[Cancer registration in Iceland for 70 years - incidence, mortality and survival].

INTRODUCTION: The Icelandic Cancer Registry (ICR) was founded seventy years ago by the Icelandic Cancer Society. In 2007 the ICR became one of the health registers of the Directorate of Health. In this paper we present cancer incidence, mortality, and survival in Iceland over 70 years. MATERIAL AND METHODS: The ICR receives information on cancer diagnoses from histopathological laboratories, the Hospital Discharge Registry and the Cause of Death Registry. Iceland participates in the Nordic cancer database NORDCAN. Because of the small population size, random variation in numbers is very prominent. Therefore, data from ICR are published as five-year averages. RESULTS: For all malignancies combined, age-standardized incidence (ASI) in men rose steadily until around 15 years ago when a decline started. This is in line with prostate- and lung cancer incidence trends. In women, the ASI was lower than in men, but it is still on the rise despite declining lung cancer incidence. ASI for breast cancer, the most common cancer in women, is increasing. Simultaneously, cancer mortality for both sexes has declined in recent years and cancer survival is improving. CONCLUSIONS: Population-based cancer registration for over 70 years makes it possible to monitor the epidemiology of cancer in Iceland and compare with other countries. The changes in trends in ASI are in line with changes of cancer risk factors and diagnostic policy. The decline in cancer mortality and improvement in survival reflects advances in cancer treatment as well as effects of early detection and prevention.

[Perioperative stroke after aortic valve replacement for aortic stenosis - incidence, risk factors and short-term outcome].

INTRODUCTION: One of the most serious complications of surgical aortic valve replacement (SAVR) is stroke that can result in increased rates of complications, morbidity and mortality postoperatively. The aim of this study was to investigate incidence, risk factors and short-term outcome in a well defined cohort of SAVR-patients. MATERIALS AND METHOD: A retrospective study on 740 consecutive aortic stenosis patients who underwent SAVR in Iceland 2002-2019. Patients with stroke were compared with non-stroke patients; including preoperative risk factors of cardiovascular disease, echocardiogram-results, rate of early postoperative complications other than stroke and 30 day mortality. RESULTS: Mean age was 71 yrs (34% females) with 57% of the patients receiving stented bioprosthesis, 31% a stentless Freestyle®-valve and 12% a mechanical valve. Mean EuroSCORE-II was 3.6, with a maximum preop-gradient of 70 mmHg and an estimated valvular area of 0.73 cm2. Thirteen (1.8%) patients were diagnosed with stroke where hemiplegia (n=9), loss of consciousness (n=3) and/or aphasia (n=4) were the most common presenting symptoms. In 70% of cases the neurological symptoms resolved or disappeared in the first weeks and months after surgery. Only one patient out of 13 died within 30-days (7.7%). Stroke-patients had significantly lower BMI than non-stroke patients, but other risk factors of cardiovascular diseases, intraoperative factors or the rate of other severe postoperative complications than stroke were similar between groups. Total length of stay was 14 days vs. 10 days median, including 2 vs. 1 days in the ICU, in the stroke and non-stroke-groups, respectively. CONCLUSIONS: The rate of stroke after SAVR was low (1.8%) and in line with other similar studies. Although a severe complication, most patients with perioperative stroke survived 30 days postoperatively and in majority of cases neurological symptoms recovered.

An epidemiological and clinicopathological study of type 1 vs. type 2 morphological subtypes of papillary renal cell carcinoma- results from a nation-wide study covering 50 years in Iceland.

INTRODUCTION: Papillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10-15% of cases. Traditionally, pRCC is divided into type 1 and type 2, although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period. MATERIALS AND METHODS: A Population based retrospective study including consecutive cases of RCC in Iceland from 1971-2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan-Meier method and Cox regression were used for outcome analysis. RESULTS: A total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p < 0.001). Age standardized cancer specific mortality (ASCSM) of pRCC was 0.6/100.000 and 0.19/100.000 for males and females, respectively. The annual average increase in ASI was 3.6% for type 1 pRCC, but the ASI for type 2 pRCC and ASCSM for both subtypes did not change significantly. Male to female ratio was 4.4 for type 1 pRCC and 2.3 for type 2. The average tumor size for type 1 and 2 was 58.8 and 73.7 mm, respectively. Metastasis at diagnosis was found in 8.7% in the type 1 pRCC, compared to 30.0% of patients with type 2 pRCC (p < 0.001). Estimated 5-year cancer-specific survival (CSS) were 94.4%, 80.7%, and 69.3% for chRCC, pRCC and ccRCC, respectively (p < 0.001). For the pRCC subtypes, type 1 was associated with better 5-year CSS than type 2 (86.3% vs. 66.0%, p < 0.001), although this difference was not significant after adjusting for cancer stage and grading. CONCLUSIONS: pRCC histology was slightly less common in Iceland than in other countries. Males are more than three times more likely to be diagnosed with pRCC, compared to other RCC histologies. The subtype of pRCC was not found to be an independent risk factor for worse survival, and as suggested by the most recent WHO Classification of Urinary Tumors, grade and TNM-stage seem to be the most important factors for estimation of survival for pRCC patients.

TNM stage in the Nordic Cancer Registries 2004-2016: Registration and availability.

BACKGROUND AND PURPOSE: Stage at cancer diagnosis is an important predictor of cancer survival. TNM stage is constructed for anatomic solid cancer diagnoses from tumor size (T), nodal spread (N) and distant metastasis (M) and categorized in groups 0-I, II, II and IV. TNM stage is imperative in cancer diagnosis, management and control, and of high value in cancer surveillance, for example, monitoring of stage distributions. This study yields an overview of TNM availability and trends in stage distribution in the Nordic countries for future use in monitoring and epidemiologic studies. MATERIAL AND METHODS: TNM information was acquired from the cancer registries in Denmark, Norway, Sweden, and Iceland during 2004-2016 for 26 cancer sites in the three former countries and four in Iceland. We studied availability, comparability, and distribution of TNM stage in three periods: 2004-2008, 2009-2013, and 2014-2016, applying a previously validated algorithm of 'N0M0 for NXMX'. For cancers of colon, rectum, lung, breast, and kidney, we examined TNM stage-specific 1-year relative survival to evaluate the quality in registration of TNM between countries. RESULTS: Denmark, Sweden, and Iceland exhibited available TNM stage proportions of 75-95% while proportions were lower in Norway. Proportions increased in Sweden over time but decreased in Denmark. One-year relative survival differed substantially more between TNM stages than between countries emphasizing that TNM stage is an important predictor for survival and that stage recording is performed similarly in the Nordic countries. INTERPRETATION: Assessment and registration of TNM stage is an imperative tool in evaluations of trends in cancer survival between the Nordic countries.

Evaluating screening for autism spectrum disorder using cluster randomization.

We evaluated the rate of autism spectrum disorder (ASD) in a group invited to a screening program compared to the rates in two groups who received usual care. The population eligible for screening was all children in Iceland registered for their 30-month well-child visits at primary healthcare centers (PHCs) from March 1, 2016, to October 31, 2017 (N = 7173). The PHCs in the capital area of Reykjavik were the units of cluster randomization. Nine PHCs were selected for intervention (invited group), while eight PHCs received usual care (control group 1). PHCs outside the capital area were without randomization (control group 2). An interdisciplinary team, including a pediatrician contributing with physical and neurological examination, a psychologist evaluating autism symptoms using a diagnostic instrument, and a social worker interviewing the parents, reached a consensus on the clinical diagnosis of ASD according to the ICD-10 diagnostic system. Children in the population were followed up for at least two years and 119 cases were identified. The overall cumulative incidence of ASD was 1.66 (95% confidence interval (CI): 1.37, 1.99). In the invited group the incidence rate was 2.13 (95% CI: 1.60, 2.78); in control group 1, the rate was 1.83 (95% CI: 1.31, 2.50); and in control group 2, the rate was 1.02 (95% CI: 0.66, 1.50). Although the rate of ASD was higher in the invited group than in the control groups, the wide confidence intervals prevented us from concluding definitively that the screening detected ASD more readily than usual care.

Childbirth experiences in women with polycystic ovary syndrome: A cohort study.

INTRODUCTION: Women with polycystic ovary syndrome (PCOS) have more pregnancy complications like gestational diabetes, hypertension, and preterm labor than other women. Metformin has been used in an attempt to improve pregnancy outcomes. Our study aims to explore childbirth experiences in women with PCOS compared with a reference population. It also explores the potential influence of metformin, obesity, pregnancy complications, and the duration and mode of birth on childbirth experiences. MATERIAL AND METHODS: This study is a cohort study combining data from two randomized trials conducted in Norway, Sweden and Iceland. The PregMet2 study (ClinicalTrials.gov, NCT01587378) investigated the use of metformin vs. placebo in pregnant women with PCOS. The Labour Progression Study (ClinicalTrials.gov, NCT02221427) compared the WHO partograph to Zhang's guidelines for progression of labor and were used as the reference population. A total of 365 women with PCOS and 3604 reference women were included. Both studies used the Childbirth Experience Questionnaire (CEQ). Main outcome measures were total CEQ score and four domain scores. The CEQ scores were compared using Mann-Whitney U test for women in Robson group 1 with PCOS (n = 131) and reference women (n = 3604). CEQ scores were also compared between metformin-treated (n = 180) and placebo-treated (n = 185) women with PCOS, and for different subgroups of women with PCOS. RESULTS: There was no difference in total CEQ score between women with PCOS and reference women-Wilcoxon-Mann-Whitney (WMW)-odds 0.96 (95% confidence interval [CI] 0.78-1.17). We detected no difference in CEQ scores between the metformin- and placebo-treated women with PCOS (WMW-odds 1.13, 95% CI 0.89-1.43). Complications in pregnancy did not affect CEQ (WMW-odds 1, 95% CI 0.76-1.31). Higher body mass index (WMW-odds 0.75, 95% CI 0.58-0.96), longer duration of labor (WMW-odds 0.69, 95% CI 0.49-0.96), and cesarean section (WMW-odds 0.29, 95% CI 0.2-0.42) were associated with lower CEQ scores in women with PCOS. CONCLUSIONS: Women with PCOS experience childbirth similarly to the reference women. Metformin did not influence childbirth experience in women with PCOS, neither did pregnancy complications. Obesity, long duration of labor or cesarean section had a negative impact on childbirth experience.

[Retropharyngeal manifestation of T-cell-rich B-cell lymphoma in a 7-year-old Icelandic gelding]. / Retropharyngeale Manifestation eines T-Zell-reichen B-Zell-Lymphoms bei einem 7-jährigen Isländerwallach.

A 7-year-old Icelandic gelding was presented with acute severe dyspnea of one day duration and purulent nasal discharge that had been present for 6 weeks. Clinically, the initial examination focused on severe enlargement of the mandibular and retropharyngeal lymph nodes as well as a mixed dyspnea.The diagnosis of a malignant lymphoma was evident following laboratory diagnostics, endoscopy, and cytological examination of a fine needle aspiration of a mandibular lymph node. The gelding was euthanized due to the poor prognosis and a significantly disturbed general condition. Pathohistological examination revealed a multicentric T-cell-rich B-cell lymphoma.

Respiratory symptoms, exacerbations and sleep disturbances are more common among participants with asthma and chronic airflow limitation: an epidemiological study in Estonia, Iceland and Sweden.

BACKGROUND: Chronic airflow limitation (CAL) is a hallmark of chronic obstructive pulmonary disease but is also present in some patients with asthma. We investigated respiratory symptoms, sleep and health status of participants with and without CAL with particular emphasis on concurrent asthma using data from adult populations in Iceland, Estonia and Sweden investigated within the Burden of Obstructive Lung Disease study. METHODS: All participants underwent spirometry with measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) before and after bronchodilation. CAL was defined as postbronchodilator FEV1/FVC below the lower limit of normal. IgE-sensitisation and serum concentrations of eosinophil-derived neurotoxin (S-EDN) were assessed in a subsample. The participants were divided into four groups: no self-reported doctor's diagnosed asthma or CAL, asthma without CAL, CAL without asthma and asthma and CAL: χ2 test and analysis of variance were used in bivariable analyses and logistic and linear regression when analysing the independent association between respiratory symptoms, exacerbations, sleep-related symptoms and health status towards CAL, adjusting for centre, age, sex, body mass index, smoking history and educational level. RESULTS: Among the 1918 participants, 190 (9.9%) had asthma without CAL, 127 (6.6%) had CAL without asthma and 50 (2.6%) had CAL with asthma. Having asthma with CAL was associated with symptoms such as wheeze (adjusted OR (aOR) 6.53 (95% CI 3.53 to 12.1), exacerbations (aOR 12.8 (95% CI 6.97 to 23.6), difficulties initiating sleep (aOR 2.82 (95% CI 1.45 to 5.48), nocturnal gastro-oesophageal reflux (aOR 3.98 (95% CI 1.79 to 8.82)) as well as lower physical health status. In these analyses, those with no asthma and no CAL were the reference group. The prevalence of IgE-sensitisation was highest in both asthma groups, which also had higher levels of S-EDN. CONCLUSION: Individuals with self-reported asthma with CAL suffer from a higher burden of respiratory and sleep-related symptoms, higher exacerbation rates and lower health status when compared with participants with asthma alone or CAL alone.

[Lower Limb Amputations in Patients with Peripheral Arterial Disease and/or Diabetes in Iceland 2010-2019; revascularisation, comorbidities and risk factors].

INTRODUCTION: No recent studies exist on lower extremity amputations (LLAs) in Iceland. The aim of this study was to investigate LLA incidence in Iceland 2010-2019 and preceding procedures in amputations induced by peripheral arterial disease (PAD) and diabetes mellitus (DM). MATERIAL AND METHODS: Retrospective study on clinical records of all patients (>18 years) who underwent LLA in Iceland's two main hospitals during 2010-2019. Patients were excluded if LLA was performed for reasons other than DM and/or PAD. Symptoms, medication and circulation assessment were recorded from first hospital visit due to symptoms, and prior to the last LLA, respectively. Previous arterial surgeries and amputations were also recorded. RESULTS: A total of 167 patients underwent LLA. Thereof, 134 (77 ± 11 years, 93 men and 41 woman) due to DM and/or PAD. The LLA-rate due to those diseases increased from 4.1/100,000 inhabitants in 2010-2013 to 6.7/100,000 in 2016-2019 (p=0,04). Risk factors were mainly hypertension, 84%, and smoking, 69%. Chronic limb-threatening ischemia induced 71% of first hospital visits. Revascularisations were performed (66% endovascular) in 101 patients. Non-diabetic patients were 52% and had statins less frequently prescribed than DM patients (26:45, p<0.001). CONCLUSION: DM and/or PAD are the leading causes of LLA in Iceland. Amputation rate increased during the period but is low in an international context. Amputation is most often preceded by arterial surgery. DM is present in almost half of cases, similar or less than in most other countries. Opportunities for improved prevention should aim on earlier diagnosis and preventive treatment of non-diabetic individuals with PAD.

Uptake and availability of new outpatient cancer medicines in 2010-2021 in Nordic countries - survey of competent authorities.

BACKGROUND: Nordic countries excel in cancer care, but studies on uptake, costs, or managed entry agreements of cancer medicines have not been conducted recently. The aim of this study was to examine the uptake and availability of orally administered new cancer medicines in Nordic countries. Orally administered cancer medicines enable and are used in the community as part of outpatient care. Firstly, we studied the distribution, costs and adoption of managed entry agreements of these medicines, and secondly, uptake of and managed entry agreements for cancer medicines used in outpatient care that were granted marketing authorization in Europe in 2010-2021. METHODS: An E-mail survey of competent authorities, meaning pharmaceutical service organizers, payers or other government or non-government actors developing pharmaceutical service operations, in Denmark, Finland, Iceland, Norway, and Sweden in April-June 2022. The data were analysed using frequencies and percentages for descriptive analysis. RESULTS: The distribution of cancer medicines has similarities in Finland, Iceland, Norway, and Sweden, where cancer medicines can be distributed both via hospitals or hospital pharmacies for inpatient use, and via community pharmacies for outpatient use. In Denmark, cancer medicines are predominantly distributed via publicly funded hospitals. In all countries that provided data on the costs, the costs of cancer medicines had notably gone up from 2010 to 2021. The number of reimbursable medicines out of new cancer medicines varied from 36 products in Denmark and Iceland to 51 products in Sweden, out of 67 studied products. Managed entry agreements, often with confidential discounts, were in use in all Nordic countries. The number of agreements and the cancer types for which agreements were most often made varied from three agreements made in Iceland to 35 agreements made in Finland, out of 67 studied products. Average days from authorization to reimbursement of new cancer medicines varied from an average of 416 to 895 days. CONCLUSIONS: Nordic countries share similar characteristics but also differ in terms of the details in distribution, adopted managed entry agreements, market entry, and availability of new orally administered cancer medicines used in the outpatient care. The costs of cancer medicines have increased in all Nordic countries during the last decade. Due to differences in health care and because orally administered cancer medicines can be dispensed at community and hospital pharmacies in all studied countries other than Denmark, the number of reimbursable medicines and managed entry agreements vary between countries. However, Nordic countries show good agreement for 2010 to 2021 in entry and reimbursement decisions of novel cancer medicines.

Total removal of the fourth metacarpal bone in an Icelandic horse.

Fractures of the splint bones are the most common fractures in horses. Various treatment options for splint bone fractures (MC/MT II and IV), including conservative and surgical management, have been described. This report describes an acute splint bone fracture due to external trauma in a 17-year-old Icelandic mare. The fracture was diagnosed as an open multifragment fracture of the proximal third of the fourth metacarpal bone (MCIV) in the right front limb. Surgery was performed with the horse under general anaesthesia. The distal fragments were removed, and the distal part of the proximal remnant splint bone was cut with an osteotome. During the postoperative period, a routine x-ray-control two days after surgery showed a dislocated fracture of the remaining proximal part of the fourth metacarpal bone. In a second surgery, the proximal part of MCIV was entirely removed. After a reconvalescence period of 5 month, the horse reached her previous level of performance as a leisure horse. The mare is still free of lameness 6 years after the incident.

[Breastfeeding in Iceland: Changes in prevalence and duration over a century].

INTRODUCTION: Worldwide, the health-promoting effects of breastfeeding on children and their mothers are indisputable. The frequency and duration of breastfeeding varies greatly internationally but studies on prevalence and influencing factors of breastfeeding in Iceland are scanty and the published ones deal with small groups. The aim of this research is to describe the epidemiology of breastfeeding duration and its influencing factors in Iceland among a large cohort in a whole population over almost one century. MATERIAL AND METHODS: This is a historical cohort study, using data from The Cancer Detection Clinic Cohort of The Icelandic Cancer Society, collected retrospectively by questionnaires during the years 1964-2008. The data consisted of mothers´ reported information on breastfeeding of their 81,889 children, 36,537 first-borns and 45,352 younger siblings. The frequency and duration of breastfeeding was calculated and the effects of the following exposure variables were assessed: Maternal age, BMI (N=4950, data collected 1979-2008) and smoking (N=32.087, data collected 1995-2008), the child's year of birth and its order in the sibling group. RESULTS: The children were born in the period of 1917-2008. In the late 1970s, the average duration of breastfeeding began to increase, in all age groups of mothers, increasing rapidly from 3 months to 7-8 months. At about the same time, the breastfeeding duration increased depending on the birth order of the children, younger children were breastfed for longer than their older siblings. Women with normal weight (BMI 18.5 to 24.9) breastfed their babies the longest, while obese women breastfed the shortest. Women with any history of smoking reported shorter duration of breastfeeding than women who had never smoked. CONCLUSION: The increase in the average duration of breastfeeding in Iceland a few decades ago is in accordance with the information in the World Health Organization's database from European countries 1975-2000, where the Nordic countries and most Northern European countries promoted breastfeeding at a similar time. High BMI and maternal smoking are important variables when studying breastfeeding and this study indicates their negative association with the duration of breastfeeding.

Actionable Genotypes and Their Association with Life Span in Iceland.

BACKGROUND: In 2021, the American College of Medical Genetics and Genomics (ACMG) recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available. Evaluations of the association of actionable genotypes in these genes with life span are currently lacking. METHODS: We assessed the prevalence of coding and splice variants in genes on the ACMG Secondary Findings, version 3.0 (ACMG SF v3.0), list in the genomes of 57,933 Icelanders. We assigned pathogenicity to all reviewed variants using reported evidence in the ClinVar database, the frequency of variants, and their associations with disease to create a manually curated set of actionable genotypes (variants). We assessed the relationship between these genotypes and life span and further examined the specific causes of death among carriers. RESULTS: Through manual curation of 4405 sequence variants in the ACMG SF v3.0 genes, we identified 235 actionable genotypes in 53 genes. Of the 57,933 participants, 2306 (4.0%) carried at least one actionable genotype. We found shorter median survival among persons carrying actionable genotypes than among noncarriers. Specifically, we found that carrying an actionable genotype in a cancer gene was associated with survival that was 3 years shorter than that among noncarriers, with causes of death among carriers attributed primarily to cancer-related conditions. Furthermore, we found evidence of association between carrying an actionable genotype in certain genes in the cardiovascular disease group and a reduced life span. CONCLUSIONS: On the basis of the ACMG SF v3.0 guidelines, we found that approximately 1 in 25 Icelanders carried an actionable genotype and that carrying such a genotype was associated with a reduced life span. (Funded by deCODE Genetics-Amgen.).

Psychobiological stress response to a lung cancer diagnosis: a prospective study of patients in Iceland and Sweden.

BACKGROUND: A diagnostic work-up leading to a lung cancer diagnosis is a severely stressful experience that may impact tumor progression. Yet, prospective data are scarce on psychological and biological components of stress at the time of lung cancer diagnosis. The aim of this study was to assess pre-to-post diagnosis change in psychological distress and urinary excretion of catecholamines in patients with suspected lung cancer. METHODS: Participants were 167 patients within the LUCASS study, recruited at referral for suspected lung cancer to University Hospitals in Iceland and Sweden. Patients completed questionnaires on perceived distress (Hospital Anxiety and Depression Scale, HADS) before and after diagnosis of lung cancer or a non-malignant origin. A subpopulation of 85 patients also provided overnight urine for catecholamine analysis before and at a median of 24 days after diagnosis but before treatment. RESULTS: A lung cancer diagnosis was confirmed in 123 (73.7%) patients, with a mean age of 70.1 years. Patients diagnosed with lung cancer experienced a post-diagnosis increase in psychological distress (p = 0.010), while patients with non-malignant lung pathology showed a reduction in distress (p = 0.070). Both urinary epinephrine (p = 0.001) and norepinephrine (p = 0.032) levels were higher before the diagnosis among patients eventually diagnosed with lung cancer compared to those with non-malignant lung pathology. We observed indications of associations between pre-to-post diagnosis changes in perceived distress and changes in urinary catecholamine levels. CONCLUSION: Receiving a lung cancer diagnosis is associated with an increase in psychological distress, while elevated catecholamine levels are evident already before lung cancer diagnosis.

Evaluation of Large-Scale Proteomics for Prediction of Cardiovascular Events.

Importance: Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain. Objective: To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations. Design, Setting, and Participants: The primary analysis was a retrospective study of primary events among 13 540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018). We also analyzed a secondary event population from a randomized, double-blind lipid-lowering clinical trial (2013-2016), consisting of individuals with stable ASCVD receiving statin therapy and for whom proteomic data were available for 6791 individuals. Exposures: Protein risk scores (based on 4963 plasma protein levels and developed in a training set in the primary event population); polygenic risk scores for coronary artery disease and stroke; and clinical risk factors that included age, sex, statin use, hypertension treatment, type 2 diabetes, body mass index, and smoking status at the time of plasma sampling. Main Outcomes and Measures: Outcomes were composites of myocardial infarction, stroke, and coronary heart disease death or cardiovascular death. Performance was evaluated using Cox survival models and measures of discrimination and reclassification that accounted for the competing risk of non-ASCVD death. Results: In the primary event population test set (4018 individuals [59.0% women]; 465 events; median follow-up, 15.8 years), the protein risk score had a hazard ratio (HR) of 1.93 per SD (95% CI, 1.75 to 2.13). Addition of protein risk score and polygenic risk scores significantly increased the C index when added to a clinical risk factor model (C index change, 0.022 [95% CI, 0.007 to 0.038]). Addition of the protein risk score alone to a clinical risk factor model also led to a significantly increased C index (difference, 0.014 [95% CI, 0.002 to 0.028]). Among White individuals in the secondary event population (6307 participants; 432 events; median follow-up, 2.2 years), the protein risk score had an HR of 1.62 per SD (95% CI, 1.48 to 1.79) and significantly increased C index when added to a clinical risk factor model (C index change, 0.026 [95% CI, 0.011 to 0.042]). The protein risk score was significantly associated with major adverse cardiovascular events among individuals of African and Asian ancestries in the secondary event population. Conclusions and Relevance: A protein risk score was significantly associated with ASCVD events in primary and secondary event populations. When added to clinical risk factors, the protein risk score and polygenic risk score both provided statistically significant but modest improvement in discrimination.

Diversity under a magnifier lens: the case of Typhlotanaidae (Crustacea: Tanaidacea) in the N Atlantic.

Research focusing on 'stout-bodied' typhlotanaids collected from several sites around Iceland and adjacent N Atlantic region has resulted in the description of 15 species new to science, as well as the creation of eight new genera. Typhlotanais eximius Hansen, 1913 is redescribed and transferred to a new genus, while Typhlotanais crassus and Peraeospinosus adipatus are transferred to the genus Larsenotanais. The morphological and the molecular data were combined to consolidate and confirm the validity of the results obtained from both approaches. The polyphyletic nature of the Typhlotanaidae and its serious of its taxonomic diversity are emphasized, although molecular analysis reveals that the 'stout-bodied' Typhlotanaidae form monophyletic clade. Depth and temperature are identified as the main environmental parameters determining the distribution of this group of Typhlotanaidae. Several species are clearly associated with the shelf and upper bathyal of Iceland. The Greenland-Iceland-Faroe Ridge is shown to be a distinct zoogeographical barrier for typhlotanaids inhabiting the deeper slope and abyssal regions around Iceland.

Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts: results from the population-based iStopMM study.

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with regards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumatological disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.

Cystic echinococcosis in Iceland: a brief history and genetic analysis of a 46-year-old Echinococcus isolate collected prior to the eradication of this zoonotic disease.

Cystic echinococcosis (CE) is considered the most severe parasitic disease that ever affected the human population in Iceland. Before the start of eradication campaign in the 1860s, Iceland was a country with very high prevalence of human CE, with approximately every fifth person infected. Eradication of CE from Iceland by 1979 was a huge success story and served as a leading example for other countries on how to combat such a severe One Health problem. However, there is no genetic information on Echinococcus parasites before eradication. Here, we reveal the genetic identity for one of the last Echinococcus isolates in Iceland, obtained from a sheep 46 years ago (1977). We sequenced a large portion of the mitochondrial genome (8141 bp) and identified the isolate as Echinococcus granulosus sensu stricto genotype G1. As G1 is known to be highly infective genotype to humans, it may partly explain why such a large proportion of human population in Iceland was infected at a time . The study demonstrates that decades-old samples hold significant potential to uncover genetic identities of parasites in the past.

Preliminary impact of the adoption of the Icelandic Prevention Model in Tarragona City, 2015-2019: A repeated cross-sectional study.

Background: There is a great need for effective primary prevention intervention strategies to reduce and delay onset of adolescent substance use. The Icelandic Prevention Model (IPM) showed great success in Iceland over the past twenty plus years, however, evidence for the transferability of model is still somewhat limited. Using data collected in Tarragona during regional efforts to begin adoption of the IPM in Catalonia, this study tested the transferability and stability of the core risk and protective factor assumptions of the IPM overtime and examined trends of lifetime smoking, e-cigarette-use, alcohol-use, intoxication, and cannabis-use within the same time period. Methods: This study includes responses from 15- to 16-years-olds from two region-wide samples taken in 2015 and 2019 in Tarragona (N = 2,867). Survey questions assessed frequency of lifetime: smoking, e-cigarette-use, alcohol-use, intoxication, and cannabis-use, and the core model assumptions. Demographic data were also collected. Logistic regression models of main effects with and without time interaction were used to test assumptions and their stability across time. Chi-square tests and Wilcoxon-Mann-Whitney U tests were used to compare prevalence of substance use and mean scores of primary prevention variables respectively. Results: Lifetime: smoking (-7%, p < 0.001) and cannabis-use (-4%, p < 0.001) decreased, and e-cigarette-use increased (+33%, p < 0.001) in Tarragona. Lifetime intoxication (-7%, p < 0.001) decreased in a single zone exclusively. Most core model assumptions held in their hypothesised direction across time. The strongest positive association was observed between time spent with parents during weekends and reduced odds of lifetime smoking (OR: 0.62, 95%CI: 0.57-0.67) and the strongest negative association was observed between being outside after midnight and increased odds of lifetime intoxication (OR: 1.41, 95%CI: 1.32-1.51). Mean scores of primary prevention variables also changed disproportionately in Tarragona. Conclusion: This study confirms that the core IPM assumptions are similar in Tarragona as in Iceland and other contexts previously examined. They also indicate that prevalence of lifetime smoking, intoxication, and cannabis-use decreased disproportionately in Tarragona between 2015 and 2019 during the first phase of regional adoption of the model. Thus, targeting model assumptions represents a viable primary prevention strategy for communities that hope to reduce smoking, alcohol-use, intoxication, and cannabis-use among adolescents.

[Maternal death in Iceland 1976-2015].

INTRODUCTION: Maternal deaths are rare and an indirect measure of the societal framework surrounding pregnancy and childbirth. We surveyed and classified maternal mortality in Iceland using international guidelines, calculating changes over a 40-year period. MATERIAL AND METHODS: Information from Statistics Iceland on women aged 15-49 years who died in 1985-2015 were cross-checked against birth registration and hospital admission data to identify women who died in pregnancy or ≤42 and within 43-365 days from birth or termination of a pregnancy. Data for 1976-1984 were searched manually. Case records and autopsy reports were scrutinized. Deaths were classified as direct, indirect or coincidental and as early or late. RESULTS: Among 1600 women 48 died in pregnancy or within a year after pregnancy. Births totaled 172369 and overall maternal mortality was 27.8/100.000 births. Maternal mortality by World Health Organization criteria (direct/indirect ≤42 days) occurred in 14 instances giving a maternal mortality ratio (MMR) of 8.1/100.000. Rates lowered between the first and last 10-year periods, particularly initially followed by a lesser downward trend. Direct deaths were 6, indirect 20, coincidental 22 (accidents, diseases). Causes of direct deaths were severe preeclampsia, pulmonary embolism and choriocarcinoma. Underlying causes of indirect deaths included cancer, diabetes, brain/heart conditions and suicide. No deaths occurred from ectopic pregnancy, hemorrhage or anesthesia. CONCLUSIONS: Maternal mortality in Iceland is among the lowest reported. Women died because of the pregnancy, from worsening of underlying conditions or coincidentally. Risk groups require better support. Continued attention to adverse health connected to maternity is essential.