New Author Guidelines for Displaying Data and Reporting Data Analysis and Statistical Methods in Experimental Biology.

The American Society for Pharmacology and Experimental Therapeutics has revised the Instructions to Authors for Drug Metabolism and Disposition, Journal of Pharmacology and Experimental Therapeutics, and Molecular Pharmacology These revisions relate to data analysis (including statistical analysis) and reporting but do not tell investigators how to design and perform their experiments. Their overall focus is on greater granularity in the description of what has been done and found. Key recommendations include the need to differentiate between preplanned, hypothesis-testing, and exploratory experiments or studies; explanations of whether key elements of study design, such as sample size and choice of specific statistical tests, had been specified before any data were obtained or adapted thereafter; and explanation of whether any outliers (data points or entire experiments) were eliminated and when the rules for doing so had been defined. Variability should be described by S.D. or interquartile range, and precision should be described by confidence intervals; S.E. should not be used. P values should be used sparingly; in most cases, reporting differences or ratios (effect sizes) with their confidence intervals will be preferred. Depiction of data in figures should provide as much granularity as possible, e.g., by replacing bar graphs with scatter plots wherever feasible and violin or box-and-whisker plots when not. This editorial explains the revisions and the underlying scientific rationale. We believe that these revised guidelines will lead to a less biased and more transparent reporting of research findings.

Toward a Consensus on Applying Quantitative Liquid Chromatography-Tandem Mass Spectrometry Proteomics in Translational Pharmacology Research: A White Paper.

Quantitative translation of information on drug absorption, disposition, receptor engagement, and drug-drug interactions from bench to bedside requires models informed by physiological parameters that link in vitro studies to in vivo outcomes. To predict in vivo outcomes, biochemical data from experimental systems are routinely scaled using protein quantity in these systems and relevant tissues. Although several laboratories have generated useful quantitative proteomic data using state-of-the-art mass spectrometry, no harmonized guidelines exit for sample analysis and data integration to in vivo translation practices. To address this gap, a workshop was held on September 27 and 28, 2018, in Cambridge, MA, with 100 experts attending from academia, the pharmaceutical industry, and regulators. Various aspects of quantitative proteomics and its applications in translational pharmacology were debated. A summary of discussions and best practices identified by this expert panel are presented in this "White Paper" alongside unresolved issues that were outlined for future debates.

Reported needs of information resources, research tools, connectivity and infrastructure among African Pharmacological Scientists to improve future patient care and health.

INTRODUCTION: The potentials of Africa for growth and economic transformation through science remains challenging because of existing gaps in knowledge and infrastructure. The Africa Pharmacological Science Gateway project and the Medicines Utilization Research in Africa Group seek to meet the research needs of African pharmacologists. This study aimed at identifying priority needs that might be met by access to information and tools through e-infrastructure. METHODS: A web-based cross-sectional study among 472 members of pharmacological societies in Africa to obtain information on their research interests and skills, available resources, needs, and knowledge gaps. Descriptive analyses were done. RESULTS: A total of 118 responses from 13 countries were received, mostly from Nigeria (48.3%) and South Africa (21.3%). Respondents had wide ranges of research interests predominantly in drug utilization research. The desired resources included drug utilization research training and tools, pharmacokinetics and pharmacometrics modeling training and tools, drug-drug interaction and medicine prices resources, statistical analysis resources, access to journals, training in specific laboratory techniques, equipment and funding for research-related activities. CONCLUSIONS: Key areas of needs not currently provided by the African Pharmacological Science Gateway e-infrastructure were identified to guide the further provision of resources on the e-infrastructure and potentially enhance research capacity within the continent.

Progress and assessment of a contextualized teaching session of pharmacology.

BACKGROUND: Learning transfer, in medical teaching, remains an essential question and optimizing it is the main preoccupation of every trainer in medical sciences. Some learning methods showed their efficacy as the contextualized learning in the framework of a professional activity or in a situation recalling it in a realistic manner. AIM: To describe steps of planning and progress of a session of clarification, illustration, application et participation (CIAP) of pharmacology teaching students from second cycle of medical studies (DCEM) and to assess the session. METHODS: We performed a descriptive transversal study in April 2017 in the Faculty of Medicine of Tunis. Our work was composed of two parts. The first part consisted in a description of the preparation and the progress of the CIAP session entitled antiepileptic drugs, which is comprised in the pharmacology teaching of the certificate of Neurology to the students of DCEM. The second part consisted in an assessment of knowledge acquisition and the progress of the session by the students. RESULTS: We proceeded to a planning of the session which resulted in a contextualized teaching and induced an active participation and an interactivity of the students. Comparison of the results of the pretest and the posttest showed a statistically significant difference in terms of good responses. The assessment of the session progress was good. CONCLUSION: Our study demonstrated the feasibility of a session of contextualized teaching session or CIAP of pharmacology and its input in terms of knowledge to the students.

The Enduring Legacy of 250 Years of Pharmacology in Edinburgh.

In 1768, 250 years ago, the University of Edinburgh appointed Francis Home to the first chair of materia medica, the accumulated knowledge of materials used in healing. Francis Home and his colleagues were determined to improve the quality of medical training in Edinburgh by introducing a final examination and compiling a catalog of medicines validated by the Royal College of Physicians of Edinburgh. The catalog, known as the Edinburgh Pharmacopoeia, was a great success, partly due to the orderly nature of its contents, its routine editing to eliminate worthless entries, and the introduction of new treatments whose preparation was precisely documented. In a relatively short time, the worth of the Edinburgh Pharmacopoeia was recognized throughout Europe, America, and the British Empire. Today, the British and European Pharmacopoeias are catalogs of publicly available, legally enforceable standards for active pharmaceutical ingredients and finished dosage forms of pharmaceutical products and medical devices. Home and the many luminaries who succeeded him would surely take pleasure and pride in the fact that the mantra of today's medicines regulators worldwide is little different from that of these early visionaries: "To take better advantage of the best possible science in the service of the public health and our health-care systems" ( 1 , p. 492).

Strategic establishment of an International Pharmacology Specialty Laboratory in a resource-limited setting

Background: A growing number of drug development studies that include pharmacokinetic evaluations are conducted in regions lacking a specialised pharmacology laboratory. This necessitated the development of an International Pharmacology Specialty Laboratory (IPSL) in Zimbabwe.Objectives: The aim of this article is to describe the development of an IPSL in Zimbabwe.Methods: The IPSL was developed collaboratively by the University of Zimbabwe and the University at Buffalo Center for Integrated Global Biomedical Sciences. Key stages included infrastructure development, establishment of quality management systems and collaborative mentorship in clinical pharmacology study design and chromatographic assay development and validation.Results: Two high performance liquid chromatography instruments were donated by an instrument manufacturer and a contract research organisation. Laboratory space was acquired through association with the Zimbabwe national drug regulatory authority. Operational policies, standard operating procedures and a document control system were established. Scientists and technicians were trained in aspects relevant to IPSL operations. A high performance liquid chromatography method for nevirapine was developed with the guidance of the Clinical Pharmacology Quality Assurance programme and approved by the assay method review programme. The University of Zimbabwe IPSL is engaged with the United States National Institute of Allergy and Infectious Diseases Division of AIDS research networks and is poised to begin drug assays and pharmacokinetic analyses.Conclusions: An IPSL has been successfully established in a resource-limited setting through the efforts of an external partnership providing technical guidance and motivated internal faculty and staff. Strategic partnerships were beneficial in navigating challenges leading to laboratory development and training new investigators. The IPSL is now engaged in clinical pharmacology research

Modificar la especificación técnica del producto farmacéutico Factor VIIA o EPTACOG ALFA (Activado) 2 punto 4 mg/vial + sdiluyente - AM incluido en el Petitorio Farmacológico de ESSALUD / MModify the technical specification of the pharmaceutical product Factor VIIA or EPTACOG ALFA (Activated) 2 score 4 mg / vial + solvent-AM included in the Pharmacological Request of ESSALUD

La Carta Número 304-DETS-IETSI-ESSALUD-2016 y el Informe Número 135-SDEPFyOT-DETS-IETSI-ESALUD-2016 que sustenta la modificación del producto farmacéutico FACTOR VIIA o EPTACOG ALFA (Activado) 2.4 mg/vial + diluyente - AM en el Petitorio Farmacológico de ESSALUD. SE RESUELVE: MODIFICAR: La especificación técnica del producto farmacéutico FACTOR VIIA o EPTACOG ALFA (Activado) 2.4 mg/vial + diluyente - AM en el Petitorio Farmacológico de ESSALU según consta en tabla de la Resolución. DISPONER: que la Dirección de Evaluación de Tecnologías Sanitarias del Instituto de Evaluación de Tecnologías en Salud e Investigación haga de conocimiento a todos los órganos desconcentrados, órganos prestadores nacionales, establecimientos de salud y demás órganos que correspondan, la presente Resolución. DISPONER: que la Dirección de Evaluación de Tecnologías Sanitarias del Instituto de Evaluación de Tecnologías en Salud e Investigación coordine con la Gerencia Central de Tecnologías de Información y Comunicaciones, la publicación de la inclusión de los referidos medicamentos en el Petitorio Farmacológico en la pagina WEB de ESSALUD.

Modificar en el Petitorio Farmacológico de ESSALUD la unidad de manejo del producto lípidos / Modify in the Pharmacological Request of ESSALUD the product handling unit lipids

Resolución de Instituto de Evaluación de Tecnologías en Salud e Invstigación Número 30 -IETSI-ESSALUD-2016. Vista: La carta Número 272-DETS-IETSI-ESSALUD-2016, el Informe Número 110-S Modificar en el Petitorio Farmacológico de ESSALUD, el siguiente producto farmacéutico: Codigo: 011050115 - Denominación Según DCI: Lipidos - Especificaciones Tecnicas: 20% x 250 mL a 500 mL (apto para mezclas con lípidos incorporados) - Unidad de Manejo: cm³ - Restricción de Uso: 1,7. Disponer que la Dirección de Evaluación de Tecnologías Sanitarias del Instituto de Evaluación de Tecnología en Salud e Investigación haga de conocimiento a todos los órganos desconcentrados, órganos prestadores nacionales, establecimientos de salud y demás órganos que correspondan, la presente Resolución. Disponer que la Dirección de Evaluación de Tecnologías Sanitarias del Instituto de Evaluación de Tecnología en Salud e Investigación coordine con la Gerencia Central de Tecnologías de Información y Comunicaciones, la publicación de lo dispuesto en la presente resolución, en la página Web de ESSALUD.

Incluir en el Petitorio Farmacológico de ESSALUD, 11 productos farmacéuticos, de acuerdo a la Lista Complementaria de Medicamentos para el Tratamiento de la Tuberculosis, ITS, VIH/SIDA, y malaria, aprobada por Resolución Ministerial N° 577-2015-/MINSA / Include in the Pharmacological Request of ESSALUD 11 pharmaceutical products, according to the Complementary List of Medications for the Treatment of Tuberculosis, STIs, HIV / AIDS, and malaria, approved by Ministerial Resolution No. 577-2015-/MINS

Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 01 -IETSI-ESSALUD-2016. Vistos: La Carta N° 123-DETS-IETS-ESSALUD-2015 y el Informe Técnico N° 030-SDEPFyOT-DETS-IETSI-ESSALUD-2015, a través del cual Sub Dirección de Evaluación de Productos Farmacéuticos y Otras Tecnologías Sanitarias de la Dirección de Evaluación de Tecnologías Sanitarias sustenta la inclusión de 11 medicamentos correspondientes a la Lista Complementaria de Medicamentos para el Tratamiento de la Tuberculosis, de las ITS Complementaria de Medicamentos para el Tratamiento de la Tuberculose, de las ITS VIH/SIDA y la Malaria, incorporada al Documento Técnico: Petitorio Nacional Único de Medicamentos Esenciales mediante Resolución Ministerial N° 577-2015/MINSA. Incluir el Petitorio Farmacológico de ESSALUD, los productos farmacéuticos que constan en la presente Resolucción. Disponer que la Dirección de Evaluación de Tecnologías Sanitarias del Instituto de Evaluación de Tecnología en Salud e Investigación haga de conocimiento a todos los órganos desconcentrados, órganos prestadores nacionales, establecimientos de salud y demás órganos que corresopndan, la presente Resolución. Disponer que la Dirección de Evaluación de Tecnologías Sanitarias del Instituto de Evaluación de Tecnología en Salud e Investigació coordine con la Gerencia Central de Tecnologías de Información y Comunicaciones, la publicación de la inclusión de los referidos medicamentos en el Petitorio Farmacológico en la página Web de ESSALUD.

[Academician Nikolai Pavlovich Kravkov: on his 150th birthday].

The article outlines the life and activities of academician N. P. Kravkov (1865-1924), the founder of pharmacology in Russia. During his 25 years of service as Head of the Department of Pharmacology at the Military Medical Academy in St. Petersburg, N. P. Kravkov established a large national school of pharmacological science. He was the author of a number of fundamental discoveries, which enriched the Russian and world science.

The shifting landscape of safety pharmacology in 2015.

The relative importance of the discipline of safety pharmacology (which integrates physiology, pharmacologyand toxicology) has evolved since the incorporation of the Safety Pharmacology Society (SPS) as an entity on August 10, 2000. Safety pharmacology (SP), as a synthesis of these other fields of knowledge, is concerned with characterizing the safety profile (or potential undesirable pharmacodynamic effects) of new chemical entities (NCEs) and biologicals. Initially focused on the issue of drug-induced QT prolongation it has developed into an important discipline over the past 15years with expertise beyond its initial focus on torsades de pointes (TdP). It has become a repository for interrogation of models for drug safety studies and innovative non-clinical model development, validation and implementation. Thus, while safety pharmacology consists of the triumvirate obligatory cardiovascular, central nervous system (CNS) and respiratory system core battery studies it also involves assessing drug effects on numerous other physiological systems (e.g., ocular, auditory, renal, gastrointestinal, blood, immune) leveraging emerging new technologies in a wide range of non-clinical drug safety testing models. As with previous editorials that preface the themed issue on safety pharmacology methods published in the Journal of Pharmacological and Toxicological Methods (JPTM), we highlight here the content derived from the most recent (2014) SPS meeting held in Washington, DC. The dynamics of the discipline remain fervent and method development, extension and refinement are reflected in the content. This issue of the JPTM continues the tradition of providing a publication summary of articles (reviews, commentaries and methods) with impact on the discipline of safety pharmacology.

Inyecciones intravítreas: ¿y qué prefieren los pacientes? Análisis de satisfacción y preferencias sobre la ubicación de la realización de inyección intravítrea. Respuesta de los autores / Intravitreal inyections: What do patients prefer? Analysis of patient's satisfaction and preferences about where to perform intravitreal injection. Author's reply

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From HTS to Phase I: the Institute for Therapeutics Discovery and Development at the University of Minnesota.

The high-throughput screening core at the University of Minnesota is part of the Institute for Therapeutics Discovery and Development (ITDD), a comprehensive drug discovery and development center. The Institute provides scientific services to both academic and business communities and supports translational medicine via collaborations and contractual work. The ITDD is well-known for its broad range of screening capabilities and offers extensive medicinal chemistry expertise along with GMP scale-up and pre-clinical pharmacology support.

[Collaborative projects with academia for regulatory science studies on biomarkers].

Biomarkers are useful tools to be utilized as indicators/predictors of disease severity and drug responsiveness/safety, and thus are expected to promote efficient drug development and to accelerate proper use of approved drugs. Many academic achievements have been reported, but only a small number of biomarkers are used in clinical trials and drug treatments. Regulatory sciences on biomarkers for their secure development and proper qualification are necessary to facilitate their practical application. We started to collaborate with Tohoku University and Nagoya City University for sample quality, biomarker identification, evaluation of their usage, and making guidances. In this short review, scheme and progress of these projects are introduced.

ÉPICO project. Development of educational recommendations using the DELPHI technique on invasive candidiasis in non-neutropenic critically ill adult patients.

BACKGROUND: Although there has been an improved management of invasive candidiasis in the last decade, controversial issues still remain, especially in the diagnostic and therapeutic approaches. AIMS: We sought to identify the core clinical knowledge and to achieve high level agreement recommendations required to care for critically ill adult patients with invasive candidiasis. METHODS: A prospective Spanish survey reaching consensus by the DELPHI technique was made. It was anonymously conducted by electronic mail in a first term to 25 national multidisciplinary experts in invasive fungal infections from five national scientific societies, including intensivists, anesthesiologists, microbiologists, pharmacologists and infectious diseases specialists, who answered to 47 questions prepared by a coordination group after a strict review of the literature in the last five years. The educational objectives spanned five categories, including epidemiology, diagnostic tools, prediction rules, and treatment and de-escalation approaches. The level of agreement achieved among the panel experts in each item should exceed 75% to be selected. In a second term, after extracting recommendations from the selected items, a face to face meeting was performed where more than 80 specialists in a second round were invited to validate the preselected recommendations. RESULTS: In the first term, 20 recommendations were preselected (Epidemiology 4, Scores 3, Diagnostic tools 4, Treatment 6 and De-escalation approaches 3). After the second round, the following 12 were validated: (1) Epidemiology (2 recommendations): think about candidiasis in your Intensive Care Unit (ICU) and do not forget that non-Candida albicans-Candida species also exist. (2) Diagnostic tools (4 recommendations): blood cultures should be performed under suspicion every 2-3 days and, if positive, every 3 days until obtaining the first negative result. Obtain sterile fluid and tissue, if possible (direct examination of the sample is important). Use non-culture based methods as microbiological tools, whenever possible. Determination of antifungal susceptibility is mandatory. (3) Scores (1 recommendation): as screening tool, use the Candida Score and determine multicolonization in high risk patients. (4) Treatment (4 recommendations): start early. Choose echinocandins. Withdraw any central venous catheter. Fundoscopy is needed. (5) De-escalation (1 recommendation): only applied when knowing susceptibility determinations and after 3 days of clinical stability. The higher rate of agreement was achieved in the optimization of microbiological tools and the withdrawal of the catheter, whereas the lower rate corresponded to de-escalation therapy and the use of scores. CONCLUSIONS: The management of invasive candidiasis in ICU patients requires the application of a broad range of knowledge and skills that we summarize in our recommendations. These recommendations may help to identify the potential patients, standardize their global management and improve their outcomes, based on the DELPHI methodology.