tbuckley/cabot-search huggingface dataset:
Controlled ecological evaluation of an implemented exercise-training programme to prevent lower limb injuries in sport: population-level trends in hospital-treated injuries
Authors: Caroline F Finch, Shannon E Gray, Muhammad Akram, Alex Donaldson, David G Lloyd, Jill L Cook
Journal: British Journal of Sports Medicine (2018)

Exercise-training programmes have reduced lower limb injuries in trials, but their population-level effectiveness has not been reported in implementation trials. This study aimed to demonstrate that routinely collected hospital data can be used to evaluate population-level programme effectiveness.A controlled ecological design was used to evaluate the effect of FootyFirst, an exercise-training programme, on the number of hospital-treated lower limb injuries sustained by males aged 16-50 years while participating in community-level Australian Football. FootyFirst was implemented with 'support' (FootyFirst+S) or 'without support' (FootyFirst+NS) in different geographic regions of Victoria, Australia: 22 clubs in region 1: FootyFirst+S in 2012/2013; 25 clubs in region 2: FootyFirst+NS in 2012/2013; 31 clubs region 3: control in 2012, FootyFirst+S in 2013. Interrupted time-series analysis compared injury counts across regions and against trends in the rest of Victoria.After 1 year of FootyFirst+S, there was a non-statistically significant decline in the number of lower limb injuries in region 1 (2012) and region 3 (2013); this was not maintained after 2 years in region 1. Compared with before FootyFirst in 2006-2011, injury count changes at the end of 2013 were: region 1: 20.0% reduction (after 2 years support); region 2: 21.5% increase (after 2 years without support); region 3: 21.8% increase (after first year no programme, second year programme with support); rest of Victoria: 12.6% increase.Ecological analyses using routinely collected hospital data show promise as the basis of population-level programme evaluation. The implementation and sustainability of sports injury prevention programmes at the population-level remains challenging.
Tozuleristide pharmacokinetics from phase 1 studies in adult and pediatric subjects with central nervous system tumors undergoing surgery.
Authors: Dennis Michael Miller, Sarah Leary, Amy Lee, Chirag Patil, David Walker, Laura Ishak, Carolyn Gombotz, Kelly Byrnes-Blake
Journal: Journal of Clinical Oncology (2018)

e14562 Background: Tozuleristide (BLZ-100) is a fluorescent imaging agent intended to highlight tumor tissue in patients undergoing surgical tumor resection. The pharmacokinetics (PK) of BLZ-100 in adult and pediatric patients undergoing neurosurgery for tumor resection were evaluated in two clinical studies (total of 42 subjects). In both studies, a single IV bolus dose of BLZ-100 was administered at least 2 hours prior to surgery. Dose levels were 3, 9, 18, 24, and 30 mg in adult and 1.7, 3.5, 6.9, 13.9, 15, and 17.3 mg/m2 in pediatric subjects. Methods: Serum samples were analyzed for BLZ-100 concentration using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method with a LLOQ of 10 ng/mL. Noncompartmental analyses were performed to estimate Tmax, Cmax, AUC0-t, and t1/2. The effect of dose level was evaluated in each study. Additionally, these data were fit with a compartmental model for use in future studies. Results: Dose-dependent and non-linear increases in BLZ-100 Cmax and AUC0-t were observed in both adult and pediatric patients. The mean t1/2 in adults ranged from 0.2 to 0.5 hours and the mean t1/2 in pediatrics ranged from 0.4 to 0.6 hours. Although BLZ-100 has a short serum t1/2, tumor fluorescence was observed in cases as early as 4 hours and as late as 24 hours post-dose, demonstrating that the serum kinetics are not indicative of BLZ-100 exposure in tumor tissue. There were no obvious differences in BLZ-100 exposure or t1/2 values between male and female patients. At the dose level of interest for further study (15 mg/m2), infants and children under the age of 12 tended to have slightly higher ( < 2-fold) Cmax and AUC0-t values compared to adolescents and young adults. Conclusions: The adult PK data were best fit with a 1-compartment IV bolus model with 1/ŷ2 weighting. When dose level was accounted for, this model provided a good fit to the pediatric patient data in the 15 mg/m2 cohort. Clinical trial information: NCT02234297, NCT02462629.
Somatic <i>STK11/LKB1</i> mutations to confer resistance to immune checkpoint inhibitors as monotherapy or in combination in advanced NSCLC.
Authors: Maria Jure-Kunkel, Song Wu, Feng Xiao, Shaad Essa Abdullah, Guozhi Gao, Judson M. Englert, Hsin-Ju Hsieh, Pralay Mukhopadhyay, Ashok Kumar Gupta, Phillip A. Dennis, Brandon W. Higgs, Koustubh Ranade
Journal: Journal of Clinical Oncology (2018)

3028 Background: Although PD-1/PD-L1 checkpoint blockade has become standard of care for non-small cell lung cancer (NSCLC), some treated patients (pts) do not respond. A deeper understanding of mechanisms of resistance to PD-(L)1 blockade is needed to improve therapeutic decisions. The aim of this study was to identify molecular alterations associated with innate resistance to durvalumab (D) and durvalumab + tremelimumab (D + T) combination therapy in advanced non-squamous (Non-SQ) NSCLC. Methods: CP1108/NCT01693562 and ATLANTIC/NCT02087423 were nonrandomized phase 1/2 and 2 trials of D (10 mg/kg, Q2W). D4190C00006/NCT02000947 was a nonrandomized phase Ib trial of D + T (20 mg/kg + 1 mg/kg, Q4W). Circulating tumor DNA (ctDNA) analysis (Guardant360 70 gene cancer panel) was conducted in pre-treatment plasma samples for 119 and 63 Non-SQ NSCLC pts in CP1108 and ATLANTIC, respectively. Targeted sequencing of pre-treatment tumors (FoundationOne CDx™) was conducted in 120 Non-SQ NSCLC pts in D4190C00006. Association of tumor mutations and objective response rate (ORR) by RECIST v1.1 and overall survival (OS) is presented. Immune contexture of STK11 mt Non-SQ NSCLC tumors was investigated in the TCGA. Results: In two independent trials evaluating D as monotherapy (CP1108/Atlantic), and in a D + T combination trial (D4190C00006), reduced ORR and shorter survival were observed in Non-SQ NSCLC pts harboring STK11 non-synonymous mutant tumors compared to pts harboring STK11 wild type (wt) tumors (Table 1). In TCGA, STK11 mutations were not prognostic and were associated with low IFNγ signature and high G-CSF and IL-6 expression. Conclusions: In Non-SQ NSCLC, somatic STK11 mt may confer innate resistance to immune checkpoint inhibitors. Optimal therapeutic combinations for this subset of patients are being explored in HUDSON/NCT03334617. Table 1. ORR and OS in STK11 mt or wt Non-SQ NSCLC pts treated with D or D + T Clinical trial information: NCT01693562, NCT02087423, NCT02000947. ORR (n/N) Median OS (months) STK11 mt STK11 wt X2 STK11 mt (mo.) STK11 wt (mo.) log-rank p CP1108 (D) 6 (1/15) 16 (17/104) 0.05 4.9 14.2 0.008 Atlantic (D) 0 (0/6) 25 (14/57) D4190C00006 (D + T) 4 (1/23) 25 (24/97) 0.02 6.7 15.6 0.001
Impact of marital status on the survival of patients with hematologic malignancies reported to the California Cancer Registry.
Authors: Matthew Joseph Wieduwilt, Li Tao, Christina A Clarke, Theresa H.M. Keegan, Sally L Glaser, Scarlett Lin Gomez, Maria Elena Martinez
Journal: Journal of Clinical Oncology (2016)

6555 Background: Married patients with solid tumors experience significantly better survival than unmarried patients. The impact of marital status on survival of patients with hematologic malignancies is not well known. Methods: Patients newly diagnosed with a first primary acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), classical Hodgkin lymphoma (cHL), or multiple myeloma (MM) in 2000-2009 were identified through the California Cancer Registry (N = 58,606). Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause survival associated with marital status, adjusted for age, sex, race/ethnicity, treatment, insurance status, and neighborhood socioeconomic status (nSES) statewide quintile (Q). Results: 57% of patients were married. In multivariable analysis adjusted for subtype, inferior overall survival (OS) was associated with being unmarried (HR 1.21, 95% CI 1.19-1.24), male, Hispanic (relative to non-Hispanic white), a diagnosis of AML or ALL (relative to DLBCL), untreated, and of lower nSES. The deleterious effect of being unmarried on OS was present for non-Hispanic whites (HR 1.23, 95% CI 1.20-1.27), non-Hispanic blacks (HR 1.21, 95% CI 1.11-1.32), Hispanics (HR 1.18, 95% CI 1.02-1.15), and Asians/Pacific Islanders (HR 1.13, 95% CI 1.04-1.22). It was present in all nSES quintiles. Married, high nSES (Q4-5) patients had the best OS relative to other groups (Fig.1). Being unmarried negatively impacted OS for AML (HR 1.21, 95% CI 1.13-1.29), DLBCL (HR 1.21, 95% CI 1.15-1.26), FL (HR 1.43, 95% CI 1.33-1.55), cHL (HR 1.37, 95% CI 1.23-1.51), and MM (HR 1.17, 95% CI 1.12-1.22) but not ALL (1.07, 95% CI 0.96-1.20). For AML, DLBCL, FL, and MM, married patients with high nSES (Q4-5) had superior OS relative to unmarried patients and to married patients of low SES. Similar findings occurred for disease-specific survival. Conclusions: Future study should aim to identify modifiable factors, such as treatment adherence, social support or health behaviors, contributing to the reduced survival in unmarried patients with hematologic malignancies.
Validation of clinical scoring systems ART and ABCR after transarterial chemoembolization of hepatocellular carcinoma.
Authors: Roman Kloeckner, Michael Bernhard Pitton, Christoph Düber, Irene Schmidtmann, Peter R. Galle, Sandra Koch, Marcus-Alexander Worns, Arndt Weinmann
Journal: Journal of Clinical Oncology (2016)

e15593 Background: Transarterial Chemoembolization (TACE) is the standard of care for intermediate stage hepatocellular carcinoma (HCC). It remains challenging to decide whether to repeat treatment. We performed external validations of two scoring systems recently developed to evaluate TACE: the ART (assessment for retreatment with TACE) and the ABCR (alpha fetoprotein [AFP], Barcelona clinic liver cancer [BCLC] stage, Child-Pugh score, and treatment response). We also compared their prognostic value. Methods: From 2000 to 2015, 871 patients with HCC underwent TACE at our tertiary referral hospital. We acquired baseline data on BCLC-stages and AFP levels, and data measured before the second TACE on Child-Pugh scores, aspartate aminotransferase levels, and radiologic tumor responses. Overall survival was calculated. Both Scores were validated and compared with Harrell´s C-index, the integrated Brier score (IBS), and prediction error curves. Furthermore, multivariate analyses including all variables used in each score were performed in order to identify independent predictors of survival. Results: 176 patients were included. Low and high ART scores predicted median survivals of 20.8 and 15.3 months, respectively. Low, intermediate, and high ABCR scores predicted median survivals of 24.5, 15.8, and 5.8 months, respectively. Harrell´s C-indexes were 0.572 and 0.608 and IBS were 0.135 and 0.128 for ART and ABCR, respectively. For both scores, an increase in Child Pugh ≥ 2 points and a radiological response independently predicted survival. Independent predictors of survival in both scores were an increase in Child Pugh ≥ 2 points and radiological response. In the ABCR score additionally the BCLC stage proved significant (all p < 0.05). Conclusions: Both ART and ABCR scores provided some indication of which patients had a dismal prognosis, and were unlikely to benefit from repeated TACE. ABCR had slightly greater predictive value. However, neither score was sufficient to support clear-cut clinical decisions. Further effort is necessary to determine criteria for valid predictions.
Provider adherence to evidence-based supportive care practices for patients with multiple myeloma.
Authors: SarahLena Panzer, Beth Faiman, Paul B. Jacobsen, Alyssa M Cadman, Carrie Stricker
Journal: Journal of Clinical Oncology (2016)

e21587 Background: Rapidly emerging therapeutics for multiple myeloma (MM) have diverse and sometimes life-threatening toxicities, underscoring the need for proactive screening, assessment, and management to mitigate symptoms and adverse events [AEs] (i.e., “supportive care (SC) practices”). Little is known about the real-world systematic use of such strategies in routine MM clinical care. A 3 center pilot study aims to describe documented adherence to evidence-based SC practices, and then intervene with a novel ePRO and supportive care planning system (CPS) technology designed to improve adherence. Methods: 90 patients and 90 controls with MM from 3 sites are being evaluated in this pilot study. A scorecard to measure provider use of evidence-based SC practices, at the patient level, was developed by an interdisciplinary team, using an iterative process beginning with literature review and using a modified Delphi technique to gain metric consensus. The scorecard is applied to medical records of patients and controls over an 8-12 week period. Baseline data from matched controls are reported. Results: 13 baseline chart abstractions on historical controls have been conducted; remaining to be completed by presentation. Although screening for specific symptoms was fairly consistent, once identified, documentation of detailed assessments (e.g., severity, functional impact) and management strategies was poor. See tablebelow.Conclusions: Providers regularly documented symptom/AE screening, yet detailed assessments and evidence of interventions were inconsistently documented. Although documentation may not reflect actual practice, improvement in detailed assessment and management strategies is likely needed. Barriers may include the limited availability of effective interventions for symptoms such as CIPN & fatigue, as well as time barriers to effective symptom assessment and management, and its documentation. The in-progress trial will evaluate the ability of a novel technology CPS to improve this state of affairs. Symptom/AE Screen Assessment Intervention Fatigue 85% 30% 10% CIPN 69% 56% 60% Diarrhea 69% 17% -- Distress 69% -- 100% VTE 77% -- -- Received guideline-recommended prophylaxis while on IMiDs 29%
Race-specific genetic aberrations in B-acute lymphoblastic leukemia in children.
Authors: Amit Reddy, Ingrid Espinoza, Dana Johnson, Jason Schallheim, Eldrin Bhanat, Yunyun Zhou, Jovanny Zabaleta, Gail Megason, Christian Gomez
Journal: Journal of Clinical Oncology (2017)

e22000 Background: B-Acute Lymphoblastic Leukemia (B-ALL) is the most common childhood cancer and the leading cause of death in children. Studies have shown that African-American (AA) children have significantly lower survival rates compared to European-American (EA) children. This disparity is not related to socioeconomic variables, suggesting a molecular basis for the lower survival. Here we present a study showing genetic aberrations (GA) involved in race-specific leukemogenesis and contribute to health disparities in B-ALL in AA and EA children. Methods: A total of 20 newly diagnosed pediatric patients were studied (5 AA and 15 EA) at University of Mississippi Medical Center. Ages range between 1 and 18 years with a median age of 4 years. None of the patients in our study had a relapse. Frozen bone marrow (BM) aspirates were used to extract DNA and whole-exome DNA sequencing was performed, focusing on race and B-ALL specific germ-line mutations. Results: Most GA were shared between AA and EA, for example those present in the Anaplastic Lymphoma Receptor Tyrosine Kinase (ALK) gene. Some genes with GA were specific to AA and others to EA. Genetic non-synonymous germ-line aberrations were identified such as, Lipoma Preferred Partner Gene, in AA and Leukemia Inhibitory Factor Receptor, in EA. Ingenuity pathway analysis revealed these genes clustered in race-specific canonical pathways. In AA, the pathways were related to telomerase signaling and cancer signaling. While in EA, it was related to stem cell pluripotency and hereditary cancer. Conclusions: The prevalence of GA in B-ALL may contribute to differences in outcomes between AA and EA children. Aberrant biological networks revealed by our study, will provide information on distinguishing signaling networks involved in race-specific leukemogenesis. Our study provides a strong basis to develop a race-specific prognostic assay for B-ALL in BM aspirates. In the future, this can help guide risk stratification and treatments based on race and advance the prognostication of B-ALL in AA children. Funding: Hyundai Hope on Wheels Scholar Grant, UMMC Division of Pediatric Hematology Oncology.
Oncoguide System: A computerized interactive assistance system for the diagnosis and treatment of CML/MPN and MDS D.
Authors: Dirk Hempel
Journal: Journal of Clinical Oncology (2016)

e18545 Background: The project aims to develop and implement a computerized interactive assistance system for the diagnosis and treatment of CML / MPN and MDS. The system is based on modulated, established medical guidelines with reference to the individual patient information. The user is navigated through the complex recommendations of current guidelines and decision trees of the CML/MPN and MDS, similar to a car navigation system. Methods: The medical user is hereby offered a systematic decision support. In addition, the decisions are documented and visualized in an intuitive user interface. The expert system is also able to point to currently recruiting therapy studies. Technical implementation and advantages of this solution: From a technical perspective, the knowledge-based system is implemented as a client-server architecture. The server acts as a central data storage, for example, in the form of a database. As a client, for example, Internet browsers can be used. So it is possible to centrally store the accumulated knowledge and to present the current research results to each user. The advantage of such a technical solution compared to guidelines-books is rapidly adaptable knowledge on new research results, as well as the implementation of a self-learning system. The system design has to pay particular attention to an intuitive user interface. On the server's side, the knowledge of guidelines and interviews with experts have to be formalized in an appropriate manner. There are approaches based on an ontological or logic-based modeling. Results: On the client's side the system suggests the user appropriate decisions for the diagnosis and further treatment of diseases. The underlying methodology is based on approaches from artificial intelligence, such as the Bayesian inference or machine learning methods. . Conclusions: The presented computerized interactive assistance system could help to increase the accuracy of diagnosis, treatment and follow up of CML/MPN and MDS
TCT-730 Distal Transradial Access in the Anatomical Snuffbox for Coronary Angiography as an Alternative Access Site For Faster Hemostasis: A Single-Center Registry
Authors: Shunsuke Aoi, Wah Wah Htun, Samuel Lee, Victor Alfaro, John Coppola, Samir Pancholy, Tak Kwan
Journal: Journal of the American College of Cardiology (2018)
Clinical utility of ICD‐11 diagnostic guidelines for high‐burden mental disorders: results from mental health settings in 13 countries
Authors: Geoffrey M. Reed, Jared W. Keeley, Tahilia J. Rebello, Michael B. First, Oye Gureje, José Luis Ayuso‐Mateos, Shigenobu Kanba, Brigitte Khoury, Cary S. Kogan, Valery N. Krasnov, Mario Maj, Jair de Jesus Mari, Pratap Sharan, Dan J. Stein, Min Zhao, Tsuyoshi Akiyama, Howard F. Andrews, Elson Asevedo, Majda Cheour, Tecelli Domínguez‐Martínez, Joseph El‐Khoury, Andrea Fiorillo, Jean Grenier, Nitin Gupta, Lola Kola, Maya Kulygina, Itziar Leal‐Leturia, Mario Luciano, Bulumko Lusu, J. Nicolás I. Martínez‐López, Chihiro Matsumoto, Mayokun Odunleye, Lucky Umukoro Onofa, Sabrina Paterniti, Shivani Purnima, Rebeca Robles, Manoj K. Sahu, Goodman Sibeko, Na Zhong, Wolfgang Gaebel, Anne M. Lovell, Toshimasa Maruta, Kathleen M. Pike, Michael C. Roberts, María Elena Medina‐Mora
Journal: World Psychiatry (2018)

In this paper we report the clinical utility of the diagnostic guidelines for ICD-11 mental, behavioural and neurodevelopmental disorders as assessed by 339 clinicians in 1,806 patients in 28 mental health settings in 13 countries. Clinician raters applied the guidelines for schizophrenia and other primary psychotic disorders, mood disorders (depressive and bipolar disorders), anxiety and fear-related disorders, and disorders specifically associated with stress. Clinician ratings of the clinical utility of the proposed ICD-11 diagnostic guidelines were very positive overall. The guidelines were perceived as easy to use, corresponding accurately to patients' presentations (i.e., goodness of fit), clear and understandable, providing an appropriate level of detail, taking about the same or less time than clinicians' usual practice, and providing useful guidance about distinguishing disorder from normality and from other disorders. Clinicians evaluated the guidelines as less useful for treatment selection and assessing prognosis than for communicating with other health professionals, though the former ratings were still positive overall. Field studies that assess perceived clinical utility of the proposed ICD-11 diagnostic guidelines among their intended users have very important implications. Classification is the interface between health encounters and health information; if clinicians do not find that a new diagnostic system provides clinically useful information, they are unlikely to apply it consistently and faithfully. This would have a major impact on the validity of aggregated health encounter data used for health policy and decision making. Overall, the results of this study provide considerable reason to be optimistic about the perceived clinical utility of the ICD-11 among global clinicians.