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Background and Aims To improve management of patients with Crohn’s disease, objective measurements of disease activity are needed. Ileocolonoscopy is the current reference standard but has limitations that restrict repeated use. Ultrasonography is potentially useful for activity monitoring, but no validated sonographic activity index is currently in widespread use. Thus, we aimed to construct and validate a simple ultrasound score for Crohn’s disease. Methods Forty patients were prospectively examined with ultrasound and endoscopy in the development phase. The Simple Endoscopic Score for Crohn’s Disease [SES-CD] was used as a reference standard. Seven ultrasound variables [bowel wall thickness, length, colour Doppler, stenosis, fistula, stratification and fatty wrapping] were initially included, and multiple linear regression was used to select the variables that should be included in the final score. Second, the ultrasound data from each patient were re-examined for interobserver assessment using weighted kappa and intraclass correlation. Finally, the activity index was validated in a new cohort of 124 patients. Results Length, fistula and stenosis were excluded. The combination of the remaining variables provided a multiple correlation coefficient of r = 0.78. Interobserver analysis revealed poor agreement for stratification and fatty wrapping and these were thus excluded. There was excellent interobserver agreement for the remaining score consisting of wall thickness and colour Doppler. In both patient cohorts, the ultrasound score correlated well with SES-CD [Development cohort: rho = 0.83, p Conclusions A simple ultrasound activity index for Crohn’s disease consisting of bowel wall thickness and colour Doppler was constructed and validated and correlated well with endoscopic disease activity. ClinicalTrials. gov ID: NCT03481751

Aim: To examine the effect of a family-oriented multidisciplinary intervention pro-gramme to curtail weight increase in young children with obesity.Methods: Children who weighed more than one kilogram above the 97th percentile for height at the preschool assessment in Oppland County, Norway, were identified. Parents residing in one part of the county were invited to participate in a group-based three-year intervention programme while the rest had no interventions. Body mass index (BMI) and family characteristics at entry and measurements at birth were explanatory variables, and change in BMI standard deviation score (SDS) the outcome measure. For the intervention group, outcome was also related to skinfold thicknesses, waist-to-height ratio and physical ability.Results: The programme was completed by 31 families in the intervention and 33 in the control group. At entry, the respective median (interquartile) age was 5.83 (0.36) and 5.74 (0.66) years, and the BMI SDS 2.35 (1.06) and 1.95 (0.49), P = .012. The median decrease in BMI SDS was 0.19 in both groups. The decline increased with increasing BMI SDS at entry, but irrespective of group. Social or behavioural factor or other anthropometric measures were not associated with outcome.Conclusion: The intervention programme had no effect on BMI SDS. The South-Eastern Norway Regional Health Authority (Helse Sør Øst) Innlandet Hospital Trust

Aim We evaluated the role of placental pathology in predicting adverse outcomes for neonates born extremely preterm (EPT) before 28 weeks of gestation. Methods This was a prospective observational study of 123 extremely preterm singletons born in a hospital in western Norway, and the placentas were classified according to the Amsterdam criteria. The associations between histologic chorioamnionitis (HCA), by the presence or the absence of a foetal inflammatory response (FIR+ or FIR−), maternal vascular malperfusion (MVM) as a whole and adverse neonatal outcomes were evaluated by logistic regression analyses. Adverse outcomes were defined as perinatal death, necrotising enterocolitis (NEC), bronchopulmonary dysplasia (BPD), brain pathology by magnetic resonance imaging at term-equivalent age, retinopathy of prematurity and early-onset neonatal sepsis. The results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results HCA was associated with NEC (OR 12.2, 95% CI 1.1 to 137.1). HCA/FIR+ was associated with BPD (OR 14.9, 95% CI 1.8–122.3) and brain pathology (OR 9.8, 95% CI 1.4–71.6), but HCA/FIR− was not. The only neonatal outcome that MVM was associated with was low birthweight. Conclusion Placental histology provided important information when assessing the risk of adverse neonatal outcomes following EPT birth. publishedVersion

Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted. Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated. Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005). Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch). publishedVersion

Purpose To evaluate the postoperative closure rate of full-thickness macular holes (MHs) after nonsupine positioning, which means that the patients avoid upward gaze and a supine sleeping position, and to investigate the correlation between postoperative positioning compliance and closure rate. Design Prospective, multicenter study ( ClinicalTrials.gov identifier, NCT02295943 ). Participants Patients undergoing primary surgery for primary MH. Methods Patients underwent pars plana vitrectomy with internal limiting membrane peeling and sulfur hexafluoride gas tamponade followed by 3 to 5 days of nonsupine positioning. A positioning measuring device that recorded the time spent in the supine position was attached to patients’ forehead after surgery for 24 hours. Main Outcome Measures Anatomic closure rate of MH at 2 weeks or more after surgery and the time spent in supine position during the first 24 hours after surgery. Results A total of 205 participants were included, of whom 2 were lost to follow-up. Two hundred two of 203 MHs closed after a single operation, giving a closure rate of 99.5% (95% confidence interval, 97.3%–99.9%). The median time of supine positioning during the first 24 hours was 28 seconds (range, 0:00:00–01:52:28). Because of the very high closure rate, a correlation between positioning compliance and closure rate could not be established. Conclusions Pars plana vitrectomy with internal limiting membrane peeling followed by a short-term nonsupine positioning accomplished a very high MH closure rate. Thus, face-down positioning was not necessary to achieve excellent closure rates in this study.

Contains fulltext : 202775.pdf (Publisher’s version ) (Open Access) BACKGROUND: Genetic testing is increasing in patients newly diagnosed with cancer. This study investigated the levels, course and predictors of cancer-related distress, defined as intrusion and avoidance, in women undergoing BRCA1/2 testing without pretest genetic counseling shortly after a diagnosis of breast or ovarian cancer. MATERIAL AND METHODS: Unselected for family history or age, 259 women with breast cancer and 50 women with ovarian cancer, underwent BRCA1/2 testing shortly after diagnosis. Cancer-related distress was measured with the Impact of Event Scale before and after genetic testing. In order to identify predictors of distress, the subscale scores were regressed on baseline predictor variables including sociodemographic and medical variables, perceived social support, and decisional conflict regarding genetic testing. RESULTS: The mean levels of intrusion and avoidance were in the moderate range both before and after genetic testing with a statistically significant decline during follow-up. Younger age, shorter time since diagnosis, lower levels of social support, and a diagnosis of ovarian cancer predicted higher levels of both intrusion and avoidance. In addition, higher levels of decisional conflict and living with a partner predicted higher levels of intrusion. CONCLUSIONS: Women having genetic testing shortly after a diagnosis of breast or ovarian cancer had a moderate mean level of cancer-related distress, which decreased with time. Health personnel offering genetic testing to newly diagnosed women with breast or ovarian cancer should be aware of the potential predictors for increased cancer-related distress identified in this study: younger age, less perceived social support, higher levels of decisional conflict regarding genetic testing, and living with a partner.

Objectives: We studied the prevalence of atherosclerosis among ischaemic stroke patients ≤60 years and controls at the time of the index stroke, and its association with occurrence of new cardiovascular events (CVEs) and mortality at a 5-year follow-up. Methods: Prevalent atherosclerosis was assessed for 385 patients and 260 controls in seven vascular areas by electrocardiogram (ECG), ankle–arm index (AAI) and measurement of right and left carotid and femoral intima-media thickness (cIMT and fIMT) and abdominal aorta plaques (AAP). Clinical end-points were any new CVE (stroke, angina, myocardial infarction or peripheral arterial disease) or death from any cause at 5-year follow-up. All results were sex- and age-adjusted; logistic regression and Cox proportional hazards models were applied. Results: Young patients ≤49 years had prevalent atherosclerosis in 1/2 of males and 1/3 of females. Compared with controls, young female patients showed significantly higher prevalent atherosclerosis, p = 0.024. Ischaemic ECG and mean cIMT were higher in young and middle-aged female patients ( p = 0.044, p = 0.020, p = 0.023 and p Conclusion: Atherosclerosis is highly prevalent even in young stroke patients. Some areas and increasing NAA are associated with CVEs and death.

Objectives To investigate whether acute infection with Giardia lamblia is associated with fibromyalgia 10 years after infection and whether fibromyalgia is associated with irritable bowel syndrome (IBS) and chronic fatigue (CF) in this setting. Methods A cohort study was established after an outbreak of G. lamblia in Bergen, Norway, 2004. Laboratory-confirmed cases and a matched control group were followed for 10 years. The main outcome was fibromyalgia 10 years after giardiasis, defined by the 2016 revisions of the fibromyalgia diagnostic criteria using the Fibromyalgia Survey Questionnaire (FSQ). Results The prevalence of fibromyalgia was 8.6% (49/572) among Giardia exposed compared to 3.1% (21/673) in controls (pGiardia exposed compared to controls (odds ratio (OR): 2.91, 95% confidence interval (CI): 1.72, 4.91), but adjusted for IBS and CF it was not (OR: 1.05, 95% CI: 0.57, 1.95). Among participants without CF the odds for fibromyalgia was 6.27 times higher for participants with IBS than those without (95% CI: 3.31, 11.91) regardless of exposure. Among participants without IBS the odds for fibromyalgia was 4.80 times higher for those with CF than those without (95% CI: 2.75, 8.37). Conclusions We found a higher prevalence of fibromyalgia among Giardia exposed compared to controls 10 years after the acute infection. Fibromyalgia was strongly associated with IBS and CF, and the difference between the exposed and controls can be attributed to the high prevalence of IBS and CF among the Giardia exposed. Notably, this study was not designed to establish causality between Giardia exposure and the outcomes.

Objectives To evaluate cost-effectiveness of the WHO Surgical Safety Checklist. Background The clinical effectiveness of surgical checklists is largely understood. Few studies to-date have evaluated the cost-effectiveness of checklist use. Methods An economic evaluation was carried out using data from the only available randomized controlled trial of the checklist. Analyses were based on 3702 procedures. Costs considered included checklist implementation costs and length and cost of hospital stay, costs of warming blanket use, blood transfusions and antibiotics used in the operating room, and the cost of clinical time in the operating room - all calculated for each procedure and its associated admission. Nonparametric bootstrapping was used to simulate an empirical distribution of the mean effect of the checklist on total admission costs and the probability of observing a complication-free admission and to quantify sampling uncertainty around mean cost estimates. Results The overall cost of checklist implementation was calculated to be $900 per 100 admissions. Implementation of the WHO checklist resulted in an additional 5.9 complication-free admissions per 100 admissions and an average of 110 bed-days saved per 100 admissions. Accounting for all costs included in the analysis, for every 100 admissions, use of the WHO checklist was estimated to save $55,899. Conclusions Implementation of the WHO checklist was a cost-effective strategy for improving surgical safety.

ObjectiveTo examine if underweight (UW), overweight (OW) or obesity (OB), or body mass index (BMI) expressed as its SD score (BMI SDS), were associated with psychological difficulties in preschool children.DesignRegional cohort study.SettingOppland County, Norway.MethodsAt the routine school entry health assessment at 5–6 years of age, parents were invited to participate by local public health nurses. The parents completed questionnaires on sociodemographic, health and lifestyle factors of the child and the family, and on the child’s neurocognitive development. They assessed psychological health with the Strengths and Difficulties Questionnaire (SDQ). Public health nurses measured weight and height on all eligible children and reported age, sex, height and weight anonymously for the children who declined to participate.ParticipantsWe obtained information on 1088 of 1895 (57%) eligible children. The proportion of UW, OW and OB was slightly higher among the children who declined.Main outcome measuresSDQ subscale and Total Difficulties Scores.ResultsThe mean SDQ scores and proportion of scores ≥the 90th percentile had a curvilinear pattern from UW through normal weight (NW), OW and OB with NW as nadir, but the pattern was only significant for the mean Emotional problems, Peer problems and Total SDQ Scales, and for the Total SDQ Score ≥the 90th percentile (TDS90). After adjusting for relevant social, developmental, health and behavioural characteristics, TDS90 was only significantly associated with UW in multiple logistic regression analyses, and only with the lowest quartile of BMI SDS in a linear spline regression analysis.ConclusionsThe study suggests that UW and low BMI, but not OW, OB or higher BMI, are independent risk factors for having psychological symptoms in preschool children.

Background A major challenge in the follow-up of patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) is to distinguish pseudoprogression (PP) from tumor recurrence (TR). The aim of the study was to develop a clinical risk assessment score. Methods Follow-up images of 87 of 97 consecutive patients treated with SRS for 348 BM were analyzed. Of these, 100 (28.7%) BM in 48 (53.9%) patients responded with either TR (n = 53, 15%) or PP (n = 47, 14%). Differences between the 2 groups were analyzed and used to develop a risk assessment score (the Bergen Criteria). Results Factors associated with a higher incidence of PP vs. TR were as follows: prior radiation with whole brain radiotherapy or SRS (P = .001), target cover ratio ≥98% (P = .048), BM volume ≤2 cm3 (P = .054), and primary lung cancer vs. other cancer types (P = .084). Based on the presence (0) or absence (1) of these 5 characteristics, the Bergen Criteria was established. A total score 3 points were associated with 84% TR and 16% PP, P < .001. Conclusion Based on 5 characteristics at the time of SRS the Bergen Criteria could robustly differentiate between PP vs. TR following SRS. The score is user-friendly and provides a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.

Rare sequence variants in the non-coding part of the BRCA genes are often reported as variants of uncertain significance (VUS), which leave patients and doctors in a challenging position. The aim of this study was to determine the pathogenicity of the BRCA1 c.5407-25T>A variant found in 20 families from Norway, France and United States with suspected hereditary breast and ovarian cancer. This was done by combining clinical and family information with allele frequency data, and assessment of the variant’s effect on mRNA splicing. Mean age at breast (n = 12) and ovarian (n = 11) cancer diagnosis in female carriers was 49.9 and 60.4 years, respectively. The mean Manchester score in the 20 families was 16.4. The allele frequency of BRCA1 c.5407-25T>A was 1/64,566 in non-Finnish Europeans (gnomAD database v2.1.1). We found the variant in 1/400 anonymous Norwegian blood donors and 0/784 in-house exomes. Sequencing of patient-derived cDNA from blood, normal breast and ovarian tissue showed that BRCA1 c.5407-25T>A leads to skipping of exon 23, resulting in frameshift and protein truncation: p.(Gly1803GlnfsTer11). Western blot analysis of transiently expressed BRCA1 proteins in HeLa cells showed a reduced amount of the truncated protein compared with wild type. Noteworthily, we found that a small amount of full-length transcript was also generated from the c.5407-25T>A allele, potentially explaining the intermediate cancer burden in families carrying this variant. In summary, our results show that BRCA1 c.5407-25T>A leads to partial skipping of exon 23, and could represent a likely pathogenic variant with reduced penetrance.

Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS. Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery. publishedVersion

Studies indicate that stathmin expression associates with PI3K activation in breast cancer, suggesting stathmin as a marker for targetable patient subgroups. Here we assessed stathmin in relation to tumour proliferation, vascular and immune responses, BRCA1 germline status, basal-like differentiation, clinico-pathologic features, and survival. Immunohistochemical staining was performed on breast cancers from two series (cohort 1, n = 187; cohort 2, n = 198), and mass spectrometry data from 24 cases and 12 breast cancer cell lines was examined for proteomic profiles. Open databases were also explored (TCGA, METABRIC, Oslo2 Landscape cohort, Cancer Cell Line Encyclopedia). High stathmin expression associated with tumour proliferation, p53 status, basal-like differentiation, BRCA1 genotype, and high-grade histology. These patterns were confirmed using mRNA data. Stathmin mRNA further associated with tumour angiogenesis, immune responses and reduced survival. By logistic regression, stathmin protein independently predicted a BRCA1 genotype (OR 10.0, p = 0.015) among ER negative tumours. Cell line analysis (Connectivity Map) implied PI3K inhibition in tumours with high stathmin. Altogether, our findings indicate that stathmin might be involved in the regulation of tumour angiogenesis and immune responses in breast cancer, in addition to tumour proliferation. Cell data point to potential effects of PI3K inhibition in tumours with high stathmin expression.

Background The number of incidental meningiomas has increased because of the increased availability of neuroimaging. Lack of prospective data on the natural history makes the optimal management unclear. We conducted a 5-year prospective study of incidental meningiomas to identify risk factors for tumor growth. Methods Sixty-four of 70 consecutive patients with incidental meningioma were included. Clinical and radiological status was obtained at 0, 0.5, 1, 1.5, 2, 3, 4, and 5 years. GammaPlan and mixed linear regression modeling were utilized for volumetric analysis with primary endpoint tumor growth. Results None of the patients developed tumor-related symptoms during the study period, although 48 (75%) tumors increased (>15%), 13 (20.3%) remained unchanged, and 3 (4.7%) decreased (>15%) in volume. Mean time to growth was 2.2 years (range, 0.5-5.0 years). The growth pattern was quasi-exponential in 26%, linear in 17%, sigmoidal in 35%, parabolic in 17%, and continuous reduction in 5%. There was significant correlation among growth rate, larger baseline tumor volume (P < .001), and age in years (75 y: 0.85 cm3/y). Conclusion The majority of meningiomas will eventually grow. However, more than 60% display a self-limiting growth pattern. Our study provides level-2 evidence that asymptomatic tumors can be safely managed utilizing serial imaging until persistent radiological and/or symptomatic growth.

Background and purpose We have previously shown that patients with multiple sclerosis receiving immunomodulatory treatment have reduced seroprotection rates after influenza immunization. The aim of this study was to further investigate the influence of immunomodulatory therapies on the antibody response and seroprotection rates in patients immunized with seasonal influenza vaccine in 2012/2013 compared with healthy controls. Methods Ninety patients receiving fingolimod, glatiramer acetate, interferon beta-1a/1b, natalizumab or no therapy were compared with 62 healthy controls. All subjects received the inactivated split virus vaccine in 2012 and serum samples were collected pre-vaccination and 3, 6 and 12 months post-vaccination. The vaccine responses were evaluated by the hemagglutination inhibition assay and adjusted for age and gender. Results No significant differences in rates of protection against H1N1 for interferon beta-1a/1b and glatiramer acetate were observed as compared with controls at 3, 6 and 12 months. Fingolimod provided reduced protection at all time points post-vaccination, whereas natalizumab displayed reduced protection at 3 and 6 months. Patients without immunomodulation did not display protection rates that were significantly different from the controls at 3 and 12 months. Conclusion These findings suggest that patients with multiple sclerosis receiving fingolimod or natalizumab should be considered for a second dose of the vaccine in cases of insufficient protection. Our results further indicate that new immunomodulatory treatment regimens should be systematically evaluated for their influence on influenza-specific vaccine responses.

Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers. Funding Agencies|National Advisory Unit on sarcomas in Norway; Swedish Cancer Society

Background Both animal and human studies have suggested that prenatal opioid exposure may be detrimental to the developing fetal brain. However, results are somewhat conflicting. Structural brain changes in children with prenatal opioid exposure have been reported in a few studies, and such changes may contribute to neuropsychological impairments observed in exposed children. Aim To investigate the association between prenatal opioid exposure and brain morphology in school-aged children. Study design A cross-sectional magnetic resonance imaging (MRI) study of prenatally opioid-exposed children and matched controls. Subjects A hospital-based sample (n = 16) of children aged 10–14 years with prenatal exposure to opioids and 1:1 sex- and age-matched unexposed controls. Outcome measures Automated brain volume measures obtained from T1-weighted MRI scans using FreeSurfer. Results Volumes of the basal ganglia, thalamus, and cerebellar white matter were reduced in the opioid-exposed group, whereas there were no statistically significant differences in global brain measures (total brain, cerebral cortex, and cerebral white matter volumes). Conclusions In line with the limited findings reported in the literature to date, our study showed an association between prenatal opioid exposure and reduced regional brain volumes. Adverse effects of opioids on the developing fetal brain may explain this association. However, further research is needed to explore the causal nature and functional consequences of these findings.

BackgroundExercise-induced laryngeal obstruction (EILO) is common in athletes and presents with dyspnoea, chest tightness, inspiratory stridor and sometimes panic reactions. The evidence for conservative treatment is weak, but case reports suggest effects from inspiratory muscle training (IMT). We aimed to explore effects from IMT used in athletes with EILO.MethodTwenty-eight athletes, mean age 16.4 years, diagnosed with EILO at our clinic, participated in a 6-week treatment programme, using a resistive flow-dependent IMT device (Respifit S). Four athletes competed at international level, 13 at national and 11 at regional levels. Video-recorded continuous transnasal flexible laryngoscopy was performed from rest to peak exercise (continuous laryngoscopy exercise (CLE) test) and scored before and 2–4 weeks after the training period. Ergospirometric variables were obtained from this CLE set-up. Lung function was measured according to guidelines. Symptom scores and demographic variables were obtained from a questionnaire.ResultsAfter the treatment period, symptoms had decreased in 22/28 (79%) participants. Mean overall CLE score had improved after treatment (pConclusionThis explorative study underlines the heterogeneous treatment response of EILO and suggests that IMT may become an efficient conservative treatment tool in subgroups, possibly contributing to better control of the vocal folds. The signals from this study should be tested in future controlled interventional studies.

Diagnosing asthma and deciding treatment are difficult in young children. An inappropriate and too high prescription rate of inhaled corticosteroids (ICS) is suggested, but how airway symptoms are associated with prescriptions of asthma medication is less known. We studied how strongly wheeze, lower respiratory tract infections (LRTI), and atopic diseases are associated with dispensing of asthma medications during early childhood. We used data from the Norwegian Mother and Child Cohort Study and the Norwegian Prescription Database at four age‐intervals (0‐6, 6‐18, 18‐36 months, and 3‐7 years). Primary outcomes were dispensed asthma medications (no medication, short‐acting β‐2 agonist, or ICS). Relative risks (RRs) and average attributable fractions (AAFs) were estimated. Both wheeze and LRTI were positively associated with both medication groups (0‐6 months: no data on wheeze). The RRs and AAFs were higher for wheeze than LRTI. For ICS, the AAFs (95% CI) for wheeze vs LRTI were: 6 to 18 months: 69.2 (67.2, 71.2)% vs 10.4 (9.0, 11.8)%, 18 to 36 months: 33.0 (30.5, 35.5)% vs 10.0 (8.0, 12.0)%, and 3 to 7 years: 33.7 (31.0, 36.5)% vs 1.2 (0.5, 1.9)%. Except at 3 to 7 years of age, the AAFs were lower for atopic diseases than for LRTI and wheeze. Atopic diseases modified the associations between wheeze and ICS at 18 to 36 months and between LRTI or wheeze and ICS at 3 to 7 years. In conclusion, both wheeze and LRTI were associated with prescriptions of asthma medications in young children, with the strongest associations seen for wheeze. Atopic diseases contributed to these associations only in the oldest age groups. publishedVersion

The clinical relevance of antibodies that bind to glutamic acid decarboxylase 65 (GAD65) is controversial regarding diagnostic utility in screening for neurological disease or cancer. We did a retrospective study of 3152 GAD65 antibody-positive patients to examine whether analysis of the antibody levels could predict neurological disease or cancer. Serum GAD65 antibody levels were not associated with any of the following groups: neurological disease, neurological disease and diabetes, diabetes only, no neurological diagnosis and no diabetes mellitus, or cancer. Analysis of serum GAD65 antibody levels had no prognostic value in neurological disease or cancer. GAD65 antibodies should therefore be measured in selective cases of autoimmune neurological diseases.

Limited information exists regarding the natural development of loneliness and its determinants among cognitively intact nursing home residents. We aimed to examine loneliness among nursing home residents by following up for 6 years and to determine whether sociodemographic factors, diagnosis of cancer, sense of coherence, social support, and depression symptoms influence loneliness. The study was longitudinal and prospective and included baseline assessment and 6-year follow-up. After baseline assessment of 227 cognitively intact nursing home residents (Clinical Dementia Rating score ≤0.5), 52 respondents were interviewed a second time at the 5-year follow-up and 18 respondents a third time at the 6-year follow-up. Data from the interviews were recorded using a global question of loneliness, the Social Provisions Scale, Sense of Coherence Scale, and Geriatric Depression Scale. Scores on Groll’s index (p = .02) and the Sense of Coherence Scale (p = .04) were positively correlated with loneliness and negatively correlated with geriatric depression (p = .001). Having a diagnosis of cancer, social support, and age were not correlated with loneliness 6 years from baseline. Loneliness did not change during the 6 years of follow-up, and symptoms of depression and the sense of coherence appeared to be important components of loneliness. Finally, having a diagnosis of cancer and social support were not associated with loneliness. publishedVersion

Background Gastroenteritis has been associated with complications such as irritable bowel syndrome (IBS) and chronic fatigue (CF). Little is known about the implications for quality of life (QoL) in this setting. The aims of this study were to evaluate the association between exposure to Giardia infection and QoL ten years after the infection, and how this related to IBS and CF. Methods We followed 1252 patients with laboratory‐verified Giardia lamblia infection and a matched control group for 10 years after an epidemic in Bergen, Norway, in 2004. The main outcome was QoL after ten years as defined by the Short‐form 12 version 2 with a physical component summary (PCS) and a mental component summary (MCS), both with range 0‐100 (T‐score). Regression analyses were performed using mixed modeling. Key Results Mean PCS T‐score in the exposed group (51.4; 95% CI: 50.6‐52.1) was 2.8 T‐score points (95% CI: −3.8 to −1.9, P, We assessed quality of life ten years following a Giardia lamblia infection and found that exposure to Giardia was associated with a reduced quality of life as compared to a control group. The reduced quality of life was mainly due to the coexistence of irritable bowel syndrome and chronic fatigue.

Introduction: Exercise induced laryngeal obstruction (EILO) is relatively common in adolescents, with symptoms often confused with exercise induced asthma. EILO often starts with medial or inward rotation of supraglottic structures of the larynx, whereas glottic adduction appears as a secondary phenomenon in a majority. Therefore, surgical treatment (supraglottoplasty) is used in thoroughly selected and highly motivated patients with pronounced symptoms and severe supraglottic collapse. Aim: To investigate efficacy and safety of laser supraglottoplasty as treatment for severe supraglottic EILO by retrospective chart reviews. Methods: The EILO register at Haukeland University Hospital, Bergen, Norway was used to identify patients who had undergone laser supraglottoplasty for severe supraglottic EILO, verified by continuous laryngoscopy exercise (CLE) test, during 2013-2015. Laser incision in both aryepiglottic folds anterior to the cuneiform tubercles and removal of the mucosa around the top was performed in general anesthesia. Outcomes were questionnaire based self-reported symptoms, and laryngeal obstruction scored according to a defined scheme during a CLE-test performed before and after surgery. Results: Forty-five of 65 eligible patients, mean age 15.9 years, were included. Post-operatively, 38/45 (84%) patients reported less symptoms, whereas CLE-test scores had improved in all, of whom 16/45 (36%) had no signs of obstruction. Most improvements were at the supraglottic level, but 21/45 (47%) also improved at the glottic level. Two of 65 patients had complications; self-limiting vocal fold paresis and scarring/shortening of plica ary-epiglottica. Conclusion: Supraglottoplasty improves symptoms and decreases laryngeal obstruction in patients with severe supraglottic EILO, and appears safe in highly selected cases. Major funding institutions: Haukeland University Hospital and University of Bergen.

Objectives Cerebrovascular stroke is a main cause of lasting disability in older age, and initial stroke severity has been established as a main determinant for the degree of functional loss. In this study, we searched for other predictors of functional outcome in a cohort of stroke patients participating in an early supported discharge randomised controlled trial. Methods Thirty candidate variables related either to premorbid history or to the acute stroke were examined by ordered logistic regression in 229 stroke patients. Dependent variables were modified Rankin Scale (mRS) at 6 months and mRS change from baseline to 6 months. Results For mRS at 6 months, Barthel Index at stable baseline post-stroke was the main predictor, with sex, age, previous cerebrovascular disease, previous peripheral artery disease and the necessity for tube feeding in the acute phase also contributing to the final model. For mRS change, only age and previous cerebrovascular disease were significant predictors. Prestroke subjective health complaints added significantly to all final models concurrently with sex losing its predictive power. Conclusions Initial stroke severity was the main predictor of functional outcome. Subjective health complaints score was a potent predictor for both outcome and improvement from baseline to 6 months and at the same time ameliorated the predictive impact of sex. The poorer functional prognosis for women after stroke may therefore be related to their higher load of subjective health complaints rather than to their sex itself. Treating these complaints may possibly improve the functional prognosis.

Background/Aim: Laparoscopic complete mesocolic excision (CME) used in the treatment of transverse colon cancer has been questioned on the basis of the technical challenges. The aim of this study was to evaluate the medium- and long-term clinical and survival outcomes after laparoscopic and open CME for transverse colon cancer and to compare the 2 approaches. Methods: This study was a retrospective non-randomized study of patients with prospectively registered data on open and laparoscopic CME for transverse colon cancer tumour-node-metastasis stages I-III operated on between 2007 and 2014. This was a single-centre study in a community teaching hospital. A total of 56 patients with transverse colon cancer were included, excluding those with tumours in the colonic flexures. The outcome aims were 4-year time to recurrence (TTR) and cancer-specific survival (CSS). Morbidity was also measured. Results: The 4-year TTR was 93.9% in the laparoscopic group and 91.3% in the open group (p = 0.71). The 4-year CSS was 97.0% in the laparoscopic group and 91.3% in the open group (p = 0.42). Limitations: This was a prospective single-institution study with a small sample size. Conclusion: Results of the study suggest that the laparoscopic CME approach might be the preferred approach for transverse colon cancer, especially regarding its benefits in terms of short-term morbidity, length of stay and oncological outcome.

Background: Rectal cancer surgery is standardized, resulting in improved survival. Colon cancer has fallen behind and therefore more radical surgical techniques have been introduced. One technique is complete mesocolic excision. The aim of this article was to study the complications after the introduction of standardized complete mesocolic excision in a single center. Methods: Complete mesocolic excision was introduced in 2007, and data were collected from 286 patients prior to surgery (2007–2010). The surgeon decided on open or laparoscopic surgery. Follow-up information was recorded until 31 December 2015. Complications were classified according to a modified Clavien–Dindo classification. Results: Complications occurred in 47%, severe complications (grade III and IV) in 15%. In-hospital mortality was 3.5%. A total of 142 patients (49.7%) were operated by open surgery. Logistic regression revealed anemia (p = 0.001), open surgery (p Conclusion: Severe complications following the introduction of complete mesocolic excision are patient dependent and related to open surgery. Patients selected for laparoscopy had less number of complications; therefore, introducing complete mesocolic excision by laparoscopy is justified. Identification of these factors can improve selection of appropriate surgical approach and postoperative patient safety.

To investigate epidemiological trends of infective endocarditis (IE) in western Norway a retrospective study was performed.Characteristics of 706 IE admissions from 1996 to 2005 and 2006 to 2015 were analysed and compared using the Chi-square test for categorical variables and the t-test for age. Survival was analysed by multiple Cox regression and reported by the hazard ratio (HR).Mean annual incidence rates increased from 4.6 to 7.4 per 100,000 inhabitants (rate ratio: 1.97, 95% confidence interval: 1.52-2.56, p .001). Non-viridans streptococci, enterococci and Staphylococcus aureus (S. aureus), were all independently associated with increased mortality. The frequency of IE caused by enterococci increased from 3.7 to 13.0% (p .001). The proportion of intravenous drug users (IVDU) increased from 16.5 to 23.5% (p = .015) and had increasing aortic valve involvement (p = .023). Prosthetic valve endocarditis (PVE) constituted 30% of IE cases in both decades with biological PVE increasing from 9.4 to 22.1% (p .001) and mechanical PVE decreasing from 18.7 to 8.9% (p .001). In the last decade, valve replacement surgery was performed in 37.6% of the patients, of which 85.5% received a bioprosthesis.The incidence of IE increased significantly. Non-viridans streptococci, enterococci and S. aureus were all significantly associated with increased mortality. The increased number of enterococcal IE and the increased number of IVDUs with left-sided IE constituted new challenges. Biological implants were preferred in a majority of patients requiring surgery.

Background: Allogeneic hematopoietic stem cell transplantation is associated with a high risk of immune-mediated post-transplant complications. Graft depletion of immunocompetent cell subsets is regarded as a possible strategy to reduce this risk without reducing antileukemic immune reactivity. Study design and methods: We investigated the effect of hematopoietic stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on peripheral blood and stem cell graft levels of various T, B, and NK cell subsets in healthy donors. The results from flow cytometric cell quantification were examined by bioinformatics analyses. Results: The G-CSF-induced mobilization of lymphocytes was a non-random process with preferential mobilization of naïve CD4+ and CD8+ T cells together with T cell receptor αβ+ T cells, naïve T regulatory cells, type 1 T regulatory cells, mature and memory B cells, and cytokine-producing NK cells. Analysis of circulating lymphoid cell capacity to release various cytokines (IFNγ, IL10, TGFβ, IL4, IL9, IL17, and IL22) showed preferential mobilization of IL10 releasing CD4+ T cells and CD3−19− cells. During G-CSF treatment, the healthy donors formed two subsets with generally strong and weaker mobilization of immunocompetent cells, respectively; hence the donors differed in their G-CSF responsiveness with regard to mobilization of immunocompetent cells. The different responsiveness was not reflected in the graft levels of various immunocompetent cell subsets. Furthermore, differences in donor G-CSF responsiveness were associated with time until platelet engraftment. Finally, strong G-CSF-induced mobilization of various T cell subsets seemed to increase the risk of recipient acute graft versus host disease, and this was independent of the graft T cell levels. Conclusion: Healthy donors differ in their G-CSF responsiveness and preferential mobilization of immunocompetent cells. This difference seems to influence post-transplant recipient outcomes. publishedVersion

Background The association between pregnancy complications and women's later cardiovascular disease has, primarily, been evaluated in studies lacking information on important covariates. This report evaluates the prospective associations between pregnancy‐related risk factors (preeclampsia/eclampsia, gestational hypertension, pregestational and gestational diabetes mellitus, preterm delivery, and fetal growth restriction) and pharmacologically treated hypertension within 10 years after pregnancy, while adjusting for a wide range of covariates. Methods and Results Prepregnancy normotensive women participating in the MoBa (Norwegian Mother and Child Cohort Study) from January 2004 through July 2009 were linked to the Norwegian Prescription Database to identify women with pharmacologically treated hypertension beyond the postpartum period of 3 months. The burden of hypertension associated with pregnancy‐related risk factors was evaluated using an attributable fraction method. A total of 1480 women developed pharmacologically treated hypertension within the follow‐up among 60 027 women (rate of hypertension, 3.6/1000 person‐years). The proportion of hypertension associated with a history of preeclampsia/eclampsia, gestational hypertension, preterm delivery, and pregestational or gestational diabetes mellitus was 28.6% (95% confidence interval, 25.5%–31.6%) on the basis of multivariable analyses adjusting for numerous covariates. The proportion was similar for women with a healthy prepregnancy body mass index (18.5‐24.9 kg/m 2 ; attributable fraction (AF)% 25.9%; 95% confidence interval, 21.3%‐30.3%), but considerably higher for nulliparous women at baseline within the first 5 years of follow‐up. Small‐for‐gestational age, however, did not increase subsequent hypertension risk in multivariable analyses. Conclusions A structured postpartum follow‐up of high‐risk women identified through pregnancy‐related risk factors would facilitate personalized preventive strategies to postpone or avoid onset of premature cardiovascular events.

Introduction There are few data available on the optimal number of lung cancer patients needed to generate and compare estimates of quality between units managing lung cancer. The number of lung cancer patients per management unit varies considerably in Norway, where there are 42 hospitals that treated between 1 and 454 lung cancer patients in 2011. Aims To estimate the differences in quality indicators that are of sufficient importance to change a pulmonary physician's lung cancer management program, and to estimate the size of the patient samples necessary to detect such differences. Method Twenty-six physicians were asked about the relative differences from a national average of quality indicators that would change their own lung cancer management program. Sample sizes were calculated to give valid estimates of quality of a management unit based on prevalence of quality indicators and minimally important differences (MID). Results The average MID in quality indicators that would cause a change in management varied from 18% to 24% among 26 chest physicians, depending on the indicator. Conclusions To generate precise estimates for quality control of lung cancer care in Norway, the number of management units must be reduced. Given the present willingness of chest physicians to change their procedures for management of lung cancer according to the results of quality control indicators, we recommend a maximum of 10 units with a minimum of 200 incident lung cancer patients per year for each management center.

OBJECTIVES: Improving patients’ health status is a central goal for cardiac surgery. Knowledge remains sparse on how combined CABG or other factors influence long-term, self-reported health status after aortic valve replacement (AVR). The aims of this study were (i) to identify significant factors influencing self-reported health status of patients assessed up to 13 years after AVR; and (ii) to compare their health with the age- and gender-matched general population. METHODS: A survey questionnaire was sent to 1191 patients who had undergone AVR with or without concomitant CABG between 2000 and 12. Physical and mental sum scores of Short Form 12 were used as dependent variables and 34 independent variables including the Minnesota living with Heart Failure Questionnaire (MLHFQ) were evaluated by hierarchical linear regression. A comparison was made with the Norwegian general population. Clinical data were obtained from the local cardiac surgery database. RESULTS: In all, 912 patients (77%) responded (mean age: 73 years; 63% men). Of these, 59% had an isolated AVR. The mean assessment interval since surgery was 6 years. Several factors significantly predicted worse physical health: low education level (b: −2.8, P= 0.005), higher preoperative EuroSCORE (b: −0.88, P= 0.007), high NYHA class (b: −4.5, P< 0.001), depression (b: −5.62, P= 0.012), worse MLHFQ physical scores (b: −0.70, P< 0.001), arthritis (b: −5.13, P= 0.003), osteoporosis (b: −6.96, P= 0.010) and cancer (b: −4.48, P= 0.047) accounting for 60% of the variation (P< 0.001). Living alone (b: −3.60, P< 0.001), anxiety (b: −12.99, P< 0.001), depression (b: −6.82, P< 0.001) and worse MLHFQ emotional score (b: −0.50, P< 0.001) predicted poor mental health status, and explained 58% of the variation among AVR patients (P< 0.001). Both genders had poorer physical and mental health than their age-matched general population peers, particularly those in older age groups. CONCLUSIONS: AVR patients, regardless of gender, had worse physical and mental health than the general population. Living alone, educational level, physical symptom status, anxiety and depression were the most important predictors of physical and mental health status after AVR. Implementing new screening protocols for psychosocial risk factors and individualized rehabilitation programmes may contribute to improved health in AVR patients.

ObjectivesTo investigate symptoms and self-reported health of patients conservatively treated for aortic stenosis (AS) and to identify factors associated with treatment decision and patient outcomes.DesignA cross-sectional survey with an 18-month follow-up.SettingOne tertiary university hospital in Western Norway.ParticipantsIn all, 1436 patients were diagnosed with AS between 2000 and 2012, and those 245 still under conservative treatment in 2013 were included in this study.Primary and secondary outcome measuresPrimary outcome measures were symptoms and self-reported health status. Secondary outcomes were treatment decision and patient survival after 18 months.ResultsA total of 136 patients with mean (SD) age 79 (12) years, 52% men responded. Among conservatively treated patients 77% were symptomatic. The symptom most frequently experienced was dyspnoea. Symptomatic patients reported worse physical and mental health compared with asymptomatic patients (effect size 1.24 and 0.74, respectively). In addition, symptomatic patients reported significantly higher levels of anxiety and depression compared with asymptomatic patients. However, symptom status did not correlate with haemodynamic severity of AS. After 18 months, 117 (86%) were still alive, 20% had undergone surgical aortic valve replacement (AVR) and 7% transcatheter aortic valve implantation (TAVI). When adjusting for age, gender, symptomatic status, severity of AS and European system for cardiac operative risk evaluation (EuroSCORE), patients with severe AS had more than sixfold chance of being scheduled for AVR or TAVI compared with those with moderate AS (HR 6.3, 95% CI 1.9 to 21.2, p=0.003). Patients with EuroSCORE ≥11 had less chance for undergoing AVR or TAVI compared with those with EuroSCORE ≤5 (HR 0.06, 95% CI 0.01 to 0.46, p=0.007).ConclusionsSymptoms affected both physical and mental health in conservatively treated patients with AS. Many patients with symptomatic severe AS are not scheduled for surgery, despite the recommendations in current guidelines. The referral practice for AVR is a path for further investigation.

OBJECTIVELung cancer (LC) patients who develop brain metastases (BMs) have a poor prognosis. Estimations of survival and risk of treatment-related deterioration in quality of life (QOL) are important when deciding on treatment. Although we know of several prognostic factors for LC patients with BMs, the role of QOL has not been established. Authors of this study set out to evaluate changes in QOL following Gamma Knife surgery (GKS) for BMs in LC patients and QOL as a prognostic factor for survival.METHODSForty-four of 48 consecutive LC patients with BMs underwent GKS in the period from May 2010 to September 2011, and their QOL was prospectively assessed before and 1, 3, 6, 9, and 12 months after GKS by using the Functional Assessment of Cancer Therapy–Brain (FACT-BR) questionnaire. A mixed linear regression model was used to identify potential predictive factors for QOL and to assess the effect of GKS and the disease course on QOL at follow-up.RESULTSMean QOL as measured by the brain cancer subscale (BRCS) of the FACT-BR remained stable from baseline (score 53.0) up to 12 months post-GKS (57.1; p = 0.624). The BRCS score improved for 32 patients (72.3%) with a total BM volume ≤ 5 cm3. Mean improvement in these patients was 0.45 points each month of follow-up, compared to a decline of 0.50 points each month despite GKS treatment in patients with BM volumes > 5 cm3 (p = 0.04). Asymptomatic BMs (p = 0.01), a lower recursive partitioning analysis (RPA) classification (p = 0.04), and a higher Karnofsky Performance Scale (KPS) score (p < 0.01) at baseline were predictors for a high, stable QOL after GKS. After multivariate analysis, a high KPS score (p < 0.01) remained the only positive predictor of a high, stable QOL post-GKS.Median survival post-GKS was 5.6 months (95% CI 1.0–10.3). A higher BRCS score (p = 0.01), higher KPS score (p = 0.01), female sex (p = 0.01), and the absence of liver (p = 0.02), adrenal (p = 0.02), and bone metastases (p = 0.03) predicted longer survival in unadjusted models. However, in multivariate analyses, a higher BRCS score (p < 0.01), female sex (p = 0.01), and the absence of bone metastases (p = 0.02) at GKS remained significant predictors. Finally, the BRCS score’s predictive value for survival was compared with the values for the variables behind well-known prognostic indices: age, KPS score, extracranial disease status, and number and volume of BMs. Both BRCS score (p = 0.01) and BM volume (p = 0.05) remained significant predictors for survival in the final model.CONCLUSIONSPatient-reported QOL according to the BRCS is a predictor of survival in patients with BMs and may be helpful in deciding on the optimal treatment. Gamma Knife surgery is a safe and effective therapeutic modality that improves QOL for LC patients with a BM volume ≤ 5 cm3 at treatment. Careful follow-up and salvage therapy on demand seem to prevent worsening of QOL due to relapse of BMs.

Background and objective An adverse intrauterine environment may affect offspring growth and development. Our aim was to explore whether preeclampsia (PE) exposure in utero influences growth from birth to 13 years. Methods In a nested case-control study, 229 children were exposed to PE (mild/moderate: n = 164, severe: n = 54) and 385 were unexposed. Length/height and weight were abstracted from records at birth, 3 and 6 months, 1 and 4 years, and measured along with waist circumference and skinfolds at follow-up at 11/12 (girls/boys) and 13 years (both sexes). Associations between PE and z-scores for growth were analyzed by multiple linear and fractional polynomial regression with adjustment for potential confounders. Results In boys, exposure to mild/moderate PE was positively associated with linear growth after 0.5 years, but severe PE was negatively associated with linear growth in all ages. In girls, both exposure to mild/moderate and severe PE were negatively associated with linear growth. Exposure to PE was negatively associated with weight and body mass index (BMI) during infancy, but positively associated with weight and BMI thereafter, except that boys exposed to severe PE consistently had a lower weight and BMI compared to the unexposed. Exposure to severe PE only was positively associated with waist-to-height ratio at 11/12 (girls/boys) and 13 years (both sexes). Conclusions From birth to adolescence, linear growth, weight and BMI trajectories differed between the sexes by severity of exposure to PE. In general, PE exposure was negatively associated with linear growth, while in girls; positive associations with weight and BMI were observed. This underlines fetal life as a particularly sensitive period affecting subsequent growth and this may have implications for targeted approaches for healthy growth and development.

Jorunn Drageset,1,2 Geir Egil Eide,3,4 Anne Corbett5 1Department of Nursing, Faculty of Health and Social Sciences, Western Norway University of Applied Sciences, 2Department of Public Health and Primary Health Care, University of Bergen, 3Centre for Clinical Research, Western Norway Health Region Authority, 4Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway; 5Institute of Health Research, Exeter University Medical School, University of Exeter, Exeter,UK Background: Limited information exists regarding the natural development of health-related quality of life (HRQOL) and its determinants among mentally intact nursing home (NH) residents. We aimed to examine HRQOL over time during a 6-year period among residents of NHs, who are not cognitively impaired, and to examine whether sense of coherence and a diagnosis of cancer influence HRQOL. Methods: The study was prospective and included baseline assessment and 6-year follow-up. After baseline assessment of 227 cognitively intact NH residents (Clinical Dementia Rating score ≤ 0.5), we interviewed 52 living respondents a second time at the 5-year follow-up and 18 respondents a third time at the 6-year follow-up. We recorded data from the interviews using the Short Form-36 (SF-36) Health Survey and the Sense of Coherence Scale. To study different developments over time for residents without and with cancer, we tested interactions between cancer and time. Results: The subscores of physical functioning and role limitation–physical domains declined with time (P&nbsp

Background Women carrying BRCA-mutations are facing significant challenges, including decision making regarding surveillance and risk-reducing surgery. They often report that they are left alone with these important decisions. In order to enhance the genetic counselling session we organized a group-based patient education (GPE) course for women with BRCA-mutations. The study aims were to characterize women attending a group-based patient education (GPE) course for hereditary breast and ovarian cancer, consider the usefulness of the course, evaluate symptoms of anxiety and depression among the participants, and finally investigate whether their levels of anxiety and depression changed from before to after the course session. Methods A prospective study was conducted. Two weeks before (T1) and 2 weeks after (T2) attending the GPE-course the participants received questionnaires by mail. We collected information on demographic- and medical variables, anxiety and depression using Hospital Anxiety and Depression Scale (HADS), self-efficacy using The Bergen Genetic Counseling Self-Efficacy scale (BGCSES) and coping style using the Threatening Medical Situations Inventory (TMSI). A total of N = 100 (77% response rate) women participated at baseline and 75 (58% response rate) also completed post-course assessment. Results The mean level of anxiety symptoms was elevated among participants but decreased significantly during follow-up. Lower anxiety symptom levels were associated with “longer time since disclosure of gene test result”, “higher levels of self-efficacy” and having experienced “loss of a close relative due to breast or ovarian cancer”. Lower depression symptom levels were associated with “higher levels of education” and “loss of a close relative due to breast or ovarian cancer”. Conclusion The women in this study seemed to benefit from the GPE course. Women newly diagnosed with a BRCA mutation who reported lower levels of self-efficacy and lower levels of education were more vulnerable. These women need special attention.

Extremely preterm (EP) birth is associated with a series of adverse health outcomes, some of which may be alleviated by improved physical fitness. However, EP-born subjects are reportedly less physically active than term-born peers. Exercise capacity is poorly described in this group, and longitudinal data are needed.To compare exercise capacity of adults born EP and at term, and to address developmental patterns from adolescence to adulthood.An area-based cohort of adults, born in 1982-1985 at gestational age 28 weeks or earlier, or with birth weight of 1,000 g or less, originally examined at 18 years of age, were re-examined at 25 years of age together with individually matched term-born control subjects, using an identical maximal cardiopulmonary treadmill exercise test and validated questionnaires.A total of 34 (76%) eligible preterm and 33 (85%) term control subjects successfully completed the exercise test at age 25 years. In the two groups, average (95% confidence interval) peak oxygen consumption was 40.7 (37.9-43.5) and 44.2 (41.0-47.4) ml ⋅ kg(-1)⋅min(-1), respectively, whereas the distance completed on the treadmill was 910 (827-993) m and 1,020 (927-1,113) m. Peak oxygen consumption was unrelated to neonatal factors and current FEV1, but was positively associated with leisure-time physical activity and negatively associated with age at examination. Values obtained at age 18 and 25 years were strongly correlated and within normal range at both examinations.Exercise capacity was modestly reduced in EP-born adults; however, values were within a normal range, positively associated with self-reported physical activity and unrelated to neonatal factors and current airway obstruction.

Summary The cytokine interferon gamma (IFN-γ) stimulates neopterin release and tryptophan degradation into kynurenines through the kynurenine pathway. High levels of neopterin were associated with increased hip fracture risk, as were some of the kynurenines, suggesting a role of IFN-γ-mediated inflammation in the processes leading to hip fracture. Introduction Low-grade systemic inflammation has been associated with bone loss and risk of fractures. Interferon gamma (IFN-γ) initiates macrophage release of neopterin and also stimulates degradation of tryptophan along the kynurenine pathway as part of cell-mediated immune activation. Plasma neopterin and the kynurenine/tryptophan ratio (KTR) are thus markers of IFN-γ-mediated inflammation. Risk of hip fracture was investigated in relation to markers of inflammation and metabolites in the kynurenine pathway (kynurenines). Methods Participants (71 to74 years, N = 3,311) in the community-based Hordaland Health Study (HUSK) were followed for hip fractures from enrolment (1998–2000) until 31 December 2009. Plasma C-reactive protein (CRP), neopterin, KTR, and six kynurenines were investigated as predictors of hip fracture, using Cox proportional hazards regression analyses. Results A hazard ratio (HR) of 1.9 (95 % confidence interval (CI) 1.3–2.7) for hip fracture was found in the highest compared to the lowest quartile of neopterin (p trend across quartiles

Studies of hospitalisation of cognitively intact nursing home (NH) residents with cancer are scarce. Knowledge about associations between socio-demographic, medical and social support variables and hospital admissions aids in preventing unnecessary admissions. This is part of a prospective study from 2004 to 2005 with follow-up to 2010 for admission rates. We studied whether residents with cancer have more admissions and whether socio-demographic and medical variables and social support subdimensions are associated with admission among cognitively intact NH residents with (n = 60) and without (n = 167) cancer aged ≥65 years scoring ≤0.5 on the Clinical Dementia Rating Scale and residing ≥6 months. We measured social support by face-to-face interview. We identified all respondents through NH medical records for hospital admission, linking their identification numbers to the hospital record system to register all admissions. We examined whether socio-demographic and medical variables (medical records) and social support subscales were associated with the time between inclusion and first admission. Residents with cancer had more admissions (25/60) than those without (53/167) (odds ratio 1.7). Social integration was correlated with admission (P = 0.04) regardless of cancer diagnosis. Residents with cancer had more hospital admissions than those without. Higher social integration gave more admissions independent of cancer diagnosis.

Anthropometry is the general tool for defining overweight and obesity with body mass index (BMI; kg/m2) as the most common variable, using sex and age-adjusted cut-offs for children (Cole et al., 2000). We rely on BMI in identifying overweight, but the accuracy of BMI in predicting overweight and obesity varies with degree of fatness, with a high accuracy in fat children, less so in thin children (Freedman and Sherry, 2009). Annual increases in BMI during childhood have been shown to be attributed to increases in lean mass more than increases in fat mass, but varied according to sex and age (Maynard et al., 2001). Hence, changes in BMI percentile do not necessarily reflect changes in adiposity in children over time, especially not in children with lower BMI values (Demerath et al., 2006). Waist circumference (WC) as well as waist to height ratio (WHtR), have been shown to correlate with amount of abdominal fat, as well as cardiovascular and metabolic risk factors (Bluher et al., 2013; Grober-Gratz et al., 2013). Skinfolds in various combinations have proven to correlate with adverse health risk, as well as being able to predict % body fat better than BMI (Brambilla et al., 2013; Nooyens et al., 2007). During childhood and adolescence, the ratio between the upper and the lower body segment changes considerably, and especially during adolescence growth of the lower segment tends to precede the growth of the upper segment by several months. Sitting height excludes the growth of lower extremities, but little is known about the impact of sitting height on BMI during childhood. In spite of available BMI definitions, a major concern regarding the overweight epidemic among children is the inability of parents, as well as healthcare workers, to recognize that a child is overweight. Several studies have demonstrated that parents in general underestimate their child's weight, and that the age and sex of the child affect their judgments. This is especially evident among the youngest children (He and Evans, 2007; Juliusson et al., 2010b). The same applies to healthcare workers (Isma et al., 2012; Turner et al., 2009). This is serious, as obesity tracking throughout childhood represents a consistent predictor of adult metabolic risk (Janssen et al., 2005). We wonder whether differences in anthropometric measurements related to weight could contribute to this discrepancy between parental perception and weight status, observed particularly in young children. In this work, we have studied a cohort of Norwegian children 4–16 years of age from the Bergen Growth Study with the purpose of analyzing how BMI and other variables of weight status in children associate during different ages. The main research questions were: how does BMI correlate to WC, WHtR, subscapular skinfold (SSF), triceps skinfolds (TSF), and waist to sitting height ratio (WSHtR) during different ages in childhood, and which of these anthropometric variables contribute most to variation in BMI during childhood?

In Norway, there were parallel increases and subsequent decreases in birth weight (BW) and consumption of sugar-sweetened carbonated soft drinks (SSC) during the period 1990–2010, and by an ecological approach, we have suggested that the relationship was causal. The objective of this study was to examine if such a relationship was present in a prospectively followed cohort of pregnant women. The study population included 62,494 term singleton mother–infant dyads in the Norwegian Mother and Child Cohort Study (MoBa), a national prospective cohort study in Norway from 1999 to 2008. The association between SSC consumption and BW was assessed using multiple regression analyses with adjustment for potential confounders. Each 100 ml intake of SSC was associated with a 7.8 g (95% confidence interval [CI]: −10.3 to −5.3) decrease in BW, a decreased risk of BW > 4,500 g (odds ratio [OR]: 0.94, 95% CI: 0.90 to 0.97) and a near significantly increased risk of BW < 2,500 g (OR: 1.05, 95% CI: 0.99 to 1.10). The negative association with SSC consumption was aggravated by smoking, lack of exercise, and obesity. For mothers with gestational diabetes mellitus, we observed an increased risk of BW > 4,500 g (OR: 1.18, 95% CI: 1.00 to 1.39) and a trend towards significant increase in mean BW (25.1 g, 95% CI: −2.0 to 52.2) per 100 ml SSC. Our findings suggest that increasing consumption of rapidly absorbed sugar from SSC had opposite associations with BW in normal pregnancies and pregnancies complicated by gestational diabetes mellitus. publishedVersion

The number of lymph nodes retrieved from the specimen may be a surrogate measure of the adequacy of extensive colon cancer surgery, but many variables may influence the total lymph node yield of any specimen. We examined which variables would be influential both for negative and positive node sampling.The combined results from 428 patients from three hospitals A to C treated in 2007-2009 with single colon cancers having R0 segmental resections were analysed. The surgical technique and pathology staining methods were slightly different between the hospitals.The mean number of lymph nodes was 15.8 (range 1-60). Twelve or more lymph nodes were harvested in 78% of the specimens. In the multivariate Poisson regression analysis of all TNM stages, the factors associated with the total lymph node harvest were age, pathology handling, tumour location and size (p < 0.001), whereas for TNM stage III alone the pathology handling (p < 0.001) and a radical operating technique (p = 0.003) were highly significant. The total number of lymph nodes was the only significant factor for the number of positive lymph nodes (Posln) according to the multivariate negative regression analysis (p = 0.02) but the analysis of the lymph node ratio (LNR) detected no statistically significant variable.Several factors, and especially the specimen processing technique, were important for the total number of harvested lymph nodes. The number of Posln varied between segments and increased with the total number of harvested lymph nodes, but for LNR no variable was important. LNR seemed to abolish the combined effect of tumour location and the total lymph node yield in prognosis assessment.

To examine whether combined magnetic resonance imaging (MRI) findings are related to the degree of disability and low back pain (LBP) in candidates for lumbar disc prosthesis surgery.This cross-sectional study included 170 disc prosthesis candidates (mean age 41 years; 88 women) with chronic non-radicular LBP and localized disc degeneration. Experienced radiologists rated Modic changes and disc findings at L4-S1 on pre-treatment MRIs. An MRI total score (0-10) for findings at L4/L5 plus L5/S1 was calculated for Modic type I and/or II changes, a posterior high intensity zone (HIZ) in the disc, dark/black nucleus pulposus signal, and ≥40 % disc height decrease. We analyzed the relationship of the MRI total score to the Oswestry Disability Index (ODI) (n = 170) and LBP intensity scores (0-100 visual analogue scale, n = 165) using multiple linear regression and adjusting for age, gender, body mass index, smoking, and anxiety/depression.The MRI total score was not related to ODI (regression coefficient 0.12, p = 0.79) or LBP intensity (regression coefficient 0.64, p = 0.37). When individual MRI findings were analyzed, patients with HIZ at L5/S1 had slightly lower ODI scores (4.7 points, p = 0.02). In post hoc analyses, results remained unchanged after adding facet arthropathy to the MRI total score and adjusting also for physical workload and physical leisure-time activity.The combined MRI findings were not related to the degree of disability or the intensity of LBP. These degenerative MRI findings cannot explain variation in pre-treatment disability and pain in patients with chronic LBP accepted for disc prosthesis surgery.

Background Studies are lacking on how anxiety and depression symptoms influence mortality among cognitively intact older people in nursing homes (NHs) with a diagnosis of cancer versus those without cancer. Objective We hypothesized that anxiety or depression was associated with survival and has greater effects on survival for residents with cancer than for those without cancer. Methods A cohort of 227 cognitively intact (Clinical Dementia Rating scale score ≤0.5) older residents (60 with cancer and 167 without) from 30 NHs were followed from 2004-2005 to 2010. Data were collected using face-to-face interviews. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale subscales. Sociodemographic variables and medical diagnoses were obtained from the records. Results The overall survival after 5 years was 17% for residents with cancer and 22% for residents without cancer. Depression and comorbidity were associated with significantly worse survival independent of a cancer diagnosis. Residents with cancer and symptoms of anxiety (subscores at least 8) had worse survival than those without anxiety symptoms (P = .02), but this was not found among the noncancer group. Conclusions Independent of a cancer diagnosis, depression symptoms and comorbidity were associated with mortality among cognitive intact NH residents. Having symptoms of anxiety predicted shorter survival among residents with a cancer diagnosis. Implications for practice Nurses should pay attention to depression symptoms among NH residents with and without a cancer diagnosis. Giving attention to residents with cancer and anxiety symptoms is especially important.

The aim of this study was to examine teratogenic risk perceptions and confidence in the use of medicines in pairs of pregnant women and general practitioners (GPs) through assessments of medicines information texts from patient information leaflets (PILs). A questionnaire was handed out to women attending regular ultrasound examination in week 17–19 of pregnancy. The women stated name and address of their GP and questionnaires were sent to the GPs’ clinic. The questionnaires contained texts regarding pregnancy from PILs for pivmecillinam, metoclopramide, paracetamol, escitalopram, Valeriana officinalis and dexchlorpheniramine. For each PIL, teratogenic risk (scale from 0: never teratogenic to 10: always teratogenic), confidence in use of medicines (yes or no) and clarity of the text (scale from 0: exceptionally clear to 3: exceptionally unclear) were assessed. In total, 171 pregnant women and 74 GPs participated, of which 98 pairs were identified. Pregnant women had significantly higher perceptions of teratogenic risks and lower confidence in use of medicines compared to GPs. Differences in teratogenic risk perceptions and confidence in use were highest for escitalopram and lowest for dexchlorpheniramine, representing texts with different phrasing and length. Neither pregnant women nor GPs were confident in using Valeriana officinalis. Perceptions of teratogenic risks and confidence in use of medicines during pregnancy differ within pairs of pregnant women and their GP when they assess PILs. Phrasing of medicines information texts can influence teratogenic risk perceptions and thereby prescribing of medicines and adherence.

Background: Complete mesocolic excision (CME) and a high (apical) vascular tie may improve oncologic outcome after surgery for colon cancer. Our primary aim was to emulate a previous national result of 73.8% overall survival (OS) with both the open and laparoscopic techniques. Methods: A prospective study of radical colon cancer was initiated in a Norwegian community teaching hospital in 2007 and comprised a consecutive group of 251 patients with TNM stages I-III that had surgery according to the CME principle. Oncological outcome was assessed as OS, disease-free survival (DFS) and cancer-specific survival (CSS), as well as time to recurrence (TTR), using Cox regression analysis. Results: In-hospital mortality was 3.6%, 2.3% for laparoscopic surgery and 4.9% for open management. Significantly more patients in the open CME group developed complications in the short term (p < 0.001). Twelve or more lymph nodes were retrieved from 82.9% (208/251) of the specimens. Overall 3-year OS was 84.5%, DFS 77.4%, CSS 91.5% and TTR 86.8%. The surgical approach was not a significant predictor for any of the survival parameters. Conclusions: There was no survival difference between open and laparoscopic CME colonic resections, and the present OS improved from a previous OS from 2000.

Aim To analyse the effect of lifestyle factors on the prevalence of overweight and obesity in 6–15-year-old Norwegian children. Methods Questionnaire data on lifestyle factors (sedentary behaviour, activity and eating habits) and prevalence numbers of overweight and obesity based on measured height and weight were analysed using multinomial logistic regression in a sample of 2281 children included in the Bergen Growth Study. Results More screen time increased the risk of overweight (odds ratio (OR): 1.25; p = 0.02) and obesity (OR: 1.12; p = 0.02) as did the presence of a TV in the child's bedroom (OR: 1.26 (overweight), OR: 1.81 (obese); p = 0.04). The obese children reported less sugar intake than the not overweight children (OR: 0.58; p = 0.01). Higher parental education was associated with less screen time (p = 0.02), lower frequency of TV in the child's bedroom (p = 0.001), more sports (p = 0.005), as well as eating more fruit and vegetables, less sweets, soft drinks and fast food, and more regular meals (for all, p

Background and Purpose Positive family history (FH+) of cardiovascular disease (CVD) is a risk factor for own CVD. We aimed to analyze the effect of different types of FH (stroke, coronary heart disease (CHD), peripheral artery disease (PAD) on carotid intima-media thickness (cIMT) in young and middle-aged ischemic stroke patients. Methods First-degree FH of CVD was assessed in ischemic stroke patients ≤ 60y using a standardized interview. Carotid ultrasound was performed and far wall cIMT in three carotid artery segments was registered, representing the common carotid (CCA-IMT), carotid bifurcation (BIF-IMT) and the internal carotid artery (ICA-IMT). Measurements were compared between FH+ and FH negative groups and stepwise backward regression analyses were performed to identify factors associated with increased cIMT. Results During the study period 382 patients were enrolled, of which 262 (68%) were males and 233 (61%) reported FH of CVD. Regression analyses adjusting for risk factors revealed age as the most important predictor of cIMT in all segments. The association between FH+ and cIMT was modified by age (p = 0.014) and was significant only regarding ICA-IMT. FH+ was associated with increased ICA-IMT in patients aged < 45y (p = 0.001), but not in patients ≥ 45y (p = 0.083). The association with ICA-IMT was present for a FH of stroke (p = 0.034), but not a FH+ of CHD or PAD. Conclusions FH of stroke is associated with higher ICA-IMT in young ischemic stroke patients. Subtyping of cardiovascular FH is important to investigate heredity in young ischemic stroke patients. Trial Registration ClinicalTrials.gov NCT01597453