tbuckley/cabot-search huggingface dataset:
Randomised controlled trials for complex physiotherapy interventions are perfectly possible
Authors: Leonardo Oliveira Pena Costa
Journal: British Journal of Sports Medicine (2018)

Randomised controlled trials (RCTs) are widely recognised as the strongest scientific approach to measuring the effects of interventions. If a clinician chooses to ignore evidence from RCTs to make clinical decisions and rely only on clinical observation, overestimation of treatment effects is very likely to occur. The latter occurs because changes in outcomes and the effects of interventions are completely different constructs.

Change in a given outcome is all a clinician can observe in clinical practice, and is basically the difference between an outcome measured after the intervention compared with the baseline assessment (ie, within-group difference). However, there are a number of factors that play a key role on the changes in outcomes. These factors are scientifically known as confounders and include (1) natural history, (2) regression to the mean, (3) placebo effect, (4) polite patients and (5) recall bias. Improvements observed in patients in clinical practice are contaminated with these …
Changes in Gut Microbiota–Related Metabolites and Long-term Successful Weight Loss in Response to Weight-Loss Diets: The POUNDS Lost Trial
Authors: Yoriko Heianza, Dianjianyi Sun, Steven R. Smith, George A. Bray, Frank M. Sacks, Lu Qi
Journal: Diabetes Care (2018)

Adiposity and the gut microbiota are both related to the risk of type 2 diabetes. We aimed to comprehensively examine how changes induced by a weight-loss diet intervention in gut microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors (choline and l-carnitine), were associated with improvements in adiposity and regional fat deposition.This study included 510 overweight and obese individuals who were randomly assigned one of four diets varying in macronutrient intake. We examined associations of 6-month changes in blood metabolites (TMAO, choline, and l-carnitine) with improvements in body weight (BW), waist circumference (WC), body fat composition, fat distribution, and resting energy expenditure (REE).Individuals with a greater reduction of choline (P < 0.0001) and l-carnitine (P < 0.01) rather than TMAO showed significant losses of BW and WC at 6 months. The reduction of choline was significantly predictive of decreases in body fat composition, fat distribution, and REE. Results of sensitivity analysis showed that the baseline diabetes risk status, such as the presence of hyperglycemia (31% of the total participants) and fasting glucose levels, did not modify the associations. Early changes in choline and l-carnitine were significantly predictive of weight loss over 2 years (P < 0.05 for all). Individuals with increases in choline or l-carnitine were 2.35-times (95% CI 1.38, 4.00) or 1.77-times (1.06, 2.95) more likely to fail to lose weight (-5% or more loss) at 2 years.Overweight and obese individuals who showed decreases in circulating choline or l-carnitine levels achieved greater improvements of adiposity and energy metabolism by eating a low-calorie weight-loss diet, suggesting that such metabolites are predictive of individuals' response to the treatment. Further investigations are necessary to confirm our findings, particularly in a population with prediabetes that is more representative of the U.S. population with obesity.
Health Care Provider Counseling for Physical Activity or Exercise Among Adults with Arthritis — United States, 2002 and 2014
Authors: Jennifer M. Hootman, Louise B. Murphy, John D. Omura, Teresa J. Brady, Michael Boring, Kamil E. Barbour, Charles G. Helmick
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Arthritis affects an estimated 54 million U.S. adults and, as a common comorbidity, can contribute arthritis-specific limitations or barriers to physical activity or exercise for persons with diabetes, heart disease, and obesity (1). The American College of Rheumatology's osteoarthritis management guidelines recommend exercise as a first-line, nonpharmacologic strategy to manage arthritis symptoms (2), and a Healthy People 2020 objective is to increase health care provider counseling for physical activity or exercise among adults with arthritis.* To determine the prevalence and percentage change from 2002 to 2014 in receipt of health care provider counseling for physical activity or exercise (counseling for exercise) among adults with arthritis, CDC analyzed 2002 and 2014 National Health Interview Survey (NHIS) data. From 2002 to 2014, the age-adjusted prevalence of reporting health care provider counseling for exercise among adults with arthritis increased 17.6%, from 51.9% (95% confidence interval [CI] = 49.9%-53.8%) to 61.0% (CI = 58.6%-63.4%) (p<0.001). The age-adjusted prevalence of reporting health care provider counseling for exercise among persons with arthritis who described themselves as inactive increased 20.1%, from 47.2% (CI = 44.0%-50.4%) in 2002 to 56.7% (CI = 52.3%-61.0%) in 2014 (p = 0.001). Prevalence of counseling for exercise has increased significantly since 2002; however, approximately 40% of adults with arthritis are still not receiving counseling for exercise. Improving health care provider training and expertise in exercise counseling and incorporating prompts into electronic medical records are potential strategies to facilitate counseling for exercise that can help adults manage their arthritis and comorbid conditions.
Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals
Authors: Laurel Yong-Hwa Lee, Do Lien Anh Ha, Cameron Simmons, Menno D. de Jong, Nguyen Van Vinh Chau, Reto Schumacher, Yan Chun Peng, Andrew J. McMichael, Jeremy J. Farrar, Geoffrey L. Smith, Alain R.M. Townsend, Brigitte A. Askonas, Sarah Rowland-Jones, Tao Dong
Journal: Journal of Clinical Investigation (2012)
Selling Patents to Indian Tribes to Delay the Market Entry of Generic Drugs
Authors: Gregory Ablavsky, Lisa Larrimore Ouellette
Journal: JAMA Internal Medicine (2018)

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Phase II study of the hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with CD-20 positive ALL.
Authors: Elias Jabbour, Hagop M. Kantarjian, Deborah A. Thomas, Guillermo Garcia-Manero, Simon Abi Aad, Rebecca Garris, Jorge E. Cortes, Tapan M. Kadia, Farhad Ravandi, Srdan Verstovsek, Susan Mary O'Brien
Journal: Journal of Clinical Oncology (2014)

7065 Background: The hyperCVAD regimen is an effective frontline program for de novo adult ALL. CD20 expression was identified as an adverse prognostic factor, associated with a higher incidence of relapse and lower 3-year OS rates. Addition of rituximab to the hyperCVAD program in patients with CD20+ ALL improved outcome with 3-year CRD and OS rates by 68% and 65%, respectively. Ofatumumab targets a membrane proximal small-loop epitope on the CD20 molecule and was found to be more potent than rituximab. Combination of the hyperCVAD regimen and ofatumumab may be associated with better responses and higher 3-year PFS and OS rates. Methods: Pts with newly diagnosed ALL and pts who received 1 prior course of chemotherapy received 8 courses of hyperCVAD alternating MTX-Ara-C; ofatumumab was given on courses 1 through 4. This treatment is to be followed by POMP maintenance therapy for approximately 30 months, interrupted by intensifications months 6, 7 and 18, 19 with MTX/Pegylated asparaginase and hyperCVAD-ofatumumab. CNS prophylaxis was administered. Results: 21 pts with de novo ALL and 2 pts in CR previously treated have received a median of 7 cycles; 7 pts did not receive the full 8 planned courses. 15 pts are receiving maintenance in CR. Median age is 50 years. All but 1 pt (95%) achieved CR after cycle 1; 1 pt died of septic shock at C1D21. 22/23 pts (95%) achieved MRD negativity as assessed by FCI; of whom 14 (64%) after induction. Grade ≥ 3 toxicity included increased LFT’s in 7 pts (30%), increased bilirubin in 6 (26%), thrombotic events in 1 (4%) and neuropathy in 1 (4%). Febrile neutropenia episodes during induction and consolidation cycles were reported at rates of 71% and 77%, respectively. With a median follow-up of 12 months, 21 pts are alive; two patients developed sepsis and died at C1D21 and C3D17, respectively. 2 pts have undergone ASCT: due to the lack of MRD negativity achievement in one and a highly complex karyotype at diagnosis in the second; the first relapsed 7 months post ASCT. The 1-year PFS and OS rates were 91% and 91% respectively. Conclusions: The combination of hyperCVAD/ofatumumab is safe and highly effective in pts with CD20 + ALL. Clinical trial information: NCT01363128.
Abstract 9998: Prognosis of Low Normal Left Ventricular Ejection Fraction in an Asymptomatic Population -based Adult Cohort. MESA
Authors: Joseph Yeboah, Waqas Qureshi, Carlos Rodriguez, Songtao Liu, Jeffrey J Carr, Joao A Lima, Gregory W Hundley, David M Herrington
Journal: Circulation (2015)

Introduction: A reduced left ventricular ejection fraction (LVEF) is associated with adverse cardiovascular events; however, the optimal threshold for a “normal” LVEF is uncertain. In general a LVEF ≥ 55% is considered “normal” by guidelines, with a low normal designation for LVEF 50-55%. We assess the prognosis of participants with low normal LVEF (LN-EF) in the Multi Ethnic Study of Atherosclerosis. All participants were asymptomatic and had no known clinical CVD at baseline. Methods: 4669 out of 5004 had LVEF of ≥ 50% assessed using cardiac MRI (SSFP), had no significant valvular disease (- VD), did not have MI during follow up (-MI), had complete data and included in analysis. 475/4669(10.2%) had LN-EF. Cox proportional hazard and cubic spline analyses were used to assess the association of low normal LVEF and 10 years of adjudicated incident congestive heart failure(CHF) and all- cause mortality adjusting for age gender and race( model 1) and model 2: model 1 + DM, smoking, SBP, BP meds, BMI, creatinine, LDL, family history and educational status. Model 3: model 2 + LV mass. Results: Age averaged 61± 10yrs, 46% were men, 35% had BP meds, 8% T2DM. After 10.2 years of follow up, 112 developed CHF and 425 died. 87/112 CHF events had LVEF available at diagnosis [45 had a LVEF≥ 50%-HFPEF and 42 had LVEF&lt;50%-HFREF]. Table 1 shows our results.. Using LVEF of 55% as reference the risk of CHF in individuals with LVEF≥ 50% is non- linear (Figure 1). Conclusion: In asymptomatic population based adults -VD, -MI, LN-EF is prevalent(10.2%) and is an independent predictor of future clinical CHF. LN-EF is not associated with mortality. Future CHF prevention measures should also focus on individuals with LN-EF.
Abstract 16789: Activation Sequence within the Pulmonary Vein as the Driving Sources of Atrial Fibrillation: Three-dimensional Analysis Using a Non-contact Mapping System
Authors: Hiroshige Yamabe, Hisanori Kanazawa, Tadashi Hoshiyama, Miwa Ito, Shozo Kaneko, Hisao Ogawa
Journal: Circulation (2015)

Background: The mechanisms how the activation within the pulmonary vein (PV) drives the atrial fibrillation (AF) has not been elucidated. Objectives: To define the AF maintenance mechanism by PV, we analyzed the activation sequence within the PV during AF. Methods: Selective endocardial mapping of the left superior PV (LSPV) was performed during AF in 11 patients with paroxysmal AF using a three-dimensional non-contact mapping system (EnSite 3000). In addition, we analyzed how the circumferential radiofrequency energy applications around the LSPV alter the activation of the LSPV and terminate AF. Results: Complex fractionated electrograms (CFE) were observed at the second half of the proximal LSPV at the roof (n=5), ridge (n=11) and carina (n=7). Mean CFE area was 9.1±3.4 cm2, which occupied the 19.8% of the LSPV area. Frequent episodes of pivoting activation associated with wave break and fusion was observed at this CFE area. The frequency of pivoting activation around the functional conduction block, wave break and fusion at the CFE region were significantly higher than those at the non-CFE region (32.5±12.2 vs. 4.6±5.8 times/sec; p&lt;0.0001, 9.2±5.1 vs. 1.4±3.1 times/sec; p=0.0007, and 12.9±4.8 vs. 6.4±4.4 times/sec, p=0.0044). After isolation of ipsilateral right PV, subsequent circumferential radiofrequency energy applications around the left PV terminate the AF with a mean number of 13.5±7.8 applications, including LSPV roof (n=3.0±2.2) and LSPV ridge (n=5.6±1.9) lesions. AF was terminated before left PV isolation in all patients. The frequency of pivoting activation, wave break and fusion at all PV area just before the AF termination were significantly lower than those before ablation (8.1±11.7 vs. 37.0±14.7 times/sec; p&lt;0.0001, 2.3±5.8 vs. 10.6±6.6 times/sec; p=0.005, 6.9±6.8 vs. 19.3±7.1 times/sec, p=0.0004), suggesting that linear lesion eliminate the random wave propagation over the CFE area. Conclusions: AF was driven by the high frequent episodes of pivoting activation associated with wave break and wave fusion observed over the CFE area at the proximal PV. Linear lesions along the left PV including CFE area of the LSPV eliminate the meandering activation over the CFE area, resulting in the termination of AF.
Abstract 17950: Irisin Protects the Heart Against Myocardial Ischemia and Reperfusion Injury
Authors: Hao Wang, Shouyan Zhang, Yu T Zhao, Jianfeng Du, Ting C Zhao
Journal: Circulation (2016)

Introduction: Irisin has been identified as a newly identified cardiokine. However, whether irisin protects the heart against ischemia and /reperfusion (I/R) injury remains unknown. Hypothesis: Thi...
Abstract 15468: Inhibition of NAD(P)H Oxidase 4 Ameliorates Angiotensin II-Induced Protein Degradation via Improving Mitochondrial Dysfunction in Skeletal Myocytes
Authors: Tomoyasu Kadoguchi, Kazunori Shimada, Tomoyuki Shiozawa, Shuhei Takahashi, Hamad Al Shahi, Tatsuro Aikawa, Shohei Ouchi, Yurina Sugita, Tetsuro Miyazaki, Koji Akita, Kikuo Isoda, Hiroyuki Daida
Journal: Circulation (2016)

Background: Skeletal muscle atrophy is a debilitating phenotype that is associated with a variety conditions, including chronic kidney disease and heart failure. We have previously demonstrated tha...
Abstract 19780: ABCA1 Response to Atherogenic Lipid Exposure is Reduced in Cultured Human Aortic Smooth Muscle Cells Compared to Human Monocyte-Derived Macrophages
Authors: Joshua A Dubland, Sima Allahverdian, Ying Wang, Collin S Pryma, Teddy Chan, Gordon A Francis
Journal: Circulation (2016)

Introduction:  Retention of low density (LDL) and other apolipoprotein B (apoB)-containing lipoproteins in the intima of the artery wall initiates atherosclerotic lesion formation. It has been commonly thought that the majority of the lipid overloaded “foam cells” in atherosclerosis are of leukocyte origin. Recently we reported that ≥ 50% of the foam cells in coronary artery atherosclerosis are of smooth muscle cell (SMC) origin, and that the rate-limiting cholesterol exporter, ATP-binding cassette transporter protein A1 (ABCA1), has reduced expression in intimal SMCs compared to leukocytes. Upregulation of ABCA1 expression is dependent on normal flux of lipoprotein-derived cholesterol out of lysosomes. Mechanisms by which macrophages process and store lipoprotein-derived cholesterol in lysosomal and cytosolic compartments are well described, whereas less is known about SMCs.   Hypothesis:  Human aortic SMCs have reduced ABCA1 levels compared to macrophages in response to atherogenic lipoprotein exposure.   Methods:  Conditions were optimized to load human aortic SMCs and macrophages with aggregated LDL for 24 hrs, followed by a 24 hr equilibration without lipids to allow lysosomal processing of lipoproteins. Cellular cholesterol and cholesteryl ester mass were measured using HPLC tandem mass spectrometry. Response levels to lipid loading were investigated by Western blot for ABCA1.   Results:  Cholesteryl ester mass in macrophages increased from 1.5±1.8 to 345.4±21.6 nmol/mg protein in response to aggregated LDL, and 17.4±8.7 to 74.0±16.0 nmol/mg protein in SMCs (mean±SEM, n=9-12 replicates). In macrophages fold change in ABCA1 with exposure to aggLDL was 2.24±0.31 (mean±SEM, n=8 replicates). Preliminary data indicate no significant increase in ABCA1 in SMCs with aggLDL loading. Confocal microscopy indicates increased lipid accumulation following aggLDL loading in the lysosomes of SMCs but not macrophages.   Conclusions:  These data suggest that impaired lysosomal processing of excess atherogenic lipoproteins is responsible for impaired upregulation of ABCA1 in cultured human aortic SMCs when compared to macrophages. This provides a potential mechanism for preferential formation of smooth muscle foam cells in human atherosclerosis.
Abstract 15628: The Use of Antibiotic Prophylaxis to Prevent Infective Endocarditis is Cost Effective
Authors: Matthew Franklin, Allan Wailoo, Mark J Dayer, Simon Jones, Bernard Prendergast, Larry M Baddour, Peter B Lockhart, Martin H Thornhill
Journal: Circulation (2016)

Introduction:  In March 2008, the National Institute for Health and Care Excellence (NICE) recommended stopping antibiotic prophylaxis (AP) for those at risk of infective endocarditis (IE) undergoing dental procedures in the UK, citing a lack of efficacy and cost-effectiveness. We performed a new health economic evaluation comparing ‘AP’ to ‘No AP’ using present-day estimates of efficacy, adverse events and resource-use.   Methods:  A decision analytic cost-effectiveness model was used. Health service costs and benefits were measured as Quality Adjusted Life Years (QALYs). Rates of IE before and after the NICE guidelines were used to estimate AP efficacy. AP adverse event rates (congestive heart failure, valve replacement, AP side effects and mortality) were derived from recent UK data and resource implications (hospitalisation, outpatient and primary care, and medications) were based on national Hospital Episode Statistics.   Results:  AP was less costly and more effective than no AP for all patients at risk of IE. The results are sensitive to AP efficacy, but efficacy would have to be substantially lower for AP not to be cost-effective. AP was even more cost-effective in patients at high-risk of IE. Only a marginal reduction in annual IE rates (1·56 cases, high-risk; 35 cases, all-at-risk) would be required for AP to be considered cost-effective at £20,000 ($28,381/є25,166) per QALY. Annual cost savings of £5·3-7·9m ($7.5-11.2m/є6.7-9.9m) and health gains >2,500 QALYs could be gained from reinstating AP in England. A conservative expected value of perfect information (EVPI) estimate was £25.9m ($36.8m/є32.6m) when uncertainty around AP efficacy was increased. This indicates that any randomised controlled trial costing    Conclusions:  AP is cost-effective for preventing IE, particularly in those at high-risk of IE. These findings support the cost-effectiveness of guidelines recommending AP use in high-risk individuals, such as recommended in current American Heart Association and European Society of Cardiology guidelines.
Yes-Associated Protein Promotes Angiogenesis via Signal Transducer and Activator of Transcription 3 in Endothelial Cells
Authors: Jinlong He, Qiankun Bao, Yan Zhang, Mingming Liu, Huizhen Lv, Yajin Liu, Liu Yao, Bochuan Li, Chenghu Zhang, Shuang He, Guijin Zhai, Yan Zhu, Xin Liu, Kai Zhang, Xiu-Jie Wang, Ming-Hui Zou, Yi Zhu, Ding Ai
Journal: Circulation Research (2018)

Angiogenesis is a complex process regulating endothelial cell (EC) functions. Emerging lines of evidence support that YAP (Yes-associated protein) plays an important role in regulating the angiogenic activity of ECs.The objective of this study was to specify the effect of EC YAP on angiogenesis and its underlying mechanisms.In ECs, vascular endothelial growth factor reduced YAP phosphorylation time and dose dependently and increased its nuclear accumulation. Using Tie2Cre-mediated YAP transgenic mice, we found that YAP promoted angiogenesis in the postnatal retina and tumor tissues. Mass spectrometry revealed signal transducer and activator of transcription 3 (STAT3) as a potential binding partner of YAP in ECs. Western blot and immunoprecipitation assays indicated that binding with YAP prolonged interleukin 6-induced STAT3 nuclear accumulation by blocking chromosomal maintenance 1-mediated STAT3 nuclear export without affecting its phosphorylation. Moreover, angiopoietin-2 expression induced by STAT3 was enhanced by YAP overexpression in ECs. Finally, a selective STAT3 inhibitor or angiopoietin-2 blockage partly attenuated retinal angiogenesis in Tie2Cre-mediated YAP transgenic mice.YAP binding sustained STAT3 in the nucleus to enhance the latter's transcriptional activity and promote angiogenesis via regulation of angiopoietin-2.