tbuckley/cabot-search huggingface dataset:
Hospital admission and mortality rates for non-covid diseases in Denmark during covid-19 pandemic: nationwide population based cohort study
Authors: Jacob Bodilsen, Peter Brønnum Nielsen, Mette Søgaard, Michael Dalager-Pedersen, Lasse Ole Zacho Speiser, Troels Yndigegn, Henrik Nielsen, Torben Bjerregaard Larsen, Flemming Skjøth
Journal: BMJ (2021)

Abstract Objective To determine the incidence of hospital admissions and associated mortality rates for non-covid medical conditions during the covid-19 pandemic. Design Nationwide, population based cohort study. Setting Denmark from 13 March 2019 to 27 January 2021. Participants All Danish residents &gt;1 year of age. Main outcomes measures Population based healthcare registries that encompass the entire Danish population were used to compare hospital admission and mortality rates during the covid-19 pandemic (from 11 March 2020 to 27 January 2021) with the prepandemic baseline data (from 13 March 2019 to 10 March 2020). Hospital admissions were categorised as covid-19 when patients were assigned a diagnosis code for covid-19 within five days of admission. All patients were followed until migration, death, or end of follow-up, whichever came first. Rate ratios for hospital admissions were computed using Poisson regression and were directly standardised using the Danish population on 1 January 2019 as reference. 30 day mortality rate ratios were examined by Cox regression, adjusted for age and sex, and covid-19 diagnosis was used as a competing risk. Results 5 753 179 residents were identified during 567.8 million person weeks of observation, with 1 113 705 hospital admissions among 675 447 people. Compared with the prepandemic baseline period (mean hospital admission rate 204.1 per 100 000/week), the overall hospital admission rate for non-covid-19 conditions decreased to 142.8 per 100 000/week (rate ratio 0.70, 95% confidence interval 0.66 to 0.74) after the first national lockdown, followed by a gradual return to baseline levels until the second national lockdown when it decreased to 158.3 per 100 000/week (0.78, 0.73 to 0.82). This pattern was mirrored for most major diagnosis groups except for non-covid-19 respiratory diseases, nervous system diseases, cancer, heart failure, sepsis, and non-covid-19 respiratory infections, which remained lower throughout the study period. Overall 30 day mortality rates were higher during the first national lockdown (mortality rate ratio 1.28, 95% confidence interval 1.23 to 1.32) and the second national lockdown (1.20, 1.16 to 1.24), and these results were similar across most major diagnosis groups. For non-covid-19 respiratory diseases, cancer, pneumonia, and sepsis, the 30 day mortality rate ratios were also higher between lockdown periods. Conclusions Hospital admissions for all major non-covid-19 disease groups decreased during national lockdowns compared with the prepandemic baseline period. Additionally, mortality rates were higher overall and for patients admitted to hospital with conditions such as respiratory diseases, cancer, pneumonia, and sepsis. Increased attention towards management of serious non-covid-19 medical conditions is warranted.
AB0270 EFFECTIVENESS OF A SWITCH FROM TOFACITINIB TO BARICITINIB IN RHEUMATOID ARTHRITIS: A RETROSPECTIVE ANALYSIS OF REAL-WORLD DATA IN SWITZERLAND
Authors: S. Kellerhals, J. Amsler, H. Schulze-Koops, T. Hügle, M. J. Nissen, H. Paul, D. Kyburz, R. Muller
Journal: Annals of the Rheumatic Diseases (2021)

Background: Janus Kinase Inhibitors (JAKi) have recently been approved for the treatment of rheumatoid arthritis (RA) over the last years. JAKi differ in their specificity for the different JAK family members (JAK1, JAK2, JAK3 and TYK2). All three JAKis that are currently approved in Switzerland seem to have comparable efficacy on different disease stages of RA. Whether a JAKi can be effective after discontinuation of another JAKi is one of the open questions of interest according to the EULAR RA guidelines [1] . Objectives: To study the effectiveness of baricitinib in patients with RA after discontinuation of tofacitinib. Methods: Longitudinal, retrospective chart review conducted between October 2019 and December 2020 of patients with RA at two Swiss centers (Kantonsspital Aarau and Inselspital Bern). Disease activity was assessed by DAS 28. Results: 12 patients (1 male, 11 female) were treated with 4mg baricitinib/d after tofacitinib was discontinued. Mean age of the patients was 61 years, disease duration 140 months. Patients were previously treated with at least two conventional synthetic DMARDs and 75% with at least one biological DMARD. 58% of patients were positive for ACPA, 42% for rheumatoid factor. 50% of the patients suffered from erosive disease. Tofacitinib was stopped in 92% of the patients because of an insufficient response after a mean of 25.8 months. Moderate EULAR response was achieved in 83.3% of the patients after an average of 8 months treatment with baricitinib, and good EULAR response in 58.3% after an average of 10 months. There were no serious adverse events, neoplasms, opportunistic or serious infections during follow-up. Conclusion: The first retrospective analysis of real-world data of baricitinib following tofacitinib shows that there is a good clinical response in 70% of cases. Although limited by the number of patients this study therefore supports the notion that baricitinib after discontinuation of tofacitinib in RA patients may be an effective therapeutic option. References: [1]Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Annals of the Rheumatic Diseases . 2020;79(6):685-699. doi:10.1136/annrheumdis-2019-216655, p. 695 Disclosure of Interests: Simon Kellerhals: None declared, Jennifer Amsler: None declared, Hendrik Schulze-Koops: None declared, Thomas Hügle Consultant of: GSK, Abbvie, Pfizer, Jansen, Novartis, Eli Lilly., Michael J. Nissen Consultant of: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis and Pfizer., Hasler paul Consultant of: Abbvie, Lilly, Diego Kyburz Consultant of: Abbvie, Gilead, Lilly, Novartis and Pfizer, outside of the submitted work, Rudiger Muller Consultant of: Abbvie, Novartis, Grant/research support from: Bebro Pharma
Abstract 10341: Prevalence and Factors Associated With Statin Use Among a Nationally Representative Sample of US Adults - National Health and Nutrition Examination Survey, 2011-2012
Authors: Demilade Adedinsewo, Anekwe Onwuanyi
Journal: Circulation (2015)

Background: The 2013 AHA/ACC guidelines recommend the use of statins for adults ≤75 years who have clinical ASCVD (IA) and for primary prevention among persons aged 40 – 75 with diabetes mellitus and LDL btw 70 - 189mg/dl (IA). The aim of this study was to estimate the prevalence and likelihood of statin use among selected statin benefit groups. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) for the 2011 - 2012 cycle, we examined 5,319 adults aged 20 years and older. We estimated weighted frequencies and proportions with confidence intervals for the entire sample and for persons with diabetes and LDL ≥70 or a diagnosis of dyslipidemia, denoted statin benefit group 1 (SBG1) and for persons with history of ASCVD, statin benefit group 2 (SBG2). We constructed a multivariable logistic regression model to estimate the odds of statin use among persons in SBG1. All analyses were conducted using SAS survey procedures for complex sample data and evaluated at α=0.05. Results: Among persons in SBG1 (mean age: 61yrs), 59.5% (95% CI: 53.0 – 66.1), an estimated 10.6 million persons and 63.5% (95% CI: 55.6 – 71.4) of persons in SBG2 (mean age: 65yrs), an estimated 10.8 million persons were on a statin. A sub-population analysis among persons aged 40 – 75 showed statin use to be 58.8% (95% CI: 51.5 – 66.1) for persons in SBG1. Overall, an estimated 38.6 million Americans are on a statin, an increase from 24 million in 2003-2004. In adjusted models, uninsured persons and Hispanics compared to Whites were less likely to be on a statin. Conclusion: The prevalence of statin use among US adults has tripled since 1999-2000. However racial disparities and lack of insurance remain a barrier to statin use. Our study provides a baseline estimate of statin use in the noninstitutionalized civilian adult population just prior to the introduction of the new guidelines and provides a reference for evaluating the impact of the 2013 guidelines on statin utilization.
Loss of balance between protective and pro-inflammatory synovial tissue T-cell polyfunctionality predates clinical onset of rheumatoid arthritis
Authors: Achilleas Floudas, Nuno Neto, Carl Orr, Mary Canavan, Phil Gallagher, Conor Hurson, Michael G Monaghan, Sunil Nagpar, Ronan H Mullan, Douglas J Veale, Ursula Fearon
Journal: Annals of the Rheumatic Diseases (2021)

Objectives This study investigates pathogenic and protective polyfunctional T-cell responses in patient with rheumatoid arthritis (RA), individuals at risk (IAR) and healthy control (HC) synovial-tissue biopsies and identifies the presence of a novel population of pathogenic polyfunctional T-cells that are enriched in the RA joint prior to the development of clinical inflammation. Methods Pathway enrichment analysis of previously obtained RNAseq data of synovial biopsies from RA (n=118), IAR (n=20) and HC (n=44) was performed. Single-cell synovial tissue suspensions from RA (n=10), IAR (n=7) and HC (n=7) and paired peripheral blood mononuclear cells (PBMC) were stimulated in vitro and polyfunctional synovial T-cell subsets examined by flow cytometric analysis, simplified presentation of incredibly complex evaluations (SPICE) and FlowSom clustering. Flow-imaging was utilised to confirm specific T-cell cluster identification. Fluorescent lifetime imaging microscopy (FLIM) was used to visualise metabolic status of sorted T-cell populations. Results Increased plasticity of Tfh cells and CD4 T-cell polyfunctionality with enriched memory Treg cell responses was demonstrated in RA patient synovial tissue. Synovial-tissue RNAseq analysis reveals that enrichment in T-cell activation and differentiation pathways pre-dates the onset of RA. Switch from potentially protective IL-4 and granulocyte macrophage colony stimulating factor (GMCSF) dominated polyfunctional CD4 T-cell responses towards pathogenic polyfunctionality is evident in patient with IAR and RA synovial tissue. Cluster analysis reveals the accumulation of highly polyfunctional CD4 + CD8 dim T-cells in IAR and RA but not HC synovial tissue. CD4 + CD8 dim T-cells show increased utilisation of oxidative phosphorylation, a characteristic of metabolically primed memory T-cells. Frequency of synovial CD4 + CD8 dim T-cells correlates with RA disease activity. Conclusion Switch from potentially protective to pathogenic T-cell polyfunctionality pre-dates the onset of clinical inflammation and constitutes an opportunity for therapeutic intervention in RA.
Evaluation of Oncology Trial Results Reporting Over a 10-Year Period
Authors: Xu Liu, Yuan Zhang, Wen-Fei Li, Everett Vokes, Ying Sun, Quynh-Thu Le, Jun Ma
Journal: JAMA Network Open (2021)

Unreported clinical trial results represent a violation of human rights. Oncology trials account for nearly 30% of interventional biopharmaceutical clinical studies registered on ClinicalTrials.gov and are the most numerous among all disciplines.To analyze the reporting of results among all interventional oncology trials registered on ClinicalTrials.gov from 2007 through 2017.This cohort study analyzed all clinical studies registered between June 1, 2007, and May 8, 2017, on ClinicalTrials.gov, the largest public clinical trial registry in the world. Trials with a recruitment status of completed or terminated and a primary completion date of on or before September 30, 2017, were selected. Data were analyzed between February 20, 2021, and February 26, 2021.The main outcome was the percentage of trials that reported results either on ClinicalTrials.gov or in journal publications within 24 months of the primary completion date. Journal publication was ascertained by searching ClinicalTrials.gov for a link to the publication, PubMed using national clinical trial number, and Embase using national clinical trial number and filters.Of the 12 240 clinical trials registered in ClinicalTrials.gov, 7425 trials (60.7%; 95% CI, 60.0%-61.5%) reported results, with a 34.0% (95% CI, 30.3%-37.7%) increase in 24-month reporting rate from 2007 to 2017. Multivariable analyses confirmed that more recent trials (adjusted hazard ratio [HR], 1.11 per year increase; 95% CI, 1.10-1.13) and trials with larger sample sizes (51-100 patients: adjusted HR, 1.17 [95% CI, 1.09-1.24]; >100 patients: adjusted HR, 1.43 [95% CI, 1.33-1.54]) were more likely to report results. Terminated trials were less likely to report results compared with completed trials (adjusted HR, 0.88; 95% CI, 0.83-0.93). Compared with trials funded by industry, those funded by the National Institutes of Health were more likely to report results (adjusted HR, 1.39; 95% CI, 1.29-1.49), whereas those funded by other academic or nonprofit organizations were less likely to report results (adjusted HR, 0.66; 95% CI, 0.62-0.70). Among all 7425 trials, the results of 2807 trials (37.8%; 95% CI, 36.7%-38.9%) were posted only on ClinicalTrials.gov. These trials tended to be terminated early and to have small sample sizes (≤50 patients) compared with trials that published results in journals.This study found a gradual improvement in results reporting among oncology trials over a 10-year period. Trial registries could serve as a results reporting platform for unpublished trials and as a data source of trial outcomes for future studies.
Mapping the colorectal tumor microbiota
Authors: CL Murphy, M Barrett, P Pellanda, S Killeen, M McCourt, E Andrews, M O’ Riordain, F Shanahan, Pw O’Toole
Journal: Gut Microbes (2021)

The gut microbiome in patients with colorectal cancer (CRC) is different than that of healthy controls. Previous studies have profiled the CRC tumor microbiome using a single biopsy. However, since the morphology and cellular subtype vary significantly within an individual tumor, the possibility of sampling error arises for the microbiome within an individual tumor. To test this hypothesis, seven biopsies were taken from representative areas on and off the tumor in five patients with CRC. The microbiome composition was strikingly similar across all samples from an individual. The variation in microbiome alpha-diversity was significantly greater between individuals' samples then within individuals. This is the first study, to our knowledge, that shows that the microbiome of an individual tumor is spatially homogeneous. Our finding strengthens the assumption that a single biopsy is representative of the entire tumor, and that microbiota changes are not limited to a specific area of the neoplasm.
Concentration‐dependent clinical and prognostic importance of high‐sensitivity cardiac troponin T in heart failure and a reduced ejection fraction and the influence of empagliflozin: the <scp>EMPEROR</scp>‐Reduced trial
Authors: Milton Packer, James L. Januzzi, Joao Pedro Ferreira, Stefan D. Anker, Javed Butler, Gerasimos Filippatos, Stuart J. Pocock, Martina Brueckmann, Waheed Jamal, Daniel Cotton, Tomoko Iwata, Faiez Zannad
Journal: European Journal of Heart Failure (2021)

Circulating troponin is an important measure of risk in patients with heart failure, but it has not been used to determine if disease severity influences the responses to drug treatments in randomized controlled trials.In the EMPEROR-Reduced trial, patients with class II-IV heart failure and a reduced ejection fraction were randomly assigned to placebo or empagliflozin 10 mg daily and followed for the occurrence of serious heart failure and renal events. High-sensitivity cardiac troponin T (hs-cTnT) was measured in 3636 patients (>97%) at baseline, and patients were divided into four groups based on the degree of troponin elevation. With increasing concentrations of hs-cTnT, patients were progressively more likely to have diabetes and atrial fibrillation, to have New York Heart Association class III-IV symptoms and been hospitalized for heart failure within the prior year, and to have elevated levels of natriuretic peptides and worse renal function (P-trend < 0.0001 for all comparisons), but importantly, the troponin groups did not differ with respect to ejection fraction. A linear relationship was observed between the logarithm of hs-cTnT and the combined risk of cardiovascular death or hospitalization for heart failure (P = 0.0015). When treated with placebo, patients with the highest levels of hs-cTnT had risks of cardiovascular death and hospitalization for heart failure that were 3-5 fold greater than those with values in the normal range. Patients with higher levels of hs-cTnT were also more likely to experience worsening of renal function and serious adverse renal events and showed the least improvement in health status (as measured by the Kansas City Cardiomyopathy Questionnaire). When compared with placebo, empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure, regardless of the baseline level of hs-cTnT, whether the effects of treatment were analysed as hazard ratios or absolute risk reductions.Elevations in hs-cTnT reflect the clinical severity, stability and prognosis of patients with heart failure and a reduced ejection fraction, with biomarkers, comorbidities, clinical course and risks that are proportional to the magnitude of hs-cTnT elevation. Empagliflozin exerted favourable effects on heart failure and renal outcomes, regardless of the baseline concentration of hs-cTnT.
POS0359 MOLECULAR PROFILING OF RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS PATIENTS REVEALS AN ASSOCIATION BETWEEN INNATE AND ADAPTIVE CELL POPULATIONS AND THERAPEUTIC RESPONSE TO ADALIMUMAB
Authors: D. Sobral, A. F. Fernandes, A. Mashayekhi Sardoo, M. Bernardes, P. Pinto, H. Santos, J. L. Gomes, J. Tavares-Costa, J. Silva, J. Madruga Dias, A. Bernardo, J. Gaillard, J. Armengaud, V. Benes, R. Pinheiro Torres, L. Domingues, S. Maia, J. Branco, A. V. Coelho, F. Pimentel dos Santos
Journal: Annals of the Rheumatic Diseases (2021)

Background: The response to treatment in spondylarthropaties is heterogeneous, due to factors yet to be better described. For that reason, it is important to find tools that might help clinicians to decide what is the best available therapeutic option for each patient. Objectives: The goal of this study is to use comprehensive molecular profiling to characterize clinical response to therapy in a real-world setting. Specifically, to identify molecular biomarkers differentiating good responders and non-responders to TNF inhibitors (TNFi) treatment, using adalimumab, in radiographic axial spondyloarthritis | ankylosing spondylitis (r-axSpA|AS) patients context. Methods: Whole-blood mRNA and plasma proteins were measured in a cohort of biologic naïve r-axSpA|AS patients (n = 35) from the Bioefficacy study (Biomarkers identification of anti-TNF alpha agent efficacy in AS patients using RNA sequencing and mass spectrometry), pre and post (14 weeks) TNFi treatment using adalimumab. Response to treatment was categorized according to ASAS20. Results of differential expression analysis were used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. Results: A treatment-related signature, independent of the type of response, suggests a reduction in inflammatory disease activity. We found genes and proteins robustly differentially expressed between baseline and week 14 in responders, including the GWAS AS-associated genes TNFRSF1A, FCGR2A, TYK2, TBKBP1, IL1R1, IL6R, ICOSLG, IL7R, HHAT and LTBR. Moreover, CRP and HP proteins showed strong and early decrease in the plasma of AS patients, while a cluster of apolipoproteins (APO1, APO2, APO3) showed an increased expression at week 14. Good responders to TNFi treatment tend to have higher expression of innate immunity genes at baseline, and lower expression of markers associated with adaptive immunity, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender and Gene x , the top differentially expressed gene at baseline between responders and non-responders, enabled an accurate prediction of response to adalimumab in our cohort (AUC=0.97). Conclusion: Differences in disease activity and/or innate/adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in r-axSpA|AS. Alternatively, a model including clinical and gene expression variables could be considered, particularly in patients with mild disease activity. Disclosure of Interests: None declared
Greater Overlap of Rome IV Disorders of Gut-Brain Interactions Leads to Increased Disease Severity and Poorer Quality of Life
Authors: Ami D. Sperber, Tamar Freud, Imran Aziz, Olafur S. Palsson, Douglas A. Drossman, Dan L. Dumitrascu, Xuicai Fang, Shin Fukudo, Uday C. Ghoshal, John Kellow, Rutaba Khatun, Edith Okeke, Eamonn M.M. Quigley, Max Schmulson, Magnus Simren, Jan Tack, William E. Whitehead, Peter Whorwell, Shrikant I. Bangdiwala
Journal: Clinical Gastroenterology and Hepatology (2021)
Single-Cell Characterization of the Immune Microenvironment of Melanoma Brain and Leptomeningeal Metastases
Authors: Inna Smalley, Zhihua Chen, Manali Phadke, Jiannong Li, Xiaoqing Yu, Clayton Wyatt, Brittany Evernden, Jane L. Messina, Amod Sarnaik, Vernon K. Sondak, Chaomei Zhang, Vincent Law, Nam Tran, Arnold Etame, Robert J.B. Macaulay, Zeynep Eroglu, Peter A. Forsyth, Paulo C. Rodriguez, Y. Ann Chen, Keiran S.M. Smalley
Journal: Clinical Cancer Research (2021)

Melanoma brain metastases (MBM) and leptomeningeal melanoma metastases (LMM) are two different manifestations of melanoma CNS metastasis. Here, we used single-cell RNA sequencing (scRNA-seq) to define the immune landscape of MBM, LMM, and melanoma skin metastases.scRNA-seq was undertaken on 43 patient specimens, including 8 skin metastases, 14 MBM, and 19 serial LMM specimens. Detailed cell type curation was performed, the immune landscapes were mapped, and key results were validated by IHC and flow cytometry. Association analyses were undertaken to identify immune cell subsets correlated with overall survival.The LMM microenvironment was characterized by an immune-suppressed T-cell landscape distinct from that of brain and skin metastases. An LMM patient with long-term survival demonstrated an immune repertoire distinct from that of poor survivors and more similar to normal cerebrospinal fluid (CSF). Upon response to PD-1 therapy, this extreme responder showed increased levels of T cells and dendritic cells in their CSF, whereas poor survivors showed little improvement in their T-cell responses. In MBM patients, therapy led to increased immune infiltrate, with similar T-cell transcriptional diversity noted between skin metastases and MBM. A correlation analysis across the entire immune landscape identified the presence of a rare population of dendritic cells (DC3) that was associated with increased overall survival and positively regulated the immune environment through modulation of activated T cells and MHC expression.Our study provides the first atlas of two distinct sites of melanoma CNS metastases and defines the immune cell landscape that underlies the biology of this devastating disease.