tbuckley/cabot-search huggingface dataset:
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome Measures in Rheumatology Consensus‐Based Recommendations and Research Agenda for Use of Composite Measures and Treatment Targets in Psoriatic Arthritis
Authors: Laura C. Coates, Oliver FitzGerald, Joseph F. Merola, Josef Smolen, Leonieke J. J. van Mens, Heidi Bertheussen, Wolf‐Henning Boehncke, Kristina Callis Duffin, Willemina Campbell, Maarten de Wit, Dafna Gladman, Alice Gottlieb, Jana James, Arthur Kavanaugh, Lars Erik Kristensen, Tore K. Kvien, Thomas Luger, Neil McHugh, Philip Mease, Peter Nash, Alexis Ogdie, Cheryl F. Rosen, Vibeke Strand, William Tillett, Douglas J. Veale, Philip S. Helliwell
Journal: Arthritis & Rheumatology (2017)

A meeting was convened by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) to further the development of consensus among physicians and patients regarding composite disease activity measures and targets in psoriatic arthritis (PsA).Prior to the meeting, physicians and patients completed surveys on outcome measures. A consensus meeting of 26 rheumatologists, dermatologists, and patient research partners reviewed evidence on composite measures and potential treatment targets plus results of the surveys. The meeting consisted of plenary presentations, breakout sessions, and group discussions. International experts including members of GRAPPA and OMERACT were invited to the meeting, including the developers of all of the measures discussed. After discussions, participants voted on proposals for use, and consensus was established in a second survey.Survey results from 128 health care professionals and 139 patients were analyzed alongside a systematic literature review summarizing evidence. A weighted vote was cast for composite measures. For randomized controlled trials, the most popular measures were the PsA disease activity score (40 votes) and the GRAPPA composite index (28 votes). For clinical practice, the most popular measures were an average of scores on 3 visual analog scales (45 votes) and the disease activity in PsA score (26 votes). After discussion, there was no consensus on a composite measure. The group agreed that several composite measures could be used and that future studies should allow further validation and comparison. The group unanimously agreed that remission should be the ideal target, with minimal disease activity (MDA)/low disease activity as a feasible alternative. The target should include assessment of musculoskeletal disease, skin disease, and health-related quality of life. The group recommended a treatment target of very low disease activity (VLDA) or MDA.Consensus was not reached on a continuous measure of disease activity. In the interim, the group recommended several composites. Consensus was reached on a treatment target of VLDA/MDA. An extensive research agenda was composed and recommends that data on all PsA clinical domains be collected in ongoing studies.
Integration and expansion of palliative care work force.
Authors: Lynn Bowlby, Robin Turner, David Casarett, Fred Johnson, Ebony Boulware, Jason Webb, Morgan Bain
Journal: Journal of Clinical Oncology (2017)

126 Background: The specialty of Hospice and Palliative Medicine has grown out of the need for care of patients who are living longer with cancer and other serious illness and struggle with symptoms, decisions and care. Cancer patients and others often do not have access to Palliative Care services due to availability or accessibility of PC services. Since 2012, fellowship training is required for board eligibility but available programs do not meet the workforce need. As described by Weissman and Meier, viewing Palliative care services in the context of a primary, secondary or tertiary focus , allows for the expansion of these services outside of the traditional fellowship training. With additional intensive training, it is possible that experienced physicians can fill workforce gaps by providing primary palliative care in the providers practice area such as a clinic. Methods: The faculty member who will participate in a yearlong training program based in the Palliative Care Clinic is the Director of the Outpatient Clinic. This clinic is the center of the Duke resident ambulatory experience for the duration of their training. The complexity of these patients is high and often the DOC is the only place that these patients receive care. The Palliative Care training program will provide the faculty member the opportunity to see patients in the cancer center with board certified palliative care physicians. There will be 3 areas of focus for the trainee: clinical experience, didactic information and mentorship from a board certified palliative care provider around faculty identified cases from her own practice. Results: We have developed a yearlong intensive training program for experienced faculty to gain skills in Palliative Care. Conclusions: 1. It is hoped that this will allow for integration of primary palliative care into patient care areas where there is no formal palliative care program. 2. Integration of Palliative Care principles in the clinic to address symptoms of chronic severe illness as well as difficult conversations with more confidence and skill. 3. Earlier palliative care management–develop a systematic approach to assessing needs in high risk populations ie. Hospital Discharge reviews, now commonly done at the clinic.
Development and differentiation of early innate lymphoid progenitors
Authors: Christelle Harly, Maggie Cam, Jonathan Kaye, Avinash Bhandoola
Journal: The Journal of Experimental Medicine (2017)

Early innate lymphoid progenitors (EILPs) have recently been identified in mouse adult bone marrow as a multipotential progenitor population specified toward innate lymphoid cell (ILC) lineages, but their relationship with other described ILC progenitors is still unclear. In this study, we examine the progenitor–successor relationships between EILPs, all-lymphoid progenitors (ALPs), and ILC precursors (ILCps). Functional, bioinformatic, phenotypical, and genetic approaches collectively establish EILPs as an intermediate progenitor between ALPs and ILCps. Our work additionally provides new candidate regulators of ILC development and clearly defines the stage of requirement of transcription factors key for early ILC development.
Integration of palliative care into oncology: A curriculum development project.
Authors: Charles F. Von Gunten, Vj Periyakoil, Ally Brown, Ben Yzaguirre, Sam Spiegel, Andrew Paris, Stephen Bender, Jamie H. Von Roenn
Journal: Journal of Clinical Oncology (2017)

202 Background: Program Directors of Oncology Fellowships cite lack of adequate faculty to teach communication skills, prognostication and symptom management to oncology fellows as a barrier to ensuring oncologists integrate palliative care into their own practice. We partnered with ASCO and its Training Program directors to develop, evaluate and disseminate a PC curriculum using an innovative format. Methods: All of the fellows in a program were randomized as a single group to one of 3 cohorts: digital education, digital education plus a 4-week palliative care rotation or delayed digital education (control). In the intervention, each fellow received 2 MCQs (on their phones or other device) focused on a particular teaching point, every other day. If answered incorrectly, focused education material was forwarded to the learner and the testing point was retested at a later date. Fellows in cohort 2 also participated in a clinical rotation at an ACGME approved PC program. Cohort 3 received the same training as cohort one, but beginning fellowship year 2, as a delayed control. Fellows’ PC knowledge was assessed during the in-training exam pre- and post-intervention. Opioid prescribing behavior was tracked after graduation and compared with a control group( group 4). Results: 283 fellows from 71 programs were quasi-randomized. The average ITE score of PC MCQs ranged from 70-73% correct across all groups and all years, for pre- and post-test scores. All fellows randomized to the PC rotation, completed it. Prescribing data was based on NPI numbers and available for all providers. 72% of cohort 1 prescribed opioids appropriately, 57% cohort 2, 72% cohort 3, 46% in a group 4 (1 vs 4, p=.0008; 2 vs 4, p=.2231; 3 vs l, p=.0011). Conclusions: Spaced education via a hand held device is acceptable, efficient and cost-effective. All groups showed acceptable knowledge on the in-training examination. Yet, opioid prescribing behavior improved as a result of the education intervention. The favorable impact on opioid-prescribing behavior was extinguished by the PC rotation, raising the question about the role of a PC clinical rotation.
Surveillance de la résistance primaire aux antibiotiques de Helicobacter pylori en Angleterre et au Pays de Galles sur une période de six ans (2000-2005)
Authors: S A Chisholm, E L Teare, K Davies, R J Owen
Journal: Eurosurveillance (2007)

La resistance aux antibiotiques est un facteur essentiel dans l’echec des traitements visant a eradiquer Helicobacter pylori ; pourtant, il existe peu de programmes de surveillance des resistances au niveau local, national ou international.
Response to Comment on Farren et al. The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial. Diabetes Care 2017;40:759–763
Authors: Maria Farren, Michael J. Turner, Sean Daly
Journal: Diabetes Care (2017)

We thank Drs. Pintaudi and Di Vieste for their comments (1) on our article (2). They highlight diversity among our study cohort. However, we believe this does not explain the ineffectiveness of inositol in preventing gestational diabetes mellitus (GDM). First, of the 240 women, 151 had a family history of diabetes as their only risk factor, with 74 in the intervention group and 77 in the control group. The incidence of GDM was 17.6% in the intervention group compared with 10.4% in the control group ( P = 0.2). The authors highlight that most women in the study were Irish-born. The Irish population is increasingly diverse, and 39 women …
Impact of IQ on the diagnostic yield of chromosomal microarray in a community sample of adults with schizophrenia
Authors: Chelsea Lowther, Daniele Merico, Gregory Costain, Jack Waserman, Kerry Boyd, Abdul Noor, Marsha Speevak, Dimitri J. Stavropoulos, John Wei, Anath C. Lionel, Christian R. Marshall, Stephen W. Scherer, Anne S. Bassett
Journal: Genome Medicine (2017)

Schizophrenia is a severe psychiatric disorder associated with IQ deficits. Rare copy number variations (CNVs) have been established to play an important role in the etiology of schizophrenia. Several of the large rare CNVs associated with schizophrenia have been shown to negatively affect IQ in population-based controls where no major neuropsychiatric disorder is reported. The aim of this study was to examine the diagnostic yield of microarray testing and the functional impact of genome-wide rare CNVs in a community ascertained cohort of adults with schizophrenia and low (< 85) or average (≥ 85) IQ. We recruited 546 adults of European ancestry with schizophrenia from six community psychiatric clinics in Canada. Each individual was assigned to the low or average IQ group based on standardized tests and/or educational attainment. We used rigorous methods to detect genome-wide rare CNVs from high-resolution microarray data. We compared the burden of rare CNVs classified as pathogenic or as a variant of unknown significance (VUS) between each of the IQ groups and the genome-wide burden and functional impact of rare CNVs after excluding individuals with a pathogenic CNV. There were 39/546 (7.1%; 95% confidence interval [CI] = 5.2–9.7%) schizophrenia participants with at least one pathogenic CNV detected, significantly more of whom were from the low IQ group (odds ratio [OR] = 5.01 [2.28–11.03], p = 0.0001). Secondary analyses revealed that individuals with schizophrenia and average IQ had the lowest yield of pathogenic CNVs (n = 9/325; 2.8%), followed by those with borderline intellectual functioning (n = 9/130; 6.9%), non-verbal learning disability (n = 6/29; 20.7%), and co-morbid intellectual disability (n = 15/62; 24.2%). There was no significant difference in the burden of rare CNVs classified as a VUS between any of the IQ subgroups. There was a significantly (p=0.002) increased burden of rare genic duplications in individuals with schizophrenia and low IQ that persisted after excluding individuals with a pathogenic CNV. Using high-resolution microarrays we were able to demonstrate for the first time that the burden of pathogenic CNVs in schizophrenia differs significantly between IQ subgroups. The results of this study have implications for clinical practice and may help inform future rare variant studies of schizophrenia using next-generation sequencing technologies.
Efficacy and safety of CapeIRI plus bevacizumab therapy as a second-line treatment for patients with metastatic colorectal cancer
Authors: Y. Sunagawa, G. Nakayama, N. Hattori, K. Ezaka, H. Uda, S. Umeda, B. Sato, S. Yamada, H. Sugimito, M. Koike, Y. Kodera
Journal: Annals of Oncology (2017)
Optimizing lonafarnib treatment for the management of chronic delta hepatitis
Authors: Cihan Yurdaydin, Onur Keskin, Çağdaş Kalkan, Fatih Karakaya, Aysun Çalişkan, Ersin Karatayli, Senem Karatayli, A. Mithat Bozdayi, Christopher Koh, Theo Heller, Ramazan Idilman, Jeffrey S. Glenn
Journal: Hepatology (2017)

In a proof‐of‐concept (POC) study, the oral prenylation inhibitor, lonafarnib (LNF), decreased hepatitis D virus (HDV) RNA during 4 weeks of treatment. Here, we explored optimal LNF regimens. Fifteen patients (five groups; 3 per group) completed dosing as follows: (1) LNF 200 mg twice‐daily (BID; 12 weeks); (2) LNF 300 mg BID (12 weeks); (3) LNF 100 mg thrice‐daily (5 weeks); (4) LNF 100 mg BID + pegylated interferon alfa (PEG‐IFNα) 180 μg once‐weekly (QW; 8 weeks); and (5) LNF 100 mg BID + ritonavir (RTV) 100 mg once‐daily (QD; 8 weeks). Tolerability and efficacy were assessed. Higher LNF monotherapy doses had greater decreases in HDV viral load than achieved in the original POC study. However, this was associated with increased gastrointestinal adverse events. Addition of RTV 100 mg QD to a LNF 100 mg BID regimen yielded better antiviral responses than LNF 300 mg BID monotherapy and with less side effects. A similar improvement was observed with LNF 100 mg BID + PEG‐IFNα 180 μg QW. Two of 6 patients who received 12 weeks of LNF experienced transient posttreatment alanine aminotransferase (ALT) increases resulting in HDV‐RNA negativity and ALT normalization. Conclusion: The cytochrome P450 3A4 inhibitor, RTV, allows a lower LNF dose to be used while achieving higher levels of postabsorption LNF, yielding better antiviral responses and tolerability. In addition, combining LNF with PEG‐IFNα achieved more substantial and rapid HDV‐RNA reduction, compared to historical responses with PEG‐IFNα alone. Twelve weeks of LNF can result in posttreatment HDV‐RNA negativity in some patients, which we speculate results from restoring favorable immune responses. These results support further development of LNF with RTV boosting and exploration of the combination of LNF with PEG‐IFN. (Hepatology 2018;67:1224‐1236)
Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Hugh Calkins, Domenico Corrado, Frank Marcus
Journal: Circulation (2017)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ventricular arrhythmias and an increased risk of sudden cardiac death. Although structural abnormalities of the right ventricle predominate, it is well recognized that left ventricular involvement is common, particularly in advanced disease, and that left-dominant forms occur. The pathological characteristic of ARVC is myocyte loss with fibrofatty replacement. Since the first detailed clinical description of the disorder in 1982, significant advances have been made in understanding this disease. Once the diagnosis of ARVC is established, the single most important clinical decision is whether a particular patient’s sudden cardiac death risk is sufficient to justify placement of an implantable cardioverter-defibrillator. The importance of this decision reflects the fact that ARVC is a common cause of sudden death in young people and that sudden death may be the first manifestation of the disease. This decision is particularly important because these are often young patients who are expected to live for many years. Although an implantable cardioverter-defibrillator can save lives in individuals with this disease, it is also well recognized that implantable cardioverter-defibrillator therapy is associated with both short- and long-term complications. Decisions about the placement of an implantable cardioverter-defibrillator are based on an estimate of a patient’s risk of sudden cardiac death, as well as their preferences and values. The primary purpose of this article is to provide a review of the literature that concerns risk stratification in patients with ARVC and to place this literature in the framework of the 3 authors’ considerable lifetime experiences in caring for patients with ARVC. The most important parameters to consider when determining arrhythmic risk include electric instability, including the frequency of premature ventricular contractions and sustained ventricular arrhythmia; proband status; extent of structural disease; cardiac syncope; male sex; the presence of multiple mutations or a mutation in TMEM43; and the patient’s willingness to restrict exercise and to eliminate participation in competitive or endurance exercise.
Polymer nitric oxide donors potentiate the treatment of experimental solid tumours by increasing drug accumulation in the tumour tissue
Authors: M. Studenovsky, L. Sivak, O. Sedlacek, R. Konefal, V. Horkova, T. Etrych, M. Kovar, B. Rihova, M. Sirova
Journal: Journal of Controlled Release (2017)
P2.04-013 ElevatION:NSCLC-101 – A Phase 1b Study of PDR001 Combined with Chemotherapy in PD-L1 Unselected, Metastatic NSCLC Patients
Authors: J. Vansteenkiste, E. Felip, F. Shepherd, L. Paz-Ares, F. Barlesi, S. Burgers, C. Cai, F. Kiertsman, J. Scott, T. Mcculloch, Y.Y. Lau, D. Morgensztern
Journal: Journal of Thoracic Oncology (2017)
A molecular signature predictive of indolent prostate cancer (Science Translational Medicine (2013) 5, (203er9))
Authors: S Irshad, M Bansal, M Castillo-Martin, T Zheng, A Aytes, S Wenske, C Le Magnen, P Guarnieri, P Sumazin, M C Benson, M M Shen, A Califano, C Abate-Shen
Journal: Science Translational Medicine (2013)
A phase 1, open-label study to evaluate the safety and pharmacokinetics of the anti ErbB3 antibody, KTN3379, alone or in combination with targeted therapies in patients with advanced tumors.
Authors: Todd Michael Bauer, Jeffrey R. Infante, Joseph Paul Eder, Patricia LoRusso, Theresa LaVallee, Rich Gedrich, Carolyn Sidor, Gerald Steven Falchook
Journal: Journal of Clinical Oncology (2015)

2598 Background: KTN3379 is a human monoclonal antibody against a unique epitope of human epidermal growth factor receptor-3 (ErbB3) blocking ligand (neuregulin (NRG)) dependent and independent activation. This trial assessed safety and pharmacokinetics (PK) of KTN3379 alone or with each of four targeted agents in advanced cancers and evaluated potential biomarkers of KTN3379 activity. Methods: Part I evaluated KTN3379 in a single agent dose escalation design. Part II evaluated KTN3379 with each of cetuximab, erlotinib, vemurafenib and trastuzumab in patients with refractory SCCHN, CRC, NSCLC, melanoma and HER2+ breast cancer (n = 6 each). Dose limiting toxicities (DLT) were evaluated in the first treatment cycle, RECIST tumor measurements every 3rd treatment cycle and PK and blood pharmacodynamic (PD) assessments each treatment cycle. Archival tumor tissue was evaluated for biomarkers and correlated with KTN3379 activity. Results: In Part I, no DLTs were observed in the 16 patients treated with KTN3379 at doses of 5 up to its maximally administered dose of 20 mg/kg IV every 3 weeks. PK parameters were linear, supported every 3-week dosing, and trough blood levels following dosing of KTN3379 at 10-20 mg/kg were consistent with maximum antitumor activity in preclinical models. Grade 3 or higher treatment related AE was reported in 1 patient (diarrhea). Other treatment related AEs were low grade diarrhea (n = 5), mucositis (n = 3), rash (n = 3), anemia (n = 2), and fatigue (n = 2). Patients in Part II to date had a similar profile, with low grade diarrhea, mucositis and rash being the most common AEs. In both Parts, elevations of soluble ErbB3 were noted after treatment. Other blood biomarkers and NRG expression are being evaluated. The best tumor response to date has been stable disease. Conclusions: Doses of 10-20 mg/kg exceed target blood concentrations. KTN3379 doses of 20 mg/kg with other targeted agents are safe and PK supports 3-week dosing. KTN3379 has the potential to benefit patients in combination with other targeted agents against ErbB family members, and NRG may be a predictive biomarker of response to KTN3379 in future studies. Clinical trial information: NCT02014909.
Abstract 18818: Sodium Glucose Co-Transporter 1 (SGLT1) is a Novel Contributor to Cardiac Ischemia/Reperfusion (I/R) Injury Through PKC- and ERK-Dependent Mechanisms
Authors: Zhao Li, Lindsey Gifford, Ferhaan Ahmad
Journal: Circulation (2016)

Introduction: We have shown that AMP-activated protein kinase (AMPK) upregulates SGLT1, which contributes to cardiac ischemia/reperfusion (I/R) injury by activating NADPH oxidase 2 (Nox2). AMPK is ...
The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus
Authors: D M Nathan, S Genuth, J Lachin, P Cleary, O Crofford, M Davis, L Rand, C Siebert
Journal: New England Journal of Medicine (1993)

Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.
Brote de infecciones por Clostridium histolyticum en los usuarios de drogas inyectadas en Inglaterra y Escocia
Authors: J S Brazier, M Gal, V Hall, T E Morris
Journal: Eurosurveillance (2004)

Las infecciones por clostridios en los usuarios de drogas inyectadas en el Reino Unido representan un fenomeno relativamente reciente que aparecio en 2000 con la identificacion de casos de enfermedad grave y de fallecimientos debidos a Clostridium novyi. Entre diciembre de 2003 y abril de 2004, el laboratorio de referencia de anaerobios recibio doce aislamientos de un patogeno extremadamente raro, Clostridium histolyticum, procedente de usuarios de drogas inyectadas. Los aislamientos venian de nueve hospitales diferentes en Inglaterra y Escocia. La tipificacion molecular de los aislamientos por dos metodos diferentes de electroforesis en campo pulsado y ribotipificacion por PCR mostraron que todos ellos eran indistinguibles. Estos resultados indican una fuente comun de las infecciones, muy probablemente una partida de heroina recientemente distribuida en todo Reino Unido.
Effect of HIV-1 low-level viraemia during antiretroviral therapy on treatment outcomes in WHO-guided South African treatment programmes: a multicentre cohort study
Authors: Lucas E Hermans, Michelle Moorhouse, Sergio Carmona, Diederick E Grobbee, L Marije Hofstra, Douglas D Richman, Hugo A Tempelman, Willem D F Venter, Annemarie M J Wensing
Journal: The Lancet Infectious Diseases (2017)