tbuckley/cabot-search huggingface dataset:
Results of the Quad wild type arm of the AGITG ICECREAM study: A randomised phase II study of cetuximab alone or in combination with irinotecan in patients with refractory metastatic colorectal cancer with no mutations in <i>KRAS, NRAS, BRAF</i> or <i>PIK3CA</i>.
Authors: Jeremy David Shapiro, Subotheni Thavaneswaran, Craig Underhill, Kristy Pamela Robledo, Christos Stelios Karapetis, Fiona Lee Day, Louise M. Nott, Michael Jefford, Lorraine A. Chantrill, Nick Pavlakis, Niall C. Tebbutt, Timothy Jay Price, Mustafa Khasraw, Guy A. Van Hazel, Paul Michael Waring, Sabine Tejpar, John Simes, Val Gebski, Jayesh Desai, Eva Segelov
Journal: Journal of Clinical Oncology (2017)

3572 Background: Cetuximab (cet) increases survival in RAS wild-type (WT) metastatic colorectal cancer (mCRC) in first-line and chemorefractory patients (pts). Adding irinotecan (iri) to cet in refractory pts who had progressed on iri increased response and delayed progression in the BOND trial, which was conducted prior to recognition that RAS mutations are predictive of EGFR-inhibitor (EGFR-I) resistance. Subsequent trials in chemorefractory pts used single agent EGFR-I as standard. In the era of biomarker selection, the benefit of continuing iri versus single agent EGFR-I had not been resolved. Methods: ICECREAM is a randomised phase II trial evaluating cet v cet + iri in chemotherapy-refractory mCRC, stratified for KRAS G13D mutation (previously reported) or no mutations in KRAS, NRAS, BRAF and PI3KCA (Quad WT ). EGFR-I naïve, ECOG PS 0-1 pts, progressing within 6 months of iri and refractory (or intolerant) to fluoropyrimidine and oxaliplatin were randomised to cet 400mg/m 2 IV loading then 250mg/m 2 weekly +/- iri 180mg/m 2 q2 wks. The primary endpoint was progression-free survival at 6 months (6m PFS); secondary endpoints were response rate (RR), overall survival (OS), toxicity and quality of life (QOL). Results: From Nov 2012 to June 2016, 48 Quad WT pts were recruited: 2 ineligible (not iri-refractory, BRAF mutation) wre not included for analyses and a further 2 not evaluable for response. Characteristics were balanced between cet (n = 21) v cet-iri (n = 25), except for sex (male 62 v 72%) and primary site (left 95 v 68%). 6m PFS rate was 14% v 41%; HR 0.39 (95% CI: 0.20–0.78, p = 0.008). RR was 10% (2 PR) v 36% (1 CR, 8 PR); p = 0.04. Toxicities were higher with cet-iri; at least one grade 3/4 adverse event in 50 v 23%. No differences in global or specific QOL were seen. Conclusions: The AGITG ICECREAM trial confirms a significant synergy for the addition of iri to cet and improved PFS in Quad WT chemorefractory mCRC, echoing data in molecularly unselected pts. Clinical trial information: ACTRN12612000901808.
AB1243-HPR Using information-communication technologies and opportunities for telerehabilitation in occupational therapy
Authors: B Huzjan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The use of information and communication technology (ICT) in occupational therapy should allow management of chronic diseases by providing support programs in education including the use of multimedia services. <h3>Objectives</h3> In order to determine the presence of information and communication technologies use in the options of telerehabilitation, a survey was conducted 224 newly diagnosed patients with rheumatoid arthritis (RA). <h3>Methods</h3> The quantitative research approach was used with the newly created detected patients with RA treated on Department of Rheumatology at the University Medical Centre Ljubljana. The questionnaire included basic demographic information and questions about the use extent and possibilities for using ICT. The population also accounted for patients with RA diagnosed between 1 January 2014 and 31 December 2015. The data obtained was statistically analysed with the SPSS program IMB 20. The total of 64 survey questionnaires were completed, which represents 28% of the selected population. <h3>Results</h3> 23.4% RA patients don9t use internet. 48.4% RA patients use personal computers (PC), and 51.6% patients use smart phones. 35.3% of patients that use PC use it for e-mailing, searching health information (35.4%), video calls (13.3%) and sending messages (15%). Patients who use smart phones use them for calls (31.9%), texting and calls (26.7%), e-mailing (25%), searching health information (12.9%), and video calls (3.4%). There is a positive correlation between the use of modern ICT and the opinion that the interviewed patients would use telerehabilitation services during their rehabilitation. Pearson correlation coefficients are statistically significant with all the ICT. With using a PC (r =0.602) and smart phones (r =0.542) there is a medium strong positive correlation Positive coefficients indicate that the surveyed patients who are increasingly using ICT think they could help themselves with telerehabilitation. Increased frequency of ICT usage is associated with potentially greater possibility of using telerehabilitation. <h3>Conclusions</h3> The need for rapid access and exchange of information is the main reason for the use of information and communication technologies in healthcare, and is conditional for the development of e-health. Research provided answers questions about the possibilities of using information and communication technology and rehabilitation services at a distance – telerehabilitation in occupational therapy. <h3>Disclosure of Interest</h3> None declared
Thank you to our peer reviewers
Authors: Zoë Mullan
Journal: The Lancet Global Health (2017)

As the scholarly community recognises Peer Review Week, and to coincide with the Peer Review Congress in Chicago, IL, USA, we once again take the opportunity to name (appendix) and thank the legion of reviewers who have given up their time to make The Lancet Global Health a better journal over the past year. We do not have an elite pool of reviewers that we draw from—there are no tests to pass nor hands to shake. Anyone can be a reviewer as long as they have themselves published on a relevant topic in a peer-reviewed journal indexed in Scopus. Reviewing is not an easy job, and those with fewer options to receive high-quality mentoring may struggle. However, there are many free resources at hand, including the Committee on Publication Ethics' (COPE's) recently updated Ethical Guidelines for Peer Reviewers1Committee on Publication EthicsEthical guidelines for peer reviewers.https://publicationethics.org/resources/guidelines-new/cope-ethical-guidelines-peer-reviewersGoogle Scholar (also available in Mandarin) and the interactive courses and online lectures on Elsevier's Publishing Campus (some available in Portuguese). Peer review is an extremely valuable service to a journal and researchers who devote unpaid time to the role deserve credit. At The Lancet Global Health, we offer this modest public recognition, a 30-day complementary subscription to Scopus, and a small gift at the end of the year. Those who quite rightly point out that one cannot put these items on a curriculum vitae (resumé) can make use of the increasing number of reviewer recognition platforms (eg, Elsevier's). Thank you. I declare no competing interests. Download .pdf (.38 MB) Help with pdf files Supplementary appendix
Genomic determinants of response to pembrolizumab in head and neck squamous cell carcinoma (HNSCC).
Authors: Robert I. Haddad, Tanguy Y. Seiwert, Laura Quan Man Chow, Shilpa Gupta, Jared Weiss, Iris Gluck, Joseph Paul Eder, Barbara Burtness, Makoto Tahara, Bhumsuk Keam, Hyunseok Kang, Kei Muro, Andrew Albright, Lingkang Huang, Mark Ayers, Robin Mogg, Razvan Cristescu, Jonathan D. Cheng, Ranee Mehra
Journal: Journal of Clinical Oncology (2017)

6009 Background: Somatic mutational load (ML) is associated with response to anti CTLA-4 and PD-1/-L1 immunotherapies in select tumors, due to formation of neoepitopes not subject to central immune tolerance. Neoepitopes specific to HPV, EBV virus infection are also present in some HNSCC. An IFNγ gene expression profile (GEP) characteristic of tumor inflammation is also related to response to anti PD-1/-L1 therapy. This study evaluated relationships between ML and clinical outcome and independent predictive values of ML and GEP in patients with HNSCC treated with pembrolizumab. Methods: Whole exome sequencing (WES) and GEP were assessed in FFPE tumor specimens of patients with HNSCC (KEYNOTE 012; subsets of B1 [PD-L1 + , n = 34] and B2 [PD-L1 + / ‒ , n = 73] cohorts). ML, neoantigen load (NL), HPV/EBV status and clonality were assessed by standard WES analytical methods. GEP score is a weighted sum of normalized expression values of 18 genes. Statistical testing of ML and response, and ML and GEP relationship by HPV/EBV status was prespecified. Results: There were 73 patients identified as HPV ‒ and EBV ‒ (n = 25 in B1; n = 48 in B2). In HPV ‒ and EBV ‒ patients in B1 and B2 cohorts, respectively, associations between ML and objective response (OR) (P = 0.029 and 0.055; AUROC 0.89 and 0.63), and GEP and OR (P = 0.064 and 0.01; AUROC 0.82 and 0.74) were statistically significant. In combined cohorts of HPV ‒ and EBV ‒ patients, ML and GEP were significantly associated with OR (P = 0.009 and 0.002; AUROC 0.70 and 0.76, respectively). ML and GEP were only weakly correlated (r = 0.173). In a joint model, ML was significantly associated with response (p = 0.020) after adjusting for GEP (also significant, p = 0.006). NL and clonality weighted ML were also significantly associated with response (P = 0.026 and 0.006, respectively). In HPV + or EBV + subjects, OR association was not significant for ML, possibly due to a dominance of viral vs somatic neoepitopes; GEP was significant, likely due to tumor inflammation. Conclusions: ML and GEP are independently predictive of response to pembrolizumab in HPV ‒ /EBV ‒ patients with HNSCC; GEP was predictive regardless of viral status. ML and GEP may have utility in characterizing responses to anti PD-1 therapies and novel cancer regimens in HNSCC. Clinical trial information: NCT01848834.
AB0299 Atlantoaxial subluxation as a problem in patients with rheumatoid arthritis
Authors: S Misevska Percinkova, AA Kuchi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Atlantoaxial subluxation (AAS) is important and potentially life threatening complication of Rheumatoid arthritis (RA). It is defined when the space between odontoid process from C2 and arch of the atlas exceeds more than 3 mm. Instability in atlantoaxial joint may result with numerous neurological symptoms, compression of spinal cord and ultimately quadriparesis or quadriplegia. <h3>Objectives</h3> Aim of the study was to determine the frequency and the characteristics of atlantoaxial instability among our patients with RA and its dependence on the nature of the disease. <h3>Methods</h3> 92 outpatients from University Rheumatology Clinic in Skopje, with classical RA (ACR criteria 1988) were examined for the AAS. In all cases were analysed the duration of the disease, haematological and serological tests, disease activity (DAS 28), visual analogue scale (VAS) for the degree of articular pain and verbal rating scale (VRS).for cervical-occipital pain. All patients underwent native and functional x-ray, CT scan and MRI of cervical spine. A complete neurological examination was obtained, with SEP of the n. medianus et n. tibialis. <h3>Results</h3> Atlantoaxial instability, with expressed cervical-occipital symptomatology, occurred in 54 from 92 (58,69%) patients with RA. AAS appeared significantly more often in patients with longer duration of the disease (p&lt;0,0001), in cases with significant cervical-occipital pain (VRS p&lt;0,0001), with stronger joint pains (VAS), with higher values of SR (p=0,002), CRP (p=0,023), RF (p=0,000005), anti CCP (p=0,00003), and DAS 28 (p&lt;0,0001). Anaemia and thrombocytosis (p=0,0008) appeared significantly more in cases with AAS. Anterior AAS, (mostly combined with other types) was the most frequent type, presented in 41 participants (75,92%). In one case posterior AAS was detected, what is very rare finding. Positive SEP was significantly higher in the group with AAS <h3>Conclusions</h3> AAS is serious extra-articular manifestation of RA. Cervical subluxation may be a general anesthetic risk and risk for a neck injury. Routine cervical radiographs with the head in flexed position should be recommended in need of general anaesthesia and in situations with risk for a neck injury. <h3>Acknowledgements</h3> Rheumatoid arthritis, atlantoaxial subluxation. <h3>Disclosure of Interest</h3> None declared
TH1 signatures are present in the lower airways of children with severe asthma, regardless of allergic status
Authors: Julia A. Wisniewski, Lyndsey M. Muehling, Jacob D. Eccles, Brian J. Capaldo, Rachana Agrawal, Debbie-Ann Shirley, James T. Patrie, Lisa J. Workman, Alexander J. Schuyler, Monica G. Lawrence, W. Gerald Teague, Judith A. Woodfolk
Journal: Journal of Allergy and Clinical Immunology (2017)
AB0423 Minimally invasive surgical treatment of temporomandibular joint in patients with various rheumatic disorders
Authors: I Zaslavskiy, A Drobyshev, T Dubinina, S Erdes, A Kuznetsov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Currently, maxillofacial surgery to actively develop and improve minimally invasive surgical methods for the treatment of patients with diseases of temporomandibular joint (TMJ). These types of surgical treatments like arthroscopy and artrolavazh TMJ are less traumatic and therefore can be effective in patients with rheumatic pathology. <h3>Objectives</h3> To evaluate the efficacy of minimally invasive surgical treatment of TMJ in patients with rheumatic diseases (RD). <h3>Methods</h3> In the study were included 64 pts aged from 18 to 65 years with various rheumatic disorders and lesions of the TMJ. Of these, rheumatoid arthritis (RA) - 43 (67.2%), psoriatic arthritis (PsA) 11 (17.2%), systemic lupus erythematosus - 8 (12.5%) and ankylosing spondylitis (AS) - 2 (3.1%). Before and after 14 days, a month and 6 months after surgery were assessed the following parameters: the level of pain in the TMJ (VAS), the aperture of mouth opening. All the patients at baseline and at 6 months after treatment was performed MRI of the TMJ. Interpretation of the TMJ MRI studies performed by the presence of signs of pathological changes in the joint, which were scored according to the number of pathological signs (from 0 to 8 points). As a preparatory stage before surgery all patients – splint therapy during 1 month was performed. Surgery included arthrolavage and arthroscopy TMJ followed by the introduction of hyaluronic acid. <h3>Results</h3> Before treatment all patients had severe involvement of the TMJ by Wilkes international classification: III of St is 62.5%, IV – by 21.9%, V – 15,6%. 6 months after surgical treatment the level of pain in the TMJ decreased 9.8 times (from 4.9 to 0.5, p&lt;0,0001). Mouth opening increased 2.3 times (from 17.5 mm to 40.9 mm, p&lt;0,0001), was reached from 96.7% of patients normal value. In the control MRI study of the TMJ at 6 months after surgery, the quantity of signs of pathological changes in the joints were reduced by 2.7 times in comparison with the initial level. The best results were achieved in patients with RA and PsA. The lowest result was achieved in the group of patients with AS. <h3>Conclusions</h3> Minimally invasive methods of surgical treatment of TMJ (arthrolavage and arthroscopy), the most effective and appropriate for the treatment of patients with RD lesion of the temporomandibular joint. <h3>Disclosure of Interest</h3> None declared
Tyrosine kinase inhibition increases the cell surface localization of FLT3-ITD and enhances FLT3-directed immunotherapy of acute myeloid leukemia
Authors: K Reiter, H Polzer, C Krupka, A Maiser, B Vick, M Rothenberg-Thurley, K H Metzeler, D Dörfel, H R Salih, G Jung, E Nößner, I Jeremias, W Hiddemann, H Leonhardt, K Spiekermann, M Subklewe, P A Greif
Journal: Leukemia (2017)

The fms-related tyrosine kinase 3 (FLT3) receptor has been extensively studied over the past two decades with regard to oncogenic alterations that do not only serve as prognostic markers but also as therapeutic targets in acute myeloid leukemia (AML). Internal tandem duplications (ITDs) became of special interest in this setting as they are associated with unfavorable prognosis. Because of sequence-dependent protein conformational changes FLT3-ITD tends to autophosphorylate and displays a constitutive intracellular localization. Here, we analyzed the effect of tyrosine kinase inhibitors (TKIs) on the localization of the FLT3 receptor and its mutants. TKI treatment increased the surface expression through upregulation of FLT3 and glycosylation of FLT3-ITD and FLT3-D835Y mutants. In T cell-mediated cytotoxicity (TCMC) assays, using a bispecific FLT3 × CD3 antibody construct, the combination with TKI treatment increased TCMC in the FLT3-ITD-positive AML cell lines MOLM-13 and MV4-11, patient-derived xenograft cells and primary patient samples. Our findings provide the basis for rational combination of TKI and FLT3-directed immunotherapy with potential benefit for FLT3-ITD-positive AML patients.
AB1227-HPR Validation and applicability of a novel osteomalacia knowledge based educational instrument (OKQ)
Authors: S Robinson, R Waxman, D Walker, P Helliwell, A Adebajo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteomalacia is caused by a deficiency of vitamin D and can be corrected by changes in diet, lifestyle and supplementation. Consequently, it is a condition where education has a primary role in prevention. <h3>Objectives</h3> If educational interventions are to be developed and evaluated, then an instrument for measuring knowledge is required. This has led us to develop a novel Osteomalacia Knowledge Questionnaire (OKQ). <h3>Methods</h3> Based on nominal group technique, a steering group of people who are knowledgeable about osteomalacia, educational theory and questionnaire development was convened. The group decided to use true and false questions. Important areas of knowledge of osteomalacia were first determined by the group and then relevant statements which were true or false were written and grouped into 8 sections of 5 questions, each covering the different areas of knowledge. This resulted in a knowledge instrument with 40 questions in all. The questions were tested for utility and ambiguity in the group and modified and replaced accordingly. The questionnaire was then trialled in 37 people of South Asian origin (an osteomalacia susceptible population), in three groups. Participants were initially administered the OKQ and then received an educational intervention comprising a practitioner led education session on osteomalacia, including a presentation and written or electronic material. Participants were re tested with the OKQ after 6 weeks. Although there is no "gold standard" for measuring knowledge about osteomalacia, if effective, increased knowledge should lead to an increase in vitamin D (Vit D) levels and a decrease in parathormone (Pth) levels. Vitamin D and Parathormone levels were measured alongside the OKQ in 2 of the groups before and after the educational intervention <h3>Results</h3> Baseline knowledge about osteomalacia was low pre education averaging only 12.7 out of 40 (range 0–29) (n=37). A total of 30 participants (81%) attended for the follow up test. They averaged a score of 13.9 at baseline and 23.4 at follow up. This was statistically significant (p=0.002 Mann Whitney) and demonstrated sensitivity to change of the OKQ. Knowledge at baseline was correlated with vit D and Pth blood levels for two of the groups (n=27). This showed correlation coeficients of 0.128 and -0.407 respectively. For change of knowledge and change of parathormone (n=21) the r value was -0.324 suggesting a relationship between knowledge and Pth that is worthy of confirmation through further studies. <h3>Conclusions</h3> A novel questionnaire has been developed that has face validity for testing knowledge about osteomalacia. It has proved feasible and shown sensitivity to change. It has also shown promising correlation with biochemical measures of osteomalacia. <h3>Acknowledgements</h3> This study was funded by Arthritis Research United Kingdom. <h3>Disclosure of Interest</h3> None declared
Clarifying Confusion
Authors: Thomas Perneger, Michael J. Klag
Journal: Annals of Internal Medicine (1991)

Letters1 June 1991Clarifying ConfusionThomas Perneger, MD, MPH, Michael J. Klag, MD, MPHThomas Perneger, MD, MPHSearch for more papers by this author, Michael J. Klag, MD, MPHSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-114-11-991_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: By developing the new confusion assessment method (CAM), Inouye and colleagues (1) contributed a much-needed tool for clinicians and clinical epidemiologists who work with elderly patients. However, we are concerned that their conclusion that "because the CAM is highly sensitive, rapid, and simple, it may be useful for widespread, daily assessment of delirium in persons in high risk settings" may be premature.Although the CAM may take only 5 minutes to administer, it was based on at least a 20-minute assessment, including the Mini-Mental State Examination, the immediate story recall, an interview with another observer, and, at...Reference1. Inouyevan DyckAlessiBalkinSiegalHorwitz SCCSAR. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113:941-8. LinkGoogle Scholar1. Inouyevan DyckAlessiBalkinSiegalHorwitz SCCSAR. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990;113:941-8. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Johns Hopkins Medical Institutions Baltimore, MD 21205 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1991Volume 114, Issue 11Page: 991-992KeywordsClinical epidemiologyDeliriumElderlyMini mental state examination Issue Published: 1 June 1991 PDF downloadLoading ...