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Objectives: Prior studies on the association of estimated glomerular filtration rate (eGFR) and mortality have failed to include methods to account for repeated eGFR determinations. The aim of this study was to estimate the association between eGFR and mortality in the general population in Iceland employing a joint model., Methods: We obtained all serum creatinine and urine protein measurements from all clinical laboratories in Iceland in the years 2008-16. Clinical data were obtained from nationwide electronic medical records. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and categorized as follows: 0-29, 30-44, 45-59, 60-74, 75-89, 90-104 and >104 mL/min/1.73 m2. A multiple imputation method was used to account for missing urine protein data. A joint model was used to assess risk of all-cause mortality., Results: We obtained 2 120 147 creatinine values for 218 437 individuals, of whom 84 364 (39%) had proteinuria measurements available. Median age was 46 (range 18-106) years and 47% were men. Proteinuria associated with increased risk of death for all eGFR categories in persons of all ages. In persons ≤65 years, the lowest risk was observed for eGFR of 75-89 mL/min/1.73 m2 without proteinuria. For persons aged >65 years, the lowest risk was observed for eGFR of 60-74 mL/min/1.73 m2 without proteinuria. eGFR of 45-59 mL/min/1.73 m2 without proteinuria did not associate with increased mortality risk in this age group. eGFR >104 mL/min/1.73 m2 associated with increased mortality., Conclusions: These results lend further support to the use of age-adapted eGFR thresholds for defining chronic kidney disease. Very high eGFR needs to be studied in more detail with regard to mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Information on the incidence of chronic kidney disease (CKD) in the general population is scarce. This study examined the incidence and risk factors of CKD stages 1-5 in Iceland, based on multiple markers of kidney damage., Methods: All serum creatinine (SCr) values, urine protein measurements and diagnosis codes for kidney diseases and comorbid conditions for people aged ≥18 years were obtained from electronic medical records of all healthcare institutions in Iceland in 2008-2016. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria as evidence for kidney damage and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 for >3 months. Alternatively, CKD was defined using age-adapted eGFR thresholds. Mean annual age-standardized incidence of CKD was calculated for persons without CKD at study entry. Risk factor assessment was based on International Classification of Diseases diagnosis codes. Incidence was reported per 100 000 population., Results: We retrieved 1 820 990 SCr values for 206 727 persons. Median age was 45 years (range, 18-106) and 47% were men. Mean annual age-standardized incidence of CKD per 100 000 was 649 in men and 694 in women, and 480 in men and 522 in women using age-adapted eGFR thresholds. The incidence reached over 3000 in men and women aged >75 years. Traditional CKD risk factors, such as acute kidney injury, diabetes, hypertension and cardiovascular disease, as well as less well characterized risk factors, including chronic lung disease, malignancy and major psychiatric illness were associated with increased risk of CKD, and the same was true for obesity and sleep apnoea in women., Conclusion: The annual incidence of CKD, with strict adherence to the KDIGO criteria, was <0.7% but markedly lower using age-adapted eGFR thresholds. Apart from acute kidney injury, the observed risk factors comprised chronic and potentially modifiable disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Malignant hyperthermia (MH) susceptibility is a rare life-threatening disorder that occurs upon exposure to a triggering agent. MH is commonly due to protein-altering variants in RYR1 and CACNA1S. The American College of Medical Genetics and Genomics recommends that when pathogenic and likely pathogenic variants in RYR1 and CACNA1S are incidentally found, they should be reported to the carriers. The detection of actionable variants allows the avoidance of exposure to triggering agents during anesthesia. First, we report a 10-year-old Icelandic proband with a suspected MH event, harboring a heterozygous missense variant NM&#95;000540.2:c.6710G>A r.(6710g>a) p.(Cys2237Tyr) in the RYR1 gene that is likely pathogenic. The variant is private to four individuals within a three-generation family and absent from 62,240 whole-genome sequenced (WGS) Icelanders. Haplotype sharing and WGS revealed that the variant occurred as a somatic mosaicism also present in germline of the proband's paternal grandmother. Second, using a set of 62,240 Icelanders with WGS, we assessed the carrier frequency of actionable pathogenic and likely pathogenic variants in RYR1 and CACNA1S. We observed 13 actionable variants in RYR1, based on ClinVar classifications, carried by 43 Icelanders, and no actionable variant in CACNA1S. One in 1450 Icelanders carries an actionable variant for MH. Extensive sequencing allows for better classification and precise dating of variants, and WGS of a large fraction of the population has led to incidental findings of actionable MH genotypes., (© 2021. The Author(s).)

Most epidemiological studies on chronic kidney disease (CKD) are based solely on estimated glomerular filtration rate (eGFR). Few studies have included proteinuria, while the chronicity criterion is usually omitted. To explore this, we examined the prevalence of CKD stages 1-5 in Iceland based on multiple markers of kidney damage. All serum creatinine values, urine protein measurements and diagnostic codes for kidney diseases and comorbid conditions for people aged 18 years and older were obtained from electronic medical records of all healthcare institutions in Iceland in 2008-2016. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline using diagnoses indicative of a chronic kidney disease, proteinuria and/or an eGFR under 60 mL/min/1.73 m 2 for over three months. Mean annual age-standardized prevalence of CKD stages 1-5 was calculated based on the KDIGO criteria and age-adapted eGFR thresholds from 2,120,147 creatinine values for 218,437 individuals, 306,531 proteinuria measurements for 86,364 individuals and 6973 individuals carrying a kidney disease diagnosis. Median age was 63 years (range, 18-106) and 47% were male. The mean annual age standardized CKD prevalence was 5.13% for men and 6.75% for women using the KDIGO criteria but by age-adapted eGFR cut-offs, the prevalence was 3.27% for men and 4.01% for women. Thus, our nationwide study, defining CKD in Iceland with strict adherence to the KDIGO criteria, demonstrates a lower prevalence of CKD than anticipated from most previous studies., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Despite the presence of several microorganisms, other than Borrelia burgdorferi sensu lato (Bbsl) and TBE virus, in Ixodes ricinus ticks from the Nordic countries, data is lacking on their pathogenic potential in humans. In this study, we wanted to investigate the aetiology and clinical manifestations of tick-transmitted infections in individuals seeking medical care following a tick-bite. The sampling frame was participants of a large-scale, prospective, multi-centre, follow-up study of tick-bitten volunteers recruited in Sweden, Finland and Norway in the years 2007-2015. Participants who sought medical care during the three-month follow-up period and from whom blood samples were collected during this healthcare visit (n = 92) were tested, using PCR, for exposure to spotted fever group (SFG) Rickettsia spp., Anaplasma phagocytophilum and Babesia spp. Moreover, 86 of these individuals had two serum samples, collected three months apart, tested serologically for six tick-borne microorganisms. The selected organisms - Bbsl, SFG rickettsiae, Anaplasma phagocytophilum, TBE virus, Babesia microti and Bartonella henselae - have all been detected in field-collected ticks from the Nordic countries. Medical records were reviewed and questionnaires were completed to determine clinical manifestations. We found Lyme borreliosis to be the most common tick-transmitted infection as seen in 46 (54%) of the 86 participants with available medical records. Among the 86 participants with paired sera, serological or molecular evidence of recent exposure to other microorganisms than Bbsl could be demonstrated in eight (9%). Five participants (6%) exhibited serological evidence of recent concomitant exposure to more than one tick-borne microorganism. Clinical presentations were mild with one exception (TBE). In conclusion, our data suggest a low risk of infection with tick-borne microorganisms, other than Bbsl, in immunocompetent tick-bitten persons from the examined regions, a low occurrence of co-infection and mostly mild or no overt clinical signs of infection in immunocompetent persons exposed to the studied agents., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: The aim of this study was to examine acute kidney injury (AKI) diagnosis based on different computerized algorithms compared with a nephrologist's diagnosis in patients visiting an emergency department (ED) of a university hospital., Methods: In this retrospective study, we used electronic medical records at the University Hospital in Reykjavik to identify all patients aged ≥18 years, who presented to the ED in the year 2010 with an elevated serum creatinine (SCr) level. All SCr values were reviewed and a nephrologist determined whether AKI was present using the KDIGO SCr criteria and clinical data. Computerized algorithms based on the KDIGO SCr criteria, accounting for various time intervals for baseline SCr and changes in follow-up SCr, were constructed using the statiscal software R., Results: At 53,816 ED visits, SCr was measured in 15,588 patients for a total of 21,559 measurements. Elevated SCr was observed in 2878 (18.4%) patients. Strict adherence to the KDIGO SCr criteria yielded a 79% sensitivity, 94% specificity, 68% positive predictive value (PPV) and 96% negative predictive value (NPV) for the diagnosis of AKI. Allowing for a longer time frame (>365 days) for baseline SCr, resulted in 93% sensitivity, 96% specificity, 80% PPV and 99% NPV. The algorithms which included a decrease in SCr from the index ED value yielded a sensitivity of 97% but lower specificity, 74% and 80%., Conclusions: The algorithms that perform best yield excellent sensitivity and specificity and could be used to identify patients with AKI in the ED to enhance early diagnosis and treatment., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Over the past 30 years evidence has been growing that cannabis use increases the risk for psychosis which could develop into schizophrenia in a proportion of cases. Over the past decade many studies have been published which clarify the association between cannabis use and psychosis. The aim of this review is to examine this association. A systematic search yielded 14 cohort studies carried out in 9 cohorts and 9 case-control studies. When the results of these studies are taken together they unambiguously support that cannabis use is an independent risk factor for psychosis and may also give rise to chronic psychotic disorders like schizophrenia. A dose dependent link is present because more frequent use associates with greater risk. The studies also show that cannabis-use in adolescence is associated with greater risk of developing psychosis than commencing the use of cannabis in adulthood. Further studies are needed to explain this association since psychotic disorders take years to evolve and it remains difficult to measure both the explanatory and the response variable and their complex relationship. The results emphasize the need to enhance public knowledge on the possible consequences of cannabis use and the fact that it cannot be predicted who will experience transient psychosis and who will develop a chronic psychotic disorder.