bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/III trial of atezolizumab with carboplatin and etoposide in ES-SCLC in first-line setting (IMpower133).
Authors: Horn Leora , Mansfield Aaron Scott , Reck Martin , Mok Tony , Spira Alexander I. , Tang Xiongwen , Lam Sivuonthanh , Kabbinavar Fairooz F. , Lopez-Chavez Ariel , Sandler Alan , Liu Stephen V. 
Published: September 2018

TPS8584 Background: The first-line standard of care for the majority of patients (pts) with extensive-stage small-cell lung cancer (ES-SCLC) is platinum-based chemotherapy with etoposide, but survival outcomes remain poor (median OS, < 1 year) despite initial response rates ranging from 50-70%. Atezolizumab (atezo), an anti–PD-L1 mAb, prevents the binding of PD-L1 with its receptors PD-1 and B7.1 and restores anticancer T-cell activity. Tolerable safety with promising durability of response has been shown with atezo in pts with ES-SCLC: confirmed ORR was 6% (n = 1/17 [partial response]; DOR of 7 mo) by RECIST v1.1 and 24% by immune-related response criteria (irRC; n = 4/17, with 2 pts on atezo for ≥ 12 mo). Preliminary data also indicate the potential synergy between atezo and platinum-based chemotherapy in NSCLC, whereby durable responses may translate into improved survival over atezo alone. IMpower133 (NCT02763579), a global, Phase I/III, randomized, multicenter, double-blinded, placebo-controlled trial will evaluate the efficacy and safety of 1L atezo + carboplatin + etoposide compared with placebo + carboplatin + etoposide in treatment-naive pts with ES-SCLC. Methods: Pts with measurable (RECIST v1.1) ES-SCLC, who have ECOG PS 0-1 and no prior systemic anticancer treatment, are eligible for the study. Exclusion criteria include untreated CNS metastases and history of autoimmune disease. The study requires submission of tumor tissue, but pts will be enrolled regardless of biomarker status. Pts will be stratified by sex, ECOG PS and presence of treated brain metastases. Eligible pts will be randomized 1:1 to receive four 21-day cycles of atezo (1200 mg IV) or placebo in combination with carboplatin (AUC 5 mg/mL/min IV, d 1) and etoposide (100 mg/m2 IV, d 1-3), followed by maintenance therapy with atezo or placebo until PD per RECIST v1.1. Pts can continue with treatment until persistent radiographic PD, symptomatic deterioration or unacceptable toxicity. Co-primary endpoints are investigator-assessed PFS per RECIST v1.1 and OS. Secondary efficacy endpoints include investigator-assessed ORR and DOR. Safety and tolerability will also be assessed. Approximately 400 pts will be enrolled. Clinical trial information: NCT02763579.
NIVORAD: A randomised phase 2 trial of nivolumab and stereotactic ablative body radiotherapy in advanced non-small cell lung cancer, progressing after first or second line chemotherapy.
Authors: Mitchell Paul , Siva Shankar , Kok Peey Sei , O'Byrne Ken , Yeung Annie , Livingstone Ann , Donoghoe Mark , Yip Sonia , Stockler Martin R. ,   Australasian Lung Cancer Trials Group (ALTG)
Published: September 2018

TPS9097 Background: Recent data has demonstrated improvements in overall survival in patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab. Radiation may augment the immune response through abscopal effects - evidence of tumour control at sites other than those irradiated. We hypothesize that the addition of stereotactic ablative body radiotherapy (SABR) to immunotherapy with nivolumab will improve progression free survival (PFS) compared with nivolumab alone. Methods: DESIGN: Open label, randomised phase II trial with 25 sites across Australia and New Zealand. ELIGIBILITY: Metastatic NSCLC progressing after 1 or 2 lines of chemotherapy with an extrapulmonary metastasis suitable for SABR. STRATIFICATION: Age, lines of chemotherapy, histology and treating institution. TREATMENT: A single dose of SABR (18-20Gy) plus nivolumab or nivolumab alone (240mg 2-weekly) given until disease progression or prohibitive adverse events. ENDPOINTS: PFS at 6 months (PFS6; primary), objective tumour response rate, adverse events, overall survival, PFS at 1 and 2 years. Tertiary correlative objectives include associations between possible prognostic/ predictive biomarkers and outcomes (including PD-L1 expression). STATISTICS:Total sample size of 120 participants allocated in a ratio of 2:1, 80 to nivolumab + SABR and 40 nivolumab alone to provide 80% power, one-sided type I error rate of 5% for PFS6 of 50% (worthy of pursuit) vs 35% (not worthy of pursuit). BIOSPECIMENS: Tumour tissue and serial bloods (4 time points) will be collected for translational research. CURRENT ENROLLMENT (as of Feb 2017): 2 out of 20 sites are open. NIVORAD is an investigator-initiated, cooperative-group trial led by the ALTG in collaboration with the NHMRC Clinical Trials Centre, University of Sydney and the Trans Tasman Radiation Oncology Group (TROG). Australian New Zealand Clinical Trials Registry: ACTRN12616000352404.
Design of ALTA-1L (ALK in lung cancer trial of brigatinib in first-line), a randomized phase 3 trial of brigatinib (BRG) versus crizotinib (CRZ) in tyrosine kinase inhibitor (TKI)-naive patients (pts) with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
Authors: Tiseo Marcello , Popat Sanjay , Gettinger Scott N. , Peters Solange , Haney Jeff , Kerstein David , Camidge D. Ross 
Published: September 2018

TPS9098 Background: BRG is an investigational, next-generation ALK inhibitor with potent preclinical activity against rearranged ALK and CRZ-resistant mutants. In an ongoing phase 1/2 trial, BRG has shown promising intracranial and whole-body activity in ALK+ NSCLC pts with or without prior CRZ therapy ( Lancet Oncol. 2016;17:1683-96). In an ongoing pivotal randomized phase 2 trial (ALTA) evaluating 2 BRG regimens (90 mg qd and 180 mg qd with a 7-d lead-in at 90 mg), BRG has shown substantial objective response rates (ORRs) and robust progression-free survival (PFS) in pts with CRZ-resistant ALK+ NSCLC, particularly at 180 mg (with lead-in), and acceptable safety ( J Thorac Oncol. 2017;12:S612-3). Based on these results, the ALTA-1L trial was designed to assess the efficacy and safety of BRG vs CRZ in pts with advanced ALK+ NSCLC naive to TKI therapy (including ALK inhibitors). Methods: ALTA-1L (NCT02737501) is an open-label, multicenter, randomized phase 3 trial. Pts (≥18 y of age) are required to have locally advanced or metastatic ALK+ NSCLC, no prior TKI therapy, and ≤1 prior systemic anticancer regimen in the advanced setting. Approximately 270 pts will be stratified by presence of brain metastases at baseline and prior chemotherapy (yes/no) and randomized 1:1 to receive oral BRG (180 mg qd with a 7-d lead-in at 90 mg) or CRZ (250 mg bid). The primary endpoint is PFS per RECIST v1.1 assessed by a blinded independent review committee (BIRC); secondary endpoints include ORR, duration of response, overall survival, safety/tolerability, pt-reported outcomes, and intracranial ORR/PFS. The primary endpoint will be analyzed with the Kaplan-Meier method and a 2-sided stratified log-rank test after 198 events; 2 interim analyses are planned after approximately 50% and 75% of expected events. CRZ-treated pts may cross over to BRG (180 mg [with lead-in]) after BIRC-assessed disease progression. ALTA-1L was initiated in April 2016; 150 sites are planned in North America, Europe, and the Asia-Pacific region. 97 pts were enrolled as of February 6, 2017. Clinical trial information: NCT02737501.
B-F1RST: Assessment of novel blood-based biomarkers in patients with first-line advanced or metastatic NSCLC receiving atezolizumab monotherapy.
Authors: Kim Edward S. , Socinski Mark A. , Dakhil Shaker R. , Mackler Niklas J. , Ikhlaque Nadeem , Mekhail Tarek , Volterra Fabio , El Khoury Christian Antoine , Schiller Joan H. , Tsai Michaela L. , Hayek Fadi , Neidhart Jeffrey D. , Hunis Brian , Hu Sylvia , Paul Sarah M. , Shames David S. , Phan See-Chun , Yun Cindy , Velcheti Vamsidhar 
Published: September 2018

TPS9103 Background: The anti–PD-L1 monoclonal antibody atezolizumab inhibits the interaction of PD-L1 with its receptors PD-1 and B7.1, thereby restoring T-cell immunity. In the Phase III OAK study, patients with previously treated advanced NSCLC had improved mOS in the atezolizumab arm (13.8 mo) vs the docetaxel arm (9.6 mo) (HR 0.73 [95%CI: 0.62, 0.87]; P= 0.0003), irrespective of PD-L1 expression or histology. A Phase III clinical trial of atezolizumab monotherapy for first-line, PD-L1–selected patients with NSCLC is underway; however, first-line atezolizumab monotherapy for NSCLC treatment in a biomarker-unselected population has not yet been investigated. Current assays to measure PD-L1 expression by IHC require tumor biopsies, which can be difficult to obtain in some patients. Novel blood-based biomarkers will be evaluated retrospectively in B-F1RST (Blood-First-Line Ready Screening Trial) in patients receiving atezolizumab monotherapy in first-line NSCLC. Methods: A Phase II, open-label, single-arm study, B-F1RST (NCT02848651), will evaluate the efficacy and safety of atezolizumab in PD-L1–unselected patients with first-line locally advanced or metastatic NSCLC. Eligibility criteria include stage IIIB-IVB NSCLC, ECOG PS 0-1, measurable disease per RECIST v1.1 and adequate hematologic and end-organ function. Exclusion criteria include the presence of EGFRmutations or ALKfusions, active CNS metastases and prior immunotherapy for NSCLC. Patients will receive atezolizumab 1200 mg IV q3w until disease progression or loss of clinical benefit. Prospective collection of blood samples is mandatory; collection of tissue biopsies is optional. The co-primary endpoints of the study are investigator-assessed ORR per RECIST v1.1 for the efficacy objective and PFS per RECIST v1.1 for evaluating blood-based predictive biomarkers for atezolizumab efficacy, including mutation status. Approximately 150 patients will be enrolled at 25 or more centers in the United States. Clinical trial information: NCT02848651.
CARSKIN: Pembrolizumab as first line therapy in patients with unresectable cutaneous squamous cell carcinoma (cSCC).
Authors: Maubec Eve , Helfen Sabine , Scheer-Senyarich Isabelle , Boubaya Marouane , Schischmanoff Olivier , Alloux Céline , Deschamps Lydia , Petrow Peter , Lopez Isabelle , Tibi Annick , Levy Vincent ,   GCC
Published: September 2018

TPS9596 Background: Treatment options are limited for patients (pts) with locally advanced or metastatic cSCCs. Cisplatin-based combinations have some efficacy but their toxicity often prohibits their use, particularly for the elderly. New therapeutic options are needed. Tumors divert the programmed death receptor 1 (PD-1) pathway suppressing immune control. Pembrolizumab (MK-3475) is a high-affinity humanized monoclonal anti-PD-1 antibody. It leads to dual PD-1 ligand (PD-L1 and PD-L2) blockade that may reactivate the immune surveillance and elicit anti-tumor response. It has antitumor activity in several tumors including head and neck SCCs. Moreover, an efficacy of pembrolizumab in cSCCs has been reported recently in a series of 6 cases. Methods: CARSKIN (ClinicalTrials.gov, NCT02883556) is a French multicenter, open-label, nonrandomized phase 2 trial, designed to evaluate the efficacy and safety of pembrolizumab in 39 pts with unresectable and/or metastatic cSCCs, naive of chemotherapy and of EGFR inhibitors. Pembrolizumab is administered (200 mg IV Q3W) for up to 24 months or until disease progression or unacceptable toxicity. Eligible pts must undergo a baseline biopsy of the tumor prior to treatment for PD-L1 evaluation. Response is to be assessed at baseline, wk 9, 15 and 24, and thereafter Q12W by central radiology review per RECIST 1.1 and per modified RECIST v1.1. The primary objective is response rate (RR) at wk 15 per RECIST 1.1. Secondary efficacy objectives are to assess whether patients with PD-L1+ tumors have a better RR than the whole sample at wk 15 and to assess in the whole sample and in PD-L1+ pts, disease control rate (DCR) at wk15, RR at wk 24, best RR, overall survival (OS), progression free survival (PFS), duration of response / control and time to disease progression. A Simon optimal two-stage design will be used. Four responders among 19 pts will be needed in the 1st step to continue the trial. Overall 9 responses will be needed to conclude the effectiveness. Kaplan-Meier statistics will assess PFS and OS. Adverse events (AEs) will be assessed throughout the study and for 30 d thereafter (6 m for serious AEs) and graded per NCI CTCAE v4.0. Clinical trial information: NCT02883556.
Advanced clinical practitioners in emergency care: past, present and future
Authors: Crouch Robert , Brown Ruth 
Published: September 2018

Developing a consistent and skilled workforce is critical to the sustainability of any clinical service. Nurses and paramedics have formed part of the emergency care workforce for many years and the extended role of these staff groups has supported patient care as the demand has risen and outstripped the capacity of the medical staff. In many hospitals and health-care systems, these extended roles have developed in response to local demand and case mix, resulting in inconsistent role descriptions and lack of transportable qualifications. Even for established roles such as emergency nurse practitioners, there is no UK-wide defined scope of practice or curriculum to support the role. In 2014 a joint working group of the Royal College of Emergency Medicine and Health Education England agreed a programme of work to support a sustainable emergency care workforce. One stream of that work focused on developing non-medical roles within emergency care and in particular the role of the advanced clinical practitioner in emergency medicine. Advanced practice has developed in the UK in many specialties and the new advanced practice framework from Health Education England (2017) allows a cross-discipline understanding of the principles and key aspects of advanced practice. However, this framework is naturally generic and does not focus on what a practitioner is capable of within a specific clinical area, but more on the core capabilities. This article outlines the development of a UK-wide curriculum and credentialing process for emergency care advanced clinical practitioners and reports on progress to date.
MRI and sonography in Legg-Calvé-Perthes disease: Clinical relevance of containment and influence on treatment
Authors: Jandl N. M. , Schmidt T. , Schulz M. , Rüther W. , Stuecker M. H. F. 
Published: September 2018

Purpose The containment orientated treatment of Legg-Calvé-Perthes disease (LCPD) affected hip joints is broadly accepted in the literature. The prerequisite is early recognition of loss of containment. An often-used quantitative MRI containment parameter is the cartilaginous acetabulum-head-index (CAHI). Based on ultrasound (US), we analyzed the newly created ‘femoral head extrusion angle’ (HA) as a containment parameter in comparison with the CAHI in severe LCPD. Methods In a prospective study with 40 children (mean age 5.8 years sd 2.3) with unilateral LCPD classified as Catterall group III/IV, we measured the CAHI versus HA to assess the containment of the femoral head. HA in US was determined by the tangent from the bony acetabular rim to the cartilaginous cranio-lateral femoral head. Results The HA was significantly higher in LCPD-affected hip joints (25° sd 7°) than in healthy ones (13° sd 5°; p < 0.001). Correlation analysis of all hip joints revealed a significant correlation between HA and CAHI (r = −0.69; p < 0.001). Hip joints with a low CAHI indicating loss of containment showed a higher HA in sonography. Conclusion The results of our study suggest that the HA in US is a reliable containment parameter in severe LCPD with a HA > 22° defining a pathologic value. In comparison with the CAHI, HA measurement in ultrasound is easier than the assessment of various parameters to calculate an index. Frequent sonographical follow-up assessment in critical joints is an alternative if MRI is not available, helping to detect an impending loss of containment early enough. Level of Evidence Level II
Aspects of ecological anatomy of Traganum nudatum Del. (Amaranthaceae) from the Northeast of the Algerian Sahara
Authors: Kherraze Mohamed Elhafed , Belhamra Mohamed , Grigore Marius-Nicuşor 
Published: September 2018

This study focuses on the anatomical strategies developed by the Traganum nudatum Del., prevalent in the Algerian Sahara, particularly in the region of Oued Righ, which allows to this species to survive in a harsh environment (aridity and salinity). The anatomical structure of this species was studied using fresh materials (roots, stems and leaves). These materials have been collected from several individuals in different saline habitats. Some interesting features such as successive cambia phenomenon, calcium oxalate crystals, Kranz anatomy (salsoloid subtype), succulence, low stomata density, low stomata index, the presence of the papillae, paracytic stomata and other structures have been noticed. We can conclude that the ecological significance of evidenced adaptations by T. nudatum is supported in this article by the analysis of adaptations of other species belonging either to the Amaranthaceae or to other botanical families; and that this adaptation has no link with botanical families. In these species, the key adaptation is the ability to maintain growth processes and water saving under difficult living conditions (high summer temperatures or salty soils), regardless of the evolutionary level of the taxon.
Standard for the Development of Competition as a Special Model of Antitrust Policy at the Regional Level
Authors: RODIONOVA Daria Nikolaevna , BAZAROV Alexey Tsyrenovich , MUNKUEVA Irina Sergeevna , TSYRENOV Dashi Dashanimaevich , TULOKHONOV Oleg Sergeevich 
Published: September 2018

Abstract:
The aim of this paper is to study the nature and sense of the antitrust policy of the state from the perspective of introduction of a special policy document –the Standard for the Development of Competition in the Administrative Regions of the Russian Federation (SDCAR). The article covers the specifics and the importance of governing competitive relations in the market business environment; the data on the Republic of Buryatia are considered as working material. The methodological basis of the study is the systematic approach, a comprehensive study of the competitive relationships governance practices. The authors analyzed measures to develop and strengthen competition parameters in the region, carried out in accordance with the provisions of the SDCAR. The article describes the algorithm for implementation of activities, adapting the concept on improvement of the quality of assessment of the antitrust regulation efficiency in connection with business entities. The authors identified a set of factors that influence the formation of the approaches to implementation of competition policy in Buryatia. The conclusions and recommendations offered herein can be used by federal and regional authorities in the development and adoption of laws and other regulations on the formation of a favorable competitive environment; by municipal authorities – in the analysis and monitoring of the status and development of the local competitive environment in the area.
Current Trends in the Financial Market Development
Authors: ZATSARINNYI Еlena I. , MALYKH Natalya I. , SEVERINA Yulia N. , GENDON Angelica L. , MINNULLINA Anna Yu. , MALYSHENKO Kostyantyn A. 
Published: September 2018

The paper shows that the modern tendencies of financial market based on the possibility of stratification and infrastructural development of the economy as a whole. The authors found that special attention should be given to development of infrastructural support from the state, and the formation of technological trends in the structure of public consumption.
The article indicates that financial market conditions are set on the basis of the calculation of both financial and investment risks, which facilitate the effective use of capital. The authors note a trend in which the rapid processes of globalization have transformed the infrastructure of the financial market on one of the dominant redistribution of capital not only within national economies but also on a global scale. It is established that financial market participants form a functional component of infrastructure capacity because of accumulation of financial resources has a functional purpose. The functional component of the infrastructural capacity of the financial market is in the process of transformation. This is a withdrawal from the market of a number of financial intermediaries, reduced the volume of assets of financial institutions, reduced demand for their services, which in the long run it will escalate the competition for the consumer between them. This will stimulate the emergence of new financial services and will contribute to the infrastructural capacity of the financial market.
The Choosing Wisely initiative and laboratory test stewardship
Authors: Baird Geoffrey S. 
Published: September 2018

Abstract
The United States Choosing Wisely initiative was started in 2012 by the American Board of Internal Medicine Foundation and focused on reducing medical resource overutilization. Since its inception in the US, similar efforts have arisen in at least a dozen countries. Strongly patient-focused, and in fact started in collaboration with the consumer magazine Consumer Reports, the effort has resulted in a collection of greater than 500 recommendations from over 80 US professional societies intended to inform both patients and doctors about medical practices whose necessity should be questioned or discussed. Targets of recommendations include practices that lack a basis in scientific evidence, practices that may be duplicative of other care already received, practices that may be harmful and practices that are simply unnecessary. While critiques have been levied against the Choosing Wisely initiative over its intent, methods and efficacy, it is clear that many of its recommendations have been adopted by large medical practices, and several positive outcomes, i.e. reductions in perceived waste, have been reported in relation to many of the recommendations, including those specifically targeting laboratory tests. The future success of Choosing Wisely will likely hinge on whether or not significantly positive and durable outcomes can be demonstrated, especially at a time where there is increasing pressure to drive down costs in medical care while concomitantly increasing quality.