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Abstract Aim To evaluate placental pathology in term and post-term births, investigate differences in clinical characteristics, and assess the risk of adverse neonatal outcome. Methods This prospective observational study included 315 singleton births with gestational age (GA) > 36 weeks + 6 days meeting the local criteria for referral to placental histopathologic examination. We applied the Amsterdam criteria to classify the placentas. Births were categorized according to GA; early-term (37 weeks + 0 days to 38 weeks + 6 days), term (39 weeks + 0 days to 40 weeks + 6 days), late-term (41 weeks + 0 days to 41 weeks + 6 days), and post-term births (≥ 42 weeks + 0 days). The groups were compared regarding placental pathology findings and clinical characteristics. Adverse neonatal outcomes were defined as 5-minute Apgar score

Abstract Purpose To study development trajectories to 34 years of age of health-related quality of life (HRQoL) and subjective health complaints in extremely preterm (EP) born subjects with and without disability, and to compare with term-born controls. Methods A Norwegian longitudinal population-based cohort of subjects born in 1982–85 at gestational age ≤ 28 weeks or with birth weight ≤ 1000 g and matched term-born controls completed the Norwegian version of the Short Form Health Survey-36 at ages 24 and 34 and the Health Behaviour in School-aged Children–Symptom Checklist at ages 17, 24 and 34 years. Data were analysed by unadjusted and adjusted mixed effects analyses with time by subject group as interaction term. Results A total of 35/49 (73%) surviving EP-born and 36/46 (78%) term-born controls participated at this third follow-up. EP-born subjects with severe disability reported clinical significant lower mean score in all domains compared to the term-born controls. Healthy EP-born subjects reported significantly lower mean scores for vitality, role emotional and mental health, and significantly higher mean score for total and psychological health complaints compared to term-born controls. There were no significant interactions with age regarding HRQoL and somatic health complaints, while there were significant differences in psychological health complaints; the EP-born scored higher at age 24 and lower at age 34. Conclusions EP-born adults at age 34 reported inferior HRQoL versus term-born peers, especially in the mental health domains, indicating that the negative differences observed at 24 years remained unchanged.

Objective: To investigate changes and predictors of change in physical and mental function over a 3-year period after rehabilitation. Design: Prospective cohort. Participants: Patients, across diseases, living in western Norway, accepted for somatic specialized interprofessional rehabilitation (n = 984). Methods: Physical and mental function were assessed at admittance (baseline), and after 1 and 3 years using the Medical Outcome Study Short Form 36 (SF-36). Associations between changes in SF-36 component summary scores and sense of coherence, pain, disease group (musculoskeletal, neoplasm, cardiovascular, neurological, other), exercise habits and demographic variables were analysed using linear mixed modelling. Results: In the total group, mean (standard deviation) physical component summary scores improved by 2.9 (8.4) and 3.4 (9.3) points at 1 and 3 years, respectively. Mental component summary scores improved by 2.1 (9.7) and 1.6 (10.8) points. Improvement in physical component summary was significantly greater for patients with higher sense of coherence (b = 0.09, p = 0.001) and for the neoplasm disease group (b = 2.13, p = 0.046). Improvement in mental component summary was significantly greater for patients with low sense of coherence (b = –0.13, p = < 0.001) and higher level of education (b = 3.02, p = 0.0302). Interaction with age (physical component summary: b = 0.22, p = 0.039/mental component summary b = 0.51, p = 0.006) indicated larger effect at 1 year than at 3 years. Conclusion: Physical and mental function improved in the total study group over the 3-year period. Sense of coherence at baseline was associated with improved physical and mental function, suggesting that coping resources are important in rehabilitation. LAY ABSTRACT Rehabilitation aims to improve function among people with disabilities. This study investigated how physical and mental function change in a 3-year period after rehabilitation, and the factors related to these changes. In a cohort of 984 rehabilitation patients, physical and mental function were measured before rehabilitation (baseline) and at 1 and 3 years after rehabilitation. Both physical and mental function improved over a period of 3 years, with the greatest improvement from baseline to 1 year. Improved function at 1 year remained relatively stable over time. Participants with higher coping resources at baseline, measured by sense of coherence, had the greatest improvement in physical function, and less improvement in mental function. Participants’ disease group influenced change in physical function. Participants with a higher level of education demonstrated greater improvement in mental function. These results imply that coping resources should be addressed as an important part of rehabilitation.

Objective To 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.Design Regional cohort study.Setting Oppland County, Norway.Methods At 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.Participants We 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 measures SDQ subscale and Total Difficulties Scores.Results The 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.Conclusions The 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.

Abstract 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

Objectives Our primary objective was to study the impact of the Norwegian National Patient Safety Campaign and Program on Surgical Safety Checklist (SSC) implementation and on safety culture. Secondary objective was associations between SSC fidelity and safety culture. We hypothesised that the programme influenced on SSC use and operating theatre personnel’s safety culture perceptions.Setting A longitudinal cross-sectional study was conducted in a large Norwegian tertiary teaching hospital.Participants We invited 1754 operating theatre personnel to participate in the study, of which 920 responded to the surveys at three time points in 2009, 2010 and 2017.Primary and secondary outcome measures Primary outcome was the results of the patient safety culture measured by the culturally adapted Norwegian version of the Hospital Survey on Patient Safety Culture. Our previously published results from 2009/2010 were compared with new data collected in 2017. Secondary outcome was correlation between SSC fidelity and safety culture. Fidelity was electronically recorded.Results Survey response rates were 61% (349/575), 51% (292/569) and 46% (279/610) in 2009, 2010 and 2017, respectively. Eight of the 12 safety culture dimensions significantly improved over time with the largest increase being ‘Hospital managers’ support to patient safety’ from a mean score of 2.82 at baseline in 2009 to 3.15 in 2017 (mean change: 0.33, 95% CI 0.21 to 0.44). Fidelity in use of the SSC averaged 88% (26 741/30 426) in 2017. Perceptions of safety culture dimensions in 2009 and in 2017 correlated significantly though weakly with fidelity (r=0.07–0.21).Conclusion The National Patient Safety Program, fostering engagement from trust boards, hospital managers and frontline operating theatre personnel enabled effective implementation of the SSC. As part of a wider strategic safety initiative, implementation of SSC coincided with an improved safety culture.

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.

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.

Abstract Background An association between body weight in childhood and subsequent lung function and asthma has been suggested, but few longitudinal studies exist. Our aim was to explore whether weight-related anthropometric measurements through childhood were associated with lung function in late childhood. Methods From an original nested case-control study, a cohort study was conducted, where lung function was measured in 463 children aged 12.8 years, and anthropometry was measured at several ages from birth through 12.8 years of age. Associations between anthropometrics and lung function were analysed using multiple linear and fractional polynomial regression analysis. Results Birthweight and body mass index (BMI; kg/m2) at different ages through childhood were positively associated with forced vital capacity in percent of predicted (FVC %) and forced expiratory volume in the first second in percent of predicted (FEV1%) at 12.8 years of age. BMI, waist circumference, waist-to-height ratio and skinfolds at 12.8 years of age and the change in BMI from early to late childhood were positively associated with FVC % and FEV1% and negatively associated with FEV1/FVC and forced expiratory flow at 25–75% of FVC/FVC. Interaction analyses showed that positive associations between anthropometrics other than BMI and lung function were mainly found in girls. Inverse U-shaped associations were found between BMI at the ages of 10.8/11.8 (girls/boys) and 12.8 years (both genders) and FVC % and FEV1% at 12.8 years of age. Conclusions Weight-related anthropometrics through childhood may influence lung function in late childhood. These findings may be physiological or associated with air flow limitation. Inverse U-shaped associations suggest a differential impact on lung function in normal-weight and overweight children. Trial registration This study was observational without any health care intervention for the participants. Therefore, no trial registration number is available.

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.

Abstract Purpose This systematic review aims to explain the heterogeneity in results of interventions to promote physical activity and healthy eating for overweight and obese adults, by exploring the differential effects of behaviour change techniques (BCTs) and other intervention characteristics. Methods The inclusion criteria specified RCTs with ≥ 12 weeks’ duration, from January 2007 to October 2014, for adults (mean age ≥ 40 years, mean BMI ≥ 30). Primary outcomes were measures of healthy diet or physical activity. Two reviewers rated study quality, coded the BCTs, and collected outcome results at short (≤6 months) and long term (≥12 months). Meta-analyses and meta-regressions were used to estimate effect sizes (ES), heterogeneity indices (I2) and regression coefficients. Results We included 48 studies containing a total of 82 outcome reports. The 32 long term reports had an overall ES = 0.24 with 95% confidence interval (CI): 0.15 to 0.33 and I2 = 59.4%. The 50 short term reports had an ES = 0.37 with 95% CI: 0.26 to 0.48, and I2 = 71.3%. The number of BCTs unique to the intervention group, and the BCTs goal setting and self-monitoring of behaviour predicted the effect at short and long term. The total number of BCTs in both intervention arms and using the BCTs goal setting of outcome, feedback on outcome of behaviour, implementing graded tasks, and adding objects to the environment, e.g. using a step counter, significantly predicted the effect at long term. Setting a goal for change; and the presence of reporting bias independently explained 58.8% of inter-study variation at short term. Autonomy supportive and person-centred methods as in Motivational Interviewing, the BCTs goal setting of behaviour, and receiving feedback on the outcome of behaviour, explained all of the between study variations in effects at long term. Conclusion There are similarities, but also differences in effective BCTs promoting change in healthy eating and physical activity and BCTs supporting maintenance of change. The results support the use of goal setting and self-monitoring of behaviour when counselling overweight and obese adults. Several other BCTs as well as the use of a person-centred and autonomy supportive counselling approach seem important in order to maintain behaviour over time. Trial Registration PROSPERO CRD42015020624

Background Early detection of abnormal weight gain in childhood may be important for preventive purposes. It is still debated which annual changes in BMI should warrant attention. Aim To analyse 1-year increments of Body Mass Index (BMI) and standardised BMI (BMI SDS) in childhood and explore conditional change in BMI SDS as an alternative method to evaluate 1-year changes in BMI. Subjects and methods The distributions of 1-year increments of BMI (kg/m2) and BMI SDS are summarised by percentiles. Differences according to sex, age, height, weight, initial BMI and weight status on the BMI and BMI SDS increments were assessed with multiple linear regression. Conditional change in BMI SDS was based on the correlation between annual BMI measurements converted to SDS. Results BMI increments depended significantly on sex, height, weight and initial BMI. Changes in BMI SDS depended significantly only on the initial BMI SDS. The distribution of conditional change in BMI SDS using a two-correlation model was close to normal (mean = 0.11, SD = 1.02, n = 1167), with 3.2% (2.3–4.4%) of the observations below −2 SD and 2.8% (2.0–4.0%) above +2 SD. Conclusion Conditional change in BMI SDS can be used to detect unexpected large changes in BMI SDS. Although this method requires the use of a computer, it may be clinically useful to detect aberrant weight development.

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 (p

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.

Aim: To investigate whether airflow limitation is associated with bone mineral density (BMD) and risk of hip fractures. Methods: A community sample of 5,100 subjects 47–48 and 71–73 years old and living in Bergen was invited. Participants filled in questionnaires and performed a post-bronchodilator spirometry measuring forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). All attendants were invited to have a BMD measurement of the hip. During 10 years of follow-up, information on death was collected from the Norwegian Cause of Death Registry, and incident hip fractures were registered from regional hospital records of discharge diagnoses and surgical procedure codes. Results: The attendance rate was 69% (n=3,506). The prevalence of chronic obstructive pulmonary disease (COPD) (FEV1/FVC

The 2013–2016 outbreak of Ebola virus disease (EVD) in West Africa infected >28,000 people, including >11,000 who died, and disrupted social life in the region. We retrospectively studied clinical signs and symptoms and risk factors for fatal outcome among 31 Ebola virus–positive patients admitted to the Ebola Treatment Center in Moyamba District, Sierra Leone. We found a higher rate of bleeding manifestations than reported elsewhere during the outbreak. Significant predictors for death were shorter time from symptom onset to admission, male sex, high viral load on initial laboratory testing, severe pain, diarrhea, bloody feces, and development of other bleeding manifestations during hospitalization. These risk factors for death could be used to identify patients in need of more intensive medical support. The lack of fever in as many as one third of EVD cases may have implications for temperature-screening practices and case definitions.

Objective: To explore whether information regarding potentially alcohol-related health incidents recorded in electronic patient records might aid in earlier identification of alcohol use disorders. Design: We extracted potentially alcohol-related information in electronic patient records and tested if alcohol-related diagnoses, prescriptions of codeine, tramadol, ethylmorphine, and benzodiazepines; elevated levels of gamma-glutamyl-transferase (GGT), and mean cell volume (MCV); and new sick leave certificates predicted specific alcohol use disorder. Setting: Nine general practitioner surgeries with varying size and stability. Subjects: Totally 20,764 patients with active electronic patient record until data gathering and with a history of at least four years without a specific alcohol use disorder after turning 18 years of age. Methods: The Cox proportional hazard analysis with time-dependent covariates of potential accumulated risks over the previous four years. Main outcome measures: Time from inclusion until the first specific alcohol use disorder, defined by either an alcohol specific diagnostic code or a text fragment documenting an alcohol problem. Results: In the unadjusted and adjusted Cox-regression with time-dependent covariates all variables were highly significant with adjusted hazard ratios ranging from 1.25 to 3.50. Addictive drugs, sick leaves, GGT, MCV and International Classification for Primary Care version 2 (ICPC-2), and International Classification of Diseases version 10 (ICD-10) diagnoses were analyzed. Elevated GGT and MCV, ICD-10-diagnoses, and gender demonstrated the highest hazard ratios. Conclusions: Many frequent health problems are potential predictors of an increased risk or vulnerability for alcohol use disorders. However, due to the modest hazard ratios, we were unable to establish a clinically useful tool.KEY POINTS Alcohol is potentially relevant for many health problems, but current strategies for identification and intervention in primary health care have not been successful. Many frequent clinical problems recorded in electronic patient records may indicate an increased risk for alcohol related health problems. The hazard ratios were modest and the resulting predictive model was unsatisfactory for diagnostic purposes. If we accepted a sensitivity as low as 0.50, the specificity slightly exceeded 0.75. With a low prevalent condition, it is obvious that the false positive problem will be vast. In addition to responding to elevated blood levels of liver enzymes, general practitioners should be aware of alcohol as a potentially relevant factor for patients with repeated events of many mental and psychosocial diagnoses and new sick leaves and repeated prescriptions of addictive drugs.

BackgroundAllogeneic 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 methodsWe 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.ResultsThe 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.ConclusionHealthy donors differ in their G-CSF responsiveness and preferential mobilization of immunocompetent cells. This difference seems to influence post-transplant recipient outcomes.

BackgroundThe 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 ResultsPrepregnancy 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/m2; 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. ConclusionsA 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.

The purpose of this study was to investigate disability among patients who were accepted for admission to a Norwegian rehabilitation center and to identify predictors of disability.In a cross-sectional study including 967 adult participants, the World Health Organization Disability Assessment Schedule version 2.0 36-item version was used for assessing overall and domain-specific disability as outcome variables. Patients completed the Hospital Anxiety and Depression Scale (HADS), EuroQoL EQ-5D-5L and questions about multi-morbidity, smoking and perceived physical fitness. Additionally, the main health condition, sociodemographic and environmental variables obtained from referrals and public registers were used as predictor variables. Descriptive statistics and linear regression analyses were performed.The mean (standard error) overall disability score was 30.0 (0.5), domain scores ranged from 11.9 to 44.7. Neurological diseases, multi-morbidity, low education, impaired physical fitness, pain, and higher HADS depressive score increased the overall disability score. A low HADS depressive score predicted a lower disability score in all domains.A moderate overall disability score was found among patients accepted for admission to a rehabilitation center but "life activities" and "participation in society" had the highest domain scores. This should be taken into account when rehabilitation strategies are developed.

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.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.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).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.

Background: Symptoms of depression are often reported among patients with a cancer diagnosis. Strong sense of coherence (SOC) is shown to be associated with less depression in the general older population and among nursing homes (NH) residents in particular. Knowledge about mixed-methods perspectives that examine symptoms of depression and SOC among cognitively intact NH residents with cancer is scarce. Aim: To investigate symptoms of depression and SOC among NH residents who are cognitively intact and have cancer. Methods: We used a quantitatively driven mixed-methods design with sequential supplementary qualitative components. We facilitated the collection of quantitative survey data of 60 NH residents (≥ 65 years) with cancer using the Geriatric Depression Scale (GDS) and SOC scale. The supplementary psychosocial component comprised qualitative research interviews about experiences related to depression with nine respondents from the same cohort. Results: In fully adjusted multiple regression analysis of the sociodemographic variables, the GDS was significantly correlated with SOC (P < 0.001). The experience of sadness was identified by the following theme: sadness. Coping with the experience of symptoms of depression was dominated by coping with sadness. Conclusion: More than half the NH residents reported symptoms of depression, and the SOC was associated with reduced symptoms. A mixed-methods design contributed to nuanced and detailed information about the meaning of depression, and the supplementary component informs and supports the core component. To improve the situation of NH residents with cancer, more attention should be paid to the residents’ experience of symptoms of depression and their SOC.

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.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.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.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.ClinicalTrials.gov NCT01597453.

Background. Knowledge of long-term health related outcomes in contemporary populations born extremely preterm (EP) is scarce. We aimed to explore developmental trajectories of health-related quality of life (HRQoL) and behavior from mid-childhood to early adulthood in extremely preterm and term-born individuals.Methods. Subjects born at gestational age ≤28 weeks or with birth weight ≤1,000 g within a region of Norway in 1991–92 and matched term-born control subjects were assessed at 10 and 18 years. HRQoL was measured with the Child Health Questionnaire (CHQ) and behavior with the Child Behavior Checklist (CBCL), using parent assessment at both ages and self-assessment at 18 years.Results. All eligible EP (n = 35) and control children participated at 10 years, and 31 (89%) and 29 (83%) at 18 years. At 10 years, the EP born boys were given significantly poorer scores by their parents than term-born controls on most CHQ and CBCL scales, but the differences were minor at 18 years; i.e., significant improvements had occurred in several CHQ (self-esteem, general health and parental impact-time) and CBCL (total problem, internalizing and anxious/depressed) scales. For the girls, the differences were smaller at 10 years and remained unchanged by 18 years. Emotional/behavioral difficulties at 10 years similarly predicted poorer improvement on CHQ-scales for both EP and term-born subjects at 18 years. Self-assessment of HRQoL and behavior at 18 years was similar in the EP and term-born groups on most scales.Conclusions. HRQoL and behavior improved towards adulthood for EP born boys, while the girls remained relatively similar, and early emotional and behavioral difficulties predicted poorer development in HRQoL through adolescence. These data indicate that gender and a longitudinal perspective should be considered when addressing health and wellbeing after extremely preterm birth.

RAS and BRAF mutations impact treatment and prognosis of metastatic colorectal cancer patients (mCRC), but the knowledge is based on trial patients usually not representative for the general cancer population. Patient characteristics, treatment and efficacy according to KRAS, BRAF and MSI status were analyzed in a prospectively collected unselected population-based cohort of 798 non-resectable mCRC patients. The cohort contained many patients with poor performance status (39% PS 2-4) and elderly (37% age>75), groups usually not included in clinical trials. Patients without available tissue micro array (TMA) (42%) had worse prognostic factors and inferior survival (all patients; 7m vs 11m, chemotherapy-treated;12m vs 17m). The 92 patients (21%) with BRAF mutation had a poor prognosis regardless of microsatellite instability, but receipt of 1-2nd chemotherapy was similar to wildtype BRAF patients. Median survival in this cohort varied from 1 month in BRAF mutated patients not given chemotherapy to 26 months in wildtype KRAS/BRAF patients

Purpose. To investigate the predictive role of relevant social and psychosocial determinants on emotional distress among patients after cardiac rehabilitation. Methods. A longitudinal prospective study examined short-term (6 months) and long-term (2 years) impact of predictors on anxiety and depression complaints in 183 patients with 6-months follow-up data attending a four-week rehabilitation stay at the Krokeide Centre in Bergen, Norway. The patients mainly suffered from coronary heart disease. Emotional distress, coping, social support, socioeconomic status, and negative expectations were measured by means of internationally validated questionnaires. A composite score of anxiety and depression complaints was used as the outcome measure in the study. Results. This study revealed that task-oriented coping improved emotional status in long-term followup, and negative expectations were associated with emotional distress in short-term followup. A higher socioeconomic status and more social support predicted improved emotional status in short- as well as long-term followup. Conclusions. Fewer negative expectations and functional coping along with social support are important factors for the prevention of emotional distress after cardiac disease. Such elements should be addressed and encouraged in patients during cardiac rehabilitation.

INTRODUCTION: We aimed to examine the longitudinal association between Myasthenia Gravis (MG) clinical severity and concentration of acetylcholine receptor (AChR)-antibodies to evaluate if AChR-antibody variations correlate to disease severity. A positive AChR-antibody test is specific for MG. MATERIAL AND METHODS: All patients from western Norway who had two or more AChR- antibody tests in the period 1983-2013 were identified. The Myasthenia Gravis Foundation of America (MGFA) Clinical Classification was used to grade disease development. Multiple ordinal logistic regression analysis was used to estimate a possible predictive effect for AChR-antibody concentration on MGFA classification result. RESULTS: In 67 patients two or more AChR-antibody tests with a corresponding MGFA-score were performed, with a total of 309 tests. 56 patients were treated with immunosuppressive drugs and 11 by pyridostigmine only. There was a positive association between concentration of AChR-antibodies and longitudinal MGFA-score for the subgroup with immunosuppressive treatment, but not for those treated with pyridostigmine only. This association between AChR-antibody concentration and MGFA score declined with increasing time since onset (p = 0.005 for the interaction of group×time×concentration). CONCLUSIONS: For MG patients with immunosuppressive treatment, repeated AChR-antibody measurements give information about clinical development, and can therefore be of support in therapeutic decisions.

Hospital admissions from nursing homes have not previously been investigated in Norway. During 12 months all hospital admissions (acute and elective) from 32 nursing homes in Bergen were recorded via the Norwegian ambulance register. The principal diagnosis made during the stay, length of stay, and the ward were sourced from the hospital's data register and data were merged. Altogether 1,311 hospital admissions were recorded during the 12 months. Admissions from nursing homes made up 6.1% of the total number of admissions to medical wards, while for surgical wards they made up 3.8%. Infections, fractures, cardiovascular and gastri-related diagnoses represented the most frequent admission diagnoses. Infections accounted for 25.0% of admissions, including 51.0% pneumonias. Of all the admissions, fractures were the cause in 10.2%. Of all fractures, hip fractures represented 71.7. The admission rate increased as the proportion of short-term beds increased, and at nursing homes with short-term beds, admissions increased with increasing physician coverage. Potential reductions in hospitalizations for infections from nursing homes may play a role to reduce pressure on medical departments as may fracture prevention. Solely increasing physician coverage in nursing homes will probably not reduce the number of hospitalizations.