA and DHA supplementation on growth and body composition in infants born before 29 weeks of gestation. Furthermore, we aimed to study associations between human milk feeding, growth patterns and body composition., Methods: The ImNuT-trial randomized 121 infants to receive a daily supplement with medium chain triglycerides (control) or 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) from the second day of life until 36 weeks postmenstrual age. Growth and body composition were evaluated up to 3 months corrected age., Results: The ARA:DHA group showed better linear growth from birth to term equivalent age compared to the control group; mean difference in z score change from birth for length was 0.74 ([95% CI, 0.17-1.3]; p = 0.010). There were no differences in growth and body composition outcomes at 3 months corrected age between the groups. An increase in z score for weight after 36 weeks postmenstrual age and breastfeeding at 3 months corrected age were the strongest positive predictors of fat mass% at 3 months corrected age (both, p < 0.001)., Conclusion: Early enhanced supplementation of ARA and DHA may be beneficial with respect to somatic growth in very preterm infants., Clinical Trial Registration: The trial has been registered on www., Clinicaltrials: gov, ID: NCT03555019., Competing Interests: Conflict of interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Abstract: Prognostic prediction models for 3 different definitions of nonrecovery were developed in the Back Complaints in the Elders study in the Netherlands. The models' performance was good (optimism-adjusted area under receiver operating characteristics [AUC] curve ≥0.77, R2 ≥0.3). This study aimed to assess the external validity of the 3 prognostic prediction models in the Norwegian Back Complaints in the Elders study. We conducted a prospective cohort study, including 452 patients aged ≥55 years, seeking primary care for a new episode of back pain. Nonrecovery was defined for 2 outcomes, combining 6- and 12-month follow-up data: Persistent back pain (≥3/10 on numeric rating scale) and persistent disability (≥4/24 on Roland-Morris Disability Questionnaire). We could not assess the third model (self-reported nonrecovery) because of substantial missing data (>50%). The models consisted of biopsychosocial prognostic factors. First, we assessed Nagelkerke R2 , discrimination (AUC) and calibration (calibration-in-the-large [CITL], slope, and calibration plot). Step 2 was to recalibrate the models based on CITL and slope. Step 3 was to reestimate the model coefficients and assess if this improved performance. The back pain model demonstrated acceptable discrimination (AUC 0.74, 95% confidence interval: 0.69-0.79), and R2 was 0.23. The disability model demonstrated excellent discrimination (AUC 0.81, 95% confidence interval: 0.76-0.85), and R2 was 0.35. Both models had poor calibration (CITL <0, slope <1). Recalibration yielded acceptable calibration for both models, according to the calibration plots. Step 3 did not improve performance substantially. The recalibrated models may need further external validation, and the models' clinical impact should be assessed., (Copyright © 2023 International Association for the Study of Pain.)

Introduction:  During the last quarter of a century, new surgical techniques in neonates have been introduced, and neonatal intensive care has developed. Few studies have explored the implementation of new techniques and if outcomes in neonates undergoing gastrointestinal surgery have improved in the last decades. Therefore, this study aimed to investigate possible changes in postoperative outcomes and surgical techniques in all neonates operated for congenital duodenal obstruction (CDO) 1995 to 2020 in Norway., Material and Methods:  This is a national multicenter retrospective study of all neonates undergoing surgery for CDO in Norway from 1995 to 2020. Results from three periods (1995-2003, 2004-2012, and 2013-2020) were compared. The study was approved by the local data protection officers (2020/13386) and (2020/15125)., Results:  We included 186 patients: 41 in period 1 (1995-2003), 83 in period 2 (2004-2012), and 62 in period 3 (2013-2020). Seventy (38%) neonates had Down syndrome and 104 (62%) had additional malformations/disorders. Birth weight, gender, frequency of Down syndrome, and other malformations/disorders did not differ between the three periods. We observed an increased rate of prenatal diagnosis throughout the study period ( p  < 0.001). The only change in surgical technique was the increased use of transanastomotic feeding tubes ( p  < 0.001). Length of stay, postoperative complication rate, days with parenteral nutrition, and 30-day mortality rate were stable over time., Conclusion:  Perioperative treatment and postoperative outcomes in neonates with CDO have been surprisingly unchanged during the last quarter of a century. Only an increased rate of prenatal diagnosis and more frequent use of transanastomotic feeding tubes were observed., Competing Interests: None declared., (Thieme. All rights reserved.)

Background/objective: There is no international consensus about the optimal approach to screening and diagnosis of gestational diabetes mellitus (GDM). Fasting plasma glucose (FPG) has been proposed as an alternative universal screening test to simplify the diagnosis of GDM. We investigate the ability of the FPG to predict a 2-hour glucose value below the cut-off for GDM, thereby "ruling out" the necessity of a full OGTT and assess the proportion of GDM-related complications associated with the identified FPG level., Materials and Methods: This study included secondary data from four Norwegian pregnancy cohorts (2002-2013), encompassing 2960 women universally screened with late mid-pregnancy 75g OGTT measuring FPG and 2-hour glucose. For a range of FPG thresholds, we calculated sensitivity to predict elevated 2-hour glucose, number of OGTTs needed and percentage of GDM cases missed, applying modified World Health Organization (WHO) 2013 criteria ( 2013 WHO) and 2017 Norwegian criteria ( 2017 Norwegian). We analyzed pregnancy outcomes for women above and below our selected threshold., Results: The prevalence of GDM was 16.6% ( 2013 WHO) and 10.1% ( 2017 Norwegian). A FPG threshold of 4.7 mmol/L had a sensitivity of 76% ( 2013 WHO) and 80% ( 2017 Norwegian) for detecting elevated 2-hour glucose, with few missed GDM cases (2.0% of those ruled out and 7.5% of all GDM cases for 2013 WHO, and 1.1% of those ruled out and 7% of all GDM cases for 2017 Norwegian). When excluding women with FPG <4.7mmol/l and those with GDM based on FPG, only 24% ( 2013 WHO) and 29% ( 2017 Norwegian) would require OGTT. Women with FPG <4.7mmol/l, including missed GDM cases, had low risk of large-for-gestational-age newborns, cesarean section and operative vaginal delivery., Conclusion: A FPG threshold of 4.7mmol/l as a first step when screening for GDM could potentially eliminate the need for OGTT in 70-77% of pregnancies. Women with FPG below this threshold appear to carry low risk of GDM-associated adverse pregnancy outcomes., Competing Interests: The 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 © 2023 Rai, Sletner, Jenum, Øverby, Stafne, Qvigstad, Pripp and Sagedal.)

Objectives: This study evaluates the six-month cost-effectiveness and cost-benefits of motivational interviewing (MI) or a stratified vocational advice intervention (SVAI) added to usual case management (UC) for workers on sick leave due to musculoskeletal disorders., Methods: This study was conducted alongside a three-arm RCT including 514 employed workers on sick leave for at least 50% for ≥ 7 weeks. All participants received UC. The UC + MI group received two MI sessions, and the UC + SVAI group received 1-4 SVAI sessions. Sickness absence days, quality-adjusted life-years (QALYs), and societal costs were measured between baseline and six months., Results: Adding MI to UC, resulted in incremental cost-reduction of -2580EUR (95%CI -5687;612), and a reduction in QALYs of -0.001 (95%CI -0.02;0.01). Secondly, adding MI to UC resulted in an incremental cost-reduction of -538EUR (95%CI -1358;352), and reduction of 5.08 (95%CI -3.3;13.5) sickness-absence days. Financial return estimates were positive, but not statistically significant. Adding SVAI to UC, resulted in an incremental cost-reduction of -2899 EUR (95% CI -5840;18), and a reduction in QALYs of 0.002 (95% CI -0.02;0.01). Secondly, adding SVAI to UC resulted in an statistically significant incremental cost-reduction of -695 EUR (95% CI -1459;-3), and a reduction of 7.9 (95% CI -0.04;15.9) sickness absence days. Financial return estimates were positive and statistically significant. The probabilities of cost-effectiveness for QALYs were high for adding MI or SVAI (ceiling ratio 0.90)., Conclusions: In comparison to UC only, adding MI to UC tends to be cost-effective. Adding SVAI to UC is cost-effective for workers on sick leave due to musculoskeletal disorders., Trial Registration: ClinicalTrials.gov (identifier: NCT03871712)., (© 2023. The Author(s).)

Objective: A statistically significant improvement in nasal obstruction ratings following septoplasty is not necessarily clinically important. This study aimed to establish useful measures of septoplasty success, namely the minimal clinically important difference and the desirable clinically important difference., Methods: Patients rated nasal obstruction on a 0-100 visual analogue scale pre-operatively and at 5.5 months post-operatively. Global outcome rating (completely, much, or somewhat improved, unchanged or worse) served as the anchor post-operatively. Minimal clinically important difference is the visual analogue scale value between 'somewhat improved' and 'unchanged', and the desirable clinically important difference is that between 'much' and 'somewhat improved'., Results: Statistically significant improvement in visual analogue scale scores was not clinically important. The minimal clinically important difference (daytime value of 9.5) represented 15.1 per cent improvement and the desirable clinically important difference (daytime value of 28.5) represented 45.2 per cent, without gender or age differences., Conclusion: Clinical success can be defined using a minimal clinically important difference of 15 per cent improvement over a patient's baseline value. Other studies' ratings of 'satisfactory' outcome coincided with a desirable clinically important difference of 45 per cent over baseline. These values are suggested as relevant indicators of septoplasty success.

Background and Purpose: Radiostereometric analysis (RSA) is the gold standard for evaluation of migration of implants. CT-RSA has been shown to have precision at the level of RSA in hip, shoulder, and knee joint replacements. We aimed to assess the impact of dose reduction on precision of CT-RSA on tibial implants, comparing it with previously published data on precision of standard dose CT-RSA on tibial implants., Material and Methods: We performed a total knee arthroplasty on a porcine knee cadaver, and subsequent CT-RSA with low effective doses (0.02 mSv). We compared the results with previously published CT-RSA data with standard (0.08 mSv) dose. The primary outcome variable was the difference in precision of the maximum total translation (MTT). Secondary variables included ratios of variances and standard deviations, and precision of peripheral point translations, center-of-mass translations, and rotations. A difference of more than 0.1 mm in precision was defined as clinically relevant. Our hypothesis was that precisions of low and standard CT-RSA doses were equal., Results: Low dose (mean 0.07, 95% confidence interval [CI] 0.06-0.08) and standard dose CT-RSA (0.08, CI 0.07-0.09) achieve similar precision, with difference in precision of MTT of 0.01, CI 0.00-0.02 mm. The F-statistic (0.99, CI 0.63-1.55) and sdtest (1.05, CI 0.43-2.58) also supported this., Conclusion: We conclude that the precision of low dose CT-RSA for tibial implants on a porcine cadaver is equal to standard dose CT-RSA. However, these findings should be confirmed in clinical trials.

Background: Non-cardiac chest pain is common and associated with increased anxiety and reduced health-related quality of life. Randomized controlled trials on psychological interventions for patients with non-cardiac chest pain have reported mixed results. Patients with non-cardiac chest pain are a heterogeneous group. Identifying sub-groups that could potentially benefit more (or less) from an intervention would be valuable knowledge. We have conducted a randomized controlled trial where internet-based cognitive behavioural therapy (iCBT) had effect on reducing cardiac anxiety and increasing health-related quality of life at 12-month follow-up. The aim of the present study was to explore potential effect modifiers of iCBT in patients with non-cardiac chest pain on cardiac anxiety and/or health related quality of life at 12-month follow-up., Methods: We analysed data from our randomized, controlled trial where 161 patients with non-cardiac chest pain were included and randomized to either iCBT or a treatment as usual (control). Cardiac anxiety measured by the Cardiac Anxiety Questionnaire and health-related quality of life measured by the EuroQol Visual Analog Scale at 12 month follow-up were the primary outcomes. Four potential baseline characteristics where identified as potential effect modifiers by a theory-based approach: (1) depression measured by the Patient Health Questionnaire; (2) anxiety measured by the Body Sensations Questionnaire; (3) prior healthcare contacts measured by a self-developed question; and (4) chest pain frequency measured by a self-developed question. Each potential effect modifier was analysed in a linear regression model where cardiac anxiety and EQ-VAS scores at 12-month follow-up, separately, were used as dependent variables. The potential differential treatment effect for each effect modifier was assessed by the interaction term: effect modifier x treatment group., Results: Depression symptoms at baseline predicted a differential treatment effect at 12-month follow-up on health-related quality of life in favor of the iCBT group (regression coefficient of the interaction term: -1.85 (CI -3.28 to -0.41), p = 0.01), but not on cardiac anxiety at 12-month follow-up. Fear of bodily symptoms, chest pain frequency and prior health care contacts at baseline did not predict a treatment effect on either health-related quality of life or cardiac anxiety., Conclusions: Depression symptoms at baseline predicted a positive treatment effect of iCBT on health-related quality of life in patients suffering from non-cardiac chest pain. This indicates that it is important to identify patients with non-cardiac chest pain and co-occurring depression symptoms given that they are particularly likely to benefit from iCBT., Trial Registration: ClinicalTrials.gov NCT03096925 ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To compare treatment effects between ultrasound guided lavage with corticosteroid injection and sham lavage with and without corticosteroid injection in patients with calcific tendinopathy of the shoulder., Design: Pragmatic, three arm, parallel group, double blinded, sham controlled, randomised, superiority trial with repeated measurements over 24 months., Setting: Six hospitals in Norway and Sweden., Participants: 220 adults with calcific tendinopathy of the shoulder, persistent for at least three months., Interventions: Ultrasound guided deposit lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (lavage+steroid); sham lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (sham lavage+steroid); or sham lavage plus subacromial injection of 10 mL 1% lidocaine hydrochloride (sham). All patients received a physiotherapeutic treatment regimen consisting of four home exercises., Main Outcome Measures: The primary outcome was the result on the 48 point scale (0=worst; 48=best) of the Oxford Shoulder Score (OSS) at four month follow-up. Secondary outcomes included measurements on the short form of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) and of pain intensity up to 24 months. The influence of the size of the deposit at baseline and of the persistence or disappearance of the deposit was investigated., Results: Data from 218 (99%) participants were included in the primary analysis. Differences between groups on the OSS at four months were not significant: lavage+steroid versus sham 0.2 (95% confidence interval -2.3 to 2.8; P=1.0); sham lavage+steroid versus sham 2.0 (-0.5 to 4.6; P=0.35); lavage+steroid versus sham lavage+steroid -1.8 (-4.3 to 0.7; P=0.47). After four months, 143 patients with insufficient treatment effect received supplementary treatment. At 24 months, none of the study procedures was superior to sham. No serious adverse events were reported., Conclusions: This study found no benefit for ultrasound guided lavage with a corticosteroid injection or for sham lavage with a corticosteroid injection compared with sham treatment in patients with calcific rotator cuff tendinopathy of the shoulder., Trial Registration: NCT02419040EudraCT 2015-002343-34; Ethical committee Norway 2015-002343-34; Ethical committee Sweden 2015/79-31; Clinicaltrials.gov NCT02419040., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Bergersen Foundation, Aase Bye and Trygve J.B. Hoffs foundation, Smith and Nephew, and the Medical Research Council of Southeast Sweden; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Identifying attention-deficit/hyperactivity disorder (ADHD) in pre-schoolers may improve their development if treated, but it is unclear whether ADHD symptoms from this age are stable enough to merit treatment. We aimed to investigate the stability of parent- and teacher-reported ADHD symptoms and ADHD classified above the diagnostic symptom thresholds, including for hyperactivity-impulsivity (HI), inattention and combined presentations from age 3 to 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. At child age 3 years, parents were interviewed and teachers rated ADHD symptoms. At age 8 years, parents (n = 783) and teachers (n = 335) reported ADHD symptoms by the Child Symptom Inventory-4. We found a significant reduction in the mean number of parent-reported ADHD and HI symptoms from age 3 to 8 years, but otherwise similar mean numbers. Parent-reported ADHD symptoms were moderately correlated between ages, while correlations were low for teachers. A total of 77/108 (71%) of the children classified with parent-reported HI presentation at age 3 years were no longer classified within any ADHD presentation at age 8 years, the only clear trend across time for either informant. There was a low to moderate parent-teacher-agreement in the number of reported symptoms, and very low informant agreement for the classified ADHD presentations. Overall, clinicians should exercise caution in communicating concern about HI symptoms in preschool children. Age 3 years may be too early to apply the ADHD diagnostic symptom criteria, especially if parents and teachers are required to agree., (© 2022. The Author(s).)