Efficacy of naproxen in patients with sciatica: multicentre, randomized, double-blind, placebo-controlled trial.

ABSTRACT: This trial assessed the efficacy of naproxen in patients with sciatica in outpatient clinics across 4 Norwegian hospitals. A total of 123 adults with radiating pain below the knee (≥4 on a 0-10 numeric rating scale) and signs consistent with nerve root involvement were included. Participants were randomized to receive either naproxen 500 mg or a placebo twice daily for 10 days. The primary outcome, daily leg pain intensity measured on a 0 to 10 numeric rating scale throughout the treatment period, revealed a statistically significant difference in favor of naproxen, with an adjusted mean difference of -0.5 (95% CI -0.8 to -0.1, P = 0.015). In the naproxen group, the treatment effect was significantly related to time, and over the whole 10-day period, the average adjusted difference was -0.6 (95% CI -0.8 to -0.5). Mean numbers needed to treat for 30% and 50% improvement were 9.9 (95% CI 4.7-15.0) and 20.7 (8.7-32.7), respectively. The adjusted mean difference for back pain was -0.4 (95% CI -0.8 to 0.0), and for Roland Morris Disability Questionnaire for Sciatica, it was -1.5 (95% CI -3.0 to 0.0). No differences were found for sciatica bothersomeness or consumption of rescue medication or opioids. Participants in the naproxen group exhibited an adjusted odds ratio of 4.7 (95% CI 1.3-16.2) for improvement by 1 level on the global perceived change scale. In conclusion, naproxen treatment showed small, likely clinically unimportant benefits compared with placebo in patients with moderate-to-severe sciatica.

Physical activity following pulmonary embolism and clinical correlates in selected patients: a cross-sectional study.

Background: There is limited knowledge regarding physical activity and clinical correlates among people who have suffered a pulmonary embolism (PE). Objectives: To assess physical activity levels after PE and potential clinical correlates. Methods: One hundred forty-five individuals free of major comorbidities were recruited at a mean of 23 months (range, 6-72) after PE diagnosis. Physical activity was assessed by steps/day on the Sensewear monitor for 7 consecutive days, exercise capacity with the incremental shuttle walk test, and cardiac function with left ventricular ejection fraction (LVEF). The association between physical activity and other variables was analyzed by a mixed-effects model. Results: Participants achieved a mean of 6494 (SD, 3294; range, 1147-18.486) steps/day. The mixed-effects model showed that physical activity was significantly associated with exercise capacity (ß-coefficient, 0.04; 95% CI, 0.03-0.05) and LVEF (ß-coefficient, -0.81; 95% CI, -1.42 to -0.21). The analysis further showed that men became less physically active with increasing age (ß-coefficient, -0.14; 95% CI, -0.24 to -0.04), whereas no change with age could be detected for women. Conclusion: In selected post-PE patients, physical activity seems to be associated with exercise capacity and LVEF but not with quality of life, dyspnea, or characteristics of the initial PE. Men appear to become less physically active with increasing age.

Impulsivity across severe mental disorders: a cross-sectional study of immune markers and psychopharmacotherapy.

BACKGROUND: Impulsivity is a transdiagnostic feature linked to severe clinical expression and a potential target for psychopharmacological strategies. Biological underpinnings are largely unknown, but involvement of immune dysregulation has been indicated, and the effects of psychopharmacological agents vary. We investigated if impulsivity was associated with circulating immune marker levels and with a range of psychopharmacological treatment regimens in severe mental disorders. METHODS: Impulsivity was assessed in a sample (N = 657) of patients with schizophrenia or schizophreniform disorder (SCZ) (N = 116) or bipolar disorder (BD) (N = 159) and healthy participants (N = 382) using the Barratt Impulsiveness Scale (BIS-11) questionnaire. Plasma levels of systemic immune markers (RANTES, IL-1RA, IL-18, IL-18BP, sTNFR-1) were measured by enzyme immunoassays. Patients underwent thorough clinical assessment, including evaluation of psychotropic medication. Associations were assessed using linear regressions. RESULTS: Impulsivity  was positively associated with SCZ (p < 0.001) and BD (p < 0.001) diagnosis and negatively associated with age (p < 0.05), but not significantly associated with any of the circulating immune markers independently of diagnostic status. Among patients, impulsivity was negatively associated with lithium treatment (p = 0.003) and positively associated with antidepressant treatment (p = 0.011) after controlling for diagnosis, psychotropic co-medications, manic symptoms, and depressive symptoms. CONCLUSIONS: We report elevated impulsivity across SCZ and BD but no associations to systemic immune dysregulation based on the current immune marker selection. The present study reveals associations between impulsivity in severe mental disorders and treatment with lithium and antidepressants, with opposite directions. Future studies are warranted to determine the causal directionality of the observed associations with psychopharmacotherapy.

The relationship between the brain-derived neurotrophic factor and neurocognitive response to physical exercise in individuals with schizophrenia.

OBJECTIVE: Physical exercise can improve neurocognition in individuals with schizophrenia, presumably by facilitating neuroplasticity. There is, however, large inter-individual variation in response. The brain-derived neurotrophic factor (BDNF) has been proposed to mediate these effects. The current aim was to investigate the sparsely studied relationship between peripheral resting BDNF and neurocognitive response to physical exercise in individuals with schizophrenia. METHOD: The current study reports secondary analyses of data from a randomized controlled trial (RCT), ClinicalTrials.gov number 02205684, recently reported according to the CONSORT guidelines. Eighty-two individuals with schizophrenia (mean age 37 ± 14 years old, 61% men) were randomly allocated to high-intensity interval training (HIIT) or a comparison group performing low-intensity active video gaming (AVG). Both interventions consisted of 2 sessions/week for 12 weeks. In previously published primary RCT analyses, HIIT and AVG showed comparable small to moderate improvements in neurocognition. We now address the inter-individual variability in neurocognitive response. We apply mediation and moderation analyses for repeated measures designs (MEMORE) and mixed effects models. RESULTS: Baseline neurocognition was not significantly correlated with baseline levels of mature BDNF (baseline-mBDNF) or the precursor proBDNF. Nonetheless, baseline-mBDNF, but not baseline proBDNF, moderated the effect of exercise on neurocognition (p = 0.025) and explained 7% of the variance. The neurocognitive improvement increased with increasing baseline-mBDNF values. The moderating effect of baseline-mBDNF remained significant in a more complex model adding the moderating effects of exercise mode, sex, age, duration of illness and baseline VO2max on the outcome (neurocognition). Mean baseline-mBDNF significantly decreased from baseline to post-intervention (p = 0.036), regardless of exercise mode, differing by sex and associated with improved VO2max but not with change in neurocognition. A mediating role of mBDNF on the effect of physical exercise on neurocognition was not supported. Values of proBDNF mainly remained stable from baseline to post-intervention. CONCLUSION: We found that baseline-mBDNF moderated the effect of physical exercise on neurocognition in individuals with schizophrenia and explained a small part of the inter-individual variation in neurocognitive response. Mean mBDNF decreased from baseline to post-intervention, regardless of exercise mode. A mediating role of mBDNF on the effect of exercise on neurocognition was not supported. The inter-individual variation in neurocognitive response and the complex role of peripheral BDNF in physical exercise is still to be elucidated.

Does the clot burden as assessed by the Mean Bilateral Proximal Extension of the Clot score reflect mortality and adverse outcome after pulmonary embolism?

Background: Rapid diagnosis and risk stratification are important to reduce the risk of adverse clinical events and mortality in acute pulmonary embolism (PE). Although clot burden has not been consistently shown to correlate with disease outcomes, proximally located PE is generally perceived as more severe. Purpose: To explore the ability of the Mean Bilateral Proximal Extension of the Clot (MBPEC) score to predict mortality and adverse outcome. Methods: This was a single center retrospective cohort study. 1743 patients with computed tomography pulmonary arteriography (CTPA) verified PE diagnosed between 2005 and 2020 were included. Patients with active malignancy were excluded. The PE clot burden was assessed with MBPEC score: The most proximal extension of PE was scored in each lung from 1 = sub-segmental to 4 = central. The MBPEC score is the score from each lung divided by two and rounded up to nearest integer. Results: We found inconsistent associations between higher and lower MBPEC scores versus mortality. The all-cause 30-day mortality of 3.9% (95% CI: 3.0-4.9). The PE-related mortality was 2.4% (95% CI: 1.7-3.3). Patients with MBPEC score 1 had higher all-cause mortality compared to patients with MBPEC score 4: Crude Hazard Ratio (cHR) was 2.02 (95% CI: 1.09-3.72). PE-related mortality was lower in patients with MBPEC score 3 compared to score 4: cHR 0.22 (95% CI: 0.05-0.93). Patients with MBPEC score 4 did more often receive systemic thrombolysis compared to patients with MBPEC score 1-3: 3.2% vs. 0.6% (p < .001). Patients with MBPEC score 4 where more often admitted to the intensive care unit: 13% vs. 4.7% (p < .001). Conclusion: We found no consistent association between the MBPEC score and mortality. Our results therefore indicate that peripheral PE does not necessarily entail a lower morality risk than proximal PE.

The Effects of Exercise Training in Patients With Persistent Dyspnea Following Pulmonary Embolism: A Randomized Controlled Trial.

BACKGROUND: Persistent dyspnea, functional limitations, and reduced quality of life (QoL) are common following pulmonary embolism (PE). Rehabilitation is a potential treatment option, but the scientific evidence is limited. RESEARCH QUESTION: Does an exercise-based rehabilitation program improve exercise capacity in PE survivors with persistent dyspnea? STUDY DESIGN AND METHODS: This randomized controlled trial was conducted at two hospitals. Patients with persistent dyspnea following PE diagnosed 6 to 72 months earlier, without cardiopulmonary comorbidities, were randomized 1:1 to either the rehabilitation or the control group. The rehabilitation program consisted of two weekly sessions of physical exercise for 8 weeks and one educational session. The control group received usual care. The primary end point was the difference in Incremental Shuttle Walk Test between groups at follow-up. Secondary end points included differences in the Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D and Pulmonary Embolism-QoL questionnaires) and dyspnea (Shortness of Breath questionnaire). RESULTS: A total of 211 subjects were included: 108 (51%) were randomized to the rehabilitation group and 103 (49%) to the control group. At follow-up, participants allocated to the rehabilitation group performed better on the ISWT compared with the control group (mean difference, 53.0 m; 95% CI, 17.7-88.3; P = .0035). The rehabilitation group reported better scores on the Pulmonary Embolism-QoL questionnaire (mean difference, -4%; 95% CI, -0.09 to 0.00; P = .041) at follow-up, but there were no differences in generic QoL, dyspnea scores, or the ESWT. No adverse events occurred during the intervention. INTERPRETATION: In patients with persistent dyspnea following PE, those who underwent rehabilitation had better exercise capacity at follow-up than those who received usual care. Rehabilitation should be considered in patients with persistent dyspnea following PE. Further research is needed, however, to assess the optimal patient selection, timing, mode, and duration of rehabilitation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03405480; URL: www. CLINICALTRIALS: gov.

SARS-CoV-2 vaccines are not associated with hypercoagulability in apparently healthy people.

Background: SARS-CoV-2 adenoviral vector DNA vaccines have been linked to the rare but serious thrombotic postvaccine complication vaccine-induced immune thrombotic thrombocytopenia. This has raised concerns regarding the possibility of increased thrombotic risk after any SARS-CoV-2 vaccines. Objectives: To investigate whether SARS-CoV-2 vaccines cause coagulation activation leading to a hypercoagulable state. Methods: This observational study included 567 health care personnel; 521 were recruited after the first dose of adenoviral vector ChAdOx1-S (Vaxzevria, AstraZeneca) vaccine and 46 were recruited prospectively before vaccination with a messenger RNA (mRNA) vaccine, either Spikevax (Moderna, n = 38) or Comirnaty (Pfizer-BioNTech, n = 8). In the mRNA group, samples were acquired before and 1 to 2 weeks after vaccination. In addition to the prevaccination samples, 56 unvaccinated blood donors were recruited as controls (total n = 102). Thrombin generation, D-dimer levels, and free tissue factor pathway inhibitor (TFPI) levels were analyzed. Results: No participant experienced thrombosis, vaccine-induced immune thrombotic thrombocytopenia, or thrombocytopenia (platelet count <100 × 109/L) 1 week to 1 month postvaccination. There was no increase in thrombin generation, D-dimer level, or TFPI level in the ChAdOx1-S vaccine group compared with controls or after the mRNA vaccines compared with baseline values. Eleven of 513 (2.1%) participants vaccinated with ChAdOx1-S had anti-PF4/polyanion antibodies without a concomitant increase in thrombin generation. Conclusion: In this study, SARS-CoV-2 vaccines were not associated with thrombosis, thrombocytopenia, increased thrombin generation, D-dimer levels, or TFPI levels compared with baseline or unvaccinated controls. These findings argue against the subclinical activation of coagulation post-COVID-19 vaccination.

High-intensity interval training may reduce depressive symptoms in individuals with schizophrenia, putatively through improved VO2max: A randomized controlled trial.

Introduction: High-intensity interval training (HIIT) may improve cardiorespiratory fitness (CRF) and mental health. The current observer-blinded RCT investigates the sparsely studied efficiency of HIIT in reducing psychotic and non-psychotic symptoms in schizophrenia and complements previous studies by investigating whether symptom reduction following HIIT is associated with, putatively partly mediated by, increased VO2max. Methods: Participants (outpatients meeting diagnostic criteria for schizophrenia) were randomized to HIIT (n = 43) or a comparison group performing low-intensity active video gaming (AVG) to control for social interaction (n = 39). Both interventions consisted of two supervised sessions/week for 12 weeks and a 4 months follow-up. Effects on overall symptoms and symptom domains [PANSS (0-6 scale), five-factor model] were estimated using mixed-effects models (intention-to-treat, n = 82). Underlying mechanisms were analyzed using moderated mediation analyses (n = 66). We anticipated that HIIT would reduce overall symptoms, particularly depressive symptoms, more than AVG, and symptom reduction would be associated with, putatively mediated through, improved VO2max. Results: Depressive symptoms (baseline score 3.97, 95% CI: 3.41, 4.52), were -1.03 points more reduced in HIIT than AVG at post-intervention (95% CI: -1.71, -0.35, p = 0.003), corresponding to a small to moderate effect size (d = 0.37) and persisting at follow-up. There was a small reduction in overall symptoms, but no significant between-group differences were observed. Change in VO2max correlated negatively with the change in depressive symptoms. Mediation analysis showed a significant effect of change in VO2max on change in depressive symptoms within HIIT. The total effect was moderated by group, and depressive symptoms were more reduced in HIIT. Direct effects, not mediated through VO2max, were non-significant. Indirect effects, mediated through VO2max, were non-significant, but the moderated mediation test indicated a non-significant trend of 0.4 points (95% CI: -1.188, 0.087) and a larger reduction in depressive symptoms through VO2max in HIIT. Conclusion: HIIT reduced depressive symptoms more than AVG, which persisted at follow-up. HIIT may serve as a complementing treatment option targeting these symptoms in individuals with schizophrenia, even before they reach clinical depression. Depressive symptoms are important to prevent, stabilize, and treat due to their negative implications for psychological wellbeing and long-term functional outcome. Reduction in depressive symptoms was associated with improved VO2max, and non-significant trends in the data supported that improved VO2max may be part of the complex mechanisms underlying the anti-depressive effect of HIIT. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02205684].

NSAIDs in sciatica (NIS): study protocol for an investigator-initiated multicentre, randomized placebo-controlled trial of naproxen in patients with sciatica.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat sciatica, despite insufficient evidence from placebo-controlled trials. NSAIDs may cause serious side effects; hence, there is a strong need to clarify their potential beneficial effects in patients with sciatica. METHODS: This is a multicentre, randomized, placebo-controlled, parallel-group superiority trial. Participants will be recruited among sciatica patients referred to outpatient clinics at hospitals in Norway who have radiating pain below the knee with a severity score of ≥ 4 on a 0-10 numeric rating scale and clinical signs of nerve root or spinal nerve involvement. The intervention consists of oral naproxen 500 mg or placebo twice daily for 10 days. Participants will report the outcomes and adverse events daily using an electronic case report form. The primary endpoint is change in leg pain intensity from baseline to day 10 based on daily observations. The secondary outcomes are back pain intensity, disability, sciatica symptom severity, rescue medication (paracetamol) consumption, opioid use, ability to work or study, 30% and 50% improvement in leg pain, and global perceived change of sciatica/back problem. The outcomes will be analysed using mixed effects models for repeated measurements. The total duration of follow-up is 12 (± 2) days. DISCUSSION: This trial aims to evaluate the benefits of naproxen, a non-selective NSAID, in patients with sciatica. No important differences in efficacy have been demonstrated between different NSAIDs in the management of musculoskeletal disorders; hence, the results of this trial will likely be applicable to other NSAIDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03347929 . Registered on November 20, 2017.

Interleukin-18 signaling system links to agitation in severe mental disorders.

OBJECTIVE: Agitation is a challenging clinical feature in severe mental disorders, but its biological correlates are largely unknown. Inflammasome-related abnormalities have been linked to severe mental disorders and implicated in animal models of agitation. We investigated if levels of circulating inflammasome-related immune markers were associated with agitation in severe mental disorders. METHODS: Individuals with a psychotic or affective disorder (N = 660) underwent blood sampling and clinical characterization. Plasma levels of interleukin (IL)-18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), and IL-1 receptor antagonist (IL-1RA) were measured. Agitation levels were estimated with the Positive and Negative Syndrome Scale Excited Component. Multiple linear- and logistic regression were used to investigate the associations between agitation and the immune markers, while controlling for confounders. The influence of psychotic and affective symptoms was assessed in follow-up analyses. RESULTS: Agitation was positively associated with IL-18BP (ß = 0.13, t = 3.41, p = 0.0007) after controlling for multiple confounders, including BMI, smoking, medication, and substance use. Adjustment for psychotic, manic, and depressive symptoms did not affect the results. There were no significant associations between agitation and the other investigated immune markers (IL-1RA (ß = 0.06, t = 1.27, p = 0.20), IL-18 (ß = 0.05, t = 1.25, p = 0.21), IL-18R1 (ß = 0.04, t = 1.01, p = 0.31), IL-18RAP (odds ratio = 0.96, p = 0.30)). In a subsample (N = 463), we also adjusted for cortisol levels, which yielded unaltered results. CONCLUSION: Our findings add to the accumulating evidence of immune system disturbances in severe mental disorders and suggest the IL-18 system as a part of the biological correlate of agitation independent of affective and psychotic symptoms.

Antitumour necrosis factor alpha treatment in Crohn's disease: long-term efficacy, side effects and need for surgery.

OBJECTIVES: To examine the long-term efficacy and side effects of antitumour necrosis factor alpha (anti-TNF) therapy in patients with Crohn's disease (CD), the need for surgery and the clinical outcome after discontinuing anti-TNF therapy. MATERIAL AND METHODS: Data were collected from the inflammatory bowel disease (IBD)-TNF register at Østfold Hospital Trust. Clinical and sociodemographic data were recorded for patients initiating anti-TNF therapy from January 2000 until December 2011. Follow-up was conducted until December 2017. RESULTS: Complete remission (CR) was achieved in 40/154 (26%) patients at the last follow-up (median follow-up time 10 years). A total of 40 (26%) patients had to discontinue treatment due to serious side effects, and malignancy was recorded in 10 (6.5%) patients. Surgical resection was performed in 55 (36%) patients during follow-up. Patients with Montreal phenotype B2 before anti-TNF therapy were estimated to have a 2.54-fold greater risk of surgery than patients with phenotype B1 (p = .001). Of those with phenotype B1 before anti-TNF therapy, 19 (24%) of them developed stenosis in need of surgical resection ('phenotype migration'). In patients followed up after discontinuing anti-TNF therapy (n = 89, median observational time six years), CR was achieved in most patients. CONCLUSIONS: Long-term complete remission was achieved in only one in four patients receiving anti-TNF therapy, and one in four patients had to discontinue therapy due to side effects. Despite anti-TNF therapy, one in four patients with a baseline luminal disease phenotype needed subsequent surgical resection.

Association between myocardial fibrosis, as assessed with cardiac magnetic resonance T1 mapping, and persistent dyspnea after pulmonary embolism.

BACKGROUND: Persistent dyspnea is a common symptom after pulmonary embolism (PE). However, the pathophysiology of persistent dyspnea is not fully clarified. This study aimed to explore possible associations between diffuse myocardial fibrosis, as assessed by cardiac magnetic resonance (CMR) T1 mapping, and persistent dyspnea in patients with a history of PE. METHODS: CMR with T1 mapping and extracellular volume fraction (ECV) calculations were performed after PE in 51 patients with persistent dyspnea and in 50 non-dyspneic patients. Patients with known pulmonary disease, heart disease and CTEPH were excluded. RESULTS: Native T1 was higher in the interventricular septum in dyspneic patients compared to non-dyspneic patients; difference 13 ms (95% CI: 2-23 ms). ECV was also significantly higher in patients with dyspnea; difference 0.9 percent points (95% CI: 0.04-1.8 pp). There was no difference in native T1 or ECV in the left ventricular lateral wall. Native T1 in the interventricular septum had an adjusted Odds Ratio of 1.18 per 10 ms increase (95% CI: 0.99-1.42) in predicting dyspnea, and an adjusted Odds Ratio of 1.47 per 10 ms increase (95% CI: 1.10-1.96) in predicting Incremental Shuttle Walk Test (ISWT) score < 1020 m. CONCLUSION: Septal native T1 and ECV values were higher in patients with dyspnea after PE compared with those who were fully recovered suggesting a possible pathological role of myocardial fibrosis in the development of dyspnea after PE. Further studies are needed to validate our findings and to explore their pathophysiological role and clinical significance.

Effects of prebiotics on postprandial GLP-1, GLP-2 and glucose regulation in patients with type 2 diabetes: A randomised, double-blind, placebo-controlled crossover trial.

AIMS: We aimed to investigate the effect of prebiotic inulin-type fructans (ITF) versus a control supplement on postprandial levels of glucagon-like peptide-1 and -2 (GLP-1 and -2), glucose and insulin in people with type 2 diabetes. METHODS: Adult men and women with type 2 diabetes were randomised in a double-blind, placebo-controlled crossover study. The study participants received 16 g/d ITF and 16 g/d control supplement (maltodextrin) for 6 weeks each in two phases separated by a 4-week washout. A standardised mixed-meal test was performed before and after each intake period. The primary end point was changes in the GLP-1 response, and secondary end points were GLP-2, glucose and insulin responses. Data were analysed using mixed-model analysis. RESULTS: A total of 29 participants were included in the study. Differences between and within the two treatments in estimated area under the curves were not significant. Yet, the predicted means for meal-induced GLP-1 response in plasma showed a 4.8% decline after the prebiotic treatment and an 8.6% increase after the control treatment (difference in changes between the treatments, p < 0.001). Fasting or postprandial glucose, insulin or GLP-2 levels were not changed. CONCLUSIONS: Our findings do not support that ITF improve incretin responses or glucose regulations in this population. Clinicaltrials.gov (NCT02569684).

Effect of bariatric surgery on employment status-a 7 years controlled nationwide registry study.

BACKGROUND: Severe obesity is associated with a reduced ability to work. Bariatric surgery is the most effective method to achieve a sustained weight loss. Previous studies have reported conflicting results regarding the effect of bariatric surgery on employment status. To address this, we investigated the effect of bariatric surgery on employment status in the Danish population. METHODS: In this nationwide study, we identified 5450 subjects who underwent bariatric surgery and 10 900 control subjects matched for age, sex and municipality. From accessible registries, we extracted data regarding employment, absenteeism, sick leave and pension. Using a multistate model, we compared time in occupational states and transitions between these states to determine the effect of bariatric surgery on employment status. FINDINGS: Before surgery, cases had an absolute risk increase (95% CI)(ARI (CI)) and a relative risk (RR (CI)) of being in full-time employment of -0.12 (-0.14 to -0.10) and 0.84 (0.82 to 0.86) and were more often unemployed or in a subsidised job than the background population. Taking into account the employment status before surgery, the bariatric surgery group increased their probability of being in full-time employment 1-3 years after bariatric surgery. However, this positive effect was not present with a longer duration of follow-up. Being male, above 50 years of age, or employed as a craftsman or office worker were associated with a sustained positive effect of being in full-time employment (ARI (CI) and RR (CI) 0.05 (0.04 to 0.05) and 1.05 (1.04 to 1.06), 0.06 (0.06 to 0.07) and 1.08 (1.07 to 1.09) and 0.05 (0.05 to 0.06) and 1.05 (1.05 to 1.06), respectively). INTERPRETATION: Compared with a matched control group, those undergoing bariatric surgery did not improve their employment status in the long term. Certain subgroups had a more sustained positive effect.

Exploring intervention components in association with changes in preschool children's vegetable intake: the BRA-study.

OBJECTIVE: The present study aimed to explore kindergarten staffs' perceived usefulness of intervention components in association with changes in children's vegetable intake and vegetables served in the kindergarten. Assessment of the perceived usefulness of intervention components consisted of a paper-based questionnaire for the kindergarten staff assessing usefulness of posters, supplementary material and 1-day inspirational course. Children's vegetable intake in the kindergarten was assessed by direct observation, while vegetables served was assessed by a 5-day weighted vegetable diary. RESULTS: Seventy-three kindergartens in two counties in Norway participated (response rate 15%) and parental consent was obtained for 633 children 3-5 years of age at baseline (response rate 39%). Mixed effect models indicated a tendency that posters were associated with increased child vegetable intake (P = 0.062). Surprisingly, a low degree of perceived usefulness of supplementary material was associated with the largest increase in child vegetable intake (P = 0.020). No significant associations between perceived usefulness of intervention components and vegetables served in the kindergarten were found. This study indicated a tendency that posters were associated with increased child vegetable intake; however, this may also be due to synergies between multiple intervention components. Trial registration International Standard Randomized Controlled Trials ISRCTN51962956 ( http://www.isrctn.com/ISRCTN51962956 ). Registered 21 June 2016 (retrospectively registered).

Circadian, Week-to-Week, and Physical Exercise-Induced Variation of Serum Microfibrillar-Associated Protein 4.

Serum microfibrillar-associated protein 4 (sMFAP4) has been investigated as a biomarker for various diseases and is demonstrated to show significant gradual increase with severity of liver fibrosis. Ideal biomarkers used for disease diagnosis or prognosis should display deviating levels in affected individuals only and be robust to factors unrelated to the disease. Here we show the impact of normal physiological variation of sMFAP4 by characterizing the circadian variation, week-to-week variation, and physical exercise-induced levels. Serum samples from 3 groups of healthy volunteers were drawn: 7 times during a 24-hour period, 5 times during a 3-week period, and before and after a standardized physical exercise challenge. sMFAP4 was determined by AlphaLISA. Statistical analysis was performed using mixed effects modeling of repeated measurements. Circadian variation of sMFAP4 was demonstrated, with time of peak and nadir values depending on age and gender. For males, the peak values were observed during nighttime whereas for females, peak values were observed in the morning. Individual sMFAP4 levels remained stable over a period of 3 weeks and physical exercise inferred a mild negative influence. In conclusion, the circadian sMFAP4 variation was significant, and the levels could be influenced by physical activity. However, these variations were of limited magnitude relative to previously observed disease-induced levels in support of the biomarker potential of sMFAP4.

Altered Antibody Response to Epstein-Barr Virus in Patients With Rheumatoid Arthritis and Healthy Subjects Predisposed to the Disease. A Twin Study.

Objectives: To study Epstein-Barr virus (EBV) antibody patterns in twin individuals with rheumatoid arthritis (RA) and their healthy co-twins, and to determine the heritability of antibody responses against the EBV encoded EBNA1 protein. Methods: Isotypes of EBNA1 antibodies were measured in 137 RA affected- and 150 healthy twin pairs. We estimated the effect of RA and RA predisposition, anti-citrullinated antibodies (ACPA), IgM rheumatoid factor (RF), the shared epitope (SE) and the PTPN22-T allele (PTPN22) on the level of EBNA1 antibodies. We also determined the heritability of EBNA1 antibody levels. Results: IgA-EBNA1 antibody levels were increased in twins from RA discordant twin pairs irrespective of RA, ACPA or IgM-RF status. The IgG-EBNA1 antibody level was elevated in healthy co-twins from RA discordant twin pairs but not in RA affected twins. The IgM-EBNA1 antibody level was elevated in both RA twins and their healthy co-twins. The effect of RA on the IgA-EBNA1 antibody level was reversed when SE was present and with no effect of PTPN22. The heritability of IgA-, IgG- and IgM-EBNA1 antibody level was 40.6, 65.5, and 54.3%, with no effect of environment shared by the twins. Conclusion: EBNA1 antibody levels are distinctively different between patients with RA and healthy subjects but also between relatives of RA strongly predisposed to RA and healthy subjects. The high level of IgA EBNA1 antibodies associated with RA and a family predisposition to RA is attributable to both genetics incl. the shared epitope and environmental variation.

Pulmonary and cardiac variables associated with persistent dyspnea after pulmonary embolism.

INTRODUCTION: Persistent dyspnea is common in follow-up after pulmonary embolism (PE), but the underlying mechanisms are poorly understood. MATERIAL AND METHODS: This cross-sectional study included subjects aged 18-75 years with confirmed PE by computed tomography pulmonary angiography (CTPA) 6-72 months earlier. A total of 180 participants underwent clinical examination, incremental shuttle walk test, laboratory tests, transthoracic echocardiography, pulmonary function tests and ventilation/perfusion scintigraphy. In further analysis, we divided participants into two groups; "dyspnea" or "no dyspnea", based on interview and questionnaires at inclusion. The association of cardiac and pulmonary variables with persistent dyspnea was assessed using multiple logistic regression analysis. RESULTS: In total, 44% (95% CI: 39%-51%) of the participants reported persistent dyspnea after PE. Age (adjusted odds ratio (aOR) 0.93 per year, 95% CI: 0.90-0.97, P = 0.001), body mass index (BMI) (aOR 1.14 per kg/m2, 95% CI: 1.04-1.25, P = 0.004), recurrent venous thromboembolism (VTE) (aOR 3.69, 95% CI: 1.45-9.38, P = 0.006) and diffusion capacity of the lung for carbon monoxide (DLCO) (aOR 0.95 per increase of 1%, 95% CI: 0.92-0.98, P = 0.001) were independently associated with persistent dyspnea. CONCLUSIONS: Persistent dyspnea was prevalent after PE. Age, BMI and recurrent VTE were independently associated with dyspnea. Apart from reduced DLCO, no other cardiac or pulmonary variables were associated with persistent dyspnea.

Pulmonary rehabilitation to improve physical capacity, dyspnea, and quality of life following pulmonary embolism (the PeRehab study): study protocol for a two-center randomized controlled trial.

BACKGROUND: Recently, a large group of patients with persistent dyspnea, poor physical capacity, and reduced health-related quality of life (HRQoL) following pulmonary embolism (PE) has been identified and clustered under the name "post pulmonary embolism syndrome" (PPS). These patients seem good candidates for pulmonary rehabilitation. The aim of the study is to explore whether a pulmonary rehabilitation program can improve physical capacity, dyspnea, and HRQoL in PPS patients. METHODS: A two-center randomized controlled trial (RCT) is being performed at Østfold Hospital and Akershus University Hospital in Norway. Patients with PPS are 1:1 randomized into an intervention or a control group. The intervention consists of a supervised, outpatient rehabilitation program twice weekly (1 h) for 8 weeks provided by experienced physiotherapists. The intervention involves individually adapted exercises based on existing pulmonary rehabilitation programs (relaxation, interval, and resistance training), and an educational session including topics such as normal anatomy and physiology of the respiratory and circulatory system, information on PE/PPS, breathing strategies, and benefits of exercise/physical activity. Patients randomized to the control group receive usual care without specific instructions to exercise. Participants in the intervention and control groups will be compared based on assessments conducted at baseline, 12 weeks, and 36 weeks after inclusion using the incremental shuttle walk test (primary outcome) and endurance shuttle walk test (exercise capacity), Sensewear activity monitor (daily physical activity), the modified Medical Research Council scale, the Shortness of Breath Questionnaire (dyspnea), and EQ-5D-5L and the Pulmonary Embolism Quality of Life Questionnaire (HRQoL). Recruitment of 190 patients is currently ongoing. DISCUSSION: Results from this study may provide a currently untreated group of PPS patients with an effective treatment resulting in reduced symptoms of dyspnea, improved exercise capacity, and better HRQoL following PE. TRIAL REGISTRATION: Clinical Trials NCT03405480 . Registered prospectively on September 2017. Protocol version 1 (from original protocol September 2017). The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 1).