53 research outputs found
Strategies to design clinical studies to identify predictive biomarkers in cancer research
The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological frameworkâthe DESIGN guidelinesâto standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field
DIFFERENTIATION BETWEEN Nocardia spp. AND Mycobacterium spp.: CRITICAL ASPECTS FOR BACTERIOLOGICAL DIAGNOSIS
The clinical impact of using complex molecular profiling strategies in routine oncology practice
Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patientsâ treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10â50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice
Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)
Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic
Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial
Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population
Gemcitabine and oxaliplatin combination: A multicenter phase II trial in unfit patients with locally advanced or metastatic urothelial cancer
Integrated methodology to characterize hydro-geochemical properties in an alluvial coastal aquifer affected by seawater intrusion (SWI) and submarine groundwater discharge (SGD)
Coastal zones are increasingly demanded spots for human settlements and economic
development, which subject alluvial coastal aquifers to the threat of seawater intrusion
(SWI). But they are also strategic areas for the chemical exchange between the continent and
marine ecosystems, providing a source of nutrients from the submarine groundwater
discharge (SGD) from the aquifer. Furthermore, in these contexts, the characteristics of the
freshwater-seawater interface (FW-SWI) and its dynamics are strongly conditioned by the
lithology and, among others, the typology of the discharge, density contrasts and tides.
The proper management of such enclaves requires full understanding of the SWI-SGD
system, which can only be achieved through a multidisciplinary and multi-scale
characterization of the considered aquifer.
For that purpose, we have developed an experimental field site in a coastal alluvial aquifer
close to the mouth of a temporary stream in the Maresme coast line (Barcelona, Spain). The
aquifer is formed by unconsolidated heterogeneous and polygenic alluvial sediments ranging
from very fine to very coarse grained sand with discontinuous interfingering lenses of gravel
and silt. All these sediments have around 20 m thickness and are overlying a weathered
granitic basement.
Several boreholes were drilled perpendicular and parallel to the shoreline, at various depths
to reach different hydraulic conductivity areas along the mixing zone. Geophysical
techniques including electrical resistivity tomography, fiber optics and different types of
logging (induction, spectral gamma ray and magnetic susceptibility) have been performed to
characterize the salinity gradient and distinguish sedimentary bodies. Moreover, a fully
hydrochemical investigation was carried out to define the initial groundwater composition
using TOC/DOC measurements, mayor and minor elements analysis and radium and radon
isotopes quantifications. Also lithological description, sedimentological correlation and
geochemical analysis of the cores obtained after drilling (X-ray diffraction, rock total
analysis for chemical composition, cation exchange capacity, BET surface area, radium
content and grain size distribution) were integrated to fully characterize the initial stage of
the experimental site. This integrated multidisciplinary and multi-scale methodology will
enable understanding the coupled effects of SWI and SGD in FW-SWI dynamics and give
some insights for the study of seawater intrusion processes in many other sites.Acknowledgements
This work was funded by the projects CGL2013-48869- C2-1- R/2-R and CGL2016-77122-
C2-1- R/2-R of the Spanish Government. We would like to thank SIMMAR (Serveis
Integrals de Manteniment del Maresme) and the Consell Comarcal del Maresme in the
construction of the research site.Peer reviewe
Facing geological heterogeneity impact on reciprocal coastal systems
Coastal zones are increasingly demanded spots for human settlements and economic development. In these areas, aquifers are subjected
to the threat of landward entrance of seawater caused by overexploitation of fresh groundwater resources. In some contexts, a coeval
groundwater flow of freshwater seaward can also take place, often linked to the surficial discharge of ephemeral streams. Understand the
interactions between this two reciprocal flows in coastal aquifers is needed to be able to characterize the freshwater-saltwater interface
and the effects on rate of submarine groundwater dischargeThis work was funded by the project CGL2016-77122-C2-1-R/2-R of the Spanish Government. We would like to thank SIMMAR (Serveis Integrals de Manteniment del Maresme) and the Consell Comarcal del Maresme in the construction of the research site.Peer reviewe
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