tbuckley/cabot-search huggingface dataset:
Pre-diabetes and breast cancer outcomes: Abrogating the confounding effect of anti-diabetic therapy.
Authors: Varinder Kaur, Ahmad Mazen Safar, Eric R Siegel, Jousheghany Fariba, Srikanth Medarametla, Thomas Kieber-Emmons, Karbassi Monzavi Behjatolah
Journal: Journal of Clinical Oncology (2015)

1584 Background: Multiple studies indicate that type II diabetes is associated with an increased mortality in breast cancer. However, in these studies the class of anti-diabetic therapy, remains an obvious confounding factor. Higher mortality has been reported in breast cancer patients treated with insulin than with metformin. Choosing a population of breast cancer patients with pre-diabetes, not receiving anti-diabetic therapy, could overcome such confounders. Methods: We conducted a retrospective cohort study to evaluate the relationship between elevated random blood sugar (RBS) levels and breast cancer outcomes. Only patients without a previous history of diabetes and who were not receiving any anti-diabetic therapy were included. The effect of elevated RBS on overall survival (OS), event-free survival (EFS) and time to tumor recurrence (TTR) were analyzed using Kaplan-Meier curves and log-rank test, and reanalyzed adjusting for age, race and obesity using multivariate Cox regression. Fisher’s exact test was used to compare binary proportions and Spearman rank correlations were used for ordinal category data in conjunction with correlation chi-square tests. Results: 234 patients with stage I-III breast cancer (mostly stage II, 177) were analyzed, of which 159 patients had a documented RBS level. 72 patients had elevated RBS ( > 120 mg/dL) and 87 had RBS < 120 mg/dL. We observed that patients with elevated RBS experienced significantly shorter OS (HR = 2.89; p = 0.0001), shorter EFS (HR = 2.44; p = 0.0006) and shorter TTR (HR = 2.16; p = 0.023). After adjusting for age ( < / ≥ 50), obesity and race via Cox regression, elevated RBS continued to display a high and statistically significant association with shorter OS (HR = 3.63; p < 0.0001), shorter EFS (HR = 3.20; p = 0.0002) and shorter TTR (HR = 3.52; p = 0.001). Additionally, among patients under 50 years of age, elevated RBS levels were associated with a significantly greater frequency of high grade tumors compared to RBS < 120 mg/dL(80% vs 45%; p = 0.02), suggesting that elevated RBS may have more impact in younger patients. Conclusions: High random blood sugar levels, reflective of a pre-diabetic state, are associated with shorter overall survival in breast cancer patients.
Abstract P095: Temporal Associations Between Lifestyle Self-Efficacy and Adherence to Calorie Goal
Authors: Yaguang Zheng, Christopher Imes, Susan M Sereika, Stephen L Rathbun, Lora E Burke
Journal: Circulation (2019)

Introduction: Research has shown self-efficacy (SE) to be positively associated with adherence to calorie goal when assessment is based on participants’ recall; however, when assessed in real-time, their association is unclear. Our aim was to examine temporal associations between SE for adhering to the daily recommended lifestyle plan and adherence to calorie goal collected in real-time over 12 months. Methods: Ecological momentary assessment (EMA) was used to assess SE for adhering to the daily recommended lifestyle plan in real-time during a behavioral weight loss study. SE was assessed by one question at the beginning of each day in the person’s natural setting “How confident are you that you will be able to stick to your healthy lifestyle plan today?” SE scores ranged from 1 to 10, with 1 reflecting lowest SE. Daily dietary intake was recorded using the Lose It! app. We calculated adherence to the calorie goal by dividing the total number of calories consumed each day by the daily calorie goal, then multiplying by 100 to express the value as a percentage. Adherence for each day was defined as 85%–115%. The mean weekly SE scores and mean weekly number of days adherent to dietary goals were calculated. Random coefficient modeling was used for analysis. Results: The sample (N=150) was 90.7% female, 80.7% white, with a mean age (±SD) of 51.1±10.2 years and a mean BMI of 34.0±4.6 kg/m 2 . Mean weekly SE score (b=-0.02, p&lt;.001) decreased from 7.5 to 6.7 beginning at 3 months, while a decline in mean weekly number of days adherent to calorie goal (b=-0.04, p&lt;.001) began immediately (see figure). Weekly SE score was positively associated with weekly number of days adherent to calorie goal (b1=0.17, p&lt;.001). Conclusion: Our study found declines in self-efficacy and adherence to calorie goal assessed in real-time and the positive association between them. Future weight loss interventions need to develop strategies to sustain self-efficacy and prevent declines in adherence to a diet that can support a heart healthy lifestyle.
Abstract 17539: Conventional vs. Transcatheter Aortic Valve Replacement - Propensity Score Adjusted Comparison of 3,751 Unselected Patients
Authors: Jochen Börgermann, Eric Emmel, Smita Scholtz, Stephan Ensminger, Werner Scholtz, Tobias Becker, Armin Zittermann, Dieter Horstkotte, Oliver Kuss, Jan F Gummert
Journal: Circulation (2015)

Background and Hypothesis: Transcatheter aortic valve replacement (TAVR) is an established method in high-risk patients. Two aspects of this procedure are currently under discussion: 1.) Do the data acquired from randomized studies and registers justify expansion of the procedure to include younger and healthier patients? 2.) Is the transfemoral approach superior to the transapical approach with regard to mortality and periprocedural complications? Against this background we examined the mortality and morbidity of all patients who received an isolated conventional, transapical or transfemoral aortic valve replacement in accordance with the criteria of the Valve Academic Research Consortium (VARC)-2. Methods: A prospective register was taken from a single center recording all conventional (CONV, n=2,881), transapical (TAVR-TA, n=363) and transfemoral (TAVR-TF, n=570) aortic valve implantations during the period from 07/2009 to 10/2014. Using propensity score (PS) matching, first CONV and TAVRall (TA+TF) and then TAVR-TA and TAVR-TF were paired on the basis of 21 risk variables, creating comparable groups. Results: 393 pairs CONV vs. TAVRall within a moderate risk could be created (EuroSCORE 18.7 vs. 18.5; STS 5.0 vs. 5.4). Comparison revealed no difference for 30d mortality (4.6% CONV vs. 5.1% TAVRall, p=0.74), stroke (2.8% vs. 2.0%, p=0.48) or myocardial infarction (0.0 vs. 0.3%, p=0.50). Bleeding complications were significantly more frequent in the CONV, SM implantations and vascular complications in the TAVRall group. In the PS-adjusted comparison TAVR-TA vs. TAVR-TF (289 pairs; EuroSCORE 25.1 vs. 22.1; STS 6.8 vs. 6.7) there was also no difference in the hard endpoints (30d mortality 4.9% TA vs. 4.2% TF, p=0.70; stroke 3.1% vs. 2.8%, p=0.81; myocardial infarction 0.4% vs. 0.4%, p=1.00). Here bleeding complications were significantly more frequent in the TA group, SM implantations and vascular complications in the TF group. Subgroup analyses show an advantage of the TAVR procedure in patients with high STS or low LVEF. Conclusions: These data show that 1.) conventional aortic valve replacement and TAVR are comparable in the moderate risk group, and 2.) the two approaches, transapical and transfemoral, produce comparable results.
KEYNOTE-365 cohort C updated results: Pembrolizumab (pembro) plus enzalutamide (enza) in abiraterone (abi)-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: William R. Berry, Peter C.C. Fong, Josep M. Piulats, Leonard Joseph Appleman, Henry Jacob Conter, Susan Feyerabend, Neal D. Shore, Gwenaelle Gravis, Brigitte Laguerre, Howard Gurney, Margitta Retz, Emanuela Romano, Loic Mourey, Johann S. De Bono, Audrey E. Kam, Urban Emmenegger, Helen Wu, Charles Schloss, Christian Heinrich Poehlein, Evan Y. Yu
Journal: Journal of Clinical Oncology (2020)

102 Background: KEYNOTE-365 (NCT02861573) is a phase 1b/2 study evaluating pembro in combination with other agents in mCRPC. An earlier report of cohort C showed activity and acceptable safety with pembro + enza. Updated results from cohort C are reported. Methods: Pts who failed or became intolerant to ≥4 wks of abi in prechemotherapy mCRPC state and whose disease progressed within 6 mo of screening per PSA progression or radiologic bone or soft tissue progression enrolled. Pts received pembro 200 mg IV Q3W with enza 160 mg/day PO. Primary end points: safety, PSA response rate (confirmed PSA decline ≥50%), and objective response rate (ORR) per blinded independent central review. Key secondary end points: disease control rate (DCR), duration of response (DOR), time to PSA progression, rPFS, and OS. Results: Of 102 treated pts, 73 discontinued, primarily due to progression (60%). Median age was 70 y (range, 43-87), 29% were PD-L1+, 17% had visceral disease, and 39% had measurable disease. Median follow up was 13 mo for all patients (n=102) and 17 mo for patients with ≥27 wks’ follow-up (n=69). See Table for efficacy outcomes. Treatment-related AEs occurred in 92 pts (90%); most frequent (≥20%) were fatigue (38%), nausea (22%), and rash (20%). Grade 3-5 treatment-related AEs occurred in 40 pts (39%). Three pts died of AEs (1 AE was treatment related [cause unknown]). Conclusions: With additional follow-up, pembro + enza continued to show activity in pts with abi-pretreated mCRPC. Safety of the combination was consistent with known profiles of pembro and enza. Clinical trial information: NCT02861573. [Table: see text]
In patients with previous dilated cardiomyopathy, withdrawal of HF drugs increased relapse at 6 months
Authors: Harriette G.C. Van Spall
Journal: Annals of Internal Medicine (2019)

Source Citation Halliday BP, Wassall R, Lota AS, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019;393:61-73. 30429050
Abstract 11684: Involvement of Enhanced Inflammatory Changes in the Perivascular Adipose Tissue in the Pathogenesis of Coronary Hyperconstricting Responses After Drug-Eluting Stent Implantation in Pigs in vivo (Best of Basic Science Abstract)
Authors: Kazuma Ohyama, Yasuharu Matsumoto, Hirokazu Amamizu, Hironori Uzuka, Kensuke Nishimiya, Michinori Hirano, Jun Takahashi, Kenta Ito, Hiroaki Shimokawa
Journal: Circulation (2015)

Background: Recent studies implicated that perivascular adipose tissue (PVAT) plays an important role in cardiovascular disease as a source of various inflammatory mediators with resultant coronary vasomotion abnormalities. In this study, we examined whether inflammatory changes in the PVAT are associated with coronary hyperconstricting responses after drug-eluting stent (DES) implantation in pigs in vivo. Methods and Results: Everolimus-eluting stents (EES) were randomly implanted in pigs into either the left anterior descending or circumflex coronary artery while non-stented artery was used as a control. At 1 month after the implantation, coronary vasoconstricting responses to intracoronary serotonin (100 μg/kg) were examined by coronary angiography in vivo. Then, stented vessels were harvested for immunohistological study for inflammatory changes in the PVAT at the stent edges. Coronary vasoconstricting responses to serotonin were significantly enhanced at the edges of the EES site as compared with the...
Abstract P080: Gut Microbiota, Gut-Derived Metabolites and Glucose Metabolism: Findings From a Monozygotic Twin Study
Authors: Yun Zhu, Eric Strachan, Emily Fowler, Tamara Bacus, Peter Roy-Byrne, Jinying Zhao
Journal: Circulation (2019)

Background: Gut microbiota dysbiosis disturbs metabolic homeostasis and contributes to a range of metabolic disorders including CVD and diabetes. Previous epidemiological studies using unrelated individuals may be confounded by age, sex, maternal diet, and early familial factors as well as many unknown or unmeasured factors. Using a well-matched co-twin control design, we examined the relationship between gut microbiome, gut-derived metabolites, and glucose metabolism in monozygotic twin pairs. Objective: To identify gut microbiome (both composition and abundance) and microbial metabolites associated with host plasma glucose and HbA1c, independent of potential confounding factors. Methods: This study included 37 monozygotic twin pairs (N=74, mean age 38.2 years old, 68.4% females). Gut microbiome profiles were assessed by 16S rRNA sequencing of the V4 hypervariable region. Concentrations of gut-derived metabolites in plasma were detected using untargeted LC-MS. After stringent QC, we obtained 89 operational taxonomic units (OTUs) at the genus level and 43 microbial metabolites in all twin pairs. The correlation between α-diversity (within-sample diversity, a higher α indicates higher richness of a bacterial species) and plasma glucose or HbA1c was estimated by Spearman correlation. The association of plasma glucose or HbA1c with each OTU or concentration of microbial metabolites was examined by matched twin pair analysis, adjusting for BMI, lipids, smoking, alcohol drinking and depression. Multiple testing was controlled by Bonferroni correction (P&lt;0.0005 for OTUs, P&lt;0.001 for metabolites). Results: The α-diversity measured by Simpson Index was positively correlated with both HbA1c (r 2 =0.51, p=0.032) and fasting glucose (r 2 =0.48, p=0.043). Of the 89 OTUs at the genus level, abundances of Ruminococcaceae, Lactobacillus, Lachnospiraceae , and Oscillibacter were positively associated with both HbA1c (adjusted-P&lt;0.0004) and fasting glucose (adjusted-P&lt;0.0005), whereas abundances of Holdemanella and Solobacterium were positively associated with HbA1c (adjusted-P &lt; 0.0005). Two microbial metabolites, TMAO and threonine , were significantly associated with HbA1c and glucose (all adjusted-P &lt; 0.001). Conclusions: Altered gut microbiota (both composition and abundance) and gut-derived microbial metabolites are associated with glucose metabolism, independent of potential confounding variables.
The ethical impact of economic sanctions in Iranian cancer health care.
Authors: Jennifer K Stedman, Hooman Fazlalizadeh, Regina Ram, Ahmad Shariftabrizi, Shohreh Shahabi
Journal: Journal of Clinical Oncology (2015)

e17514 Background: The Islamic Republic of Iran has been subject to international sanctions by various entities since 1979. However, in 2012, the Iranian economy collapsed under the economic strain of sanctions installed to stop Iran from violating the international Nuclear Non- Proliferation Treaty. While the current sanctions imposed by the United States, the European Union, the United Nations, and various other countries do not formally target healthcare or patients’ access to drugs, the sanctions have indirectly led to serious healthcare concerns, specifically in devoping a standardized system of cancer care in Iran. Methods: Data and information was obtained through PubMed searches to include the following key terms: Iran, health policy, sanctions, ethics, and cancer from 1996 – 2015 in the English language. Results: The Program of Action for Cancer Therapy, which was created within the International Atomic Energy Agency with the mission of action against cancer, evaluated the National Cancer Control Program (NCCP) in Iran. The comprehensive view about NCCP’s status in Iran has significant deficits in all aspects of care, including prevention, early detection, diagnosis/treatment, palliative care, monitoring, and technology. A serious drug shortage for cancer care is also present. Conclusions: There is mounting evidence that economic sanctions simply harm vulnerable populations in target countries, while blocking the globalization process and doing little to effect political or social change. The drug accessibility for cancer patients in Iran is a human rights concern. Improvement of the NCCP status is not feasible unless sanctions are lifted. Economic warfare should be guided by rule of humanitarian law to reduce effects on civilians, as the current situation is allowing for slow, yet deadly sanctions to impact the weakest in the population, without achieving the desired peaceful end.
David Frederick Harrison
Authors: Roger D Parkin, Jonathan K Bynoe
Journal: BMJ (2019)

David Frederick Harrison was the archetypal country family doctor. In 1960 David and his wife, Gillian—both graduates from Leeds University School of Medicine—moved to Sherburn-in-Elmet, where David joined the well established village practice. In 1966 he became the senior partner. Under his leadership the practice introduced many innovations, in the wake of the GP contract of 1966. He supported the educational objectives of the Royal College of General Practitioners and took his membership examination in 1972. In the early 1970s, David and his partners, who were pioneers of the cost rent scheme, oversaw the development of new purpose built premises. The practice became a training practice and also taught undergraduates from the Leeds University …
Are breast density and family history associated with pre-operative breast MRI use?
Authors: Louise Henderson, Rebecca Hubbard, Karen Wernli, Karla Kerlikowske, Diana SM Buist, Brian Sprague, Martha Goodrich, Wendy DeMartini, Elissa Ozanne, Weiwei Zhu, Cristina O'Donoghue, Beth A. Virnig, Anna NA Tosteson, Tracy Onega
Journal: Journal of Clinical Oncology (2015)

e17543 Background: Pre-operative breast magnetic resonance imaging (MRI) use among women with newly diagnosed breast cancer is increasing. National Comprehensive Cancer Network guidelines state MRI is optional for invasive breast cancer, with no further specifications by patient factors such as breast density or family history of breast cancer. However, these risk factors may influence MRI use decisions, but their association with utilization is unknown. Methods: We used 2005-2010 Breast Cancer Surveillance Consortium data linked to administrative data (Medicare or HMO) to assess the association of mammographic breast density and family history of breast cancer with pre-operative MRI use. We included 3,270 women age > 65 with stage 0-III breast cancer. We used multivariable logistic regression to estimate adjusted odds ratios (OR) for the association of MRI use with density (fatty/scattered vs. heterogeneous/extremely dense) and family history, adjusting for patient and tumor characteristics. Results: Pre-operative MRI use was 13.6% in women with DCIS (n = 563) and 18.1% in women with invasive cancer (n = 2,707). The unadjusted proportion of women receiving breast MRI was similar by breast density (DCIS: 13.7% in women with less and more dense breasts; invasive: 17.9% among less dense vs. 18.3% among more dense) and family history (DCIS: 12.3% family history vs. 14.1% no family history; invasive: 19.4% family history vs. 17.7% no family history). Adjusted models found no difference in pre-operative MRI use by breast density (DCIS: OR = 0.93 for more vs. less dense,95%CI:0.56-1.54; invasive: OR = 0.92,95%CI:0.74-1.14) or family history (DCIS: OR = 0.81,95%CI: 0.45-1.44; invasive: OR = 1.07,95%CI:0.84-1.37). Conclusions: Among women ages 65+ with newly diagnosed breast cancer, two common risk factors, family history and breast density, were not associated with receipt of pre-operative MRI. Additional studies should examine if these risk factors influence utilization in younger women.
Macroeconomic burden of firearm-related fatality across OECD countries: an estimate of annual and cumulative gross domestic product losses, 2018–30
Authors: Alexander W Peters, Rachel R Yorlets, Mark G Shrime, Blake C Alkire
Journal: The Lancet Global Health (2019)

BackgroundIn 2015, firearm-related unintentional injuries, physical violence, and self-harm caused over 36 000 deaths and 100 000 injuries in the USA, and over 250 000 deaths worldwide. Of these deaths, more than 64 000 were in OECD countries. Nevertheless, firearm injury risk reduction remains socially and politically controversial. Although the costs of treating firearm injuries has been estimated, little is known about the macroeconomic impact of firearm deaths. Here, we aim to estimate the future macroeconomic burden of deaths in OECD countries.MethodsUsing value-of-lost-output methodology, which estimates the macroeconomic burden of deaths in terms of lost economic productivity, we estimated the annual and cumulative gross domestic product (GDP) lost due to firearm-related fatalities from 2018 to 2030 in all 36 OECD countries. We used mortality data from the 2016 Global Burden of Disease study to project mortality rates from 2018 to 2030. We then applied these projections to an adapted version of the WHO EPIC (Projecting the Economic Cost of Ill-health) model to project GDP losses attributable to firearm-related deaths.FindingsAcross OECD countries, we estimated macroeconomic losses from firearm mortality at US$272·1 billion in lost economic output between 2018 and 2030 ($124·9 billion from physical violence, $135·7 billion from self-harm, and $11·4 billion from unintentional injury), with $8·0 billion in annual losses in 2018 growing to an estimated loss of $35·9 billion in 2030. This amount represents 0·051% of total estimated 2030 GDP, or $1 lost for every $1944 of potential economic output. The USA is estimated to lose more than other OECD nations, with annual GDP losses of $24·5 billion in 2030, representing 0·10% of US GDP in 2030, and $180·6 billion cumulative losses from 2018 to 2030. Mexico's estimated loss in 2030 is $6·3 billion, which represents 0·20% of Mexican GDP in 2030, and $50·3 billion cumulatively from 2018 to 2030. No other OECD country had estimated cumulative losses greater than $10·6 billion in the study period, nor greater than 0·04% of GDP in 2030. Considered as a proportion of 2030 GDP, the USA's projected losses were 93·0% higher and Mexico's losses were 290·6% higher than the mean proportional losses across all OECD countries in 2030.InterpretationFirearm-related deaths are expected to cause disproportionately high macroeconomic losses in the USA and Mexico from 2018 to 2030 compared with other OECD countries. These losses represent an important proportion of GDP, and should be considered in broader social, economic, and health policy decisions about firearm regulation. Future studies might consider cost-benefit analyses that weigh the costs of risk reduction interventions against the potential economic savings of reducing firearm mortality.FundingNone.