Publications by authors named "J Javier Castrodeza Sanz"

1,331 Publications

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International Changes in COVID-19 Clinical Trajectories Across 315 Hospitals and 6 Countries: a 4CE Consortium Study.

J Med Internet Res 2021 Sep 2. Epub 2021 Sep 2.

Institute for Biomedical Informatics, University of Kentucky, Lexington, US.

Background: Many countries have experienced two predominant waves of COVID-19-related hospitalizations. Comparing the clinical trajectories of patients hospitalized in separate waves of the pandemic enables further understanding of the evolving epidemiology, pathophysiology, and healthcare dynamics of the COVID-19 pandemic.

Objective: In this retrospective cohort study, we analyzed electronic health record (EHR) data from patients with SARS-CoV-2 infections hospitalized in participating healthcare systems representing 315 hospitals across six countries. We compared hospitalization rates, severe COVID-19 risk, and mean laboratory values between patients hospitalized during the first and second waves of the pandemic.

Methods: Using a federated approach, each participating healthcare system extracted patient-level clinical data on their first and second wave cohorts and submitted aggregated data to the central site. Data quality control steps were performed at the central site to correct for implausible values and harmonize units. Statistical analyses were performed by computing individual healthcare system effect sizes and synthesizing these using random effects meta-analyses to account for heterogeneity. We focused the laboratory analysis on C-reactive protein (CRP), ferritin, fibrinogen, procalcitonin, D-dimer, and creatinine based on their reported associations with severe COVID-19.

Results: Data were available for 79,613 patients, of which 32,467 were hospitalized in the first wave and 47,146 in the second wave. The prevalence of male patients and patients aged 50-69 decreased significantly between the first and second wave. Patients hospitalized in the second wave had a 9.9% reduction in risk of severe COVID-19 compared to patients hospitalized in the first wave (95% CI: 8.5-11.3%). Demographic subgroup analyses indicated that patients aged 26-49 and 50-69; male and female patients; and Black patients had significantly lower risk for severe disease in the second wave compared to the first wave. At admission, the mean values of CRP were significantly lower in the second wave compared to the first. On the seventh hospital day, mean values of CRP, ferritin, fibrinogen, and procalcitonin were significantly lower in the second wave compared to the first. In general, countries exhibited variable changes in laboratory testing rates from the first to the second wave. At admission, there was a significantly higher testing rate for D-dimer in France, Germany, and Spain.

Conclusions: Patients hospitalized in the second wave were at significantly lower risk for severe COVID-19. This corresponded to mean laboratory values in the second wave that were more likely to be in typical physiological ranges on the seventh hospital day compared to the first wave. Our federated approach demonstrated the feasibility and power of harmonizing heterogeneous EHR data from multiple international healthcare systems to rapidly conduct large-scale studies to characterize how COVID-19 clinical trajectories evolve.

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http://dx.doi.org/10.2196/31400DOI Listing
September 2021

Mumps virus outbreak related to a water pipe (narghile) shared smoking.

Enferm Infecc Microbiol Clin (Engl Ed) 2021 Sep 13. Epub 2021 Sep 13.

Consorcio de Investigación Biomédica de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Laboratorio Regional de Salud Pública de la Comunidad de Madrid, Dirección General de Salud Pública, Consejería de Sanidad Comunidad de Madrid, Madrid, Spain.

Introduction: This study describes a mumps outbreak among a group of young people who shared a same narghile to smoking. Saliva and blood samples were obtained from 3 cases for RT-PCR and serology respectively.

Methods: The notification of a mumps case started an epidemiological investigation. Information of other 6 additional symptomatic persons who had gathered with the case in a discotheque where they smoking in a same narghile was achieved. RT-PCR positive samples were genotyped by sequencing.

Results: The 7 patients resided in 3 different municipalities, and they do not have get together for more than a month until the meeting in the discotheque. Four cases were confirmed by RT-PCR and/or IgM determinations. The genomic investigation showed identical nucleic sequences.

Conclusions: This outbreak is consequence of the common use of a narghile to smoking. The public usage of these water pipes should be regulated.
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http://dx.doi.org/10.1016/j.eimce.2021.09.002DOI Listing
September 2021

Inter-hairpin linker sequences determine the structure of the ββ-solenoid fold: a "bottom-up" study of pneumococcal LytA choline-binding module.

Int J Biol Macromol 2021 Sep 8;190:679-692. Epub 2021 Sep 8.

Centro de Investigaciones Biológicas Margarita Salas, Spanish National Research Council (CSIC), Madrid, Spain; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Elche, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain. Electronic address:

The ββ-solenoid structures are part of many proteins involved in the recognition of bacterial cell wall. They are elongated polypeptides consisting of repeated β-hairpins connected by linker sequences and disposed around a superhelical axis stabilised by short-range interactions. Among the most studied ββ-solenoids are those belonging to the family of choline-binding modules (CBMs) from the respiratory pathogen Streptococcus pneumoniae (pneumococcus) and its bacteriophages, and their properties have been employed to develop several biotechnological and biomedical tools. We have carried out a theoretical, spectroscopic and thermodynamic study of the ββ-solenoid structure of the CBM from the pneumococcal LytA autolysin using peptides of increasing length containing 1-3 repeats of this structure. Our results show that hints of native-like tertiary structure are only observed with a minimum of three β-hairpins, corresponding to one turn of the solenoid superhelix, and identify the linker sequences between hairpins as the major directors of the solenoid folding. This study paves the way for the rational structural engineering of ββ-solenoids aimed to find novel applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.223DOI Listing
September 2021

Association of Antiosteoporotic Medication Bisphosphonates and Denosumab with Primary Breast Cancer: An Electronic Health Record Cohort Study.

Womens Health Rep (New Rochelle) 2021 16;2(1):316-324. Epub 2021 Aug 16.

University of California at Los Angeles, Clinical and Translational Science Institute, Los Angeles, California, USA.

The risks of osteoporosis and breast cancer are increasing in elderly women. Bisphosphonates and denosumab are recommended for treatment of osteoporosis. They have different and overlapping pharmacodynamics and previous studies have shown conflicting results regarding their risk association with breast cancer. We intend to further look into this issue through a comparative study. Electronic health records of 91,626 women older than 50 years with no previous history of malignancy and no nonbreast cancer during follow-up were retrieved from southern California and retrospectively analyzed using univariate, bivariate, and log-rank tests. Medication use, breast cancer risk, and associated demographic and clinical history were assessed. Over an average of 3.6 years follow-up, the breast cancer relative risks (RRs) counted after 365 days of latency are 1.12 (95% confidence interval [CI]: 0.64-1.97) for denosumab ever users and 0.37 (95% CI: 0.21-0.66) for bisphosphonates ever users, when covariates are comparable. The significant difference is supported by the Log-rank test ( = 0.0004). Excluding statins coprescribers, the breast cancer RR is 1.31 (0.71, 2.43) in denosumab group and 0.26 (0.11, 0.62) in bisphosphonates group. There is a reduced RR in statins ever users (0.47, 95% CI: 0.38-0.58), and the breast cancer risk difference is not significant between concomitant denosumab/statins and bisphosphonates/statins ever users with RR 0.65 (0.16, 2.58) versus 0.55 (0.26, 1.16),  = 0.692. Our data support an association of lower breast cancer risk with bisphosphonates use in elderly women. We did not observe a lower breast cancer risk in denosumab group; however, our data revealed a potential lower breast cancer risk in denosumab users with concurrent statins use and this requires further study.
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http://dx.doi.org/10.1089/whr.2020.0120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409235PMC
August 2021

Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis.

J Clin Invest 2021 Sep 2. Epub 2021 Sep 2.

Program in Infectious Diseases and Global Health, The Research Institute of the McGill University Health Centre, Montréal, Canada.

Persons living with HIV (PLWH) are at increased risk of tuberculosis (TB). HIV-associated TB is often the result of recent infection with Mycobacterium tuberculosis (Mtb) followed by rapid progression to disease. Alveolar macrophages (AM) are the first cells of the innate immune system that engage Mtb, but how HIV and antiretroviral therapy (ART) impact on the anti-mycobacterial response of AM is not known. To investigate the impact of HIV and ART on the transcriptomic and epigenetic response of AM to Mtb, we obtained AM by bronchoalveolar lavage from 20 PLWH receiving ART, 16 control subjects who were HIV-free (HC), and 14 subjects who received ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection. Following in-vitro challenge with Mtb, AM from each group displayed overlapping but distinct profiles of significantly up- and down-regulated genes in response to Mtb. Comparatively, AM isolated from both PLWH and PrEP subjects presented a substantially weaker transcriptional response. In addition, AM from HC subjects challenged with Mtb responded with pronounced chromatin accessibility changes while AM obtained from PLWH and PrEP subjects displayed no significant changes in their chromatin state. Collectively, these results revealed a stronger adverse effect of ART than HIV on the epigenetic landscape and transcriptional responsiveness of AM.
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http://dx.doi.org/10.1172/JCI148013DOI Listing
September 2021
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