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Background: Innate and adaptive immune responses are pivotal in atherosclerosis, but their association with early-stage atherosclerosis in humans is incompletely understood. In this regard, untreated children with familial hypercholesterolaemia may serve as a human model to investigate the effect of elevated low-density lipoprotein (LDL)-cholesterol.Objectives: We aimed to study the immunological and inflammatory pathways involved in early atherosclerosis by examining mRNA molecules in peripheral blood mononuclear cells (PBMCs) from children with FH.Methods: We analysed the level of 587 immune-related mRNA molecules using state-of-the-art Nanostring technology in PBMCs from children with (n = 30) and without (n = 21) FH, and from FH children before and after statin therapy (n = 10).Results: 176 genes (30%) were differentially expressed between the FH and healthy children at P < 0.05. Compared to healthy children, the dysregulated pathways in FH children included the following: T cells (18/19); B cells (5/6); tumour necrosis factor super family (TNFSF) (6/8); cell growth, proliferation and differentiation (5/7); interleukins (5/9); toll-like receptors (2/5); apoptosis (3/7) and antigen presentation (1/7), where the ratio denotes higher expressed genes to total number of genes. Statin therapy reversed expression of thirteen of these mRNAs in FH children.Conclusion: FH children display higher PBMC expression of immune-related genes mapped to several pathways, including T and B cells, and TNFSF than healthy children. Our results suggest that LDL-C plays an important role in modulating expression of different immune-related genes, and novel data on the involvement of these pathways in the early atherosclerosis may represent future therapeutic targets for prevention of atherosclerotic progression. [ABSTRACT FROM AUTHOR]

Background/objectives: Cardiovascular (CV) disease is the leading cause of death after renal transplantation. Marine n-3 polyunsaturated fatty acids (PUFAs) exert potential cardio-protective metabolic effects and might reduce CV morbidity and mortality in renal transplant recipients (RTRs).Subjects/methods: In this cross-sectional study of 1990 Norwegian RTRs, transplanted between 1999 and 2011, associations between plasma phospholipid marine n-3 PUFA levels and various CV risk markers at 10 weeks after transplant were evaluated.Results: Higher plasma marine n-3 PUFA levels were associated with lower resting heart rate (rHR), lower fasting plasma glucose (fPG) levels, lower plasma triglyceride levels and higher plasma high-density lipoprotein (HDL) cholesterol levels. Plasma levels of eicosapentaenoic acid, but not docosahexaenoic acid, showed a positive association with plasma HDL cholesterol levels. Plasma marine n-3 PUFA levels were not associated with plasma low-density lipoprotein cholesterol levels, pulse wave velocity or systolic and diastolic blood pressure. A negative association between plasma marine n-3 PUFA levels and CV mortality was weakened by additional adjustment for plasma triglyceride levels and rHR. The ratio of n-6 to n-3 PUFAs showed similar associations with CV risk markers as absolute plasma marine n-3 PUFA levels.Conclusions: This is the first study in RTRs showing that marine n-3 PUFAs are negatively associated with rHR and fPG in addition to beneficial effects on plasma HDL cholesterol and triglyceride levels. Especially, effects on autonomic nervous function and triglyceride metabolism might contribute to explain the lower CV mortality risk with higher plasma marine n-3 PUFA levels previously shown in this cohort. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) patients in Denmark and England have historically had worse outcomes than patients diagnosed in other high-income countries with similar healthcare coverage. This survival deficit may be partly explained by differences in stage distribution due to delays in cancer diagnosis, however, differences in stage-specific survival suggest that differences in treatment also explain the survival gap. Aim: We aim to provide a comparison of stage-specific survival of CRC patients diagnosed in Denmark, England, Norway and Sweden, and compare the probability of receiving potentially curative surgery (PCS) by patient and tumor characteristics to understand whether differences in stage and treatment help explain the international differences in survival. Methods: Population-based information on patients aged 18-99 years diagnosed with primary malignant colon or rectal cancer in Denmark, England, Norway, and Sweden during 2010-2012 was extracted from national CRC registries. We compared the prevalence of PCS by stage and age category, and estimated the probability of receiving it using multivariate logistic regression. Age-standardized net survival was estimated using a multivariable modeling approach. Results: There were 13,230 patients diagnosed with CRC in Denmark, 99,869 in England, 11,754 in Norway, and 17,584 in Sweden between 2010 and 2012. The proportion of patients with missing stage information was higher in England than in the other countries. Stage distribution was otherwise similar. Survival of patients with stage I-II tumors was generally comparable between the countries, but lower in England and - to a lesser degree - in Denmark for stage III-IV disease. Patients with unknown stage had lower survival than staged patients in all countries. We found marked disadvantages in the probability of receiving PCS in older patients with stage II-IV disease in England, and stage IV colon cancer patients in Denmark. The proportion of surgically-treated rectal cancer patients (and their survival) was comparable between Denmark, Norway and Sweden for each combination of age group and stage, except for patients diagnosed with stage I disease. The proportion of patients receiving surgery and survival from rectal cancer was generally lower in England. Conclusion: Denmark seems to be catching up with Norway and Sweden, especially in rectal cancer survival. Despite recent improvements, CRC survival in England remains lower than in Sweden and Norway. Survival generally paralleled countries' relative performance in the provision of potentially curative surgery. Differences in patient selection for surgery, especially in older patients and/or with advanced disease, may partly explain the survival deficit. Increases in the proportion treated, in combination with efforts in postoperative care and with other treatment modalities, may translate into better longer-term outcomes, especially for frail patients. [ABSTRACT FROM AUTHOR]

The mTOR-inhibitor everolimus is a precision drug with antiepileptogenic properties approved for treatment of epilepsy in persons with tuberous sclerosis complex (TSC) in combination with other antiseizure medications (ASMs). However, the pharmacokinetic variability of everolimus is scarcely described, and the available information on pharmacokinetic interactions is scarce. The purpose of this study was to investigate pharmacokinetic variability of everolimus in patients with TSC, and the impact of age, sex and comedication. In this retrospective observational study we used anonymized data from medical records of patients with TSC using everolimus in Norway and Denmark, 2012 to 2020. Long-term therapeutic drug monitoring (TDM) identified inter-patient and intra-patient variability. The study included 59 patients, (36 females (61%)), median age 22 (range 3-59 years). Polytherapy was used in 50 patients (85%). The most frequently used ASMs were lamotrigine (n = 21), valproate (n = 17), and levetiracetam (n = 13). Blood concentrations of everolimus were measured in all patients. Pharmacokinetic variability of everolimus between patients was extensive, as demonstrated by a 24-fold variability from minimum-maximum concentration/dose (C/D)-ratios. The coefficient of variation (CV) for intra-patient (n = 59) and inter-patient variability (n = 47, ≥3 measurements) was 40% and 43%, respectively. The C/D-ratio of everolimus was 50% lower in 13 patients (22%) using enzyme-inducing ASMs compared to the 30 patients who did not (0.7 vs 1.4 ng/mL mg, P < .05). Age and sex were not significantly associated with changes in C/D-ratios of everolimus. Long-term TDM identified extensive variability in concentrations over time for everolimus both within and between patients, where comedication with enzyme-inducing ASMs was an important contributing factor. The findings suggest a need for TDM in patients with TSC treated with everolimus., Competing Interests: The other authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study was undertaken to characterize the use of higher doses of folic acid (≥1 mg daily) in relation to pregnancy in Denmark, Norway, and Sweden in women with epilepsy treated with antiseizure medication (ASM)., Methods: In this observational study, we used data from national medical birth, patient, and prescription registers in Denmark, Norway, and Sweden to retrospectively identify pregnancies in women with epilepsy treated with ASM from 2006 to 2017. The proportion of higher dose folic acid supplementation in pregnancies among women receiving ASM for epilepsy was calculated according to country of origin, time period, and type of ASM. Logistic regression with restricted cubic splines was used to model country-specific time trends., Results: Among a total of 2 748 882 pregnancies, we identified 8695 (.3%) pregnancies after restricting the population to women with ASM-treated epilepsy. A prescription for higher dose folic acid was filled in 4719 (54.3%) of these pregnancies. The proportion supplemented with higher dose folic acid was highest in Sweden (74.3%) and lower in Norway (41.4%) and Denmark (34.3%). Furthermore, we observed a decreasing trend of higher dose folic acid use in Denmark and Norway from year 2012 to 2017. Among those who used higher dose folic acid, 42% did not start preconception supplementation with higher dose folic acid., Significance: Supplementation with higher dose folic acid occurred in approximately half of pregnancies in women with ASM-treated epilepsy, with many not starting supplementation until after becoming pregnant. Considerable variability was observed in the use of higher dose folic acid across the countries, despite similar population characteristics and health care systems. Future guidelines should be simplified with clear recommendations developed in a collaborative manner by relevant specialists including neurologists, obstetricians, pediatricians, and public health specialists to enhance real-world applicability., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: To investigate if air pollution and greenness exposure from birth till adulthood affects adult asthma, rhinitis and lung function., Methods: We analysed data from 3428 participants (mean age 28) in the RHINESSA study in Norway and Sweden. Individual mean annual residential exposures to nitrogen dioxide (NO 2 ), particulate matter (PM 10 and PM 2.5 ), black carbon (BC), ozone (O 3 ) and greenness (normalized difference vegetation index (NDVI)) were averaged across susceptibility windows (0-10 years, 10-18 years, lifetime, adulthood (year before study participation)) and analysed in relation to physician diagnosed asthma (ever/allergic/non-allergic), asthma attack last 12 months, current rhinitis and low lung function (lower limit of normal (LLN), z-scores of forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC below 1.64). We performed logistic regression for asthma attack, rhinitis and LLN lung function (clustered with family and study centre), and conditional logistic regression with a matched case-control design for ever/allergic/non-allergic asthma. Multivariable models were adjusted for parental asthma and education., Results: Childhood, adolescence and adult exposure to NO 2 , PM 10 and O 3 were associated with an increased risk of asthma attacks (ORs between 1.29 and 2.25), but not with physician diagnosed asthma. For rhinitis, adulthood exposures seemed to be most important. Childhood and adolescence exposures to PM 2.5 and O 3 were associated with lower lung function, in particular FEV 1 (range ORs 2.65 to 4.21). No associations between NDVI and asthma or rhinitis were revealed, but increased NDVI was associated with lower FEV 1 and FVC in all susceptibility windows (range ORs 1.39 to 1.74)., Conclusions: Air pollution exposures in childhood, adolescence and adulthood were associated with increased risk of asthma attacks, rhinitis and low lung function in adulthood. Greenness was not associated with asthma or rhinitis, but was a risk factor for low lung function., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate the change in zonisamide (ZNS) serum concentration and its consequences in pregnant women with epilepsy., Methods: Six hospitals in Norway and Denmark screened their records for women who had been using ZNS during pregnancy. Absolute serum concentrations as well as concentration/dose (CD)-ratios were compared to non-pregnant values. Descriptive data on seizure control and obstetrical data were also collected., Results: 144 serum concentrations from 23 pregnancies in 15 individual women with epilepsy were included (six on monotherapy). The mean ZNS serum concentration fell to a minimum of 58.6 ± 15.1%, while the C/D-ratio fell to as low as 55.1 ± 15.3% of the non-pregnant-value. The lowest values were seen in gestational months six to nine, and the individual nadir varied considerably (range: 24-81% of the non-pregnant value). Four out of ten previously seizure-free patients experienced breakthrough seizures. Gestational age, weight at birth and head circumference of the newborns were within the reference ranges., Conclusions: ZNS serum concentrations may fall by over 40% during pregnancy, with large interindividual variability. In some patients, this may lead to worsened seizure control. These findings are in line with reports on other AEDs and suggest that regular therapeutic drug monitoring and dose adjustments may be useful., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) is a multi-factorial disease in which diet is believed to play a role. Little is known about the health effects of specific regional diets. The Nordic diet is high in fat and sugar but also includes a range of traditional products with anticipated health-promoting effects. The aim of this cohort study was to determine whether a healthy Nordic food index consisting of fish, cabbage, rye bread, oatmeal, apples, pears and root vegetables was related to CRC incidence. Data were obtained from a prospective cohort study of 57,053 Danish men and women aged 50-64 years, of whom 1025 developed CRC (13 years' follow-up). Incidence rate ratios (IRR) with 95 % CI were calculated from Cox proportional hazard models. Women who strongly adhered to a healthy Nordic food index had a 35 % lower incidence of CRC than women with poor adherence (adjusted IRR, 0·65; 95 % CI 0·46, 0·94); a similar tendency was found for men. Women had a 9 % lower incidence of CRC per point adherence to the healthy Nordic food index, but no significant effect was found for men. A regional diet based on healthy Nordic food items was therefore associated with a lower incidence of CRC in women. The protective effect was of the same magnitude as previously found for the Mediterranean diet, suggesting that healthy regional diets should be promoted in order to ensure health; this will also preserve cultural heredity and the environment.

Background: Women diagnosed with breast cancer at young age have been shown to be at higher risk of developing a new primary cancer than women diagnosed at older ages, but little is known about whether adjustment for calendar year of breast cancer diagnosis, length of follow-up, and/or breast cancer treatment alters the risk pattern by age., Methods: We identified 304,703 women diagnosed with breast cancer during 1943 to 2006 in the Cancer Registries of Denmark, Norway, and Finland. Relative risks (RR) of subsequent non-breast cancer by age at cancer diagnosis were calculated using Poisson regression models adjusted for country, calendar period, length of follow-up, and treatment. Excess absolute risks (EAR) were also calculated., Results: The RR for all cancer sites except breast cancer decreased with increasing age both with and without adjustments. The RR and the EAR differed for each age at diagnosis category until the women reached their late 70s. Many specific cancer forms contributed to the overall risk pattern by age with endometrial cancer as 1 exception., Conclusions: The age at breast cancer diagnosis is an essential risk factor for being diagnosed with a new primary non-breast cancer and the level of risk for specific ages at diagnosis may hold for many years after the diagnosis. Occurrence of endometrial cancer after breast cancer seems to follow a distinct age pattern different from that seen for most other cancer types., Impact: Future studies should aim at exploring the underlying explanations for the age-related findings., (©2011 AACR.)

Enterobacter cloacae was isolated from 69 patients hospitalized at the University Hospital of Tromsø, Norway, during a period of 18 months. The total lethality was 11.6% (8/69) and death occurred most often in patients with a serious underlying condition. Death due to septicaemia occurred in 4/10 patients. Multiple beta-lactam resistant strains were present in 15 patients and were associated with septicaemiae (7/10, p less than 0.0005). Cephalosporin treatment had been given to every third patient (24/69), and nearly half of them (10/24) were infected by multiple beta-lactam resistant E cloacae. E cloacae occurred mainly as a nosocomial infection, since more than 70% of all patients infected had been treated by an invasive procedure prior to isolation of the bacterium. A high number of E cloacae strains were from operation wounds, especially among patients at the Department of Surgery (22/30). At this Department, the total number of E cloacae, and especially the number of multiresistant strains, was markedly reduced during restricted use of cefalosporins.