scholarly journals SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe

2020 ◽  
Author(s):  
Eva SL Pedersen ◽  
Myrofora Goutaki ◽  
Amanda L Harris ◽  
Lucy Dixon ◽  
Michele Manion ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Severe Symptom ◽  
Demographic Data ◽  
Severe Disease ◽  
Median Number ◽  
Disease Course ◽  
Increased Risk ◽  
Using Data ◽  
Ciliary Dyskinesia

AbstractPeople with pre-existing chronic health conditions are reportedly at high risk of getting the coronavirus disease (COVID-19) and of having a severe disease course but little data exist on rare diseases such as Primary Ciliary Dyskinesia (PCD). We studied risk and severity of SARS-CoV-2 infections among people with PCD using data from the COVID-PCD, a participatory study that collects data in real-time directly from people with PCD. Data was collected using online questionnaires. A baseline questionnaire collected information on demographic data, information about the PCD diagnosis and severity. A short weekly questionnaire collected information about current symptoms and incident SARS-CoV-2 infections. 578 people participated in the COVID-PCD by December 7, 2020, with a median number of follow-up weeks of 9 (interquartile range: 4-19 weeks). 256 (45%) of the participants had been tested for SARS-CoV-2 and 12 tested positive prior to study entry or during study follow up (2.1% of the total included population, 95% confidence interval (CI) 1.1-3.6%). 4 people tested positive during the study follow-up, corresponding to an incidence rate of 2.5 per 100 person-years (95% CI: 0.9-6.5). Overall, reported severity was mild with two reporting no symptoms, eight reporting mild symptoms, one reporting severe symptom without hospitalisation, and one reporting hospitalisation for 9 days. The study suggests that with careful personal protection, people with PCD do not seem to have an increased risk of infection with SARS-COV-2, nor an especially severe disease course.Take home messageIn this longitudinal study of people with PCD followed weekly via online questionnaires, the incidence rate of COVID-19 and the proportion of participants infected were low, and the observed severity mostly mild.

scholarly journals A serum protein network predicts the need for systemic immunomodulatory therapy in autoimmune uveitis

2021 ◽  
Author(s):  
Jonas J.W. Kuiper ◽  
Fleurieke H. Verhagen ◽  
Sanne Hiddingh ◽  
Roos A.W. Wennink ◽  
Anna M. Hansen ◽  
...  
Keyword(s):  
Serum Protein ◽  
Clinical Decision Making ◽  
Severe Disease ◽  
Protein Network ◽  
Immunomodulatory Therapy ◽  
Anatomical Location ◽  
Disease Course ◽  
Autoimmune Uveitis ◽  
Increased Risk

Objective biomarkers that can predict a severe disease course of autoimmune uveitis are lacking, and warranted for early identification of high-risk patients to improve visual outcome. The need for non-steroid immunomodulatory therapy (IMT) to control autoimmune uveitis is indicative of a more severe disease course. We used aptamer-based proteomics and a bioinformatic pipeline to uncover the serum protein network of 52 treatment-free patients and 26 healthy controls, and validation cohorts of 114 and 67 patients. Network-based analyses identified a highly co-expressed serum signature (n=85 proteins) whose concentration was consistently low in controls, but varied between cases. Patients that were positive for the signature at baseline showed a significantly increased risk for IMT during follow-up, independent of anatomical location of disease. In an independent cohort (n=114), we established robust risk categories and confirmed that patients with high levels of the signature at diagnosis had a significantly increased risk to start IMT during follow-up. Finally, we further validated the predictive association of the signature in a third cohort of 67 treatment-naive North-American patients. A serum protein signature was highly predictive for IMT in human autoimmune uveitis and may serve as an objective blood biomarker to aid in clinical-decision making.

scholarly journals A multiple sclerosis disease progression measure based on cumulative disability

2021 ◽  
pp. 135245852098863
Author(s):  
Ali Manouchehrinia ◽  
Elaine Kingwell ◽  
Feng Zhu ◽  
Helen Tremlett ◽  
Jan Hillert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Severe Disease ◽  
Area Under The Curve ◽  
Disease Course ◽  
Cross Sectional ◽  
Age Related ◽  
Similar Disease ◽  
Longitudinal Comparison ◽  
Using Data

Background: Existing severity measurements in multiple sclerosis (MS) are often cross-sectional, making longitudinal comparisons of disease course between individuals difficult. Objective: The objective of this study is to create a severity metric that can reliably summarize a patient’s disease course. Methods: We developed the nARMSS – normalized ARMSS (age-related MS severity score) over follow-up, using the deviation of individual ARMSS scores from the expected value and integrated over the corresponding time period. The nARMSS scales from −5 to +5; a positive value indicates a more severe disease course for a patient when compared to other patients with similar disease timings. Results: Using Swedish MS registry data, the nARMSS was tested using data at 2 and 4 years of follow-up to predict the most severe quartile during the subsequent period up to 10 years total follow-up. The metric used was area under the curve of the receiver operating characteristic (AUC-ROC). This resulted in measurements of 0.929 and 0.941. In an external Canadian validation cohort, the equivalent AUC-ROCs were 0.901 and 0.908. Conclusion: The nARMSS provides a reliable, generalizable and easily measurable metric which makes longitudinal comparison of disease course between individuals feasible.

scholarly journals Use of incretin-based drugs and risk of cholangiocarcinoma: Scandinavian cohort study

Diabetologia ◽  
2021 ◽  
Author(s):  
Peter Ueda ◽  
Viktor Wintzell ◽  
Mads Melbye ◽  
Björn Eliasson ◽  
Ann-Marie Svensson ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Cox Regression ◽  
Absolute Rate ◽  
Dipeptidyl Peptidase 4 ◽  
Rate Difference ◽  
Receptor Agonists ◽  
Dpp4 Inhibitors ◽  
Increased Risk ◽  
Increase In Risk

Abstract Aims/hypothesis Concerns have been raised regarding a potential association of use of the incretin-based drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists with risk of cholangiocarcinoma. We examined this association in nationwide data from three countries. Methods We used data from nationwide registers in Sweden, Denmark and Norway, 2007–2018, to conduct two cohort studies, one for DPP4 inhibitors and one for GLP-1-receptor agonists, to investigate the risk of incident cholangiocarcinoma compared with an active-comparator drug class (sulfonylureas). The cohorts included patients initiating treatment episodes with DPP4 inhibitors vs sulfonylureas, and GLP-1-receptor agonists vs sulfonylureas. We used Cox regression models, adjusted for potential confounders, to estimate hazard ratios from day 366 after treatment initiation to account for cancer latency. Results The main analyses of DPP4 inhibitors included 1,414,144 person-years of follow-up from 222,577 patients receiving DPP4 inhibitors (median [IQR] follow-up time, 4.5 [2.6–7.0] years) and 123,908 patients receiving sulfonylureas (median [IQR] follow-up time, 5.1 [2.9–7.8] years) during which 350 cholangiocarcinoma events occurred. Use of DPP4 inhibitors, compared with sulfonylureas, was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.15 [95% CI 0.90, 1.46]; absolute rate difference 3 [95% CI -3, 10] events per 100,000 person-years). The main analyses of GLP-1-receptor agonists included 1,036,587 person-years of follow-up from 96,813 patients receiving GLP-1-receptor agonists (median [IQR] follow-up time, 4.4 [2.4–6.9] years) and 142,578 patients receiving sulfonylureas (median [IQR] follow-up time, 5.5 [3.2–8.1] years) during which 249 cholangiocarcinoma events occurred. Use of GLP-1-receptor agonists was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.25 [95% CI 0.89, 1.76]; absolute rate difference 3 [95% CI -5, 13] events per 100,000 patient-years). Conclusions/interpretation In this analysis using nationwide data from three countries, use of DPP4 inhibitors and GLP-1-receptor agonists, compared with sulfonylureas, was not associated with a significantly increased risk of cholangiocarcinoma. Graphical abstract

Emotional states and future risk of venous thromboembolism

2012 ◽  
Vol 107 (03) ◽  
pp. 485-493 ◽  
Author(s):  
Sigrid K. Brækkan ◽  
Ida J. Hansen-Krone ◽  
John-Bjarne Hansen ◽  
Kristin F. Enga
Keyword(s):  
Venous Thromboembolism ◽  
Incidence Rate ◽  
Population Based ◽  
Emotional States ◽  
Depressive Feelings ◽  
Increased Risk ◽  
Adjusted Incidence Rate ◽  
Adjusted Incidence ◽  
Reduced Risk

SummaryEmotional states of depression and loneliness are reported to be associated with higher risk and optimism with lower risk of arterial cardiovascular disease (CVD) and death. The relation between emotional states and risk of venous thromboembolism (VTE) has not been explored previously. We aimed to investigate the associations between self-reported emotional states and risk of incident VTE in a population-based, prospective study. The frequency of feeling depressed, lonely and happy/optimistic were registered by self-administered questionnaires, along with major co-morbidities and lifestyle habits, in 25,964 subjects aged 25–96 years, enrolled in the Tromsø Study in 1994–1995. Incident VTE-events were registered from the date of inclusion until September 1, 2007. There were 440 incident VTE-events during a median of 12.4 years of follow-up. Subjects who often felt depressed had 1.6-fold (95% CI:1.02–2.50) higher risk of VTE compared to those not depressed in analyses adjusted for other risk factors (age, sex , body mass index, oes-trogens), lifestyle (smoking, alcohol consumption, educational level) and co-morbidities (diabetes, CVD, and cancer). Often feeling lonely was not associated with VTE. However, the incidence rate of VTE in subjects who concurrently felt often lonely and depressed was higher than for depression alone (age-and sex-adjusted incidence rate: 3.27 vs. 2.21). Oppositely, subjects who often felt happy/optimistic had 40% reduced risk of VTE (HR 0.60, 95% CI: 0.41–0.87). Our findings suggest that self-reported emotional states are associated with risk of VTE. Depressive feelings were associated with increased risk, while happiness/ optimism was associated with reduced risk of VTE.

scholarly journals An Objective Search for Unrecognized Bias in Validated COVID-19 Prediction Models

2021 ◽  
Author(s):  
Hossein Estiri ◽  
Zachary Strasser ◽  
Sina Rashidian ◽  
Jeffrey Klann ◽  
Kavishwar Wagholikar ◽  
...  
Keyword(s):  
Predictive Models ◽  
Medical Records ◽  
Prediction Models ◽  
Evaluation Studies ◽  
Protected Group ◽  
Increased Risk ◽  
Using Data ◽  
Bias Evaluation ◽  
Algorithmic Bias

The growing recognition of algorithmic bias has spurred discussions about fairness in artificial intelligence (AI) / machine learning (ML) algorithms. The increasing translation of predictive models into clinical practice brings an increased risk of direct harm from algorithmic bias; however, bias remains incompletely measured in many medical AI applications. Using data from over 56 thousand Mass General Brigham (MGB) patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we evaluate unrecognized bias in four AI models developed during the early months of the pandemic in Boston, Massachusetts that predict risks of hospital admission, ICU admission, mechanical ventilation, and death after a SARS-CoV-2 infection purely based on their pre-infection longitudinal medical records. We discuss that while a model can be biased against certain protected groups (i.e., perform worse) in certain tasks, it can be at the same time biased towards another protected group (i.e., perform better). As such, current bias evaluation studies may lack a full depiction of the variable effects of a model on its subpopulations. If the goal is to make a change in a positive way, the underlying roots of bias need to be fully explored in medical AI. Only a holistic evaluation, a diligent search for unrecognized bias, can provide enough information for an unbiased judgment of AI bias that can invigorate follow-up investigations on identifying the underlying roots of bias and ultimately make a change.

scholarly journals Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Priyatharsan Yoganathan ◽  
Jean-Benoit Rossel ◽  
Sebastian Bruno Ulrich Jordi ◽  
Yannick Franc ◽  
Luc Biedermann ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Severe Disease ◽  
Regulatory Region ◽  
Disease Course ◽  
Pyrin Domain ◽  
Homozygous Genotype ◽  
Increased Risk ◽  
Major Allele ◽  
The Impact

Abstract Background Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.

Psoriasis and Psoriatic Arthritis in the Context of the COVID-19 Pandemic: A Plenary Session From the GRAPPA 2020 Annual Meeting

2021 ◽  
pp. jrheum.201671
Author(s):  
Philip J. Mease ◽  
Leonard H. Calabrese ◽  
Kristina Callis Duffin ◽  
Rebecca H. Haberman ◽  
Rodrigo Firmino ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Annual Meeting ◽  
Severe Disease ◽  
Vaccine Safety ◽  
Global Scale ◽  
Disease Course ◽  
Risk Of Infection ◽  
Psoriatic Disease ◽  
Increased Risk ◽  
Infectious Disease Specialists

The coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic has affected the healthcare system on a global scale, and we utilized the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 annual meeting to examine how COVID-19 might affect patients with psoriatic disease (PsD) and the clinicians who care for them. Pressing issues and concerns identified included whether having psoriasis increased the risk of acquiring COVID-19, vaccine safety, and the acceptability of telehealth. The general message from rheumatologists, dermatologists, infectious disease specialists, and patient research partners was that data did not suggest that having PsD or its treatment significantly increased risk of infection or more severe disease course, and that the telehealth experience was a success overall.

scholarly journals Relapsing and progressive MS: the sex-specific perspective

2020 ◽  
Vol 13 ◽  
pp. 175628642095649
Author(s):  
Paulus Stefan Rommer ◽  
David Ellenberger ◽  
Kerstin Hellwig ◽  
Judith Haas ◽  
Dieter Pöhlau ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Sex Ratio ◽  
Demographic Data ◽  
Age At Onset ◽  
Symptomatic Treatment ◽  
Decisive Factor ◽  
Disease Course ◽  
Male Ratio ◽  
Female Sex

Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease whose aetiology is not fully understood. The female sex is clearly predominant, with a sex ratio between 2 and 3. In primary progressive MS the sex ratio almost balances out. Since the age at onset is higher for patients with progressive onset (POMS) than for relapsing onset (ROMS), it can be hypothesized that the age at onset is a decisive factor for the sex ratio. Methods: To address this aspect, we compare clinical and demographic data between females and males for the different disease courses within the population of the German MS Register by the German MS Society. Only patients with complete details in mandatory data items and a follow-up visit since 01. Jan 2018 were included. Results: A total of 18,728 patients were included in our analyses, revealing a female-to-male ratio of 2.6 (2.7 for patients with ROMS and 1.3 for POMS). The age at diagnosis is higher in patients with POMS (43.3 and 42.3 years for females and males versus 32.1 and 33.2 years, respectively). Females irrespective of disease course are statistically significantly more often affected by cognitive impairment (POMS: p = 0.013, ROMS: p = 0.001) and depression (POMS: p = 0.002, ROMS: 0.001) and suffer more often from pain (POMS and ROMS: p < 0.001). Fatigue is significantly more often seen in females with ROMS ( p < 0.001) but not in POMS. Females with ROMS retire significantly ( p < 0.001) earlier (42.8 versus 44.2 years) and to a greater extent than males (28 versus 24%). Disease progression was similar for women and men. Conclusion: Our analysis shows that clinical and demographic data differ more between disease courses than between men and women. For pain, depression and cognitive impairment the female sex is the decisive factor. Whether these factors are responsible for the earlier retirement of females with ROMS is not clear. Appropriate measures for optimization of symptomatic treatment as well as to promote employment should be taken.

scholarly journals Early Description of Coronavirus 2019 Disease in Kidney Transplant Recipients in New York

2020 ◽  
Vol 31 (6) ◽  
pp. 1150-1156 ◽  
Author(s):  
Keyword(s):  
New York ◽  
Kidney Transplant ◽  
Severe Disease ◽  
Treatment Protocol ◽  
Current Treatment ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Radiographic Findings ◽  
Increased Risk

BackgroundThe novel SARS-CoV-2 virus has caused a global pandemic of coronavirus disease 2019 (COVID-19). Although immunosuppressed individuals are thought to be at an increased risk of severe disease, little is known about their clinical presentation, disease course, or outcomes.MethodsWe report 15 kidney transplant recipients from the Columbia University kidney transplant program who required hospitalization for confirmed COVID-19, and describe their management, clinical course, and outcomes.ResultsPatients presented most often with a fever (87%) and/or cough (67%). Initial chest x-ray most commonly showed bilateral infiltrates, but 33% had no acute radiographic findings. Patients were managed with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin. Although 27% of our patients needed mechanical ventilation, over half were discharged home by the end of follow-up.ConclusionsKidney transplant recipients with COVID-19 have presentations that are similar to that of the general population. Our current treatment protocol appears to be associated with favorable outcomes, but longer follow-up of a larger cohort of patients is needed.

scholarly journals OP12 The incidence and disease course of perianal Crohn’s disease: A Danish nationwide cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S012-S012
Author(s):  
M D Wewer ◽  
M Zhao ◽  
A Nordholm-Carstensen ◽  
J B Seidelin ◽  
J Burisch
Keyword(s):  
Rectal Cancer ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Incidence Rate ◽  
Anal Cancer ◽  
Perianal Fistula ◽  
Disease Course ◽  
Perianal Crohn’S Disease ◽  
Increased Risk ◽  
Perianal Crohn's Disease

Abstract Background Perianal Crohn’s disease (pCD) has a major negative impact on patients’ quality of life and is complex to treat. Despite its putative high frequency and burden for patients, only a few studies have investigated the incidence, disease course and associated cancer-risk in a population-based setting. The aim was to assess the incidence and course of pCD in adult patients with CD within a 19-year period. Specifically, describing changes in medical and surgical management as well as rates of cancer. Methods The cohort comprised all individuals &gt;18 years diagnosed with CD in Denmark between 1 January 1997 and 31 December 2015. Patients were identified in the National Patient Registry. Chi-square test, Mann–Whitney–Wilcoxon test and multivariate Cox regression analysis were used. Results A total of 1,697/9,739 (17%) patients with CD were found to have pCD. Perianal fistulas were the most common manifestation accounting for 943 (56%) cases. The onset of pCD before CD diagnosis occurred in 32%. The overall incidence of pCD was 20/1,000 patient-years. The incidence of pCD remained stable over time. More patients with pCD were treated with immunomodulators (70%) and biologics (35%) than those without pCD (51%, p &lt; 0.001 and 15%, p &lt; 0.001, respectively). Defunctioning stoma was performed in 157/943 (17%) of perianal fistula patients. Stoma formation in relation to resection was performed in 112/943 (12%) of perianal fistula patients. Patients with pCD were found to have a significantly increased risk of undergoing major abdominal surgery compared with patients without pCD (hazard ratio: 1.52, 95% CI: 1.40 to 1.65, p &lt; 0.001). The incidence rate ratios of anal and rectal cancer in pCD patients were 12.46 (95% CI: 5.07 to 30.59, p &lt; 0.001) and 2.41 (95% CI: 1.31 to 4.42, p = 0.003) respectively, when compared with non-IBD matched controls. The incidence rate ratio of anal and rectal cancer in pCD patients was 2.36 (95% CI: 0.86 to 6.50, p = 0.09) and 1.35 (95% CI: 0.68 to 2.68, p = 0.38) respectively, when compared with CD patients without pCD. Conclusion In this nationwide study, 17% of the CD patients developed pCD. The continuing high incidence of pCD suggests a limited disease-modifying effect of biologics. Patients with pCD were at increased risk of undergoing major surgery compared with non-pCD patients. The risk of rectal or anal cancer was increased in patients with pCD compared with non-IBD matched controls. These findings encourage surveillance of rectal and anal cancer.

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