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  • Comparison of Spasticity in Spinal Cord Injury and Stroke Patients Using Reflex Period in Pendulum Test.

    Kristinsdottir, Kristjana; Magnusdottir, Gigja; Chenery, Belinda; Gudmundsdottir, Vilborg; Gudfinnsdottir, Halla Kristin; Karason, Halldor; Ludvigsdottir, Gudbjorg K; Helgason, Thordur; 1Health Technology Center, Reykjavik University - Landspitali-University Hospital, Reykjavik, Iceland. 2Rehabilitation Department at Grensas, Landspitali-University Hospital, Reykjavík, Iceland. (PAGEPRESS PUBL, 2020-04-01)
    Spasticity is a motor impairment present in patients with both stroke and spinal cord injury. In this research, the results from the Wartenberg pendulum test, performed on stroke and spinal cord injury patients using goniometers and electromyogram recordings of the quadriceps, were reviewed and a new parameter to quantify spasticity was extracted. The Reflex Period (RP) of the pendulum test was defined as the time span from 50% of the maximum velocity of the leg swing to the activation of muscle contraction in the quadriceps, determined from the EMG. The results suggest that the reflex period in stroke patients is generally shorter than in those suffering from spinal cord injury. Keywords: Spasticity; Spinal Cord Injury; Stroke; Wartenberg pendulum test.
  • Using high density EEG to assess TMS treatment in patients with schizophrenia.

    Marcu, Sara; Pegolo, Elena; Ívarsson, Eysteinn; Jónasson, Aron D; Jónasson, Viktor D; Aubonnet, Romain; Gargiulo, Paolo; Banea, Ovidiu C; 1Reykjavik University, School of Science and Engineering, Biomedical Engineering, Reykjavik, Iceland. 2Department of Information Engineering, University of Padova, Italy. 3Clinical Neurophysiology Unit, Neurology Department, National University Hospital of Iceland. 4Psychiatric Department, National University Hospital of Iceland. (PAGEPRESS PUBL, 2020-04-01)
    We present preliminary results from the ongoing study entitled "Icelandic AVH-TMS" which aim is to study the effectiveness of repetitive transcranial magnetic stimulation (rTMS) treatment for patients with schizophrenia and with persistent auditory verbal hallucinations (AVH) using symptoms and psychometric scales and high-density EEG system (256 channels). The aim of the present work was to describe cortical topography of the auditory evoked responses like P50 and N100-P300 complex in healthy participants and patients with schizophrenia and to define a robust methodology of signal quantification using dense-array EEG. Preliminary data is shown for three healthy participants and three patients in baseline conditions and for two patients we show the results recorded before and after 10 days rTMS treatment. Our results show differences in sensory gating (P50 suppresion) and a stronger N100-P300 response to rare audio stimulus after the treatment. Moreover we show the value of assessing brain electrical activity from high-density EEG (256 channels) analyzing the results in different regions of interest. However, it is premature and hazardous to assume that rTMS treatment effectiveness in patients with AVH can be assessed using P50 suppression ratio. Keywords: P300; P50; Transcranial magnetic stimulation; high density EEG; schizophrenia.
  • Machine learning predictive system based upon radiodensitometric distributions from mid-thigh CT images.

    Recenti, Marco; Ricciardi, Carlo; Edmunds, Kyle; Gislason, Magnus K; Gargiulo, Paolo; 1Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland. 2Department of Advanced Biomedical Sciences, University Hospital of Naples 'Federico II', Naples, Italy. 3Department of Science, Landspítali, Reykjavík, Iceland. (PAGEPRESS PUBL, 2020-04-01)
    The nonlinear trimodal regression analysis (NTRA) method based on radiodensitometric CT images distributions was developed for the quantitative characterization of soft tissue changes according to the lower extremity function of elderly subjects. In this regard, the NTRA method defines 11 subject-specific soft tissue parameters and has illustrated high sensitivity to changes in skeletal muscle form and function. The present work further explores the use of these 11 NTRA parameters in the construction of a machine learning (ML) system to predict body mass index and isometric leg strength using tree-based regression algorithms. Results obtained from these models demonstrate that when using an ML approach, these soft tissue features have a significant predictive value for these physiological parameters. These results further support the use of NTRA-based ML predictive assessment and support the future investigation of other physiological parameters and comorbidities. Keywords: Computed Tomography; Machine learning; body mass index; isometric leg strength; soft tissue.
  • Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study

    Hanly, John G.; Li, Qiuju; Su, Li; Urowitz, Murray B.; Gordon, Caroline; Bae, Sang Cheol; Romero-Diaz, Juanita; Sanchez-Guerrero, Jorge; Bernatsky, Sasha; Clarke, Ann E.; et al. (Wiley, 2020-01-01)
    Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients. Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate. Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy. Conclusion: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.
  • Associations of physical activity with vitamin D status depends on obesity status in old adults.

    OG, Geirsdottir; M, Chang; Pv, Jonsson; I, Thorsdottir; A, Ramel; 1The Icelandic Gerontological Research Center, Reykjavik, Iceland; Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland. 2The Icelandic Gerontological Research Center, Reykjavik, Iceland; Sport Science, School of Science and Engineering, Reykjavik University, Reykjavik, Iceland. 3The Icelandic Gerontological Research Center, Reykjavik, Iceland; Department of Geriatrics, National University Hospital of Iceland, Reykjavik, Iceland. 4School of Health Sciences, University of Iceland, Reykjavik, Iceland. 5The Icelandic Gerontological Research Center, Reykjavik, Iceland; Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland. Electronic address: alfonsra@hi.is. (Elsevier, 2020-07-12)
    Purpose: Obesity has been associated with low 25-hydroxy-vitamin D (25OHD). The causes of hypovitaminosis D in obese individuals are not known. The present work aimed to investigate 25OHD in obese and normal-/overweight subjects with consideration of leisure-time physical activity (LTPA). Methods: Community-dwelling old adults (N = 229, 73.7 ± 5.7yrs, 58.2% female) from the Reykjavik capital area in Iceland participated in this cross-sectional study. LTPA, vitamin D intake, body composition and background variables were assessed. 25OHD was measured in fasting blood samples. Results: Mean LTPA was 5.7 ± 5.6 h/week and the common activities were walking and gardening. Mean 25OHD was 66.7 ± 28.1 nmol/L and 8.5/21.2% were below 30 and 50 nmol/L, respectively. Obese participants (n = 84) had lower 25OHD (-11.0 ± 3.8 nmol/L,P < 0.001) and lower LTPA (-2.5 + 0.8 h/week,P = 0.001) than normal-/overweight subjects (n = 145). Linear models showed that LTPA (h/week) was associated with higher 25OHD in normal-/overweight participants only (1.3 nmol/L, P < 0.001) but not in obese (-0.7 nmol, P = 0.245). Fish oil intake was associated with higher 25OHD both in normal-/overweight (19.2 ± 4.5 nmol/L, P = 0.001) and obese subjects (13.4 ± 5.3 nmol/L, P = 0.013). Conclusions: Obese community-dwelling old adults in Iceland have lower 25OHD than their normal-/overweight counterparts. LTPA was associated with a higher 25OHD in normal-/overweight, but not in obese participants. However, fish oil was associated with higher 25OHD independently from obesity status. Thus, vitamin D supplementation is important for obese old adults to maintain vitamin D levels. Keywords: Aging; Fish oil; Leisure-time physical activity; Obesity; Vitamin D.
  • Promoter CpG Density Predicts Downstream Gene Loss-of-Function Intolerance.

    Boukas, Leandros; Bjornsson, Hans T; Hansen, Kasper D; 1Human Genetics Training Program, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA; Department of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA. 2Department of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD 21287, USA; Faculty of Medicine, University of Iceland, Sturlugata 8, 101 Reykjavik, Iceland; Landspitali University Hospital, Hringbraut, 101 Reykjavik, Iceland. Electronic address: hbjorns1@jhmi.edu. 3Department of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD 21205, USA. Electronic address: khansen@jhsph.edu. (Cell Press, 2020-08-14)
    The aggregation and joint analysis of large numbers of exome sequences has recently made it possible to derive estimates of intolerance to loss-of-function (LoF) variation for human genes. Here, we demonstrate strong and widespread coupling between genic LoF intolerance and promoter CpG density across the human genome. Genes downstream of the most CpG-rich promoters (top 10% CpG density) have a 67.2% probability of being highly LoF intolerant, using the LOEUF metric from gnomAD. This is in contrast to 7.4% of genes downstream of the most CpG-poor (bottom 10% CpG density) promoters. Combining promoter CpG density with exonic and promoter conservation explains 33.4% of the variation in LOEUF, and the contribution of CpG density exceeds the individual contributions of exonic and promoter conservation. We leverage this to train a simple and easily interpretable predictive model that outperforms other existing predictors and allows us to classify 1,760 genes-which are currently unascertained in gnomAD-as highly LoF intolerant or not. These predictions have the potential to aid in the interpretation of novel variants in the clinical setting. Moreover, our results reveal that high CpG density is not merely a generic feature of human promoters but is preferentially encountered at the promoters of the most selectively constrained genes, calling into question the prevailing view that CpG islands are not subject to selection. Keywords: CpG density; CpG islands; GC content; dosage sensitivity; epigenetics; gnomAD; haploinsufficiency; loss-of-function; promoters; selection.
  • The Power of EEG to Predict Conversion from Mild Cognitive Impairment and Subjective Cognitive Decline to Dementia.

    Engedal, Knut; Barca, Maria Lage; Høgh, Peter; Bo Andersen, Birgitte; Winther Dombernowsky, Nanna; Naik, Mala; Gudmundsson, Thorkell Eli; Øksengaard, Anne-Rita; Wahlund, Lars-Olof; Snaedal, Jon; et al. (Karger, 2020-07-01)
    Introduction: The aim of this study was to examine if quantitative electroencephalography (qEEG) using the statistical pattern recognition (SPR) method could predict conversion to dementia in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: From 5 Nordic memory clinics, we included 47 SCD patients, 99 MCI patients, and 67 healthy controls. EEGs analyzed with the SPR method together with clinical data recorded at baseline were evaluated. The patients were followed up for a mean of 62.5 (SD 17.6) months and reexamined. Results: Of 200 participants with valid clinical information, 70 had converted to dementia, and 52 had developed Alzheimer's disease. Receiver-operating characteristic analysis of the EEG results as defined by a dementia index (DI) ranging from 0 to 100 revealed that the area under the curve was 0.78 (95% CI 0.70-0.85), corresponding to a sensitivity of 71%, specificity of 69%, and accuracy of 69%. A logistic regression analysis showed that by adding results of a cognitive test at baseline to the EEG DI, accuracy could improve. Conclusion: We conclude that applying qEEG using the automated SPR method can be helpful in identifying patients with SCD and MCI that have a high risk of converting to dementia over a 5-year period. As the discriminant power of the method is of moderate degree, it should be used in addition to routine diagnostic methods. Keywords: Dementia; EEG; Mild cognitive impairment; Subjective cognitive decline.
  • Midwifery students' perspectives on how role models contribute to becoming a midwife: A qualitative study.

    Nieuwenhuijze, Marianne J; Thompson, Suzanne M; Gudmundsdottir, Embla Yr; Gottfreðsdóttir, Helga; 1Research Centre of Midwifery Science Maastricht, Zuyd University, The Netherlands. Electronic address: m.nieuwenhuijze@av-m.nl. 2Research Centre of Midwifery Science Maastricht, Zuyd University, The Netherlands. 3Department of Midwifery, Faculty of Nursing, University of Iceland, Reykjavík, Iceland; Women´s Clinic, Landspitali University Hospital, 101 Reykjavik, Iceland. (Elsevier, 2019-10-12)
    Background: The dynamics of maternal and newborn care challenge midwifery education programs to keep up-to-date. To prepare for their professional role in a changing world, role models are important agents for student learning. Objective: To explore the ways in which Dutch and Icelandic midwifery students identify role models in contemporary midwifery education. Methods: We conducted a descriptive, qualitative study between August 2017 and October 2018. In the Netherlands, 27 students participated in four focus groups and a further eight in individual interviews. In Iceland, five students participated in one focus group and a further four in individual interviews. All students had clinical experience in primary care and hospital. Data were analyzed using inductive content analysis. Results: During their education, midwifery students identify people with attitudes and behaviors they appreciate. Students assimilate these attitudes and behaviors into a role model that represents their 'ideal midwife', who they can aspire to during their education. Positive role models portrayed woman-centered care, while students identified that negative role models displayed behaviors not fitting with good care. Students emphasized that they learnt not only by doing, they found storytelling and observing important aspects of role modelling. Students acknowledged the impact of positive midwifery role models on their trust in physiological childbirth and future style of practice. Conclusion: Role models contribute to the development of students' skills, attitudes, behaviors, identity as midwife and trust in physiological childbirth. More explicit and critical attention to how and what students learn from role models can enrich the education program. Keywords: Childbirth; Education; Midwifery; Qualitative research; Role model.
  • The association of missed nursing care and determinants of satisfaction with current position for direct-care nurses-An international study.

    Bragadóttir, Helga; Burmeister, Elizabeth A; Terzioglu, Fusun; Kalisch, Beatrice J; 1Faculty of Nursing, University of Iceland, Reykjavik, Iceland. 2Landspitali University Hospital, Reykjavik, Iceland. 3RANCARE Action, European Union. 4Princess Alexandra Hospital, University of Queensland, Brisbane, Australia. 5Atilim University, Ankara, Turkey. 6University of Michigan School of Nursing, Ann Arbor, MI, USA. (Wiley, 2020-05-22)
    Aim: To describe the association of missed nursing care and to identify the determinants of satisfaction with current position for direct-care nurses. Background: Missed nursing care and job satisfaction are important issues regarding quality patient care and safety in health care, globally. Method: This was a cross-sectional quantitative study using MISSCARE Survey data. Participants were 7,079 nursing staff providing direct patient care in hospitals in Australia, Iceland, Turkey and the USA. Multivariable nested models were used to identify the relationship between missed nursing care and nurses' satisfaction with current position. Results: More missed nursing care was associated with less satisfaction with current position. Other determinants of job satisfaction included country, nursing experience, overtime worked, adequacy of staffing and the number of shifts missed during the previous 3 months. Conclusion(s): Internationally, more missed nursing care is associated with less nursing job satisfaction and is influenced by work experience, overtime worked, levels of staffing and absenteeism. Implications for nursing management: This study identifies that the association between missed nursing care and satisfaction with nursing position is of global concern. Other factors requiring the attention of nurse managers are staffing levels, absenteeism and work experience. Keywords: international study; job satisfaction; missed nursing care; nursing.
  • Assessment of Interobserver Reliability of Nephrologist Examination of Urine Sediment.

    Palsson, Ragnar; Colona, Mia R; Hoenig, Melanie P; Lundquist, Andrew L; Novak, James E; Perazella, Mark A; Waikar, Sushrut S; 1Renal Division, Brigham and Women's Hospital, Boston, Massachusetts. 2Division of Nephrology, National University Hospital of Iceland, Reykjavik, Iceland. 3Renal Section, Department of Medicine, Boston University Medical Center, Boston, Massachusetts. 4Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 5Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts. 6Division of Nephrology, Henry Ford Hospital, Detroit, Michigan. 7Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut. (American Medical Association, 2020-08-03)
    Importance: Urine sediment microscopy is commonly performed during the evaluation of kidney disease. Interobserver reliability of nephrologists' urine sediment examination has not been well studied. Objective: Assess interobserver reliability of the urine sediment examination. Design, setting, and participants: In this diagnostic test study, urine samples were prospectively collected from a convenience sample of adult patients from an academic hospital in the United States undergoing kidney biopsy from July 11, 2018, to March 20, 2019. Digital images and videos of urine sediment findings were captured using a bright-field microscope. These images and videos along with urine dipstick results were incorporated in online surveys and sent to expert nephrologists at 15 US teaching hospitals. They were asked to identify individual sediment findings and the most likely underlying disease process. Exposures: Urine dipstick results and urine sediment images from patients undergoing native kidney biopsy. Main outcomes and measures: Interobserver reliability of urine sediment microscopy findings estimated by overall percent agreement and Fleiss κ coefficients. Secondary outcomes included concordance of diagnoses suspected by nephrologists with corresponding kidney biopsy results. Results: In total, 10 surveys from 10 patients containing 76 study questions on individual features were sent to 21 nephrologists, 14 (67%) of whom completed them all. Their combined 1064 responses were analyzed. Overall percent agreement for casts was an estimated 59% (95% CI, 50%-69%), κ = 0.52 (95% CI, 0.42-0.62). For other sediment findings, overall percent agreement was an estimated 69% (95% CI, 61%-77%), κ = 0.65 (95% CI, 0.56-0.73). The κ estimates ranged from 0.13 (95% CI, 0.10-0.17) for mixed cellular casts to 0.90 (95% CI, 0.87-0.94) for squamous epithelial cells. Conclusions and relevance: In this study, substantial variability occurred in the interpretation of urine sediment findings, even among expert nephrologists. Educational or technological innovations may help improve the urine sediment as a diagnostic tool.
  • EGFR mutation status in a series of Turkish non-small cell lung cancer patients.

    Calibasi-Kocal, Gizem; Amirfallah, Arsalan; Sever, Tolga; Umit Unal, Olcun; Gurel, Duygu; Oztop, Ilhan; Ellidokuz, Hulya; Basbinar, Yasemin (Spandidos Publications, 2020-06-02)
    Epidermal growth factor receptor (EGFR) mutations are potential markers driving carcinogenesis, and may alter the response to EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). The frequency of EGFR mutations in patients with NSCLC differs according to sex, smoking habits and regional-based ethnicity differences. The aim of the present study was to determine the frequency of EGFR mutations in Turkish patients with NSCLC to highlight the importance of regional differences, and their associations with patient characteristics. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tumor tissue sections of 409 NSCLC patients. The most common EGFR mutations in exons 18, 19, 20 and 21 were detected using BioFilmChip-based microarray assay. The overall EGFR mutation frequency was 16.6%, and the highest mutation frequencies were observed in exon 19 (6.4%) and exon 21 (7.3%). There was a higher frequency of EGFR mutations in females compared with males and in never-smokers compared with smokers (both P≤0.05). These results were similar to other European population-based studies, but not consistent Middle-Eastern based studies. The present study may contribute to understanding the gradient frequency of EGFR mutation across different ethnicities, and in designing genome wide-based collaborations that may reveal novel decision making and susceptibility mutations in EGFR in patients with NSCLC.
  • The Malignant Role of Exosomes as Nanocarriers of Rare RNA Species.

    Zimta, Alina-Andreea; Sigurjonsson, Olafur Eysteinn; Gulei, Diana; Tomuleasa, Ciprian; 1Research Center for Advanced Medicine-Medfuture, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania. 2The Blood Bank, Landspitali University Hospital, 121 Reykjavik, Iceland. 3School of Science and Engineering, Reykjavik University, 107 Reykjavik, Iceland. 4Department of Hematology, Oncology Institute Prof. Dr. Ion Chiricuta, 400015 Cluj-Napoca, Romania. (MDPI, 2020-08-15)
    Nowadays, advancements in the oncology sector regarding diagnosis methods allow us to specifically detect an increased number of cancer patients, some of them in incipient stages. However, one of the main issues consists of the invasive character of most of the diagnosis protocols or complex medical procedures associated with it, that impedes part of the patients to undergo routine checkups. Therefore, in order to increase the number of cancer cases diagnosed in incipient stages, other minimally invasive alternatives must be considered. The current review paper presents the value of rare RNA species isolated from circulatory exosomes as biomarkers of diagnosis, prognosis or even therapeutic intervention. Rare RNAs are most of the time overlooked in current research in favor of the more abundant RNA species like microRNAs. However, their high degree of stability, low variability and, for most of them, conservation across species could shift the interest toward these types of RNAs. Moreover, due to their low abundance, the variation interval in terms of the number of sequences with differential expression between samples from healthy individuals and cancer patients is significantly diminished and probably easier to interpret in a clinical context.
  • Basal cell carcinoma: an emerging epidemic in women in Iceland.

    Adalsteinsson, J A; Ratner, D; Olafsdóttir, E; Grant-Kels, J; Ungar, J; Silverberg, J I; Kristjansson, A K; Jonasson, J G; Tryggvadottir, L; 1University of Iceland, Saemundargata 2, 101 Reykjavik, Iceland. 2University of Connecticut Department of Dermatology, 263 Farmington Ave, Farmington, CT, 06003, USA. 3NYU Langone Health, Department of Dermatology, New York, NY, 10016, USA. 4Icelandic Cancer Registry, Skogarhlid 8, 105 Reykjavik, Iceland. 5Mount Sinai Department of Dermatology, One Gustave L. Levy Place, NY, 10029, USA. 6The George Washington University School of Medicine and Health Sciences, Washington, DC, USA. 7Faculty of Medicine, University of Iceland, Saemundargata 2, 101 Reykjavik, Iceland. 8Department of Pathology, Landspitali National-University Hospital, Hringbraut 101, 101 Reykjavik, Iceland. (Wiley, 2020-02-07)
    Background: An epidemic of basal cell carcinoma (BCC) has led to a significant healthcare burden in white populations. Objectives: To provide an update on incidence rates and tumour burden in an unselected, geographically isolated population that is exposed to a low level of ultraviolet radiation. Methods: This was a whole-population study using a cancer registry containing records of all cases of BCC in 1981-2017. We assessed BCC incidence according to age, residence and multiplicity and assessed trends using join-point analysis. Age-standardized and age-specific incidence rates were calculated along with cumulative and lifetime risks. Results: During the study period, the age-standardized incidence rates increased from 25·7 to 59·9 for men, and from 22·2 to 83·1 for women (per 100 000). Compared with the single-tumour burden, the total tumour burden in the population was 1·72 times higher when accounting for multiplicity. At the beginning of the study period, the world-standardized rates in men and women were similar, but by the end of the study period the rates were 39% higher in women (83·1 per 100 000, 95% confidence interval 77·9-88·3) than in men (59·9 per 100 000, 95% confidence interval 55·6-64·2). This increase was most prominent in women on sites that are normally not exposed to ultraviolet radiation in Iceland: the trunk and legs. Conclusions: This is the only reported population in which the incidence of BCC is significantly higher in women than in men. The period of notable increase in BCC lesions correlates with the period of an increase in tanning beds and travel popularity. The high multiplicity rates suggest that the total tumour burden worldwide might be higher than previously thought.
  • Quantitative 3D imaging parameters improve prediction of hip osteoarthritis outcome.

    Turmezei, T D; Treece, G M; Gee, A H; Sigurdsson, S; Jonsson, H; Aspelund, T; Gudnason, V; Poole, K E S; 1Department of Radiology, Norfolk and Norwich University Hospital, Norwich, UK. tom.turmezei@nnuh.nhs.uk. 2Cambridge University Engineering Department, Cambridge, UK. 3Icelandic Heart Association, Kopavogur, Iceland. 4Department of Rheumatology, Landspitalinn University Hospital, Reykjavik, Iceland. 5Department of Medicine, University of Iceland, Reykjavik, Iceland. 6Department of Medicine, University of Cambridge, Cambridge, UK. (Nature Publishing Group, 2020-03-05)
    Osteoarthritis is an increasingly important health problem for which the main treatment remains joint replacement. Therapy developments have been hampered by a lack of biomarkers that can reliably predict disease, while 2D radiographs interpreted by human observers are still the gold standard for clinical trial imaging assessment. We propose a 3D approach using computed tomography-a fast, readily available clinical technique-that can be applied in the assessment of osteoarthritis using a new quantitative 3D analysis technique called joint space mapping (JSM). We demonstrate the application of JSM at the hip in 263 healthy older adults from the AGES-Reykjavík cohort, examining relationships between 3D joint space width, 3D joint shape, and future joint replacement. Using JSM, statistical shape modelling, and statistical parametric mapping, we show an 18% improvement in prediction of joint replacement using 3D metrics combined with radiographic Kellgren & Lawrence grade (AUC 0.86) over the existing 2D FDA-approved gold standard of minimum 2D joint space width (AUC 0.73). We also show that assessment of joint asymmetry can reveal significant differences between individuals destined for joint replacement versus controls at regions of the joint that are not captured by radiographs. This technique is immediately implementable with standard imaging technologies.
  • Accidental poisoning, intentional self-harm and event of undetermined intent mortality over 20 years in Iceland: a population-based cohort study.

    Gunnarsdottir, Oddny Sigurborg; Rafnsson, Vilhjálmur; 1Office of Education, Research and Development, Landspitali-the National University Hospital of Iceland, Reykjavík, Iceland. 2Department of Preventive Medicine, Faculty of Medicine, University of Iceland, Reykjavík, Iceland vilraf@hi.is. (BMJ Publishing Group, 2020-05-20)
    Objectives: The aim was to study mortality due to suicide, accidental poisoning, event of undetermined intent and drug-related deaths through 20 years in Iceland. Design: A population-based register study. Participants: Individuals who died due to road traffic injury, suicide, accidental poisoning, event of undetermined intent and drug-related deaths in the population of Iceland during the years 1996-2015. Annual age-standardised rates were calculated, and the trend analysed by Pearson correlation and joinpoint regression. Setting: The population of Iceland framed the study material, and the data were obtained from nationwide registries for information on number of deaths and age-specific mean population in each year by gender. Results: The crude overall suicide rate during the last 10 years was 12.2 per 100 000 persons per year (95% CI 7.4 to 18.1), while the crude overall rate due to road traffic injuries was 4.6 per 100 000 persons per year (95% CI 2.0 to 8.3). Among men, suicide rates decreased, however not significantly (r(19)=-0.22, p=0.36), and for overdose by narcotics the rates increased significantly (r(19)=0.72, p<0.001) during the study period. Among women, the suicide rates increased, however not significantly (r(19)=0.35, p=0.13), for accidental poisoning, suicide and event of undetermined intent combined the rates increased significantly (r(19)=0.60, p=0.006); and the rates for overdose by sedative and overdose by narcotics both increased significantly r(19)=0.49, p=0.03, and r(19)=0.67, p=0.001, respectively. Conclusion: The suicide rates have not changed during 1996 to 2015; however, the rates for the combined accidental poisoning, suicide and event of undetermined intent increased significantly for women. The rise of the overdose rates for sedative among women and for narcotics among both genders are consistent with reports elsewhere. Keywords: epidemiology; public health; statistics & research methods; substance misuse; suicide & self-harm.
  • Þegar orkuna skortir – áhrif hlutfallslegs orkuskorts í íþróttum (RED-s) á heilsu og árangur

    Birna Varðardóttir; Sigríður Lára Guðmundsdóttir1; Anna Sigríður Ólafsdóttir; Deild heilsueflingar, íþrótta og tómstunda, menntavísindasviði Háskóla Íslands (Læknafélag Íslands, 2020-09)
    Mikilvægt er að íþróttafólk á öllum aldri tileinki sér mataræði sem styður sem best við heilsu og vellíðan, þjálffræðilega aðlögun, endurheimt og meiðslaforvarnir. Tiltæk orka vísar til þeirrar orku sem stendur eftir fyrir grunnstarfsemi líkamans þegar búið er að draga þá orku sem varið er við líkamlega þjálfun frá orkunni sem fæst úr fæðunni sem neytt er dag hvern. Hlutfallslegur orkuskortur í íþróttum (Relative Energy Deficiency in Sport, RED-s) stafar af viðvarandi skorti á tiltækri orku og hefur víðtæk áhrif á íþróttafólk, óháð kyni og getustigi. Áhrif RED-s geta meðal annars falið í sér skerðingu á efnaskiptahraða, hormónastarfsemi og tíðahring kvenna, beinheilsu, ónæmisvörnum, nýmyndun próteina og starfsemi hjarta- og æðakerfis. Slíkar truflanir á líkamsstarfsemi geta haft neikvæð áhrif á heilsu og íþróttaárangur til lengri og skemmri tíma. Þekkt er að RED-s getur átt sér mismunandi orsakir og birtingarmyndir. Samkvæmt erlendum rannsóknum er algengi breytilegt eftir íþróttagreinum og sérhæfingum innan þeirra en áhættan er talin hvað mest í úthaldsíþróttum, fagurfræðilegum íþróttum og þyngdarflokkaíþróttum. Greinin tekur saman þekkingu á áhrifum RED-s á heilsu og árangur, mikilvægi skimunar og snemmbærs inngrips. Þörf er á rannsóknum á RED-s meðal íslensks íþróttafólks sem gætu lagt grunninn að íslenskum ráðleggingum auk þess að efla forvarnir og meðferð
  • Samanburður á greiningu og meðferð ífarandi brjóstakrabbameina milli Íslands og Svíþjóðar

    Lilja Dögg Gísladóttir; Helgi Birgisson; Bjarni A. Agnarsson; Þorvaldur Jónsson; Laufey Tryggvadóttir; Ásgerður Sverrisdóttir; 1 Læknadeild Háskóla Íslands, 2 Landspítala, 3Krabbameinsskrá Krabbameinsfélags Íslands. (Læknafélag Íslands, 2020-09)
    TILGANGUR Rannsóknin var liður í innleiðingu gæðaskráningar brjóstakrabbameina á Íslandi og markmiðið að bera saman greiningu og meðferð ífarandi brjóstakrabbameina á Íslandi og í Svíþjóð. EFNIVIÐUR OG AÐFERÐIR Upplýsingar um alla einstaklinga sem greindust með ífarandi brjóstakrabbamein á Íslandi 2016-2017 fengust frá Krabbameinsskrá. Breytur úr sjúkraskrám voru skráðar í eyðublöð í Heilsugátt að fyrirmynd sænsku gæðaskráningarinnar og voru niðurstöður bornar saman við niðurstöður fyrir ífarandi brjóstakrabbamein af heimasíðu sænsku krabbameinsskrárinnar. Notað var tvíhliða kí-kvaðrat-próf til að bera saman hlutföll. NIÐURSTÖÐUR Á rannsóknartímabilinu greindust 486 ífarandi brjóstakrabbamein á Íslandi og 15.325 í Svíþjóð. Hlutfallslega færri 40-69 ára konur greindust við hópleit á Íslandi (46%) en í Svíþjóð (60%) (p<0,01). Á Íslandi voru haldnir heldur færri samráðsfundir fyrir fyrstu meðferð (92%) og eftir aðgerð (96%) miðað við Svíþjóð árið 2016 (98% og 99%) (p<0,05) en ekki var marktækur munur 2017. Varðeitlataka var gerð í 69% aðgerða á Íslandi en í 94% aðgerða í Svíþjóð (p<0,01). Ef æxlið var ≤30 mm var á Íslandi gerður fleygskurður í 48% tilvika en í 80% tilvika í Svíþjóð (p<0,01). Á Íslandi fengu 87% geislameðferð eftir fleygskurð en 94% í Svíþjóð (p<0,01). Ef eitlameinvörp greindust í brottnámsaðgerð þá fengu 49% geislameðferð eftir aðgerð á Íslandi en 83% í Svíþjóð (p<0,01). ÁLYKTANIR Marktækur munur er á ýmsum þáttum greiningar og meðferðar ífarandi brjóstakrabbameina milli Íslands og Svíþjóðar. Með gæðaskráningu brjóstakrabbameina á Íslandi er hægt að fylgjast með og setja markmið um ákveðna þætti greiningar og meðferðar í því skyni að veita sem flestum einstaklingum bestu meðferð.
  • Characteristics of incidence hip fracture cases in older adults participating in the longitudinal AGES-Reykjavik study.

    Skuladottir, S S; Ramel, A; Hjaltadottir, I; Launer, L J; Cotch, M F; Siggeirsdottir, K; Gudnason, V; Sigurdsson, G; Steingrimsdottir, L; Halldorsson, T; et al. (Springer, 2020-08-18)
    Poor physical function and body composition my partly predict the risk of falls leading to fracture regardless of bone mineral density. Introduction: To examine the relationship between body composition, physical function, and other markers of health with hip fractures in older community-dwelling Icelandic adults. Methods: A prospective cohort of 4782 older adults from the AGES-Reykjavik study. Baseline recruitment took place between 2002 and 2006, and information on hip fractures occurring through 2012 was extracted from clinical records. Using multivariate regression analyses, baseline measures of bone health, physical function, and body composition were compared between those who later experienced hip fractures and to those who did not. Associations with the risk of fractures were quantified using Cox regression. Results: Mean age was 76.3 years at baseline. After adjustment for age, regression showed that male hip fracture cases compared with non-cases had (mean (95% confidence interval)) significantly lower thigh muscle cross-sectional area - 5.6 cm2 (- 10.2, - 1.1), poorer leg strength - 28 N (- 49, - 7), and decreased physical function as measured by longer timed up and go test 1.1 s (0.5, 1.7). After adjustment for age, female cases had, compared with non-cases, lower body mass index - 1.5 kg/m2 (- 2.1, - 0.9), less lean mass - 1.6 kg (- 2.5, - 0.8), thigh muscle cross-sectional area - 4.4 cm2 (- 6.5, - 2.3), and worse leg strength - 16 N (- 25, - 6). These differences largely persisted after further adjustment for bone mineral density (BMD), suggesting that body composition may contribute to the risk of fracture independent of bone health. When examining the association between these same factors and hip fractures using Cox regression, the same conclusions were reached. Conclusions: After accounting for age and BMD, older adults who later experienced a hip fracture had poorer baseline measures of physical function and/or body composition, which may at least partly contribute to the risk of falls leading to fracture. Keywords: Aging; Biomarkers; Body composition; Hip fracture; Physical function.
  • A gene expression-based single sample predictor of lung adenocarcinoma molecular subtype and prognosis.

    Liljedahl, Helena; Karlsson, Anna; Oskarsdottir, Gudrun N; Salomonsson, Annette; Brunnström, Hans; Erlingsdottir, Gigja; Jönsson, Mats; Isaksson, Sofi; Arbajian, Elsa; Ortiz-Villalón, Cristian; et al. (Wiley, 2020-08-03)
    Disease recurrence in surgically treated lung adenocarcinoma (AC) remains high. New approaches for risk stratification beyond tumor stage are needed. Gene expression-based AC subtypes such as the Cancer Genome Atlas Network (TCGA) terminal-respiratory unit (TRU), proximal-inflammatory (PI) and proximal-proliferative (PP) subtypes have been associated with prognosis, but show methodological limitations for robust clinical use. We aimed to derive a platform independent single sample predictor (SSP) for molecular subtype assignment and risk stratification that could function in a clinical setting. Two-class (TRU/nonTRU=SSP2) and three-class (TRU/PP/PI=SSP3) SSPs using the AIMS algorithm were trained in 1655 ACs (n = 9659 genes) from public repositories vs TCGA centroid subtypes. Validation and survival analysis were performed in 977 patients using overall survival (OS) and distant metastasis-free survival (DMFS) as endpoints. In the validation cohort, SSP2 and SSP3 showed accuracies of 0.85 and 0.81, respectively. SSPs captured relevant biology previously associated with the TCGA subtypes and were associated with prognosis. In survival analysis, OS and DMFS for cases discordantly classified between TCGA and SSP2 favored the SSP2 classification. In resected Stage I patients, SSP2 identified TRU-cases with better OS (hazard ratio [HR] = 0.30; 95% confidence interval [CI] = 0.18-0.49) and DMFS (TRU HR = 0.52; 95% CI = 0.33-0.83) independent of age, Stage IA/IB and gender. SSP2 was transformed into a NanoString nCounter assay and tested in 44 Stage I patients using RNA from formalin-fixed tissue, providing prognostic stratification (relapse-free interval, HR = 3.2; 95% CI = 1.2-8.8). In conclusion, gene expression-based SSPs can provide molecular subtype and independent prognostic information in early-stage lung ACs. SSPs may overcome critical limitations in the applicability of gene signatures in lung cancer. Keywords: gene expression; lung adenocarcinoma; molecular subtypes; prognosis; single sample predictor.
  • GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer.

    Zhou, Wei; Brumpton, Ben; Kabil, Omer; Gudmundsson, Julius; Thorleifsson, Gudmar; Weinstock, Josh; Zawistowski, Matthew; Nielsen, Jonas B; Chaker, Layal; Medici, Marco; et al. (Nature Publishing Group, 2020-08-07)
    Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors.

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