tbuckley/cabot-search huggingface dataset:
Abstract 13154: Cardiovascular Risk in Users of Mirabegron Relative to Users of Antimuscarinic Treatments for Overactive Bladder: Findings From a Non-interventional, Real-world Data Safety Study
Authors: Veena Hoffman, Jesper Hallas, Marie Linder, Andrea Margulis, Brandon T Suehs, Alejandro Arana, Cheryl Enger, Libby Horter, Ingvild Odsbu, Morten Olesen, Susana Perez Gutthann, Yihua Xu, Nina S Kristiansen, Kwame Appenteng, Stefan de Vogel, John D Seeger
Journal: Circulation (2020)

Introduction: During clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased heart rate and systolic/diastolic blood pressure vs placebo in patients with overactive bladder (OAB). We studied the association between mirabegron and cardiovascular (CV) outcomes in an observational post-marketing safety study using real-world data. Methods: The study population was identified within five data sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (US), and Humana (US). Episodes of time when patients were new users of mirabegron or antimuscarinic medications (AMs) from 2012 to 2018 were sourced from prescription/dispensing information and matched on propensity scores. Major adverse CV events (MACE), acute myocardial infarction (AMI), stroke, and CV and all-cause mortality were identified from register linkage or validated through medical record review or physician questionnaires. Incidence rates of these outcomes during person-time of current use were estimated along with hazard ratios (HRs) from Cox models. Results: In total, 152,026 mirabegron episodes were matched to an equal number of AM episodes. The study population was 63.2% female and 72.6% were ≥65 years old. Baseline CV risk factors were similar between matched groups. There were no appreciable differences in the incidence rates of MACE, AMI, and stroke among current users of mirabegron relative to AMs (Table). The incidence rates of CV mortality (HR: 0.83, 95% confidence interval [CI]: 0.73, 0.95) and all-cause mortality (HR: 0.80, CI: 0.76, 0.84) were no higher with mirabegron vs AMs. Results restricted to episodes at high risk for CV events or stratified by age (&lt;65, ≥65 years) or prior OAB medication use were consistent with overall findings. Conclusions: This large, multinational study found no higher risk of MACE, AMI, stroke, or CV or all-cause mortality among current users of mirabegron relative to users of AMs.
Abstract 15801: Early and Late Risk of Mortality or Development of Severe Pulmonary Hypertension Following Closure of Ventricular Septal Defects in Children With Severe Pulmonary Hypertension and Elevated Pulmonary Vascular Resistance Using Traditional or Uni-directional Flap Valve Patch Closure
Authors: William M Novick, Oleksandr Golovenko, Vasyl Lazorhyshynets, Vitaly Dedovich, Iryna Perepeka, Maya Rudenko, Lilia Prokopovych, Thomas G DiSessa
Journal: Circulation (2020)

Introduction: Children with large ventricular septal defects, severe pulmonary hypertension (PHT), and elevated pulmonary vascular resistance (PVR) are frequently denied operation in low and middle-income countries secondary to concerns of high mortality and development of severe pulmonary hypertension following operation, early and late. Hypothesis: We hypothesized that closure with a uni-directional flap valve patch (DP) would provide lower mortality and better survival without severe PHT. Methods: From 5/96 - 12/2016 all patients undergoing VSD closure with severe PHT and elevated PVR by either traditional (TP) or DP closure were followed annually. Baseline and O 2 provocation catheterization were performed before operation. Echocardiograms were performed at discharge and follow-up. The decision on TP or DP closure was based upon age and surgeon preference. Beginning in 2005 all patients regardless of technique received sildenafil 3 mgs/kg/day for 3 months before operation. Results: The number of patients receiving operation was 129, of which 40 received the DP. Males were 66/129, age and weight differed significantly for DP group compared to the TP group (7.5 vs 2.6 years, p&lt;0.001 and 20 vs 11.5 kgs, p&lt;0.001).Catheterization baseline data, PVR 9.0 vs 7.4 for DP and TP respectively (p&lt;0.001), negative vasoactive test 32.5% vs 13.5% for DP and TP respectively (p=0.016). Mortality was 1/40 for DP and 9/89 for TP. Pulmonary to Systemic systolic pressure ratio was lower at discharge vs baseline cath (0.38 vs 0.99, p&lt;0.001). Predictors of late severe pulmonary hypertension were PVR/SVR &gt;0.5, p&lt;0.024; and a negative vasoactive test of &lt;10% decrease, p&lt;0.001. PHT at last follow-up, none or mild 86/115 (74.8%), moderate 16/115 (13.9%) or severe 13/115 (11.3%). Conclusions: DP patients had less risk of death and both groups had few patients with severe PHT at late follow-up..
Abstract 15837: Particulate Matter 2.5 Exposure Increases Risk of Subsequent Myocardial Infarction
Authors: John K Maxi, Matthew Herzog, Jonathan Entwisle, Jonathan K Wilt, Richard V Milani
Journal: Circulation (2020)

Introduction: Particulate matter 2.5 (PM 2.5 ) are airborne particles small enough to be inhaled into the pulmonary alveoli, and are associated with increased hospitalization rates, morbidity, and mortality. The purpose of this study was to evaluate the levels of PM 2.5 in southeastern Louisiana and describe associated cardiovascular outcomes in patients with a history of myocardial infarction (MI). Methods: Air quality monitoring stations were placed around southeastern Louisiana and were analyzed from March 1 st , 2019 to March 1 st , 2020. Samples were collected every 80 seconds, and values were aggregated at the hourly and daily level. We used conditional logistic regression models to determine the risk of MI. Control observations per patient were created using PM 2.5 exposure on the same day of the week for the two weeks before and after the event. Temperature, pressure, humidity, and their interactions with PM 2.5 were included in the model. Results: The average PM 2.5 exposure for the year was 10.41 ug/m 3 +/- 5.57 ug/m 3 , with a daily low of 1.93 ug/m 3 and a daily high of 31.32 ug/m 3 . Peaks from individual sensors reached PM 2.5 concentrations greater than 100 ug/m 3 . PM 2.5 concentration showed a significant, weakly positive correlation with daily average temperature and a significant, weakly negative correlation with daily average barometric pressure. Among patients (n=263) with history of MI, risk of subsequent MI increased by 24.3% per 10 ug/m 3 increase in PM 2.5 exposure with a lag of three days after exposure. (Figure) No significant risk associated with PM 2.5 exposure was observed at shorter lag times. Conclusion: Although the average PM 2.5 levels in southeastern Louisiana were within the WHO guidelines of air quality, PM 2.5 exposure remained a significant risk factor for MI among a those with previous MI.
Abstract 17285: Metabolite-Derived Network Reveals Cluster of Acylcholine Metabolites Associated With Better Diet Quality and Lower Prevalence of Type 2 Diabetes: Findings From the Boston Puerto Rican Health Study
Authors: Danielle E Haslam, Dong Wang, Liming Liang, Rachel S Kelly, Clemens Wittenbecher, Clary Clish, Jose M Ordovos, Chao-Qiang Lai, Frank B Hu, Katherine L Tucker, Joann E Manson, Shilpa N Bhupathiraju
Journal: Circulation (2020)

Introduction: Puerto Rican (PR) adults living on the US mainland are at high risk for developing type 2 diabetes (T2D), and dietary factors may contribute to this increased risk. Network analysis is a data-reduction tool that can identify correlated clusters of co-regulated metabolites that reflect mechanisms underlying diet-T2D associations. Hypothesis: Diet quality will associate with T2D-associated metabolite clusters among PR adults. Methods: We used LC/MS to measure fasting plasma metabolites (&gt;700) among Boston PR Health Study participants, aged 45-75 years, with (n=258) and without (n=421) T2D. We applied an unsupervised correlation network-based method to identify metabolite clusters within a global metabolite network and calculated a score for each cluster using a weighted sum of metabolite concentrations. To estimate diet quality, we calculated a modified version of a previously validated American Heart Association diet score (AHA-DS). Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D, and linear regression was used to assess associations between the continuous AHA-DS and T2D-associated metabolite clusters among controls, adjusting for potential confounders and correcting for multiple testing. Results: We identified 7 metabolite clusters that were associated with prevalent T2D ( p &lt;0.05). For every 1-standard deviation (SD) increase in cluster score, the odds ratios for prevalent T2D and 95% confidence intervals were as the follows: acylcholines [0.40 (0.31, 0.50)], aromatic hydrocarbon derivatives [0.33 (0.22, 0.47)], sphingolipids [0.46 (0.33, 0.64)], tricarboxylic acid (TCA) cycle amino acids/peptides [0.39 (0.25, 0.62)], branched-chain amino acid metabolites [4.1 (2.9, 6.0)], acylcarnitines [1.8 (1.3, 2.5)], and TCA cycle/energy metabolites [2.0 (1.4, 3.0)]. The AHA-DS was only significantly associated with the acylcholine metabolites cluster [β (standard error) = 0.01 (0.004) SD increase in cluster score, p=0.02]. Conclusions: In individuals of PR descent, we identified a cluster of acylcholine metabolites where concentrations are higher among those with better diet quality and lower among those with prevalent T2D.
The association between loneliness and depressive symptoms among adults aged 50 years and older: a 12-year population-based cohort study
Authors: Siu Long Lee, Eiluned Pearce, Olesya Ajnakina, Sonia Johnson, Glyn Lewis, Farhana Mann, Alexandra Pitman, Francesca Solmi, Andrew Sommerlad, Andrew Steptoe, Urszula Tymoszuk, Gemma Lewis
Journal: The Lancet Psychiatry (2020)
Abstract 250: Effect of Coaching on Dispatch-assisted Cardiopulmonary Resuscitation: A Randomized Simulation Study
Authors: Hidetada Fukushima, Keisuke Takano, Hideki Asai
Journal: Circulation (2020)

Introduction: Immediate bystander cardiopulmonary resuscitation (CPR) is essential for the good outcome of sudden cardiac arrest victims. Current guidelines recommend dispatch-assisted CPR (DACPR). Its quality, however, varies from case to case. The aim of this study was todetermine the effectiveness of dispatch coaching on the quality of CPR by lay rescuers. Methods: We conducted a DACPR simulation study. Participants with no prior CPR training within 1 year were assigned randomly to one of two DACPR simulations (No Coaching Group: callers were told to perform CPR and the dispatcher sometimes confirmed if the caller was performing CPR or Coaching Group: the dispatcher coached, encouraged, and counted out loud with a metronome). The study participants performed CPR for 2 minutes under the study dispatcher. All performances were recorded by video camera and Resusci Anne® QCPR (Laerdal, Norway). Results: Forty-nine participants aged 20s to 50s were recruited, and 48 completed the simulation (Coaching Group, 27, 9 males and No Coaching Group, 21, 16 males). The average rate of chest compressions was 102.5/min in Coaching Group and 109.3/min in No Coaching group (p=0.270). The average compression depth was slightly deeper in Coaching group (43.0mm vs 41.5mm, p=0.695). When compared the average depth of the first 10 compressions to the total average in each group, the depth significantly improved in Coaching group while that decreased in No Coaching Groups (38.4mm to 43.0mm; p=0.020, 42.3mm to 41.5mm; p=0.431, respectively). The chest compression fraction was also high in Coaching Group (99.4% vs 93.0%, p=0.005). Conclusions: Participants in Coaching Group performed better CPR compared to No Coaching Group in terms of high flow fraction. Although the average compression depth was below the guideline recommendation in both groups, it significantly improved in Coaching group. This study indicates that dispatch coaching can optimize the performance of bystander CPR.
FRI0023 Laboratory testing in rheumatoid arthritis patients on disease modifying antirheumatic drugs: clinical evaluation and cost analysis
Authors: D Aletaha, JS Smolen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Laboratory tests during disease modifying antirheumatic drug (DMARD) therapy are necessary to ensure that certain adverse events are not present,<sup>1,2</sup> but often are costly. Current guidelines on monitoring DMARD therapy are mostly derived by consensus.<sup>3</sup> <h3>Objectives</h3> To assess the value and costs of routine laboratory tests for the detection of toxicity of DMARD-therapy in rheumatoid arthritis, and to find evidence-guided proposals concerning types and frequencies of such tests. <h3>Methods</h3> Data were collected from the outpatient charts of 362 RA-patients during 1386 patient-years (DMARD type, dosage, duration, reason for discontinuation and all details of adverse events). Clinically relevant laboratory abnormalities (mainly ALAT, ASAT, CBC, creatinine, protein excretion) were analysed to assess the effectiveness of laboratory tests in detecting abnormalities induced by DMARDs. On this basis, proposals were derived and then tested using data from a validation cohort of 231 patients (986 patient years) from another rheumatic disease centre. Cost analyses were performed using a cost catalogue. <h3>Results</h3> Abnormal results of laboratory examinations accounted for approx. 10% of DMARD discontinuations. All significant abnormalities occurred or were heralded during the first 4 months of therapy. It was concluded that laboratory examinations could be limited to a small number of variables for individual DMARDs and that after the initial 4 months of therapy screening frequencies could be significantly reduced. These conclusions were proved to be correct in 98.3% of the independent second patient cohort. Adhering to such strategy could save up to 86% of costs incurring compared to published recommendations for monitoring DMARD therapies. <h3>Conclusion</h3> Only a limited number of laboratory tests are necessary for safety monitoring of patients on DMARDs. These tests need to be performed more frequently (monthly) only in the first four months of therapy, and if not revealing abnormal results, examinations can thereafter be reduced to two to four times per year. Thus, the costs of routine laboratory tests during DMARD therapy can be significantly decreased with no increase in the risk of overseeing adverse events. <h3>References</h3> Fries JF, Williams CA, Ramey D, Bloch DA. The relative toxicity of disease-modifying antirheumatic drugs. Arthritis Rheum. 1993;36:297–306 Wolfe F. Adverse drug reactions of DMARDs and DC-ARTs in rheumatoid arthritis. Clin Exp Rheumatol. 1997;15(Suppl 17):75–81 American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for monitoring drug therapy in rheumatoid arthritis. Arthritis Rheum. 1996;39:723–31
Abstract 19092: Cyclooxygenase 2 Mediates Increased Endothelium-Dependent Vascular Contraction in Hyperhomocysteinemia and Hyperlipidemia
Authors: Zhongjian Cheng, Xiaohua Jiang, William Durante, Warren D. Kruger, Xiaofeng Yang, Hong Wang
Journal: Circulation (2013)

Objectives: We recently reported that elevation of plasma homocysteine level_hyperhomocysteinemia (HHcy) accelerates atherosclerosis and vascular inflammation in hyperlipidemia (HLP). In this study, we examined the role of cyclooxygenase 2 (COX2)[[Unable to Display Character: —]]an inducible isoform of COX in responsible to inflammation, in HHcy/HPL-induced endothelial dysfunction (ED). Methods: Endothelial function was assessed in the thoracic aorta of a novel severe HHcy (plasma Hcy=221 μM) mouse model: human cystathionine β-synthase (CBS) transgenic, mouse CBS and apolipoprotine E gene deficient mouse fed with a high fat diet for 8 weeks (HHcy/HLP Cbs-/-¬ mice). Results: Endothelium-dependent relaxation to acetylcholine (ACh) was significantly impaired in HHcy/HLP Cbs-/- mice compared to HHcy/HLP Cbs+/+ mice. In the presence of eNOS inhibitor N(G)-nitro-L-Arg-methyl ester (L-NAME), ACh induced endothelium-dependent contraction in HHcy/HLP Cbs-/- but not in HHcy/HLP Cbs+/+ mice. L-NAME plus COX1/2 inhibitor indomethacin (INDO) completely blocked the HHcy/HLP-induced endothelium-dependent contraction. Moreover, INDO, COX2 inhibitor nimesulide, and thromboxane A2/prostaglandin H2 receptor antagonist SQ29548, but not COX1 inhibitor SC560, improved vascular relaxation to ACh in HHcy/HLP Cbs-/-¬ mice, indicating that COX2 plays a major role. Preincubation the aorta with antioxidants Tempol, polyethylene glycol superoxide dismutase and apocynin also improved endothelial function in HHcy/HLP Cbs-/- mice. Expression of COX2 and 3-nitrotyrosin (3-NT), but not COX1, was markedly increased in the endothelium of aorta of HHcy/HLP Cbs-/- mice. ICAM-1, VCAM-1, and TNFα were markedly increased in the aorta of HHcy/HLP Cbs-/- mice. Moreover, COX2 and 3-NT, but not COX1, was significantly increased in cultured human aortic endothelial cells treated with a combination of DL-Hcy (500 μM) and oxidized-LDL (200 μg/ml) for 48 hrs. Furthermore, DL-Hcy/oxidized-LDL-induced COX2 was prevented by PEG-SOD. Finally, HHcy markedly accelerated urinary 2,3-dinor TXB2, TXB2, 8-isoprostan and 6-keto prostaglandin F1α levels in HPL. Conclusions: COX2 mediates HHcy-induced endothelium-dependent vascular contraction in HPL via oxidative stress-dependent pathway.
Reducing oral corticosteroids in severe asthma (ROSA Project): a nationwide Portuguese consensus
Authors: Claudia Chaves Loureiro, Manuel Branco Ferreira, Jorge Ferreira, Ricardo Lima, João Marques, Anna Sokolova, Fernanda S. Tonin, Filipa Duarte Ramos
Journal: Pulmonology (2020)

We aimed to build a national consensus to optimize the use of oral corticosteroids (OCS) in severe asthma in Portugal.A modified 3-round Delphi including 65 statements (topics on chronic systemic corticotherapy, therapeutic schemes, asthma safety and monitoring) was performed via online platform (October-November 2019). A five-point Likert-type scale was used (1-'strongly disagree'; 5-'strongly agree'). Consensus threshold was established as a percentage of agreement among participants ≥90% in the 1st round and ≥85% in the 2nd and 3rd rounds. The level of consensus achieved by the panel was discussed with the participants (face-to-face meeting).Forty-eight expert physicians in severe asthma (specialists in allergology and pulmonology) participated in the study. Almost half of the statements (28/65; 43.1%) obtained positive consensus by the end of round one. By the end of the exercise, 12 (18.5%) statements did not achieve consensus. Overall, 87% of physicians agree that further actions for OCS cumulative risk assessment in acute asthma exacerbations are needed. The vast majority (91.7%) demonstrated a favorable perception for using biological agents whenever patients are eligible. Most participants (95.8%) are more willing to accept some degree of lung function deterioration compared to other outcomes (worsening of symptoms, quality of life) when reducing OCS dose. Monitoring patients' comorbidities was rated as imperative by all experts.These results can guide an update on asthma management in Portugal and should be supplemented by studies on therapy access, patients' adherence, and costs.
Transfusion in the mechanically ventilated patient
Authors: Nicole P. Juffermans, Cécile Aubron, Jacques Duranteau, Alexander P. J. Vlaar, Daryl J. Kor, Jennifer A. Muszynski, Philip C. Spinella, Jean-Louis Vincent
Journal: Intensive Care Medicine (2020)

Red blood cell transfusions are a frequent intervention in critically ill patients, including in those who are receiving mechanical ventilation. Both these interventions can impact negatively on lung function with risks of transfusion-related acute lung injury (TRALI) and other forms of acute respiratory distress syndrome (ARDS). The interactions between transfusion, mechanical ventilation, TRALI and ARDS are complex and other patient-related (e.g., presence of sepsis or shock, disease severity, and hypervolemia) or blood product-related (e.g., presence of antibodies or biologically active mediators) factors also play a role. We propose several strategies targeted at these factors that may help limit the risks of associated lung injury in critically ill patients being considered for transfusion.
COVID-19 and acute pancreatitis: examining the causality
Authors: Enrique de-Madaria, Gabriele Capurso
Journal: Nature Reviews Gastroenterology & Hepatology (2020)

Case reports and retrospective cohort studies have reported an association between acute pancreatitis and COVID-19. As SARS-CoV-2 (the causative agent of COVID-19) receptors are expressed in the pancreas and endothelial damage can occur, this association is plausible. However, this hypothesis has many biases and needs further investigation.
Abstract 14900: Human Atrial Fibrillation Drivers Revealed by Machine Learning Using Multicomponent Electrograms and 3D CE-MRI Structural Features
Authors: Aleksei Mikhailov, Brian Hansen, Matthew Fazio, Stanislav Zakharkin, Jichao Zhao, Aaqel Nalar, James Kennelly, Megan Subr, Miguel Rodrigo, Ning LI, Mylavarapu Uma, Anuradha Kalyanasundaram, Benjamin Buck, Paul M Janssen, Peter J Mohler, Bryan Whitson, Nahush Mokadam, John Hummel, Vadim V Fedorov
Journal: Circulation (2020)

Introduction: Conventional multielectrode mapping is not sufficient to reveal subsurface intramural activation. Thus, atrial fibrillation (AF) driver identification remains challenging. To overcome these limitations we utilized machine learning (ML) to identify AF drivers based on the combination of electrogram (EGM) and 3D structural magnetic resonance imaging (MRI) features. Hypothesis: Detailed electrogram features analysis, including minor deflections, combined with local structural features, can be used to define AF driver. Methods: Sustained AF was mapped in coronary perfused explanted human atria (n=7) with near-infrared optical mapping (NIOM) (0.3-0.9mm 2 resolution) and 64-electrode mapping catheter (3mm 2 resolution). Unipolar EGMs were analyzed for multiple features of the steepest negative deflection and the 2nd-4th steepest deflections in multicomponent EGMs. Atria underwent 9.4T MRI (154-180μm 3 resolution) with gadolinium enhancement and histology validation of fibrosis. Both 3D structural and EGM data from NIOM defined driver and non-driver regions were processed by ML algorithms (LR; PLSDA; GBM; CRF; PSVM; RSVM) using double cross-validation. Results: AF drivers’ reentrant tracks were defined by NIOM activation mapping, the gold-standard, and confirmed by targeted ablation. The best performing ML algorithm (PLSDA) correctly classified mapped driver region with 76.1% accuracy on the testing data. The most important features included sub-endocardial fibrosis, sub-epicardial fiber orientation, local wall thickness, beat-to-beat variability of multicomponent EGM deflections. Conclusions: The ML models pre-trained on combined EGM and structural features allow efficient classification of AF driver vs non-driver regions defined by the NIOM gold-standard. The results suggest that AF driver substrates formed by the combination of 3D fibrotic structural features, which correlate with local EGM characteristics.