Leveraging multi-omics data to empower quantitative systems pharmacology in immuno-oncology.

Understanding the intricate interactions of cancer cells with the tumor microenvironment (TME) is a pre-requisite for the optimization of immunotherapy. Mechanistic models such as quantitative systems pharmacology (QSP) provide insights into the TME dynamics and predict the efficacy of immunotherapy in virtual patient populations/digital twins but require vast amounts of multimodal data for parameterization. Large-scale datasets characterizing the TME are available due to recent advances in bioinformatics for multi-omics data. Here, we discuss the perspectives of leveraging omics-derived bioinformatics estimates to inform QSP models and circumvent the challenges of model calibration and validation in immuno-oncology.

Oral Medicine and Pharmacology Teleconsulting Sessions of the Telehealth Program in one Southeastern State of Brazil

ABSTRACT Objective: To evaluate questions concerning oral medicineand pharmacology-related specialties of asynchronous dental teleconsulting sessions of the Telehealth Brazil Networks Program. Material and Methods: Data were collected from secondary databases of asynchronous dental teleconsulting sessions of the telehealth centers of Minas Gerais from July 2015 to July 2017. The variables for dental underlying fields and the types of questions were evaluated. Descriptive analysis was performed with the SPSS v.22.0 program. Results: 3,920 teleconsulting sessions were referred to the telehealth centers of Minas Gerais during the study period. Regarding oral medicine-related questions (n=745), most (n=469; 62.95%) addressed diagnosis, whereas the underlying field questions mostly regarded fungal, viral, and bacterial infections (17.3%), biopsies (16.4%), developmental defects and dental abnormalities (9.9%), and soft tissue tumors (9.4%). Pharmacology-related questions (n=738) mostly addressed general approaches (n=672; 91.06%), and the most common questions were about underlying fields' prescriptions (44.7%), anesthetics (17.6%), adverse effects of medications and anesthetics (10.2%), and selection of anesthetics for patients with systemic conditions (9.8%). Conclusion: Most teleconsulting sessions regarded conditions or procedures common in primary health care and essential for diagnosis and treatment planning at all care levels, which suggests a need for more academic learning processes for healthcare professionals, especially in dentistry primary fields.

Modalidades Fisioterapêuticas no Manejo da Dor Neuropática Induzida pelo Tratamento do Câncer de Mama: Revisãoda Literatura / Physiotherapeutic Modalities in the Management of Neuropathic Pain Induced by Breast Cancer Treatment: Literature Review / Modalidades Fisioterapéuticas en el Manejo Del Dolor Neuropático Inducido por el Tratamiento del Cáncer de Mama: Revisión de la Literatura

A sobrevida de mulheres após o tratamento do câncer de mama tem aumentado em virtude de avanços na detecção precoce e terapias disponíveis. Porém, as sobreviventes comumente enfrentam efeitos adversos após o tratamento que representam grande carga física e psicológica. Além da fadiga, a dor é o sintoma persistente mais frequente após o tratamento. Objetivo: Sistematizar os resultados de ensaios clínicos randomizados sobre a intervenção fisioterapêutica na dor neuropática periférica induzida pelos tratamentos para o câncer de mama. Método: Busca realizada nas bases de dados MEDLINE via portal PubMed e Cochrane. Foram selecionados ensaios clínicos randomizados publicados a partir de 2017, em língua inglesa, que abordassem as modalidades fisioterapêuticas como intervenção, a dor neuropática periférica induzida por tratamentos oncológicos como desfecho, e mulheres sobreviventes ao câncer de mama como população de interesse. A qualidade metodológica dos estudos foi avaliada pela ferramenta Cochrane para o risco de viés. Resultados: Quatro estudos foram revisados na íntegra. Majoritariamente, os efeitos adversos do tratamento oncológico se devem a regimes quimioterápicos à base de taxanos. Os desfechos avaliados incluem, além da dor, demais sinais neuropáticos e influência nas atividades de vida diária. Os estudos variaram quanto à intervenção e fase de tratamento. Apenas um dos estudos demonstrou resultado significativamente positivo a favor do grupo intervenção. Conclusão: Estudos clínicos randomizados disponibilizam evidências escassas quanto aos efeitos positivos da intervenção fisioterapêutica na dor neuropática periférica induzida pelos tratamentos para o câncer de mama.

Women's survival after breast cancer treatment has increased due to advances in early detection and available therapies. However, great physical and psychological burden are the result of adverse effects that survivors commonly face. In addition to fatigue, pain is the most common persistent symptom after cancer treatment. Objective: Systematize the results of randomized clinical trials on physiotherapeutic intervention in peripheral neuropathic pain induced by breast cancer treatments . Method:The search was carried out on the MEDLINE databases via PubMed and Cochrane portals. Randomized clinical trials published since 2017 in English, that addressed physiotherapeutic modalities as intervention, peripheral neuropathic pain induced by oncological treatments as outcome were selected, and the population of interest were women surviving breast cancer. The Cochrane-risk-of-bias tool was applied to evaluate the methodological quality of the studies. Results: Four studies were fully reviewed. Most of the adverse effects of cancer treatment are due to taxane-based chemotherapy regimens. The outcomes assessed include, in addition to pain, other neuropathic signs and influence on activities of daily living. The studies varied in terms of intervention and treatment phase. Only one of the studies demonstrated a significantly positive result in favor of the intervention group. Conclusion: Randomized clinical studies provide scant evidence regarding the positive effects of physiotherapeutic intervention on peripheral neuropathic pain induced by breast cancer treatments.

La supervivencia de las mujeres después del tratamiento del cáncer de mama ha aumentado debido a los avances en la detección temprana y las terapias disponibles. Sin embargo, los supervivientes suelen enfrentarse a efectos adversos después del tratamiento que representan una gran carga física y psicológica. Además de la fatiga, el dolor es el síntoma persistente más común después del tratamiento del cáncer. Objetivo: Sistematizar los resultados de ensayos clínicos aleatorizados sobre intervención fisioterapéutica en el dolor neuropático periférico inducido por tratamientos para el cáncer de mama. Método: La búsqueda se realizó en las bases de datos MEDLINE a través de los portales PubMed y Cochrane. Se seleccionaron ensayos clínicos aleatorizados publicados desde 2017, en inglés, que abordaron modalidades fisioterapéuticas como intervención, dolor neuropático periférico inducido por tratamientos oncológicos como resultado y mujeres sobrevivientes de cáncer de mama como población de interés. La calidad metodológica de los estudios se evaluó mediante la herramienta Cochrane de Riesgo de Sesgo. Resultados: Se revisaron en su totalidad cuatro estudios. La mayoría de los efectos adversos del tratamiento del cáncer se deben a los regímenes de quimioterapia basados en taxanos. Los resultados evaluados incluyen, además del dolor, otros signos neuropáticos y su influencia en las actividades de la vida diaria. Los estudios variaron en términos de intervención y fase de tratamiento. Sólo uno de los estudios demostró un resultado significativamente positivo a favor del grupo de intervención. Conclusión: Los estudios clínicos aleatorizados aportan escasa evidencia sobre los efectos positivos de la intervención fisioterapéutica sobre el dolor neuropático periférico inducido por los tratamientos del cáncer de mama

Development of bispecific T cell engagers: harnessing quantitative systems pharmacology.

Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development.

Quantitative Systems Pharmacology for Rare Disease Drug Development.

Though hundreds of drugs have been approved by the US Food and Drug Administration (FDA) for treating various rare diseases, most rare diseases still lack FDA-approved therapeutics. To identify the opportunities for developing therapies for these diseases, the challenges of demonstrating the efficacy and safety of a drug for treating a rare disease are highlighted herein. Quantitative systems pharmacology (QSP) has increasingly been used to inform drug development; our analysis of QSP submissions received by FDA showed that there were 121 submissions as of 2022, for informing rare disease drug development across development phases and therapeutic areas. Examples of published models for inborn errors of metabolism, non-malignant hematological disorders, and hematological malignancies were briefly reviewed to shed light on use of QSP in drug discovery and development for rare diseases. Advances in biomedical research and computational technologies can potentially enable QSP simulation of the natural history of a rare disease in the context of its clinical presentation and genetic heterogeneity. With this function, QSP may be used to conduct in-silico trials to overcome some of the challenges in rare disease drug development. QSP may play an increasingly important role in facilitating development of safe and effective drugs for treating rare diseases with unmet medical needs.

Quantitative systems pharmacology of the eye: Tools and data for ocular QSP.

Good eyesight belongs to the most-valued attributes of health, and diseases of the eye are a significant healthcare burden. Case numbers are expected to further increase in the next decades due to an aging society. The development of drugs in ophthalmology, however, is difficult due to limited accessibility of the eye, in terms of drug administration and in terms of sampling of tissues for drug pharmacokinetics (PKs) and pharmacodynamics (PDs). Ocular quantitative systems pharmacology models provide the opportunity to describe the distribution of drugs in the eye as well as the resulting drug-response in specific segments of the eye. In particular, ocular physiologically-based PK (PBPK) models are necessary to describe drug concentration levels in different regions of the eye. Further, ocular effect models using molecular data from specific cellular systems are needed to develop dose-response correlations. We here describe the current status of PK/PBPK as well as PD models for the eyes and discuss cellular systems, data repositories, as well as animal models in ophthalmology. The application of the various concepts is highlighted for the development of new treatments for postoperative fibrosis after glaucoma surgery.

From Cold to Hot: Changing Perceptions and Future Opportunities for Quantitative Systems Pharmacology Modeling in Cancer Immunotherapy.

Immuno-oncology (IO) is a fast-expanding field due to recent success using IO therapies in treating cancer. As IO therapies do not directly kill tumor cells but rather act upon the patients' own immune cells either systemically or in the tumor microenvironment, new and innovative approaches are required to inform IO therapy research and development. Quantitative systems pharmacology (QSP) modeling describes the biological mechanisms of disease and the mode of action of drugs with mathematical equations, which has significant potential to address the big challenges in the IO field, from identifying patient populations that respond to different therapies to guiding the selection, dosing, and scheduling of combination therapy. To assess the perspectives of the community on the impact of QSP modeling in IO drug development and to understand current applications and challenges, the IO QSP working group-under the QSP Special Interest Group (SIG) of the International Society of Pharmacometrics (ISoP)-conducted a survey among QSP modelers, non-QSP modelers, and non-modeling IO program stakeholders. The survey results are presented here with discussions on how to address some of the findings. One of the findings is the differences in perception among these groups. To help bridge this perception gap, we present several case studies demonstrating the impact of QSP modeling in IO and suggest actions that can be taken in the future to increase the real and perceived impact of QSP modeling in IO drug research and development.

El trabajo educativo curricular desde el tema Medicamentos antiulcerosos en la asignatura Farmacología II / Curricular educational work on the topic of anti-ulcer medications in the subject Pharmacology II

El trabajo educativo consiste en transmitir un mensaje coherente desde la propia ciencia y estimula la motivación del aprendizaje de los estudiantes y su propia actividad cognoscitiva. El propósito de la educación médica superior es egresar un profesional integral; por tanto, se trata de instruir y educar a los estudiantes en los más altos valores patrióticos, morales y éticos en cada uno de los escenarios docentes, desde la propia ciencia. El objetivo de esta comunicación es ejemplificar algunos contenidos sobre la temática referente a medicamentos antiulcerosos en los que se puede intencionar el trabajo educativo desde la propia ciencia.

The educational work consists of transmitting a coherent educational message from science itself and stimulates the students' learning motivation and their own cognitive activity. The purpose of higher medical education is to graduate a comprehensive professional; therefore, it is about instructing and educating students in the highest patriotic, moral and ethical values in each of the teaching scenarios, from science itself. The objective of this research paper is to exemplify some content on the subject related to antiulcer drugs from which educational work can be intentioned from science itself.

Transformaciones en el programa de la asignatura Farmacología General: análisis comparativo de planes de estudio / Changes in the syllabus of the General Pharmacology subject: comparative analysis of study plans

Introducción: los sistemas de conocimientos y habilidades de cada profesión deben responder a los cambios sociales; esto implica el análisis constante para perfeccionarlos permanentemente. Objetivo: comparar los elementos fundamentales de los planes de estudio C, D y E de la asignatura Farmacología General para contribuir a la preparación de los docentes y mejorar el proceso enseñanza aprendizaje. Métodos: se realizó una revisión bibliográfica sistemática y documental que incluyó varias fuentes, entre ellas: resoluciones, programas de la asignatura Farmacología General, libros, artículos originales y de revisión. Se seleccionaron 24 fuentes teniendo en cuenta su pertinencia y actualización según el objetivo del trabajo. La búsqueda digital se realizó en las bases de datos Scopus, SciELO y Medline de los últimos cinco años. Las palabras claves utilizadas fueron: proceso docente educativo, farmacología general, plan de estudio, programa y educación médica. Desarrollo: se constató coherencia sistémica en los temas básicos de los programas, ajuste en sus objetivos, contenidos y evaluación de acuerdo con el modelo del profesional que se aspira a formar, con transformaciones en las horas clase, contenidos y formas organizativas de la enseñanza, responde al modelo del profesional que se aspira a formar; sin embargo, es susceptible de ser perfeccionado. Conclusiones: el programa de la asignatura Farmacología General ha experimentado un constante proceso de transformación según los cambios experimentados en el sistema de salud cubano, en busca de un mejor desarrollo del proceso docente educativo y de elevar su calidad y pertinencia.

Introduction: the knowledge and skills systems of each profession must respond to social changes; this implies constant analysis to improve them permanently. Objective: to compare the fundamental elements of the C, D and E study plans of the General Pharmacology subject to contribute to the preparation of teachers and improve the teaching-learning process. Methods: a systematic and documentary bibliographic review was carried out that included several sources, among them: resolutions, General Pharmacology subject programs, books, original and review articles. 24 sources were selected taking into account their relevance and updating according to the objective of the work. The digital search was carried out in the Scopus, SciELO and Medline databases of the last five years. The keywords used were educational teaching process, general pharmacology, study plan, program and medical education. Development: systemic coherence was verified in the basic topics of the programs, adjustment in their objectives, contents, and evaluation in accordance with the model of the professional desired to train, with transformations in class hours, contents, and organizational forms of teaching, responds to the model of the professional to train; however, it is capable of being perfected. Conclusions: the program of the General Pharmacology subject has undergone a constant transformation process according to the changes experienced in the Cuban health system, in search of a better development of the teaching-learning process and to raise its quality and relevance.

Seroconversión posterior a la aplicación de vacuna Pfizer anticovid-19 en personal de la salud / Seroconversión rates following covid-19 Pfizer vaccine application among health personnel

Introducción: la pandemia por COVID-19 constituyó un problema de salud que requirió la realización de esfuerzos sin precedentes para la fabricación de vacunas en tiempo récord. Dada la emergencia no se podían llevar a cabo los protocolos establecidos que componen la fármacovigilancia, razón por la cual es importante realizar estudios locales que contribuyan al conocimiento y vigilancia clínica y farmacológica. Objetivos: evaluar los niveles de anticuerpos desarrollados en quienes recibieron la vacuna Pfizer, determinar los efectos secundarios más frecuentes y describir la mortalidad por todas las causas a un año en este grupo. Métodos: estudio prospectivo, de corte transversal de una cohorte de 105 pacientes, se realizó estadística descriptiva en el análisis univariado y bivariado para los niveles de anticuerpos, se describe la correlación de la edad con los niveles de anticuerpos y la mortalidad cruda de los pacientes a 1 año. Resultados: la edad media de los 105 pacientes fue 36,45 años (DE 10,11), con tendencia al aumento de los niveles de anticuerpos en la segunda toma y descenso en la tercera; se encontró una correlación negativa significativa entre edad y niveles de anticuerpos en la segunda toma. Conclusiones: en los sujetos más jóvenes se presentaron mayores títulos de anticuerpos que disminuyeron con el tiempo, la variabilidad en la titulación puede depender de varios factores como edad, género, imnunosupresores y comorbilidades. Es necesaria la medición para realizar una vacunación periódica e individualizarla. La mortalidad a un año fue de 0%.

Introduction: the COVID-19 pandemic prompted unprecedented efforts to manufacture vaccines in record time. Given the emergency, to conduct the established pharmacovigilance protocols was not possible, thus, the importance of carrying out local studies which contribute to gain understanding and clinical and pharmacological surveillance. Objectives: to evaluate antibody levels developed in subjects who received the Pfizer vaccine; to determine the most frequent side effects; and describe all-cause 1-year mortality in this group. Methods: a prospective, cross-sectional study in a cohort of 105 patients. Descriptive statistics were conducted by univariate and bivariate analyses of antibody levels. The correlation between age and antibody levels and the crude 1-year mortality rate among patients is described. Results: mean age was 36.45 years (SD 10.11), with a tendency for antibody levels to increase with the second dose and decrease with the third dose. A significant negative correlation was found between age and antibody levels in the second dose. Conclusions: younger subjects had higher antibody titers, which decreased over time. The variability of titer estimates may depend on several factors such as, age, gender, immunosuppressive therapies and comorbidities. Measurements are essential for periodic and individualized vaccination. One-year mortality rate was 0%.

[Issues to be required for the education of pharmacology for nursing care from the clinical scenes].

Among the fields of medical treatments, pharmacological therapy is most the therapy that nurses are most concerned in. Under the clinical practical scenes, nurses are required to have high specialized knowledge and proper judgment ability. In the basic education of nursing care, in clinical pharmacology, we learn pharmacological therapy in terms of principal pharmacological efficacy and adverse effects, methods of administrations, and management methods of management. As pharmacology for nursing care, we lean comprehensive understanding of diseases, life style, and psychological situations. Under the actual nursing education following clinical scenes, in addition to these issues, we are required to learn knowledge and skill of performing safety pharmacological treatment of patients. It is important that we improve high specialized knowledge and proper judgment ability and we guarantee the quality of pharmacological treatments in accordance with patients safety. Especially in the university hospitals, Drug treatment using anti-cancer drugs and agents having serious side effects, and high-level clinical test drugs, are performed. Nurses are involved in the pharmacological treatment of patients as team with doctors and pharmacist. Therefore, the guarantee of pharmacological treatment is almost identical to the guarantee of quality of nursing care. In order that nurses are able to perform pharmacological treatments to patients safely, and obtain treatment efficacy, in addition to systematic and practical education, the promotion of communication of personnel interchange between clinical fields to a faculty is very useful, leading to establishment of motivation of continual education.

Fundamentos teóricos de una estrategia didáctica interdisciplinaria entre la Farmacología y las asignaturas clínicas estomatológicas en la Universidad de Ciencias Médicas de Santiago de Cuba / Theoretical foundations of an interdisciplinary didactic strategy between Pharmacology and stomatological clinical subjects in a Cuban medical university

El desarrollo de la interdisciplinariedad, a través del proceso de enseñanza aprendizaje enmarcado en el trabajo conjunto de la unidad curricular de Farmacología y las asignaturas clínicas de la Disciplina Principal Integradora de la carrera de Estomatología, resulta esencial para la sistematización de los contenidos de Farmacología y el desarrollo de habilidades teórico-prácticas en la prescripción racional de medicamentos de uso estomatológico por parte de estudiantes. En el presente ensayo se exponen los fundamentos teóricos que sustentan la estrategia didáctica diseñada para lograr lo antes expuesto. El análisis de los referentes teóricos existentes permitió precisar fundamentos filosóficos, sociológicos, psicológicos, pedagógicos, didácticos y de la educación médica cubana. Finalmente, se consideró que dichos fundamentos permitieron otorgar a la estrategia didáctica diseñada la estructura y coherencia necesarias y el carácter científico, con lo cual se contribuye a la formación integral de los estudiantes y, por consiguiente, al futuro egresado de la carrera de Estomatología.

The development of interdisciplinarity through the teaching-learning process between the Pharmacology curricular unit and the clinical subjects of the Main Integrative Discipline in the Stomatology career, is essential for the systematization of the essential contents of Pharmacology and to develop theoretical skills in the students' practices for the rational prescription of drugs for stomatological use. In this essay, the theoretical foundations that support a designed didactic strategy to achieve the above are exposed. The analysis of the existing theoretical references allowed to specify the philosophical, sociological, psychological, pedagogical, didactic and of Cuban Medical Education foundations. Finally, it was considered that these foundations allowed to give the designed didactic strategy the necessary structure and coherence and scientific character, thereby contributing to the comprehensive training of students and, consequently, of future graduates of the Stomatology career.

Simulations of tumor growth and response to immunotherapy by coupling a spatial agent-based model with a whole-patient quantitative systems pharmacology model.

Quantitative systems pharmacology (QSP) models and spatial agent-based models (ABM) are powerful and efficient approaches for the analysis of biological systems and for clinical applications. Although QSP models are becoming essential in discovering predictive biomarkers and developing combination therapies through in silico virtual trials, they are inadequate to capture the spatial heterogeneity and randomness that characterize complex biological systems, and specifically the tumor microenvironment. Here, we extend our recently developed spatial QSP (spQSP) model to analyze tumor growth dynamics and its response to immunotherapy at different spatio-temporal scales. In the model, the tumor spatial dynamics is governed by the ABM, coupled to the QSP model, which includes the following compartments: central (blood system), tumor, tumor-draining lymph node, and peripheral (the rest of the organs and tissues). A dynamic recruitment of T cells and myeloid-derived suppressor cells (MDSC) from the QSP central compartment has been implemented as a function of the spatial distribution of cancer cells. The proposed QSP-ABM coupling methodology enables the spQSP model to perform as a coarse-grained model at the whole-tumor scale and as an agent-based model at the regions of interest (ROIs) scale. Thus, we exploit the spQSP model potential to characterize tumor growth, identify T cell hotspots, and perform qualitative and quantitative descriptions of cell density profiles at the invasive front of the tumor. Additionally, we analyze the effects of immunotherapy at both whole-tumor and ROI scales under different tumor growth and immune response conditions. A digital pathology computational analysis of triple-negative breast cancer specimens is used as a guide for modeling the immuno-architecture of the invasive front.

Development of and insights from systems pharmacology models of antibody-drug conjugates.

Antibody-drug conjugates (ADCs) have gained traction in the oncology space in the past few decades, with significant progress being made in recent years. Although the use of pharmacometric modeling is well-established in the drug development process, there is an increasing need for a better quantitative biological understanding of the pharmacokinetic and pharmacodynamic relationships of these complex molecules. Quantitative systems pharmacology (QSP) approaches can assist in this endeavor; recent computational QSP models incorporate ADC-specific mechanisms and use data-driven simulations to predict experimental outcomes. Various modeling approaches and platforms have been developed at the in vitro, in vivo, and clinical scales, and can be further integrated to facilitate preclinical to clinical translation. These new tools can help researchers better understand the nature and mechanisms of these targeted therapies to help achieve a more favorable therapeutic window. This review delves into the world of systems pharmacology modeling of ADCs, discussing various modeling efforts in the field thus far.

Virtual Populations for Quantitative Systems Pharmacology Models.

Quantitative systems pharmacology (QSP) places an emphasis on dynamic systems modeling, incorporating considerations from systems biology modeling and pharmacodynamics. The goal of QSP is often to quantitatively predict the effects of clinical therapeutics, their combinations, and their doses on clinical biomarkers and endpoints. In order to achieve this goal, strategies for incorporating clinical data into model calibration are critical. Virtual population (VPop) approaches facilitate model calibration while faced with challenges encountered in QSP model application, including modeling a breadth of clinical therapies, biomarkers, endpoints, utilizing data of varying structure and source, capturing observed clinical variability, and simulating with models that may require more substantial computational time and resources than often found in pharmacometrics applications. VPops are frequently developed in a process that may involve parameterization of isolated pathway models, integration into a larger QSP model, incorporation of clinical data, calibration, and quantitative validation that the model with the accompanying, calibrated VPop is suitable to address the intended question or help with the intended decision. Here, we introduce previous strategies for developing VPops in the context of a variety of therapeutic and safety areas: metabolic disorders, drug-induced liver injury, autoimmune diseases, and cancer. We introduce methodological considerations, prior work for sensitivity analysis and VPop algorithm design, and potential areas for future advancement. Finally, we give a more detailed application example of a VPop calibration algorithm that illustrates recent progress and many of the methodological considerations. In conclusion, although methodologies have varied, VPop strategies have been successfully applied to give valid clinical insights and predictions with the assistance of carefully defined and designed calibration and validation strategies. While a uniform VPop approach for all potential QSP applications may be challenging given the heterogeneity in use considerations, we anticipate continued innovation will help to drive VPop application for more challenging cases of greater scale while developing new rigorous methodologies and metrics.

[A new curriculum to strengthen pharmacology and clinical pharmacology training in fundamental nursing education].

Among medical care incidents in Japan, an increase in medicine-related errors by nurses have been reported. These errors may be caused by a lack of knowledge of clinical pharmacology and drug interactions. It is important for nurses to acquire risk-management skills based on clinical pharmacology. In order to improve fundamental knowledge in pharmacology and clinical pharmacology for nurses, various training programs exist. We reviewed a number of educational programs in medicine and report our results. Based on our results, it is necessary for medical education programs to include the following 5 essential elements: 1) An analysis of frequently-occurring medication errors in the field of clinical pharmacology, 2) drugs administer for patient characteristic and patient observation practices, 3) an emphasis on the interactions between drugs and food or other drugs, 4) assessment of patient symptoms, risk-management, and the efficacy of drugs, 5) the necessity of using the package inserts. In a new curriculum, it is necessary to have systematic, step by step training in pharmacology and clinical pharmacology. It is also necessary to develop these teaching methods in cooperation with specialists and experts in the field.

Competencias profesionales del farmacólogo en farmacoepidemiología / The pharmacologist's professional competences in pharmacoepidemiology

Introducción: Los retos y las exigencias del mundo contemporáneo requieren de profesionales de la salud con una formación académica basada en competencias. La especialidad de Farmacología en Cuba no ha definido sus competencias profesionales. Objetivo: Definir las competencias profesionales de los especialistas en Farmacología para su desempeño como farmacoepidemiólogos. Métodos: Estudio de desarrollo en el que se obtuvieron las competencias profesionales genéricas y específicas que los especialistas en Farmacología debían alcanzar para desempeñarse como farmacoepidemiólogos. El trabajo se realizó en La Habana entre marzo de 2018 y febrero de 2019. Se aplicaron técnicas cualitativas y revisiones documentales sobre las temáticas relacionadas con el objeto de la investigación. Se trabajó con dos grupos de expertos en dos etapas. Se empleó la metodología Delphi. Resultados: Se construyeron 24 competencias, genéricas y específicas, de las áreas funcionales asistencial, investigativa, docente y gerencial, que los especialistas en Farmacología debían alcanzar para desempeñarse como farmacoepidemiólogos. Conclusiones: Las competencias definidas permiten al farmacoepidemiólogo lograr un uso racional de los medicamentos, lo cual tributa a su propósito clave: una atención de calidad durante el proceso salud-enfermedad(AU)

Introduction: The challenges and demands of the contemporary world require health professionals with competency-based academic training. The specialty of pharmacology in Cuba has not defined its professional competencies. Objective: To define the professional competences of pharmacology specialists for their performance as pharmacoepidemiologists. Methods: Development study that allowed obtaining the generic and specific professional competences that pharmacology specialists should reach to practice as pharmacoepidemiologists. The work was carried out in Havana between March 2018 and February 2019. Qualitative techniques were applied, together with documental reviews on the topics related to the research object. Two groups of experts participated in the work during two stages. The Delphi methodology was used. Results: Twenty-four competencies, either generic or specific, were determined, belonging to the functional areas of care, research, teaching and management, which pharmacology specialists should achieve to practice as pharmacoepidemiologists. Conclusions: The competencies defined allow the pharmacoepidemiologist to achieve a rational use of drugs, which contributes to the key purpose of the specialized profession: quality care during the health-disease process(AU)

Monocytes as a convergent nanoparticle therapeutic target for cardiovascular diseases.

Due to the increasing population of individuals with cardiovascular diseases and related comorbidities, there is an increasing need for development of synergistic therapeutics. Monocytes are implicated in a broad spectrum of diseases and can serve as a focal point for therapeutic targeting. This review discusses the role of monocytes in cardiovascular diseases and highlights trends in monocyte targets nanoparticles in three cardiovascular-related diseases: Diabetes, Atherosclerosis, and HIV. Finally, the review offers perspectives on how to develop nanoparticle monocyte targeting strategies that can be beneficial for treating co-morbidities.