Barriers of Access to Opioid Medicines within the Context of Palliative Care in Latin America: The Perception of Health Professionals.

Background: Different sets of barriers have been identified to explain the difficulties in the access and availability of opioid analgesics in palliative care, particularly in low- and middle-income countries, including Latin America. Objective: To validate a structured questionnaire for the access to opioid medicines and to investigate the perception of health professionals regarding access barriers to opioid analgesics in 17 countries of the Latin American Region. Design: Survey to identify the domains and barriers of access to opioid medicines according to health professionals, including physicians, nurses, and pharmacists affiliated to institutions that provide palliative care in Latin America between August 2019 and October 2020. Results: We analyzed responses from 426 health professionals. The median age was 44 years old (ranging from 23 to 73 years) with an average experience in palliative care of 10 years (range: 1-35), 71.8% were women, and 49.8% were affiliated to specialized health care facilities of urban areas (94.6%). The main barriers perceived to be extremely relevant by the respondents were "belief that patients can develop addiction" and "financial limitations of patients" for the patient's domain and the "appropriate education, instruction, and training of professionals" for health professional's domain. Conclusions: It is necessary to develop strategies to strengthen less-developed health systems of the region to review legal frameworks, ensure integrated palliative care systems, and deploy multidisciplinary strategies for sensitizing, training, and raising the awareness of patients, caregivers and, particularly, health professionals regarding appropriate prescription and rational use of opioid analgesics.

Reacciones adversas a medicamentos utilizados para la COVID-19 en cinco países de América Latina / Adverse reactions to drugs used for COVID-19 in five Latin American countries / Reações adversas a medicamentos utilizados para a COVID-19 em cinco países da América Latina

RESUMEN Objetivo. Caracterizar y describir las notificaciones de sospechas de reacciones adversas de un grupo de medicamentos que se utilizaron en Colombia, Costa Rica, Cuba, Chile, El Salvador, México y Perú para tratar o prevenir la enfermedad por el coronavirus (COVID-19, por su sigla en inglés) entre el 1 de marzo y el 31 de agosto del 2020. Métodos. Se elaboró una lista de los 13 medicamentos utilizados para tratar o prevenir la COVID-19, según fuentes oficiales y no oficiales. Desde las bases de datos de los programas nacionales de farmacovigilancia de los países participantes, se recopilaron las notificaciones de sospechas de reacciones adversas a estos medicamentos recibidas en el período comprendido entre el 1 de marzo y 31 de agosto de año 2020. Resultados. Se recibieron 3 490 notificaciones de sospechas de reacciones adversas desde los programas de farmacovigilancia de Perú (n = 3 037), Cuba (n = 270), Colombia (n = 108), Chile (n = 72) y El Salvador (n = 3). Los medicamentos con mayor número de notificaciones de reacciones adversas fueron la azitromicina, la ivermectina y la hidroxicloroquina. La diarrea fue el evento más frecuente (15,0%). Del total de las sospechas de reacciones adversas, 11,9% fueron notificadas como graves. La más frecuente fue la prolongación del intervalo QT posterior al uso de hidroxicloroquina. De estas sospechas de reacciones adversas graves, 54,5% ocurrieron en personas mayores de 65 años. Conclusión. Si bien no es posible establecer una relación causal a partir de la evaluación de informes espontáneos, el presente estudio confirma la presencia de reacciones adversas, algunas graves, con medicamentos que se utilizaron para tratar o prevenir la COVID-19.

ABSTRACT Objective. Characterize and describe reports of suspected adverse reactions to a group of drugs used in Colombia, Costa Rica, Cuba, Chile, El Salvador, Mexico, and Peru to treat or prevent coronavirus disease (COVID-19) between 1 March and 31 August 2020. Methods. A list of the 13 drugs used to treat or prevent COVID-19 was prepared, based on official and unofficial sources. Drawing on the databases of the national pharmacovigilance programs of the participating countries, reports of suspected adverse reactions to these drugs were collected for the period from 1 March and 31 August 2020. Results. A total of 3 490 reports of suspected adverse reactions were received from the pharmacovigilance programs of Peru (n = 3 037), Cuba (n = 270), Colombia (n = 108), Chile (n = 72), and El Salvador (n = 3). The drugs with the highest number of reported adverse reactions were azithromycin, ivermectin, and hydroxychloroquine. Diarrhea was the most frequent event (15.0%). Of the total suspected adverse reactions, 11.9% were reported as serious. The most frequent was QT prolongation following use of hydroxychloroquine. Of these suspected serious adverse reactions, 54.5% occurred in people over 65 years of age. Conclusions. While it is not possible to establish a causal relationship from the evaluation of spontaneous reports, the present study confirms the presence of adverse reactions—some of them serious—involving drugs used to treat or prevent COVID-19.

RESUMO Objetivo. Caracterizar e descrever as notificações de suspeitas de reações adversas a um grupo de medicamentos utilizados na Colômbia, Costa Rica, Cuba, Chile, El Salvador, México e Peru, para tratar ou prevenir a doença do coronavírus (COVID-19), entre 1º de março e 31 de agosto de 2020. Métodos. Foi elaborada uma lista dos 13 medicamentos usados para tratar ou prevenir a COVID-19, segundo fontes oficiais e não oficiais. A partir das bases de dados dos programas nacionais de farmacovigilância dos países participantes, foram coletadas notificações de suspeitas de reações adversas a esses medicamentos, recebidas no período entre 1º de março e 31 de agosto de 2020. Resultados. Foram recebidas 3.490 notificações de suspeitas de reações adversas dos programas de farmacovigilância do Peru (n = 3.037), Cuba (n = 270), Colômbia (n = 108), Chile (n = 72) e El Salvador (n = 3). Os medicamentos com maior número de notificações de reações adversas foram azitromicina, ivermectina e hidroxicloroquina. A diarreia foi o evento mais frequente (15,0%). Do total de suspeitas de reações adversas, 11,9% foram notificadas como graves. A mais frequente foi o prolongamento do intervalo QT após o uso de hidroxicloroquina. Dessas suspeitas de reações adversas graves, 54,5% ocorreram em pessoas com mais de 65 anos. Conclusão. Embora não seja possível estabelecer uma relação causal com base na avaliação de relatos espontâneos, o presente estudo confirma a presença de reações adversas - algumas graves - a medicamentos que foram usados para tratar ou prevenir a COVID-19.

Regulatory convergence and harmonization: barriers to effective use and adoption of common standards / La convergencia y la armonización regulatorias: barreras en el uso y la adopción eficaces de normas comunes

ABSTRACT Objective To evaluate 1) the level of use and adoption of eight Technical Documents (TDs) published by the Pan American Network for Drug Regulatory Harmonization (PANDRH) member states and 2) identify the hurdles that can prevent countries from successfully adopting a common standard. Methods An in-depth analysis of the incorporation of PANDRH Technical Document No. 1 (“TDNo1”) recommendations in member states’ national requirements was carried out. Results The results illustrate the role of PANDRH in promoting convergence/harmonization among its members. Conclusions The study results show that the rate of use of TDs varied greatly by product/area and country. Timing, TD content, and product/area, and, more importantly, national capacities, are critical determinants of the level of TD guideline adoption. While PANDRH TDs have proven instrumental for the harmonization/convergence of member states’ national requirements, as shown by the level of convergence across a majority of the national requirements issued for vaccine licensing, several countries had yet to incorporate common standards due, in large part, to weak national regulatory capacities. Therefore, harmonization/convergence initiatives should include the strengthening of national regulatory capacities as part of their core strategy, which will, in turn, allow for the incorporation and deployment of common standards in all participating countries.

RESUMEN Objetivo Evaluar (1) la medida en que se usan y se han adoptado ocho documentos técnicos (DT) publicados por los estados miembros de la Red Panamericana para la Armonización de la Reglamentación Farmacéutica (Red PARF) y (2) definir los obstáculos que pueden impedir que los países adopten una norma común. Métodos Se realizó un análisis minucioso de la incorporación de las recomendaciones contenidas en el Documento Técnico No. 1 (“DTNo1”) de la Red Panamericana para la Armonización de la Reglamentación Farmacéutica en los requisitos nacionales de los estados miembros. Resultados Los resultados ilustran el papel que desempeña la Red Panamericana para la Armonización de la Reglamentación Farmacéutica en la promoción de la convergencia y armonización entre sus miembros. Conclusiones Los resultados del estudio indican que el uso de los DT varía enormemente según el producto o el área y el país. El momento, el contenido del DT, el producto o área y, lo que es más importante, la capacidad nacional son factores determinantes del grado de adopción de las directrices contenidas en los DT. Si bien los DT de la Red Panamericana para la Armonización de la Reglamentación Farmacéutica han sido decisivos en la armonización y convergencia de los requisitos nacionales de los estados miembros, como demuestra el grado de convergencia de la mayor parte de los requisitos nacionales emitidos para la concesión de licencias para vacunas, varios países no habían incorporado normas comunes todavía debido, en gran parte, a una capacidad de reglamentación nacional deficiente. Por lo tanto, las iniciativas en pro de la armonización y convergencia deben comprender el fortalecimiento de la capacidad de reglamentación nacional como parte de su estrategia central, lo cual permitirá, a su vez, que se incorporen y desplieguen normas comunes en todos los países participantes.

Microtubule-dependent intracellular transport of murine polyomavirus.

The mechanisms used by murine polyomavirus for intracellular migration are yet to be clarified. In this work we selectively depolymerized microtubules or actin fibers and then studied the progression of polyomavirus infection in cultured cells. Our results demonstrate that microtubule depolymerization prevents polyomavirus migration toward the nucleus and from the nucleus to the cell surface, being also involved in viral release, while disruption of the actin microfilaments appears to have no detrimental effect on the virus ability to reach the nucleus. The ultrastructural observation of polyomavirus nonenveloped particles interacting with the free end and the lateral sides of microtubules together with the coimmunoprecipitation of tubulin and viral VP-1 further supports the idea that polyomavirus intracellular migration seems to be mediated by the interaction of polyomavirus major capsid protein VP-1 with tubulin.