[Psychedelics and treatment of mental disorders: A survey of attitudes and knowledge among psychiatrists, general practitioners and psychologists in Iceland].

INTRODUCTION: Interest in the use of psychedelics has increased following reports of their possible therapeutic potential. However, little is known about the knowledge of and attitudes towards the substances among health care professional who provide treatment for mental disorders in Iceland. An online survey was therefore conducted among members of the Icelandic associations of psychiatrists, general practitioners and psychologists. METHODS: Respondents were 256 in total, including 177 psychologists, 38 psychiatrists and 41 general practitioners that provided information on their background, type of work, knowledge of and attitude towards different types of psychedelic substances and their views on optimal service delivery if psychedelics were approved by licencing authorities and used for treatment. RESULTS: Around half of psychiatrists reported having received questions about treatment with psychedelics in their clinical work, compared to only 14,6% of general practitioners and 17,5% of psychologists. The majority of respondents had little, or no knowledge of the substances targeted in the survey. A majority also expressed negative attitudes towards treatment with psilocybin mushrooms, but was positive towards ongoing scientific research and felt that such a treatment should be prescribed and provided by psychiatrists. Moreover, the majority view was that psilocybin treatment should be provided in specialised clinics or psychiatric units in a hospital setting. Scientific articles on the topic, discussions with colleagues and information in the media were identified as having had most influence on respondents´ attitudes towards psychedelics. Most respondents were interested in further education on psychedelics. CONCLUSIONS: Respondents among these three professions felt that the time has not yet come to use psychedelics in the treatment of mental disorders in Iceland but thought more education on psychedelics, their potential efficacy and adverse health effects is important given the increased interest in psychedelics.

Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study.

BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.

Persistent symptoms are commonly reported after SARS-CoV-2 infection, and this is often described as long Covid. We compared different symptoms reported following SARS-CoV- 2 infection with the results obtained during various medical evaluations that are often used to assess health, such as blood tests, smell tests, taste tests, hearing tests, etc. We compared symptoms and test results between 1,706 Icelanders who had been infected previously with SARS-CoV-2 infection (cases) and 14,398 individuals who had not been infected (controls). Out of 88 assessed symptoms, 41 were more common in cases than controls. However, relatively few differences were seen in the results obtained from the various medical evaluations (cases had poorer smell and taste test results, slightly less grip strength, and slightly poorer memory recall than controls). The differences seen between symptoms and results of medical evaluations suggests that conventional clinical tests may not be informative in relating symptoms to a past SARS-CoV-2 infection.

Prevalence of modifiable risk factors in primary elective arthroplasty and their association with infections.

BACKGROUND AND PURPOSE: The aim of this study was to identify the prevalence of modifiable risk factors of surgical site infections (SSI) in patients undergoing primary elective total joint arthroplasty (TJA) receiving conventional preoperative preparation, and to explore their association with infectious outcomes. PATIENTS AND METHODS: Information regarding modifiable risk factors (anemia, diabetes, obesity, nutritional status, smoking, physical activity) was prospectively gathered in patients undergoing primary TJA of hip or knee in 2018-2020 at a single institution with 6 weeks' follow-up time. RESULTS: 738 patients (median age 68 years [IQR 61-73], women 57%) underwent TJA (knee 64%, hip 36%). Anemia was detected in 8%, diabetes was present in 9%, an additional 2% had undiagnosed diabetes (HbA1c > 47 mmol/mol), and 8% dysglycemia (HbA1c 42-47 mmol/mol). Obesity (BMI ≥ 30) was observed in 52%. Serum albumin, total lymphocyte count, and vitamin D below normal limits was identified in 0.1%, 18%, and 16%, respectively. Current smokers were 7%. Surgical site complications occurred in 116 (16%), superficial SSI in 57 (8%), progressing to periprosthetic joint infection in 7 cases. Univariate analysis identified higher odds of superficial SSI for BMI ≥ 30 (OR 2.1, 95%CI 1.2-3.8) and HbA1c ≥ 42 mmol/mol (OR 2.2, CI 1.1-4.2), but no association was found with other factors. CONCLUSION: In a general population undergoing primary TJA an association was found between obesity (52%) and dysglycemia/diabetes (19%) and superficial SSI (8%), which progressed to PJI in 12% of cases, generating a 1% total rate of PJI. Modification of these risk factors might mitigate infectious adverse outcomes.

[Migraine prevalence, migraine incidence and migraine drug prescriptions in primary care in the capital region of Iceland].

INTRODUCTION: The study aim was to describe migraine incidence over the ten-year periods, 2000-2009 and 2010-2019, in individuals aged 10-79 years in primary healthcare centre (PHCC) Sólvangur and Fjörður, Hafnarfirði. Another aim was to estimate migraine prevalence in primary care clinics in the capital area of Iceland over the period 2010-2019 and describe prescriptions for migraine specific drugs and other drugs used for migraine. MATERIAL AND METHODS: This is a retrospective study based on data from medical records from the primary care clinics of the capital region of Iceland. The cohort consisted of individuals aged 10-79 years who were diagnosed with migraine, G43 according to the ICD-10 classification system. RESULTS: Migraine incidence at age 10-79 years over the ten-year period 2000-2009 at the primary care clinic Sólvangur was estimated 3.4 cases per 1000 person-years, during the period 2010-2019 in both Sólvangur and Fjörður clinics migraine incidence was estimated 2.9 cases per 1000 person-years. Increase was shown between the two periods in prescriptions of triptan drugs, opioids, and beta-blockers, where two-thirds of the migraineurs got prescription over the two periods. Women were three times more likely to be diagnosed with migraine than men, but men were diagnosed at younger age than women. Migraine prevalence at age 10-79 years in PHCCs in the capital area of Iceland was 4.4% over the period 2010-2019. CONCLUSION: Migraine prevalence in the PHCCs of the capital area of Iceland was only one third of migraine prevalence in the population-based cohort pilot study Heilsusaga Íslendinga. Increase in opioid drug prescriptions for individuals diagnosed with migraine is of concern and needs further study.

Has the COVID-19 Pandemic Led to Changes in the Tasks of the Primary Care Workforce? An International Survey among General Practices in 38 Countries (PRICOV-19).

The COVID-19 pandemic has had a large and varying impact on primary care. This paper studies changes in the tasks of general practitioners (GPs) and associated staff during the COVID-19 pandemic. Data from the PRICOV-19 study of 5093 GPs in 38 countries were used. We constructed a scale for task changes and performed multilevel analyses. The scale was reliable at both GP and country level. Clustering of task changes at country level was considerable (25%). During the pandemic, staff members were more involved in giving information and recommendations to patients contacting the practice by phone, and they were more involved in triage. GPs took on additional responsibilities and were more involved in reaching out to patients. Problems due to staff absence, when dealt with internally, were related to more task changes. Task changes were larger in practices employing a wider range of professional groups. Whilst GPs were happy with the task changes in practices with more changes, they also felt the need for further training. A higher-than-average proportion of elderly people and people with a chronic condition in the practice were related to task changes. The number of infections in a country during the first wave of the pandemic was related to task changes. Other characteristics at country level were not associated with task changes. Future research on the sustainability of task changes after the pandemic is needed.

Genetic variants associated with platelet count are predictive of human disease and physiological markers.

Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring. We found genetic sharing between platelet count and counts of other blood cells (except red blood cells), in addition to several other quantitative traits, including markers of cardiovascular, liver and kidney functions, height, and weight. Platelet count polygenic risk score was predictive of myeloproliferative neoplasms, rheumatoid arthritis, ankylosing spondylitis, hypertension, and benign prostate hyperplasia. Taken together, these results advance understanding of diverse aspects of platelet biology and how they affect biological processes in health and disease.

Artificial intelligence in the GPs office: a retrospective study on diagnostic accuracy.

OBJECTIVE: Machine learning (ML) is expected to play an increasing role within primary health care (PHC) in coming years. No peer-reviewed studies exist that evaluate the diagnostic accuracy of ML models compared to general practitioners (GPs). The aim of this study was to evaluate the diagnostic accuracy of an ML classifier on primary headache diagnoses in PHC, compare its performance to GPs, and examine the most impactful signs and symptoms when making a prediction. DESIGN: A retrospective study on diagnostic accuracy, using electronic health records from the database of the Primary Health Care Service of the Capital Area (PHCCA) in Iceland. SETTING: Fifteen primary health care centers of the PHCCA. SUBJECTS: All patients that consulted a physician, from 1 January 2006 to 30 April 2020, and received one of the selected diagnoses. MAIN OUTCOME MEASURES: Sensitivity, Specificity, Positive Predictive Value, Matthews Correlation Coefficient, Receiver Operating Characteristic (ROC) curve, and Area under the ROC curve (AUROC) score for primary headache diagnoses, as well as Shapley Additive Explanations (SHAP) values of the ML classifier. RESULTS: The classifier outperformed the GPs on all metrics except specificity. The SHAP values indicate that the classifier uses the same signs and symptoms (features) as a physician would, when distinguishing between headache diagnoses. CONCLUSION: In a retrospective comparison, the diagnostic accuracy of the ML classifier for primary headache diagnoses is superior to GPs. According to SHAP values, the ML classifier relies on the same signs and symptoms as a physician when making a diagnostic prediction.KeypointsLittle is known about the diagnostic accuracy of machine learning (ML) in the context of primary health care, despite its considerable potential to aid in clinical work. This novel research sheds light on the diagnostic accuracy of ML in a clinical context, as well as the interpretation of its predictions. If the vast potential of ML is to be utilized in primary health care, its performance, safety, and inner workings need to be understood by clinicians.

Large-Scale Screening for Monogenic and Clinically Defined Familial Hypercholesterolemia in Iceland.

Objective: Familial hypercholesterolemia (FH) is traditionally defined as a monogenic disease characterized by severely elevated LDL-C (low-density lipoprotein cholesterol) levels. In practice, FH is commonly a clinical diagnosis without confirmation of a causative mutation. In this study, we sought to characterize and compare monogenic and clinically defined FH in a large sample of Icelanders. Approach and Results: We whole-genome sequenced 49 962 Icelanders and imputed the identified variants into an overall sample of 166 281 chip-genotyped Icelanders. We identified 20 FH mutations in LDLR, APOB, and PCSK9 with combined prevalence of 1 in 836. Monogenic FH was associated with severely elevated LDL-C levels and increased risk of premature coronary disease, aortic valve stenosis, and high burden of coronary atherosclerosis. We used a modified version of the Dutch Lipid Clinic Network criteria to screen for the clinical FH phenotype among living adult participants (N=79 058). Clinical FH was found in 2.2% of participants, of whom only 5.2% had monogenic FH. Mutation-negative clinical FH has a strong polygenic basis. Both individuals with monogenic FH and individuals with mutation-negative clinical FH were markedly undertreated with cholesterol-lowering medications and only a minority attained an LDL-C target of <2.6 mmol/L (<100 mg/dL; 11.0% and 24.9%, respectively) or <1.8 mmol/L (<70 mg/dL; 0.0% and 5.2%, respectively), as recommended for primary prevention by European Society of Cardiology/European Atherosclerosis Society cholesterol guidelines. Conclusions: Clinically defined FH is a relatively common phenotype that is explained by monogenic FH in only a minority of cases. Both monogenic and clinical FH confer high cardiovascular risk but are markedly undertreated.

Distinction between the effects of parental and fetal genomes on fetal growth.

Birth weight is a common measure of fetal growth that is associated with a range of health outcomes. It is directly affected by the fetal genome and indirectly by the maternal genome. We performed genome-wide association studies on birth weight in the genomes of the child and parents and further analyzed birth length and ponderal index, yielding a total of 243 fetal growth variants. We clustered those variants based on the effects of transmitted and nontransmitted alleles on birth weight. Out of 141 clustered variants, 22 were consistent with parent-of-origin-specific effects. We further used haplotype-specific polygenic risk scores to directly test the relationship between adult traits and birth weight. Our results indicate that the maternal genome contributes to increased birth weight through blood-glucose-raising alleles while blood-pressure-raising alleles reduce birth weight largely through the fetal genome.

Prescriptions of antibiotics in out-of-hours primary care setting in Reykjavik capital area.

OBJECTIVE: To describe antibiotic prescriptions in out-of-hour (OOH) service in primary care setting in Iceland and to study the indications for prescriptions. DESIGN: A population based retrospective study, using electronic data from the OOH registration system. SETTING: OOH primary care setting in Reykjavik capital area in Iceland. SUBJECTS: All patients that received a prescription for oral antibiotic drug at an OOH service in Reykjavik capital area over a one-year period. MAIN OUTCOME MEASURES: Number of oral antibiotic prescriptions and diagnosis connected to the prescriptions according to age and sex. RESULTS: There were 75,582 contacts with the OOH primary care of which 25,059 contacts resulted in prescription of an oral antibiotic (33%). The most common antibiotic prescribed in total, and for the diagnosis studied, was amoxicillin with clavulanic acid. It was most often prescribed for acute otitis media. Of those diagnosed with otitis media 50% were treated with amoxicillin with clavulanic acid and 40% of those diagnosed with pneumonia received that treatment. The second most prescribed antibiotic was amoxicillin. Most often it was prescribed for sinusitis, in 47% of cases with that diagnosis. CONCLUSION: Antibiotics are often prescribed in OOH primary care in Iceland and a substantial number of the patients diagnosed in OOH primary care with acute otitis media or pneumonia are prescribed broad-spectrum antibiotics. Key points Antibiotic prescription rate is high and broad-spectrum drugs often prescribed in OOH primary care service in Iceland. The results should encourage general practitioners in Iceland to review antibiotic prescriptions in OOH service.

[Vitamin D status of Icelandic children and youngsters: Longitudinal study]. / D-vítamínbúskapur íslenskra barna og ungmenna. Langtímarannsókn

OBJECTIVE: Vitamin D plays a key role for children's growth and physical developement, not only by promoting bone health but also by its influence on extraskeletal systems. The Icelandic Directorate of Health recommends a vitamin D concentration in blood of at least 50 nmol/l. The object of this study was to evaluate the vitamin D status of Icelandic children and youngsters at four different ages, and furthermore to evaluate changes in vitamin D concentrations over time and connection to parathyroid hormone status (S-PTH). MATERIAL AND METHODS: The subjects were students from six elemen-tary schools in Reykjavík, born in 1999. Blood tests were taken four times, in 2006, 2008, 2015 og 2017. Some of the subjects took part in all four tests, but more students joined in 2015 and 2017. RESULTS: In all the tests, around 60% of the subjects had lower vitamin D concentrations than recommended by The Icelandic Directorate of Health. Only 13% met the recommended criteria of a concentration over 50 nmol/l in repeated tests and 38.9% of the subjects had lower concentrations than recommended in at least two tests. There was no significant difference between sexes except that 17 year old girls had significantly higher Vitamin D concentrations than boys (p=0.04). S-PTH was negatively correlated to vitamin D concentrations at ages 7, 15 and 17 but there was not a significant correlation at age 9. S-PTH values were lowest at age 7 and then increased with age. CONCLUSION: The majority of Icelandic children and youngsters have vitamin D concentrations under the values recommended by The Icelandic Directorate of Health. In many cases, the concentrations are repeatedly too low. It is clear that there is a need for increased vitamin D intake within this group if the goal regarding recommended concentrations is to be achieved. However, the influence of vitamin D deficiency on public health is not fully known.

Sequence variants with large effects on cardiac electrophysiology and disease.

Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.

Variants in NKX2-5 and FLNC Cause Dilated Cardiomyopathy and Sudden Cardiac Death.

BACKGROUND: Dilated cardiomyopathy (DCM) is an important cause of heart failure. Variants in >50 genes have been reported to cause DCM, but causative variants have been found in less than half of familial cases. Variants causing DCM in Iceland have not been reported before. METHODS: We performed a genome-wide association study on DCM based on whole genome sequencing. We tested the association of 32.5 million sequence variants in 424 cases and 337 689 population controls in Iceland. RESULTS: We identified 2 DCM variants in established cardiomyopathy genes, a missense variant p.Phe145Leu in NKX2-5 carried by 1 in 7100 Icelanders ( P=7.0×10-12) and a frameshift variant p.Phe1626Serfs*40 in FLNC carried by 1 in 3600 Icelanders ( P=2.1×10-10). Both variants associate with heart failure and sudden cardiac death. Additionally, p.Phe145Leu in NKX2-5 associates with high degree atrioventricular block and atrial septal defect ( P<1.4×10-4). The penetrance of serious heart disease among carriers of the NKX2-5 variant is high and higher than that of the FLNC variant. CONCLUSIONS: Two rare variants in NKX2-5 and FLNC, carried by 1 in 2400 Icelanders, cause familial DCM in Iceland. These genes have recently been associated with DCM. Given the serious consequences of these variants, we suggest screening for them in individuals with DCM and their family members, with subsequent monitoring of carriers, offering early intervention.

A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta.

Aims: Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment. It is increasingly recognized as a highly heritable condition. The aim of the study was to search for sequence variants that affect the risk of CoA. Methods and results: We performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing. We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10-22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein. Approximately 20% of individuals with CoA in Iceland carry this mutation. We show that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic valve. We have previously reported broad effects of p.Arg721Trp on cardiac electrical function and strong association with sick sinus syndrome and atrial fibrillation. Conclusion: Through a population approach, we found that a rare missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on the risk of CoA and explains a substantial fraction of the Icelanders with CoA. This is the first mutation associated with non-familial or sporadic form of CoA at a population level. The p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity and emphasizes the importance of sarcomere integrity for cardiac development and function.

Genome-wide analysis yields new loci associating with aortic valve stenosis.

Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.