• Exploratory assessment of pineal gland volume, composition, and urinary 6-sulfatoxymelatonin levels on prostate cancer risk.

      Bazzi, Latifa A; Sigurdardottir, Lara G; Sigurdsson, Sigurdur; Valdimarsdottir, Unnur; Torfadottir, Johanna; Aspelund, Thor; Czeisler, Charles A; Lockley, Steven W; Jonsson, Eirikur; Launer, Lenore; et al. (Wiley, 2021-04-16)
      Introduction: Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined. Materials and methods: We utilized data from 864 men from the AGES-Reykjavik Study with complete pineal gland volumes and urinary 6-sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6-sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6-sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6-sulfatoxymelatonin level. Results: Parenchyma volume was moderately correlated with urinary 6-sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6-sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6-sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04). Conclusions: Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk. Keywords: circadian rhythm; melatonin; pineal gland; prostate cancer.
    • HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry.

      Konte, Bettina; Walters, James T R; Rujescu, Dan; Legge, Sophie E; Pardiñas, Antonio F; Cohen, Dan; Pirmohamed, Munir; Tiihonen, Jari; Hartmann, Annette M; Bogers, Jan P; et al. (Nature Publishing Group, 2021-04-12)
      The atypical antipsychotic clozapine is the only effective medication for treatment-resistant schizophrenia. However, it can also induce serious adverse drug reactions, including agranulocytosis and neutropenia. The mechanism by which it does so is largely unknown, but there is evidence for contributing genetic factors. Several studies identified HLA-DQB1 variants and especially a polymorphism located in HLA-DQB1 (6672G>C, rs113332494) as associated with clozapine-induced agranulocytosis and neutropenia. We analysed the risk allele distribution of SNP rs113332494 in a sample of 1396 controls and 178 neutropenia cases of which 60 developed agranulocytosis. Absolute neutrophil counts of 500/mm3 and 1500/mm3 were used for defining agranulocytosis and neutropenia cases, respectively. We also performed association analyses and analysed local ancestry patterns in individuals of European ancestry, seeking replication and extension of earlier findings. HLA-DQB1 (6672G>C, rs113332494) was associated with neutropenia (OR = 6.20, P = 2.20E-06) and agranulocytosis (OR = 10.49, P = 1.83E-06) in individuals of European ancestry. The association signal strengthened after including local ancestry estimates (neutropenia: OR = 10.38, P = 6.05E-08; agranulocytosis: OR = 16.31, P = 1.39E-06), with effect sizes being considerably larger for agranulocytosis. Using local ancestry estimates for prediction, the sensitivity of rs113332494 increased from 11.28 to 55.64% for neutropenia and from 16.67 to 53.70% for agranulocytosis. Our study further strengthens the evidence implicating HLA-DQB1 in agranulocytosis and neutropenia, suggesting components of the immune system as contributing to this serious adverse drug reaction. Using local ancestry estimates might help in identifying risk variants and improve prediction of haematological adverse effects.
    • Lower or higher oxygenation targets for acute hypoxemic respiratory failure

      Schjørring, Olav L.; Klitgaard, Thomas L.; Perner, Anders; Wetterslev, Jørn; Lange, Theis; Siegemund, Martin; Bäcklund, Minna; Keus, Frederik; Laake, Jon H.; Morgan, Matthew; et al. (Massachusetts Medical Society, 2021-04-08)
      BACKGROUND Patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao2) would result in lower mortality than using a higher target. METHODS In this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao2 of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higher-oxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days. RESULTS At 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P=0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P=0.24). CONCLUSIONS Among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days.
    • Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

      Deloria Knoll, Maria; Bennett, Julia C; Garcia Quesada, Maria; Kagucia, Eunice W; Peterson, Meagan E; Feikin, Daniel R; Cohen, Adam L; Hetrich, Marissa K; Yang, Yangyupei; Sinkevitch, Jenna N; et al. (MDPI, 2021-04-02)
      Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon. Keywords: global; invasive pneumococcal disease; pneumococcal conjugate vaccines; pneumococcal meningitis; surveillance.
    • Acute gastrointestinal bleeding among patients on antiplatelet and anticoagulant therapy after percutaneous coronary intervention.

      Sveinsdottir, Asdis; Gudmundsdottir, Ingibjörg J; Hreinsson, Johann P; Andersen, Karl; Björnsson, Einar S; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Department of Internal Medicine, Division of Cardiology, Landspitali - The National University Hospital of Iceland, Reykajvik, Iceland. 3Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. (Taylor & Francis, 2021-04-01)
      Background: Patients undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy and some require additional anticoagulation. We aimed to investigate the incidence of acute gastrointestinal bleeding (AGIB) among PCI patients receiving antiplatelet and anticoagulant therapy. Methods: A population-based study that included all patients undergoing PCI during 2008-2016 in Iceland. Data from the Icelandic Medicines Registry were obtained on all outpatient prescriptions 1 year after first PCI. Patients receiving single or dual-antiplatelet therapy with or without anticoagulation cotherapy were analyzed. Rehospitalization for AGIB and endoscopic data were obtained within the 12-month follow-up period. Results: A total of 5166 patients (male 75%) underwent PCI during the study period. The incidence of AGIB was 1% (54/5166) per year. The mean age among non-bleeders 65 (±11) years was lower than among bleeders 69 (±9) years (p = .002). The proportion of acute upper GIB (AUGIB) was 56%, whereas lower GIB occurred in 44%. Overall, 41% with AUGIB had PPIs compared to 39% of non-bleeders (NS). The incidence of AGIB among patients on single antiplatelet therapy combined with an anticoagulant was 2.5% compared to 0.9% among those on single antiplatelet treatment alone (p = .028). The number needed to harm (NNH) for treatment with single antiplatelet therapy and anticoagulant therapy compared to single antiplatelet therapy was 62 but no deaths related to AGIB. Conclusions: The 1-year incidence of AGIB was low with no mortality. Bleeding risk was found to be higher among patients on single antiplatelet therapy combined with anticoagulant therapy compared to patients on single antiplatelet therapy alone. Keywords: Acute gastrointestinal bleeding; anticoagulant therapy; antiplatelet therapy; dual antiplatelet therapy; incidence; number needed to harm; percutaneous coronary intervention.
    • Toward Predicting Motion Sickness Using Virtual Reality and a Moving Platform Assessing Brain, Muscles, and Heart Signals.

      Recenti, Marco; Ricciardi, Carlo; Aubonnet, Romain; Picone, Ilaria; Jacob, Deborah; Svansson, Halldór Á R; Agnarsdóttir, Sólveig; Karlsson, Gunnar H; Baeringsdóttir, Valdís; Petersen, Hannes; et al. (Frontiers Media, 2021-04-01)
      Motion sickness (MS) and postural control (PC) conditions are common complaints among those who passively travel. Many theories explaining a probable cause for MS have been proposed but the most prominent is the sensory conflict theory, stating that a mismatch between vestibular and visual signals causes MS. Few measurements have been made to understand and quantify the interplay between muscle activation, brain activity, and heart behavior during this condition. We introduce here a novel multimetric system called BioVRSea based on virtual reality (VR), a mechanical platform and several biomedical sensors to study the physiology associated with MS and seasickness. This study reports the results from 28 individuals: the subjects stand on the platform wearing VR goggles, a 64-channel EEG dry-electrode cap, two EMG sensors on the gastrocnemius muscles, and a sensor on the chest that captures the heart rate (HR). The virtual environment shows a boat surrounded by waves whose frequency and amplitude are synchronized with the platform movement. Three measurement protocols are performed by each subject, after each of which they answer the Motion Sickness Susceptibility Questionnaire. Nineteen parameters are extracted from the biomedical sensors (5 from EEG, 12 from EMG and, 2 from HR) and 13 from the questionnaire. Eight binary indexes are computed to quantify the symptoms combining all of them in the Motion Sickness Index (I MS ). These parameters create the MS database composed of 83 measurements. All indexes undergo univariate statistical analysis, with EMG parameters being most significant, in contrast to EEG parameters. Machine learning (ML) gives good results in the classification of the binary indexes, finding random forest to be the best algorithm (accuracy of 74.7 for I MS ). The feature importance analysis showed that muscle parameters are the most relevant, and for EEG analysis, beta wave results were the most important. The present work serves as the first step in identifying the key physiological factors that differentiate those who suffer from MS from those who do not using the novel BioVRSea system. Coupled with ML, BioVRSea is of value in the evaluation of PC disruptions, which are among the most disturbing and costly health conditions affecting humans.
    • Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

      Garcia Quesada, Maria; Yang, Yangyupei; Bennett, Julia C; Hayford, Kyla; Zeger, Scott L; Feikin, Daniel R; Peterson, Meagan E; Cohen, Adam L; Almeida, Samanta C G; Ampofo, Krow; et al. (MDPI, 2021-04-01)
      Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.
    • Use of psychiatric medication in three Arctic nursing homes: association with dementia and psychiatric symptoms.

      Gisladottir, Sigurveig; Sigurdardottir, Arun K; Hjaltadottir, Ingibjörg; 1Fossahlid Nursing Home, Health Care Institution of Eastern Iceland. 2University of Akureyri, School of Health Sciences, Akureyri, Iceland. 3Akureyri Hospital, Akureyri, Iceland. 4Faculty of Nursing, University of Iceland. 5Division of Clinical Services Landspítali, National University Hospital, Reykjavik, Iceland. (Taylor & Francis, 2021-04)
      As more people reaches advanced age, more people experience cognitive impairment and dementia. Dementia is a degenerative disease in which behavioural and psychological symptoms frequently occur, resulting in admissions to nursing homes (NHs), where the most common treatment has been medical treatment. The aim was to compare three rural Arctic NHs in Iceland in their use of psychiatric medication, type of dementia among residents, level of cognitive impairment and selected quality indicators, as well as considering national data, for the period 2016-2018. Data from the interRAI-MDS 2.0 evaluation were used. Residents with severe cognitive impairment used more antipsychotic medications, and residents with mild and severe cognitive impairment used more antidepressants than residents with no cognitive impairment did. Diagnoses of Alzheimer's Disease and Related Dementias (ADRD) are more common in the capital area and the national average than they are in the rural NHs. This indicates need for diagnostic assessments of ADRD to be conducted in rural areas. Benchmarking is beneficial for local and national regulatory bodies to find areas for improvement. The NHs did not have a lower quality of care compared with the whole country, but areas for improvement were identified. One of the NHs has already started this process. Keywords: Nursing homes; arctic areas; dementia; psychiatric medication.
    • Long-Term Effect of Receiving a Family Strengths-Oriented Intervention on Family Cancer Caregiver Stress, Anxiety, and Depression Symptoms: A Longitudinal Quasi-Experimental Study.

      Petursdottir, Asta B; Rayens, Mary Kay; Sigurdardottir, Valgerdur; Svavarsdottir, Erla Kolbrun; 1School of Health Sciences, Faculty of Nursing, University of Iceland, Reykjavík, Iceland. 2Landspitali The National University Hospital, Reykjavík, Iceland. 3University of Kentucky, Lexington, USA. (SAGE Publications, 2021-03-31)
      The aim of this longitudinal study was to evaluate the long-term effects of providing a therapeutic conversation intervention, based on Family Systems Nursing, to family caregivers of a close relative with advanced cancer over the period before and during bereavement. To prevent adverse outcomes, caregivers need ongoing support that begins pre-loss and extends into the post-loss period. This study employed a one-group pre-test, post-test quasi-experimental design. Twenty-four caregivers participated in two intervention trials conducted over a 42-month period, receiving two intervention sessions pre-loss (Trial 1) and one intervention session post-loss (Trial 2). Significant decreases in anxiety and stress were noted over the three post-loss assessments. The final post-loss stress outcome was significantly lower than the first pre-loss score. For the depression score, there was not a significant change over time within the pre- or post-loss period. The findings provide evidence of decreasing anxiety and stress following the implementation of an extended family nursing intervention for bereaved family caregivers. Keywords: Family Systems Nursing; advanced cancer; bereavement; family caregiver; longitudinal research; palliative care.
    • Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome.

      Sheppard, Sarah E; Campbell, Ian M; Harr, Margaret H; Gold, Nina; Li, Dong; Bjornsson, Hans T; Cohen, Julie S; Fahrner, Jill A; Fatemi, Ali; Harris, Jacqueline R; et al. (Wiley, 2021-03-30)
      Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS. Keywords: KMT2A; MLL1; Wiedemann-Steiner syndrome; hypertrichosis; syndromic intellectual disability; syndromic short stature.
    • Statins are associated with increased risk of squamous cell carcinoma of the skin: a whole-population study from Iceland.

      Adalsteinsson, Jonas A; Muzumdar, Sonal; Waldman, Reid; Hu, Chaoran; Wu, Rong; Ratner, Désirée; Feng, Hao; Ungar, Jonathan; Silverberg, Jonathan I; Olafsdottir, Gudridur H; et al. (Springer, 2021-03-27)
      Statins have been associated with an increased risk of keratinocyte carcinoma but data are limited and conflicting. Statins are hypothesized to contribute to KC through immunomodulation. A whole-population case-control study of the Icelandic population was conducted using the Icelandic Cancer Registry and Icelandic Prescription Medicine Register. These are high-quality registers which include all cancer diagnoses, as well as every prescription in the country. Cases included all first-time histologically confirmed diagnoses of (BCC), in situ squamous cell carcinoma (SCCis) and invasive SCC between 2003 and 2017. Each case was paired with 10 age- and sex-matched controls. Multivariate conditional logistic regression analysis was performed. Four thousand seven hundred patients with BCC, 1167 patients with SCCis and 1013 patients with invasive SCC were identified and paired with 47,292, 11,961 and 10,367 controls, respectively. Overall statin use was associated with an increased risk of invasive SCC and SCCis but not BCC (adjusted OR [95% CI]: 1.29 [1.11-1.50]; 1.43 [1.24-1.64]; 1.03 [0.95-1.12], respectively). Subgroup analysis demonstrated that statins were significantly associated with invasive SCC and SCCis in patients over 60, but not in those under 60. Atorvastatin was only associated with an increased risk of SCCis; whereas, simvastatin was associated with an increased risk of both invasive SCC and SCCis. This whole-population study of Iceland demonstrates that statin exposure is associated with increased risk of SCC, but not BCC, in a low UV environment. The reasons are unclear, but our results may suggest that individuals receiving atorvastatin and simvastatin have differing levels of baseline keratinocyte cancer risk or that properties of a statin other than 'statin intensity' affect association with SCC. Keywords: Atorvastatin; Basal cell carcinoma; Nonmelanoma skin cancer; Simvastatin; Squamous cell carcinoma; Statins.
    • Changes in Invasive Pneumococcal Disease Caused by Serotype 1 Following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project.

      Bennett, Julia C; Hetrich, Marissa K; Garcia Quesada, Maria; Sinkevitch, Jenna N; Deloria Knoll, Maria; Feikin, Daniel R; Zeger, Scott L; Kagucia, Eunice W; Cohen, Adam L; Ampofo, Krow; et al. (MDPI, 2021-03-27)
      Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04-0.06) for all ages, 0.05 (0.04-0.05) for <5 years of age, 0.08 (0.06-0.09) for 5-17 years, 0.06 (0.05-0.08) for 18-49 years, 0.06 (0.05-0.07) for 50-64 years, and 0.05 (0.04-0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed.
    • Vitamin D status and association with gestational diabetes mellitus in a pregnant cohort in Iceland.

      Magnusdottir, Kristin S; Tryggvadottir, Ellen A; Magnusdottir, Ola K; Hrolfsdottir, Laufey; Halldorsson, Thorhallur I; Birgisdottir, Bryndis E; Hreidarsdottir, Ingibjorg T; Hardardottir, Hildur; Gunnarsdottir, Ingibjorg; 1Unit for Nutrition Research, Landspitali University Hospital and Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland. 2Institution of Health Science Research, University of Akureyri and Akureyri Hospital, Akureyri, Iceland. 3Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. 4Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavík, Iceland. 5Faculty of Medicine, University of Iceland, Reykjavík, Iceland. (Swedish Nutrition Foundation, 2021-03-23)
      Background: Vitamin D deficiency has been associated with an increased risk of gestational diabetes mellitus (GDM), one of the most common pregnancy complications. The vitamin D status has never previously been studied in pregnant women in Iceland. Objective: The aim of this research study was to evaluate the vitamin D status of an Icelandic cohort of pregnant women and the association between the vitamin D status and the GDM incidence. Design: Subjects included pregnant women (n = 938) who attended their first ultrasound appointment, during gestational weeks 11-14, between October 2017 and March 2018. The use of supplements containing vitamin D over the previous 3 months, height, pre-pregnancy weight, and social status were assessed using a questionnaire, and blood samples were drawn for analyzing the serum 25‑hydroxyvitamin D (25OHD) concentration. Information regarding the incidence of GDM later in pregnancy was collected from medical records. Results: The mean ± standard deviation of the serum 25OHD (S-25OHD) concentration in this cohort was 63±24 nmol/L. The proportion of women with an S-25OHD concentration of ≥ 50 nmol/L (which is considered adequate) was 70%, whereas 25% had concentrations between 30 and 49.9 nmol/L (insufficient) and 5% had concentrations < 30 nmol/L (deficient). The majority of women (n = 766, 82%) used supplements containing vitamin D on a daily basis. A gradual decrease in the proportion of women diagnosed with GDM was reported with increasing S-25OHD concentrations, going from 17.8% in the group with S-25OHD concentrations < 30 nmol/L to 12.8% in the group with S-25OHD concentrations ≥75 nmol/L; however, the association was not significant (P for trend = 0.11). Conclusion: Approximately one-third of this cohort had S-25OHD concentrations below adequate levels (< 50 nmol/L) during the first trimester of pregnancy, which may suggest that necessary action must be taken to increase their vitamin D levels. No clear association was observed between the vitamin D status and GDM in this study. Keywords: cod liver oil; gestational diabetes mellitus; nutritional status; pregnancy; supplements; vitamin D.
    • Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency.

      Runolfsdottir, Hrafnhildur L; Sayer, John A; Indridason, Olafur S; Edvardsson, Vidar O; Jensson, Brynjar O; Arnadottir, Gudny A; Gudjonsson, Sigurjon A; Fridriksdottir, Run; Katrinardottir, Hildigunnur; Gudbjartsson, Daniel; et al. (Nature Publishing Group, 2021-03-11)
      Adenine phosphoribosyltransferase deficiency is a rare, autosomal recessive disorder of purine metabolism that causes nephrolithiasis and progressive chronic kidney disease. The small number of reported cases indicates an extremely low prevalence, although it has been suggested that missed diagnoses may play a role. We assessed the prevalence of APRT deficiency based on the frequency of causally-related APRT sequence variants in a diverse set of large genomic databases. A thorough search was carried out for all APRT variants that have been confirmed as pathogenic under recessive mode of inheritance, and the frequency of the identified variants examined in six population genomic databases: the deCODE genetics database, the UK Biobank, the 100,000 Genomes Project, the Genome Aggregation Database, the Human Genetic Variation Database and the Korean Variant Archive. The estimated frequency of homozygous genotypes was calculated using the Hardy-Weinberg equation. Sixty-two pathogenic APRT variants were identified, including six novel variants. Most common were the missense variants c.407T>C (p.(Met136Thr)) in Japan and c.194A>T (p.(Asp65Val)) in Iceland, as well as the splice-site variant c.400 + 2dup (p.(Ala108Glufs*3)) in the European population. Twenty-nine variants were detected in at least one of the six genomic databases. The highest cumulative minor allele frequency (cMAF) of pathogenic variants outside of Japan and Iceland was observed in the Irish population (0.2%), though no APRT deficiency cases have been reported in Ireland. The large number of cases in Japan and Iceland is consistent with a founder effect in these populations. There is no evidence for widespread underdiagnosis based on the current analysis.
    • Stroke survivors' experiences with rebuilding life in the community and exercising at home: A qualitative study.

      van Dongen, Lisa; Hafsteinsdóttir, Thóra B; Parker, Ethna; Bjartmarz, Ingibjörg; Hjaltadóttir, Ingibjörg; Jónsdóttir, Helga; 1Julius Center for Health Sciences and Primary Care, Nursing Science Department, University Medical Center Utrecht, Utrecht, The Netherlands. 2Faculty of Nursing, School of Health Sciences, University of Iceland, Reykjavík, Iceland. 3Landspítali University Hospital, Reykjavík, Iceland. (Wiley, 2021-03-10)
      Aim: This study aimed to explore how stroke survivors deal with stroke-related impairments when rebuilding their lives in the community and their experiences of exercising at home. Design: An explorative and descriptive qualitative study. Methods: A purposive sample of ten stroke survivors residing at home was recruited to explore experiences of rebuilding their lives in the community and exercising at home. One focus group interview was conducted followed by semi-structured interviews. Data were analysed using thematic analysis. Results: Three main themes were identified: "Framing exercise within the context of everyday life" describes how stroke survivors integrate exercise in everyday activities with varying success and the social importance of exercising; "Managing the challenges of physical impairment" describes the taxing undertakings in daily living, loss of concentration and identity; "Long-term challenges of everyday life" describes how the stroke survivors manage depression and live with a sense of uncertainty. Keywords: home rehabilitation; qualitative research; rehabilitation; stroke patients; stroke rehabilitation.
    • Health technology assessment through Six Sigma Methodology to assess cemented and uncemented protheses in total hip arthroplasty.

      Latessa, Imma; Ricciardi, Carlo; Jacob, Deborah; Jónsson, Halldór; Gambacorta, Monica; Improta, Giovanni; Gargiulo, Paolo; 1University Hospital of Naples "Federico II", Department of Public Health, Naples, Italy; Reykjavík University, Institute for Biomedical and Neural Engineering, Reykjavík. immalatessa@gmail.com. 2Reykjavík University, Institute for Biomedical and Neural Engineering, Reykjavík, Iceland; University Hospital of Naples 'Federico II', Department of Advanced Biomedical Sciences, Naples. carloricciardi.93@gmail.com. 3Reykjavík University, Institute for Biomedical and Neural Engineering, Reykjavík. dcrjacob@gmail.com. 4University of Iceland, Faculty of Medicine, Reykjavík, Iceland; Landspítali Hospital, Orthopaedic Clinic, Reykjavík. halldor@landspitali.is. 5Umberto I Hospital, Local Health Unit of Salerno, Salerno. m.gambacorta@aslsalerno.it. 6University Hospital of Naples "Federico II", Department of Public Health, Naples. ing.improta@gmail.com. 7Reykjavík University, Institute for Biomedical and Neural Engineering, Reykjavík, Iceland; Landspítali Hospital, Department of Science, Reykjavík. paologar@landspitali.is. (PagePress, 2021-03-09)
      The purpose of this study is to use Health Technology Assessment (HTA) through the Six Sigma (SS) and DMAIC (Define, Measure, Analyse, Improve, Control) problem-solving strategies for comparing cemented and uncemented prostheses in terms of the costs incurred for Total hip arthroplasty (THA) and the length of hospital stay (LOS). Multinomial logistic regression analysis for modelling the data was also performed. Quantitative parameters extracted from gait analysis, electromyography and computed tomography images were used to compare the approaches, but the analysis did not show statistical significance. The variables regarding costs were studied with the Mann-Whitney and Kruskal-Wallis tests. No statistically significant difference between cemented and uncemented prosthesis for the total cost of LOS was found, but the cost of the surgeon had an influence on the overall expenses, affecting the cemented prosthetic approach. The material costs of surgery for the uncemented prosthesis and the cost of theatre of surgery for the cemented prosthesis were the most influential. Multinomial logistic regression identified the Vastus Lateralis variable as statistically significant. The overall accuracy of the model is 93.0%. The use of SS and DMAIC cycle as tools of HTA proved that the cemented and uncemented approaches for THA have similar costs and LOSy.
    • Diffuse idiopathic skeletal hyperostosis in elderly Icelanders and its association with the metabolic syndrome: the AGES-Reykjavik Study.

      Auðunsson, A B; Elíasson, G J; Steingrímsson, E; Aspelund, T; Sigurdsson, S; Launer, L; Gudnason, V; Jonsson, H; 1Department of Radiology, Landspitali University Hospital, Reykjavík, Iceland. 2Department of Radiology, Domus Medica, Reykjavík, Iceland. 3Icelandic Heart Association, Kopavogur, Iceland. 4Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 5National Institute on Aging (NIA), National Institutes of Health (NIH), Bethesda, MD, USA. 6Department of Rheumatology, Landspitali University Hospital, Reykjavík, Iceland. (Taylor & Francis, 2021-03-07)
      Objective: To describe the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in a large population-based study of elderly Icelanders, with particular reference to weight-related factors and the metabolic syndrome.Method: The study population comprised 5321 participants aged 68-96 years (2276 males, mean ± sd age 76 ± 5 , and 3045 females, age 77 ± 6) from the AGES-Reykjavik Study. DISH diagnosis was based on computed tomography (CT) scans, and interpreted strictly by the Resnick criteria and additional suggestions for CT interpretation by Oudkerk et al. Radiology readings were taken by a radiology resident and sample readings by two experienced radiologists.Results: A diagnosis of DISH was made in 13.7% of males and 2.8% of females. There was no association with age, but a strong association was seen with the metabolic syndrome [odds ratio (OR) 2.12, 95% confidence interval (CI) 1.69-2.64, p = 3.9 × 10-11]. Among the components of the metabolic syndrome, the association with DISH was significant for the insulin resistance criterion (OR 1.66, 95% CI 1.32-2.01, p < 0.001) and the body mass index (BMI) criterion (OR 2.16, 95% CI 1.70-2.74, p < 0.001). Other weight-related variables (midlife BMI, weight, and abdominal circumference) showed similar associations.Conclusions: This study, which to our knowledge is the largest published study on the prevalence of DISH, shows an association with the metabolic syndrome, particularly with the insulin resistance and BMI criteria. This is analogous with previous reports linking DISH with metabolic causes. In this age category, we did not observe any increase in prevalence with age.
    • Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010.

      Loeber, J Gerard; Platis, Dimitris; Zetterström, Rolf H; Almashanu, Shlomo; Boemer, François; Bonham, James R; Borde, Patricia; Brincat, Ian; Cheillan, David; Dekkers, Eugenie; et al. (MDPI, 2021-03-05)
      Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together. Keywords: ISNS; International Society for Neonatal Screening; congenital endocrine disorders; congenital metabolic disorders; dried blood spot screening; neonatal screening; newborn screening; public health; rare diseases.
    • Effects of intensive upright mobilisation on outcomes of mechanically ventilated patients in the intensive care unit: a randomised controlled trial with 12-months follow-up

      Amundadottir, Olof R.; Jónasdóttir, Rannveig J.; Sigvaldason, Kristinn; Gunnsteinsdottir, Ester; Haraldsdottir, Brynja; Sveinsson, Thorarinn; Sigurdsson, Gisli H.; Dean, Elizabeth; a School of Health Sciences, University of Iceland, Reykjavik, Iceland b Department of Physiotherapy, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland c Department of Anaesthesiology and Intensive Care Medicine, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland d Department of Physical Therapy, Faculty of Medicine, The University of British Columbia, Vancouver, Canada (Taylor & Francis, 2021-03-04)
      Objective: To examine effects of intensive upright mobilisation on short- and long-term outcomes in critically ill mechanically ventilated patients. Methods: A randomised controlled trial compared patient outcomes after intensive twice-daily (n = 29) or daily mobilisation (n = 21). Patients in the intensive care unit (ICU), mechanically ventilated for over 48 hours, were randomly assigned to one of the two groups. Outcomes were duration of mechanical ventilation, ICU and hospital lengths of stay; health-related quality of life and physical function. Results: The twice-daily mobilisation group began upright mobilisation on day seven of ICU stay, and were mobilised upright on 31% of ICU days compared with the daily mobilisation group, who began upright mobilisation on day eight (p >= .05), and mobilised upright on 22% of ICU days (p = .03). No difference between groups was observed for any variable of interest across time-points over one year. Conclusions: The intensive twice-daily mobilisation group neither started upright mobilisation early nor yielded superior short- or long-term outcomes compared to the daily mobilisation group. Both groups showed poor physical health-related quality of life and exercise capacity one year after ICU discharge. Our findings support the need for targeted and tailored upright mobilisation in the ICU and after discharge.
    • How do we use biologics in rheumatoid arthritis patients with a history of malignancy? An assessment of treatment patterns using Scandinavian registers.

      Chatzidionysiou, Katerina; Delcoigne, Bénédicte; Frisell, Thomas; Hetland, Merete L; Glintborg, Bente; Dreyer, Lene; Cordtz, René; Zobbe, Kristian; Nordström, Dan; Trokovic, Nina; et al. (BMJ Publishing Group, 2021-03)