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Background: This article summarizes the knowledge about the effect of the sibling intervention SIBS for children with chronic health conditions. The intervention is based on family systemic theory with elements from resilience theory, family communication, understanding of illness and health knowledge as well as cognitive behavioral therapy. The intervention is a manual-based group intervention where siblings and a parent participate over five sessions. Three of the five sessions are separate child and parent groups. The overarching goal is to strengthen the quality of communication between parents and children in order to reduce the risk of developing psychological problems in siblings. The intervention is offered by the Frambu competence center for rare diagnoses, which provides training. It is owned by Frambu and the University of Oslo. Methods: This systematic review is based on a systematic literature search in the databases Embase, Medline and Psykinfo, NORART, Cochrane, Cristin, NORA, SCOPUS and SweMed. International scientific databases have also been searched for evidence as well as information about the intervention obtained from the owner. Literature searches and other obtained information were reviewed to identify Nordic impact studies, international review studies and possibly other Norwegian studies about the intervention. Results:One Nordic effect study of the intervention SIBS was identified and included. The effect study, which had a pre-posttest design without a control group, was conducted in Norway and included sibling-parent dyads. The intervention is well described in manuals, and the measure has a good theoretical justification. Overall, the effect study has been evaluated as having good research methodological quality, but somewhat weaker internal and external validity due to the lack of a control group, high dropout rates and characteristics of the families. The effect sizes in the study were small to moderate. Overall, the intervention has a good implementation strategy, but lacks specification of how compliance with the core components of the intervention is ensured and how the municipal service can record benefits and maintenance of effects in participants. Conclusion: There is one Nordic study that has evaluated the effect of the intervention. The study has relatively good research methodological quality, and effect sizes calculated to be small to moderate. The main finding was an improvement in the quality of parent-sibling communication over time. Secondary findings were improvement in the sibling's mental health symptoms and adaptation to the disability, as well as increased knowledge about the disability. It is therefore considered that there is an indication that theintervention is effective, but more effect studies that include a control group are necessary to establish that the intervenytion is effective for many in the target group. SIBS is classified at evidence level 3 – as an intervention with some documentation of effect., Bakgrunn: Denne artikkelen oppsummerer kunnskapen om effekten av søskenintervensjonen SIBS til barn med kroniske helsetilstander. Intervensjonen baserer seg på familiesystemisk teori med elementer fra resiliensteori, familiekommunikasjon, forståelse av sykdom og helsekunnskap samt kognitiv atferdsterapi. Intervensjonen er et manualbasert gruppetiltak der søsken og en forelder deltar over fem økter. Tre av de fem øktene er separate barne- og foreldregrupper. Det overordnede målet er å styrke kvaliteten på kommunikasjonen mellom foreldre og barn for slik å redusere risiko for utvikling av psykiske plager hos søsken som pårørende. Tiltaket tilbys av Frambu kompetansesenter for sjeldne diagnoser som gir opplæring i tiltaket og utdanner gruppeledere. Det eies av Frambu og Universitetet i Oslo. Metode: Denne kunnskapsoppsummeringen bygger på et systematisk litteratursøk i databasene Embase, Medline og Psykinfo, NORART, Cochrane, Cristin, NORA, SCOPUS og SweMed. Det er også søkt i internasjonale kunnskapsdatabaser om evidens samt innhentet informasjon om tiltaket fra tiltakseier. Litteratursøk og annen innhentet informasjon ble gjennomgått for å identifisere nordiske effektstudier, internasjonale oppsummeringsstudier og eventuelt andre norske studier om tiltaket. Resultater:En nordisk effektstudie av tiltaket SIBS ble identifisert og inkludert. Effektstudien som hadde et pre-posttest design uten kontrollgruppe, var gjennomført i Norge og inkluderte søsken-foreldre dyader. Tiltaket er godt beskrevet i manualer, og tiltaket har en god teoretisk begrunnelse. Effektstudien er samlet sett evaluert til å ha god forskningsmetodisk kvalitet, men noe svakere indre og ytre validitet grunnet mangel på kontrollgruppe, høyt frafall og kjennetegn ved familiene. Effektstørrelsene i studien var små til moderate. Tiltaket har samlet sett god implementeringsstrategi, men mangler spesifisering av hvordan etterlevelse av kjernekomponentene i tiltaket sikres og hvordan førstelinjen kan registrerer utbytte og vedlikehold av effekter hos deltakere. Konklusjon: Det foreligger en nordisk studie som har evaluert effekten av tiltaket. Studien har relativt god forskningsmetodisk kvalitet, og effektstørrelser beregnet til små og moderat. Hovedfunnet var bedring i kvaliteten på foreldre-søsken kommunikasjon over tid. Sekundære funn var bedring i søskens psykiske helsesymptomer og tilpasning til funksjonsnedsettelsen, samt økt kunnskap om funksjonsnedsettelsen. Det vurderes derfor at det er indikasjon på at tiltaket er virksomt, men flere effektstudier som inkluderer kontrollgruppe er nødvendig for å slå fast at tiltaket er virksomt for mange i målgruppen. SIBS klassifiseres på evidensnivå 3 – som et tiltak med noe dokumentasjon på effekt.

Background - This study investigates the use of health and dental care services in adults with intellectual disability in the last 12 months according to Norwegian recommendations and in relation to age and intellectual disability levels. Method - A cross-sectional community-based survey including 214 participants (56% men). POMONA health indicators were used for data collection. Results - Health checks and contact with general practitioners in the last year increased with age but were less frequent in those with more severe intellectual disability. Hospital admissions were age independent. Less than one-fifth of women had undergone cancer screening, with small variations according to intellectual disability severity levels. Few had an individual plan. More than one-third experienced poor dental health despite frequent controls. Conclusions - The use of health checks was lower than recommended, especially in individuals with more severe intellectual disability. Service access and individual plan use need to be enhanced, and dental care services should be improved.

This study examined the psychometric properties of the Norwegian version of the Developmental Behavior Checklist – Parent (DBC-P) in an intellectual and developmental disabilities (IDD) sample of children and adolescents (N = 168). Internal consistency was adequate to excellent for all scales (Cronbach’s alpha ranged between .70–.96). The DBC-P showed meaningful overlap with and differentiation from the Aberrant Behavior Checklist, clinical diagnoses, the Vineland Adaptive Behavior Scales, and the Full Scale IQ. The Norwegian scale scores for a mild IDD level were comparable with the American norms. Further research including severe IDD levels is needed on the Norwegian DBC-P. In summary, the study shows that the Norwegian DBC-P has both adequate reliability and validity.

Background: The Strengths and Difficulties Questionnaire (SDQ) is a frequently used behavioral screening instrument. However, its psychometric properties have been rarely examined among children with intellectual and developmental disabilities (IDD). Aims: The main aims of this study were to examine the internal consistency (i.e., McDonald’s Omega), the convergent validity (by correlating the Total difficulties score with the Aberrant Behavior Checklist [ABC]), the divergent validity (by correlating the Total difficulties score with the Vineland Adaptive Behavior Composite; VABS-II Total) and the factorial validity (by the means of confirmatory factor analyses [CFA]) of the SDQ self-report-, parent-, and teacher version in a sample of children with IDD. Method: Participants were 365 children and adolescents (males n = 238; 65 %) aged 4–18 years (M = 10.11, SD = 3.82) referred for a developmental/neurological assessment to the neuropediatric outpatient clinics in the specialist health services. The SDQ was filled inn by 115 children, 337 parents, and 248 teachers. Results: McDonald’s Omega was overall lowest for the self-report version. Correlations of the SDQ Total difficulties score and the ABC subscales were strongest for the parent version. The results of the CFA indicated best model fit for the six-factor model that included a method factor for all three versions of the SDQ, however, model fit was overall not good. Conclusions: Further research that examines the psychometric properties of the SDQ among multiple informants in large samples of children with IDD is needed.

Introduction: Cognitive impairment is one of the main disabilities in dementia. Physical activity (PA) has been suggested as protective for dementia. However, the findings are disparate in studies, and the question of whether this is because of reverse causality is still open. We aimed to explore the association of PA with cognition in people who later developed dementia compared to those who did not. Method: Since 2001, 11,512 (55% women) participants over the age of 50 years had taken at least one cognitive test in the Tromsø Study. Of these, 1,123 (58% women) later developed dementia. The cases were extracted from hospital journals and entered into an endpoint registry. Leisure time PA (LTPA) was self-reported. Multilevel mixed-effects linear regression was used to address whether LTPA was associated with cognition, stratified by those later developing dementia, and dementia-free in a separate analysis. Results: Leisure time PA was associated with scores in cognitive tests that were 55% (z-score 0.14) higher in those who did not develop dementia. For those in a preclinical phase of dementia, there was no association with LTPA on global cognitive scores. However, in a multifactorial test on processing speed and memory, women had a positive association with processing speed and memory. Conclusion: Leisure time PA had a positive association with global cognition function only for those who did not develop dementia. In women who were developing dementia, LTPA had a positive association with processing speed and memory, while in men, there were no such associations.

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Background: In addition to symptoms of neurodevelopmental disorders, functional impairment is crucial to the determination of clinical significance. The aim of this study was to examine partial validity and usefulness of the Strengths and Difficulties Questionnaire’s (SDQ) impact supplement (SDQ impact) in measuring functional impairment in children and adolescents diagnosed with attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) in neuropediatric clinics. Methods: Participants were children and adolescents (N = 337) referred to neuropediatric outpatient clinics for neurodevelopmental assessment. Functional impairment was evaluated using three instruments: the SDQ impact, the Vineland Adaptive Behavior Scale (VABSII), and the Children’s Global Assessment Scale (CGAS). Mental health symptoms and intellectual function were also assessed. We investigated convergent and concurrent validity of the SDQ impact. Results: The convergent validity of the SDQ impact was shown by its significant correlations with the VABS-II composite score and the CGAS total score. The concurrent validity of the SDQ impact was demonstrated by its significant relationship with ADHD and ASD diagnoses in logistic regression analyses. Using established cutoffs, the sensitivity of the SDQ impact to reveal functional impairment in children with ADHD and ASD diagnoses was demonstrated in this neuropediatric sample, but at the cost of low specificity. Conclusion: The SDQ impact is an easy-to-use tool, and the overall study results indicate that it is partially valid, suggesting it may be used for the screening of general functional impairment in the neuropediatric population.

About 80% of colorectal cancers (CRCs) have chromosomal instability, which is an integral part of aggressive malignancy development, but the importance of specific copy number aberrations (CNAs) in modulating gene expression, particularly within the framework of clinically relevant molecular subtypes, remains mostly elusive. We performed DNA copy number profiling of 257 stage I-IV primary CRCs and integrative gene expression analysis in 151 microsatellite stable (MSS) tumors, focusing on high-level amplifications and the effect of CNAs on the characteristics of the gene expression-based consensus molecular subtypes (CMS). The results were validated in 323 MSS tumors from TCGA. Novel recurrent high-level amplifications (≥15 additional copies) with a major impact on gene expression were found for TOX3 (16q) at 1.5% frequency, as well as for CCND2 (12p) and ANXA11 (10q) at 1% frequency, in addition to the well-known targets ERBB2 (17q) and MYC (8q). Focal amplifications with ≥15 or ≥5 additional copies of at least one of these regions were associated with a poor overall survival among patients with stage I-III MSS CRCs (multivariable hazard ratio ≥3.2, p ≤ 0.01). All high-level amplifications were focal and had a more consistent relationship with gene expression than lower amplitude and/or broad-range amplifications, suggesting specific targeting during carcinogenesis. Genome-wide, copy number driven gene expression was enriched for pathways characteristic of the CMS2-epithelial/canonical subtype, including DNA repair and cell cycle progression. Furthermore, 50% of upregulated genes in CMS2-epithelial/canonical MSS CRCs were driven by CNAs, an enrichment compared with the other CMS groups, and associated with the stronger correspondence between CNAs and gene expression in malignant epithelial cells than in the cells of the tumor microenvironment (fibroblasts, endothelial cells, leukocytes). In conclusion, we identify novel recurrent amplifications with impact on gene expression in CRC and provide the first evidence that CMS2 may have a stronger copy-number related genetic basis than subtypes more heavily influenced by gene expression signals from the tumor microenvironment. publishedVersion

BackgroundIn addition to patient evaluations, caregiver evaluations and experiences are important indicators of the quality of health services. The aim of this study was to examine determinants of caregiver satisfaction with and perceived benefit of child neurodevelopmental assessment in neuropaediatric clinics.MethodsThe study was conducted among caregivers of children and adolescents aged 4–18 years (N = 330) referred for neurodevelopmental assessment in two neuropaediatric clinics in the specialised health service in Northern Norway. The Generic Short Patient Experiences Questionnaire (GS-PEQ) for child psychiatric outpatient patients was distributed to caregivers immediately following the assessment, and two of its items were used as measurements of caregiver satisfaction with and perceived benefit of the assessment.ResultsCaregiver satisfaction with the assessment was correlated with a better general level of function in the child, higher socioeconomic status, Norwegian mother tongue, referral from a specialist, and the respondent being a woman. Higher perceived benefit of the assessment was correlated with higher socioeconomic status, Norwegian mother tongue, and younger age of the child. Regression analysis revealed that caregivers’ perception that the assessment was suited to their child’s situation and that there was good cooperation with other public services (e.g., primary care and social/educational services) seemed more fundamental to caregiver satisfaction with neuropaediatric clinics’ services than any background variable. Younger age of the child, in addition to caregivers’ perception that the assessment was suited to their child and receiving sufficient information about the child’s diagnosis/afflictions, were essential to the perceived benefit of the assessment.ConclusionsCaregiver satisfaction with child neurodevelopmental assessment in neuropaediatric clinics partly depends on variables not related to the assessment experience per se. An assessment that was suited to the child, good cooperation with other public services such as primary health care and social/educational services, and giving sufficient information about the child’s diagnosis are essential to an overall positive caregiver evaluation of neurodevelopmental assessments.

Background - This study investigated the completion rates, scores and factors associated with non-completion and low scores on physical capability tests in a health survey administered to adults with intellectual disabilities. Method - Assessment comprised body mass index (BMI), the Short Physical Performance Battery (SPPB), the timed up-and-go (TUG) test, the one-legged stance (OLS) test; and gross motor, communication and behavioural functioning tests. Results - The completion rates among 93 participants (aged 17–78) were 46% for the SPPB, 42% for the TUG, and 31% for the OLS. More severe intellectual disability (OR = 3.12, p Conclusions - Including physical capability tests in health surveys among adults with intellectual disabilities is important to monitor functional status and guide prevention strategies.

Background and Objectives : The aim of the study was to evaluate the incidence of peritoneal carcinomatosis (PC) in a prospectively recorded series of colon cancer patients from a defined cohort and to compare clinicopathological characteristics, survival, and TP53 mutation status in primary tumors from patients with and without PC. Methods : Clinical data from all colon cancer patients admitted in 1993–2006 were registered prospectively (n = 1,124). In a subset of PC patients, DNA was retrieved from tumor tissue and TP53 mutations analyzed and compared to the mutation status in a historical series. Results : In the prospective series 10% of female and 7% of male patients had PC (P = 0.05). The PC patients were younger than those without PC (median 4 years, P = 0.002). The incidence of PC was 10.3% and 6.2% (P = 0.03) in patients with primary tumors in the right and left colon, respectively. TP53 was mutated in 57% of the PC patients as compared to 41% in the series of patients without PC (P = 0.05). Conclusions : The incidence of PC was higher in right-sided colon cancer and among women. PC patients were younger than non-PC patients, and PC was independently associated with TP53 mutation in the primary tumor. J. Surg. Oncol. © 2011 Wiley Periodicals, Inc.

Introduction Colorectal cancer (CRC) is a molecularly diverse disease with few targeted treatment options. Focal and high-amplitude DNA copy number aberrations are potential tumour drivers, and their identification may contribute to improved therapeutic outcomes in small patient subgroups, as recently illustrated by targeting the over-expression of HER2 protein resulting from high-level ERBB2 amplification in KRAS wild-type metastatic CRC. However, few recurrent amplifications have been detected in CRC. Material and methods We analysed focal high-level amplifications in 203 microsatellite stable (MSS) primary colorectal tumours using genome-wide high-resolution Affymetrix SNP6.0 arrays. The ASCAT algorithm was used to derive discrete allele specific copy number estimates. Results and discussions The overall copy number profiles confirmed the frequent gains and losses previously described in MSS CRC studies. Extreme focal amplifications (defined as >15 copies and ERBB2 , which was amplified to 97, 27 and 22 additional copies in tumours from three individual patients (amplification frequency 1.5%). The transcription factor TOX3 (16q) was also recurrently amplified in 1.5% of the patients, while MYC (8q), CCND2 (12 p) and a region on 10q22.3-q23.1, where ANXA11 was nominated as a likely target by GISTIC analysis, were recurrent in 1% of the patients. Regions with extreme and focal amplifications were also investigated for lower-amplitude aberrations (5–15 additional DNA copies), revealing a 3% amplification frequency of TOX3 in our cohort. Conclusion We have identified several recurrent amplifications in cancer-critical genes in CRC MSS tumours, including the transcription factor TOX3 , suggesting novel drug targets for preclinical studies.

Background: Cardiovascular disease (CVD) is a common comorbidity in Chronic Obstructive Pulmonary Disease (COPD). Cardiac troponin elevation, indicating myocardial injury, is frequent during acute COPD exacerbations and associated with increased mortality. The prognostic value of circulating cardiac troponin T among COPD patients in the stable state of the disease is still unknown. Aims and objectives: To assess the association between circulating cardiac troponin T measured by a high sensitive assay (hs-cTnT) and all-cause mortality among patients with stable COPD. Methods: In a prospective cohort study we included 275 patients with stable COPD without prior diagnosis of CVD from the Akershus University Hospital9s outpatient clinic and from Glittreklinikken, a pulmonary rehabilitation clinic, and recorded time to all-cause death. Results: After a mean follow-up time of 2.8 years, 47 patients (17.1%) died. 180 patients (65%) had measurable hs-cTnT and 66 patients (24 %) had hs-cTnT above the normal range (≥14.0 ng/L). hs-cTnT concentrations in the ranges Conclusions: hs-cTnT elevation is frequently present and associated with increased mortality in stable COPD, independent of COPD-severity.

Purpose In patients with a high life expectancy at the time of surgery for colorectal cancer (CRC), the long-term outcome may be influenced by factors other than their cancer. We aimed to investigate the long-term outcome and cause of death beyond a 5-year surveillance programme. Methods We evaluated the overall survival (OS) and cancer-specific survival (CSS) of a population-based cohort of stage I–III CRC patients Results In total, 161 patients P P n = 119), 14 (12 %) died of CRC during additional long-term follow-up (7 each for pN0 and pN+), and 6 patients (5 %; all pN0) died of other cancers. Patients aged Conclusions The long-term survival beyond 5-year survivorship for stage I–III CRC is very good. Nonetheless, cancer-related deaths are encountered in one-third of patients and occur most frequently in patients who are

The article was originally published in PLoS One, under a creative commons attribution license. See DOI: 10.1371/journal.pone.0122391. Abstract Objective We sought to investigate various molecular subtypes defined by genomic instability that may be related to early death and recurrence in colon cancer. Methods We sought to investigate various molecular subtypes defined by instability at microsatellites (MSI), changes in methylation patterns (CpG island methylator phenotype, CIMP) or copy number variation (CNV) in 8 genes. Stage II-III colon cancers (n = 64) were investigated by methylation-specific multiplex ligated probe amplification (MS-MLPA). Correlation of CNV, CIMP and MSI, with mutations in KRAS and BRAFV600E were assessed for overlap in molecular subtypes and early recurrence risk by uni- and multivariate regression. Results The CIMP phenotype occurred in 34% (22/64) and MSI in 27% (16/60) of the tumors, with noted CIMP/MSI overlap. Among the molecular subtypes, a high CNV phenotype had an associated odds ratio (OR) for recurrence of 3.2 (95% CI 1.1-9.3; P = 0.026). Losses of CACNA1G (OR of 2.9, 95% CI 1.4-6.0; P = 0.001), IGF2 (OR of 4.3, 95% CI 1.1-15.8; P = 0.007), CDKN2A (p16) (OR of 2.0, 95% CI 1.1-3.6; P = 0.024), and RUNX3 (OR of 3.4, 95% CI 1.3-8.7; P = 0.002) were associated with early recurrence, while MSI, CIMP, KRAS or BRAF V600E mutations were not. The CNV was significantly higher in deceased patients (CNV in 6 of 8) compared to survivors (CNV in 3 of 8). Only stage and loss of RUNX3 and CDKN2A were significant in the multivariable risk-model for early recurrence. Conclusions A high copy number variation phenotype is a strong predictor of early recurrence and death, and may indicate a dose-dependent relationship between genetic instability and outcome. Loss of tumor suppressors RUNX3 and CDKN2A were related to recurrence-risk and warrants further investigation.

Elevated microsatellite alterations at selected tetranucleotides (EMAST), a variation of microsatellite instability (MSI), has been reported in a variety of malignancies (e.g., neoplasias of the lung, head and neck, colorectal region, skin, urinary tract and reproductive organs). EMAST is more prominent at organ sites with potential external exposure to carcinogens (e.g., head, neck, lung, urinary bladder and colon), although the specific molecular mechanisms leading to EMAST remain elusive. Because it is often associated with advanced stages of malignancy, EMAST may be a consequence of rapid cell proliferation and increased mutagenesis. Moreover, defects in DNA mismatch repair enzyme complexes, TP53 mutation status and peritumoural inflammation involving T cells have been described in EMAST tumours. At various tumour sites, EMAST and high-frequency MSI share no clinicopathological features or molecular mechanisms, suggesting their existence as separate entities. Thus EMAST should be explored, because its presence in human cells may reflect both increased risk and the potential for early detection. In particular, the potential use of EMAST in prognosis and prediction may yield novel types of therapeutic intervention, particularly those involving the immune system. This review will summarise the current information concerning EMAST in cancer to highlight the knowledge gaps that require further research. publishedVersion