tbuckley/cabot-search huggingface dataset:
Using the National Cancer Data Base (NCDB) and Oncotype DX data to predict adjuvant therapy effect on overall survival (OS) of N0 &amp; N1 breast cancer patients.
Authors: Amila Orucevic, Heidel Robert, John Lawrence Bell
Journal: Journal of Clinical Oncology (2018)

e12529 Background: The newest 4.2017 version of the NCCN guidelines incorporates the Oncotype DX (ODX) breast cancer (BC) assay into the algorithm for utilization of systemic adjuvant therapy (tx) for hormone receptor positive, HER2 negative, pT1-pT3, N0/N1mi BC patients (pts). Endocrine therapy (ET) alone is recommended for ODX low recurrence score (RS 0-17); chemotherapy (CTx) followed by ET for high RS (31-100), and either for intermediate RS (18-30) or when no assay is performed. Recommendations are category 1 evidence based on published 5-year results from the TAILORx trial that used ODX scores to guide tx, although with different RS cutoff points. The ongoing RxPONDER trial examines the same algorithms in pts with 1-3 + lymph nodes. Methods: We analyzed the impact of ODX utilization on 5-year (yr) OS of invasive BC pts in a retrospective observational study of the NCDB following TAILORx & RxPONDER pts’ inclusion criteria: 6-50 mm tumors, N0/N1, M0, ER+/HER2-, ±postsurgical adjuvant systemic tx, no comorbidities and pts' age from 18-75. Demographic and clinical variables of pts with and without ODX results collected in 2010 were compared (ODX vs No ODX; last follow-up day 12/2015). Frequencies, chi-square, Kaplan-Meier, Cox and logistic regression analyses were used. Results: There were 27,697 T1-T2, N0 pts: 9,607 ODX & 18,090 No ODX; 8,006 T1-T2, N1 pts: 1,537 ODX & 6,469 No ODX. When compared to No ODX, ODX pts were: younger, had larger, higher grade tumors, lower number of positive lymph nodes (ODX N1), ODX N0 received more CTx and more ET, but less CTx when ODX N1 (p < 0.05). Significant predictors of mortality were: no ODX testing, older age, black race, larger tumors, higher grade, N1 status (p < 0.05). Five yr OS of ODX pts was better than No ODX (97.3% vs 96.2% for N0; 95.9 vs 93.5% for N1, p < 0.05); however, the duration of this advantage although significant was short (0.8 months). ODX linear RS result was predictive of CTx benefit for OS in N0 pts, but not for N1 pts. Conclusions: Our results showed that ODX linear RS result was predictive of CTx benefit for OS in N0 pts, but not N1 pts. The predictive value of ODX testing for OS in N1 pts will likely be clarified in the RxPONDER trial.
Airway Microbiota Is Associated with Upregulation of the PI3K Pathway in Lung Cancer
Authors: Jun-Chieh J. Tsay, Benjamin G. Wu, Michelle H. Badri, Jose C. Clemente, Nan Shen, Peter Meyn, Yonghua Li, Ting-An Yie, Tenzin Lhakhang, Evan Olsen, Vivek Murthy, Gaetane Michaud, Imran Sulaiman, Aristotelis Tsirigos, Adriana Heguy, Harvey Pass, Michael D. Weiden, William N. Rom, Daniel H. Sterman, Richard Bonneau, Martin J. Blaser, Leopoldo N. Segal
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

In lung cancer, upregulation of the PI3K (phosphoinositide 3-kinase) pathway is an early event that contributes to cell proliferation, survival, and tissue invasion. Upregulation of this pathway was recently described as associated with enrichment of the lower airways with bacteria identified as oral commensals.
How fast is fast enough? Walking cadence (steps/min) as a practical estimate of intensity in adults: a narrative review
Authors: Catrine Tudor-Locke, Ho Han, Elroy J Aguiar, Tiago V Barreira, John M Schuna Jr, Minsoo Kang, David A Rowe
Journal: British Journal of Sports Medicine (2018)

Background Cadence (steps/min) may be a reasonable proxy-indicator of ambulatory intensity. A summary of current evidence is needed for cadence-based metrics supporting benchmark (standard or point of reference) and threshold (minimums associated with desired outcomes) values that are informed by a systematic process. Objective To review how fast, in terms of cadence, is enough, with reference to crafting public health recommendations in adults. Methods A comprehensive search strategy was conducted to identify relevant studies focused on walking cadence and intensity for adults. Identified studies (n=38) included controlled (n=11), free-living observational (n=18) and intervention (n=9) designs. Results There was a strong relationship between cadence (as measured by direct observation and objective assessments) and intensity (indirect calorimetry). Despite acknowledged interindividual variability, ≥100 steps/min is a consistent heuristic (e.g, evidence-based, rounded) value associated with absolutely defined moderate intensity (3 metabolic equivalents (METs)). Epidemiological studies report notably low mean daily cadences (ie, 7.7 steps/min), shaped primarily by the very large proportion of time (13.5 hours/day) spent between zero and purposeful cadences (&lt;60 steps/min) at the population level. Published values for peak 1-min and 30-min cadences in healthy free-living adults are &gt;100 and &gt;70 steps/min, respectively. Peak cadence indicators are negatively associated with increased age and body mass index. Identified intervention studies used cadence to either prescribe and/or quantify ambulatory intensity but the evidence is best described as preliminary. Conclusions A cadence value of ≥100 steps/min in adults appears to be a consistent and reasonable heuristic answer to ’How fast is fast enough?' during sustained and rhythmic ambulatory behaviour. Trial registration number NCT02650258
WPA Position Statement on Banning the Participation of Psychiatrists in the Interrogation of Detainees
Authors: Pau Pérez‐Sales, Joost Jan den Otter, Lilla Hardi, Thomas Wenzel, Gabriel Diaconu, Graciela Cors, Marianne Kastrup
Journal: World Psychiatry (2018)

Though torture is illegal, as stipulated by a number of well-known conventions and treaties, and thus subjected to international prosecution, psychiatrists have been sometimes involved in situations connected to ill-treatment and torture which are also ethically unacceptable on any grounds. The purpose of this Position Statement is to provide ethical guidelines for practice, in which psychiatrists are explicitly forbidden, and must refrain, from participating in any procedure linked to the interrogation of a detainee. An exception is the specific case of assessing the liability, when the person is being or has been submitted to ill-treatment or torture, and such events and possible consequences have to be documented. Many regimes around the world put pressure on the medical profession. If the reader feels this is his/her case or wishes to contact the WPA Section on Psychological Consequences of Torture and Persecution, the relevant e-mail address is pauperez@arrakis.es. Pau Pérez-Sales1,2, Joost Jan den Otter1, Lilla Hardi1,3, Thomas Wenzel1,4, Gabriel Diaconu1,5, Graciela Cors1,6, Marianne Kastrup1,7 1WPA Section on Psychological Consequences of Torture and Persecution; 2SiR(a) Centre, Madrid, Spain; 3Cordelia Foundation, Budapest, Hungary; 4Medical University of Vienna, Vienna, Austria; 5Medlife Memorial Hospital, Bucharest, Romania; 6Latif Clinics, Shfar'am, Israel; 7Copenhagen, Denmark
Abstract 13189: CV-Ecosystem Model: Workplace Wellness With Individualized Medicine
Authors: Chayakrit Krittanawong, Cindy A Kermott, Zhen Wang, HongJu Zhang, Tweet S Marysia, Sakkarin Chirapongsathorn, Sharonne Hayes
Journal: Circulation (2015)

Introduction: At-work stress is rapidly becoming a significant contributory cause of occupational disease, while sedentary work and dietary indiscretion, taken together, have contributed to cardiovascular disease, known to be associated with substantial morbidity and mortality. The aim of the CV-Ecosystem Model is to provide an individual approach by systematic environmental modification of the work site. Methods and Results: Our model which we term the CV-Ecosystem Model includes two basic tenets: 1) Workstation technologic design 2) Flexible physiologic activity. Workstation technologic design utilizes the services of a certified Ergonomist to engineer a comfortable, safe, and effective work environment. It is tailored to the unique physiologic needs of the worker while enhancing productivity within different environments. Computer aided design software would evaluate ergonomics to maximally mitigate the risk and incidence of eye strain, musculoskeletal disorders, repetitive movement disorders such as Carpal Tunnel Syndrome, etc unique to that work activity. Flexible physiologic activity would permit a worker to actively focus on basic needs during work time, on site; this would include exercise activity and food intake, channeled into healthy options. Exercise time would provide a sense of calm during stressful projects and enhance emotional well-being. In this regard, a three hour period of time, weekly, could be allocated to fitness or meditation. Conveniently located food stations could provide a variety of healthy, plant-based, fresh food options. Both would come with flexible, relative control and scheduling of these activities, within a social environment and context. Conclusions: The CV Ecosystem Model, due to its simple technology and relative low cost, could be successfully implemented in a number of enterprises, including all healthcare facilities, with benefit to employee health, wellbeing, and favorable to the business bottom line.
FOLFIRINOX in advanced pancreatic cancer patients with the double-variant type of UGT1A1 polymorphism: A multicenter, retrospective study.
Authors: Kumiko Umemoto, Hideaki Takahashi, Chigusa Morizane, Ikuhiro Yamada, Satoshi Shimizu, Kazuhiko Shioji, Yukio Yoshida, Masayo Motoya, Nobumasa Mizuno, Yasushi Kojima, Takeshi Terashima, Kazuhiro Uesugi, Masafumi Ikeda, Makoto Ueno, Junji Furuse
Journal: Journal of Clinical Oncology (2018)

484 Background: UGT1A1 *28 or *6 polymorphism is associated with reduced enzyme activity and severe toxicity of irinotecan, especially in patients homozygous for UGT1A1*28 or *6 and heterozygous for both UGT1A1*28 and *6 (double-variant-type: DV). FOLFIRINOX (FFX) is one of the standard treatments in patients with advanced pancreatic cancer (APC). In Japanese guideline for FFX in patients with APC, full-dose regimen of FFX is not recommended in patients with DV, but dose adjustment for patients with DV is not established yet. The purpose of this study was to evaluate the safety and efficacy of FFX in Japanese APC patients with DV. Methods: APC patient of DV treated with FFX from December 2013 to March 2016 in 16 hospitals in Japan were enrolled. Results: A total of 31 patients were enrolled. Irinotecan were variously administered at the first cycle of dose ranged from 70 to 180mg/m2. The proportion of the patients receiving standard dose of oxaliplatin, 5-FU infusion and 5-FU continuous infusion at the first cycle of FFX were 97%, 19% and 97%, respectively. Severe adverse events were observed 8 of 31 patients. Main grade 3 or 4 adverse events were included neutropenia (65%), febrile neutropenia (13%) and diarrhea (6%). Response rate (RR) and overall survival (OS) receiving FFX as first-line treatment were 23% and 13.5 months, respectively. In this study, patients receiving irinotecan 150mg/m2 was high frequency of 80% (4/5), otherwise, grade 4 neutropenia in all patients was observed in 29% (9/31) Conclusions: The results of neutropenia in this study indicated that irinotecan 150mg/m2 may not be tolerable in DV patients. RR and OS were almost the same as previous reports. We are planning the dose finding study of FFX in APC patients with DV.
Recurrence risk factors and outcome stratification in stage II colon cancer patients: A subanalysis of the SACURA trial.
Authors: Megumi Ishiguro, Eiji Nakatani, Hideki Ueno, Toshiaki Ishikawa, Hiroyuki Uetake, Yasuhiro Shimada, Keiichi Takahashi, Kenjiro Kotake, Masahiko Watanabe, Naohiro Tomita, Hidetaka Mochizuki, Satoshi Teramukai, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2017)

3611 Background: Efficacy of adjuvant chemotherapy for stage II colon cancer is still controversial. We conducted the SACURA trial, a phase III study which evaluated the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone in stage II colon cancer. However, survival benefit of 1-year UFT to surgery alone was not demonstrated (ASCO2016 abst#3617). We herein aimed to identify risk factors for recurrence in the stage II patients “without adjuvant chemotherapy”, and to stratify the prognosis by using these factors. Methods: Among a total of 982 patients without adjuvant chemotherapy enrolled to the SACURA trial, we extracted the factors correlated to recurrence using a univariate and multivariate Cox proportional hazard model. 943 and 935 patients in the surgery alone group and UFT group were divided to subgroups according to the number of risk factors, and the recurrence rate in each subgroup was evaluated. Results: Among the conventional clinicopathological characteristics, the multivariate analysis identified pT4, elevated CEA, and examined lymph nodes less than 12 as significant risk factors for recurrence. The rate of patients with 0, 1, 2, and 3 risk factors were 45.0%, 42.4%, 11.5%, and 1.1%, respectively. The recurrence rate for each subgroup was shown in the table: the recurrence rate increased with number of risk factors, while 10.2% of patients without any risk factors developed recurrence. Difference in the recurrence rate between the treatment groups was significant in patients without risk factor, marginal in patients with 1 risk factor, and none in patients with &gt;1 factors. Conclusions: pT4, elevated CEA, and examined lymph nodes less than 12 were identified as risk factors for recurrence in stage II colon cancer patients. The recurrence rate was divided by the number of these risk factors, but we could not extract the very-low risk group in whom adjuvant therapy is unnecessary. Induction of novel risk factors other than conventional clinicopathological characteristics is recommended. Clinical trial information: NCT00392899. [Table: see text]
Radium-223 Dichloride in Combination with Vascular Endothelial Growth Factor–Targeting Therapy in Advanced Renal Cell Carcinoma with Bone Metastases
Authors: Rana R. McKay, Dominick Bossé, Kathryn P. Gray, M. Dror Michaelson, Katherine Krajewski, Heather A. Jacene, Meghara Walsh, Joaquim Bellmunt, Mark Pomerantz, Lauren C. Harshman, Toni K. Choueiri
Journal: Clinical Cancer Research (2018)

Purpose: This study investigates the biologic activity of radium-223 with VEGF-targeted therapy in patients with advanced renal cell carcinoma (aRCC) and bone metastases.Patients and Methods: Fifteen treatment-naïve patients (n = 15) received pazopanib 800 mg orally once daily, and 15 previously treated patients received sorafenib 400 mg orally twice daily. Radium-223 55 kilobecquerel/kg was administered concurrently every 4 weeks for up to six infusions in both cohorts. The primary endpoint was decline in bone turnover markers (Procollagen I Intact N-Terminal, N-telopeptide, C-telopeptide, osteocalcin, and bone-specific alkaline phosphatase) compared with baseline. Secondary endpoints included safety, rate of symptomatic skeletal event (SSE) and time to first SSE, objective response rate, change in analgesic use, and quality of life. Exploratory analysis of tumor genomic alterations was performed.Results: Of the 30 patients enrolled, 83% had IMDC intermediate- or poor-risk disease, 33% had liver metastases, and 83% had a history of SSE prior to enrollment. No dose-limiting toxicity was observed. All bone turnover markers significantly declined from baseline at week 8 and 16. Forty percent of patients experienced treatment-related grade ≥3 adverse events. Response rates were 15% and 18% per RECIST v1.1 and bone response was 50% and 30% per MD Anderson criteria, in the pazopanib and sorafenib cohort, respectively. Median SSE-free interval was 5.8 months and not reached, respectively. Analgesic use remained stable over the study time.Conclusions: Radium-223 combined with VEGF-targeted therapy is biologically active and safe. Randomized-controlled trials are needed to define the role of radium-223 in aRCC with skeletal metastases. Clin Cancer Res; 24(17); 4081-8. ©2018 AACR.
Rate of Recurrence of Lentigo Maligna Treated With Off-Label Neoadjuvant Topical Imiquimod, 5%, Cream Prior to Conservatively Staged Excision
Authors: Jessica M. Donigan, Mark A. Hyde, David E. Goldgar, Michael L. Hadley, Marianne Bowling, Glen M. Bowen
Journal: JAMA Dermatology (2018)

Staged excision of lentigo maligna (LM) often requires multiple stages and can result in significant cosmetic morbidity. Imiquimod cream has been used off-label as monotherapy in the treatment of LM and may be used in the neoadjuvant setting prior to staged excision as a strategy to reduce the size of the surgical margins required to confirm negative histologic margins.To examine the rate of recurrence of LM in patients treated with neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions.This was a retrospective medical record review of 334 patients with 345 biopsy-confirmed LM tumors from June 2004 to January 2012 who were treated with imiquimod prior to undergoing staged excisions at the University of Utah Medical Center and Huntsman Cancer Institute, large academic hospitals in Salt Lake City.Patients were treated with off-label imiquimod, 5%, cream 5 nights per week for 2 to 3 months. Those deemed to have an inadequate inflammatory response were also treated with tazarotene, 0.1%, gel twice weekly. Conservatively staged excisions, beginning with 2-mm margins, were then performed.The rate of recurrence of LM after long-term follow-up.Patients included 235 men (70%) and 99 women (30%) with a mean (SD) age of 67 (13) years. Patients were treated with imiquimod cream for a mean of 2.5 months prior to undergoing conservatively staged excisions. There were 12 local recurrences (a rate of 3.9%) with a mean time to recurrence of 4.3 years and a mean length of follow-up of 5.5 years.Neoadjuvant topical imiquimod, 5%, cream prior to conservatively staged excisions for LM allowed for negative histologic margins with a median final margin of 2 mm and a rate of recurrence similar to reported recurrence rates with standard staged excisions by either Mohs surgery or en face permanent sections.
Impact of Primary Care Intensive Management on High-Risk Veterans' Costs and Utilization
Authors: Jean Yoon, Evelyn Chang, Lisa V. Rubenstein, Angel Park, Donna M. Zulman, Susan Stockdale, Michael K. Ong, David Atkins, Gordon Schectman, Steven M. Asch
Journal: Annals of Internal Medicine (2018)

Primary care models that offer comprehensive, accessible care to all patients may provide insufficient resources to meet the needs of patients with complex conditions who have the greatest risk for hospitalization.To assess whether augmenting usual primary care with team-based intensive management lowers utilization and costs for high-risk patients.Randomized quality improvement trial. (ClinicalTrials.gov: NCT03100526).5 U.S. Department of Veterans Affairs (VA) medical centers.Primary care patients at high risk for hospitalization who had a recent acute care episode.Locally tailored intensive management programs providing care coordination, goals assessment, health coaching, medication reconciliation, and home visits through an interdisciplinary team, including a physician or nurse practitioner, a nurse, and psychosocial experts.Utilization and costs (including intensive management program expenses) 12 months before and after randomization.2210 patients were randomly assigned, 1105 to intensive management and 1105 to usual care. Patients had a mean age of 63 years and an average of 7 chronic conditions; 90% were men. Of the patients assigned to intensive management, 487 (44%) received intensive outpatient care (that is, ≥3 encounters in person or by telephone) and 204 (18%) received limited intervention. From the pre- to postrandomization periods, mean inpatient costs decreased more for the intensive management than the usual care group (-$2164 [95% CI, -$7916 to $3587]). Outpatient costs increased more for the intensive management than the usual care group ($2636 [CI, $524 to $4748]), driven by greater use of primary care, home care, telephone care, and telehealth. Mean total costs were similar in the 2 groups before and after randomization.Sites took up to several months to contact eligible patients, limiting the time between treatment and outcome assessment. Only VA costs were assessed.High-risk patients with access to an intensive management program received more outpatient care with no increase in total costs.Veterans Health Administration Primary Care Services.
Genome-wide association studies suggest that APOL1-environment interactions more likely trigger kidney disease in African Americans with nondiabetic nephropathy than strong APOL1–second gene interactions
Authors: Carl D. Langefeld, Mary E. Comeau, Maggie C.Y. Ng, Meijian Guan, Latchezar Dimitrov, Poorva Mudgal, Mitzie H. Spainhour, Bruce A. Julian, Jeffrey C. Edberg, Jennifer A. Croker, Jasmin Divers, Pamela J. Hicks, Donald W. Bowden, Gary C. Chan, Lijun Ma, Nicholette D. Palmer, Robert P. Kimberly, Barry I. Freedman
Journal: Kidney International (2018)
Implementation of an electronic referral smoking cessation tool into clinical practice across cancer clinics of different disease sites and institutions.
Authors: Tamoor Afzaal, Lina Chen, Justine Baek, Tiffany Tse, Kelvin K. Chan, M. Catherine Brown, Doris Howell, Peter Selby, Meredith Elana Giuliani, Jennifer M. Jones, Amy Skitch, Christine B. Brezden, Lawson Eng, Andrea Eisen, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

112 Background: Cancer Care Ontario, the government's cancer management agency, mandated routine collection of smoking data province wide (catchment of &gt; 13 million individuals), but did not mandate specifics of a smoking cessation program for cancer patients, despite known benefits. Referral rates to smoking cessation clinics for cancer patients are low. In 2014, Princess Margaret Cancer Centre developed an electronic, patient-driven e-referral tool shown to improve referral rates, known as the smoking Cessation E-referrAl SystEm (CEASE). The objective of this study is to assess the feasibility for expanding this program through adoption and implementation of the CEASE tool to 5 additional clinics across 3 different Cancer Centres. Methods: The Canadian Institute of Health Research’s Knowledge-to- Action (CHIR KTA) framework guided the assessment. Feasibility was addressed through situational assessments, pilot implementation, and clinic/patient feedback in at least two cycles, with procedural changes made at the conclusion of each cycle. Clinics were selected to cover a wide range of hospital, clinic styles, and disease sites. Results: Pilot implementation occurred over 21 clinic days (Jun 2017- Aug 2017); 123 patients were enrolled in the pilot studies in breast, gastrointestinal, head and neck, and thoracic sites. Feasibility assessment in each clinic identified similarities and differences in resource availability, access to authority figures, and patient flow patterns. After the feasibility assessment, a pilot implementation identified English as a second language and the lack of patient's tablet/technological experience as the main barriers for implementation in 4 of 5 clinics. The use of volunteers assisting patients with the survey helped address these barriers. Strong internet connection, short survey length and staff engagement were seen as universal common facilitators to implementation in all 5 clinics. Conclusions: Despite different outpatient environments, common barriers and potential solutions were identified, which will help with scalable future widespread implementation of CEASE across the province of Ontario.