Population-based Study In Iceland Research Articles

Prior cancer and risk of monoclonal gammopathy of undetermined significance: a population-based study in Iceland and Sweden.

There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with higher prevalence or increased progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might therefore present a target population for MGUS screening. This two-part study is the first study to evaluate the relationship of MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS. Next, we evaluated the association of prior cancer and the progression of MGUS to MM and related disorders in a population-based cohort of 13,790 Swedish individuals with MGUS. A history of prior cancer was associated with a modest increase in the risk of MGUS (odds ratio (OR)= 1.10; 95% confidence interval (CI): 1.00-1.20). This excess risk was limited to prior cancers in the year preceding MGUS screening. A history of prior cancer associated with the progression of MGUS, except for myeloid malignancies which were associated with lower risk of progression (hazard ratio (HR)=0.37; 95%CI: 0.16-0.89; p=0.028). Our findings indicate that a prior cancer are not a significant aetiological factor in plasma cell disorders. The findings do not warrant MGUS screening or different management of MGUS in those with a prior cancer.

Nationwide study of sudden cardiac death among children and young adults in Iceland

Abstract Introduction Sudden cardiac death (SCD) in children and young adults is a devastating event. Ischemic heart disease is the predominant cause of sudden cardiac death in older persons. Whereas among persons 1–35 years of age, SCD is more often caused by structural heart disease or purely arrhythmogenic causes. In studies on SCD in the young up to 40% of all autopsies show no cardiac abnormalities. Which raises suspicion of underlying arrhythmogenic causes. Many of these arrhythmogenic causes of SCD have an underlying genetic basis and are inherited. Purpose In Iceland, the true impact of SCD in children and young adults is unknown. The aim of this investigation is to study the incidence and causes of SCD in persons aged 1–35 years in nationwide settings. Methods This is a nationwide retrospective population-based study in Iceland. All deaths in persons aged 12–35 years in 1974–2015 and all deaths in persons aged 1–12 years 2005–2015 were included. Death certificates, autopsy reports and medical records were reviewed to confirm SCD. Medical records were also reviewed for medical history and circumstances of death. Individuals that were resuscitated after cardiac arrest but died later in hospitals were included. Individuals that fulfilled the criteria of SUDEP (sudden unexpected death in epilepsy) were excluded from the study. Results We found 73 (68% male) cases of SCD, of which 64 (88%) were autopsied. The most common find in autopsy was structurally normal heart (16%), myocarditis (16%), hypertrophic cardiomyopathy (16%) and ischemic heart disease (16%). Death occurred during daily activities in 36% of cases, sleep in 27% cases and physical activities in 19% of cases. Incidence rate was 1.4 per 100.000 in 1–35 years old in the years 2005–2015 and 1.6 per 100.000 for 12–35 years old in the years 1974–2015. Conclusion Incidence of SCD in the young in Iceland is similar as for other nations. Post-mortem diagnoses are often difficult to establish. Because of the possibility of unrecognized underlying inherited cardiac disorder it is important to consider genetic analysis as a part of the post-mortem examination. Majority of SCD in the young occurred related to normal daily activities or during sleep or at rest. This raises many questions about the connections between any underlying cause of SCD and behaviour. It is important to discuss and study further the connection between sudden unexplained death in epilepsy (SUDEP) and SCD. SUDEP is most often unwitnessed events with cases found deceased in bed. SUDEP is characterized by an absence of any identifiable cause of death post-mortem, which can suggest underlying arrhythmogenic cause. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Adult cardiac surgery and the COVID-19 pandemic: Aggressive infection mitigation strategies are necessary in the operating room and surgical recovery

The COVID-19 pandemic necessitates aggressive infection mitigation strategies to reduce the risk to patients and healthcare providers. This document is intended to provide a framework for the adult cardiac surgeon to consider in this rapidly changing environment. Preoperative, intraoperative, and postoperative detailed protective measures are outlined. These are guidance recommendations during a pandemic surge to be used for all patients while local COVID-19 disease burden remains elevated.

Spread of SARS-CoV-2 in the Icelandic Population

BackgroundDuring the current worldwide pandemic, coronavirus disease 2019 (Covid-19) was first diagnosed in Iceland at the end of February. However, data are limited on how SARS-CoV-2, the virus that causes Covid-19, enters and spreads in a population.MethodsWe targeted testing to persons living in Iceland who were at high risk for infection (mainly those who were symptomatic, had recently traveled to high-risk countries, or had contact with infected persons). We also carried out population screening using two strategies: issuing an open invitation to 10,797 persons and sending random invitations to 2283 persons. We sequenced SARS-CoV-2 from 643 samples.ResultsAs of April 4, a total of 1221 of 9199 persons (13.3%) who were recruited for targeted testing had positive results for infection with SARS-CoV-2. Of those tested in the general population, 87 (0.8%) in the open-invitation screening and 13 (0.6%) in the random-population screening tested positive for the virus. In total, 6% of the population was screened. Most persons in the targeted-testing group who received positive tests early in the study had recently traveled internationally, in contrast to those who tested positive later in the study. Children under 10 years of age were less likely to receive a positive result than were persons 10 years of age or older, with percentages of 6.7% and 13.7%, respectively, for targeted testing; in the population screening, no child under 10 years of age had a positive result, as compared with 0.8% of those 10 years of age or older. Fewer females than males received positive results both in targeted testing (11.0% vs. 16.7%) and in population screening (0.6% vs. 0.9%). The haplotypes of the sequenced SARS-CoV-2 viruses were diverse and changed over time. The percentage of infected participants that was determined through population screening remained stable for the 20-day duration of screening.ConclusionsIn a population-based study in Iceland, children under 10 years of age and females had a lower incidence of SARS-CoV-2 infection than adolescents or adults and males. The proportion of infected persons identified through population screening did not change substantially during the screening period, which was consistent with a beneficial effect of containment efforts. (Funded by deCODE Genetics–Amgen.)

Suicide attempts and self-harm during a dramatic national economic transition: a population-based study in Iceland.

Macroeconomic downturns have been associated with increased suicide rates. This study examined potential changes in suicide attempts and self-harm in Iceland during a period of major economic transition (2003-12). Data were retrieved from the National University Hospital in Reykjavik (population size: 204.725), containing all ICD-10 diagnoses connected to potential suicidal behaviour. Poisson regression models were used to compare attendance rates before and after the 2008 economic collapse. During the study period, a total of 4537 attendances of 2816 individuals were recorded due to suicide attempts or self-harm. We noted a significant change in total attendance rates among men, characterized by an annual increase in attendance rate pre-collapse of 1.83 per 100.000 inhabitants and a decrease of 3.06 per 100.000 inhabitants post-collapse ( P = 0.0067). Such pattern was not observed among women. When restricting to first attendances only, we found a reduced incidence post-crisis among both men (RR: 0.85; 0.76-0.96) and women (RR: 0.86; 0.79-0.92). We further found 1% increase in unemployment rate and balance of trade to be associated with reduced attendance rates among men (RR: 0.84; 0.76-0.93 and RR: 0.81; 0.75-0.88, respectively) but not among women. These data suggest no overall increase in attendance rates due to suicide attempts or self-harm following the 2008 Icelandic economic collapse. In fact, a high-point in self-harm and suicide attempts was observed among men at the height of the economic boom and a decrease in new attendances among both men and women after the economic collapse.

Biliary tract malignancies: a population-based study on incidence, prognosis and management of patients

Background: Biliary tract malignancies are uncommon and few population-based studies are available.Methods: This nationwide population-based study in Iceland included all patients diagnosed with intra- and extrahepatic cholangiocarcinoma, gallbladder and ampullary cancer from 1984 to 2012. Patients were identified through the Icelandic Cancer Registry. Clinical information was obtained from patient records.Results: Overall 245 patients were identified: 38 had intrahepatic cholangiocarcinoma, 66 extrahepatic cholangiocarcinoma, 73 gallbladder cancer (GBC) and 68 ampullary cancer. Overall incidence for bile tract malignancies was 1–3 per 100,000 person-years and less than 1 by sub-type. The overall bile tract malignancies in males increased from 1.3 (95% CI 0.8–1.8) to 2.5 (1.9–3.1) per 100,000 inhabitants. The incidence of GBC among females decreased from 1.1 (0.7–1.5) to 0.5 (0.2–0.7). Surgery decreased for extrahepatic cholangiocarcinoma (56 to 23%, p = .027), ampullary cancer (80 to 48%, p = .03) and overall bile tract cancer (61 to 32%, p < .0001) but use of chemotherapy increased (4 to 32%, p < .0001). Five-year relative survival rates for men were 15% and 24% for women. No significant improvement was found in survival.Conclusions: Overall incidence of bile tract malignancies increased in males and GBC decreased in women. Long-term survival is poor and did not improve despite changes in treatment.

Incidence and Natural History of Idiopathic Chronic Inflammatory Demyelinating Polyneuropathy: A Population-Based Study in Iceland

Background and Aim: We report a population-based study conducted in Iceland to determine the incidence, clinical characteristics and prognosis of idiopathic chronic inflammatory demyelinating polyneuropathy (CIDP) during a 21-year period. Methods: Cases were identified from the records of all practicing neurologists in the country, the only neurology department in the country and both neurophysiology laboratories. All index cases met the 2010 European Federation of Neurological Societies/Peripheral Nerve Society criteria for CIDP. Results: Nineteen individuals fulfilled the diagnostic criteria during the study period. The average annual incidence was 0.3/100,000 (95% CI 0.04-2.47). There were 14 men (74%) in a gender ratio of 1:2.8. The mean age at diagnosis was 57 (range 19-81 years): women, 36 years and men, 63 years; p = 0.0006. The disease course was remitting-relapsing in 21% and chronic progressive or monophasic in 79%. The average length of follow-up was 6.9 years. The standardized mortality ratio for the 21-year study period was 0.9 (95% CI 0.3-2.2). Conclusion: We believe we have identified all diagnosed with CIDP in Iceland during a 21-year period. Many had no or only limited disease progression over the years and mortality is not increased compared with the general population.

Suicidal risk and sexual orientation in adolescence: a population-based study in Iceland.

Suicidality is an important public health problem, particularly among lesbian, gay, and bisexual (LGB) adolescents and young adults. The purpose of the present study is to compare the rate of suicide ideations and attempts among LGB adolescent to that of non-LGB adolescents in a population-based sample, and to identify important protective factors as well as risk factors Method: We used the Icelandic data set from the 2009/2010 Health Behaviour in School-aged Children (HBSC) study. The sample consisted of 3813 grade 10 Icelandic adolescents; 1876 girls and 1937 boys. The participants were asked about attraction and/or activity, as well as about suicidal ideation and/or attempts. The questionnaire also included various other items regarding health and lifestyle. LGB adolescents were five to six times more likely to have had frequent suicidal ideations. Factors that were associated with less suicide ideations and fewer attempts were easy communication and liking school. The LGB girls were six times more likely to have had frequent suicide attempts, whilst the LGB boys were 17 times more likely to have attempted suicide that often. No specific protective or risk factors were identified for suicidality in LGB adolescents other than bullying. Adolescents that had engaged in heterosexual activity and those that had LGB attraction had similarly heightened risk for suicidality, but sexually active LGB adolescents were far more likely to have suicidal ideations or to have attempted suicide.

Tall cell variant of papillary thyroid carcinoma: a population-based study in Iceland.

The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is an aggressive variant of PTC that is believed to have worse outcomes than classical PTC. The objective of this study was to investigate the incidence, survival, and disease recurrence of patients with TCV and compare them with other PTC in a whole population. Information on all thyroid carcinomas diagnosed in Iceland from 1990 to 2009 was obtained from the Icelandic Cancer Registry. PTC diagnosed postmortem was excluded. The date of diagnosis, sex, and age at diagnosis were registered. All histopathology material was re-evaluated, and papillary thyroid tumors classified as either TCV or other types of PTC. Tumors were classified as TCV if >50% of cells were tall (height > twice the width). TNM stage was determined for all the cases. Endpoints were thyroid cancer-specific death and thyroid cancer recurrence. Out of 376 patients diagnosed with PTC in the study period, 49 (13%) were classified as TCV. Patients with TCV were older (66 years vs. 49 years, p<0.001), more often had pT4 tumors (71% vs. 15%, p<0.001), had higher rates of nodal metastasis (51% vs. 22%, p<0.001), and more often distant metastasis (14% vs. 2%, p<0.001). The age-adjusted incidence of TCV for men was 0.5/100,000 [confidence interval (CI) 0.3-0.7] and for women 0.7/100,000 [CI 0.4-1.0] between 1990 and 2009. The five-year disease-specific survival for TCV was 83% [CI 68-91] compared to 98% [CI 96-99] for other PTC respectively (p<0.001). In multivariate analysis, TCV histology was an independent risk factor for recurrence (hazard ratio (HR) 3.18 [CI 1.48-6.84]) but not for disease specific survival (HR 1.86 [CI 0.77-4.73]). TCV comprises 13% of all diagnosed PTC in Iceland with an incidence of 0.5/100,000 for men and 0.7/100,000 for women. Patients diagnosed with TCV have worse five-year disease-specific survival than patients with other PTC. TCV histology is an independent risk factor for disease recurrence but not for disease-specific survival.

Incidence, Presentation, and Outcomes in Patients With Drug-Induced Liver Injury in the General Population of Iceland

Little is known about the incidence of drug-induced liver injury (DILI) in the general population. We investigated the incidence and the quantitative risk of DILI in a population-based cohort. We performed a prospective study and collected data from 96 individuals diagnosed with DILI in Iceland from 2010 through 2011 (54 women; median age, 55 y). Liver injury was defined based on levels of alanine aminotransferase that were more than 3-fold the upper limit of normal and/or alkaline phosphatase levels more than 2-fold the upper limit of normal. Patients with acetaminophen toxicity were excluded. Drug history and clinical outcome were analyzed. Causality was assessed using the Roussel Uclaf Causality Assessment Method. The patients were registered in prescription databases for outpatients and inpatients. The crude annual incidence rate of DILI was 19.1 (95% confidence interval [CI], 15.4-23.3) cases per 100,000 inhabitants. DILI was caused by a single prescription medication in 75% of cases, by dietary supplements in 16% of cases, and by multiple agents in 9% of cases. The most commonly implicated drugs were amoxicillin-clavulanate (21 of 96; 22%), diclofenac (6%), azathioprine (4%), infliximab (4%), and nitrofurantoin (4%). The median duration of therapy was 20 days (range, 8-77 days); 26 patients had jaundice (27%) and 22 patients were hospitalized (23%) for a median of 5 days (range, 2-8 days). Overall 35,252 patients received amoxicillin-clavulanate as outpatients, and DILI occurred in 1 of 2350 (43 of 100,000; 95% CI, 24-70). DILI also occurred in 1 of 9480 patients taking diclofenac (11 of 100,000; 95% CI, 4-24), 1 of 133 patients taking azathioprine (752 of 100,000; 95% CI, 205-1914), 1 of 148 patients taking infliximab (675 of 100,000; 95% CI, 184-718), and 1 of 1369 patients taking nitrofurantoin (73 of 100,000; 95% CI, 20-187). In a population-based study in Iceland, the incidence of DILI was the highest reported to date. Amoxicillin-clavulanate was the most commonly implicated agent. The highest risk of hepatotoxicity was associated with azathioprine and infliximab, but the actual number of cases attributed to these agents was small.

Paracetamol intoxications: a retrospective population-based study in Iceland

Objective. Paracetamol is the most common cause of acute liver failure (ALF) in many countries. Much data on paracetamol toxicity originate from liver transplant centers and tertiary referral institutions. The authors analyzed the population-based annual incidence of paracetamol overdoses and ALF, and described the risk factors for hepatotoxicity. Methods. A search was undertaken for the diagnosis of paracetamol overdoses in the diagnoses registry of the National University Hospital of Iceland from 2004 to 2009 serving a population of 219,249 inhabitants. Relevant information was collected from medical records. Results. A total of 1913 drug-related poisoning episodes were identified and reviewed, 352 (18%) involved paracetamol overdoses. The annual incidence of paracetamol overdoses declined from 30.0 (2004) to 16.0/100,000 per year (2009) (p < 0.05). The female/male ratio was 3.0 and the largest age group was 16–25 years. After the initial examination, 26% were discharged home. Hospitalized index visits were 182 with accidental overdoses constituting 16 (9%) with no gender difference. Compared with intentional overdose the accidental group had higher aminotransferases (p < 0.005). ALF occurred in 3.8% (7/182) of the index visits and the incidence was 0.7/100,000 per year. In the intentional group, 1.2% (2/163) developed ALF versus 25% (4/16) of the accidental group (p = 0.001). Only one patient died from ALF and none underwent liver transplantation. Conclusion. The annual incidence of paracetamol overdoses was high in this population-based study but declined. Young females with intentional overdose accounted for most of the cases, whereas accidental overdoses were more common in older patients. The occurrence of ALF was low and mostly associated with accidental overdose.

Molecular epidemiology of late recurrent candidaemia—a population-based study in Iceland

Candidaemia is associated with high patient mortality. Among those who survive an initial episode of candidaemia, the incidence of recurrent episodes has been incompletely defined. All patients in Iceland with candidaemia in 1980–2008 were identified, and clinical information was reviewed. Episodes of candidaemia in the same patient were considered to be separate if they occurred ≥1 month apart or were caused by different Candida species. The isolates were genotyped by using PCR fingerprinting, and antifungal susceptibility was determined. During the 29-year period, candidaemia was diagnosed in 307 patients in Iceland, 298 of whom (97.1%) had a single episode. Overall, 206 patients survived >1 month from the first episode and were therefore at risk of recurrence, yielding 1062 patient-years of observation in the survivors. Of those, nine (4.4%) later developed recurrent candidaemia. The median time between recurrences was 6 months (range, <1 month to 14 years). Patients with late recurrences were younger (p 0.012) and more likely to have underlying gastrointestinal diseases than patients with single episodes (55.6% vs. 18.5%, respectively; p 0.017). The recurrences were caused by identical Candida sp. genotypes in two of 13 cases (15%), but by different species or dissimilar genotypes in eight of 13 (62%); isolates were missing in three cases. In conclusion, late recurrent candidaemia was a relatively rare event, and younger patients with gastrointestinal disorders were more prone to recurrent infections. The majority of late recurrences represented re-infections with new Candida strains that were susceptible to common antifungal agents.

Infertility in women with epilepsy

Studies suggest that women with epilepsy (WWE) have reduced fertility rates when compared to the general population. Wallace and colleagues,1 using the General Practice Research Database in the United Kingdom, reported that fertility rates among women with epilepsy were 33% lower than in women in the general population. Not all studies have demonstrated such findings, however. In their population-based study in Iceland, Olafsson and colleagues2 found no evidence of reduced fertility in WWE. All previously published studies assessing fertility rates in WWE are retrospective. Potential contributing factors to reduced fertility in WWE include lower marriage rates, reproductive endocrine dysfunction secondary to antiepileptic (AED) drug exposure and seizure type, fear of malformations secondary to AED exposure, concern of increased risk of epilepsy in offspring, and social stigmatization of epilepsy.1,3 AEDs may influence fertility. Enzyme-inducing AEDs are known to affect concentrations of sex steroid hormones and sex hormone binding globulin. Reduced sex steroid hormones and elevated sex hormone binding globulin together reduce the bioavailability of reproductive …

The efficacy of HPV 16/18 vaccines on sexually active 18–23 year old women and the impact of HPV vaccination on organized cervical cancer screening

Evaluate the efficacy of catch-up HPV vaccination in sexually active young women and the potential impact of HPV vaccines on the practice of organized screening. (1) Women enrolled in the Future II study and (2) from a separate population-based study in Iceland. (1) Analysis of cytological and histological results and colposcopic examinations among 710 women, aged 18-23, with less than five sexual partners, irrespectively of baseline HPV status at enrolment. (2) The impact on screening practice as determined by evaluating the distribution of 12 oncogenic HPV types in 582 cervical intraepithelial lesions (CIN 2-3) and cancer cases. (1) Distribution of evaluated parameters according to age at enrolment. (2) Age distribution of four HPV groups, within age classes and HPV groups: mean time to development of lesions, mean time to development of CIN 2-3+, cumulative frequency for CIN 2-3+ lesions after the last normal smear. (1) After an average 52 months of post-enrolment follow-up, significant reductions in all evaluated parameters were observed in women aged 18-19 at enrolment. (2) Among women <25 years, the proportion of cases with only HPV 16/18 was significantly lower and the proportion containing HPV16/18 plus > or =1 out of 10 non-vaccine HPV types (31/33/45/52/58/35/39/51/56/59) was higher than at age 25-49. The proportion of cases containing only the non-vaccine types was the same within all age groups. Cases with HPV 16/18 and some non-vaccine types decreased significantly with age and accumulated more slowly after the last negative smear. Catch-up vaccination of younger women should be considered in the context of sexual practices and the effects of prevalent disease on observed vaccine efficacy. Current data do not support a change in the lower age limit or screening intervals for women.

Risk of epilepsy in long-term survivors of surgery for aneurysmal subarachnoid hemorrhage: a population-based study in Iceland.

Epilepsy is known to result from aneurysmal subarachnoid hemorrhage (SAH). There are no population-based estimates of the absolute risk or the duration for which this risk is elevated. We have conducted a population-based study in Iceland of the risk of epilepsy after a ruptured cerebral aneurysm to address these questions. The index patients are all of the patients who presented with SAH caused by ruptured cerebral aneurysm in Iceland during an 11-year period (1958 to 1968) and survived more than 6 months. We determined the number of index patients who developed epilepsy. The observed number of cases of epilepsy was compared with that expected based on the incidence of epilepsy in Iceland. There were 44 index patients; 11 (25%) developed epilepsy, all within 4 years of the insult. Seven (70%) of 10 patients with acute symptomatic seizures (defined as seizures during the first 2 weeks after the hemorrhage) developed epilepsy (relative risk, 7.0; 95% confidence interval, 2.3-21.6). Epilepsy was more frequent in patients with severe neurological residua (48%) compared with patients without (20%) (relative risk, 2.5; 95% confidence interval, 0.9-6.3). The risk for epilepsy among survivors of SAH caused by ruptured cerebral aneurysm is substantially increased. Both acute symptomatic seizure and persistent neurological impairment are associated with a further increase in the risk of epilepsy.

Pregnancies of women with epilepsy: a population-based study in Iceland.

Women with epilepsy who become pregnant are commonly considered to be at high risk for complications during pregnancy or delivery. The offspring are also considered to have increased risk of perinatal mortality, congenital malformations, and maturational delay. Because few of these studies are population based, potential bias exists because of selection. We performed a historical population-based cohort study in Iceland to determine the prevalence of epilepsy among pregnant women, to identify pregnancy and delivery complications in women with epilepsy, and to determine the outcome of their pregnancies as compared with that in the general population of Iceland. We identified all women with active epilepsy who gave birth during a 19-year period in Iceland. In this population, 3.3 in 1,000 pregnancies involve mothers with active epilepsy. The frequency of adverse events (AE) during pregnancy in the women with epilepsy is similar to that observed among all live births in the population, but cesarean section was performed twice as frequently as in the general population. Perinatal mortality rate and mean birth weight are not significantly different in the offspring of women with epilepsy as compared with rest of the population. The risk of major congenital malformations (MGM) is increased 2.7-fold over that expected when a mother is treated with antiepileptic drugs (AEDs) during a pregnancy. Our study indicates that the rate of complications of pregnancy in mothers with active epilepsy is low and similar to that of the general population with epilepsy. Use of AEDs by the mother during pregnancy significantly increases the risk of MGM in the offspring.