The incidence and mortality of refeeding syndrome in older hospitalized patients, based on three different diagnostic criteria: A longitudinal study.

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/m2. 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).

Comparative effectiveness and persistence of SB4 and reference etanercept in patients with psoriatic arthritis in Norway.

OBJECTIVE: We aim to compare drug effectiveness and persistence between reference etanercept (ETN) and ETN biosimilar SB4 in psoriatic arthritis (PsA) patients naïve to ETN and to investigate drug effectiveness and persistence in those undergoing mandatory non-medical switch from ETN to SB4. METHODS: Retrospective comparative database study including 1138 PsA patients 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 propensity score (PS) to adjust for confounders. Drug persistence was analyzed with Kaplan-Meier method. RESULTS: In unmatched analyses, difference in change from baseline between ETN (n=140) and SB4 (n=132) for DAS28 at 1 year was mean 0.67 (95% confidence interval [95%CI] 0.38-0.96) in favor of ETN. In PS-matched analyses, difference in change from baseline between ETN (n=54) and SB4 (n=54) was 0.09 (95%CI -0.33-0.50) and mean difference assessed with ANCOVA model 0.01 (95%CI -0.38-0.40), both within predefined equivalence margin (±0.6). Drug persistence at 1 year was 0.75 (95%CI 0.71-0.78) for ETN, 0.58 (95%CI 0.51-0.63) for SB4, HR 2.45 (95%CI 2.02-2.97) in unmatched analysis, and 0.55 (95%CI 0.46-0.63) for ETN, 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 1 year, outcomes for PsA disease activity and drug persistence were comparable for patients treated with either ETN or SB4. In patients undergoing mandatory non-medical switch from ETN to SB4, drug effectiveness was maintained in 2-year period.

A practical guide to estimating treatment effects in patients with rheumatic diseases using real-world data.

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.

Modifiable prognostic factors of high societal costs among people on sick leave due to musculoskeletal disorders: findings from an occupational cohort study.

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.

Do maternal anxiety and depressive symptoms predict anxiety in children with and without ADHD at 8 years?

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.

Parental Stress, Infant Feeding and Well-being in Families Affected by Cleft Lip and/or Cleft Palate: The Impact of Early Follow-up.

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.

Tailored implementation of national recommendations on fall prevention among older adults in municipalities in Norway (FALLPREVENT trial): a study protocol for a cluster-randomised trial.

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.

Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants; a double blind RCT.

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.

Lung function in preterm infants at 3 months corrected age after neonatal LC-PUFA supplementation.

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 (tPTEF /tE ) and tidal volume (VT ) 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 tPTEF /tE ratio (MD: 0.01, 95% confidence interval [CI]: -0.04 to 0.05; p = .77) or VT (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 tPTEF /tE ratio ≤ 0.25 (p = .03) and that an increase in z score for length after 36 weeks PMA correlated positively with VT (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.

Detection of severe congenital heart defects in live-born infants in Norway 2017-2020.

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.

In vivo distribution of cerebrospinal fluid tracer in human upper spinal cord and brain stem.

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.

Employing fasting plasma glucose to safely limit the use of oral glucose tolerance tests in pregnancy: a pooled analysis of four Norwegian studies.

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 (2013WHO) and 2017 Norwegian criteria (2017Norwegian). We analyzed pregnancy outcomes for women above and below our selected threshold. Results: The prevalence of GDM was 16.6% (2013WHO) and 10.1% (2017Norwegian). A FPG threshold of 4.7 mmol/L had a sensitivity of 76% (2013WHO) and 80% (2017Norwegian) 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 2013WHO, and 1.1% of those ruled out and 7% of all GDM cases for 2017Norwegian). When excluding women with FPG <4.7mmol/l and those with GDM based on FPG, only 24% (2013WHO) and 29% (2017Norwegian) 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.

Mechanisms behind changes of neurodegeneration biomarkers in plasma induced by sleep deprivation.

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-ß 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-ß 40 and 42 were reduced, but not the ratio, and concentrations of the other biomarkers were unchanged. The overnight change in amyloid-ß 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-ß 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-ß and tau plasma concentrations. Clearance capacity of meningeal lymphatics seems more important for sleep-induced changes in amyloid-ß 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.

Six-month cost-effectiveness of adding motivational interviewing or a stratified vocational advice intervention to usual case management for workers with musculoskeletal disorders: the MI-NAV economic evaluation.

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).

Effect of arachidonic and docosahexaenoic acid supplementation on quality of growth in preterm infants: A secondary analysis of a randomized controlled trial.

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.

Patients with depression symptoms are more likely to experience improvements of internet-based cognitive behavioral therapy: a secondary analysis of effect modifiers in patients with non-cardiac chest pain in a randomized controlled trial.

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 .

The Bone Cement Hypercoagulation Syndrome: Pathophysiology, Mortality, and Prevention.

Since Charnley introduced acrylic cement to seal metallic hip prostheses in the 1950s, reports of perioperative fatal cardiorespiratory and vascular dysfunctions have been published. Studies on humans and animals have shown neurogenic stimulation and substantial local and systemic activation of coagulation are caused by surgical bone marrow damage and chemical cell destruction by toxic monomeric methyl methacrylate from the implanted cement and other tissue-released substances. Venous blood-borne cell fragments and conjugates of activated cells from the surgical site are sequestered and trapped in the pulmonary microcirculation. A substantial hypercoagulation occurs in the lung circulation. Hypercoagulable blood is passed over to the arterial side and may cause vessel obliteration and organ damage. This process may affect the brain, heart, and kidneys and, through the release of vasoactive substances, introduce hemodynamic imbalances that can lead to fatal outcomes in susceptible populations such as elderly patients with hip fractures. The main underlying pathophysiologic processes leading to these occasionally devastating outcomes are a substantial activation of coagulation and cell destruction caused by the toxic substance released by curing bone cement and several vasoactive substances.

Ultrasound guided lavage with corticosteroid injection versus sham lavage with and without corticosteroid injection for calcific tendinopathy of shoulder: randomised double blinded multi-arm study.

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.

Anxiety and depression from age 3 to 8 years in children with and without ADHD symptoms.

Childhood anxiety and depressive symptoms may be influenced by symptoms of attention deficit/hyperactivity disorder (ADHD). We investigated whether parent- and teacher-reported anxiety, depressive and ADHD symptoms at age 3 years predicted anxiety disorders and/or depression in children with and without ADHD at age 8 years. This study is part of the longitudinal, population-based Norwegian Mother, Father and Child Cohort Study. Parents of 3-year-olds were interviewed, and preschool teachers rated symptoms of anxiety disorders, depression and ADHD. At age 8 years (n = 783), Child Symptom Inventory-4 was used to identify children who fulfilled the diagnostic criteria for anxiety disorders and/or depression (hereinafter: Anx/Dep), and ADHD. Univariable and multivariable logistic regression analyses were used. In the univariable analyses, parent-reported anxiety, depressive and ADHD symptoms, and teacher-reported anxiety symptoms at age 3 years all significantly predicted subsequent Anx/Dep. In the multivariable analyses, including co-occurring symptoms at age 3 years and ADHD at 8 years, parent-reported anxiety and depressive symptoms remained significant predictors of subsequent Anx/Dep. At age 3 years, regardless of ADHD symptoms being present, asking parents about anxiety and depressive symptoms, and teachers about anxiety symptoms, may be important to identify children at risk for school-age anxiety disorders and/or depression.