Comparison of WHO versus national COVID-19 therapeutic guidelines across the world: not exactly a perfect match.

BACKGROUND: The COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines. METHODS: Ministries of Health or accessed National Infectious Disease websites and other relevant bodies and experts were contacted to obtain national guidelines (NGs) for COVID-19 treatment. NGs were included only if they delineated specific pharmacological treatments for COVID-19, which were stratified by disease severity. We conducted a retrospective review using the adapted Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG) survey checklist and a derived comparative metric based on the WHO guidelines was performed. RESULTS: COVID-19 therapeutics NGs could be obtained from 109 of the 194 WHO member states. There was considerable variation in guidelines and in disease severity stratifications. Therapeutic recommendations in many NGs differed substantially from the WHO guidelines. Overall in late 2022, 93% of NGs were recommending at least one treatment which had proved to be ineffective in large randomised trials, and was not recommended by WHO. Corticosteroids were not recommended in severe disease in nearly 10% of NGs despite overwhelming evidence of their benefit. NGs from countries with low-resource settings showed the greatest divergence when stratified by gross domestic product per year, Human Development Index and the Global Health Security Index. DISCUSSION: Our study is limited to NGs that were readily accessible, and it does not reflect the availability of recommended medicines in the field. Three years after the start of the SARS-CoV-2 pandemic, available COVID-19 NGs vary substantially in their therapeutic recommendations, often differ from the WHO guidelines, and commonly recommend ineffective, unaffordable or unavailable medicines.

Assessment of the nlmixr R package for population pharmacokinetic modeling: A metformin case study.

AIM: nlmixr offers first-order conditional estimation (FOCE), FOCE with interaction (FOCEi) and stochastic approximation estimation-maximisation (SAEM) to fit nonlinear mixed-effect models (NLMEM). We modelled metformin's pharmacokinetic data using nlmixr and investigated SAEM and FOCEi's performance with respect to bias and precision of parameter estimates, and robustness to initial estimates. METHOD: Compartmental models were fitted. The final model was determined based on the objective function value and inspection of goodness-of-fit plots. The bias and precision of parameter estimates were compared between SAEM and FOCEi using stochastic simulations and estimations. For robustness, parameters were re-estimated as the initial estimates were perturbed 100 times and resultant changes evaluated. RESULTS: The absorption kinetics of metformin depend significantly on food status. Under the fasted state, the first-order absorption into the central compartment was preceded by zero-order infusion into the depot compartment, whereas for the fed state, the absorption into the depot was instantaneous followed by first-order absorption from depot into the central compartment. The means of relative mean estimation error (rMEE) ( ME E SAEM ME E FOCEi ) and rRMSE ( RMS E SAEM RMS E FOCEi ) were 0.48 and 0.35, respectively. All parameter estimates given by SAEM appeared to be narrowly distributed and were close to the true value used for simulation. In contrast, the distribution of estimates from FOCEi were skewed and more biased. When initial estimates were perturbed, FOCEi estimates were more biased and imprecise. DISCUSSION: nlmixr is reliable for NLMEM. SAEM was superior to FOCEi in terms of bias and precision, and more robust against initial estimate perturbations.

Ayudantías universitarias: influencia académica percibida en el desempeño en el examen de residencias médicas municipales / Teaching assistants: perceived academic influence on performance in municipal medical residency exams

Introducción: el ejercicio de la docencia universitaria por parte de estudiantes de Medicina ofrecería múltiples beneficios. Sin embargo, no hay evidencia de que mejore el desempeño en los exámenes estandarizados en el posgrado. El objetivo de este estudio fue describir la diferencia de los puntajes en el examen de residencias médicas municipales entre ayudantes y no ayudantes, y evaluar la autopercepción del efecto de ser ayudante sobre el desempeño en dicho examen y sobre las habilidades académicas. Métodos: estudio observacional, descriptivo, de corte transversal, con un muestreo por conveniencia de médicos participantes del examen de residencias médicas municipales de la Ciudad Autónoma de Buenos Aires (CABA) de 2018, a partir del listado oficial. Se excluyeron aquellos a quienes fue imposible contactar, que se negaran a participar o cuya identidad discrepara con la de la persona seleccionada para incluir en el estudio. Resultados: de los 3579 médicos que concursaron en el examen de residencias médicas básicas municipales de CABA 2018, se tomó una muestra aleatoria de 300 sujetos, de los cuales se contactó a 87. De ellos, 20 sujetos cumplían con criterios de exclusión; por lo tanto fueron 67 sujetos los que finalmente participaron del estudio. La proporción de respuestas con respecto a los sujetos que pudieron ser contactados mediante redes sociales fue 77%. El puntaje de examen entre los ayudantes fue de 32,3 ± 5,7 puntos mientras que entre los no ayudantes fue 29,5 ± 6,1 puntos. Entre los ayudantes, el 68% informó percibir que el hecho de haber realizado una ayudantía en el pregrado tuvo un efecto de levemente a muy positivo sobre su desempeño en el examen, un 76% refirió la profundización de conocimientos específicos, el 73% informó una mejoría en sus habilidades comunicacionales y el 59% una mayor capacidad para jerarquizar contenidos. Conclusión: el desarrollo de una actividad docente en el pregrado sería percibida por quienes la desarrollan como una actividad promotora de habilidades comunicacionales y de jerarquización de contenidos y, ulteriormente, como una influencia positiva en el desempeño académico en el examen de residencias médicas municipales. Estas conclusiones deben confirmarse con estudios futuros. (AU)

Introduction: medical students could benefit from teaching university courses. However, there is no evidence showing that this activity improves academic performance on standardized tests in graduate school. The objective of this study was to describe the differences in scores on the municipal medical residency exam between physicians who were teaching assistants and those who weren't, and to evaluate the self-perception of the effect of being a teaching assistant on the performance on this exam and on academic skills in general. Methods: this is an observational, descriptive, cross-sectional study, with a convenience sample of physicians participating in the 2018 municipal medical residency exam of the Autonomous City of Buenos Aires (CABA) based on official lists. Those who could not be contacted, refused to participate, or whose identity diverged from the person selected to include in the study, were excluded. Results: of the 3,579 physicians who participated in the basic municipal medical residency exam in CABA 2018, a random sample of 300 subjects was taken, of which 87 were contacted. Of those, 20 subjects met the exclusion criteria, having 67 subjects finally participating in the study. The proportion of subjects who could be contacted through social networks was 77%. The exam score among physicians who were teaching assistants was 32.3 ± 5.7 points while among the non-teaching assistants it was 29.5 ± 6.1 points. Among the teaching assistants, 68% perceived that the fact of having been a teaching assistant as an undergraduate had a slight to very positive effect on their performance in the exam, 76% referred the deepening of their specific knowledge on the subject they taught, 73% reported an improvement in their communication skills, and 59% referred a greater ability to rank content. Conclusions: undergraduate teaching would be perceived as an activity that promotes communication skills and ability to rank content and, therefore, as a positive influence on academic performance in the municipal medical residency exam. These conclusions need to be confirmed with future studies. (AU)