Regional Strategies of Multinational Pharmaceutical Firms

This paper examines the R&D and strategies of the world’s largest firms in the pharmaceuticals sector and finds a high degree of intra-regional sales. R&D and sales are more concentrated within North America and Europe than in Asia. In addition, the relative size of the U.S. market, compared to other parts of the triad, creates imbalances with respect to R&D, sales and international strategy.

Comunicación en Nueva España: Una metodología desde la complejidad

El propósito de esta tesis es integrar conceptos de sistemas complejos a las metodologías utilizadas en las ciencias sociales y las humanidades. En particular, se pretende poner el énfasis en la naturaleza de los seres humanos, sus interacciones, procesos de auto-ordenación y emergencia y fenómenos sistémicos como path-dependence y retornos crecientes, de manera que el resultado contribuya a una metodología para el estudio de la complejidad de los sistemas de cultura. El trabajo está dividido en dos partes. La primera parte introduce conceptos desarrollados en investigaciones de sistemas complejos y proporciona ejemplos de su aplicación a las ciencias sociales y humanidades. La segunda parte presenta los beneficios de utilizar estos conceptos en estudios específicos del ámbito de las ciencias sociales y las humanidades y aplica estos conceptos a tres estudios de casos relacionados con la comunicación en la época colonial en Mesoamérica. Los tres estudios de caso son: (1) Aprendizaje de lenguas indígenas por parte de españoles en Nueva España en los primeros cien años después de la conquista; (2) Textos cosmogónico-religiosos de las civilizaciones nahuas y españolas. Narrativas inestables como ejes simbólicos de sistemas de comunicación socializadores y; (3) La coexistencia de dos sistemas de contaduría, el español e indígena, y la adaptación de éstos en un ambiente de contacto entre dos cultura

Juan Everardo Nithard, protagonista de «La estatua de Prometeo» de Calderón de la Barca

Este artículo parte de la polémica que se desarrolla alrededor de la interpretación que hace Greer del texto político en La estatua de Prometeo. En su lectura, Greer asocia al personaje principal, el ilustrado Prometeo, con Don Juan José de Austria, enemigo de la Reina, a la vez que argumenta que la obra lo sugiere como la mejor opción para resolver los problemas del imperio. Este artículo provee una interpretación alternativa que alinea el mensaje con la posición política y personal de la Reina sobre los eventos políticos que se están tratando. Esta nueva lectura resuelve los elementos más polémicos que derivan de la interpretación de Greer, lo que tiene consecuencias en como entendemos el nivel de libertad expresión que disfrutaban los dramaturgos del Siglo de Oro.This article discusses Greer’s controversial interpretation of La estatua de Prometeo’s political text, which argued that the protagonist, the enlightened Prometeo, is a dramatization of the Queen´s enemy, Don Juan José of Austria and that Calderón is suggesting him as the best option for governing the troubled Spanish Empire. This article provides an alternative interpretation that better aligns with the personal and political position of the Queen regarding the political events that are being dramatized and resolves the contradictions that arose from Greer’s interpretations. This, in turn, contributes to our understanding of the level of freedom of expression enjoyed by Golden Age playwrights

El currículum de Ciencias Naturales de la Educación Secundaria. Retos y desafíos de cara al futuro : dossier

Fil: Ferreyra, Horacio Ademar. Universidad Católica de Córdoba. Facultad de Educación; Argentin

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Escuela secundaria posible

REPENSAR LA EDUCACIÓN SECUNDARIA Colección de infografías II Parte Seguimiento de medios de comunicación 2017-2019Fil: Ferreyra, Horacio Ademar. Universidad Católica de Córdoba. Facultad de Educación; ArgentinaFil: Di Francesco, Adriana Carlota. Universidad Católica de Córdoba. Facultad de Educación; ArgentinaFil: Equipo de investigación en educación de adolescentes y jóvenes. Unidad Asociada CONICET. Universidad Católica de Córdoba. Facultad de Educación; Argentina

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Cognition, Adherence and Stigma in Schizophrenia. The COAST study

Schizophrenia is a serious stigmatizing illness. Antipsychotic medication is a cornerstone in treatment. Non-adherence is a predictor of poor outcome leading to relapse, poor functioning, high mortality and costs. Reported adherence rates vary (8-86%). Most adherence studies are small, short and use subjective adherence measures known to underestimate non-adherence. The overall aim of this thesis is to increase knowledge about factors related to adherence to oral antipsychotics and to stigma in a large cohort of patients with schizophrenia or schizophrenia-like psychosis, followed for one year. The specific aims are: to examine adherence to antipsychotics and to compare objective and subjective measures of adherence; to investigate predictors of adherence; to explore stigma and discrimina¬tion and to test for potential associations between a) different types of stigma and b) stigma and adherence; to study stigma experiences and the relationship between associated stigma and burden in relatives to persons with schizophrenia. Adherence was monitored for a year in 117 outpatients at Sahlgrenska University Hospital, Gothenburg, Sweden. Adherence was determined by the Medication Event Monitoring System (MEMS®), considered the reference standard, pill count, a composite measure of plasma levels and adherence to lab visits, and patient, staff, psychiatrist and close informant ratings. Symptom burden, insight, cognition, psychoso¬cial function (PSP) and side effects were rated (n=112). Experiences of stigma (n=111) and drug attitude (using the Drug Attitude Inventory, DAI-10) of patients (n=112) and informants (n=65), as well as burden in relatives (n=65) were assessed. Non-adherence (MEMS® adherence ≤ 0.80) was observed in 27% of the patients. In Study I MEMS® adherence was highly correlated with pill count but very poorly correlated with the plasma level measure. In Study II low patient-rated DAI-10 scores and poor function emerged as predictors of non-adherence. Positive symptom burden, psychiatric side effects, lack of insight and low DAI-10 informant scores also predicted non-adherence. No association between stigma and adherence could be shown in Study III. Almost two-thirds of the patients reported discrimination in social relationships and “anticipated stigma”. One-half felt discriminated against by mental health staff. In Study IV a fifth of the relatives avoided situations that might elicit stigma, but there was no association between experienced or anticipated stigma and burden. Stigma impact regarding the relatives’ personal quality of life was associated with overall burden. In conclusion, structured pill count might be a useful clinical tool to objectively follow adherence. The large discrepancy between MEMS® and the plasma level measure needs further study. Positive drug attitude in combination with good psychosocial functioning emerged as predictors of MEMS® monitored adherence. Associations were found neither between stigma and adherence nor the relatives’ stigma and burden, and both phenomena need to be investigated further