tbuckley/cabot-search huggingface dataset:
Abstract P016: Lifestyle Factors Substantially Contributed to Urban-Rural Disparity in All-Cause Mortality Among the Oldest-Old in China
Authors: Shangzhi Xiong, Yaxi Li, Lijing Yan
Journal: Circulation (2019)

Introduction: With rapid population aging, the number of the oldest old population (≥ 80 years old) will increase dramatically in the coming decades in China. In this population, previous studies have demonstrated large health disparities between urban and rural China. Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we aim to assess the hypothesis that individual-level lifestyle factors contribute to the disparity in all-cause mortality of the oldest old between urban and rural China. Methods: The CLHLS study sampled 862 randomly selected counties and districts in 22 of the 34 provinces in China. Our study included a total of 32,999 oldest old residents (13,767 urban, 19,232 rural) from seven waves of the CLHLS: 1998, 2000, 2002, 2005, 2008, 2011-12, and 2014. Five lifestyle factors were examined: smoking, drinking, diet (fruits, vegetables, fish, eggs, salted vegetables, sugar, tea, garlic, meat, and beans), physical activity, and leisure activity (housework, fieldwork, reading, petting, majong, gardening, and watching television). All-cause mortality was ascertained through death registry and information from next of kin with a median follow up of 2.3 years (range: 1-16.5 years). We used Cox Proportional Hazard Models to examine the urban-rural disparity of all-cause mortality: the basic model including residence (rural/urban) and demographic variables (age, gender, education, occupation, marriage, co-residence, and ethnic), five separate models including each lifestyle factor and all variables in the basic model, and a model with all lifestyle factors added to the basic model. Results: There were significant differences between urban and rural participants in their smoking, drinking, physical activity, diet, and leisure activities ( P &lt;0.005 for all). All seven Cox Regression models showed large urban-rural disparities in mortality. The basic model showed that rural mortality was 11.2% higher than urban (95% Confidence Interval: 8.2, 14.3). Adjusting for diet, physical activity, and leisure activities, separately reduced the disparity by 10.3%, 25.3%, and 34.7% respectively. Adjusting for smoking and drinking did not cause substantial changes to the disparity. When put together in the same model, these five lifestyle factors collectively reduced the disparity by 37.5%. Conclusions: In conclusion, lifestyle factors, especially diet, physical activity, and leisure activities, contributed substantially to the urban-rural disparity in all-cause mortality of the oldest old in China. Interventions and policies targeting lifestyle factors are expected to reduce the disparity in China among the oldest old population.
Critical role of ASCT2-mediated amino acid metabolism in promoting leukaemia development and progression
Authors: Fang Ni, Wen-Mei Yu, Zhiguo Li, Douglas K. Graham, Lingtao Jin, Sumin Kang, Michael R. Rossi, Shiyong Li, Hal E. Broxmeyer, Cheng-Kui Qu
Journal: Nature Metabolism (2019)
David Oliver: The health secretary and upstanding nurses
Authors: David Oliver
Journal: BMJ (2019)

I’m worried about what our health secretary’s remarks at the chief nursing officers’ conference reveal about his understanding of the modern health service. The full text of Matt Hancock’s speech can be found on the government’s website,1 and he made some valid points about recognising the skills of our nursing workforce.

Sadly, he also said: “I find it shocking that, in my grandmother’s day, nurses were expected to stand up when a doctor entered the room. And worse, I find that’s still the case in some antiquated, archaic corners of the NHS. I want it to stop. If anything, it should be doctors standing up for nurses. Because who runs a hospital at 2 am in the morning? Who keeps the show on the road?”

The reaction to these remarks …
Finding a new balance to cure Charcot-Marie-Tooth 2A
Authors: Keiko Iwata, Luca Scorrano
Journal: Journal of Clinical Investigation (2019)

Motoneurons are particularly sensitive to mutations in mitofusin-2 (MFN2) that cause the neurological disorder Charcot-Marie-Tooth disease type 2A (CMT2A). MFN2 is a mitochondrial outer membrane protein that, together with its homologue MFN1, fuses mitochondria in most tissues. In this issue of the JCI, Zhou and colleagues show that increasing MFN1 expression in neurons can curtail neurological defects in a CMT2A mouse model. These results show that the ratio of MFN1 to MFN2 can explain the tissue specificity of CMT2A and indicate that augmentation of MFN1 in the nervous system has potential as a possible therapeutic strategy for CMT2A.
Risk factors for interval advanced colorectal neoplasia after screening colonoscopy.
Authors: Laura W. Musselwhite, Catherine M. Thomas, David H. Abbott, Elizabeth R. Hauser, Laura K. Wagner, Sara F. Morris, David G. Weiss, David A. Lieberman, Dawn T. Provenzale
Journal: Journal of Clinical Oncology (2015)

3539 Background: Knowledge of risk factors for interval colorectal neoplasia could inform screening strategies in asymptomatic individuals. Few studies have evaluated risk factors for advanced neoplasia at 5 years in individuals who have had screening colonoscopy. Methods: We studied 1193 participants aged 50-75 to identify factors associated with interval advanced neoplasia during a 5-year follow-up period. Participants underwent screening and 5-year colonoscopy from 1994-1997 at 13 Veterans Affairs Medical Centers. Advanced neoplasia included an adenoma ≥ 1cm, villous histology, high-grade dysplasia, or carcinoma. Risk factors were self-reported at baseline. We performed a multivariable logistic regression analysis of risk for interval advanced neoplasia, adjusting for age, smoking, alcohol use, BMI, colon cancer in first degree relatives, diabetes, cardiovascular disease, and prior outcome. Results: Participants were mostly male (97%) and white (83%). At 5 years, 392 participants (33%) had small adenomas < 1cm, and 92 participants (7.7%) had advanced neoplasia. In multivariable analyses, risk for interval advanced neoplasia was associated with age in 10-year increments (OR, 2.09; 95% CI, 1.39-3.13), diabetes (OR, 1.95; 95% CI, 1.12-3.41), prior small adenomas (OR, 4.02; 95% CI, 1.65-9.80), and prior advanced neoplasia (OR, 12.41; 95% CI, 5.08-30.30). Conclusions: In this prospective screening study, we identified diabetes as an independent risk factor for interval advanced neoplasia. Future guidelines should consider enhanced follow up of diabetic patients.
Abstract P088: Assessing the Use of a Preventive Cardiology Lifestyle Screening (PCLS) Tool in a Pediatric Sub-Specialty Lipid Clinic
Authors: Suzanne Skylar Griggs
Journal: Circulation (2019)

Objective: Lifestyle modification is recommended to improve cholesterol levels in the pediatric population with the goal of reducing CVD risk. Existing tools assessing pediatric lifestyle habits are cumbersome and lack specificity. We developed the Preventive Cardiology Lifestyle Screen (PCLS) to assess behaviors relevant to CVD risk, and evaluated its use in a subspecialty lipid clinic at a large pediatric teaching hospital. Methods: Eligible participants were 2-21 years old, English speaking and presenting for care in a pediatric lipid clinic. We evaluated test-retest agreement using weighted kappa statistics, and validity of PCLS compared to longer research questionnaires [Block Food and Activity Questionnaires and Rapid Eating Assessment for Patients (REAP)] using Spearman correlation coefficients. Results: Participants (n = 138) had a mean age of 13 years; 50% were female, 22% reported a household income &lt;$50,000. Median non-HDL cholesterol was 149.2 mg/dL and HDL cholesterol was 48 mg/dL. Of participants 2-17 years old (n=122), 15% were overweight and 46% were obese. Test re-test agreement for those ≥10 years (n=24) was good (weighted kappa &gt;.75) for fruits and vegetables (0.83, 0.82 respectively), chicken no skin (0.89), processed meats (0.78) and sports drinks (.75). Test-retest agreement was poor (weighted kappa &lt;.50) for regular soda intake (0.40), regular fat dairy (0.47), and eating lunch (0.45). Activity (sports 0.94 gym class 0.77) and inactivity (weekend video games 0.88 hours of sleep 0.78) overall had high test-retest agreement for most questions. Examining across dietary domains, the PCLS performed well at baseline compared to the BLOCK and REAP surveys in the domains of saturated fat, glycemic index, sodium and fiber (Table 1). Conclusion: The PCLS performed well on test re-test agreement, and responses correlated with previously validated research tools in most domains. This tool shows promise for use in the care of children with CVD lipid disorders.
Abstract P392: Association Between Migration to the US, Cardiovascular Disease, and Cardiovascular Risk Factors Among Mexican Migrants and Non-Migrants
Authors: Aresha Martinez-Cardoso, Arline Geronimus
Journal: Circulation (2019)

Background: Mexico-US migration represents one of the largest migration flows across the globe. However, debates abound over whether health selection is a salient driver of migration, and furthermore how migration shapes the health of Mexican migrants. Objectives: To address these gaps in the literature, we used binational data from Mexico to compare cardiovascular risk factors and health profiles of (1) Mexico-US nonmigrants and future migrants and (2) Mexico-US nonmigrants and return migrants. Methods: Data from the Mexican Family Life Survey, a nationally-representative survey with measures of migration and health, was used for the analysis. We estimated a series of mixed effects logistic regression models to assess the association between (1) cardiovascular health at baseline and future migration status and (2) exposure to the US (migration to the US and time in the US) and cardiovascular health. Cardiovascular health indicators included obesity, wasit-hip-circumference (WHC), high blood pressure, self-reported diabetes, self-reported cardiovascular disease, and smoking and physical activity behaviors. Results: Cardiovascular health was not a significant predictor of future migration to the US; that is, the health of Mexico-US migrants’ was on par with their compatriots who do not migrate. However for some cardiovascular indicators, the health of return migrants with exposure to the US was worse than non-migrants. Return migrants had higher levels of adiposity, obesity (OR=1.38, 95% CI 1.05,1.80), and elevated WHC (OR=1.45, 95% CI 1.07,1.95). Furthermore, time spent in the US was significantly associated with obesity (OR=1.005, 95% CI 1.001,1.009), elevated waist circumference (OR=1.003, 95% CI 1.001,1.007), and self-reported cardiovascular disease (OR=1.005, 95% CI 1.002,1.009). Finally, the association between exposure to the US and poorer cardiovascular health was not mediated by physical activity or smoking behavior. Conclusions: Our findings shed light on the drivers of Mexican immigrants’ health, and underscore the important of considering the social and environmental context faced by migrants in the US as an important determinant of cardiovascular health.
Attitudes and practice patterns of professionals regarding the multidisciplinary team approach in cancer management: Results from a national survey in Korea.
Authors: Yun-Gyoo Lee, Dong Hoe Koo, Sukjoong Oh, Seung-Sei Lee
Journal: Journal of Clinical Oncology (2015)

e17524 Background: The optimal management of patients with advanced cancer requires the expertise of specialists from different disciplines. This has drawn the introduction of multidisciplinary team (MDT) approach, allowing key professionals to discuss a given patient and to contribute independently to clinical decisions. To invigorate MDT in Korea, authorities decided to reimburse MDT consulting costs when patients are presented at MDT meeting. This national survey explored professionals’ attitudes, and practice patterns regarding MDT. Methods: A survey was sent by e-mail to members of Korean Society of Clinical Oncology, Surgical Oncologists, Radiation Oncologists, Pathologists and Radiologists. The questionnaire covered several topics: organizing structure, candidates for consulting, initiative of clinical decision, and responsibility for dealing with legal disputes. Results: Of 272 respondents, 249 (92%) reported that they had a MDT conference. Seventy-two percent of the respondents reported that patients attended MDT meeting. Sixty percent of the respondents stated their MDTs met regularly (two-thirds are weekly) by a medical oncologist (90%), surgical oncologist (92%), radiation oncologist (85%), pathologist (64%), radiologist (92%) and trainees (48%). Two-thirds of MDTs discussed all stage disease and 22% focused only on localized or locally advanced disease. Most (95%) MDTs discussed the optimal therapeutics after pathologic confirmation. When there was more than one opinion, the treating physicians (64%) or chairperson (18%) made the final decision, or there was a majority vote (18%). Only 10% of respondents declared that it was mandatory to implement the decisions of the MDT. However, 86% were of the opinion that the recommendations made at the MDT were implemented most of time. Regarding responsibility in case of legal disputes, 40% of respondents replied that it would be the treating doctor while 35% thought that members of the MDT would be responsible. Conclusions: This is the first nationwide survey to collect information regarding MDTs in Korea and provides objective information of composition, frequency, and function of MDTs.
Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in Patients With Type 1 Diabetes
Authors: Sascha Pilemann-Lyberg, Tine Willum Hansen, Nete Tofte, Signe Abitz Winther, Simone Theilade, Tarunveer Singh Ahluwalia, Peter Rossing
Journal: Diabetes Care (2019)

OBJECTIVE Previous studies have provided inconclusive results on the role of uric acid (UA) in risk prediction. Here we aimed to improve the power and precision of the predictive value of UA for the risk of decline in kidney function, cardiovascular events (CVEs), and mortality in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Plasma UA was measured in 670 patients with T1D and various degrees of albuminuria, ranging from normoalbuminuria to macroalbuminuria. Associations of UA with an estimated glomerular filtration rate (eGFR) decline of ≥30%, CVEs, and mortality were analyzed. The median follow-up time was 5.3 years [interquartile range (IQR) 2.7–6.2 years] for a decline in eGFR of ≥30%, 5.8 years (2.5–6.4 years) for progression in albuminuria status, 5.1 years (4.7–5.6 years) for CVE, and 6.2 years (5.8–6.7 years) for mortality. Both univariable and multivariable associations of UA with relevant outcomes and variables were reported. Hazard ratios (HRs) were calculated per doubling of the UA level. RESULTS A doubling in UA level was associated with a higher risk of decline in eGFR of ≥30% (n = 89) (HR 3.18 [IQR 1.71–5.93]; P &amp;lt; 0.001), CVE (n = 94) (HR 2.25 [IQR 1.20–4.21]; P = 0.011), and mortality (n = 58) (HR 2.58 [IQR 1.12–5.90]; P = 0.025) in adjusted analyses. Adding UA to the adjusted model including conventional risk factors improved the relative integrated discrimination index by 12.6% for a decline in eGFR of ≥30% (P &amp;lt; 0.001), 6.5% for CVE (P = 0.010), and 11.8% (P = 0.003) for mortality. A doubling in UA level was also associated with a steeper decline in eGFR (P &amp;lt; 0.0026) and a steeper increase in urine albumin-to-creatinine ratio (P &amp;lt; 0.0027) in adjusted analysis. CONCLUSIONS In individuals with T1D, a higher UA level is associated with a higher risk of decline in kidney function, CVE, and mortality, independently of other risk factors. Our results suggest that UA has a promising role in risk stratification among individuals with T1D.
Abstract P197: Factors Contributing to the Success of a Multicomponent Intervention for Blood Pressure Control in Argentina: A Mediation Analysis
Authors: Katherine T Mills, Hua He, Vilma Irazola, Rosana Poggio, Andrea Beratarrechea, Chung-Shiuan Chen, Luz Gibbons, Jing Chen, Adolfo Rubinstein, Jiang He
Journal: Circulation (2019)

Introduction: The Hypertension Control Program in Argentina (HCPIA), a cluster-randomized trial of a community health worker-led multicomponent intervention on blood pressure (BP) control in low-income patients in Argentina, previously reported a significant reduction in systolic BP in the intervention compared to the control group over 18 months (6.6 mm Hg net difference; p&lt;0.001). Understanding which elements of a multicomponent intervention are important contributors to its success is critical for future BP control efforts. We conducted a mediation analysis to determine the contributions of seven measured intervention targets to the systolic BP intervention effect. Methods: HCPIA randomized 18 primary healthcare clinics treating uninsured patients to either a multicomponent intervention, consisting of health coaching, home blood pressure monitoring, blood pressure audit and feedback, physician education, and a mobile health intervention, or usual care. A total of 1,357 hypertensive participants completed the trial and are included in the mediation analyses. Changes in seven potential mediators over the 18-month intervention were assessed: medication adherence score, medication adjustments (addition of new medication or dose titration), waist circumference, physical activity, fruit and vegetable consumption, sodium consumption, and alcohol consumption. Generalized estimating equations were used to compare changes in potential mediators between intervention groups. Path analytic models were used to test single-mediator and multiple mediator indirect intervention effects using the Lavaan package in R statistical software. Mediation was considered significant at p&lt;0.10. Results: All potential mediators were significantly improved in the intervention group compared to the control group. Fruit and vegetable consumption, medication adherence, physical activity, and salt consumption are each significant mediators accounting for 4.3, 3.8, 3.3, and 3.2%, respectively, of the intervention effect in single-mediator models. The multiple mediation model explained 15.5% (1.3 mm Hg) of the total intervention effect. Changes in fruit and vegetable consumption and medication adherence remained significant mediators in multiple mediation analysis, responsible for 3.8% and 4.3% of the net reduction in systolic BP, respectively. Other potential mediators did not account for a significant proportion of the intervention effect. Conclusions: Increases in medication adherence and fruit and vegetable consumption were responsible for the largest proportions of the explained intervention effect.
A genetic risk score to personalize prostate cancer screening, applied to population data.
Authors: Minh-Phuong Huynh-Le, Chun Chieh Fan, J Kellogg Parsons, Jenny Donovan, David Neal, Richard Martin, Ian G Mills, Ole A Andreassen, Anders M Dale, Tyler M Seibert
Journal: Journal of Clinical Oncology (2019)

181 Background: Genetic risk stratification may inform the decision of whether—and at what age—a man should undergo prostate cancer (PCa) screening. We previously validated a polygenic hazard score (PHS) for accurate prediction of age of onset of aggressive PCa and for improved screening PSA performance. The PHS is a weighted sum of 54 SNP genotypes. Here, we applied the PHS to population data to assess its potential impact on individualized screening. Methods: Age-specific PCa incidence data were obtained for men aged 40-70 years from the United Kingdom (Cancer Research UK, 2013-2015) and fit to an exponential curve as a continuous model of age-specific PCa incidence. Using hazard ratios estimated from ProtecT study data, annualized incidence rate curves were calculated for the following percentiles of genetic risk: 1, 5, 20, 50, 80, 95, and 99. The proportion of incidence classified as aggressive (Gleason score ≥7) was estimated as 59.7%, the reported result from the CAP trial. PHS was combined with incidence data to give a risk-equivalent age, when a man with given PHS percentile will have the same risk of aggressive PCa as that of a typical man at age 50 years. Results: The age-specific incidence rate of PCa for the UK population was modeled as: 0.004 e 0.203(age-40) ( R 2 = 0.957, p = 0.001). Table shows risk-equivalent age for each genetic risk percentile. For example, a man with a PHS in the 95th percentile reached PCa risk equivalent to a typical 50-year-old man at age 44 years; conversely, a man with a PHS in the first percentile does not reach this risk level until age 60 years. Initiation of screening discussions could be adjusted accordingly. Conclusions: PHS may inform PCa screening with individualized estimates of risk-equivalent age for aggressive PCa. Risk-equivalent age for aggressive prostate cancer, by PHS percentile. [Table: see text]
A Rapid Functional Screen for Small Molecule and Monoclonal Antibody Drug Sensitivity in Multiple Myeloma Patients
Authors: Zachary J Walker, Michael J VanWyngarden, Brett M Stevens, Christophe Langouët-Astrie, Clayton Smith, Brent E Palmer, Peter A Forsberg, Tomer M Mark, Craig T Jordan, Daniel W Sherbenou
Journal: Blood (2018)
Identification of a pharmacological inhibitor of Epac1 that protects the heart against acute and chronic models of cardiac stress
Authors: Marion Laudette, Antonio Coluccia, Yannis Sainte-Marie, Andrea Solari, Loubina Fazal, Pierre Sicard, Romano Silvestri, Jeanne Mialet-Perez, Sandrine Pons, Bijan Ghaleh, Jean-Paul Blondeau, Frank Lezoualc’h
Journal: Cardiovascular Research (2019)

Recent studies reported that cAMP-binding protein Epac1-deficient mice were protected against various forms of cardiac stress, suggesting that pharmacological inhibition of Epac1 could be beneficial for the treatment of cardiac diseases. To test this assumption, we characterized an Epac1-selective inhibitory compound and investigated its potential cardioprotective properties.We used the Epac1-BRET (bioluminescence resonance energy transfer) for searching for non-cyclic nucleotide Epac1 modulators. A thieno[2,3-b]pyridine derivative, designated as AM-001 was identified as a non-competitive inhibitor of Epac1. AM-001 has no antagonist effect on Epac2 or protein kinase A activity. This small molecule prevents the activation of the Epac1 downstream effector Rap1 in cultured cells, in response to the Epac1 preferential agonist, 8-CPT-AM. In addition, we found that AM-001 inhibited Epac1-dependent deleterious effects such as cardiomyocyte hypertrophy and death. Importantly, AM-001-mediated inhibition of Epac1 reduces infarct size after mouse myocardial ischaemia/reperfusion injury. Finally, AM-001 attenuates cardiac hypertrophy, inflammation and fibrosis, and improves cardiac function during chronic β-adrenergic receptor activation with isoprenaline (ISO) in mice. At the molecular level, ISO increased Epac1-G protein-coupled receptor kinase 5 (GRK5) interaction and induced GRK5 nuclear import and histone deacetylase type 5 (HDAC5) nuclear export to promote the activity of the prohypertrophic transcription factor, myocyte enhancer factor 2 (MEF2). Inversely, AM-001 prevented the non-canonical action of GRK5 on HDAC5 cytoplasmic shuttle to down-regulate MEF2 transcriptional activity.Our study represents a 'proof-of-concept' for the therapeutic effectiveness of inhibiting Epac1 activity in cardiac disease using small-molecule pharmacotherapy.