tbuckley/cabot-search huggingface dataset:
NICE consults on looking beyond RCTs when evaluating drugs and devices
Authors: Jacqui Wise
Journal: BMJ (2020)

The National Institute for Health and Care Excellence (NICE) is proposing placing more emphasis on “real world evidence” when it develops guidance on health technologies, as well as considering additional factors such as the severity of a condition or whether a treatment can reduce health inequalities.

NICE has launched a public consultation that sets out the case for changing the methods it uses to develop guidance on drugs, medical devices, and diagnostics.1 The review was first announced in July 2019 but has been delayed because of covid-19.2

The consultation document says that there should be no change to the general preference for randomised controlled trials (RCTs) to inform estimates of treatment effects but that there should be “an emphasis on the role of a comprehensive evidence base, including non-RCTs and real world evidence.” Real world evidence includes evidence from observational studies, patient registries, electronic health records, and other sources beyond RCTs.

The 60 page …
The Phosphoinositide Kinase Pikfyve Regulates Lysosomal Biogenesis in Macrophages By Modulating the Transcription Factor EB (TFEB)
Authors: Francina Gonzalez, Aae Suzuki, Jessica Guzman, Lynn Spruce, Steven H Seeholzer, Charles S. Abrams, Sang Hee Min
Journal: Blood (2017)
Planetary health approaches for dry cities: water quality and heat mitigation
Authors: Tony H F Wong, Nigel J Tapper, Stephen P Luby
Journal: BMJ (2020)

About 1.6 billion people live in countries with water scarcity, and this number is projected to double in two decades. 1 Cities tend to conflate and amplify the challenges this brings, adversely affecting the health and wellbeing of their inhabitants.
Abstract 14662: Relationships Between Physical Activity, Coronary Artery Calcium, and Cardiovascular Outcomes in the Multi-Ethnic Study of Atherosclerosis: MESA
Authors: Charles A German, Jason Fanning, Matthew J Singleton, Michael D Shapiro, Peter H Brubaker, Alain G Bertoni, Joseph Yeboah
Journal: Circulation (2020)

Introduction: Physical activity is associated with decreased rates of atherosclerotic cardiovascular disease (ASCVD) and mortality. However, high levels of physical activity (PA) have paradoxically been linked with elevated levels of coronary artery calcium (CAC). It remains unclear whether high levels of physical activity in the presence of high CAC are associated with adverse outcomes in a diverse, multi-ethnic population. Hypothesis: We hypothesized that high compared to low levels of PA are associated with a reduction in incident ASCVD and all-cause mortality, even in the presence of high CAC. Methods: Baseline total PA (MET-min/week) in the Multi-Ethnic Study of Atherosclerosis (MESA), obtained via questionnaire, was divided into quartiles. CAC was dichotomized into low (CAC &lt;100 Agatston Units (AU)) and high (CAC ≥100 AU) categories. Outcomes of interest included ASCVD and all-cause mortality. Cox proportional hazard regression analysis was used to assess associations between PA, ASCVD, and all-cause mortality among low and high CAC groups. Results: Among the 6,814 participants included in this study, the average age was 62 years, 53% were female, and 38% were non-Hispanic white. In participants with CAC &lt;100 AU and PA in the highest quartile, we observed a significant reduction in ASCVD and all-cause mortality compared with participants in the lowest PA quartile (Table1). In participants with CAC ≥100 AU and PA in the highest quartile, we observed a significant reduction in all-cause mortality, but no difference in the risk of ASCVD compared with participants in the lowest PA quartile. Conclusions: Our study suggests that high levels of PA are associated with a reduced risk of ASCVD and all-cause mortality among individuals with low CAC, and a reduced risk of all-cause mortality among individuals with high CAC. There was no evidence to suggest an increased risk of ASCVD from high levels of PA in individuals with high CAC.
“You can leave your mask on”: effects on cardiopulmonary parameters of different airway protective masks at rest and during maximal exercise
Authors: Massimo Mapelli, Elisabetta Salvioni, Fabiana De Martino, Irene Mattavelli, Paola Gugliandolo, Carlo Vignati, Stefania Farina, Pietro Palermo, Jeness Campodonico, Riccardo Maragna, Gerardo Lo Russo, Alice Bonomi, Susanna Sciomer, Piergiuseppe Agostoni
Journal: European Respiratory Journal (2021)

During the COVID-19 pandemic, the use of protective masks has been essential to reduce contagions. However, public opinion is that there is an associated subjective shortness of breath. We evaluated cardiorespiratory parameters at rest and during maximal exertion to highlight any differences with the use of protective masks. 12 healthy subjects performed three identical cardiopulmonary exercise tests, one without wearing a protective mask, one wearing a surgical mask and one with a filtering face piece particles class 2 (FFP2) mask. Dyspnoea was assessed using the Borg scale. Standard pulmonary function tests were also performed. All the subjects (40.8±12.4 years; six male) completed the protocol with no adverse events. Spirometry showed a progressive reduction of forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) from no mask to surgical to FFP2 (FEV 1 : 3.94±0.91 L, 3.23±0.81 L, 2.94±0.98 L; FVC: 4.70±1.21 L, 3.77±1.02 L, 3.52±1.21 L; p&lt;0.001). Rest ventilation, O 2 uptake ( V˙ O 2 ) and CO 2 production ( V˙ CO 2 ) were progressively lower, with a reduction in respiratory rate. At peak exercise, subjects had a progressively higher Borg scale when wearing surgical and FFP2 masks. Accordingly, at peak exercise, V˙ O 2 (31.0±23.4 mL·kg −1 ·min −1 , 27.5±6.9 mL·kg −1 ·min −1 , 28.2±8.8 mL·kg −1 ·min −1 ; p=0.001), ventilation (92±26 L, 76±22 L, 72±21 L; p=0.003), respiratory rate (42±8 breaths·min −1 , 38±5 breaths·min −1 , 37±4 breaths·min −1 ; p=0.04) and tidal volume (2.28±0.72 L, 2.05±0.60 L, 1.96±0.65 L; p=0.001) were gradually lower. There was no significant difference in oxygen saturation. Protective masks are associated with significant but modest worsening of spirometry and cardiorespiratory parameters at rest and peak exercise. The effect is driven by a ventilation reduction due to increased airflow resistance. However, because exercise ventilatory limitation is far from being reached, their use is safe even during maximal exercise, with a slight reduction in performance.
Abstract 17288: Clinical Outcomes of Hyponatremia in Patients Undergoing TAVR - A National Inpatient Sample Database
Authors: yasar sattar, Waqas Ullah, Salman Zahid, Houman Moussa Pacha, Uneza Rauf Khawaja, Fahed Darmoch, Mohamad Soud, Yasser Alkhadra, Mehmet E Demirhan, Urja Patel, David L Fischman, M Chadi M Alraies
Journal: Circulation (2020)

Introduction: The in-hospital outcomes and complications of hyponatremia in patients who are undergoing transcatheter aortic valve replacement (TAVR) remains uncertain. Hypothesis: Hyponatremia effect on TAVR outcomes Methods: We queried National Inpatient Sample (NIS) (2011-2014) using the International Classification of Disease, Ninth Edition, Clinical Modification (ICD-9-CM) codes for TAVR and hyponatremia (level&lt;135 mEq/L). Categorical and continuous variables were reported as percentages and weighted means and were compared using unadjusted odds ratio (OR) and t-test, respectively. Univariate and multiple logistic regression analyses were used to control the outcomes variables. Results: A total of 33790 (no-hyponatremia 31683, hyponatremia 2107; ,mean age = 81 year) patients were included. The unadjusted odds for in-hospital mortality (5.7% vs. 3.8%, uOR 0.43, 95% CI, 0.23-0.618, p=&lt;0.001) and new-onset seizures (0.5% vs. 0.2%%, uOR 2.15; 95% CI, 1.02-4.18, P = 0.037) were significantly higher for patients with hyponatremia compared to no-hyponatremia, respectively. Intriguingly, patients with hyponatremia had significantly higher odds of developing cardiopulmonary arrest (4.9% vs. 3.0%, uOR 0.53; 95% CI, 0.33-0.74, P=&lt;0.001) compared to patients without hyponatremia. The odds for cerebral herniation and in-hospital new-onset coma (0.2% vs 0.2%, uOR 0.31 ;95% CI, 0.60-1.2, P = 0.69) did not differ significantly between the two groups. The adjusted odds ratio based on baseline comorbidities (hypertension, renal failure, diabetes, history of seizures), demographics (race, hospital, month of admission) and age followed the unadjusted odds ratios. Outcome differences of complications of TAVR with or without hypernatremia are shown in figure 1. (bue= without hyponatremia; red=hyponatremia). Conclusions: Patients with hyponatremia undergoing TAVR have higher odds of all-cause mortality, seizures and cardiopulmonary arrest.
Abstract 15635: Myocardial Function Index Predicts Mortality in Amyloid Light Chain Cardiomyopathy
Authors: Nadia S Akhiyat, Vidhu Anand, Alexander Ryu, Vinayak Kumar, Barry A Borlaug, Omar F Abouezzeddine, Raymond J Gibbons, Bernard J Gersh, Nandan S Anavekar, Krishnaswamy Chandrasekaran
Journal: Circulation (2020)

Introduction: Cardiovascular disease remains the leading cause of morbidity and mortality in patients with amyloid light chain (AL) amyloidosis. Current prognostic evaluation in AL cardiomyopathy (AL-CM) largely relies upon disparate proxy measurements to assess mortality. With respect to observed myocardial volume changes between systole and diastole, we describe a single measurement derived from cardiac MRI (CMR) to assess mortality of AL-CM. Methods: A cohort of 129 consecutive patients with AL-CM undergoing CMR with amyloid protocol from the years 2001 - 1997 was reviewed. Myocardial volume change at end systole and end diastole was assessed by disc summation with CMR. The myocardial function index (MFI) was calculated by consolidating blood pool and myocardial volume measures as confluent components of myocardial function utilizing operator tracings. The association of MFI and death was assessed with adjusted hazard ratios (HR) derived by a Cox model. Results: Data at time of CMR was reviewed. The mean age was 60 ±10; 68% subjects were female. Median survival from CMR was 47 months. Mean LVEF was assessed by echocardiography to be 55% ± 12. Mean calculated MFI was 19.8% ±7. Univariate analysis suggested MFI is strongly associated with death (HR 0.004; 95%CI 0.00002-0.0838; p = 0.0003). A multivariate analysis re-demonstrated the strong predictive value of MFI when controlled for age (HR 0.006; 95%CI 0.00003 - 0.1156; p = 0.0006). Conclusion: MFI strongly correlates with mortality in AL-CM. In contrast to previously described assessments of ventricular function (extracellular volume imaging, myocardial perfusion imaging, and myocardial contraction fraction), MFI is easily derived from CMR and considers blood pool and myocardial volumes as confluent components of myocardial function. Further studies are needed to assess MFI amongst patients with varying etiologies of heart failure.
Abstract 241: Analysis of Characteristics and Mortality by the Level of Hospital in the Patients with Cardiac Arrest; A Nation-wide Population-based Study
Authors: Sijin Lee, Su Jin Kim, Sung Woo Lee, Kap Su Han, Eui Jung Lee
Journal: Circulation (2020)

Objectives: We intended to determine the association between hospital-level and mortality, and reveal differences in patient characteristics and potential resource utilization using the National health Insurance Service database. Methods: We selected adult patients (&gt;20 years old) with non-traumatic cardiac arrest from 2006 to 2015 using the national database. The patients were categorized into ‘Tertiary’, ‘Secondary’ and ‘Primary’ groups by the level of hospital where they were treated. Demographics, insurance type, urbanization level, previous disease, medical therapies and hospital costs were analyzed among the groups. Primary end-points were mortality rate within 30 days, 6 months and 1 year. Multiple logistic regression analysis was utilized for determining the association between hospital-level and mortality (SAS ver 9.4). Results: Tertiary, Secondary and Primary groups accounted for 32.6%, 49.6% and 17.8% of total 337,042 patients. Tertiary and Secondary groups showed the higher proportion of younger age, male patients, coverage by national health insurance, urban residents and lower Charlson Comorbidity Index than Primary group. After adjusting characteristics and pre-existing diseases in multiple logistic regression analysis, the higher hospital level was negatively associated with mortality (Adjusted Odds ratio[aOR]: 0.372 and 0.419 at 30-days, aOR: 0.504 and 0.568 at 6-months, aOR: 0.538 and 0.604 at 1-year in Tertiary and Secondary groups). Advanced treatments like PCI, CABG, ECMO, EEG and therapeutic hypothermia were provided more in the higher level hospital. With regard to guideline change in 2010, there was a downturn in use of atropine and an increment in post-resuscitation care treatments in Tertiary and Secondary groups. Conclusions: Significant variability in cardiac arrest mortality exists across hospital levels, and this variation persists despite adjustment for measured patient factors. These findings suggest that higher level hospital provided more advanced procedures and post-resuscitation care, which leaded to higher hospital cost especially in acute period, and showed good adherence to guideline updates. (NRF-2017R1A2B100 5037)
Abstract 14482: Apparent Resistant Hypertension is a Marker of Risk: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Magnus O Wijkman, Marcus Malachias, Brian Claggett, Susan Cheng, Kunihiro Matsushita, Amil M Shah, Pardeep S Jhund, Josef Coresh, Scott Solomon, Orly Vardeny
Journal: Circulation (2020)

Introduction: Apparent resistant hypertension (ARH) is a common marker of risk in patients with established cardiovascular disease. We ascertained the prevalence and prognostic significance of ARH in patients without prior cardiovascular disease. Methods: This prospective observational cohort study included 9669 community-based participants without a history of heart failure, myocardial infarction, or stroke, who completed the Atherosclerosis Risk in Communities (ARIC) study visit 4 between 1996-1998. The definition of ARH was blood pressure (BP) above goal (traditional goal &lt;140/90mmHg, more stringent goal &lt;130/80mmHg) despite use of ≥3 antihypertensive drug classes, or any BP with ≥4 antihypertensive drug classes. Participants with controlled hypertension (CH), defined as BP at goal with use of 1-3 antihypertensive drug classes, constituted the reference group. The outcome was a composite endpoint of heart failure, myocardial infarction, stroke, or death. Cox regression models were adjusted for age, sex, race, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, glucose, and diabetes. Results: Applying the traditional BP goal, 154/9669 participants (1.6%) had ARH, and there were 2311 participants with CH (23.9%). Using the more stringent BP goal, 218/9669 participants (2.3%) had ARH, and 1523 participants (15.8 %) had CH. The median follow-up time was 19 years. Apparent resistant hypertension was associated with an increased risk for the composite endpoint (adjusted hazard ratio 1.58 [95% CI 1.32-1.90] with the traditional BP goal, and adjusted hazard ratio 1.51 [95% CI 1.28-1.79] with the more stringent BP goal). Conclusions: Apparent resistant hypertension had a low prevalence but was independently associated with adverse outcome during long term follow-up, compared to controlled hypertension and even compared to uncontrolled hypertension. This was observed for both traditional and more stringent BP goals.
Expression of T-Cell Exhaustion Molecules and Human Endogenous Retroviruses as Predictive Biomarkers for Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma
Authors: Miriam Ficial, Opeyemi A. Jegede, Miriam Sant'Angelo, Yue Hou, Abdallah Flaifel, Jean-Christophe Pignon, David A. Braun, Megan Wind-Rotolo, Maura A. Sticco-Ivins, Paul J. Catalano, Gordon J. Freeman, Arlene H. Sharpe, F. Stephen Hodi, Robert J. Motzer, Catherine J. Wu, Michael B. Atkins, David F. McDermott, Sachet A. Shukla, Toni K. Choueiri, Sabina Signoretti
Journal: Clinical Cancer Research (2020)

Abstract Purpose: We sought to validate levels of CD8+ tumor-infiltrating cells (TIC) expressing PD-1 but not TIM-3 and LAG-3 (IF biomarker; Pignon and colleagues, 2019) and to investigate human endogenous retroviruses (hERV) as predictors of response to anti–PD-1 in a randomized trial of nivolumab (nivo) versus everolimus (evero) in patients with metastatic clear cell renal cell carcinoma (mccRCC; CheckMate-025). Experimental Design: Tumor tissues (nivo: n = 116, evero: n = 107) were analyzed by multiparametric immunofluorescence (IF) and qRT-PCR. Genomic/transcriptomic analyses were performed in a subset of samples. Clinical endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and durable response rate (DRR, defined as complete response or partial response with a PFS ≥ 12 months). Results: In the nivo (but not evero) arm, patients with high-IF biomarker density (24/116, 20.7%) had higher ORR (45.8% vs. 19.6%, P = 0.01) and DRR (33.3% vs. 14.1%, P = 0.03) and longer median PFS (9.6 vs. 3.7 months, P = 0.03) than patients with low-IF biomarker. By RNA sequencing, several inflammatory pathways (q &amp;lt; 0.1) and immune-related gene signature scores (q &amp;lt; 0.05) were enriched in the high-IF biomarker group. When combined with the IF biomarker, tumor cell (TC) PD-L1 expression (≥1%) further separated clinical outcomes in the nivo arm. ERVE-4 expression was associated with increased DRR and longer PFS in nivo-treated patients. Conclusions: High levels of CD8+ TIC expressing PD-1 but not TIM-3 and LAG-3 and ERVE-4 expression predicted response to nivo (but not to evero) in patients with mccRCC. Combination of the IF biomarker with TC PD-L1 improved its predictive value, confirming our previous findings.
Abstract 14385: The Exist of Enlarged Left Ventricular Diastolic Volume is Not a Predictor of Irreversible Left Ventricular Systolic Function in Patients With Atrial Arrhythmia
Authors: Hisao Matsuda, Airi Noda, Yui Nakayama, Toru Nakanishi, Mizuho Kasahara, Takayuki Warisawa, Kei Mizukoshi, Makoto Takano, Koichi Mizuno, Akira Kasagawa, Marika Yamada, Ikutarou Nakajima, Hidekazu Miyazaki, Toshiyuki Furukawa, Tomoo Harada, Yoshihiro J Akashi
Journal: Circulation (2020)

Introduction: Atrial arrhythmia (AA) and left ventricular systolic dysfunction (LVSD) frequently co-exist, which loom as burgeoning public health problems. It is difficult to determine whether a tachycardia is the indicator or consequence of LVSD in patients with tachycardia and LVSD. Tachycardia mediated cardiomyopathy (TCM) raises a “chicken or egg” question. Regardless of the etiology, the patients with severe LVSD are considered as the candidate for the implantation of cardioverter defibrillator as primary prevention. It is well known that the LVSD improves after the successful treatment of AA in TCM population. However, enlarged left ventricular end-diastolic dimension (LVDd) is considered as a parameter of irreversible LVSD. Hypothesis: Enlarged LVDd could not be a predictor for irreversible LVSD in patients with AA. Methods: We assessed patients with persistent AA and heart failure (Ejection Fraction (EF) &lt;45%) who were received aggressive rhythm control therapy and maintained sinus rhythm with catheter ablation, electrical cardioversion and anti arhythmic drugs. Echocardiographic parameters and brain natriuretic peptide (BNP) were evaluated before and after the treatment. Results: Twenty-five patients with persistent AA and LVSD (23 men; mean age 63.8±9.3 years) were enrolled in this study. After restored and maintained SR, EF and left ventricular end-systolic volume (ESV) and BNP were improved in all patients respectively (EF 30.7±10.7 to 54.0±7.3%, ESV; 82.1±32.4 to 50.6±24.1ml, BNP; 379.2±237.9 to 48.0±29.7pg/ml P&lt;0.001). In the other hand, there were no significant improvement of LVDd and left ventricular end-diastolic volume (EDV) (LVDd; 54.7±7.6 to 54.3±5.5mm P=0.68, EDV; 120.1±37.9 to 108.2±38.0ml P=0.16). Enlarged LVDd &gt;60mm were observed in 5 patients (25%) before the treatment. EF was normalized in patients with severe LVSD (EF&lt;35%, n=13; 52%). Conclusions: The unnecessary device implantation could be avoided in patients with AA and severe LVSD with aggressive rhythm control therapy. Even in the patients with severe LVSD and enlarged LVDd, LVSD is reversible when AA exists.
Abstract 16510: Acute Use Impairs Vascular Function in Exclusive Juul Users (the Jive Study)
Authors: Sana Majid, Rachel J Keith, Jessica L Fetterman, Robert M Weisbrod, Comreen Vargees, Jessica Nystoriak, Tabitha L Thomas, Andrew Stokes, Michael J Blaha, Sanjay Srivastava, Rose M Robertson, Aruni Bhatnagar, Naomi M Hamburg
Journal: Circulation (2020)

Introduction: The use of pod-based electronic cigarettes such as JUUL has especially increased among youth and young adults. Due to its popularity and high nicotine delivery as salts, JUUL warrants assessment of its cardiovascular effects. Hypothesis: JUUL use alters vascular function. Methods: In the JUUL Impact on Vascular Effects (JIVE) Study, we evaluated endothelial function and blood pressure (BP) in healthy young adults aged 18-40 who were either tobacco nonusers (N=23), exclusive combustible cigarette users (N=17) or exclusive JUUL users (N=15). Results: As shown in the figure, no differences were noted in baseline brachial artery FMD across the 3 groups. Both JUUL and combustible cigarette users had higher systolic and diastolic BP compared to nonusers (P&lt;0.01). Following 10-minute structured use, JUUL decreased FMD more than nonuse (P&lt;0.01) and was similar to combustible cigarette use (P=0.30 vs JUUL). These differences persisted in models adjusted for age, race and sex. Additionally, JUUL use induced an acute rise in systolic BP (6 ± 6mmHg) that differed from nonuse (0.3 ± 5 mmHg, P=0.001) but was similar to combustible cigarette use (8 mmHg, P=1.0). Urinary cotinine and nicotine levels were higher in combustible cigarette and JUUL users following acute exposure (general linear model adjusted for urinary creatinine with overall P&lt;0.01, combustible cigarette vs nonusers P&lt;0.01, JUUL vs nonusers P&lt;0.01). Conclusions: Our results indicate that acute and chronic JUUL use are associated with higher BP, and acute use with a decrease in endothelial function similar to acute combustible cigarette use, thereby suggesting that JUUL alters vascular function both chronically and upon acute exposure in healthy young adults. Further studies are needed to evaluate the long-term impact of JUUL use on vascular health.