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    Scopus© Citations 1  2
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    Scopus© Citations 2  2
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    Scopus© Citations 3  2
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    Effectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile
    (2023)
    Alejandro Jara
    ;
    Cristobal Cuadrado
    ;
    Eduardo A. Undurraga
    ;
    Christian García
    ;
    Manuel Nájera
    <jats:title>Abstract</jats:title><jats:p>In light of the ongoing COVID-19 pandemic and the emergence of new SARS-CoV-2 variants, understanding the effectiveness of various booster vaccination regimens is pivotal. In Chile, using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluate the effectiveness against COVID-19-related intensive care unit (ICU) admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series followed by a homologous booster, and CoronaVac primary series followed by an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimate the vaccine effectiveness weekly from February 14 to August 15, 2022, by determining hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot is 88.2% (95%CI, 86.2–89.9) against ICU admissions and 90.5% (95%CI 89.4–91.4) against death. Vaccine effectiveness shows a mild decrease for all regimens and outcomes, probably linked to the introduction of BA.4 and BA.5 Omicron sub-lineages and the waning of immunity. Based on our findings, individuals might not need additional boosters for at least 6 months after receiving a second mRNA booster shot in this setting.</jats:p>
    Scopus© Citations 11  2
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    De-escalating therapy in inflammatory bowel disease: Results from an observational study in clinical practice
    (2023)
    Alex Aren
    ;
    María José Moreta
    ;
    Ingrid Ordás
    ;
    Agnès Fernández-Clotet
    ;
    Berta Caballol
      1Scopus© Citations 1
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    Therapeutic vaccines for advanced non-small cell lung cancer
    (2019)
    Marcela Cortés-Jofré
    ;
    Rolando Uranga
    ;
    Ania Torres Pombert
    ;
    Maria del Carmen Arango Prado
    ;
    Iraida Caballero Aguirrechu
    Scopus© Citations 6  3
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    Validation of the simplified modified Rankin scale for stroke trials: Experience from the ENCHANTED alteplase-dose arm
    (2020)
    Xiaoying Chen
    ;
    Jingwei Li
    ;
    Craig S Anderson
    ;
    Richard I Lindley
    ;
    Maree L Hackett
    <jats:sec><jats:title>Background and aims</jats:title><jats:p> The structured, simplified modified Rankin scale questionnaire (smRSq) may increase reliability over the interrogative approach to scoring the modified Rankin scale (mRS) in acute stroke research and practice. During the conduct of the alteplase-dose arm of the international ENhanced Control of Hypertension ANd Thrombolysis StrokE stuDy (ENCHANTED), we had an opportunity to compare each of these approaches to outcome measurement. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Baseline demographic data were recorded together with the National Institutes of Health Stroke Scale (NIHSS). Follow-up measures obtained at 90 days included mRS, smRSq, and the 5-Dimension European Quality of life scale (EQ-5D). Agreements between smRSq and mRS were assessed with the Kappa statistic. Multiple logistic regression was used to identify baseline predictors of Day 90 smRSq and mRS scores. Treatment effects, based on Day 90 smRSq/mRS scores, were tested in logistic and ordinal logistic regression models. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> SmRSq and mRS scores had good agreement (weighted Kappa 0.79, 95% confidence interval (CI) 0.78–0.81), while variables of age, atrial fibrillation, diabetes mellitus, pre-morbid mRS (1 vs. 0), baseline NIHSS scores, and imaging signs of cerebral ischemia, similarly predicted their scores. Odds ratios for death or disability, and ordinal shift, 90-day mRS scores using smRSq were 1.05 (95% CI 0.91–1.20; one-sided P = 0.23 for non-inferiority) and 0.98 (95% CI 0.87–1.11; P = 0.02 for non-inferiority), similar to those using mRS. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> This study demonstrates the utility of the smRSq in a large, ethnically diverse clinical trial population. Scoring of the smRSq shows adequate agreement with the standard mRS, thus confirming it is a reliable, valid, and useful alternative measure of functional status after acute ischemic stroke. </jats:p></jats:sec><jats:sec><jats:title>Clinical Trial registration</jats:title><jats:p> URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616. </jats:p></jats:sec>
    Scopus© Citations 9  7
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    Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics
    (2023)
    Rodrigo Pérez-Arancibia
    ;
    Marisol Cisternas-Olmedo
    ;
    Denisse Sepúlveda
    ;
    Paulina Troncoso-Escudero
    ;
    Rene L. Vidal
    <jats:p>Neurological motor disorders (NMDs) such as Parkinson's disease and Huntington's disease are characterized by the accumulation and aggregation of misfolded proteins that trigger cell death of specific neuronal populations in the central nervous system. Differential neuronal loss initiates the impaired motor control and cognitive function in the affected patients. Although major advances have been carried out to understand the molecular basis of these diseases, to date there are no treatments that can prevent, cure, or significantly delay the progression of the disease. In this context, strategies such as gene editing, cellular therapy, among others, have gained attention as they effectively reduce the load of toxic protein aggregates in different models of neurodegeneration. Nevertheless, these strategies are expensive and difficult to deliver into the patients' nervous system. Thus, small molecules and natural products that reduce protein aggregation levels are highly sought after. Numerous drug discovery efforts have analyzed large libraries of synthetic compounds for the treatment of different NMDs, with a few candidates reaching clinical trials. Moreover, the recognition of new druggable targets for NMDs has allowed the discovery of new small molecules that have demonstrated their efficacy in pre-clinical studies. It is also important to recognize the contribution of natural products to the discovery of new candidates that can prevent or cure NMDs. Additionally, the repurposing of drugs for the treatment of NMDs has gained huge attention as they have already been through clinical trials confirming their safety in humans, which can accelerate the development of new treatment. In this review, we will focus on the new advances in the discovery of small molecules for the treatment of Parkinson's and Huntington's disease. We will begin by discussing the available pharmacological treatments to modulate the progression of neurodegeneration and to alleviate the motor symptoms in these diseases. Then, we will analyze those small molecules that have reached or are currently under clinical trials, including natural products and repurposed drugs.</jats:p>
      3Scopus© Citations 21