Search results for " burden"
showing 10 items of 325 documents
Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma.
2015
Few patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) achieve prolonged disease-free survival. Blinatumomab, a bispecific T-cell engaging antibody construct, transiently links CD3-positive T cells to CD19-positive B cells. This phase 2 study evaluated stepwise (9-28-112 μg/d with weekly dose increases; n = 23) or flat (112 μg/d; n = 2) dosing of blinatumomab by continuous infusion, with dexamethasone prophylaxis, in patients with relapsed/refractory DLBCL. Patients received a median of 3 prior lines of therapy. Median time since last regimen was 1.5 months. Seventeen patients ended treatment in cycle 1 (induction), 7 in cycle 2 (consolidation), and 1 in retreatment. Am…
Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade
2019
Abstract Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutat…
Moving Towards Precision Urologic Oncology: Targeting Enzalutamide-resistant Prostate Cancer and Mutated Forms of the Androgen Receptor Using the Nov…
2017
Abstract Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist with a chemical structure distinctly different from currently approved AR antagonists that targets both wild-type and mutated ligand binding domain variants to inhibit AR nuclear translocation. Here, we evaluate the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer (CRPC) as well as in AR mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide. Darolutamide significantly inhibited cell growth and AR transcriptional activity in enzalutamide-resistant MR49F cells in vitro, and led to decreased tumor volume and serum prostate-specific antigen l…
The burden and epidemiology of community-acquired central nervous system infections: a multinational study
2017
Ghaydaa, Shehata/0000-0002-3631-893X; Radic, Ljiljana Betica/0000-0002-8778-106X; Silva-Pinto, Andre/0000-0002-2077-3356; Cascio, Antonio/0000-0002-1992-1796; Bossi, Paolo/0000-0003-0135-0224; Stebel, Roman/0000-0001-6922-4465; Namani, Sadie/0000-0002-2411-8623; Chan, Phillip/0000-0002-4071-4409; Hargreaves, Sally/0000-0003-2974-4348; Artuk, Cumhur/0000-0003-0827-990X; Harxhi, Arjan/0000-0001-8518-7377; Larsen, Lykke/0000-0002-4113-4182; Uysal, Serhat/0000-0002-4294-5999 WOS: 000407582200010 PubMed: 28397100 Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We perfor…
Estimating Global Burden of Disease due to congenital anomaly: an analysis of European data
2017
ObjectiveTo validate the estimates of Global Burden of Disease (GBD) due to congenital anomaly for Europe by comparing infant mortality data collected by EUROCAT registries with the WHO Mortality Database, and by assessing the significance of stillbirths and terminations of pregnancy for fetal anomaly (TOPFA) in the interpretation of infant mortality statistics.Design, setting and outcome measuresEUROCAT is a network of congenital anomaly registries collecting data on live births, fetal deaths from 20 weeks’ gestation and TOPFA. Data from 29 registries in 19 countries were analysed for 2005–2009, and infant mortality (deaths of live births at age <1 year) compared with the WHO Mortality …
International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia
2019
Objective: Streptococcus pneumoniae is the most frequent bacterial pathogen isolated in subjects with Community-acquired pneumonia (CAP) worldwide. Limited data are available regarding the current global burden and risk factors associated with drug-resistant Streptococcus pneumoniae (DRSP) in CAP subjects. We assessed the multinational prevalence and risk factors for DRSP-CAP in a multinational point-prevalence study. Design: The prevalence of DRSP-CAP was assessed by identification of DRSP in blood or respiratory samples among adults hospitalized with CAP in 54 countries. Prevalence and risk factors were compared among subjects that had microbiological testing and antibiotic susceptibility…
Global, regional, and national levels of maternal mortality, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015
2016
BACKGROUND: In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015.METHODS: We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underl…
Impact of COVID-19 on global HCV elimination efforts.
2021
Background & Aims COVID-19 has placed significant strain on national healthcare systems at a critical moment in the context of hepatitis elimination. Mathematical models can be used to evaluate the possible impact of programmatic delays on hepatitis disease burden. The objective of this analysis was to evaluate the incremental change in hepatitis C liver-related deaths and liver cancer, following a 3-month, 6-month, or 1-year hiatus in hepatitis elimination program progress. Methods Previously developed models were adapted for 110 countries to include a status quo or “no delay” scenario and a “1-year delay” scenario assuming significant disruption in interventions (screening, diagnosis and …
Dyadic Wind of Change: New Approaches to Improve Biopsychological Stress Regulation in Patients with Dementia and Their Spousal Caregivers
2019
Patients with dementia (PWD) and their caregivers experience long-term stress, leading to accelerated disease progression and to stress-related morbidity. Previous research focused on intrapersonal biopsychological stress responses. Quite recently, dyadic interrelations between caregivers and PWD and their effects on stress and caregiver burden have received more attention, giving rise to dyadic intervention studies. However, while it is of importance to consider both the patient and the caregiver from a dyadic point of view, evaluation of these dyadic interventions considering underlying mechanisms is still lacking. We therefore extend the current literature on dyadic processes between PWD…
Long-term vitamin D treatment decreases human uterine leiomyoma size in a xenograft animal model
2019
Objective To study the effects of short- and long-term vitamin D treatment on uterine leiomyomas in vivo through cell proliferation, extracellular matrix (ECM) degradation, and apoptosis. Design Preclinical study of human leiomyoma treatment with vitamin D in an nonhuman animal model. Setting Hospital and university laboratories. Patient(s)/Animal(s) Human leiomyomas were collected from patients and implanted in ovariectomized NOD-SCID mice. Intervention(s) Mice were treated with vitamin D (0.5 μg/kg/d or 1 μg/kg/d) or vehicle for 21 or 60 days. Main Outcome Measure(s) Vitamin D effect in xenograft tissue was assessed by monitoring tumor size (18F-FDG positron-emission tomography/computeriz…