Landspítali University Hospital Research Archive
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Association of Social Determinants of Health with Time to Diagnosis and Treatment Outcomes in Idiopathic Subglottic Stenosis.
No full textTo access publisher's full text version of this article click on the hyperlink belowObjectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients.
Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence.
Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of 50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression.
Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.Patient-Centered Outcomes Research Institute
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Heart Lung & Blood Institute (NHLBI)
Appeared in source as:National Heart, Lung, and Blood Institute, NIH
National Institute for Deafness and other Communication Disorders, NI
Cancer screening in Iceland
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Clinical management of patients with drug‐induced liver injury (DILI)
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadDrug-induced liver injury (DILI) should be considered in all patients with recent elevation of liver tests without obvious etiology and normal hepatobiliary imaging. There is currently no biomarker that is helpful in diagnosis which relies on clinical and laboratory findings. Diagnosis is dependent on temporal relationship with a recently started drug or herbal and dietary supplement and elevated liver tests with exclusion of competing etiologies. The implicated agent should be discontinued and the patient should be observed closely. This is particularly important in patients with jaundice who have approximately 10% risk of liver related mortality and/or need for liver transplantation. There is no specific therapy for DILI which is only symptomatic such as for itching. Patients with jaundice and coagulopathy usually require hospitalization
Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadOsteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.UK Biobank Resource
UK Research & Innovation (UKRI)
Medical Research Council UK (MRC)
NIHR Nottingham BRC
University of Bristol
UK Research & Innovation (UKRI)
Medical Research Council UK (MRC
NANS-CDG: Delineation of the Genetic, Biochemical, and Clinical Spectrum.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: NANS-CDG is a recently described congenital disorder of glycosylation caused by biallelic genetic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. Sialic acid at the end of glycoconjugates plays a key role in biological processes such as brain and skeletal development. Here, we present an observational cohort study to delineate the genetic, biochemical, and clinical phenotype and assess possible correlations. Methods: Medical and laboratory records were reviewed with retrospective extraction and analysis of genetic, biochemical, and clinical data (2016-2020). Results: Nine NANS-CDG patients (nine families, six countries) referred to the Radboudumc CDG Center of Expertise were included. Phenotyping confirmed the hallmark features including intellectual developmental disorder (IDD) (n = 9/9; 100%), facial dysmorphisms (n = 9/9; 100%), neurologic impairment (n = 9/9; 100%), short stature (n = 8/9; 89%), skeletal dysplasia (n = 8/9; 89%), and short limbs (n = 8/9; 89%). Newly identified features include ophthalmological abnormalities (n = 6/9; 67%), an abnormal septum pellucidum (n = 6/9; 67%), (progressive) cerebral atrophy and ventricular dilatation (n = 5/9; 56%), gastrointestinal dysfunction (n = 5/9; 56%), thrombocytopenia (n = 5/9; 56%), and hypo-low-density lipoprotein cholesterol (n = 4/9; 44%). Biochemically, elevated urinary excretion of N-acetylmannosamine (ManNAc) is pathognomonic, the concentrations of which show a significant correlation with clinical severity. Genotypically, eight novel NANS variants were identified. Three severely affected patients harbored identical compound heterozygous pathogenic variants, one of whom was initiated on experimental prenatal and postnatal treatment with oral sialic acid. This patient showed markedly better psychomotor development than the other two genotypically identical males. Conclusions: ManNAc screening should be considered in all patients with IDD, short stature with short limbs, facial dysmorphisms, neurologic impairment, and an abnormal septum pellucidum +/- congenital and neurodegenerative lesions on brain imaging, to establish a precise diagnosis and contribute to prognostication. Personalized management includes accurate genetic counseling and access to proper supports and tailored care for gastrointestinal symptoms, thrombocytopenia, and epilepsy, as well as rehabilitation services for cognitive and physical impairments. Motivated by the short-term positive effects of experimental treatment with oral sialic, we have initiated this intervention with protocolized follow-up of neurologic, systemic, and growth outcomes in four patients. Research is ongoing to unravel pathophysiology and identify novel therapeutic targets.European Reference Network for Rare Neurological Disease
HLA-B*27 is significantly enriched in Nordic patients with psoriatic arthritis mutilans.
No full textTo access publisher's full text version of this article click on the hyperlink belowObjectives: The genetic contribution to psoriatic disease is substantial with a dominating influence of the HLA region. The profile of HLA class I genotypes likely contributes to shaping clinical phenotypes. Herein we aimed to explore such genotypes in cohorts of closely characterised subsets of psoriatic disease with special focus on psoriatic arthritis mutilans (PAM), a severe and rare form of psoriatic arthritis (PsA).
Methods: Cohorts of patients with the diagnosis of psoriasis vulgaris with or without arthritis (n=1217), psoriasis without arthritis (n=534), psoriatic arthritis without mutilating disease (n=337) and psoriatic arthritis mutilans (n=63) were collected and genotyped for HLA class I and II genes, with standardised methodologies. Cases were compared with a healthy control population (n=2468). Case-only and case-control association tests were performed to address the hypothesis of genetic contribution to clinical phenotypes.
Results: The presence of HLA-B*27 was strikingly increased in PAM (45%) compared with PsA without mutilating disease (13%) and with healthy controls (13%). However, within the PAM population, HLA-B*27 did not correlate with clinical markers such as number of mutilating joints, radiographic scoring, disease duration and age of disease onset.
Conclusions: HLA-B*27 emerges as an important genotype marker for PAM.UK Research & Innovation (UKRI)
Medical Research Council UK (MRC)
European Commission
Swedish Psoriasis Association
Finsen Foundation
Karolinska Institutet
Nordic Psoriasis Patient Society (NORDPSO
Economic Evaluation of Damage Accrual in an International Systemic Lupus Erythematosus Inception Cohort Using a Multistate Model Approach.
No full textTo access publisher's full text version of this article click on the hyperlink belowObjective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling.
Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model.
Results: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6-18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: 16,662, 1,833 (95% CI 2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: 142,318, 21,713 (95% CI 29,788) for SDI scores of 0.
Conclusion: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies.Versus Arthritis
Canadian Institutes of Health Research (CIHR)
Medical Research Council UK (MRC)
United States Department of Health & Human Services
National Institutes of Health (NIH) - US
P300 Analysis Using High-Density EEG to Decipher Neural Response to rTMS in Patients With Schizophrenia and Auditory Verbal Hallucinations.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadSchizophrenia is a complex disorder about which much is still unknown. Potential treatments, such as transcranial magnetic stimulation (TMS), have not been exploited, in part because of the variability in behavioral response. This can be overcome with the use of response biomarkers. It has been however shown that repetitive transcranial magnetic stimulation (rTMS) can the relieve positive and negative symptoms of schizophrenia, particularly auditory verbal hallucinations (AVH). This exploratory work aims to establish a quantitative methodological tool, based on high-density electroencephalogram (HD-EEG) data analysis, to assess the effect of rTMS on patients with schizophrenia and AVH. Ten schizophrenia patients with drug-resistant AVH were divided into two groups: the treatment group (TG) received 1 Hz rTMS treatment during 10 daily sessions (900 pulses/session) over the left T3-P3 International 10-20 location. The control group (CG) received rTMS treatment over the Cz (vertex) EEG location. We used the P300 oddball auditory paradigm, known for its reduced amplitude in schizophrenia with AVH, and recorded high-density electroencephalography (HD-EEG, 256 channels), twice for each patient: pre-rTMS and 1 week post-rTMS treatment. The use of HD-EEG enabled the analysis of the data in the time domain, but also in the frequency and source-space connectivity domains. The HD-EEG data were linked with the clinical outcome derived from the auditory hallucinations subscale (AHS) of the Psychotic Symptom Rating Scale (PSYRATS), the Quality of Life Scale (QoLS), and the Depression, Anxiety and Stress Scale (DASS). The general results show a variability between subjects, independent of the group they belong to. The time domain showed a higher N1-P3 amplitude post-rTMS, the frequency domain a higher power spectral density (PSD) in the alpha and beta bands, and the connectivity analysis revealed a higher brain network integration (quantified using the participation coefficient) in the beta band. Despite the small number of subjects and the high variability of the results, this work shows a robust data analysis and an interplay between morphology, spectral, and connectivity data. The identification of a trend post-rTMS for each domain in our results is a first step toward the definition of quantitative neurophysiological parameters to assess rTMS treatment.
Keywords: P300; TMS (repetitive transcranial magnetic stimulation); brain connectivity; high-density EEG; schizophrenia; spectral analysis; temporal analysis.United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Neurological Disorders & Stroke (NINDS)
Landspitali Scientific fund
Sepsis after elective surgery - Incidence, aetiology and outcome.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Sepsis requiring admission to intensive care (ICU) is a rare complication of elective surgery, but is associated with high morbidity and mortality. The aim of this study was to describe the incidence and outcome of sepsis following elective surgery.
Methods: This was a retrospective, observational study where all admissions to Icelandic ICUs during calendar years 2006, 2008, 2010, 2012, 2014 and 2016 were screened, identifing patients with sepsis following elective surgery (ACCP/SCCM criteria). The number of elective operations performed at the largest center (Landspitali) during the study years were collected. Descriptive statistics were used to assess the incidence and outcome of patients with sepsis after elective surgery.
Results: During the study years, 88 patients were admitted to Icelandic ICUs with sepsis following elective surgery. Of those, 80 were operated at Landspitali, where the incidence of sepsis was 0.19% per elective procedure, highest following pancreaticoduodenectomies (14%, CI 6-25) and esophagectomies (13%, CI 4-27), but the greatest number of patients (30% (26/88)) developed sepsis after a colorectal procedure. The most common infection sources were the abdomen (65% (57/88)) and lungs/mediastinum (22% (19/88)), frequently polymicrobial (58% (36/62) of patients with cultures). The incidence of insufficient empirical antibiotics was high (50% (30/60)). The median ICU and hospital length-of-stay were 5.5 and 26 days and the 28-day and 1-year mortality rates were 16% (14/88) and 41% (36/87), respectively.
Conclusions: Incidence of sepsis following elective surgery is low in Iceland but mortality is high. Initial antimicrobial therapy needs careful consideration in these hospital-acquired, often polymicrobial infections.
Keywords: Sepsis; nosocomial infections; post-operative complications; surgery.Landspitali Haskolasjukrahu
Azithromycin has lung barrier protective effects in a cell model mimicking ventilator-induced lung injury.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAzithromycin (AZM) is a broad-spectrum antibiotic widely used to treat infections. AZM also has been shown to have anti-inflammatory and immunomodulatory functions unrelated to its antibacterial activity that contribute to the effectiveness of this drug in chronic respiratory diseases. The mechanisms behind these beneficial effects are not yet fully elucidated. We have previously shown that AZM enhances barrier integrity of bronchial epithelial cells and directs them towards epidermal differentiation. In this study, we analyzed the effect of AZM pre-treatment of human bronchial and alveolar derived cell lines on mechanical stress in a cyclical pressure air-liquid interface device (CPAD) that models the disruption of the epithelial barrier with increased inflammatory response in lung tissue, which is associated with ventilator-induced lung injury (VILI). Immunostaining and electron microscopy showed that barrier integrity of the epithelium was compromised by cyclically stressing the cells but maintained when cells had been pre-treated with AZM. Lamellar body formation was revealed in AZM pre-treated cells, possibly further supporting the barrier-enhancing effects. RNA sequencing showed that the inflammatory response was attenuated by AZM treatment before cyclical stress. YKL-40, an emerging inflammatory marker, increased both due to cyclical stress and upon AZM treatment. These data confirm the usefulness of the CPAD to model ventilator-induced lung injury and suggest that AZM has barrier protective and immunomodulatory effects, attenuating the inflammatory response during mechanical stress, and might therefore be lung protective during mechanical ventilation. The model could be used to assess further drug candidates that influence barrier integrity and modulate inflammatory response.
Keywords: YKL-40; airway epithelium; azithromycin; immunomodulation; ventilator-induced lung injury.Icelandic Research Council
Landspitali University Hospital science fun