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Abstract Background Women with pre-pregnancy obesity have an increased risk of retaining or gaining weight postpartum and may benefit from weight loss treatment. However, evidence is lacking for weight loss strategies in women with BMIs in the higher obesity classes. A dietary treatment for postpartum weight loss resulted in a 10% weight reduction in lactating women with a mean BMI of 30 kg/m2. We aimed to examine the effects of this dietary treatment on changes in weight, markers of lipid and glucose metabolism, waist and hip circumference and postpartum weight retention (PPWR) in postpartum women with higher BMIs than tested previously. Methods At baseline, approximately 8 weeks postpartum, 29 women with a mean (SD) BMI = 40.0 (5.2) kg/m2 were randomised to a 12-week dietary treatment (n 14) or to a control treatment (n 15). Measurements were made at baseline and after 3 and 12 months. Data was analysed using mixed model. Results The mean weight change in the diet group was -2.3 (3.1) kg compared to 1.7 (3.1) kg in the control group after 3 months (P = 0.003) and -4.2 (5.6) kg compared to 4.8 (11.8) kg in the control group after 12 months (P = 0.02). The dietary treatment led to reduced waist circumference (P

Abstract Background Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. Methods This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). Results Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ P interaction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ P interaction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ P interaction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ P interaction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ P interaction ≤ 0.99). Conclusions Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

Abstract Background Lung region segmentation is an important stage of automated image-based approaches for the diagnosis of respiratory diseases. Manual methods executed by experts are considered the gold standard, but it is time consuming and the accuracy is dependent on radiologists’ experience. Automated methods are relatively fast and reproducible with potential to facilitate physician interpretation of images. However, these benefits are possible only after overcoming several challenges. The traditional methods that are formulated as a three-stage segmentation demonstrate promising results on normal CT data but perform poorly in the presence of pathological features and variations in image quality attributes. The implementation of deep learning methods that can demonstrate superior performance over traditional methods is dependent on the quantity, quality, cost and the time it takes to generate training data. Thus, efficient and clinically relevant automated segmentation method is desired for the diagnosis of respiratory diseases. Methods We implement each of the three stages of traditional methods using deep learning methods trained on five different configurations of training data with ground truths obtained from the 3D Image Reconstruction for Comparison of Algorithm Database (3DIRCAD) and the Interstitial Lung Diseases (ILD) database. The data was augmented with the Lung Image Database Consortium (LIDC-IDRI) image collection and a realistic phantom. A convolutional neural network (CNN) at the preprocessing stage classifies the input into lung and none lung regions. The processing stage was implemented using a CNN-based U-net while the postprocessing stage utilize another U-net and CNN for contour refinement and filtering out false positives, respectively. Results The performance of the proposed method was evaluated on 1230 and 1100 CT slices from the 3DIRCAD and ILD databases. We investigate the performance of the proposed method on five configurations of training data and three configurations of the segmentation system; three-stage segmentation and three-stage segmentation without a CNN classifier and contrast enhancement, respectively. The Dice-score recorded by the proposed method range from 0.76 to 0.95. Conclusion The clinical relevance and segmentation accuracy of deep learning models can improve though deep learning-based three-stage segmentation, image quality evaluation and enhancement as well as augmenting the training data with large volume of cheap and quality training data. We propose a new and novel deep learning-based method of contour refinement.

Abstract Background More than one third of Norwegian women and men between 20 and 40 years of age have elevated cholesterol concentration. Parental metabolic health around conception or during pregnancy may affect the offspring’s cardiovascular disease risk. Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied. We therefore aimed to describe the associations between maternal and paternal peri-pregnancy lipid and metabolic profile and newborn cord blood lipid and metabolic profile. Methods This study is based on 710 mother–father–newborn trios from the Norwegian Mother, Father and Child Cohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). The sample included in this study consisted of parents with and without self-reported hypercholesterolemia the last 6 months before pregnancy and their partners and newborns. Sixty-four cord blood metabolites detected by nuclear magnetic resonance spectroscopy were analyzed by linear mixed model analyses. The false discovery rate procedure was used to correct for multiple testing. Results Among mothers with hypercholesterolemia, maternal and newborn plasma high-density lipoprotein cholesterol, apolipoprotein A1, linoleic acid, docosahexaenoic acid, alanine, glutamine, isoleucine, leucine, valine, creatinine, and particle concentration of medium high-density lipoprotein were significantly positively associated (0.001 ≤ q ≤ 0.09). Among mothers without hypercholesterolemia, maternal and newborn linoleic acid, valine, tyrosine, citrate, creatinine, high-density lipoprotein size, and particle concentration of small high-density lipoprotein were significantly positively associated (0.02 ≤ q ≤ 0.08). Among fathers with hypercholesterolemia, paternal and newborn ratio of apolipoprotein B to apolipoprotein A1 were significantly positively associated (q = 0.04). Among fathers without hypercholesterolemia, no significant associations were found between paternal and newborn metabolites. Sex differences were found for many cord blood lipids. Conclusions Maternal and paternal metabolites and newborn sex were associated with several cord blood metabolites. This may potentially affect the offspring’s long-term cardiovascular disease risk.

Abstract Background Pregnancy has been identified as a contributor to obesity. We have shown that a diet intervention postpartum produced a 2-y weight loss of 8%. Here, we present the impact of the diet intervention on cost-effectiveness and explore changes in quality of life (QOL). Methods A total of 110 postpartum women with overweight/obesity were randomly assigned to diet (D-group) or control (C-group). D-group received a 12-wk diet intervention within primary health care followed by monthly emails up to the 1-y follow-up. C-group received a brochure. Changes in QOL were measured using the 36-item Short Form Health Survey and EQ-5D. The analysis of cost-effectiveness was a cost-utility analysis with a health care perspective and included costs of intervention for stakeholder, quality-adjusted life-years (QALYs) gained and savings in health care. The likelihood of cost-effectiveness was examined using the net monetary benefit method. Results The D-group increased their QOL more than the C-group at 12 wk. and 1 y, with pronounced differences for the dimensions general health and mental health, and the mental component summary score (all p

Abstract Background Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). Methods To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. Results Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. Conclusion The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. Trial registration ClinicalTrials.gov identifier NCT02627872; Retrospectively registered on December 9, 2015.

Abstract Background Smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function. Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown. The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference. Method We employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18). Multivariate modeling, pathway enrichment analysis, and correlation with clinical characteristics were performed to identify specific proteins and pathways of interest. Results More pronounced alterations both at the protein- and pathway- levels were observed in female COPD patients, involving dysregulation of the FcγR-mediated phagocytosis-lysosomal axis and increase in oxidative stress. Alterations in pathways of the phagocytosis-lysosomal axis associated with a female-dominated COPD phenotype correlated well with specific clinical features: FcγR-mediated phagocytosis correlated with FEV1/FVC, the lysosomal pathway correlated with CT

Abstract Background Patient activation refers to patients’ knowledge, confidence, skills, ability, beliefs, and willingness to manage their health and healthcare. Patient activation is an essential component of self-management and identifying patient activation levels will identify people at risk for health decline at an earlier stage. We aimed to explore patient activation in among adults attending general practice by (1) investigating differences in patient activation according to characteristics and markers of health-related behaviour; (2) examining the associations of quality of life and satisfaction with health with patient activation; and (3) comparing patient activation between persons with or without type 2 diabetes (T2D) and with or without elevated T2D risk. Methods We performed a cross-sectional study and recruited 1,173 adult patients from four Norwegian general practices between May to December 2019. The participants completed a questionnaire containing sociodemographic and clinical variables, the Patient Activation Measure (PAM-13), the quality of life and satisfaction with health items from the WHO Quality of Life-BREF, three questions about exercise (regularity, intensity and exercise time), the Finnish Diabetes Risk Score (FINDRISC) and Body Mass Index. We tested differences between groups and associations using Chi-squared tests, Fisher’s exact tests, t-tests, one-way ANOVAs and Spearman’s rho tests. Results The sample’s mean PAM-13 score was 69.8 (0–100) (SD 14.8). In the total population, we found that participants reporting higher patient activation scores also reported more favourable health-related behaviours (exercise and healthy eating). We found positive correlations between the PAM-13 scores and, respectively, the quality of life score and the satisfaction with health score. We found no differences in patient activation between people with or without T2D and those with or without elevated T2D risk. Conclusions We found that higher patient activation was associated with favourable health-related behaviours, a better quality of life and better satisfaction with health among adults attending four general practices in Norway. Assessing patient activation has the potential to help general practitioners identify patients who might benefit from closer follow-up in advance of negative health outcomes.

Abstract Background Type 2 diabetes (T2D) is a global public health problem, but the onset can be delayed or prevented with adequate intervention in individuals with increased risk. Therefore, a major challenge in general practice is to identify individuals at risk of diabetes. However, limited knowledge is available about the prevalence of high diabetes risk individuals in a primary care population. In a cohort of consecutive patients in general practice we examined the prevalence of known diabetes and estimated risk of diabetes using The Finnish Diabetes Risk Score (FINDRISC) calculator, by sociodemographic and clinical characteristics. Methods This study was a cross-sectional study conducted in four general practices in Western and Eastern Norway. A total of 1682 individuals, 20–80 years of age, were assessed for eligibility from May to December 2019. We excluded patients who actively declined participation (n = 112), were lost because of various organization challenges (n = 103) and patients who did not fulfil the inclusions criteria (n = 63). Diabetes prevalence and prevalence of individuals at risk of T2D with 95% confidence intervals (CI) were estimated for the total sample, by age group and for men and women separately. We tested for differences between groups using t-test for continuous variables and chi-square test (Pearson Chi-Square) for categorical variables. Results Of 1404 individuals, 132 reported known diabetes, yielding a prevalence of 9.9% (95% CI 8.4–11.6). Among participants without a known diagnosis of diabetes, the following estimates of elevated risk assessment scores were found: FINDRISC score ≥ 11 32.8% (95% CI 30.3–35.4) and FINDRISC ≥ 15 10.0% (95% CI 8.6–11.9). Comparable results were found between the sexes. Conclusions Detection of unknown diabetes and individuals with increased risk, is of high public health relevance for early implementation of preventive measures aimed to reduce the risk of diabetes and its complications through lifestyle modification. A simple, non-expensive questionnaire, such as FINDRISC, may be valuable as an initial screening method in general practice to identify those in need for preventive measures.

Abstract Background Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients. These drugs might just as well be efficient in other diagnostic subgroups, not investigated in pharma-led clinical studies, but their potential use on new indications is never explored due to limited number of patients. Methods In this national, investigator-initiated, prospective, open-label, non-randomized combined basket- and umbrella-trial, patients are enrolled in multiple parallel cohorts. Each cohort is defined by the patient’s tumour type, molecular profile of the tumour, and study drug. Treatment outcome in each cohort is monitored by using a Simon two-stage-like ‘admissible’ monitoring plan to identify evidence of clinical activity. All drugs available in IMPRESS-Norway have regulatory approval and are funded by pharmaceutical companies. Molecular diagnostics are funded by the public health care system. Discussion Precision oncology means to stratify treatment based on specific patient characteristics and the molecular profile of the tumor. Use of targeted drugs is currently restricted to specific biomarker-defined subgroups of patients according to their market authorization. However, other cancer patients might also benefit of treatment with these drugs if the same biomarker is present. The emerging technologies in molecular diagnostics are now being implemented in Norway and it is publicly reimbursed, thus more cancer patients will have a more comprehensive genomic profiling of their tumour. Patients with actionable genomic alterations in their tumour may have the possibility to try precision cancer drugs through IMPRESS-Norway, if standard treatment is no longer an option, and the drugs are available in the study. This might benefit some patients. In addition, it is a good example of a public–private collaboration to establish a national infrastructure for precision oncology. Trial registrations EudraCT: 2020-004414-35, registered 02/19/2021; ClinicalTrial.gov: NCT04817956, registered 03/26/2021.

Abstract Background Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index. Methods Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10–17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry. Results Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant. Conclusions Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.

Abstract Background In line with the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, Norway aims for at least 90% of people living with HIV (PLHIV) to know their HIV-status. We produced current estimates of the number of PLHIV and undiagnosed population in Norway, overall and for six key subpopulations: Norwegian-born men who have sex with men (MSM), migrant MSM, Norwegian-born heterosexuals, migrant Sub-Saharan Africa (SSA)-born heterosexuals, migrant non-SSA-born heterosexuals and people who inject drugs. Methods We used the European Centre for Disease Prevention and Control (ECDC) HIV Modelling Tool on Norwegian HIV surveillance data through 2018 to estimate incidence, time from infection to diagnosis, PLHIV, and the number and proportion undiagnosed. As surveillance data on CD4 count at diagnosis were not collected in Norway, we ran two models; using default model CD4 assumptions, or a proxy for CD4 distribution based on Danish national surveillance data. We also generated alternative overall PLHIV estimates using the Spectrum AIDS Impact Model, to compare with those obtained from the ECDC tool. Results Estimates of the overall number of PLHIV in 2018 using different modelling approaches aligned at approximately 5000. In both ECDC models, the overall number undiagnosed decreased continuously from 2008. The proportion undiagnosed in 2018 was lower using default model CD4 assumptions (7.1% [95%CI: 5.3–8.9%]), than the Danish CD4 proxy (10.2% [8.3–12.1%]). This difference was driven by results for heterosexual migrants. Estimates for Norwegian-born MSM, migrant MSM and Norwegian-born heterosexuals were similar in both models. In these three subpopulations, incidence in 2018 was

Abstract Background Patients´ own perceptions and evaluations of symptoms, functioning and other health-related factors, i.e. Patient Reported Outcomes (PROs), are important elements for providing good patient care. Symptoms are subjective and best elicited by the patient orally or by using PRO measures (PROMs), be it on paper, or as electronic assessment tools. Reference values on frequently used PROMs facilitate the interpretation of scores for use in clinics and research settings, by comparing patient data with relevant samples from the general population. Study objectives were to (1) present reference values for the M.D. Anderson Symptom Inventory (MDASI) (2) examine the occurrence and intensity of symptoms assessed by the MDASI in a general Norwegian adult population sample, and (3) examine factors associated with higher symptom burden defined as the sum score of all symptoms, and factors associated with symptoms` interference on functions. Methods In 2015, MDASI was sent by mail as part of a larger survey, to a representative sample of the general Norwegian adult population (N = 6165). Medical comorbidities were assessed by the Self-Administered Comorbidity Questionnaire. Depression was self-reported on the Patient Health Questionnaire 9 (PHQ-9). Linear multivariable regression analysis was used to examine for factors associated with MDASI sum score and factors associated with symptoms’ interference on functions. Results The response rate was 36%. More women (54%) than men (46%) responded. Mean age was 55 years (SD 14). The most frequent symptoms were fatigue (59.7%), drowsiness (56.2%) and pain (56.1%). Fatigue, pain and disturbed sleep had the highest mean scores. The presence of one or more comorbidities, increasing PHQ-9 score and lower level of education were associated with higher MDASI sum score (p

Abstract Background Several publications have addressed the need for a systematic integration of oncological care focused on the tumor and palliative care (PC) focused on the patient with cancer. The exponential increase in anticancer treatments and the high number of patients living longer with advanced disease have accentuated this. Internationally, there is now a persuasive argument that introducing PC early during anticancer treatment in patients with advanced disease has beneficial effects on symptoms, psychological distress, and survival. Methods This is a national cluster-randomized trial (C-RCT) in 12 Norwegian hospitals. The trial investigates effects of early, systematic integration of oncology and specialized PC in patients with advanced cancer in six intervention hospitals compared with conventional care in six. Hospitals are stratified on the size of local catchment areas before randomization. In the intervention hospitals, a three-part complex intervention will be implemented. The backbone of the intervention is the development and implementation of patient-centered care pathways that contain early, compulsory referral to PC and regular and systematic registrations of symptoms. An educational program must be completed before patient inclusion. A total of 680 patients with advanced cancer and one caregiver per patient are included when patients come for start of last line of chemotherapy, defined according to national treatment guidelines. Data registration, clinical variables, and patient- and caregiver-reported outcomes take place every 2 months for 1 year or until death. The primary outcome is use of chemotherapy in the last 3 months of life by comparing the proportion of patients who receive this in the intervention and control groups. Primary outcome is use of chemotherapy in the last 3 months before death, i.e. number of patients. Secondary outcomes are initiation, discontinuation and number of cycles, last 3 months of life, administration of other medical interventions in the last month of life, symptom burden, quality of life (QoL), satisfaction with information and follow-up, and caregiver health, QoL, and satisfaction with care. Discussion Results from this C-RCT will be used to raise the awareness about the positive outcomes of early provision of specialized palliative care using pathways for patients with advanced cancer receiving medical anticancer treatment. The long-term clinical objective is to integrate these patient-centered pathways in Norwegian cancer care. The specific focus on the patient and family and the organization of a predictable care trajectory is consistent with current Norwegian strategies for cancer care. Trial registration ClinicalTrials.gov , NCT03088202. Registered on 23 March 2017.

Abstract Background Mononuclear cell infiltration of exocrine glands, production of Ro/SSA and La/SSB autoantibodies, along with oral and ocular dryness, are characteristic features of primary Sjögren’s syndrome (pSS). Non-SS sicca subjects, an underexplored group in relation to pSS, display similar sicca symptoms, with possible mild signs of inflammation in their salivary glands, yet with no serological detection of autoantibody production. In this study, we investigated inflammatory manifestations in the salivary gland tissue, tear fluid and saliva of non-SS subjects, as compared to pSS patients and healthy individuals. Methods Fifteen non-SS, 10 pSS and 10 healthy subjects were included in the analyses. Histological evaluation of salivary gland biopsies was performed. Liquid chromatography-mass spectrometry (LC-MS) was conducted on tear fluid and stimulated whole saliva, and proteomic biomarker profiles were generated. Extracellular vesicle (EVs) isolation and characterisation from both fluids were also combined with LC-MS. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold. Database for Annotation, Visualization and Integrated Discovery (DAVID) and Functional Enrichment Analysis Tool (FunRich) were applied for functional analyses. Results Histopathological evaluation of salivary gland biopsies showed implications of milder inflammation in non-SS subjects through mononuclear cell infiltration, fibrosis and fatty replacement, as compared to pSS patients. Although unaffected in the non-SS group, upregulation of proinflammatory pathways and proteins involved in ubiquitination (LMO7 and HUWE1) and B cell differentiation (TPD52) were detected in tear fluid of pSS patients. Moreover, overexpression of proteins STOM, ANXA4 and ANXA1, regulating cellular innate and adaptive immunological pathways, were further identified in EVs from tear fluid of pSS patients. Finally, whole saliva and EVs isolated from whole saliva of pSS patients expressed proteins vital for innate MHC class I cellular regulation (NGAL) and T cell activation (CD44). Conclusions Non-SS sicca subjects may show implications of mild inflammation in their glandular tissue, while their protein profile was strikingly more similar to healthy controls than to pSS patients. Hence, the tear and salivary biomarkers identified could be implemented as potential non-invasive diagnostic tools that may aid in increasing diagnostic accuracy when evaluating non-SS subjects and pSS patients and monitoring disease progression.

Abstract Accurate thrombin generation determination by calibrated automated thrombinography can be sustained when reducing the plasma and reagent volumes up to half, but not for higher reductions or plasma dilutions.

Abstract Background Lack of Hepatitis C virus (HCV) incidence data in (Norwegian) high-risk groups impedes the ability to make informed decisions on prevention measures. Thus we rely on modelling to estimate the incidence and burden of HCV infections. Methods We constructed a compartmental model for HCV infections in Norway among active and former people who inject drugs (PWIDs). We based yearly transition rates on literature. The model was fitted to absolute numbers of hepatitis C associated cirrhosis, hepatocellular carcinoma (HCC) and death from national data sources (2000–2013). We estimated the number (95%CI) of HCV infections, cirrhosis, HCC and death and disability adjusted life years (DALYs) due to HCV infections in Norway, 1973–2030. We assumed treatment rates in the projected period were similar to those in 2013. Results The estimated proportion of chronic HCV (including those with cirrhosis and HCC) among PWIDs was stable from 2000 (49%; 4441/9108) to 2013 (43%; 3667/8587). We estimated that the incidence of HCV among PWIDs was 381 new infections in 2015. The estimated number of people with cirrhosis, HCC, and liver transplant was predicted to increase until 2022 (1537 people). DALYs among active PWIDs estimated to peak in 2006 (3480 DALYs) and decrease to 1870 DALYs in 2030. Chronic HCV infection contributes most to the total burden of HCV infection, and peaks at 1917 DALYs (52%) in 2007. The burden of HCV related to PWID increased until 2006 with 81/100,000 DALYs inhabitants and decreased to 68/100,000 DALYs in 2015. Conclusion The burden of HCV associated with injecting drug use is considerable, with chronic HCV infection contributing most to the total burden. This model can be used to estimate the impact of different interventions on the HCV burden in Norway and to perform cost-benefit analyses of various public health measures.

Abstract Background The aims of the present study were to assess symptoms associated with an autism spectrum disorder (ASD) in children with neurological disorders as reported by parents and teachers on the Autism Spectrum Screening Questionnaire (ASSQ), as well as the level of agreement between informants for each child. Methods The ASSQ was completed by parents and teachers of the 5781 children (11–13 years) who participated in the second wave of the Bergen Child Study (BCS), an on-going longitudinal population-based study. Out of these children, 496 were reported to have a chronic illness, including 99 whom had a neurological disorder. The neurological disorder group included children both with and without intellectual disabilities. Results Children with neurological disorders obtained significantly higher parent and teacher reported ASSQ scores than did non-chronically ill children and those with other chronic illnesses (p Conclusions The ASSQ identifies a high rate of ASD symptoms in children with neurological disorders, and a large number of children screened in the positive range for ASD. Although a firm conclusion awaits further clinical studies, the present results suggest that health care professionals should be aware of potential ASD related problems in children with neurological disorders, and should consider inclusion of the ASSQ or similar screening instruments as part of their routine assessment of this group of children.

Abstract Background High intellectual function is considered as a protective factor for children's mental health. Few studies have investigated the effect of intellectual function on mental health in children with chronic illness (CI). The aim of the present study was twofold: First, we asked if normal to high intellectual function (IQ) has a protective effect on mental health in children with CI, and secondly, if this effect is more substantial than in their peers (NCI). Methods The participants were selected among children who participated in the Bergen Child Study (BCS): 96 children with CI (the CI-group) and 96 children without CI (the NCI-group). The groups were matched on intellectual function as measured by the WISC-III by selecting the same number of children from three levels of the Full Scale IQ Score (FSIQ): "very low" (84). CI was reported by parents as part of a diagnostic interview (Kiddie-SADS-PL) that also generated the mental health measures used in the present study: the presence of a DSM-IV psychiatric diagnosis and the score on the Children's Global Assessment Scale. Results The risk of a psychiatric diagnosis was significantly lower for children with a normal to high FSIQ-level than for children with a very low and low FSIQ-level in the CI-group as well as in the NCI-group. The group differences were statistically non-significant for all three FSIQ-levels, and the effect of the interaction between the group-variable (CI/NCI) and the FSIQ-level was non-significant on both measures of mental health. Conclusion The present study showed a protective effect of normal to high intellectual function on children's mental health. This protective effect was not more substantial in children with CI than in children without CI.