Landspítali University Hospital Research Archive

    Lyfjamistök og starfsumhverfi hjúkrunarfræðinga

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    Views of Icelandic women towards genetic counseling - and testing of BRCA2 mutations

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesTILGANGUR Markmið rannsóknarinnar var að kanna viðhorf íslenskra kvenna til erfðaupplýsinga, erfðaráðgjafar og erfðaprófs vegna stökkbreytinga í BRCA-genum sem auka verulega áhættuna á illvígum krabbameinum. EFNIVIÐUR OG AÐFERÐIR Konum sem komu í krabbameinsskoðun á Leitarstöð Krabbameins­félagsins frá 12. október til 20. nóvember 2015 var boðin þátttaka. Þátttaka fólst í svörun á stuttum rafrænum spurningalista um bakgrunn, fjölskyldusögu um krabbamein ásamt þekkingu og áhuga á erfða­ráðgjöf, erfðaprófi vegna BRCA-stökkbreytinga og hvort upplýsa ætti konur sem vitað er, til dæmis vegna vísindarannsókna, að eru arfberar. Notast var við lýsandi tölfræði og kíkvaðratpróf til að skoða viðhorf kvennanna til ofangreindra þátta. NIÐURSTÖÐUR 1129 konur (69% svarhlutfall) svöruðu spurningalistanum. Meðal­aldur var 47 ár (spönn: 21-76 ára) og tæplega helmingur (47%) þekkti til BRCA-stökkbreytinga. Óháð ættarsögu um krabbamein hafði meirihluti kvenna áhuga á að fara í erfðaráðgjöf (79%) og í erfðapróf (83%), sérstaklega yngri konur (ráðgjöf: p<0,0001, erfðapróf: p<0,0001). Hins vegar höfðu einungis 4% kvennanna þegar farið í erfðaráðgjöf og 7% í erfðapróf. Konur með ættarsögu um krabbamein höfðu meiri vitneskju um BRCA-stökkbreytingarnar (p<0,0001) og virtust síður hræðast afleiðingar þess að hafa slíka stökkbreytingu (p<0,0001) samanborið við konur með litla ættarsögu. Óháð ættarsögu hafði helmingur (49%) áhyggjur af því að niðurstöður erfðaprófa hefðu áhrif á sjúkratryggingar. Nær allar konurnar (97%) voru hlynntar eða mjög hlynntar því að erfðaupplýsingar sem liggja fyrir vegna vísinda­rannsókna séu nýttar til að upplýsa arfbera stökkbreytinganna. ÁLYKTUN Viðhorf íslenskra kvenna er jákvætt gagnvart erfðaráðgjöf og erfðaprófs vegna BRCA-stökkbreytinga en um helmingur virðist hafa áhyggjur af skertum rétti til sjúkratrygginga í kjölfar jákvæðrar niðurstöðu. Þrátt fyrir það er skýr vilji fyrir því að upplýsa skuli arfbera um stöðu sína í forvarnarskyni.Introduction The aim of this study was to explore the attitudes of Icelandic women towards existing genetic information, genetic counseling and genetic testing for BRCA mutations which dramatically increase risk for aggressive cancers. Materials and methods Women attending the cancer prevention clinic in Reykjavik, capital of Iceland, from October 12th until November 20th 2015 received an invitation to participate. Participation involved answering a short online questionnaire about background, family history of cancer as well as attitudes towards genetic counseling, BRCA testing and preventive use of such information. Descriptive statistics and chi-square tests were used to describe differences in attitudes towards those questions between subgroups of women. Results 1129 women (69% response rate) answered the questionnaire. Mean age was 47 years (span 21-76 years). Around half (47%) had heard fairly much about the mutations. Independent of family history of cancer, the majority of women were positive towards receiving genetic counseling (79%) and to undergo genetic testing (83%) for BRCA mutation with younger women being more interested than older women. On the other hand, only 4% of the women had already received genetic counseling and 7% undergone genetic testing. Women with family history of cancer were more knowledgeable about BRCA mutations (p<0.0001) and were less afraid of the consequence of being a mutation carrier (p<0.0001) compared to those with little or no family history. Regardless of family history, half (49%) worried that results from genetic testing could influence their health insurance. Almost all, or 97% of the women, were positive or very positive toward using existing genetic information obtained through scientific work, to inform affected indi­viduals of their mutation status. Conclusion Icelandic women are positive towards genetic counseling and testing for BRCA mutations although half of them worry that a positive result might affect their health insurance. Nevertheless, almost all women believe that existing genetic information should be used to inform carriers for preventive purposes

    Incidence of cancer among licenced commercial pilots flying North Atlantic routes.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesTo evaluate cancer incidence among licenced commercial pilots in association with cosmic radiation.Cohort study where ionizing radiation dose of cosmic radiation was estimated from airline data and software program and cancer incidence was obtained by record linkage with nation-wide cancer registry. All licenced commercial male airline pilots were followed from 1955 to 2015, ever or never employed at airline with international routes. Standardized incidence ratios were calculated and relative risk by Poisson regression, to examine exposure-response relation.Eighty three cancers were registered compared with 92 expected; standardized incidence ratios were 0.90 (95% CI 0.71 to 1.11) for all cancers, 3.31 (95% CI 1.33 to 6.81) for malignant melanoma, and 2.49 (95% CI 1.69 to 3.54), for basal cell carcinoma of skin. The risk for all cancers, malignant melanoma, prostate cancer, basal cell carcinoma of skin, and basal cell carcinoma of trunk increased with an increase in number of employment years, cumulative air hours, total cumulative radiation dose, and cumulative radiation dose sustained up to age of 40 years. The relative risk for the highest exposure categories of cumulative radiation dose were 2.42 (95% CI 1.50 to 3.92) for all cancers, 2.57 (95% CI 1.18 to 5.56) for prostate cancer, 9.88 (95% CI 1.57 to 190.78) for malignant melanoma, 3.61 (95% CI 1.64 to 8.48) for all basal cell carcinoma, and 6.65 (95% CI 1.61 to 44.64) for basal cell carcinoma of trunk.This study was underpowered to study brain cancer and leukaemia risk. Basal cell carcinoma of skin is radiation-related cancer, and may be attributed to cosmic radiation. Further studies are needed to clarify the risk of cancers in association with cosmic radiation, other workplace exposure, host factors, and leisure sun-exposure, as clothes, and glass in cockpit windows shield pilots from the most potent ultraviolet-radiation.University of Icelan

    Respiratory symptoms are more common among short sleepers independent of obesity

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesIntroduction Sleep length has been associated with obesity and various adverse health outcomes. The possible association of sleep length and respiratory symptoms has not been previously described. The aim of this study was to investigate the association between sleep length and respiratory symptoms and whether such an association existed independent of obesity. Methods This is a multicentre, cross-sectional, population-based study performed in 23 centres in 10 different countries. Participants (n=5079, 52.3% males) were adults in the third follow-up of the European Community Respiratory Health Survey III. The mean +/- SD age was 54.2 +/- 7.1 (age range 39-67 years). Information was collected on general and respiratory health and sleep characteristics. Results The mean reported nighttime sleep duration was 6.9 +/- 1.0 hours. Short sleepers (= 9 hours per night) were n=271 (4.3%). Short sleepers were significantly more likely to report all respiratory symptoms (wheezing, waking up with chest tightness, shortness of breath, coughing, phlegm and bronchitis) except asthma after adjusting for age, gender, body mass index (BMI), centre, marital status, exercise and smoking. Excluding BMI from the model covariates did not affect the results. Short sleep was related to 11 out of 16 respiratory and nasal symptoms among subjects with BMI >= 30 and 9 out of 16 symptoms among subjects with BMI = 30. Conclusions Our results show that short sleep duration is associated with many common respiratory symptoms, and this relationship is independent of obesity.European Unio

    Critical age windows in the impact of lifetime smoking exposure on respiratory symptoms and disease among ever smokers

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBACKGROUND: Despite extensive knowledge of smoking effects on respiratory disease, there is no study including all age windows of exposure among ever smokers. The objective of this study was to assess the effects from smoking exposure in utero, early childhood, adolescence and adulthood on respiratory health outcomes in adult male and female ever smokers. METHODS: Respiratory health outcomes were assessed in 10,610 participants of the European Community Respiratory Health Survey (ECRHS) I who reported a history of ever smoking by questionnaire. The associations of maternal smoking in utero, maternal smoking during childhood, age of smoking debut and pack-years of smoking with respiratory symptoms, obstructive diseases and bronchial hyperreactivity were analysed using generalized linear regression, non-linearity between age of smoking debut and outcomes were assessed by Generalized additive mixed models. RESULTS: Respiratory symptoms and asthma were more frequent in adults if their mother smoked during pregnancy, and, in men, also if mother smoked in childhood. Wheeze and ≥3 respiratory symptoms declined with later smoking debut among women [≤10 years: OR = 3.51, 95% CI 1.26, 9.73; 11-12 years: 1.57[1.01-2.44]; 13-15 years: 1.11[0.94-1.32] and ≤10 years: 3.74[1.56-8.83]; 11-12 years: 1.76[1.19-2.56]; 13-15 years: 1.12[0.94-1.35], respectively]. Effects of increasing number of packyears were pronounced in women (Chronic Obstructive Pulmonary Disease (COPD): OR/10 packyears women: 1.33 [1.18, 1.50], men: 1.14 [1.04, 1.26] pinteraction = 0.01). CONCLUSIONS: Among ever smokers, smoking exposure in each stage of the lifespan show persistent harmful effects for adult respiratory health, while women appeared to be more vulnerable to an early age of smoking debut and amount of smoking in adulthood

    The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesIn the present study, we aimed to evaluate 2 hypotheses. First, we hypothesize that prior malignancy is a proxy for genetic susceptibility that could be a risk factor for subsequent malignancy development in multiple myeloma (MM) patients. Second, we hypothesize that survival after MM is influenced by a prior malignancy. All patients diagnosed with MM from 1 January 1973 to 31 December 2010 were identified from the Swedish Cancer Register. Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) where prior malignancy was compared in MM patients who developed a subsequent malignancy and MM patients who did not. In another Cox regression model, survival was compared in MM patients with and without a prior malignancy diagnosis. A total of 19 791 patients were diagnosed with MM. Patients with a prior malignancy diagnosis had a significantly increased risk of developing a subsequent malignancy compared with MM patients without (HR 1.42, 95% CI 1.23-1.65, P 1 prior malignancy reduces survival even further.Asrun Einarsdottir Foundation in Iceland Blodcancerfonden Swedish Cancer Society Stockholm County Council Karolinska Institutet Foundation University of Iceland Research Fund Icelandic Centre for Research Landspitali University Hospital Research Fund Marie Curie Career Integration Grant Memorial Sloan Kettering Cancer Center Core Grant by the National Cancer Institute, National Institutes of Healt

    Different incidences of knee arthroplasty in the Nordic countries.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBackground and purpose - The annual number of total knee arthroplasties (TKAs) has increased worldwide in recent years. To make projections regarding future needs for primaries and revisions, additional knowledge is important. We analyzed and compared the incidences among 4 Nordic countries Patients and methods - Using Nordic Arthroplasty Register Association (NARA) data from 4 countries, we analyzed differences between age and sex groups. We included patients over 30 years of age who were operated with TKA or unicompartmental knee arthroplasty (UKA) during the period 1997-2012. The negative binomial regression model was used to analyze changes in general trends and in sex and age groups. Results - The average annual increase in the incidence of TKA was statistically significant in all countries. The incidence of TKA was higher in women than in men in all 4 countries. It was highest in Finland in patients aged 65 years or more. At the end of the study period in 2012, Finland's total incidence was double that of Norway, 1.3 times that of Sweden and 1.4 times that of Denmark. The incidence was lowest in the youngest age groups (< 65 years) in all 4 countries. The proportional increase in incidence was highest in patients who were younger than 65 years. Interpretation - The incidence of knee arthroplasty steadily increased in the 4 countries over the study period. The differences between the countries were considerable, with the highest incidence in Finland. Patients aged 65 years or more contributed to most of the total incidence of knee arthroplasty.NordForsk gran

    Evaluation of shared genetic aetiology between osteoarthritis and bone mineral density identifies SMAD3 as a novel osteoarthritis risk locus.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOsteoarthritis (OA) is a common complex disease with high public health burden and no curative therapy. High bone mineral density (BMD) is associated with an increased risk of developing OA, suggesting a shared underlying biology. Here, we performed the first systematic overlap analysis of OA and BMD on a genome wide scale. We used summary statistics from the GEFOS consortium for lumbar spine (n = 31,800) and femoral neck (n = 32,961) BMD, and from the arcOGEN consortium for three OA phenotypes (hip, ncases=3,498; knee, ncases=3,266; hip and/or knee, ncases=7,410; ncontrols=11,009). Performing LD score regression we found a significant genetic correlation between the combined OA phenotype (hip and/or knee) and lumbar spine BMD (rg=0.18, P = 2.23 × 10-2), which may be driven by the presence of spinal osteophytes. We identified 143 variants with evidence for cross-phenotype association which we took forward for replication in independent large-scale OA datasets, and subsequent meta-analysis with arcOGEN for a total sample size of up to 23,425 cases and 236,814 controls. We found robustly replicating evidence for association with OA at rs12901071 (OR 1.08 95% CI 1.05-1.11, Pmeta=3.12 × 10-10), an intronic variant in the SMAD3 gene, which is known to play a role in bone remodeling and cartilage maintenance. We were able to confirm expression of SMAD3 in intact and degraded cartilage of the knee and hip. Our findings provide the first systematic evaluation of pleiotropy between OA and BMD, highlight genes with biological relevance to both traits, and establish a robust new OA genetic risk locus at SMAD3.Wellcome Trus

    Franski spítalinn á Fáskrúðsfirði.

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    Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn

    Pneumococcal capsular switching: a historical perspective.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Changes in serotype prevalence among pneumococcal populations result from both serotype replacement and serotype (capsular) switching. Temporal changes in serotype distributions are well documented, but the contribution of capsular switching to such changes is unknown. Furthermore, it is unclear to what extent vaccine-induced selective pressures drive capsular switching.Serotype and multilocus sequence typing data for 426 pneumococci dated from 1937 through 2007 were analyzed. Whole-genome sequence data for a subset of isolates were used to investigate capsular switching events.We identified 36 independent capsular switch events, 18 of which were explored in detail with whole-genome sequence data. Recombination fragment lengths were estimated for 11 events and ranged from approximately 19.0 kb to ≥ 58.2 kb. Two events took place no later than 1960, and the imported DNA included the capsular locus and the nearby penicillin-binding protein genes pbp2x and pbp1a.Capsular switching has been a regular occurrence among pneumococcal populations throughout the past 7 decades. Recombination of large DNA fragments (>30 kb), sometimes including the capsular locus and penicillin-binding protein genes, predated both vaccine introduction and widespread antibiotic use. This type of recombination has likely been an intrinsic feature throughout the history of pneumococcal evolution.Wellcome Trust 083511/Z/07/Z 098051 Stiftung Rheinland Pfalz fur Innovation Ciber de Enfermedades Respiratorias (Instituto de Salud Carlos III, Madrid Spain) Pfizer Vaccines GlaxoSmithKline Biological
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