tbuckley/cabot-search huggingface dataset:
Doctors shine light on legal fight against PPE contracts
Authors: Alison Shepherd
Journal: BMJ (2021)

Activist doctors took their fight for ministers to be accountable for decisions made during the pandemic to the streets of London last week, illuminating government buildings with questions for Matt Hancock, England's health secretary.EveryDoctor, a company set up by doctors to campaign on behalf of doctors and patients, aimed to highlight the start of the High Court hearing into government decisions to award contracts worth £650m (€755m; $920m) to inexperienced companies to provide personal protective equipment.Buildings targeted by the group included Department of Health and Social Care and NHS offices and the ExCeL Centre, former home of a Nightingale hospital for covid patients.Julia Patterson, EveryDoctor's chief executive, said, "We wanted to get the message across to the public about just how important this case is.Hundreds of millions of pounds were handed out to firms that, in many cases, had few assets and little or no experience of manufacturing or procuring PPE.We want to know why.
Abstract 17306: Primary Prevention Aspirin Use Trends and Associations With Health Beliefs Among African Americans, 2015-2019
Authors: Jeremy R Vant Hof, Jeffrey Misialek, Niki C Oldenburg, Russell V Luepker, Milton Eder, Sue Duval
Journal: Circulation (2020)

Introduction: Cardiovascular disease (CVD) disproportionately affects African Americans. Aspirin has long been recommended as an option to reduce cardiovascular events. However, recent clinical trials involving primary prevention aspirin have prompted changes in national guidelines restricting the aspirin recommended population. Hypothesis: Primary prevention aspirin use will decline over the 5 year period 2015-2019. Methods: Using 3 cross-sectional surveys, data were collected from self-identified African Americans in 2015, 2017 and 2019, querying information on CVD risk factors, health behaviors and beliefs, and aspirin use. Poisson regression modeling was used to estimate age- and risk-factor adjusted aspirin prevalence, trends and associations. Results: A total of 1,491 African Americans adults, ages 45-79, 61% women and no prior CVD completed surveys and were included in this analysis. There was no change in age- and risk factor-adjusted aspirin use over the 3 surveys for women (37%, 34% and 35% respectively) or men (27%, 25%, 30% respectively). However, fewer participants believed aspirin was helpful in 2019--75% vs 84% in 2015 (p&lt;0.05). In the total sample (n=1,491) aspirin discussions with a health care practitioner were highly associated with aspirin use (aRR 2.97, 95% CI 2.49-3.54), as were several health beliefs and social norms that affirm preventive behaviors and aspirin use (Figure). Conclusion: Despite major changes in national guidelines and negative perceptions of aspirin effectiveness in the media, overall primary prevention aspirin use did not significantly change in this African American sample from 2015 to 2019.
Ethnicity-specific BMI cutoffs for obesity based on type 2 diabetes risk in England: a population-based cohort study
Authors: Rishi Caleyachetty, Thomas M Barber, Nuredin Ibrahim Mohammed, Francesco P Cappuccio, Rebecca Hardy, Rohini Mathur, Amitava Banerjee, Paramjit Gill
Journal: The Lancet Diabetes & Endocrinology (2021)

National and global recommendations for BMI cutoffs to trigger action to prevent obesity-related complications like type 2 diabetes among non-White populations are questionable. We aimed to prospectively identify ethnicity-specific BMI cutoffs for obesity based on the risk of type 2 diabetes that are risk-equivalent to the BMI cutoff for obesity among White populations (≥30 kg/m2).In this population-based cohort study, we used electronic health records across primary care (Clinical Practice Research Datalink) linked to secondary care records (Hospital Episodes Statistics) from a network of general practitioner practices in England. Eligible participants were aged 18 years or older, without any past or current diagnosis of type 2 diabetes, had a BMI of 15·0-50·0 kg/m2 and complete ethnicity data, were registered with a general practitioner practice in England at any point between Sept 1, 1990, and Dec 1, 2018, and had at least 1 year of follow-up data. Patients with type 2 diabetes were identified by use of a CALIBER phenotyping algorithm. Self-reported ethnicity was collapsed into five main categories. Age-adjusted and sex-adjusted negative binomial regression models, with fractional polynomials for BMI, were fitted with incident type 2 diabetes and ethnicity data.1 472 819 people were included in our study, of whom 1 333 816 (90·6%) were White, 75 956 (5·2%) were south Asian, 49 349 (3·4%) were Black, 10 934 (0·7%) were Chinese, and 2764 (0·2%) were Arab. After a median follow-up of 6·5 years (IQR 3·2-11·2), 97 823 (6·6%) of 1 472 819 individuals were diagnosed with type 2 diabetes. For the equivalent age-adjusted and sex-adjusted incidence of type 2 diabetes at a BMI of 30·0 kg/m2 in White populations, the BMI cutoffs were 23·9 kg/m2 (95% CI 23·6-24·0) in south Asian populations, 28·1 kg/m2 (28·0-28·4) in Black populations, 26·9 kg/m2 (26·7-27·2) in Chinese populations, and 26·6 kg/m2 (26·5-27·0) in Arab populations.Revisions of ethnicity-specific BMI cutoffs are needed to ensure that minority ethnic populations are provided with appropriate clinical surveillance to optimise the prevention, early diagnosis, and timely management of type 2 diabetes.National Institute for Health Research.
Abstract 13328: Impact of Cascade Screening for Familial Hypercholesterolemia on Cardiovascular Events
Authors: Hayato Tada, Atsushi Nohara, Masakazu Yamagishi, Masayuki Takamura, Masa-aki Kawashiri
Journal: Circulation (2020)

Background: Familial hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the low-density lipoprotein (LDL) receptor or associated genes, resulting in elevated serum cholesterol levels and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Early diagnosis and timely treatment can substantially lower the risk of ASCVD. In this sense, cascade screening could be one of the most useful options. However, few data exist regarding the impact of cascade screening for FH on the reduction of risk of ASCVD events. We aimed to evaluate the prognostic impact of cascade screening for FH. Methods: We retrospectively investigated the health records of 1,050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened, who were referred to our institute. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiovascular events (MACE). The median period of follow-up was 12.3 years (interquartile range [IQR] = 9.1-17.5 years), and MACE included death from any causes or hospitalization due to ASCVD events. Results: During the observation period, 246 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P &lt; 2.2 х 10 –16 ), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.36; 95%CI = 0.22 to 0.60; P = 6.3 х 10 –5 ) when compared with the probands, even after adjusting for those known risk factors. Conclusions: The identification of patients with FH via cascade screening appeared to result in better prognoses.
Abstract 12689: Targeted Exon Sequencing of Lipid-related Genes in Patients With Clinically Diagnosed Familial Hypercholesterolemia
Authors: Takeshi Okada, Masahiro Koseki, Makoto Nishida, Katsunao Tanaka, Hiroyasu Inui, Kotaro Kanno, Ayami Saga, Tohru Ohama, Takeshi Kujiraoka, Hiroaki Hattori, Shizuya Yamashita, Yasushi Sakata
Journal: Circulation (2020)

Background: Familial hypercholesterolemia (FH) is at high risk of premature coronary artery disease (CAD). Japan Atherosclerosis Society (JAS) has published original criteria for FH. Patients are diagnosed clinical FH if at least 2 of the following criteria are satisfied: i) LDL-C ≥ 180 mg/dL, ii) Tendon/ skin xanthomas, iii) History of FH or premature CAD within 2nd degree blood relatives. Although it is easy to apply these criteria for FH-suspected patients, in fact, we are not sure whether other lipid-related genes may be overlapped in addition to those of conventional FH genes such as LDL receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Methods and Results: Ninety-one heterozygous FH (HeFH) patients in Osaka University Hospital, who met the clinical FH criteria of JAS were enrolled after obtaining informed consent. Genomic DNA for each patient was extracted from peripheral blood cells. Targeted exon sequencing was performed to investigate 36 lipid-related genes including conventional FH genes. We have defined pathogenic variants if they fulfilled i) rare protein truncating variants, ii) rare damaging missense variants, and iii) ClinVar-registered pathogenic or likely pathogenic variants. Among 91 HeFH patients (52.9 ± 14.7 years), 41 patients (45.1%) were males. We have identified LDLR pathogenic variants in 61 patients (67.0%) and PCSK9 variants in 1 patient (1.1%). Among these 62 patients, 22 patients (35.5%) additionally have pathogenic variants of other lipid-related genes, which include apolipoprotein E2 (APOE2) in 1 patient, apolipoprotein E4 (APOE4) in 10 patients, ATP-binding cassette subfamily G member 5 (ABCG5) in 2 patients, apolipoprotein C3 (APOC3) in 1 patient, and CD36 in 10 patients. As for remaining 29 patients without conventional FH gene variants, 13 patients (44.8%) have pathogenic variants of other lipid-related genes, which include APOE4 in 11 patients, apolipoprotein E5 (APOE5) in 1 patient, and variants of ABCG5 in 1 patient. Conclusion: We have identified several variants of lipid-related genes in addition to conventional FH genes in HeFH patients diagnosed according to JAS criteria. These variants may affect the atherogenicity of patients and selection of medication.
Abstract P065: Odds Of Heart Disease And Arrhythmia Associated With Exposure Dose To Homelessness
Authors: Ben King
Journal: Circulation (2021)

Background: Adults experiencing homelessness are at 40-50% greater mortality risk from cardiovascular disease (CVD) than the general population, however little is understood about how the duration or degree of homelessness increases the risk of CVD. The Vulnerability Index-Service Prioritization Decision Assistance Tool (VI-SPDAT v1, 2012) is a 50-item measure intended to proscribe appropriate levels of intervention and prioritize the waiting list for housing. The measure also includes an item to assess history of CVD. The objective of this study is to examine the relation between duration and frequency of homelessness and CVD diagnosis, while controlling for potential confounders. Method: Version 1 of the VI-SPDAT was used to assess a cohort of individuals experiencing homelessness (n=4,739 unique participants; median age=47, {17-88}) and seeking subsidized housing services in a single county in Texas between 2014 and 2017. Medical questions were validated through electronic, deterministic linkage to the Community’s Health Information Exchange (HIE) for indigent populations. Logistic regression models identified independent covariates and potential effect modifiers of a theoretical dose-response relationship between homelessness and CVD. Results: A history of heart disease or arrhythmia was reported in 24.98% of the sample. For participants with repeated assessments (n=713; median interval of homelessness: 306 days; IQR: 216-441 days) the prevalence increased from 25.6% to 30.6% (p&lt;0.05). Criterion validation of the tool using HIE data supported that this prevalence estimate was under-reported (38.67%; 26.44% adjusted for full sample). Odds of CVD increased with age (OR=1.03; 95%CI:1.02-1.04) and spending more than two years in homelessness (OR=1.45; 95%CI:1.27-1.67). Proportion of the sample with CVD was also higher for females, non-Hispanic participants (both p&lt;0.05), those reporting medication adherence issues, problems with concentration, history of traumatic brain injury, and mental health-related ED visits (all p&lt;0.001). Age at assessment (p&lt;0.001), total time spent homeless (p&lt;0.001), and recent episodes (p&lt;0.05) were all independently associated with CVD. Cognitive deficits and medication adherence issues mediated the relationship between multiple demographics, homeless episodes, and reported CVD diagnosis, but fit independently into a model with age, gender, and 2 years or more spent in homelessness. Discussion: This study presents a rare window into the complex interrelationships of the time-dose of exposure to homelessness and the concomitant social and medical vulnerabilities. Time spent in homelessness and the number of recent homelessness periods were independently associated with CVD, even while controlling for age, suggesting a complex dose-response relationship.
Abstract 15116: The Prognostic Value of Left Ventricular Mechanical Dyssynchrony in Patients With Idiopathic Dilated Cardiomyopathy
Authors: Yangjie Li, Yuanwei Xu, Siqi Tang, Xiaoyue Zhou, Yucheng Chen
Journal: Circulation (2020)

Backgrounds: The mechanical dyssynchrony has been commonly observed in idiopathic dilated cardiomyopathy (DCM) patients, and several cardiac magnetic resonance (CMR) imaging techniques were used to evaluate the mechanical dyssynchrony. Standard deviation of time-to-peak (T2Psd) and uniformity ratio estimate (URE) indices are two widely used parameters to reflect the incoordinate movement of the left ventricle. However, the prognostic value of mechanical dyssynchrony in DCM patients is not clear. Methods and Results: We prospectively enrolled 402 DCM patients undergoing CMR imaging between Jun 2012 to Sep 2018. Mechanical dyssynchrony was measured as T2Psd and URE indices by CMR deformable registration algorithm (DRA) analysis. The primary endpoint was defined as all-cause mortality and heart transplantation, and the secondary endpoint was a combination of primary endpoint, aborted sudden cardiac death, and heart failure readmission. Univariate and multivariate Cox regression analyses were performed to identify the association between variables and outcome. Survival curves were obtained by Kaplan-Meier survival analysis and compared by log-rank test. During a median follow-up of 25.1 months (IQR: 16.2-41.6), there were 57 patients reached primary endpoints, and secondary endpoints occurred in 132 patients. Circumferential uniformity ratio estimate (CURE) at basal, mid and apical level, radial uniformity ratio estimate (RURE)at mid and apical level and longitudinal uniformity ratio estimate (LURE) were significantly worse in patients with primary endpoint compared to patients without primary endpoint. While no significant differences were observed regarding the T2Psd value between patients with and without primary endpoints. In multivariate analysis, CURE at apical level was independently associated with primary endpoints (HR 0.214, P=0.005) and secondary endpoints (HR 0.402, P=0.018). Furthermore, among patients with LVEF &lt;35% or presence of LGE, those with decreased CURE at apical level (&lt;0.917) showed a significantly higher rate of adverse outcome. Conclusion: The CURE at apical level is an independent predictor of adverse cardiac events in DCM patients. Compared with T2Psd, URE index is a better predictor of adverse events.
Loss of PTEN expression induces tissue factor expression and resistance to doxorubicin in neuroblastoma
Authors: Jun Fang, Lubing Gu, Ningxi Zhu, Harry W. Findley, Carlos S. Alvarado, Muxiang Zhou
Journal: Cancer Research (2006)

729  Tissue factor (TF) is a transmembrane protein that acts as a receptor for coagulation factor VII initiating the coagulation cascade, but also mediates intracellular signaling that is relevant to tumor growth, apoptosis and metastasis. High levels of TF expression have been observed in patients with advanced and metastatic cancer. Here we report that the expression of TF was regulated by the tumor suppressor PTEN and was associated with sensitivity to chemotherapeutic drugs in neuroblastoma. Two neuroblastoma cell lines SK-N-SH and SK-N-MC were examined for the expression of TF and PTEN as well as their response to doxorubicin-induced apoptosis. SK-N-SH expressing high levels of PTEN was TF negative and sensitive to doxorubicin, whereas SK-N-MC lacking PTEN expression expressed high levels of TF and was relatively resistant to doxorubicin. Inhibition of PTEN expression in SK-N-SH cells by PTEN siRNA upregulated TF expression. In contrast, TF was downregulated in SK-N-MC cells by enforced expression of PTEN as well as treatment with the PI3k/Akt inhibitor LY294002. Both PTEN gene transfection and LY294002 sensitized SK-N-MC cells to doxorubicin, which was also obtained by direct inhibition of TF with siRNA. These results suggest that the expression of TF is regulated by the PI3k/Akt pathway, and TF-mediated cellular signaling is at least one of the mechanisms by which loss of PTEN expression confers resistance to chemotherapy and cancer progression.
Abstract 14866: Plasma B-type Natriuretic Peptide Levels Are Associated With Future Cardiovascular Events in Patients With Type 2 Diabetes Mellitus Without Known Cardiovascular Disease
Authors: Shota Ikeda, Keisuke Shinohara, Nobuyuki Enzan, Shouji Matsushima, Takeshi Tohyama, Kouta Funakoshi, Junji Kishimoto, Hiroshi Itoh, Issei Komuro, Hiroyuki Tsutsui
Journal: Circulation (2020)

Introduction: B-type natriuretic peptide (BNP) is known to predict future cardiovascular (CV) events in patients with known CV disease. However, these associations have not been investigated in patients with type 2 diabetes mellitus (T2DM) without known CV disease. We investigated whether BNP levels are associated with CV events among T2DM patients without known CV disease using the dataset of EMPATHY study. Methods and Results: The EMPATHY was a randomized controlled trial of intensive statin therapy in T2DM patients without known CV disease. CV events were defined as composite of cardiac (acute coronary syndrome and coronary revascularization [excluding heart failure]), cerebral, and vascular events. A total of 4704 patients without CV events or death during the first 12 months were included and 114 CV events occurred during a median follow-up of 37.8 months. The patients were divided based on quartile of baseline BNP levels (Q1: &lt;7.4, Q2: 7.4-14.8, Q3: 14.8-28.7, Q4: ≥28.7 [pg/mL]). Compared to the lowest quartile of BNP, only the highest quartile was associated with increased risk for CV events after adjustment (HR 2.96, 95% CI 1.29-6.79, p=0.010). Using this highest quartile cutoff, we categorized BNP &lt;28.7 pg/mL as low BNP and BNP ≥28.7 pg/mL as high BNP. Compared to patients with low BNP, the adjusted HRs for CV events were 2.12 (95% CI 1.35-3.34, p=0.001) in patients with high BNP at baseline and 2.64 (95% CI 1.67-4.17, p&lt;0.001) in those with high BNP at 12 months. In analysis using serial measurement, patients who had repeatedly high BNP or had low BNP at baseline and high BNP at 12 months were in significantly higher risk for CV events compared to those who had repeatedly low BNP (HR 3.28, 95% CI 1.90-5.66, p&lt;0.001 or HR 2.65, 95% CI 1.44-4.87, p=0.002, respectively), whereas those who had high BNP at baseline and low BNP at 12 months were not (HR 1.99, 95% CI 0.90-4.39, p=0.089). Conclusion: Increased BNP levels were associated with higher risk of CV events (excluding heart failure) in T2DM patients without known CV disease. HR for CV events was greater in patients with repeatedly high BNP than in those with high BNP at only one of the two measurements, suggesting that serial BNP measurement may be more useful for predicting future CV events in T2DM patients.
Association between proton pump inhibitor use and gastric cancer: a population-based cohort study using two different types of nationwide databases in Korea
Authors: Seung In Seo, Chan Hyuk Park, Seng Chan You, Jae Young Kim, Kyung Joo Lee, Jinseob Kim, Yerim Kim, Jong Jin Yoo, Won-Woo Seo, Hyung Seok Lee, Woon Geon Shin
Journal: Gut (2021)

The association between proton pump inhibitor (PPI) use and gastric cancer related to
Abstract P104: Higher Leptin Levels Are Associated With Increased Odds Of Coronary Artery Calcium Progression: The Multi-ethnic Study Of Atherosclerosis
Authors: Bhavya Varma, Oluseye Ogunmoroti, Chiadi Ndumele, Di Zhao, Moyses Szklo, Ty Sweeney, Matthew A Allison, Matthew Budoff, Vinita Subramanya, Alain G Bertoni, Erin Michos
Journal: Circulation (2021)

Background: Adipokines are secreted by adipose tissue, play a role in cardiometabolic pathways, and have differing associations with cardiovascular disease (CVD). Coronary artery calcium (CAC) and its progression indicate subclinical atherosclerosis and prognosticate CVD risk. However the association of adipokines with CAC progression is not well established. We examined the association of adipokines with the odds of a history of CAC progression in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: We performed an analysis of 1,904 community dwelling adults free of clinical CVD in MESA. Participants underwent measurement of serum adipokines [leptin, resistin and adiponectin] at visits 2 or 3 (randomly assigned) and a contemporaneous cardiac CT scan at same visit. Participants also had a prior cardiac CT at visit 1, at a median of 2.4 years earlier. On both CTs, CAC was quantified by Agatston score. We defined a history of CAC progression between the CT scans at visit 1 and at visit 2 or 3 as those with &gt;0 Agatston units of change per year (and compared to those with ≤0 units of change per year). We used logistic regression to examine the odds of having a history of CAC progression by adipokine tertiles using progressively adjusted models. Results: The mean participant age was 65 (10) years; 50% were women, 40% White, 13% Chinese, 21% Black and 26% Hispanic. The prevalences of CAC at visits 1 and 2/3 were 49% and 58%, respectively. There were 1,001 (53%) who had CAC progression between the 2 CT scans. In demographic-adjusted models (model 1, Table), higher leptin and lower adiponectin were associated with increased odds of prior CAC progression. In models fully adjusted for BMI and other CVD risk factors (model 3), only the highest tertile of leptin remained associated with a greater odds of prior CAC progression [OR 1.55 (95% CI 1.04, 2.30)]. Conclusions: Higher leptin levels were independently associated with a history of CAC progression. Atherosclerosis progression may be one mechanism through which leptin confers increased CVD risk