[The efficacy of magnetic transcranial stimulation in treating treatment-resistant or prolonged depression in a clinical sample].

INTRODUCTION: Depression is a common, serious and often chronic disorder and one of the leading causes of disability worldwide. The annual prevalence of depression is 5-10%, twice as high among women as men and the lifetime prevalence is at least 20%. Up to a third of depressed individuals meet criteria for treatment-resistant depression, where two antidepressants have been tried for at least 6 weeks each at therapeutic doses. As of January 2022 transcranial magnetic stimulation for adults with treatment-resistant depression that has not responded to other forms of treatment has been available by a service that is part of Primary Health Care of the Capital Area in Iceland. METHODS: This is a retrospective cohort study where participants completed a course of magnetic transcranial treatment for depression in the years 2022 and 2023. Two validated self-rating measures were used to assess depression. Information on previous treatment approaches for depression was collected from electronic health records. RESULTS: 104 individuals completed the treatment in these first two years, 60,6% women. Most had unipolar depression (86,5%), but a small subgroup had bipolar depression (13,5%). The proportion of responders varied according to the measures used, 36,1% and 45,7%, respectively, and the same was true for remission where the proportions were 12,4% and 31,5%, respectively, higher for the longer inventory. The drop-out rate was only 12,5% and no serious adverse events were reported during the treatment. CONCLUSION: The results support that magnetic transcranial stimulation, as provided by this service is effective in treating treatment-resistant or longstanding depression in a real life clinical setting and the low drop-out rate supports that the treatment is generally very well tolerated.

A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant condition characterized by aortic aneurysm, skeletal abnormalities, and lens dislocation, and is caused by variants in the FBN1 gene. To explore causes of MFS and the prevalence of the disease in Iceland we collected information from all living individuals with a clinical diagnosis of MFS in Iceland (n = 32) and performed whole-genome sequencing of those who did not have a confirmed genetic diagnosis (27/32). Moreover, to assess a potential underdiagnosis of MFS in Iceland we attempted a genotype-based approach to identify individuals with MFS. We interrogated deCODE genetics' database of 35,712 whole-genome sequenced individuals to search for rare sequence variants in FBN1. Overall, we identified 15 pathogenic or likely pathogenic variants in FBN1 in 44 individuals, only 22 of whom were previously diagnosed with MFS. The most common of these variants, NM_000138.4:c.8038 C > T p.(Arg2680Cys), is present in a multi-generational pedigree, and was found to stem from a single forefather born around 1840. The p.(Arg2680Cys) variant associates with a form of MFS that seems to have an enrichment of abdominal aortic aneurysm, suggesting that this may be a particularly common feature of p.(Arg2680Cys)-associated MFS. Based on these combined genetic and clinical data, we show that MFS prevalence in Iceland could be as high as 1/6,600 in Iceland, compared to 1/10,000 based on clinical diagnosis alone, which indicates underdiagnosis of this actionable genetic disorder.

Long-term data reveal contrasting impacts of native versus invasive nest predators in Iceland.

Bird species on islands are strongly impacted by biological invasions, with the Icelandic common eider (Somateria mollissima borealis) being particularly threatened. Down collection by local families in Breiðafjörður, West Iceland, provided long-term datasets of nests from two archipelagos, covering 95 islands over 123 years and 39 islands over 27 years, respectively. Using these exceptional datasets, we found that the arrival of the invasive semi-aquatic American mink (Neogale vison) was a more impactful driver of population dynamics than climate. This invasive predator heavily reduced eider nest numbers by ca. 60% in the Brokey archipelago. In contrast, we detected an apparently adaptive response to the return of the native fox in the Purkey archipelago, with dense nests on islands inaccessible to the fox and no apparent impact on eider populations. This difference might be due to the eiders lacking a joint evolutionary history with the mink and therefore lacking appropriate antipredator responses.

[Epidemiology of polypharmacy in primary healthcare in the Reykjavik metropolitan area 2010-2019].

INTRODUCTION: Taking medicines can induce risks leading to negative health issues that can grow in accordance with the number of medicines used. Many studies on the prevalence of polypharmacy have been carried out in other countries, but such studies are lacking in Iceland. The aim of this study was to analyse the prevalence of polypharmacy in primary care in the Reykjavik metropolitan area. METHODS: The study population consisted of individuals who had been prescribed five or more drugs by physicians in primary care in the Reykjavik metropolitan area during the study period. Data was collected on all drug prescriptions for individuals in the area. Those who had five or more drugs prescribed in the primary healthcare database from 1 January 2010 through 31 December 2019 were included in the study. According to Statistics Iceland, the total number of inhabitants in the area was 200.907 in 2010 and 228.222 in 2019. FINDINGS: The prevalence of polypharmacy increased gradually in 2010-2019, or by 37.9% during this period. Patients with polypharmacy were 9.8% (19.778) at the beginning of the study in 2010 and increased to 13.6% (30.970) in 2019. A clear association was observed between age and polypharmacy, and the study showed polypharmacy to be more common among women. The study findings revealed that the greatest relative increase in polypharmacy was among young people from 20-49 years of age. ATC class analysis showed a sharp increase in the first and third levels of the ATC subgroups. CONCLUSION: The findings suggest polypharmacy to be common in the Reykjavik metropolitan area. Similarly, its prevalence seems to be increasing in younger patients. It is important to gain a better understanding of the reasons for the development of polypharmacy and evaluate the increasing medicalisation in society. The underlying reasons, as well as the effects of polypharmacy, can lead to both positive and negative health outcomes.

Do foraging ecology and contaminants interactively predict parenting hormone levels in common eider?

Global climate change is causing abiotic shifts such as higher air and ocean temperatures, and disappearing sea ice in Arctic ecosystems. These changes influence Arctic-breeding seabird foraging ecology by altering prey availability and selection, affecting individual body condition, reproductive success, and exposure to contaminants such as mercury (Hg). The cumulative effects of alterations to foraging ecology and Hg exposure may interactively alter the secretion of key reproductive hormones such as prolactin (PRL), important for parental attachment to eggs and offspring and overall reproductive success. However, more research is needed to investigate the relationships between these potential links. Using data collected from 106 incubating female common eiders (Somateria mollissima) at six Arctic and sub-Arctic colonies, we examined whether the relationship between individual foraging ecology (assessed using δ13C, δ15N) and total Hg (THg) exposure predicted PRL levels. We found a significant, complex interaction between δ13C, δ15N and THg on PRL, suggesting that individuals cumulatively foraging at lower trophic levels, in phytoplankton-dominant environments, and with the highest THg levels had the most constant significant relationship PRL levels. Cumulatively, these three interactive variables resulted in lowered PRL. Overall, results demonstrate the potential downstream and cumulative implications of environmentally induced changes in foraging ecology, in combination with THg exposure, on hormones known to influence reproductive success in seabirds. These findings are notable in the context of continuing environmental and food web changes in Arctic systems, which may make seabird populations more susceptible to ongoing stressors.

[Resistant hypertension - pheochromocytoma].

We report a case of a man with a 30-year history of treatment-resistant hypertension, hydropoiesis, tachycardic spells and dysgeusia. Despite repeated visits to the emergency department and work-up in an out-patient clinic, the diagnosis was unknown. Three years prior to remittance to an endocrinologist, the hypertension worsened, and he developed diabetes type-II. Further work-up revealed a 3 cm extra-adrenal pheochromocytoma, a paraganglioma. After surgical removal of the tumor, he is without medication and symptom free. Pheochromocytoma and paraganglioma are rare causes of hypertension, estimated to explain 0.1-0.6% of all cases, but nonetheless an important diagnosis to make, due to serious side effects.

Global dissemination of influenza A virus is driven by wild bird migration through arctic and subarctic zones.

Influenza A viruses (IAV) circulate endemically among many wild aquatic bird populations that seasonally migrate between wintering grounds in southern latitudes to breeding ranges along the perimeter of the circumpolar arctic. Arctic and subarctic zones are hypothesized to serve as ecologic drivers of the intercontinental movement and reassortment of IAVs due to high densities of disparate populations of long distance migratory and native bird species present during breeding seasons. Iceland is a staging ground that connects the East Atlantic and North Atlantic American flyways, providing a unique study system for characterizing viral flow between eastern and western hemispheres. Using Bayesian phylodynamic analyses, we sought to evaluate the viral connectivity of Iceland to proximal regions and how inter-species transmission and reassortment dynamics in this region influence the geographic spread of low and highly pathogenic IAVs. Findings demonstrate that IAV movement in the arctic and subarctic reflects wild bird migration around the perimeter of the circumpolar north, favouring short-distance flights between proximal regions rather than long distance flights over the polar interior. Iceland connects virus movement between mainland Europe and North America, consistent with the westward migration of wild birds from mainland Europe to Northeastern Canada and Greenland. Though virus diffusion rates were similar among avian taxonomic groups in Iceland, gulls play an outsized role as sinks of IAVs from other avian hosts prior to onward migration. These data identify patterns of virus movement in northern latitudes and inform future surveillance strategies related to seasonal and emergent IAVs with potential public health concern.

Mercury contamination and potential health risks to Arctic seabirds and shorebirds.

Since the last Arctic Monitoring and Assessment Programme (AMAP) effort to review biological effects of mercury (Hg) on Arctic biota in 2011 and 2018, there has been a considerable number of new Arctic bird studies. This review article provides contemporary Hg exposure and potential health risk for 36 Arctic seabird and shorebird species, representing a larger portion of the Arctic than during previous AMAP assessments now also including parts of the Russian Arctic. To assess risk to birds, we used Hg toxicity benchmarks established for blood and converted to egg, liver, and feather tissues. Several Arctic seabird populations showed Hg concentrations that exceeded toxicity benchmarks, with 50 % of individual birds exceeding the "no adverse health effect" level. In particular, 5 % of all studied birds were considered to be at moderate or higher risk to Hg toxicity. However, most seabirds (95 %) were generally at lower risk to Hg toxicity. The highest Hg contamination was observed in seabirds breeding in the western Atlantic and Pacific Oceans. Most Arctic shorebirds exhibited low Hg concentrations, with approximately 45 % of individuals categorized at no risk, 2.5 % at high risk category, and no individual at severe risk. Although the majority Arctic-breeding seabirds and shorebirds appeared at lower risk to Hg toxicity, recent studies have reported deleterious effects of Hg on some pituitary hormones, genotoxicity, and reproductive performance. Adult survival appeared unaffected by Hg exposure, although long-term banding studies incorporating Hg are still limited. Although Hg contamination across the Arctic is considered low for most bird species, Hg in combination with other stressors, including other contaminants, diseases, parasites, and climate change, may still cause adverse effects. Future investigations on the global impact of Hg on Arctic birds should be conducted within a multi-stressor framework. This information helps to address Article 22 (Effectiveness Evaluation) of the Minamata Convention on Mercury as a global pollutant.

Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene.

Predicting the pathogenicity of biallelic missense variants can be challenging. Here, we use a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes. We follow three missense variants with a complete deficit of homozygosity and find that their pathogenic effect in homozygous state ranges from severe childhood disease to early embryonic lethality. One of these variants is in CPSF3, a gene not previously linked to disease. From a set of clinically sequenced Icelanders, and by sequencing archival samples targeted through the Icelandic genealogy, we find four homozygous carriers. Additionally, we find two homozygous carriers of Mexican descent of another missense variant in CPSF3. All six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone. Here, we show how the absence of certain homozygous genotypes from a large population set can elucidate causes of previously unexplained recessive diseases and early miscarriage.

[Hypertension Management in Primary Care in the Capital Area of Iceland].

INTRODUCTION: High blood pressure (HT) is one of the main risk factors for cardiovascular diseases which in 2010 caused one third of all mortality in the world. Untreated, HT can cause stroke, myocardial infarction, heart failure, dementia, kidney failure, atherosclerosis and eye diseases. The main aim of this study was to find out how HT is treated in primary care in the capital area of Iceland. MATERIAL AND METHODS: The study is a descriptive retrospective cross-sectional study covering the years 2010, 2014 and 2019. Information about all patients over 18 years old diagnosed with HT were gathered from computerised medical records at every primary care center in the Capital area. RESULTS: The number of individuals diagnosed with HT increased during the study period and the mean age did also increase. The sex ratio changed with more men diagnosed than women. Of 25.873 patients diagnosed with HT in the year 2010, 63.4% received drug treatment. In 2019 this percentage had dropped 60.9% (p<0,001). Of those on antihypertensive drug treatment the proportion receiving one, two or three drugs remained same from 2010-2019. The most common group of drugs used were diuretics (C03), beta-blockers (C07), calcium channel blockers (C08) and renin-angiotensin-aldosteron-system (RAAS) inhibitors (C09). The proportion af these drug groups changed significantly during the study. Fever patients were treated by diuretics (p<0,001) or beta-blockers ((p<0,001) but the number treated by calcium channel blockers (p<0,01) or RAAS inhibitors increased (p<0,001). During the whole stud period 44.1% of the patients reached the target goals. The proportion of patients who reached the target goals in different health care center was specifically for the year 2019. Just over 41% of HT patients reached the targets goals. However, two health care centers achieved notably different results with only one third of the patients attaining the goals. CONCLUSION: As has recently been shown in epidemiologic studies hypertension in Iceland is both underdiagnosed and undertreated although the country ranks high on both counts in international comparison. Furthermore, the fact that under half of hypertensive patients in general practice in the capital area reach the targeted treatment goals, cannot be considered an acceptable. Thus, it is of immense importance to improve both the diagnosis and the treatment of HT.

[Increased use of genetic health care in Iceland 2012-2017].

INTRODUCTION: A genetic counselling unit at Landspitali hospital (LSH) was established in 2006. Meanwhile, genetic testing has become an integral part of general health care. In this article we detail the outcome of genetic testing at the Department of Genetic and Molecular Medicine (DGM) at Landspitali over a five year period (2012-2017). Factors that were analyzed for the time period were: Number of patients, reason for referral, reason for genetic testing without genetic counselling and yield (proportion of positive tests) of genetic testing. METHODS: Data was analysed from two medical record databases, Shire and Saga, used by the DGM in the time period. RESULTS: The number of individuals coming for genetic counselling increased every year over the time period. Reasons for referral were cancer-related in two-thirds of cases. Other reasons for referral included various other familial disorders. Most common were autosomal dominant disorders like myotonic dystrophy, hypertrophic cardiomyopathy and autosomal recessive disorders like spinal muscular atrophy (SMA) and GM1-gangliosidosis. Most common reasons for genetic testing outside of the LSH GC unit was because of managable diseases like hemochromatosis and F5/Prothrombin-related thrombophilia. Yield of genetic testing was assessed for a) known mutation testing / carrier testing, b) single gene testing, c) gene panel testing and d) whole genome and whole exome sequencing. Known mutation testing was positive in 33% of cases and single gene testing in 46% of cases. The yield of gene panel testing for cancer was found to be lower (20%) than gene panel testing for other disorders (40%). The yield of whole exome and whole genome sequencing was 46%.

[Factors affecting general practitioners' choice of drug therapy: A study in primary healthcare in Iceland].

INTRODUCTION: This study aimed to analyse several factors that influence the decision-making of primary care physicians in Iceland in their choice of drug therapy for their patients. Also, to find which factors can act as a hindrance in making the best choices. Finally, to analyse which elements could be most important in facilitating decisions. MATERIAL AND METHODS: A questionnaire was sent by e-mail to physicians working in primary care in Iceland. The questionnaire comprised closed questions, open text boxes, and ranking questions. The data was processed and analysed using Microsoft Excel. RESULTS: The total number of primary care physicians who responded to the questionnaire was 93, a response rate of 40.7% of all the primary care physicians. The results reveal that physicians working in primary care consider clinical guidelines, the Icelandic National Formulary, and personal experience to be the most important factors when choosing a medication. Primary care physicians strongly agree that the lack of drug interaction software connected to medical records is a shortcoming. The most important factors that need improvement to facilitate primary care physicians' decision-making are drug formularies and interaction software. CONCLUSION: The results suggest some factors that support physicians in primary care in making decisions when choosing drug therapy, such as a drug formulary, drug interaction software, information about patients' drug therapy, variable length in face-to-face consultations, evidence based information on new drugs, and counselling provided by clinical pharmacists.

Nesting Synchrony and Clutch Size in Migratory Birds: Capital versus Income Breeding Determines Responses to Variable Spring Onset.

AbstractSynchronous reproduction of birds has often been explained by benefits from nesting together, but this concept fails to explain observed intraspecific variation and climate-mediated changes of breeding synchrony. Here, we present a theoretical model of birds that store resources for reproduction (capital breeders) to show how breeding synchrony, clutch size, and offspring recruitment respond to changes in timing of first possible breeding date. Our approach is based on individual fitness maximization when both prebreeding foraging and offspring development are time constrained. The model predicts less synchronous breeding, smaller clutch size, and higher chances for offspring recruitment in capital breeding birds that advance their nesting. For contrast, we also show that birds that need to acquire resources during egg laying (income breeders) do not change nesting synchrony but increase clutch size along with earlier breeding. The prediction of stronger nesting synchronization of capital breeders in years with late nesting onset is confirmed by empirical data on breeding synchrony of a high-latitude capital breeding sea duck, the common eider (Somateria mollissima). We predict that in warming high-latitude ecosystems, bird species that depend on stored reserves for reproduction are expected to desynchronize their nesting.

[Changes in prescriptions on opioids in primary health care during the years 2008-2017].

INTRODUCTION: In recent decades there has been a notable increase in the prescription of opioids in western countries. With this rise in use of opioids the risk of side effects, opioid abuse and deaths linked to opioids have become more apparent. The increase in opioid prescription may partly stem from a change in attitude in relation to pain management. Research has shown that pain is among the most common reasons people seek medical care and chronic pain is prevalent. Iceland is leading the Nordic countries in opioid prescriptions. OBJECTIVE: To examine prescriptions of opioids in primary car in Iceland for all age group from 2008 to 2017. METHODS: The research included all opioid prescription in every health clinic in the capital area in Iceland the between 2008 and 2017. Population in the capital area in this time period was between 201 and 222 thousand people. Data was collected from medical records database of the primary health care and approximatley 68.000 individuals had received a prescription for opioids during the research period. RESULTS: During the research period there was a 17,2% (p<0,01) increase in DDD/1000 inhabitants/day (Defined daily dose) for opioids. About a third of those who got the prescription were men and that ratio did not change during the period. proportionately, the biggest change in DDD/1000 inhabitants/day was in the age group made of people 90 years old and older, about 40,5% ((p<0,01)). The biggest increase in number of people getting a prescription for opioids was in the age group 30-39, about 25,5% ((p<0,01)). Number of prescriptions increased in every category of opioids, measured in DDD/1000 inhabitants/day,15,3% ((p<0,01)) in parkódin, 20,7% ((p<0,01)) in parkódín forte, 4,7% (p<0,01)) in tramadol and 85,6% (p<0,01) in the strongest opioids. DISCUSSION: the evolution of prescriptions for every type of opioid to the clients of the health clinics in the capital area that occured in the years from 2008 to 2017, proportionately highest for the strongest opioids, should encourage a review of pain treatment within the health clinics and development within that field.

Encouraging rational antibiotic prescribing behaviour in primary care - prescribing practice among children aged 0-4 years 2016-2018: an observational study.

OBJECTIVE: To study antibiotic prescriptions among 0- to 4-year-old children before and after implementing a quality project on prudent prescribing of antibiotics in primary healthcare in the capital region of Iceland. DESIGN: An observational, descriptive, retrospective study using quantitative methodology. SETTING: Primary healthcare in the Reykjavik area with a total population of approximately 220,000. SUBJECTS: A total of 6420 children 0-4 years of age presenting at the primary healthcare centres in the metropolitan area over three years from 2016 to 2018. MAIN OUTCOME MEASURES: Reduction of antibiotic prescriptions and change in antibiotic profile. Data on antibiotic prescriptions for children 0-4 years of age was obtained from the medical records. Out-of-hours prescriptions were not included in the database. RESULTS: The number of prescriptions during the study period ranged from 263.6 to 289.6 prescriptions/1000 inhabitants/year. A reduction of 9% in the total number of prescriptions between 2017-2018 was observed. More than half of all prescriptions were for otitis media, followed by pneumonia and skin infections. Amoxicillin accounted for over half of all prescriptions, increasing between 2016 and 2018 by 51.3%. During this period, the prescribing of co-amoxiclav and macrolides decreased by 52.3% and 40.7%, respectively. These changes were significant in all cases, p < 0.0001. CONCLUSION: The results show an overall decrease in antibiotic prescribing concurrent with a change in the choice of antibiotics prescribed and in line with the recommendations presented in the prescribing guidelines implemented by the Primary Healthcare of the Capital Area, and consistent with the project's goals.Key pointsA substantial proportion of antibiotic prescribing can be considered inappropriate and the antibiotic prescription rate is highest in Iceland of the Nordic countries.After implementing guidance on the treatment of common infections together with feedback on antibiotic prescribing, a decrease in the total number of prescriptions accompanied by a shift in the antibiotic profile was observed.

Environmental and life-history factors influence inter-colony multidimensional niche metrics of a breeding Arctic marine bird.

Human industrialization has resulted in rapid climate change, leading to wide-scale environmental shifts. These shifts can modify food web dynamics by altering the abundance and distribution of primary producers (ice algae and phytoplankton), as well as animals at higher trophic levels. Methylmercury (MeHg) is a neuro-endocrine disrupting compound which biomagnifies in animals as a function of prey choice, and as such bioavailability is affected by altered food web dynamics and adds an important risk-based dimension in studies of foraging ecology. Multidimensional niche dynamics (MDND; δ13C, δ15N, THg; total mercury) were determined among breeding common eider (Somateria mollissima) ducks sampled from 10 breeding colonies distributed across the circumpolar Arctic and subarctic. Results showed high variation in MDND among colonies as indicated by niche size and ranges in δ13C, δ15N and THg values in relation to spatial differences in primary production inferred from sea-ice presence and colony migratory status. Colonies with higher sea-ice cover during the pre-incubation period had higher median colony THg, δ15N, and δ13C. Individuals at migratory colonies had relatively higher THg and δ15N, and lower δ13C, suggesting a higher trophic position and a greater reliance on phytoplankton-based prey. It was concluded that variation in MDND exists among eider colonies which influenced individual blood THg concentrations. Further exploration of spatial ecotoxicology and MDND at each individual site is important to examine the relationships between anthropogenic activities, foraging behaviour, and the related risks of contaminant exposure at even low, sub-lethal concentrations that may contribute to deleterious effects on population stability over time. Overall, multidimensional niche analysis that incorporates multiple isotopic and contaminant metrics could help identify those populations at risk to rapidly altered food web dynamics.

Molecular genetics of inherited retinal degenerations in Icelandic patients.

The study objective was to delineate the genetics of inherited retinal degenerations (IRDs) in Iceland, a small nation of 364.000 and a genetic isolate. Benefits include delineating novel pathogenic genetic variants and defining genetically homogenous patients as potential investigative molecular therapy candidates. The study sample comprised patients with IRD in Iceland ascertained through national centralized genetic and ophthalmological services at Landspitali, a national social support institute, and the Icelandic patient association. Information on patients' disease, syndrome, and genetic testing was collected in a clinical registry. Variants were reevaluated according to ACMG/AMP guidelines. Overall, 140 IRD patients were identified (point prevalence of 1/2.600), of which 70 patients had a genetic evaluation where two-thirds had an identified genetic cause. Thirteen disease genes were found in patients with retinitis pigmentosa, with the RLBP1 gene most common (n = 4). The c.1073 + 5G > A variant in the PRPF31 gene was homozygous in two RP patients. All tested patients with X-linked retinoschisis (XLRS) had the same possibly unique RS1 pathogenic variant, c.441G > A (p.Trp147X). Pathologic variants and genes for IRDs in Iceland did not resemble those described in ancestral North-Western European nations. Four variants were reclassified as likely pathogenic. One novel pathogenic variant defined a genetically homogenous XLRS patient group.