tbuckley/cabot-search huggingface dataset:
Four-year effects of physical exercise during adjuvant treatment on fatigue and physical activity in breast and colon cancer patients.
Authors: Anne Maria May, Anouk E Hiensch, Lenja Witlox, Miranda Velthuis, Elsken Van Der Wall, Petra H.M. Peeters
Journal: Journal of Clinical Oncology (2018)

99 Background: A recent randomized trial, the PACT study, showed beneficial effects on fatigue and physical fitness after an 18-week supervised exercise program in breast and colon cancer patients undergoing adjuvant treatment. So far, little is known on long-term effects of exercising during adjuvant treatment on fatigue and whether physical activity levels could be maintained. The latter is important to preserve achieved beneficial health effects. The present study assessed effects of the exercise intervention on fatigue and physical activity on average 4 years after participation in the PACT study. Methods: The PACT study was a 2-armed, multicenter randomized controlled trial comparing an 18-week supervised exercise program to usual care among 204 breast cancer patients and 33 colon cancer patients undergoing adjuvant treatment including chemotherapy. Of the 237 participants, 197 patients were eligible and approached to participate in the 4-year follow-up measurements, and finally 128 patients responded (intervention (n = 70), usual care (n = 58)). Fatigue (MFI) and physical activity levels (SQUASH) was assessed at baseline, post-intervention (at 18 weeks), 36-week post-baseline and 4 years post-baseline. Results: Intention-to-treat mixed linear model analyses showed that cancer patients in the intervention group experienced less physical fatigue at 4-year post-baseline compared to the usual care group (-1.13, 95% CI -2.45;0.20, effect size (ES) = 0.22), although not statistically significant. Furthermore, cancer patients in the intervention group reported significantly higher moderate-to-vigorous total physical activity levels (141.77 min/week (CI 95% 1.31;281.61, ES = 0.22) after 4 years compared to the usual care group. Conclusions: Breast and colon cancer patients, who participated in an 18-week exercise intervention during adjuvant treatment, showed significant higher levels of moderate-to-vigorous total physical activity levels and a tendency towards lower physical fatigue levels 4-year post-baseline. Exercise during chemotherapy might be a promising strategy for minimizing treatment-related side-effects both in the short- and long-term. Clinical trial information: NTR2138.
Economic analysis of implementing virtual reality therapy for pain among hospitalized patients
Authors: Sean D. Delshad, Christopher V. Almario, Garth Fuller, Duong Luong, Brennan M. R. Spiegel
Journal: npj Digital Medicine (2018)

Virtual reality (VR) has emerged as a novel and effective non-pharmacologic therapy for pain, and there is growing interest to use VR in the acute hospital setting. We sought to explore the cost and effectiveness thresholds VR therapy must meet to be cost-saving as an inpatient pain management program. The result is a framework for hospital administrators to evaluate the return on investment of implementing inpatient VR programs of varying effectiveness and cost. Utilizing decision analysis software, we compared adjuvant VR therapy for pain management vs. usual care among hospitalized patients. In the VR strategy, we analyzed potential cost-savings from reductions in opioid utilization and hospital length of stay (LOS), as well as increased reimbursements from higher patient satisfaction as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. The average overall hospitalization cost-savings per patient for the VR program vs. usual care was $5.39 (95% confidence interval -$11.00 to $156.17). In a probabilistic sensitivity analysis across 1000 hypothetical hospitals of varying size and staffing, VR remained cost-saving in 89.2% of trials. The VR program was cost-saving so long as it reduced LOS by ≥14.6%; the model was not sensitive to differences in opioid use or HCAHPS. We conclude that inpatient VR therapy may be cost-saving for a hospital system primarily if it reduces LOS. In isolation, cost-savings from reductions in opioid utilization and increased HCAHPS-related reimbursements are not sufficient to overcome the costs of VR.
Role of cardiac reserve as a tool to unmask cardiotoxicity following anthracycline therapy and whether exercise training can attenuate cardiotoxicity.
Authors: Steve Fraser, Erin Howden, Stephen Foulkes, Ashley Bigaran, Kirstel Janssens, Rhys Beaudry, Steve Selig, Mark J. Haykowsky, Yoland Catherine Antill, Sherene Loi, Andre LaGerche
Journal: Journal of Clinical Oncology (2018)

556 Background: Anthracycline-based chemotherapy (AC) is associated with an increased risk of cardiac damage and long-term heart failure. However, diagnosis of cardiac damage is infrequent, while long-term heart failure risk is substantial. Thus, we sought to evaluate whether exercise cardiac reserve may be a more sensitive marker of cardiac toxicity than standard measures of cardiac function and if exercise training maintained cardiac function and exercise capacity during AC. Methods: 28 BC patients undergoing AC were recruited into a non-randomised trial and allocated to exercise training (ET) (46.7±9.0 yrs, n = 14) or usual care (UC; 53.2±8.9 years, n = 14), respectively. Tests including echocardiography (left ventricular ejection fraction [LVEF] and global longitudinal strain [GLS]), cardiopulmonary exercise test (peak oxygen uptake, VO2peak), and exercise cardiac magnetic resonance imaging (exCMR, cardiac reserve) were performed prior to and after completion of AC. The ET group completed a twice weekly supervised aerobic and resistance exercise program at a moderate-vigorous intensity. Results: There was a small statistically significant reduction resting in LVEF in both UC and ET, whereas GLS was unchanged (Table 1). VO2peak fell by 15% in the UC, while ET significantly attenuated the decline in fitness (~4%). Cardiac reserve was reduced following AC (Visit×Exercise P= 0.05), which was not attenuated by exercise training (Visit×Exercise×Group P= 0.06). Exercise training had no effect on resting measures of LV function (Table 1). Clinical trial information: ACTRN12616001602415. Conclusions: AC treatment caused profound reductions in peak oxygen uptake and impaired cardiac reserve. Resting measures of cardiac function did not account for the large reduction in VO2peak which was attenuated by exercise training. Effect of AC and ET on resting measures of cardiac function, biomarkers and peak oxygen uptake. Usual Care Exercise Training Visit Group × Visit Pre Post Pre Post LVEF, % 62.8 ± 4.9 59.1 ± 4.1 64.1 ± 5.0 60.6 ± 5.4 0.003 0.95 GLS, % -20.4 ± 2.1 19.5 ± 2.0 19.7 ± 2.0 19.6 ± 2.0 0.17 0.28 VO2 peak, ml/kg/min 22.0 ±5.9 18.8 ± 5.9 27.4 ± 5.7 26.3 ± 5.3 < 0.001 0.024
Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1–3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with<i>FGFR3</i>Alterations
Authors: Sumanta K. Pal, Jonathan E. Rosenberg, Jean H. Hoffman-Censits, Raanan Berger, David I. Quinn, Matthew D. Galsky, Juergen Wolf, Christian Dittrich, Bhumsuk Keam, Jean-Pierre Delord, Jan H.M. Schellens, Gwenaelle Gravis, Jacques Medioni, Pablo Maroto, Virote Sriuranpong, Chaiyut Charoentum, Howard A. Burris, Viktor Grünwald, Daniel Petrylak, Ulka Vaishampayan, Eliahu Gez, Ugo De Giorgi, Jae-Lyun Lee, Jens Voortman, Sumati Gupta, Sunil Sharma, Amir Mortazavi, David J. Vaughn, Randi Isaacs, Katie Parker, Xueying Chen, Kun Yu, Dale Porter, Diana Graus Porta, Dean F. Bajorin
Journal: Cancer Discovery (2018)

Abstract BGJ398, a potent and selective pan-FGFR antagonist, was prospectively evaluated in patients with metastatic urothelial carcinoma bearing a diverse array of FGFR3 alterations. Patients (N = 67) who were unable to receive platinum chemotherapy were enrolled. The majority (70.1%) had received two or more prior antineoplastic therapies. BGJ398 was administered orally at 125 mg/day on a 3 weeks on, 1 week off schedule until unacceptable toxicity or progression. The primary endpoint was the response rate. Among 67 patients treated, an overall response rate of 25.4% was observed and an additional 38.8% of patients had disease stabilization, translating to a disease control rate of 64.2%. The most common treatment-emergent toxicities were hyperphosphatemia, elevated creatinine, fatigue, constipation, and decreased appetite. Further examination of BGJ398 in this disease setting is warranted. Significance: BJG398 is active in patients with alterations in FGFR3, resulting in both reductions in tumor volume and stabilization of disease. Our data highlight putative mechanisms of resistance to the agent, which may be useful in following disease status. Cancer Discov; 8(7); 812–21. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 781
Restraining Network Response to Targeted Cancer Therapies Improves Efficacy and Reduces Cellular Resistance
Authors: Tirtha K. Das, Jessica Esernio, Ross L. Cagan
Journal: Cancer Research (2018)

A key tool of cancer therapy has been targeted inhibition of oncogene-addicted pathways. However, efficacy has been limited by progressive emergence of resistance as transformed cells adapt. Here, we use Drosophila to dissect response to targeted therapies. Treatment with a range of kinase inhibitors led to hyperactivation of overall cellular networks, resulting in emergent resistance and expression of stem cell markers, including Sox2. Genetic and drug screens revealed that inhibitors of histone deacetylases, proteasome, and Hsp90 family of proteins restrained this network hyperactivation. These "network brake" cocktails, used as adjuncts, prevented emergent resistance and promoted cell death at subtherapeutic doses. Our results highlight a general response of cells, transformed and normal, to targeted therapies that leads to resistance and toxicity. Pairing targeted therapeutics with subtherapeutic doses of broad-acting "network brake" drugs may provide a means of extending therapeutic utility while reducing whole body toxicity.Significance: These findings with a strong therapeutic potential provide an innovative approach of identifying effective combination treatments for cancer. Cancer Res; 78(15); 4344-59. ©2018 AACR.
Abstract 20585: Association of Fibroblast Growth Factor-23 as a Predictor of Cardiovascular Outcomes
Authors: Brissete Mancero, Jorge Torres, Andrés Mancero, Ana Palacio, Leonardo Tamariz
Journal: Circulation (2016)

Introduction:  Fibroblast growth factor (FGF)–23, a phosphate regulating hormone, accumulates in kidney disease. Patients with kidney disease have a higher incidence of cardiovascular outcomes. It is unclear if FGF-23 is a predictor of outcomes in all stages of kidney disease. Our aim was to assess the strength of the association of FGF-23 levels with cardiovascular outcomes at different stages of kidney disease.   Methods:  We searched the MEDLINE database (1966 to 2016) supplemented by manual searches of bibliographies of key relevant articles. We selected all cohort studies in which FGF-23 was measured and classified them into three groups: studies from the general population without kidney disease, studies in pre-dialysis and studies in dialysis patients. Our outcomes were all-cause mortality, incident coronary heart disease and heart failure. We calculated the pooled relative risk (RR) with the corresponding 95% confidence interval (CI) for incident outcomes by using the fixed effects method comparing higher and lower tertiles of FGF-23. To compare differences in RR’s between each group or outcome we used meta-regression.   Results:  Our search strategy yielded 3198 studies, 14 met our eligibility criteria, involving 11192 participants. We included 5 studies that measured FGF-23 in the general population, 5 in the pre-dialysis patients and 4 in patients undergoing dialysis. The table reports the RR’s for each stage of kidney disease and outcome. The RR of all-cause mortality was 1.92, 1.40 and 1.37 for the pre-dialysis, dialysis and general population, respectively. The meta-regression beta-coefficient was +0.23 (p   Conclusions:  The predictive ability of FGF23 for cardiovascular events differs by stage of kidney disease. It is useful in the pre-dialysis stage to predict all-cause mortality and heart failure. The rationale for the difference in risk deserves attention.
Body mass index (BMI), health behaviors, and perceptions in cancer survivors.
Authors: Lawson Eng, Sophia Yijia Liu, Jie Su, Dan Pringle, Mary Mahler, Chongya Niu, Hiten Naik, Rahul Mohan, Kyoko Tiessen, Henrique Hon, M Catherine Brown, Jennifer M. Jones, Doris Howell, Peter Selby, Shabbir M.H. Alibhai, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

97 Background: Obesity is associated with poorer outcomes across multiple cancer types. Health behaviour change (smoking cessation, physical activity (PA) and alcohol moderation) can improve both obesity and outcomes among cancer survivors. Methods: Cancer patients (pts) were cross-sectionally surveyed on their smoking, PA and alcohol use before and after diagnosis and their perceptions of these behaviours on quality of life (QoL), fatigue, survival (OS) and safety. Multivariable logistic regression models evaluated the association of BMI 1 year prior to diagnosis with behaviour changes and perceptions. Results: Of 1269 pts, 204 smoked at diagnosis and 58% quit afterwards; 350 met PA guidelines at diagnosis and 238 at follow-up; 661 drank alcohol at diagnosis and 50% reduced consumption afterwards. Median BMI was 25.8 (22% obese). Most pts perceived PA ( &gt; 75%) as improving outcomes, smoking ( &gt; 70%) as worsening outcomes and half (41-49%) felt alcohol worsened outcomes. At diagnosis, increased BMI was associated with being an ex-smoker (vs current smoker; P= 0.003), never using alcohol (vs former use; P= 0.05) and not meeting PA guidelines ( P= 0.01). Among smokers at diagnosis, increased BMI was associated with smoking cessation (aOR 1.08 per 1 unit BMI increase, P= 0.03) and perceiving that smoking worsens OS (aOR 1.10, P= 0.04) and fatigue (aOR 1.08, P= 0.08). Among pts not meeting PA guidelines at diagnosis, increased BMI was associated with perceiving that PA worsens fatigue (OR 1.02, P= 0.06) and is unsafe (OR 1.04, P= 0.06). Among drinkers at diagnosis, increasing BMI was associated with perceiving alcohol to be less harmful (aOR 0.93, P= 0.002), less likely to worsen OS (aOR 0.96, P= 0.04) and fatigue (aOR 0.97, P= 0.09). BMI was not associated with changes in alcohol or PA after diagnosis. BMI was not associated with counselling rates; however, 66% of current smokers received cessation counselling while only 14% of current drinkers and 13% of pts not meeting PA guidelines received counselling on their respective behaviours. Conclusions: Obese pts were more likely to quit smoking and perceive it to be harmful but less likely to perceive alcohol as harmful. Survivorship programs should consider focusing on PA and alcohol counselling in obese pts.
NF1 mutations are recurrent in adult acute myeloid leukemia and confer poor outcome
Authors: Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Alice Mims, Christopher J. Walker, James S. Blachly, Deedra Nicolet, Shelley Orwick, Sophia E. Maharry, Andrew J. Carroll, Bayard L. Powell, Jonathan E. Kolitz, Eunice S. Wang, Richard M. Stone, Albert de la Chapelle, John C. Byrd, Clara D. Bloomfield
Journal: Leukemia (2018)
Mechanically induced development and maturation of human intestinal organoids in vivo
Authors: Holly M. Poling, David Wu, Nicole Brown, Michael Baker, Taylor A. Hausfeld, Nhan Huynh, Samuel Chaffron, James C. Y. Dunn, Simon P. Hogan, James M. Wells, Michael A. Helmrath, Maxime M. Mahe
Journal: Nature Biomedical Engineering (2018)
A new mixed methods approach to uncover multi-level barriers and facilitators of cancer survivorship.
Authors: Autumn Kieber-Emmons, Benjamin F Crabtree, William Miller
Journal: Journal of Clinical Oncology (2018)

36 Background: As healthcare becomes increasingly complex, research needs to take into account multi-level interactions that contribute to public health issues. One such area ripe for multi-level investigation is cancer survivorship care, illuminated in the 2006 Lost in Transition Institute of Medicine report on cancer survivors. We have developed a novel method that aims to understand barriers and facilitators of cancer survivorship from multiple levels, including community factors, medical system features, and policy and environmental influences. Methods: Our method, focused Rapid Assessment Process (fRAP), utilizes mixed methods at multiple levels to better understand cancer survivorship care with a primary care lens. fRAP begins with Geographic Information Systems (GIS) to map variables relevant to cancer survivorship care, such as cancer mortality rates, insurance coverage, and oncology and primary care provider sites. Qualitative participant observation and semi-structured interviews of informants from each level are then undertaken to better understand how cancer survivorship care is delivered within a county or census tract. Lastly, modifiable contextual factors from all levels are identified, as potential future environmental policy change targets. Results: As a development and pilot of our novel fRAP, we have designed, tested, revised and retested our methods over the last 3 years within the framework of two national grant-funded studies on cancer survivorship in primary care. Preliminary modifiable factors of interest affecting cancer survivorship care have been identified for future dissemination. The newest and current iteration of our methods has focused on utilizing GIS specifically to identify hot spots of cervical cancer mortality disparities in order to provide the richest contextual environment for subsequent qualitative inquiry into survivorship care. Conclusions: fRAP is a novel mixed method that has potential to identify modifiable barriers and facilitators of high-quality cancer survivorship care nationally, and may aid in policy improvements in health and healthcare delivery for survivors.
PHARMacy-based interdisciplinary program for patients with Chronic Heart Failure (PHARM-CHF): rationale and design of a randomized controlled trial, and results of the pilot study
Authors: Ulrich Laufs, Nina Griese‐Mammen, Katrin Krueger, Angelika Wachter, Stefan D. Anker, Friedrich Koehler, Volker Rettig‐Ewen, Lea Botermann, Dorothea Strauch, Dietmar Trenk, Michael Böhm, Martin Schulz
Journal: European Journal of Heart Failure (2018)
The relationship between ICU hypotension and in-hospital mortality and morbidity in septic patients
Authors: Kamal Maheshwari, Brian H. Nathanson, Sibyl H. Munson, Victor Khangulov, Mitali Stevens, Hussain Badani, Ashish K. Khanna, Daniel I. Sessler
Journal: Intensive Care Medicine (2018)

Current guidelines recommend maintaining a mean arterial pressure (MAP) ≥ 65 mmHg in septic patients. However, the relationship between hypotension and major complications in septic patients remains unclear. We, therefore, evaluated associations of MAPs below various thresholds and in-hospital mortality, acute kidney injury (AKI), and myocardial injury.We conducted a retrospective analysis using electronic health records from 110 US hospitals. We evaluated septic adults with intensive care unit (ICU) stays ≥ 24 h from 2010 to 2016. Patients were excluded with inadequate blood pressure recordings, poorly documented potential confounding factors, or renal or myocardial histories documented within 6 months of ICU admission. Hypotension exposure was defined by time-weighted average mean arterial pressure (TWA-MAP) and cumulative time below 55, 65, 75, and 85 mmHg thresholds. Multivariable logistic regressions determined the associations between hypotension exposure and in-hospital mortality, AKI, and myocardial injury.In total, 8,782 patients met study criteria. For every one unit increase in TWA-MAP < 65 mmHg, the odds of in-hospital mortality increased 11.4% (95% CI 7.8%, 15.1%, p < 0.001); the odds of AKI increased 7.0% (4.7, 9.5%, p < 0.001); and the odds of myocardial injury increased 4.5% (0.4, 8.7%, p = 0.03). For mortality and AKI, odds progressively increased as thresholds decreased from 85 to 55 mmHg.Risks for mortality, AKI, and myocardial injury were apparent at 85 mmHg, and for mortality and AKI risk progressively worsened at lower thresholds. Maintaining MAP well above 65 mmHg may be prudent in septic ICU patients.
A Difficult Patient
Authors: James S. Kahn
Journal: Annals of Internal Medicine (2018)

On Being a Doctor5 June 2018A Difficult PatientJames S. Kahn, MDJames S. Kahn, MDStanford School of Medicine and Veterans Administration Palo Alto Health Care System, Palo Alto, California (J.S.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-0691 Audio Reading - “A Difficult Patient” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Difficult Patient," by J.S. Kahn. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The first time he arrived at the clinic to see me, it was with a police escort. He was a big man in a T-shirt and jeans, and his scowl was scary. He'd displayed threatening behavior in the past, stating that if he saw his primary care physician again he would “punch him in the face.” He had to check in with the police whenever he arrived on campus, and an officer escorted him to his appointments. His care was transferred to me because of past troubling interactions with various clinicians in various settings. For a year, he kept his ... Author, Article, and Disclosure InformationAffiliations: Stanford School of Medicine and Veterans Administration Palo Alto Health Care System, Palo Alto, California (J.S.K.)Corresponding Author: James S. Kahn, MD, 3801 Miranda Avenue, Mail Code 111, Palo Alto, CA 94304; e-mail, james.[email protected]gov. PreviousarticleNextarticle Advertisement Audio Reading - “A Difficult Patient” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A Difficult Patient," by J.S. Kahn. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 5 June 2018Volume 168, Issue 11Page: 830-831KeywordsBehaviorDrugsHypertensionLower back painMarijuanaOpioidsStomachSuicideToxicityUrine ePublished: 5 June 2018 Issue Published: 5 June 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...