Aerobic fitness mediates the intervention effects of a school-based physical activity intervention on academic performance. The school in Motion study - A cluster randomized controlled trial.

Little information exists on the mechanism of how physical activity interventions effects academic performance. We examined whether the effects of a school-based physical activity intervention on academic performance were mediated by aerobic fitness. The School in Motion study was a nine-month cluster randomized controlled trial between September 2017 and June 2018. Students from 30 Norwegian lower secondary schools (N = 2,084, mean age [SD] = 14 [0.3] years) were randomly assigned into three groups: the Physically Active Learning (PAL) intervention (n = 10), the Don't Worry-Be Happy (DWBH) intervention (n = 10), or control (n = 10). Aerobic fitness was assessed by the Andersen test and academic performance by national tests in reading and numeracy. Mediation was assessed according to the causal steps approach using linear mixed models. In the PAL intervention, aerobic fitness partially mediated the intervention effect on numeracy by 28% from a total effect of 1.73 points (95% CI: 1.13 to 2.33) to a natural direct effect of 1.24 points (95% CI: 0.58 to 1.91), and fully mediated the intervention effect on reading, with the total effect of 0.89 points (95% CI: 0.15 to 1.62) reduced to the natural direct effect of 0.40 points (95% CI: -0.48 to 1.28). Aerobic fitness did not mediate the effects on academic performance in the DWBH intervention. As aerobic fitness mediated the intervention effect on academic performance in one intervention, physical activity of an intensity that increases aerobic fitness is one strategy to improve academic performance among adolescents.

A study protocol for the cardiac effects of a single dose of either oxytocin 2.5 IU or carbetocin 100 µg after caesarean delivery: a prospective randomized controlled multi-centre trial in Norway.

Background: Both oxytocin and carbetocin are used to prevent uterine atony and post-partum haemorrhage after caesarean delivery in many countries, including Norway. Oxytocin causes dose-dependent ST-depression, troponin release, prolongation of QT-time and arrythmia, but little is known about myocardial effects of carbetocin. We have previously demonstrated comparable vasodilatory effects of oxytocin and carbetocin and are now undertaking a Phase 4 trial to investigate whether carbetocin causes similar changes to myocardial markers compared with oxytocin. Methods: Our randomized controlled trial will be conducted at three obstetrics units at Oslo University Hospital and Akershus University Hospital, Norway. Planned enrolment will be of 240 healthy, singleton pregnant women aged 18 to 50 years undergoing planned caesarean delivery. Based on pilot study data, each participant will receive a one-minute intravenous injection of either oxytocin 2.5 IU or carbetocin 100 µg during caesarean delivery. The prespecified primary outcome is the change from baseline in high-sensitive troponin I plasma concentrations at 6-10 hours after study drug administration. Secondary outcomes include uterine tone grade at 2.5 and five minutes after study drug administration, adverse events for up to 48 hours after study drug administration, estimated blood loss within eight hours of delivery, need for rescue treatment and direct/indirect costs. Enrolment and primary analysis are expected to be completed by the end of 2021. Discussion: Women undergoing caesarean delivery should be assessed for cardiovascular risk particularly as women with an obstetric history of pregnancy induced hypertension, gestational diabetes mellitus, preterm birth, placental abruption, and stillbirth are at increased risk of future cardiovascular disease. Any additional ischaemic myocardial risk from uterotonic agents will need to be balanced with the benefit of reducing the risk of postpartum haemorrhage. Any potential cardiotoxicity difference between oxytocin and carbetocin will help inform treatment decisions for pregnant women. Registration: Clinicaltrials.gov NCT03899961 (02/04/2019).

Effect of atorvastatin on muscle symptoms in coronary heart disease patients with self-perceived statin muscle side effects: a randomized, double-blinded crossover trial.

AIMS: To estimate the effect of atorvastatin on muscle symptom intensity in coronary heart disease (CHD) patients with self-perceived statin-associated muscle symptoms (SAMS) and to determine the relationship to blood levels of atorvastatin and/or metabolites. METHODS AND RESULTS: A randomized multi-centre trial consecutively identified 982 patients with previous or ongoing atorvastatin treatment after a CHD event. Of these, 97 (9.9%) reported SAMS and 77 were randomized to 7-week double-blinded treatment with atorvastatin 40 mg/day and placebo in a crossover design. The primary outcome was the individual mean difference in muscle symptom intensity between the treatment periods, measured by visual-analogue scale (VAS) scores. Atorvastatin did not affect the intensity of muscle symptoms among 71 patients who completed the trial. Mean VAS difference (statin-placebo) was 0.31 (95% CI: -0.24 to 0.86). The proportion with more muscle symptoms during placebo than atorvastatin was 17% (n = 12), 55% (n = 39) had the same muscle symptom intensity during both treatment periods whereas 28% (n = 20) had more symptoms during atorvastatin than placebo (confirmed SAMS). There were no differences in clinical or pharmacogenetic characteristics between these groups. The levels of atorvastatin and/or metabolites did not correlate to muscle symptom intensity among patients with confirmed SAMS (Spearman's rho ≤0.40, for all variables). CONCLUSION: Re-challenge with high-intensity atorvastatin did not affect the intensity of muscle symptoms in CHD patients with self-perceived SAMS during previous atorvastatin therapy. There was no relationship between muscle symptoms and the systemic exposure to atorvastatin and/or its metabolites. The findings encourage an informed discussion to elucidate other causes of muscle complaints and continued statin use.

Step by step: Association of device-measured daily steps with all-cause mortality-A prospective cohort Study.

INTRODUCTION: Walking is free, does not require special training, and can be done almost everywhere. Therefore, walking is a feasible behavior on which to tailor public health messages. This study assesses the prospective association and dose-response relationship between daily steps and all-cause mortality. MATERIALS AND METHODS: Daily steps were measured by waist-mounted accelerometers in 2183 individuals (53% women) for seven consecutive days at baseline (2008-09). Participants were followed for a median period of 9.1 years and associations between steps and all-cause mortality determined by registry linkage were assessed using Cox proportional hazard regression with adjustment for relevant covariates. RESULTS: Mean age was 57.0 (SD 10.9) years at baseline. Median (IQR) daily steps across ascending quartiles were 4651 (3495-5325), 6862 (6388-7350), 8670 (8215-9186), and 11 467 (10 556-13 110), respectively. During follow-up, 119 individuals died (68% men). Higher number of daily steps was associated with a lower risk of all-cause mortality with hazard ratios of 1.00 (referent), 0.52 (0.29-0.93), 0.50 (0.27-0.94), and 0.43 (0.21-0.88) across ascending quartiles of daily steps in the multivariable-adjusted model with follow-up commencing 2 years after baseline. Risk differences per 1000 individuals for ascending quartiles were 6.8 (2.9-9.3), 7.1 (0.8-11.1), and 8.0 (1.7-12.1), respectively. CONCLUSIONS: Daily steps were associated with lower mortality risk in a non-linear dose-response pattern. The risk is almost halved when comparing the least active referent against the second quartile equivalent to a difference of about 2200 daily steps. Encouraging those least active to increase their daily steps may have substantial public health implications.

Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study.

BACKGROUND: The complement system is involved in pathogenesis of cardiovascular disease, and might play a role in accelerated atherogenesis in spondylarthropathies (SpA). Hence, we examined complement activation in SpA, and its relationship to antirheumatic treatment, inflammatory and cardiovascular markers. METHODS: From PSARA, a prospective observational study, we examined 51 SpA patients (31 psoriatic arthritis (PsA), and 20 ankylosing spondylitis (AS)), starting tumor necrosis factor (TNF) inhibitor alone (n = 25), combined with methotrexate (MTX) (n = 10), or MTX monotherapy (n = 16). Complement activation was determined by the soluble terminal complement complex (sC5b-9), inflammation by erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and endothelial function by finger plethysmography (Endopat) at baseline, after 6 weeks and 6 months of treatment. RESULTS: SpA patients had sC5b-9 levels at (PsA) or above (AS) the upper limit of the estimated reference range. Median sC5b-9 levels decreased significantly from baseline to 6 weeks, with no significant difference between the AS and PsA group. Notably, a significant reduction in sC5b-9 was observed after administration of TNF inhibitor ± MTX, whereas no significant changes were observed in patients treated with MTX alone. Between 6 weeks and 6 months, sC5b-9 remained stable across all subgroups. Reduction in sC5b-9 was independently related to decreased ESR and CRP, and to increased high density cholesterol and total cholesterol. Reduction in sC5b-9 from baseline to 6 weeks was associated with improved EF in age and gender adjusted analyses. CONCLUSION: TNF-inhibition, but not MTX monotherapy, led to rapid and sustained reduction of complement activation in SpA. Thus, the observed decrease in cardiovascular morbidity in patients treated with TNF-inhibitors might be partly due to its beneficial effect on complement. TRIAL REGISTRATION: Clinical Trials (NCT00902005), retrospectively registered on the 14th of May 2009.

Differential expression of vitamin D associated genes in the aorta of coronary artery disease patients with and without rheumatoid arthritis.

BACKGROUND: Vitamin D has an important role in the immune system, and has been linked to rheumatoid arthritis (RA) and coronary artery disease (CAD). The exact mechanisms by which vitamin D is involved in these processes are still unclear. Therefore, we wanted to search for differences in expression of genes involved in the vitamin D receptor (VDR) activation pathway and genes that are known to alter upon vitamin D stimulation, in the aortic adventitia of CAD patients with and without RA. METHODS: Affymetrix microarray was used to determine gene expression profile in surgical specimens from the adventitia of the ascending aorta of CAD patients with RA (n = 8) and without RA (n = 8) from the Feiring Heart Biopsy Study. RESULTS: We identified three vitamin D associated genes that were differentially expressed between RA and non-RA patients: Growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A) (FC = 1.47; p = 0.006), Nuclear Receptor Co-repressor 1 (NCOR1) (FC = 1,21; p = 0.005) and paraoxonases 2 (PON2) (FC = -1.37; p = 0.01). High expression of GADD45A in RA tissues was confirmed by real-time qRT-PCR. GADD45A expression correlated with plasma levels of 1,25(OH)2D3 (rs = 0.69; p = 0.003). CONCLUSIONS: Microarray analyses revealed higher expression of GADD45A and NCOR1; and lower expression of PON2 in the aortic adventitia of RA than non-RA patients. Further studies are needed to elucidate if and how GADD45A, NCOR1 and PON2 are involved in the development of accelerated atherosclerosis in RA. In theory, some of these factors might have proatherogenic effects whereas others might reflect an underlying vascular pathology promoting atherogenesis (such as vascular stress).

Gender differences in all-cause, cardiovascular and cancer mortality during long-term follow-up after acute myocardial infarction; a prospective cohort study.

BACKGROUND: Gender differences in short-term mortality in acute myocardial infarction (AMI) have been studied extensively, whereas gender differences in long-term mortality and cause of death largely remain unknown. The aim of this study was to assess the long-term risk of all-cause, cardiovascular and cancer death after AMI in women compared to men. METHODS: Consecutive AMI patients were enrolled in a prospective registry between 2005 and 2011. Date and cause of death were obtained by linkage with the Norwegian Cause of Death Registry, with censoring date 31 December 2012. AMI patients with ST-segment elevation (STEMI, n = 5159) and without (NSTEMI, n = 4899) were analysed separately. RESULTS: The 5-years all-cause mortality rates in STEMI were 29% in women vs. 17% in men, and 42% vs. 29% in NSTEMI, respectively. After adjustment for age and other confounders, women with STEMI had similar (HR 1.13 [95% CI: 0.98-1.32]) and women with NSTEMI lower (HR 0.82 [95% CI: 0.73-0.92]) risk of long-term all-cause mortality compared to men. Competing-risks analysis showed no significant gender differences in age-adjusted risk of cardiovascular death nor of cancer death. In both genders, the annual risk of cardiovascular death was low after 1 year, but exceeded annual risk of cancer death throughout follow-up. CONCLUSION: During long-term follow-up, women with STEMI had similar and women with NSTEMI lower adjusted risk of all-cause mortality compared to men. Age-adjusted risk of death due to cardiovascular disease was similar in both genders and higher than risk of death due to cancer throughout the follow-up period.

Time trends in quality indicators of colonoscopy.

BACKGROUND: There is considerable variation in the quality of colonoscopy performance. The Norwegian quality assurance programme Gastronet registers outpatient colonoscopies performed in Norwegian endoscopy centres. The aim of Gastronet is long-term improvement of endoscopist and centre performance by annual feedback of performance data. OBJECTIVE: The objective of this article is to perform an analysis of trends of quality indicators for colonoscopy in Gastronet. METHODS: This prospective cohort study included 73,522 outpatient colonoscopies from 73 endoscopists at 25 endoscopy centres from 2003 to 2012. We used multivariate logistic regression with adjustment for relevant variables to determine annual trends of three performance indicators: caecum intubation rate, pain during the procedure, and detection rate of polyps ≥5 mm. RESULTS: The proportion of severely painful colonoscopies decreased from 14.8% to 9.2% (relative risk reduction of 38%; OR = 0.92 per year in Gastronet; 95% CI 0.86-1.00; p = 0.045). Caecal intubation (OR = 0.99; 95% CI 0.94-1.04; p = 0.6) and polyp detection (OR = 1.03; 95% CI 0.99-1.07; p = 0.15) remained unchanged during the study period. CONCLUSIONS: Pain at colonoscopy showed a significant decrease during years of Gastronet participation while caecal intubation and polyp detection remained unchanged - independent of the use of sedation and/or analgesics and level of endoscopist experience. This may be due to the Gastronet audit, but effects of improved endoscopy technology cannot be excluded.

Are the High Hip Fracture Rates Among Norwegian Women Explained by Impaired Bone Material Properties?

Hip fracture rates in Norway rank among the highest in the world, more than double that of Spanish women. Previous studies were unable to demonstrate significant differences between the two populations with respect to bone mass or calcium metabolism. In order to test whether the difference in fracture propensity between both populations could be explained by differences in bone material quality we assessed bone material strength using microindentation in 42 Norwegian and 46 Spanish women with normal BMD values, without clinical or morphometric vertebral fractures, no clinical or laboratory signs of secondary osteoporosis, and without use of drugs with known influence on bone metabolism. Bone material properties were assessed by microindentation of the thick cortex of the mid tibia following local anesthesia of the area using the Osteoprobe device (Active Life Scientific, Santa Barbara, CA, USA). Indentation distance was standardized against a calibration phantom of methylmethacrylate and results, as percentage of this reference value, expressed as bone material strength index units (BMSi). We found that the bone material properties reflected in the BMSi value of Norwegian women was significantly inferior when compared to Spanish women (77 ± 7.1 versus 80.7 ± 7.8, p < 0.001). Total hip BMD was significantly higher in Norwegian women (1.218 g/cm(2) versus 0.938 g/cm(2) , p < 0.001) but regression analysis revealed that indentation values did not vary with BMD r(2) = 0.03 or age r(2) = 0.04. In conclusion Norwegian women show impaired bone material properties, higher bone mass, and were taller than Spanish women. The increased height will increase the impact on bone after falls, and impaired bone material properties may further enhance the risk fracture after such falls. These ethnic differences in bone material properties may partly explain the higher propensity for fracture in Norwegian women.