Validity of chronic disease diagnoses in Icelandic healthcare registries

Aims: To evaluate the validity of recorded chronic disease diagnoses in Icelandic healthcare registries. Methods: Eight different chronic diseases from multiple sub-specialties of medicine were validated with respect to accuracy, but not to timeliness. For each disease, 30 patients with a recorded diagnosis and 30 patients without the same diagnosis were randomly selected from >80,000 participants in the iStopMM trial, which includes 54% of the Icelandic population born before 1976. Each case was validated by chart review by physicians using predefined criteria. Results: The overall accuracy of the chronic disease diagnoses was 96% (95% CI 94–97%), ranging from 92 to 98% for individual diseases. After weighting for disease prevalence, the accuracy was estimated to be 98.5%. The overall positive predictive value (PPV) of chronic disease diagnosis was 93% (95% CI 89–96%) and the overall negative predictive value (NPV) was 99% (95% CI 96–100%). There were disease-specific differences in validity, most notably multiple sclerosis, where the PPV was 83%. Other disorders had PPVs between 93 and 97%. The NPV of most disorders was 100%, except for hypertension and heart failure, where it was 97 and 93%, respectively. Those who had the registered chronic disease had objective findings of disease in 96% of cases. Conclusions: When determining the presence of chronic disease, diagnosis data from the Icelandic healthcare registries has a high PPV, NPV and accuracy. Furthermore, most diagnoses can be confirmed by objective findings such as imaging or blood testing. These findings can inform the interpretation of studies using diagnostic data from the Icelandic healthcare registries.

Childhood with a relative's excessive alcohol use, and own drinking in adult years

Objective: The aim of this study was to investigate if individuals who had been brought up by relatives (e.g. parents, siblings and grandparents) who consumed excessive alcohol effected these individuals' own alcohol use in their adult years. The participants in the study were also asked about their alcohol consumption in the past 12 months, and abstainers were asked about their reasons for choosing to live their lives without consuming alcohol. Method: A quantitative approach was used. Data collected from the Icelandic RARHA SEAS were used in this study. A panel of 2500 respondents in the age range of 18-65 years was randomly sampled and was intended to be adequately representative of the Icelandic population. There was a 34.9% response rate ( n=873). Results: Of the 873 source of this study, 26.6% (n=211) categorised as Group A had lived with relatives who excessively consumed alcohol, and this had negatively affected them in their childhood. In their adult years, Group A seemed to be more frequently intoxicated than the control group, Group B (n=659). They also experienced more negative consequences from their alcohol consumption. Group A was likely to consume alcohol to deal with difficult feelings such as depression, and they were also more likely to abstain than Group B. Conclusions: The childhood experience of living with relatives who excessively use alcohol does not impact everyone in the same way in their adult years. Some of them are more likely to use excessive alcohol as adults without relating it to their childhood experience of relatives excessively using alcohol.

Obstructive sleep apnea is an independent risk factor for severe COVID-19: a population-based study

Study Objectives Obstructive sleep apnea (OSA) has been proposed as a risk factor for severe COVID-19. Confounding is an important consideration as OSA is associated with several known risk factors for severe COVID-19. Our aim was to assess the association of OSA with hospitalization due to COVID-19 using a population-based cohort with detailed information on OSA and comorbidities. Methods Included were all community-dwelling Icelandic citizens 18 years of age and older diagnosed with SARS-CoV-2 infection in 2020. Data on demographics, comorbidities, and outcomes of COVID-19 was obtained from centralized national registries. Diagnosis of OSA was retrieved from the centralized Sleep Department Registry at Landspitali–The National University Hospital. Severe COVID-19 was defined as the composite outcome of hospitalization and death. The associations between OSA and the outcome were expressed as odds ratios (OR) with 95% confidence intervals (95% CI), calculated using logistic regression models and inverse probability weighting. Results A total of 4,756 individuals diagnosed with SARS-CoV-2 infection in Iceland were included in the study (1.3% of the Icelandic population), of whom 185 had a diagnosis of OSA. In total, 238 were hospitalized or died, 38 of whom had OSA. Adjusted for age, sex, and BMI, OSA was associated with poor outcome (OR 2.2, 95% CI 1.4 -3.5). This association was slightly attenuated (OR 2.0, 95% CI 2.0, 1.2-3.2) when adjusted for demographic characteristics and various comorbidities. Conclusions OSA was associated with twofold increase in risk of severe COVID-19, and the association was not explained by obesity or other comorbidities.

Presence of male mitochondria in somatic tissues and their functional importance at the whole animal level in the marine bivalve Arctica islandica

Metazoans normally possess a single lineage of mitochondria inherited from the mother (♀-type mitochondria) while paternal mitochondria are absent or eliminated in fertilized eggs. In doubly uniparental inheritance (DUI), which is specific to the bivalve clade including the ocean quahog, Arctica islandica, ♂-type mitochondria are retained in male gonads and, in a few species, small proportions of ♂-type mitochondria co-exist with ♀-type in somatic tissues. To the best of our knowledge, we report, for the first time in metazoan, the natural occurrence of male and female individuals with exclusively ♂-type mitochondria in somatic tissues of the bivalve A. islandica. Mitochondrial genomes differ by ~5.5% at DNA sequence level. Exclusive presence of ♂-type mitochondria affects mitochondrial complexes partially encoded by mitochondrial genes and leads to a sharp drop in respiratory capacity. Through a combination of whole mitochondrial genome sequencing and molecular assays (gene presence and expression), we demonstrate that 1) 11% of individuals of an Icelandic population appear homoplasmic for ♂-type mitochondria in somatic tissues, 2) ♂-type mitochondrial genes are transcribed and 3) individuals with ♂-type mitochondria in somatic cells lose 30% of their wild-type respiratory capacity. This mitochondrial pattern in A. islandica is a special case of DUI, highlighted in individuals from both sexes with functional consequences at cellular and conceivably whole animal level.

Outpatient physical therapy population has been aging faster than the general population: a total population register-based study

Background The Icelandic population is aging like other populations in the world, the life expectancy is high, and the national focus is to help people to age in their own homes. The objectives of this research was to describe 17 years of demographic changes among outpatient physical therapy (OPT) clients and to determine if these changes reflect aging in the total population. Methods Data was obtained from a national registry with information on all OPT clients reimbursed by Icelandic Health Insurance from 1999 to 2015, and general population data from the Statistics Iceland registry covering the same 17 years. Simple counts, proportions, Rate Ratios (RR) and 95 % Confidence Intervals (CI) were used to describe and compare the two time-points (1999 and 2015) in both populations, and regression analyses were used to estimate linear changes for each of these 17 years. Results Comparing the endpoints of the 17-year period, the proportion of older adults within the total OPT clientele increased by 23 % (from 18.3 % to 1999 to 23.5 % in 2015; RR 1.23; 95 %CI 1.19–1.27).) while in the general Icelandic population, the proportion of older adults increased by 15 % (from 11.6 % to 1999 to 13.5 % in 2015; RR 1.15; 95 % CI 1.1–1.21). For each of these 17 years, there was an overall 5 % yearly increase in the rate of older adults from the general older Icelandic population who used an OPT (accounting for population aging), and an overall 3.5 % yearly increase in the proportional contribution of older adults to the total OPT clientele. Adjusting for sex and older age group revealed that this increase in rate and proportion was most pronounced among ≥ 85-year-old men. Conclusions This case of Iceland is an example of how health-related and population-based registers may potentially be used to routinely inform and facilitate optimal planning of future health care services for older adults.

The protective mutation A673T in amyloid precursor protein gene decreases Aβ peptides production for 14 forms of Familial Alzheimer’s Disease in SH-SY5Y cells

The deposition of Aβ plaques in the brain leads to the onset and development of Alzheimer’s disease. The Amyloid precursor protein (APP) is cleaved by α-secretase (non-amyloidogenic processing of APP), however increased cleavage by β-secretase (BACE1) leads to the accumulation of Aβ peptides, which forms plaques. APP mutations mapping to exons 16 and 17 favor plaque accumulation and cause Familial Alzheimer Disease (FAD). However, a variant of the APP gene (A673T) originally found in an Icelandic population reduces BACE1 cleavage by 40%. A series of plasmids containing the APP gene, each with one of 29 different FAD mutations mapping to exon 16 and exon 17 was created. These plasmids were then replicated with the addition of the A673T mutation. Combined these formed the library of plasmids that was used in this study. The plasmids were transfected in neuroblastomas to assess the effect of this mutation on Aβ peptide production. The production of Aβ peptides was decreased for some FAD mutations due to the presence of the co-dominant A673T mutation. The reduction of Aβ peptide concentrations for the London mutation (V717I) even reached the same level as for A673T control in SH-SY5Y cells. These preliminary results suggest that the insertion of A673T in APP genes containing FAD mutations might confer a clinical benefit in preventing or delaying the onset of some FADs.

Outpatient Physical Therapists Should be Competent in Care of Older Adults: A Total Population Register-Based Study

In Iceland, outpatient physical therapy (OPT) is traditionally not focused on older clients. Yet, the Icelandic population is aging as other populations in the world, and national policies endorse aging in place. The objective of this study was to explore 17 years of demographic information on OPT clients and to identify if this information reflects the total population aging. The research was built on 17 years (1999-2015) of complete data from: the Icelandic Health Insurances register with information on the total population of OPT clients (N=172071), and the Statistics Iceland register with demographic information on the total general population. The results revealed that in 1999, older adults comprised 18.3% of all OPT clients, and in 2015 it had increased to 23.5% Therefore, OPTs were 23% more likely to treat an older adult in 2015, compared to 1999 (Risk Ratio [RR] 1.23; 95% Confidence Interval [CI] 1.19-1.27). In the same time period older people became 15% more prevalent in the general population (RR 1.15; 95%CI 1.10-1.21). Linear modelling revealed a yearly 3.45% (95%CI 3.05-3.85) increase from 1999 to 2015 in the overall proportion of older OPT clients. This yearly trend, however, varied depending on age group and sex with the highest yearly increase in the ≥ 85 years old men (9.1%; 95%CI 7.90-10.35). This case of Iceland presents 17 years of continuous growth in older adults seeking OPT service. These findings reinforce an urgent need to enhance the geriatric competence of OPTs, who in their clinical practice frequently encounter older adults.

Base editing strategy allows insertion of the A673T mutation in APP gene to prevent the development of Alzheimer’s disease

ABSTRACTAmyloid precursor protein (APP), a membrane protein mostly found in neurons, is preferentially cut by the α-secretase enzyme, however, abnormal cleavage by β-secretase leads to the formation of β-amyloid peptide plaque in the brains of Alzheimer’s patients. Genome analysis of an Icelandic population that did not appear to show symptoms of Alzheimer’s at advanced age led to the discovery of the A673T mutation, reducing β-secretase cleavage by 40%. We hypothesized that the insertion of this mutation in a patient’s genome could be an effective and sustainable method to slow down or prevent the progression of familial and sporadic forms of Alzheimer’s disease. We have thus modified the APP gene in HEK293T cells and in SH-SY5Y neuroblastoma using a Cas9n-deaminase enzyme, which changes a cytosine into a thymine, thus converting the alanine codon to a threonine. Several Cas9n-deaminase variants were tested to compare their efficiency of conversion. The results were characterized and quantified by deep sequencing. We successfully modified the APP gene in up to 56.7% of the HEK293T cells. Our approach aimed to attest to the efficiency of base editing in the development of treatments against genetic diseases as well as provide a new strategy for the treatment of Alzheimer’s.

Origin of the Trichoptera species in Iceland

This paper focuses on the origin of Trichoptera species in Iceland in light of the island biogeography of caddisflies in the North-Atlantic islands, i.e., Greenland, Svalbard, Iceland, Faroe Islands, Shetland, and Orkney, and adjacent larger regions, Norway and Britain. Three of the 12 recorded species have circumpolar distribution, the other nine are Palaearctic. The number of species declines with the distance from the mainland of Europe and is independent of the island sizes. However, the occurrence of species is stochastic, with only a few species common to the more remote islands—e.g., Iceland has 12 species and the Faroe Islands 20, but only 4 species are common to both islands. Studies on phylogeographic patterns of two species, Potamophylax cingulatus and Apatania zonella, show different history based on genetic markers. Potamophylax cingulatus in Iceland is from a western European lineage, distinct from two eastern and southern European lineages that may have diverged in southern refugia during the glacial periods of the latest Ice Age. The ancestors of the Icelandic population have migrated from the Iberian Peninsula up the west cost of Europe to the Faroe Islands and Iceland. The parthenogenetic A. zonella in Iceland originated near the Bering Strait, and has migrated along two routes, one westward through northern Eurasia and the other eastward through North America and Greenland to Iceland, where the two populations meet. Preliminary phylogeographic studies on two other circumpolar species, Limnephilus fenestratus and L. picturatus indicate possible interchanges between North America and Europe, but due to a low number of samples, it is difficult to state where the Icelandic population came from.