Prospective cohort study of patients with COVID-19 hospitalized in the Internal Medicine ward of Hospital Durand: study protocol

Fil: Melendi, Santiago E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pérez, María M. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Salas, Cintia E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Aguirre, Camila. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Baleta, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Balsano, Facundo J. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Caldano, Mariano G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Colignon, María G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Oliveira Brasil, Thayana De. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Wolodimeroff, Nicolás de. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Déramo Aquino, Andrea I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fernández de Córdova, Ana G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fontan, María B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Galvagno, Florencia I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Haedo, Mariana F. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Iturrieta Araya, Noelia S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Mollinedo Cruz,Volga S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Olivero, Agustín. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pestalardo, Ignacio. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ricciardi, María. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Saltos Navarrete, Jandry D. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Vera Rueda, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Villaverde, María C. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Xavier, Franco B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Lauko, Marcela. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ujeda, Carlos. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Leis, Rocío. Hospital General de Agudos Carlos G. Durand; Argentina.INTRODUCCIÓN: Conocer los predictores de mala evolución en pacientes con Enfermedad por Coronavirus 2019 (COVID-19) permite identificar de forma temprana a los pacientes con peor pronóstico, aportando mejores herramientas a la hora de tomar decisiones clínicas. Se presenta el protocolo de un estudio de cohorte cuyo objetivo principal es identificar factores de riesgo de infección severa, critica y mortalidad en pacientes con COVID-19 internados en el Servicio de Clínica Médica del Hospital Durand (Buenos Aires, Argentina). MÉTODOS: Estudio de cohorte prospectivo con base en un único centro. Se incluirá a todos los pacientes que ingresen al servicio de Clínica Médica con diagnóstico de COVID-19 durante el periodo de estudio. Se recolectarán las características epidemiológicas, clínicas, de laboratorio, radiológicas y los datos de tratamiento, al ingreso y al momento del alta o muerte hospitalaria. El evento final primario es la muerte en la internación; los eventos secundarios son el desarrollo de enfermedad grave y enfermedad crítica, la internación en unidad cerrada y el requerimiento de asistencia respiratoria mecánica

Prospective cohort study of patients with COVID-19 hospitalized in the Internal Medicine ward of Hospital Durand: study protocol

Fil: Melendi, Santiago E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pérez, María M. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Salas, Cintia E. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Aguirre, Camila. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Baleta, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Balsano, Facundo J. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Caldano, Mariano G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Colignon, María G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Oliveira Brasil, Thayana De. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Wolodimeroff, Nicolás de. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Déramo Aquino, Andrea I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fernández de Córdova, Ana G. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Fontan, María B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Galvagno, Florencia I. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Haedo, Mariana F. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Iturrieta Araya, Noelia S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Mollinedo Cruz,Volga S. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Olivero, Agustín. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Pestalardo, Ignacio. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ricciardi, María. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Saltos Navarrete, Jandry D. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Vera Rueda, María L. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Villaverde, María C. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Xavier, Franco B. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Lauko, Marcela. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Ujeda, Carlos. Hospital General de Agudos Carlos G. Durand; Argentina.Fil: Leis, Rocío. Hospital General de Agudos Carlos G. Durand; Argentina.INTRODUCCIÓN: Conocer los predictores de mala evolución en pacientes con Enfermedad por Coronavirus 2019 (COVID-19) permite identificar de forma temprana a los pacientes con peor pronóstico, aportando mejores herramientas a la hora de tomar decisiones clínicas. Se presenta el protocolo de un estudio de cohorte cuyo objetivo principal es identificar factores de riesgo de infección severa, critica y mortalidad en pacientes con COVID-19 internados en el Servicio de Clínica Médica del Hospital Durand (Buenos Aires, Argentina). MÉTODOS: Estudio de cohorte prospectivo con base en un único centro. Se incluirá a todos los pacientes que ingresen al servicio de Clínica Médica con diagnóstico de COVID-19 durante el periodo de estudio. Se recolectarán las características epidemiológicas, clínicas, de laboratorio, radiológicas y los datos de tratamiento, al ingreso y al momento del alta o muerte hospitalaria. El evento final primario es la muerte en la internación; los eventos secundarios son el desarrollo de enfermedad grave y enfermedad crítica, la internación en unidad cerrada y el requerimiento de asistencia respiratoria mecánica

Spatial demonstratives and perceptual space: To reach or not to reach?

There is much debate regarding the relationship between spatial demonstratives (‘this’ or ‘that’) and perceptual space. While some have argued for a close mapping between the use of demonstratives and the peripersonal/extrapersonal space distinction (Coventry et al., 2008, 2014; Diessel, 2014), others have argued that distance from a speaker does not affect demonstrative choice (e.g. Kemmerer, 1999; Peeters et al., 2015). We investigated the mapping between demonstratives and perceptual space across sagittal and lateral planes. Manipulation of object location on the lateral plane, and the hand used to point at objects (left, right) afforded a critical test of the the mapping between demonstratives and the reachability of objects. Indeed, we found that objects positioned at the same locations were described using this when the hand pointing at the object could reach it. Furthermore, we found no overall effects of handedness or visual field on demonstratives choice. This provides strong support for a mapping between perceptual space and the use of demonstratives. Such a mapping may help explain the influence of other variables on demonstrative choice, including interactive factors. The archive contains an excel sheet with the mean percentage use of this for each participant for all combinations of pointing hand and distances in the lateral and saggital planes (also noting handedness as measured by the Edinburgh Handedness Questionnaire)

Spatial demonstratives and perceptual space: To reach or not to reach?

There is much debate regarding the relationship between spatial demonstratives (‘this’ or ‘that’) and perceptual space. While some have argued for a close mapping between the use of demonstratives and the peripersonal/extrapersonal space distinction (Coventry et al., 2008, 2014; Diessel, 2014), others have argued that distance from a speaker does not affect demonstrative choice (e.g. Kemmerer, 1999; Peeters et al., 2015). We investigated the mapping between demonstratives and perceptual space across sagittal and lateral planes. Manipulation of object location on the lateral plane, and the hand used to point at objects (left, right) afforded a critical test of the the mapping between demonstratives and the reachability of objects. Indeed, we found that objects positioned at the same locations were described using this when the hand pointing at the object could reach it. Furthermore, we found no overall effects of handedness or visual field on demonstratives choice. This provides strong support for a mapping between perceptual space and the use of demonstratives. Such a mapping may help explain the influence of other variables on demonstrative choice, including interactive factors. The archive contains an excel sheet with the mean percentage use of this for each participant for all combinations of pointing hand and distances in the lateral and saggital planes (also noting handedness as measured by the Edinburgh Handedness Questionnaire)

Biological activity of interferon betas in patients with multiple sclerosis is affected by treatment regimen and neutralising antibodies

Background: MxA gene expression is one of the most appropriate markers of biological activity of exogenous interferon (IFN) beta. Methods: We quantified MxA mRNA for five consecutive days in 62 patients treated with IFN beta (16, Avonex; 10, Betaferon; 24, Rebif 22; 12, Rebif 44), by quantitative-competitive polymerase chain reaction. Every three months, IFN beta induced neutralising antibodies (NAbs) were evaluated in sera using a cytopathic effect assay. Results: Two categories of patients were identified: one group (49/62) had a sharp post-injection increase in MxA expression (defined as "IFN beta biological responder"), whereas the other group (13/62) had no MxA induction after IFN beta administrations (defined as "IFN beta biological non-responder"). In 11/13 biological non-responders, the persistent presence of NAbs correlated with abolished biological activity, independently of treatment regimen. The two remaining IFN beta biological non-responders were NAb–. Among the 49 IFN beta biological responders, biological activity was comparable between the four preparations on day 2 and 3 (+12 and +36 hours post-injection), but it was greater in Betaferon and both Rebif preparations on day 1, 4, and 5. In biological responders treated three times a week, only 82% (59/72) of injections were considered effective, compared with 100% (13/13) of Avonex injections. Conclusion: Our results suggest that an optimal IFN beta regimen is not yet available: Avonex, given once a week, shows lower cumulative biological activity. On the other hand, both Betaferon and Rebif, given three times a week, show 18% biologically ineffective injections and higher risk of developing NAbs, which abolish biological activity

Drug holiday of interferon beta 1b in multiple sclerosis: A Pilot, Randomized, Single Blind Study of Non-inferiority

Introduction: To compare a schedule with cyclic withdrawal (CW) of interferon beta (IFN-b) 1b, respect to the full regimen (FR), in relapsing-remitting MS (RR-MS). Methods: Participants were randomly assigned to CW or FR schedule and monthly monitored with brain MRI scans for 12 months (three of run-in and 9 of treatment). CW schedule included drug withdrawal for 1 month after two of treatment for a total of three quarters over the 9-month treatment period. The assessing neurologist and the expert neuroradiologists were blind. After the blind phase of the study all participants took their indicated disease modifying therapies in a prospectively planned, open-label extension phase (up to 120 months). Results: Of 60 randomized subjects 56 (29 in FR and 27 in CW group) completed the single-blind phase: the two groups were comparable, except for a non-significant difference in the number of contrast-enhanced lesions (CEL) at the end of run-in. The two-sided 90% CI for the ratio between median number of cumulative CEL was 0.29-1.07, allowing to significantly reject the null hypothesis of a ratio 651.2 and to meet the primary end-point of non-inferiority (the threshold and the ratio between median were chosen according to the non-normal distribution of the data). The differences (CW vs. FR) were also non-significant for secondary end points: mean cumulative number of T2-weighted new and enlarging lesions (3.48 \ub1 5.34 vs. 3.86 \ub1 6.76); mean number and volume (cm3) of black holes (1.24 \ub1 1.61 vs. 2.71 \ub1 4.56; 489.11 \ub1 1488.12 vs. 204.48 \ub1 396.98); number of patients with at least an active scan (21 vs. 22); mean relapse rate (0.52 \ub1 0.89 vs. 0.34 \ub1 0.66), relapse risk ratio adjusted for baseline variables (2.15 [0.64-7.18]), EDSS score (1.0 [1-1.56] vs. 1.5 [1-1.78]), proportion of patients with antibodies anti-IFN (5 [21%] vs. 8 [36%]). Fifty-four patients (27 for each study arm) completed the open-label phase. The annualized RR, EDSS, proportion of patients shifting to progressive disease and hazard ratio of shifting, adjusting for baseline covariates, were comparable between the two study groups. Conclusions: A calendar with CW was non-inferior than FR at the beginning of IFN-b therapy, and may not affect the long-term outcome