[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Bioengineering tools to speed up the discovery and preclinical testing of vaccines for SARS-CoV-2 and therapeutic agents for COVID-19.

This review provides an update for the international research community on the cell modeling tools that could accelerate the understanding of SARS-CoV-2 infection mechanisms and could thus speed up the development of vaccines and therapeutic agents against COVID-19. Many bioengineering groups are actively developing frontier tools that are capable of providing realistic three-dimensional (3D) models for biological research, including cell culture scaffolds, microfluidic chambers for the culture of tissue equivalents and organoids, and implantable windows for intravital imaging. Here, we review the most innovative study models based on these bioengineering tools in the context of virology and vaccinology. To make it easier for scientists working on SARS-CoV-2 to identify and apply specific tools, we discuss how they could accelerate the discovery and preclinical development of antiviral drugs and vaccines, compared to conventional models.

The traditional use of southern African medicinal plants in the treatment of viral respiratory diseases: A review of the ethnobotany and scientific evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral respiratory infections are amongst the most common infections globally, with most of the world's population contracting at least one infection annually. Numerous plant species are used in traditional southern African healing systems to treat these diseases and to alleviate the symptoms. Despite this, the therapeutic potential of these plants against viral respiratory diseases remains poorly explored. AIM OF THE STUDY: The aim of this study was to document the southern African plant species used in traditional medicine to treat viral respiratory infections. We also examined the extent of scientific evaluations of southern African plant species against the respiratory-infective viruses, with the aim of stimulating interest in this area and focusing on future studies. MATERIALS AND METHODS: We undertook an extensive review of ethnobotanical books, reviews and primary scientific studies to identify southern African plants which are used in traditional southern African medicine to treat viral respiratory diseases. This information was used to identify gaps in the current research that require further study. RESULTS: Two hundred and fifty-seven southern African plant species were identified as traditional therapies for viral respiratory diseases. Surprisingly, only one of those species (as well as twenty-one other species not recorded for these purposes) has been evaluated for the ability to block respiratory virus production. Furthermore, most of these studies screened against a single viral strain and none of those studies examined the mechanism of action of the plant preparations. CONCLUSIONS: Despite well documented records of the use of southern African plants to treat respiratory viral diseases, the field is poorly explored. Nearly all of the plant species used in traditional healing systems to treat these diseases are yet to be tested. Substantial further work is required to verify the efficacy of these traditional medicines.

The traditional use of southern African medicinal plants for the treatment of bacterial respiratory diseases: A review of the ethnobotany and scientific evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Multiple plant species were used traditionally in southern Africa to treat bacterial respiratory diseases. This review summarises this usage and highlights plant species that are yet to be verified for these activities. AIM OF THE STUDY: This manuscript reviews the traditional usage of southern African plant species to treat bacterial respiratory diseases with the aim of highlighting gaps in the literature and focusing future studies. MATERIALS AND METHODS: An extensive review of ethnobotanical books, reviews and primary scientific studies was undertaken to identify southern African plants which are used in traditional southern African medicine to treat bacterial respiratory diseases. We also searched for southern African plants whose inhibitory activity against bacterial respiratory pathogens has been conmfirmed, to highlight gaps in the literature and focus future studies. RESULTS: One hundred and eighty-seven southern African plant species are recorded as traditional therapies for bacterial respiratory infections. Scientific evaluations of 178 plant species were recorded, although only 42 of these were selected for screening on the basis of their ethnobotanical uses. Therefore, the potential of 146 species used teraditionally to treat bacterial respiratory diseases are yet to be verified. CONCLUSIONS: The inhibitory properties of southern African medicinal plants against bacterial respiratory pathogens is relatively poorly explored and the antibacterial activity of most plant species remains to be verified.

Evaluación positiva de medicamentos: marzo, abril y mayo 2017 / Possitive assessment of drugs: March, April and May 2017

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en marzo, abril y mayo 2017, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento (AU)

The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public in March, April and May of 2017, and considered of interest to the healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product (AU)

La reproducibilidad de las investigaciones biomédicas: Quo vadis? / Reproducibility of biomedical research: Quo vadis?

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Fármacos cannabinoides para las enfermedades neurológicas: ¿qué hay detrás? / Cannabinoid drugs for neurological diseases: what is behind?

En los últimos años se han producido avances en el desarrollo de fármacos basados en la planta Cannabis sativa o en moléculas sintéticas con una acción similar. Alguno de estos fármacos, como el aerosol bucal Sativex ®, ha sidorecientemente aprobado para el tratamiento de la espasticidad en esclerosis múltiple, pero anteriormente lo fueron otros, como Marinol ® o Cesamet ® para el tratamiento del vómito y la náusea, y el síndrome de anorexia-caquexia. Este incipiente uso clínico de fármacos cannabinoides confirma algo que ya se conocía desde tiempos bastante más antiguos yhasta prácticamente el siglo pasado, que es el potencial de esta planta para uso medicinal, algo que se vio frenado por el abuso de preparados de la planta también para uso recreacional. En cualquier caso, este incipiente uso clínico de fármacoscannabinoides no tiene detrás la mera anécdota del uso medicinal del cannabis desde tiempos antiguos, sino el impulso de la investigación científica, que ha permitido identificar las dianas moleculares que son activadas o inhibidas porestas sustancias, dianas que forman parte de un nuevo sistema de comunicación intercelular especialmente activo en elsistema nervioso central, que se ha denominado ‘sistema cannabinoide endógeno’, y que, como muchos otros sistemas, es susceptible de manipulación farmacológica. Esta revisión pretende bucear en el conocimiento científico generado entorno a este sistema en los últimos años, como paso necesario para justificar el desarrollo de fármacos basados en su activación o inhibición y que puedan ser útiles en diferentes enfermedades neurológicas (AU)

In recent years progress has been made in the development of pharmaceuticals based on the plant Cannabis sativa or on synthetic molecules with a similar action. Some of these pharmaceuticals, such as the mouth spray Sativex ®,have recently been approved for the treatment of spasticity in multiple sclerosis, but they are not the first and others, such as Marinol ® or Cesamet ® for the treatment of vomiting and nausea, and anorexia-cachexia syndrome, had already beenapproved. This incipient clinical use of cannabinoid drugs confirms something that was already known from fairly ancient times up to practically the last century, which is the potential use of this plant for medicinal applications somethingwhich was brought to a standstill by the abusive use of preparations of the plant for recreational purposes. In any case, this incipient clinical use of cannabinoid drugs is not backed just by the anecdote of the medicinal use of cannabis since ancient times, but instead the boost it has been given by scientific research, which has made it possible to identify thetarget molecules that are activated or inhibited by these substances. These targets are part of a new system of intercellularcommunication that is especially active in the central nervous system, which is called the ‘endogenous cannabinoid system’ and, like many other systems, can be manipulated pharmacologically. The aim of this review is to probe further intothe scientific knowledge about this system generated in the last few years, as a necessary step to justify the development of pharmaceuticals based on its activation or inhibition and which can be useful in different neurological diseases (AU)

Enfermedades crónicas de alta prevalencia en una población asistida por la Seguridad Social / Highly prevalent chronic diseases in a population with Social Security coverage

Objetivo: Una de las prioridades sanitarias de las políticas europeas es la obtención de información sobre enfermedades crónicas y de alta prevalencia; ésta se encuentra limitada por la calidad de los datos disponibles. El objetivo del estudio fue describir el comportamiento de las enfermedades crónicas más prevalentes a través de bases de datos de gestión administrativa. Método: Estudio transversal retrospectivo sobre medicamentos fabricados industrialmente, dispensados y financiados total o parcialmente con fondos públicos por el Servicio de Salud deCastilla-La Mancha, a través de farmacias. El estudio se realizó durante 2003 y 2004 en el área de salud de Albacete y en él se aplicó la metodología recomendada por la Organización Mundial de la Salud para los estudios de utilización de medicamentos. El valor de la dosis diaria definida permitió conocer el número que contenía cada envase y el utilizado por 1.000 usuarios y por día, variable cuantitativa asimilable al concepto de tasa poblacional. Mediante la variable cualitativa, principio activo identificado por su código ATC, se agruparon medicamentos por indicación principal y se relacionaron con la variable cuantitativa. Resultados: La mayor prevalencia se observó en la hipertensión (27,3%: 24,2-36,7), las alteraciones del metabolismo lipídico (7,4%: 5,9-10,7) y la diabetes (6,8%: 5,9-9,7); se constató un incremento en todos los casos (del 8,9, el 27,5 y el 9,2%, respectivamente). Ambas situaciones destacan en los distritos dela sierra. Conclusiones: Es posible conocer cuál es la situación de las enfermedades crónicas de alta prevalencia, con bases de datos de gestión, mediante estudios de utilización de medicamentos. Su aplicación a ámbitos y periodos diferentes requiere la adopción de criterios metodológicos similares (AU)

Objective: One of the sanitary priorities in Europe is the obtaining of information about the high prevalence and chronic diseases, which is limited by the quality of the available information. The aim of the present study was to describe the behavior of the most prevalent chronic diseases using databases of administrative management. Method: We performed a retrospective, cross-sectional study of drugs made industrially, dispensation and financed, whole or partially with public funds, by the Health Service of Castilla-La Mancha, through pharmacies. The study was conducted between the years 2003 and 2004 in the health area of Albacete; in the study the methodology recommended by the World Health Organization WHO for conducting drug utilization studies was applied. The value of the defined daily dose allowed knowing the number contained in each package and the number of them used per thousand users and per day, quantitative assimilable variability to the population rate concept. Through the qualitative variable, active drug substance identified by ATC code, drugs with the same composition and principal indication were grouped, and they were related to the quantitative variable. Results: The greater prevalence was seen in hypertension(27.3%: 24.2-36.7), lipid metabolism alterations (7.4%: 5.9-10.7) and diabetes (6.8%: 5.9-9.7); an increase was established in all the cases (of 8.9%, of 27.5% and of 9.2%, respectively). Both situations stand out in the districts of the mountain range. Conclusions: It is possible to know the status of chronic diseases and high prevalence, with management databases, by means of studies of medication use. Its application to different areas and periods requires the adoption of similar methodological criteria (AU)

[Traditional and translational medicine]. / La médecine traditionnelle et la médecine translationnelle.

In the second half of the 20th century, the development of experimental pharmacology led to the discovery of powerful new therapeutic agents, but production has since faltered, particularly in Europe. The purpose of this paper is to review how the gap in the production of novel medicines between Europe and the USA could be filled by proper use of molecular biology data. The European program entitled 'The Innovative Medicines Initiative' could facilitate the translation of information from benchtop to bedside.

Problemas relacionados con la medicación / Problems related to medication

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Chemical and biological characterization and clinical evaluation of botanical dietary supplements: a phase I red clover extract as a model.

Botanical dietary supplements, as compared with nutritional supplements or single-component pharmaceutical drugs, are typically less-refined preparations derived from bulk plant material and, as such, require a modified approach to their development, production, and evaluation. An integrated, multidisciplinary team of scientific and clinical investigators is required in order to develop high quality phytomedicines and rigorously evaluate their safety and efficacy. Research on botanicals involves unique challenges as plant source materials frequently vary in chemical content and may contain unwanted pesticides, heavy metals, contaminant plant species, or other adulterants. Ideally, a botanical formulation should be standardized, both chemically and biologically, by a combination of analytical techniques and bioassays. This combination approach provides multiple measures by which reproducible quality and efficacy of botanical supplements may be achieved, and is particularly useful for botanical products for which the active compound(s) have not yet been identified. Safety and toxicity should be evaluated during the supplement development process in both in vitro and in vivo systems. A number of liquid chromatography-mass spectrometry methods can aid in the assessment of purity, bioavailability, toxicity, metabolism, and molecular target profiling of botanical extracts. Clinical investigators must appreciate the complexity of multi-component phytomedicines and adjust trial protocols accordingly. This review highlights practical considerations of value to basic science and clinical investigators engaged in the study of botanical supplements. Lessons and examples are drawn from the authors' experience in designing and developing a red clover (Trifolium pratense L.) standardized extract for evaluation in Phase I and Phase II clinical trials.

Mejores medicinas para los niños. Acciones reguladoras sobre los medicamentos pediátricos / Medicine improvement for children. Regulatory actions on the pediatric drugs

Antes de que un adulto sea tratado con un medicamento, puede tener la certeza de que es seguro, eficaz y de alta calidad para su empleo. Una asunción similar puede no ser necesariamente correcta en el caso de las medicinas infantiles. En efecto, se estima que más del 50 por ciento de éstas, particularmente las empleadas en medicina especializada, nunca han sido estudiadas para su empleo en niños. La ausencia de medicamentos autorizados correctamente para tratar enfermedades en niños que hayan sido analizados y evaluados es un hecho que ha preocupado desde hace tiempo. Como consecuencia de ello, las medicinas de la Unión Europea (UE) frecuentemente no proporcionan información sobre seguridad y eficacia en las poblaciones pediátricas. Todo ello conduce al empleo de productos médicos no autorizados y/o al empleo de medicinas para indicaciones no descritas en el proceso de la droga en cuestión, lo que puede generar riesgos significativos, que incluyen: ausencia de eficacia y/o efectos secundarios inesperados, con el resultado incluso de fallecimiento. Este hecho ha preocupado a reguladores, Estados miembros, miembros del Parlamento Europeo, pediatras y padres. En diciembre de 2000, el Consejo Europeo de Salud (European Health Council) solicitó a la Comisión Europea tomar las correspondientes medidas para remediar este problema. Este documento esboza algunos de los elementos sugeridos para afrontar la ausencia de medicamentos convenientemente adaptados. Asimismo, examina un número de posibilidades para incentivar la protección de la propiedad intelectual, al tiempo que propone la creación de un grupo europeo de expertos, así como una red europea de pediatras con competencia específica en la vigilancia y supervisión de ensayos apropiados en niños. Se analizan los elementos de información y transparencia, así como la necesidad de asegurar los máximos estándares éticos como queda establecido en la directiva de la UE sobre Buenas Prácticas Clínicas (Good Clinical Practices) cuando se efectúa cualquier ensayo en niños. Finalmente, se analizan las fuentes de financiación para la investigación de los medicamentos en niños, que no están asociadas con ninguna protección de propiedad intelectual, explorándose algunas opiniones al respecto. Este manuscrito representa una de las primeras etapas en el cumplimiento de la obligación de la Comisión para afrontar este problema, en respuesta a una excelente reunión con los Estados miembros en el marco del Comité Farmacéutico de la Comisión (Commission's Pharmaceutical Committee), celebrada en noviembre de 2001 (AU)

Development of therapeutics: opportunities within complementary and alternative medicine.

Whereas other components of the National Institutes of Health support the discovery and subsequent development of novel chemical entities into drugs, the National Center for Complementary and Alternative Medicine (NCCAM) studies complex natural products that are marketed as dietary supplements. This article contrasts the regulatory framework for dietary supplements and drugs, outlines the challenges of evaluating dietary supplements for safety and clinical effectiveness, and describes the evolving drug model for botanicals.

From pharmacovigilance to pharmacoperformance.

The pharmaceutical industry is going through a period of enormous upheaval, as new sciences, technologies and commercial pressures reshape the way in which it performs research and development. PwC Consulting estimates that the top 20 companies will each need to launch between four and six times the number of drugs they currently produce, as well as improving the quality of those drugs, merely to maintain shareholder returns. This has huge implications for pharmacovigilance departments. More drugs means more trials, more patients and -- of course -- more safety reports for evaluation. The pharmacovigilance teams in most big companies are ill prepared for this transition being already stretched to the limit. But as demand for patients to participate in clinical trials increases -- with shorter development times, higher success rates in discovery and greater productivity -- so companies with a poor reputation for safety will suffer. What is it then that companies should be doing to remain compliant and be seen to be safe in the eyes of the consumer? Can pharmacoepidemiology support both molecules in the marketplace as well as those in research and development and what is really needed to enable this? Key to success will be the ability to capture, analyse and evaluate data (from disparate sources) in real time and to make rapid decisions on the appropriate course of action. Putting better structures, processes and technological platforms in place to cope with a big increase in throughput is only a short-term solution yet is it enough to fulfil the objective in the long-term of ensuring compliance and patient safety?

Post-modern drug evaluation. The deconstruction of evidence-based regulation.

Traditionally in medicine, nearly all prescribing decisions were made by the treating physician. The patient had relatively little input and hardly any access to alternative sources of information bearing on that decision; the cost of the prescription was covered by the patient or by an insurer, and neither was likely to provide any feedback to the physician to shape his or her decision. Now, all that has changed. Beginning with the consumerist movement of recent decades and culminating in the explosion of health-related information on the Internet, patients are increasingly vocal participants in the prescribing decision, on both clinical and economic grounds. Payers have become participants as well, and increasingly seek to influence prescribing decisions in the light of their own economic imperatives. Added to all these cross-currents is an additional wild card: the proliferation of 'alternative medicines,' 'nutraceuticals' and other nostrums that society has placed beyond the reach of the evidence-based discourse and regulations that govern conventional drug therapy. In a country where patients struggle to cover the cost of prescription therapies proven both safe and effective in rigorous clinical trials, billions of dollars per year are spent on alternative treatments in the US, unencumbered by concerns about whether they actually work or that they might be toxic. While these patterns of communication, education, disinformation and economic influence are much more chaotic than those that prevailed in the 'good old days,' this very ferment may also present opportunities for improvement of rational pharmacotherapy and public health. This paper briefly outlines the above changes in patterns of communication and influence as they relate to medication use in today's industrialised world (particularly the US), and suggests both hopeful and terrifying scenarios describing where these trends might lead in the coming decade.