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https://www.readbyqxmd.com/read/28653573/the-future-of-immune-checkpoint-cancer-therapy-after-pd-1-and-ctla-4
#1
Andrew W Hahn, David M Gill, Sumanta K Pal, Neeraj Agarwal
The adaptive immune system plays an important role in eradicating malignant cells. Co-stimulatory and co-inhibitory signals to T cells though immune checkpoint receptors are involved in tumorigenesis and metastasis. Exploitation of immune checkpoint inhibitors, PD-1 and CTLA-4, with monoclonal antibodies has created impressive clinical responses. Many other immune checkpoint co-inhibitors and co-stimulators exist, including the B7 superfamily and tumor necrosis factor receptors superfamily. Here, we will examine co-inhibitors and co-stimulators beyond PD-1 and CTLA-4 that are being investigated in active clinical trials...
June 2017: Immunotherapy
https://www.readbyqxmd.com/read/28653458/left-ventricular-only-pacing-in-heart-failure-patients-with-normal-atrioventricular-conduction-improves-global-function-and-left-ventricular-regional-mechanics-compared-with-biventricular-pacing-an-adaptive-cardiac-resynchronization-therapy-sub-study
#2
Kevin V Burns, Ryan M Gage, Antonia E Curtin, John Gorcsan, Alan J Bank
AIMS: Right ventricular (RV) pacing can impair left ventricular (LV) function. When timed with native RV activation, LV-only pacing may cause greater improvements in LV function than biventricular pacing. This study compared the chronic effects of cardiac resynchronization therapy (CRT) on LV mechanics between biventricular pacing and LV-only pacing in patients with normal atrioventricular (AV) conduction. METHODS AND RESULTS: The Adaptive CRT (aCRT) algorithm provides LV-only pacing timed with native RV activation when the AV interval is normal (≤200 ms during sinus rhythm)...
June 26, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28653390/interventions-for-preventing-high-altitude-illness-part-1-commonly-used-classes-of-drugs
#3
REVIEW
Víctor H Nieto Estrada, Daniel Molano Franco, Roger David Medina, Alejandro G Gonzalez Garay, Arturo J Martí-Carvajal, Ingrid Arevalo-Rodriguez
BACKGROUND: High altitude illness (HAI) is a term used to describe a group of cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (8202 feet). Acute hypoxia, acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude. In this review, the first in a series of three about preventive strategies for HAI, we assess the effectiveness of six of the most recommended classes of pharmacological interventions...
June 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28652249/wee1-kinase-inhibitor-azd1775-has-pre-clinical-efficacy-in-lkb1-deficient-non-small-cell-lung-cancer
#4
Amanda L Richer, Jacqueline M Cala, Kelley O'Brien, Vashti M Carson, Landon J Inge, Timothy G Whitsett
G1/S checkpoint loss contributes to carcinogenesis and increases reliance upon the G2/M checkpoint for adaptation to stress and DNA repair, making G2/M checkpoint inhibition a target for novel therapeutic development. AZD1775, an inhibitor against the critical G2/M checkpoint protein WEE1, is currently in clinical trials across a number of tumor types. AZD1775 and DNA-damaging agents have displayed favorable activity in several pre-clinical tumor models, often in the molecular context of TP53 loss. Whether AZD1775 efficacy is modulated by other molecular contexts remains poorly understood...
June 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28651951/prolyl-hydroxylase-domain-inhibitors-as-a-novel-therapeutic-approach-against-anemia-in-chronic-kidney-disease
#5
Mai Sugahara, Tetsuhiro Tanaka, Masaomi Nangaku
Anemia is a common complication of chronic kidney disease and is mainly caused by the inability of injured kidneys to produce adequate amounts of erythropoietin. Studies elucidating the regulation of erythropoietin production led to the identification of hypoxia-inducible factor (HIF), which activates the transcription of genes that mediate adaptive responses to hypoxia. HIF is a heterodimer that consists of an α and β subunit. While HIF-β is constitutively expressed, HIF-α is subjected to ubiquitination and proteasomal degradation under normoxic conditions...
June 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28651620/an-assessment-of-the-factors-affecting-the-commercialization-of-cell-based-therapeutics-a-systematic-review-protocol
#6
David Pettitt, Zeeshaan Arshad, Benjamin Davies, James Smith, Anna French, Doug Cole, Kim Bure, Sue Dopson, David DiGiusto, Jeff Karp, Brock Reeve, Richard Barker, Georg Holländer, David Brindley
BACKGROUND: Cellular-based therapies represent a platform technology within the rapidly expanding field of regenerative medicine and are distinct from conventional therapeutics-offering a unique approach to managing what were once considered untreatable diseases. Despite a significant increase in basic science activity within the cell therapy arena, alongside a growing portfolio of cell therapy trials and promising investment, the translation of cellular-based therapeutics from "bench to bedside" remains challenging, and the number of industry products available for widespread clinical use remains comparatively low...
June 26, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28651368/risk-of-recurrence-in-pituitary-neuroendocrine-tumors-a-prospective-study-using-a-five-tiered-classification
#7
Gérald Raverot, Emmanuelle Dantony, Julie Beauvy, Alexandre Vasiljevic, Sara Mikolasek, Françoise Borson-Chazot, Emmanuel Jouanneau, Pascal Roy, Jacqueline Trouillas
Background: Most pituitary neuroendocrine tumors (PitNET) show benign behavior, but a significant number are invasive, recur or resist to medical treatment. Based on a retrospective case-control study we recently proposed a classification of PitNETs of prognostic relevance. This prospective study aims to test the value of this classification in an independent patient cohort. Methods: The cohort included patients of a single center operated upon a PitNET. Using a grading system based on invasion on MRI, immunocytochemical profile (ICC), Ki-67, mitotic index, and p53 positivity, tumors were classified...
June 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28650338/ifn-%C3%AE-related-mrna-profile-predicts-clinical-response-to-pd-1-blockade
#8
Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R Kaufman, Andrew Albright, Jonathan D Cheng, S Peter Kang, Veena Shankaran, Sarina A Piha-Paul, Jennifer Yearley, Tanguy Y Seiwert, Antoni Ribas, Terrill K McClanahan
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti-PD-1 therapies, including pembrolizumab. However, whether quantifying T cell-inflamed microenvironment is a useful pan-tumor determinant of PD-1-directed therapy response has not been rigorously evaluated...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28650240/development-of-a-clinical-spasticity-scale-for-evaluation-of-dogs-with-chronic-thoracolumbar-spinal-cord-injury
#9
Melissa J Lewis, Natasha J Olby
OBJECTIVE To develop a spasticity scale for dogs with chronic deficits following severe spinal cord injury (SCI) for use in clinical assessment and outcome measurement in clinical trials. ANIMALS 20 chronically paralyzed dogs with a persistent lack of hind limb pain perception caused by an acute SCI at least 3 months previously. PROCEDURES Spasticity was assessed in both hind limbs via tests of muscle tone, clonus, and flexor and extensor spasms adapted from human scales. Measurement of patellar clonus duration and flexor spasm duration and degree was feasible...
July 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28648318/translation-revision-and-validation-of-the-diabetes-distress-scale-for-indonesian-type-2-diabetic-outpatients-with-various-types-of-complications
#10
Bustanul Arifin S Farm, Dyah Aryani Perwitasari, Jarir At Thobari, Qi Cao, Paul F M Krabbe, Maarten J Postma
OBJECTIVES: To translate, revise, and validate the Diabetes Distress Scale (DDS) instrument for Indonesian type 2 diabetes mellitus (T2DM) outpatients with various complications. METHODS: Participants were recruited from four hospitals and two primary health care centers. The study was performed with forward and backward translations, an adaptation testing with a small subset of participants, and validation analysis. Factor analysis with maximum likelihood estimation and promax rotation was then used to investigate the instrument structure...
May 2017: Value in Health Regional Issues
https://www.readbyqxmd.com/read/28648312/the-emerging-role-of-patient-reported-outcomes-pros-in-clinical-trials-an-indian-perspective
#11
Amit Dang, Raju Kanukula, Chirag Shah, Veena Shetye
In an attempt to reduce costs of clinical trials and increase recruitments, pharmaceutical companies have been shifting their trials to offshore locations in Asia, Africa, the Middle East, Eastern Europe, and Latin America. Hence, methods for conducting clinical trials need to be adapted to the varying languages, cultures, ethnicities, and socioeconomic groups of these regions. This is of prime importance in the collection of patient-reported outcome (PRO) data. To ensure correct capturing of PRO data from multiregional sites, it is important that the tools for data collection are adapted to the respective cultures, and the data collected have the same interpretation across cultures (cross-cultural equivalence)...
May 2017: Value in Health Regional Issues
https://www.readbyqxmd.com/read/28648148/debt-counselling-for-depression-in-primary-care-an-adaptive-randomised-controlled-pilot-trial-decoder-study
#12
Mark B Gabbay, Adele Ring, Richard Byng, Pippa Anderson, Rod S Taylor, Caryn Matthews, Tirril Harris, Vashti Berry, Paula Byrne, Elliot Carter, Pam Clarke, Laura Cocking, Suzanne Edwards, Richard Emsley, Mauro Fornasiero, Lucy Frith, Shaun Harris, Peter Huxley, Siw Jones, Peter Kinderman, Michael King, Liv Kosnes, Daniel Marshall, Dave Mercer, Carl May, Debbie Nolan, Ceri Phillips, Tim Rawcliffe, Alexandra V Sardani, Elizabeth Shaw, Sam Thompson, Jane Vickery, Brian Wainman, Mark Warner
BACKGROUND: Depression and debt are common in the UK. Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer) aimed to assess the clinical effectiveness and cost-effectiveness of the addition of a primary care debt counselling advice service to usual care for patients with depression and debt. However, the study was terminated early during the internal pilot trial phase because of recruitment delays. This report describes the rationale, methods and findings of the pilot study, and implications for future research...
June 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28647010/social-skills-training-for-children-and-adolescents-with-autism-spectrum-disorder-a-randomized-controlled-trial
#13
Nora Choque Olsson, Oskar Flygare, Christina Coco, Anders Görling, Anna Råde, Qi Chen, Katarina Lindstedt, Steve Berggren, Eva Serlachius, Ulf Jonsson, Kristiina Tammimies, Lars Kjellin, Sven Bölte
OBJECTIVE: Social skills group training (SSGT) for children and adolescents with autism spectrum disorder (ASD) is widely applied, but effectiveness in real-world practice has not yet been properly evaluated. This study sought to bridge this gap. METHOD: This 12-week pragmatic randomized controlled trial of SSGT compared to standard care alone was conducted at 13 child and adolescent psychiatry outpatient units in Sweden. Twelve sessions of manualized SSGT ("KONTAKT") were delivered by regular clinical staff...
July 2017: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/28642569/no-evidence-that-bonding-is-needed-for-amalgam-restorations
#14
James R Keenan, Analia Veitz-Keenan
Data sourcesRelevant databases were searched for the review such as the Cochrane Oral Health Group Trials Register, Medline, EMBASE, clinical trials.gov, WHO International Clinical Trials Registry Platform.Study selectionRandomised controlled trials comparing adhesively bonded versus non-bonded class I and II amalgam restorations in permanent molars and premolars.Data extraction and synthesisTwo reviewers independently screened papers and extracted data.ResultsOne trial with 31 patients who received 113 restorations was included...
June 23, 2017: Evidence-based Dentistry
https://www.readbyqxmd.com/read/28641095/high-dose-chemotherapy-and-autologous-stem-cell-transplantation-in-relapsed-or-refractory-hodgkin-lymphoma-emerging-questions-newer-agents-and-changing-paradigm
#15
REVIEW
Saad Akhtar
Primary treatment for adult and pediatric patients with Hodgkin lymphoma (HL) using current multiagent anthracycline-based chemotherapy with or without radiation therapy will cure approximately >70% of the patients; >95% for early stage with a favorable risk profile and 70-75% with advanced stage and high risk features. Managing refractory and relapsed disease, however, remains a challenge. High dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage 40-70% of patients with relapsed or refractory HL...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28639296/pathways-to-professionalism-quality-improvement-care-pathways-and-the-interplay-of-standardisation-and-clinical-autonomy
#16
Graham P Martin, David Kocman, Timothy Stephens, Carol J Peden, Rupert M Pearse
Care pathways are a prominent feature of efforts to improve healthcare quality, outcomes and accountability, but sociological studies of pathways often find professional resistance to standardisation. This qualitative study examined the adoption and adaptation of a novel pathway as part of a randomised controlled trial in an unusually complex, non-linear field - emergency general surgery - by teams of surgeons and physicians in six theoretically sampled sites in the UK. We find near-universal receptivity to the concept of a pathway as a means of improving peri-operative processes and outcomes, but concern about the impact on appropriate professional judgement...
June 21, 2017: Sociology of Health & Illness
https://www.readbyqxmd.com/read/28638933/-implementation-status-of-regulation-eu-536-2014-in-the-member-states
#17
REVIEW
Elke Stahl
The upcoming Regulation EU 536/2014 for clinical trials of medicinal products for human use requires multinational cooperation in the assessment of clinical trial applications by the member states concerned as well as one single decision per member state concerned, supported by the new EU Portal and database system. The implementation makes national reorganisation of the processes necessary, especially coordination and cooperation between the national competent authorities and the ethics committees, necessary...
June 21, 2017: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
https://www.readbyqxmd.com/read/28636960/mechanisms-and-therapeutic-relevance-of-neuro-immune-communication
#18
REVIEW
Sangeeta S Chavan, Valentin A Pavlov, Kevin J Tracey
Active research at the frontiers of immunology and neuroscience has identified multiple points of interaction and communication between the immune system and the nervous system. Immune cell activation stimulates neuronal circuits that regulate innate and adaptive immunity. Molecular mechanistic insights into the inflammatory reflex and other neuro-immune interactions have greatly advanced our understanding of immunity and identified new therapeutic possibilities in inflammatory and autoimmune diseases. Recent successful clinical trials using bioelectronic devices that modulate the inflammatory reflex to significantly ameliorate rheumatoid arthritis and inflammatory bowel disease provide a path for using electrons as a therapeutic modality for targeting molecular mechanisms of immunity...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#19
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28630525/a-bayesian-adaptive-design-for-clinical-trials-in-rare-diseases
#20
S Faye Williamson, Peter Jacko, Sofía S Villar, Thomas Jaki
Development of treatments for rare diseases is challenging due to the limited number of patients available for participation. Learning about treatment effectiveness with a view to treat patients in the larger outside population, as in the traditional fixed randomised design, may not be a plausible goal. An alternative goal is to treat the patients within the trial as effectively as possible. Using the framework of finite-horizon Markov decision processes and dynamic programming (DP), a novel randomised response-adaptive design is proposed which maximises the total number of patient successes in the trial and penalises if a minimum number of patients are not recruited to each treatment arm...
September 2017: Computational Statistics & Data Analysis
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