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Surrogate endpoints

Anke E Kip, Monique Wasunna, Fabiana Alves, Jan H M Schellens, Jos H Beijnen, Ahmed M Musa, Eltahir A G Khalil, Thomas P C Dorlo
The Leishmania parasite resides and replicates within host macrophages during visceral leishmaniasis (VL). This study aimed to evaluate neopterin, a marker of macrophage activation, as possible pharmacodynamic biomarker to monitor VL treatment response and to predict long-term clinical relapse of VL. Following informed consent, 497 plasma samples were collected from East-African VL patients receiving a 28-day miltefosine monotherapy (48 patients) or 11-day combination therapy of miltefosine and liposomal amphotericin B (L-AMB, 48 patients)...
2018: Frontiers in Cellular and Infection Microbiology
C L Batlevi, A Younes
No abstract text is available yet for this article.
June 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Vera Hirsh, Yin Wan, Fang-Ju Lin, Sandra Margunato-Debay, Teng Jin Ong, Marc Botteman, Corey Langer
BACKGROUND: First-line nab-paclitaxel/carboplatin was associated with a significantly improved overall response rate (primary endpoint) versus paclitaxel/carboplatin in a phase III trial of advanced non-small-cell lung cancer (NSCLC). We report the results of an analysis evaluating the correlation of response and the time to response with survival and quality-adjusted outcomes. PATIENTS AND METHODS: Using a landmark approach, progression-free survival (PFS), overall survival (OS), and quality-adjusted time without symptoms or toxicity (Q-TWiST) were compared between patients with a confirmed partial or complete response at or before 6 weeks (≤ 6-week responders) and those without (≤ 6-week nonresponders)...
May 7, 2018: Clinical Lung Cancer
Matthew W McCarthy, Thomas J Walsh
Clinical trials for invasive pulmonary aspergillosis, a potentially lethal mold infection, are complex investigations that require protracted time and extensive resources, delaying the development of new antifungal agents for this important disease. Areas Covered: In this paper, the authors examine a novel approach to study invasive pulmonary aspergillosis in humans, with a focus on the potentials and pitfalls of surrogate endpoints such as galactomannan antigenemia to evaluate therapeutic response to novel compounds...
June 13, 2018: Expert Review of Molecular Diagnostics
Arndt H Kiessling, Harald Keller, Anton Moritz
OBJECTIVES: Minimal extracorporeal circulation techniques and systems (MiECC) may reduce the negative side effects of conventional extracorporeal circulation (ECC). However, it is still unclear as to what this is caused by, the reduced priming volume and hemodilution, or the avoidance of blood-air contact and dispersion of mediastinal debris into the systemic circulation. The aim of the trial was the comparison of MiECC to an open ECC setup (openECC) or a system with reduced blood air and debris interaction (closeECC)...
May 16, 2018: Heart Surgery Forum
Areg Grigorian, Nii-Kabu Kabutey, Sebastian Schubl, Christian de Virgilio, Victor Joe, Matthew Dolich, Dawn Elfenbein, Jeffry Nahmias
BACKGROUND: Blunt carotid and vertebral artery injury, collectively termed blunt cerebrovascular injury occur in less than 1% of blunt traumas. Conventional indications for screening miss up to 20% of blunt cerebrovascular injuries. Therefore, the expanded Denver criteria were created in 2012. We hypothesized the introduction of the expanded Denver criteria would lead to an increase in the national detection of blunt cerebrovascular injury with a subsequent decrease in stroke rate. METHODS: The National Trauma Data Bank was queried for blunt trauma admissions...
June 5, 2018: Surgery
Giuseppe Cicero, Rossella De Luca, Francesco Dieli
Background: In many clinical trials designed to assess the efficacy of anticancer treatments, overall survival (OS) is often used as a primary endpoint despite its several points of weakness. Methods: This study evaluated the role of progression-free survival (PFS) in the first three lines of treatment as a potential surrogate endpoint of OS in patients with metastatic colorectal cancer (MCRC). One hundred and twenty patients with MCRC were enrolled in this study...
2018: OncoTargets and Therapy
Annelies Wilder-Smith, Kirsten Vannice, Anna Durbin, Joachim Hombach, Stephen J Thomas, Irani Thevarjan, Cameron P Simmons
BACKGROUND: Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines. DISCUSSION: Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations...
June 6, 2018: BMC Medicine
Joshua D Wallach, Joseph S Ross, Huseyin Naci
The US Food and Drug Administration has several regulatory programs and pathways to expedite the development and approval of therapeutic agents aimed at treating serious or life-debilitating conditions. A common feature of these programs is the regulatory flexibility, which allows for a customized approval approach that enables market authorization on the basis of less rigorous evidence, in exchange for requiring postmarket evidence generation. An increasing share of therapeutic agents approved by the Food and Drug Administration in recent years are associated with expedited programs...
June 2018: Clinical Trials: Journal of the Society for Clinical Trials
Michael Doumas, Κonstantinos Imprialos, Konstantinos Stavropoulos, Andromachi Reklou, Alexandros Sachinidis, Vasilios G Athyros
BACKGROUND: The treatment of type 2 diabetes mellitus (T2DM) is complex; only few patients successfully attain glycemic targets with monotherapy, most requiring drug combination therapy. METHODS: The goal of this review was to identify in PubMed the complimentary ways of action leading to clinical benefit (in lowering HbA1c, body weight, renal, and cardiac risk factors and events) of the combination of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA)...
June 3, 2018: Current Pharmaceutical Design
Douglas P Barnaby, Shannon M Fernando, Christophe L Herry, Nathan B Scales, E John Gallagher, Andrew J E Seely
BACKGROUND: Risk stratification of patients presenting to the Emergency Department (ED) with sepsis can be challenging. We derived and evaluated performance of a predictive model containing clinical, laboratory and heart rate variability (HRV) measures to quantify risk of deterioration in this population. METHODS: ED patients aged 21 and older satisfying the 1992 consensus conference criteria for sepsis and able to consent (directly or through a surrogate) were enrolled (n = 1,247)...
May 29, 2018: Shock
B K Corwin, A N Trembath, A M Hibbs
BACKGROUND: Bronchopulmonary dysplasia (BPD) is used to clinically describe the severity of lung disease and to serve as common surrogate endpoint for long-term pulmonary morbidity in clinical trials, but its performance as a surrogate end-point warrants evaluation. Our objective was to assess real-world performance of BPD as a surrogate marker for long-term pulmonary outcomes. METHODS: We performed a systematic review of large, multi-centered, blinded, randomized control trials to evaluate the use of BPD as a surrogate marker for long-term pulmonary outcomes...
May 23, 2018: Journal of Neonatal-perinatal Medicine
R Cinotti, R Dumont, L Ronchi, A Roquilly, V Atthar, M Grégoire, L Planche, E Letessier, E Dailly, K Asehnoune
BACKGROUND: In obese patients undergoing sleeve gastrectomy, the blood and fatty-tissue concentrations of cefazolin required for adequate antibiotic prophylaxis are uncertain. METHODS: This was a single centre prospective study in obese (Group A: 40≤ BMI ≤50 kg m-2 ) and severely obese (Group B: 50< BMI ≤65 kg m-2 ) patients undergoing bariatric surgery. Blood and fatty-tissue samples were collected after a cefazolin 4 g i.v. injection. The primary aim was to compare cefazolin concentrations in subcutaneous fatty tissue with a targeted tissue concentration of 4 μg g-1 according to Staphylococcus aureus resistance breakpoint...
June 2018: British Journal of Anaesthesia
Scott E Belanger, Jane M Rawlings, Ricky Stackhouse
Short to long chain alcohols have a range of ecotoxicity to aquatic life driven by hydrophobic interactions with biological membranes. Carbon chain length and octanol:water partitioning coefficients are surrogates for hydrophobicity and strongly relate to aquatic toxicity. In these investigations, the toxicity of ethanol to 1-n-dodecanol to juvenile fish in standard acute toxicity tests is reviewed. Toxicity tests employing fish embryos (zebrafish Danio rerio and fathead minnow Pimephales promelas) in the Fish Embryo Test (OECD 236) format were conducted from C2 to C10 to compare against standard juvenile fish toxicity...
April 25, 2018: Chemosphere
Sumit Kar, Sabina Paglialunga, Rafiqul Islam
Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives...
May 18, 2018: Journal of Clinical Pharmacology
Mayur S Narkhede, Bruce D Cheson
Follicular lymphoma is the second most common subtype of non-Hodgkin lymphoma with an estimated 3.18 cases per 100,000 people. Despite the prolongation of survival with chemoimmunotherapy, variability in response to initial treatment and outcome still exists. Whereas prolonging overall survival is important, it is generally an unreasonable primary endpoint in the front-line setting. The long follow-up needed and the influence of subsequent therapies creates a potential bias. Thus, clinical trials require approximately 5 to 8 years from activation to completion and analysis of outcomes...
May 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
Melissa Caron, Sabrina Hoa, Marie Hudson, Kevin Schwartzman, Russell Steele
Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression ( i.e. outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD ( i...
June 30, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
David Rhainds, Mathieu R Brodeur, Jean-Claude Tardif
Cardiovascular diseases (CVD) are the first cause of death in the world. CVD risk is influenced by multiple factors, some non-modifiable such as age, sex and genetic background, and others modifiable. Great progress has been made over the last decades in the identification of biomarkers of incident or recurrent CV risk and surrogate endpoints of CV outcomes. We present the current state of knowledge for CV biomarkers in plasma including lipids, apolipoproteins, inflammation-related, and emerging omics-based biomarkers...
May 15, 2018: Clinical Pharmacology and Therapeutics
Ola Landgren
Minimal residual disease (MRD) testing in multiple myeloma is here to stay. Studies show that MRD negativity is consistently associated with longer progression-free survival (PFS). It is just a matter of time until MRD negativity will become a regulatory endpoint for drug approval. Until that can happen, more analysis will be required to define the exact details of MRD in the regulatory setting. For example, for randomized studies there is need to define the amount of improvement in MRD negativity between the experimental arm and the control arm at a given time-point for a drug to obtain regulatory accelerated approval...
January 2018: Seminars in Hematology
Sirisha Emani, Lynn A Sleeper, David Faraoni, Michelle Mulone, Fatoumata Diallo, James A DiNardo, Juan Ibla, Sitaram M Emani
BACKGROUND: Perioperative bleeding is a common complication in pediatric patients undergoing cardiac surgery. Although thromboelastography (TEG) has been utilized in patients undergoing adult cardiac surgery, limited data are available in pediatric patients. We hypothesize that TEG parameters may be associated with surrogate endpoints for postoperative bleeding in pediatric patients undergoing complex cardiac surgery. METHODS: In a retrospective study, TEG was obtained after protamine administration and upon intensive care unit (ICU) admission in pediatric patients (≤ 18yrs) undergoing cardiac surgery requiring cardiopulmonary bypass...
May 10, 2018: Annals of Thoracic Surgery
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