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OBJECTIVE: The aim of this article is to perform a narrative review of how pharmacogenetics and pharmacogenomics is being applied in the clinic, especially in Spain. METHOD: Publications and websites of major interest have been reviewed. RESULTS: Pharmacogenes and variants used in several hospitals, available methodologies, and the implementation process are discussed.
Subject(s)
Pharmacogenetics , Precision Medicine , Humans , SpainABSTRACT
OBJECTIVE: The aim of this article was to perform a narrative review of how pharmacogenetics and pharmacogenomics is being applied in the clinics, especially in Spain. METHOD: Publications and websites of major interest have been reviewed. RESULTS: Pharmacogenes and variants used in several hospitals, available methodologies, and the implementation process are discussed.
Subject(s)
Pharmacogenetics , Precision Medicine , Humans , SpainABSTRACT
INTRODUCTION: Chronic kidney disease (CKD) of non-inherited etiology is one of the main causes of renal replacement therapy in our setting. Previous studies in other territories suggest that hereditary diseases could be one of the potential causes of this pathology, especially in younger patients. The GENSEN study will evaluate the presence of pathogenic genetic variants in subjects who have developed CKD category G5 before the age of 46 years, of non-inherited etiology. METHODS: Observational, prospective, multicenter study, which evaluates the diagnostic utility of massive high-throughput sequencing (HTS) directed to a set of genes, in the identification of the cause of CKD. Patients from all over Spain will be included, from whom a blood or saliva sample will be taken and a panel of 529 genes associated with hereditary kidney disease will be analyzed. This publication communicates the study protocol. CONCLUSION: The GENSEN study will make it possible to evaluate the diagnostic performance of the gene panel study in young subjects in our setting with the development of CKD category G5 without a clear cause. An etiological diagnosis would offer potential benefits for patients and relatives (targeted therapies, clinical trials, detection of extrarenal manifestations, evaluation of relatives for live donation, estimation of the risk of recurrence in the renal graft, genetic counseling, among others) and would allow to apply this genetic study to the nephrology of our country.
Subject(s)
Renal Insufficiency, Chronic , Humans , Prospective Studies , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/etiology , Adult , High-Throughput Nucleotide Sequencing , Middle Aged , Spain , Female , Severity of Illness Index , Male , Young AdultABSTRACT
INTRODUCTION: Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine. MATERIALS AND METHODS: A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualized dosing", "clinical routine" and "clinical practice." Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis. RESULTS: 49 articles were included for the final analysis following review by two investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNF-α agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found. CONCLUSION: The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.
ABSTRACT
Introducción: La linfohistiocitosis hemofagocítica familiar (FHL) es una enfermedad del sistema autoinmune que se presenta con un síndrome inflamatorio excesivo causado por linfocitos T activados e histiocitosis. Cursa con herencia autosómica recesiva ligada al cromosoma X. Aproximadamente el 90% de los niños diagnosticados son menores de 2 años y la incidencia es de aproximadamente 0.12 por 100.000. Se puede dividir en cinco subtipos según la variante genética causante. Las variantes patogénicas más involucradas son en los genes de la perforina 1 (PRF1) y homólogo D de la proteína UNC-13 (UNC13D). Caso clínico: Se presenta el caso de un preadolescente de 11 años, con antecedente de infecciones recurrentes, quien cursa con síndrome convulsivo asociado a fiebre, peso y talla bajas para la edad, hepatomegalia y discapacidad cognitiva. En el abordaje inicial se descartan enfermedades infecciosas, inmunológicas, hematológicas, metabólicas y oncológicas. El exoma clínico para inmunodeficiencias primarias muestra una variante patogénica p.A91V homocigota en el gen de la PRF1 de herencia autosómica recesiva, resultado relacionado con linfohistiocitosis hemofagocítica familiar tipo 2 (FHL2). Discusión y conclusión: El cambio conformacional del PRF1 alterado reduce la actividad citotóxica de la proteína y provoca la enfermedad. Los pacientes portadores de defectos en el gen PRF1 son vulnerables a infecciones, enfermedades autoinmunes y tumores malignos. Con un diagnóstico definido y preciso es posible orientar las acciones en salud, pautas de seguimiento, evaluación de riesgo de heredabilidad a través de un caso índice para así encontrar otros posibles portadores, realizar un asesoramiento genético completo, implementar e iniciar tratamientos dirigidos que aminoren la morbilidad y mortalidad asociada a esta patología. Actualmente se cuenta con varios estudios en diferentes fases de investigación sobre moléculas que pueden intervenir en la historia natural de la enfermedad. (provisto por Infomedic International)
Introduction: Familial hemophagocytic lymphohistiocytosis (FHL) is a disease of the autoimmune system that presents with an excessive inflammatory syndrome caused by activated T lymphocytes and histiocytosis. It occurs with autosomal recessive inheritance linked to the chromosome X. Approximately 90% of diagnosed children are under 2 years of age and the incidence is approximately 0.12 per 100,000. It can be divided into five subtypes depending on the causative genetic variant. The most involved pathogenic variants are in the perforin 1 (PRF1) and UNC-13 protein homolog D (UNC13D) genes. Clinical case: The case of an 11-year-old preadolescent is presented, with a history of recurrent infections, who presents with convulsive syndrome associated with fever, low weight and height for age, hepatomegaly and cognitive disability. In the initial approach, infectious, immunological, hematological, metabolic and oncological diseases are ruled out. The clinical exome for primary immunodeficiencies shows a homozygous pathogenic variant p.A91V in the PRF1 gene of autosomal recessive inheritance, a result related to familial hemophagocytic lymphohistiocytosis type 2 (FHL2). Discussion and conclusion: The altered PRF1 conformational change reduces the cytotoxic activity of the protein and causes disease. Patients carrying defects in the PRF1 gene are vulnerable to infections, autoimmune diseases and malignant tumors. With a defined and precise diagnosis, it is possible to guide health actions, follow-up guidelines, evaluation of heritability risk through an index case in order to find other possible carriers, carry out complete genetic counseling, implement and initiate targeted treatments that reduce the morbidity and mortality associated with this pathology. Currently, there are several studies in different phases of research on molecules that may intervene in the natural history of the disease. (provided by Infomedic International)
ABSTRACT
INTRODUCTION: Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine. MATERIALS AND METHODS: A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualizing dosing", "clinical routine", and "clinical practice." Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis. RESULTS: 49 articles were included for the final analysis following review by 2 investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNFα agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found. CONCLUSION: The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.
ABSTRACT
Introducción: el desarrollo de la genética en las últimas décadas ha abierto una nueva era. La medicina de precisión ha aprovechado estos avances para desempeñar un papel cada vez más importante en la prevención, el diagnóstico y tratamiento del cáncer. Objetivo: evaluar la utilidad de la medicina de precisión en la prevención, tratamiento y pronóstico en oncología. Discusión: los estudios de la carcinogénesis han llevado al descubrimiento de eventos cruciales en el desarrollo de neoplasias malignas, identificando subtipos distintos de varios tumores comunes desde el punto de vista molecular. Con ello se ha logrado una mejor caracterización de los tumores que antes solo dependía de los hallazgos histopatológicos y el desarrollo de nuevos fármacos, generando cambios en el paradigma de la atención del paciente oncológico. La identificación de mutaciones que pueden predisponer al cáncer como las mutaciones BRCA en el cáncer de mama, ha facilitado el cribado para identificar pacientes para ayudar a tomar decisiones y modificar el riesgo. Conclusiones: la eficacia de varias terapias antitumorales sugiere el inicio de una era en la que las acciones preventivas y decisiones clínicas estarán basadas en el perfil de anomalías genéticas del tumor, mejorando el pronóstico y la calidad de vida de los pacientes. Esto conducirá a que cada vez sea más frecuente este tipo de tratamiento de precisión basado en el perfil de cambios genéticos.
Introduction: advances in genetics in recent decades has ushered a new era. Precision medicine has used these advances to play an increasingly important role in cancer prevention, diagnosis and treatment. Objetive: was to evaluate the usefulness of precisión medicine in improving prevention, treatment and prognosis in oncology. Discussion: studies on carcinogenesis have propelled the discovery of crucial events in the development of malignant neoplasms, identifying specific molecular subtypes of several common tumors. This has resulted in a better charaterization of tumors, which previously depended only on anatomapathological findings, and has enabled the development of new drugs, which have shifted the oncologic care paradigm. The identification of mutations that may determine predisposition to cancer, such as, BRCA mutations in breast cáncer, has facilitated screening to identify patients and help improve decision making and modify risk. Conclusions: the efficacy of various antitumor therapies suggests the beginning of an era in which preventive actions and clinical decisions will be based on the profile of genetic abnormalities of the tumor, improving patient prognosis and quality of life. This will allow an increase in the use of this type of precision treatments based on the profile of genetic changes.
Subject(s)
HumansABSTRACT
ChatGPT is a virtual assistant with artificial intelligence (AI) that uses natural language to communicate, i.e., it holds conversations as those that would take place with another human being. It can be applied at all educational levels, including medical education, where it can impact medical training, research, the writing of scientific articles, clinical care, and personalized medicine. It can modify interactions between physicians and patients and thus improve the standards of healthcare quality and safety, for example, by suggesting preventive measures in a patient that sometimes are not considered by the physician for multiple reasons. ChatGPT potential uses in medical education, as a tool to support the writing of scientific articles, as a medical care assistant for patients and doctors for a more personalized medical approach, are some of the applications discussed in this article. Ethical aspects, originality, inappropriate or incorrect content, incorrect citations, cybersecurity, hallucinations, and plagiarism are some examples of situations to be considered when using AI-based tools in medicine.
ChatGPT es un asistente virtual con inteligencia artificial que utiliza lenguaje natural para comunicarse, es decir, mantiene conversaciones como las que se tendrían con otro humano. Puede aplicarse en educación a todos los niveles, que incluye la educación médica, en donde puede impactar en la formación, la investigación, la escritura de artículos científicos, la atención clínica y la medicina personalizada. Puede modificar la interacción entre médicos y pacientes para mejorar los estándares de calidad de la atención médica y la seguridad, por ejemplo, al sugerir medidas preventivas en un paciente que en ocasiones no son consideradas por el médico por múltiples causas. Los usos potenciales del ChatGPT en la educación médica, como una herramienta de ayuda en la redacción de artículos científicos, un asistente en la atención para pacientes y médicos para una práctica más personalizada, son algunas de las aplicaciones que se analizan en este artículo. Los aspectos éticos, originalidad, contenido inapropiado o incorrecto, citas incorrectas, ciberseguridad, alucinaciones y plagio son ejemplos de las situaciones a tomar en cuenta al usar las herramientas basadas en inteligencia artificial en medicina.
Subject(s)
Allied Health Personnel , Artificial Intelligence , Humans , Educational Status , Communication , Precision MedicineABSTRACT
Resumen La epilepsia es un trastorno neurológico caracterizado por crisis epilépticas recurrentes no provocadas, en el cual la genética tiene un factor etiológico importante. Durante las últimas décadas se ha logrado encontrar genes específicos involucrados en la patogénesis de esta condición. Actualmente existen múltiples exámenes disponibles en la práctica clínica para el diagnóstico genético, siendo los más útiles los paneles multi-genes y la secuenciación del exoma completo por medio de next generation sequencing (NGS). El tener un diagnósti co genético puede mejorar la calidad de vida de cada paciente y su familia, al mismo tiempo que nos ayuda a individualizar el tratamiento haciéndolo más eficaz. Algunos ejemplos en los que el diagnóstico genético puede modificar la conducta terapéutica incluyen el gen SCN1A en que se recomienda no utilizar medicamentos bloqueadores de canales de sodio y el gen SLC2A1 en el que se recomienda el inicio de la dieta cetogénica. El futuro de la investigación en medicina de precisión en epilepsia es muy prometedor, con el objetivo de que cada paciente reciba un tratamiento acorde a su etio logía genética.
Abstract Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. It is known that genetics play an important etiology roll. During the last decades it has been possible to find specific genes involved in the pathogenesis of this condition. There are currently multiple studies available in clinical practice for genetic diagnosis, the most useful being the next generation se quencing (NGS) techniques with multi-gene panels and whole exome sequencing. Having a genetic diagnosis can help improve the quality of life of each patient and their family, while it helps us to individualize the treatment, making it more effective. Some examples in which ge netic diagnosis can modify therapeutic conduct include the SCN1A gene, in which it is recommended not to use drugs that block Sodium channels, and the SLC2A1 gene, in which starting ketogenic diet is recommended. The future of precision medicine research in epilepsy is very promising, with the goal that each patient receives treatment according to their genetic etiology.
ABSTRACT
Resumen ChatGPT es un asistente virtual con inteligencia artificial que utiliza lenguaje natural para comunicarse, es decir, mantiene conversaciones como las que se tendrían con otro humano. Puede aplicarse en educación a todos los niveles, que incluye la educación médica, tanto para la formación, la investigación, la escritura de artículos científicos, la atención clínica y la medicina personalizada. Puede modificar la interacción entre médicos y pacientes para mejorar los estándares de calidad de la atención médica y la seguridad, por ejemplo, al sugerir medidas preventivas en un paciente que en ocasiones no son consideradas por el médico por múltiples causas. Los usos potenciales del ChatGPT en la educación médica, como una herramienta de ayuda en la redacción de artículos científicos, un asistente en la atención para pacientes y médicos para una práctica más personalizada, son algunas de las aplicaciones que se analizan en este artículo. Los aspectos éticos, originalidad, contenido inapropiado o incorrecto, citas incorrectas, ciberseguridad, alucinaciones y plagio son ejemplos de las situaciones a tomar en cuenta al usar las herramientas basadas en inteligencia artificial en medicina.
Abstract ChatGPT is a virtual assistant with artificial intelligence (AI) that uses natural language to communicate, i.e., it holds conversations as those that would take place with another human being. It can be applied at all educational levels, including medical education, where it can impact medical training, research, the writing of scientific articles, clinical care, and personalized medicine. It can modify interactions between physicians and patients and thus improve the standards of healthcare quality and safety, for example, by suggesting preventive measures in a patient that sometimes are not considered by the physician for multiple reasons. ChatGPT potential uses in medical education, as a tool to support the writing of scientific articles, as a medical care assistant for patients and doctors for a more personalized medical approach, are some of the applications discussed in this article. Ethical aspects, originality, inappropriate or incorrect content, incorrect citations, cybersecurity, hallucinations, and plagiarism are some examples of situations to be considered when using AI-based tools in medicine.
ABSTRACT
El cáncer seguirá siendo uno de los mayores desafíos para la salud pública a nivel local y mundial. Actualmente, en nuestro país, el cáncer es la principal causa de muerte. Gracias al enorme conocimiento acumulado en las últimas décadas sobre las bases celulares y moleculares del cáncer, se ha desarrollado la oncología de precisión, un enfoque que permite dirigir de manera cada vez más precisa el tratamiento farmacológico en función de los exámenes de diagnóstico. Para ello se utilizan tecnologías avanzadas, como la secuenciación de próxima generación. Es imprescindible implementar estas tecnologías en los sistemas sanitarios actuales y futuros para optimizar el arsenal de estrategias para el control del cáncer. En esta revisión, se discuten algunos alcances de la oncología de precisión, especialmente aplicada a tumores sólidos. Se aborda el estado del arte de los biomarcadores mínimos necesarios para el diagnóstico de este importante grupo de neoplasias, la situación local en cuanto a las capacidades tecnológicas instaladas en el territorio nacional ya sea con fines de investigación o diagnóstico, y el potencial impacto sanitario que tendría la aplicación de todo este conocimiento práctico al servicio de las personas con cáncer, tanto en el sector público como privado.
Cancer will remain one of the most significant challenges for public health, locally and globally. Currently, cancer is the leading cause of death in our country. Thanks to the enormous knowledge accumulated in recent decades on the cellular and molecular bases of cancer, precision oncology has been developed, an approach that allows for increasingly precise pharmacological treatment based on diagnostic tests. Advanced technologies such as next-generation sequencing are used for this purpose. It is essential to implement these technologies in current and future health systems to optimize the arsenal of strategies for cancer control. This review discusses some of the achievements of precision oncology, particularly applied to solid tumors. It addresses the state-of-the-art minimum biomarkers required for the diagnosis of this important group of neoplasms, the local situation regarding technological capabilities installed in the national territory, either for research or diagnosis, and the potential health impact of applying all this practical knowledge to serve people with cancer, both in the public and private sectors.
Subject(s)
Humans , Precision Medicine/methods , Neoplasms/diagnosis , Neoplasms/genetics , Biomarkers, Tumor/genetics , Chile , Molecular Diagnostic Techniques/methods , High-Throughput Nucleotide Sequencing/methods , Medical Oncology/methods , Medical Oncology/trendsABSTRACT
Pharmacy service is to provide individualized pharmaceutical care for patients, which should follow the current evidence-based pharmacy, and constantly verify the evidence and then produce new evidence. In pharmaceutical care, differences are often found in the efficacy and adverse reactions of drugs among individuals, even within individuals, which are closely related to patient's genetics, liver and kidney functions, disease states, and drug interactions. Back in the 1980s, therapeutic drug monitoring (TDM) has been applied to routinely monitor the blood drug concentration of patients taking antiepileptic drugs or immunosuppressants after transplantation to provide individualized dosage recommendations and accumulate a large amount of pharmacokinetic (PK)/pharmacodynamic (PD) data. As individualized pharmaceutical care proceeds, the concept of precision medicine was introduced into pharmacy services in combination with evidence-based pharmacy, PK/PD theories and big data to further promote the TDM technology and drugs, and carry out pharmacogenomics analysis. The TDM and pharmacogenomics have been applied gradually to the fields of antimicrobial, antitumor and antipsychotic drugs and immunosuppressants. Based on the concept of precision pharmacy, we adpoted approaches including PK/PD, quantitative pharmacology, population pharmacokinetics, and big data machine learning to provide more personalized pharmacy services, which is mainly for special patients, such as critical patients, patients with interaction risk of multiple drugs, patients with liver and renal insufficiency, pregnant women, children and elderly patients. As the service pattern of precision pharmacy has been constructed and constantly improved, better evidence in clinical practice will be produced to provide patients with better precision pharmacy service. (AU)
El servicio de farmacia se encarga de prestar atención farmacéutica personalizada a los pacientes. Los servicios de farmacia deben utilizar aquellas prácticas con mayor nivel de evidencia, y realizar una continua validación de dicha evidencia antes de elaborar nuevas prácticas. En la terapia farmacológica, se observan diferencias inter e intra individuales respecto a los efectos terapéuticos y a las reacciones adversas de los medicamentos, lo que está estrechamente relacionado con las variaciones genéticas, la función hepática y renal, el estado de la enfermedad y la interacción entre medicamentos. Desde la década de los 80 del siglo pasado, se utiliza la monitorización terapéutica de fármacos (MTF) de forma rutinaria para controlar las concentraciones sanguíneas de fármacos antiepilépticos o de inmunosupresores postrasplante y elaborar recomendaciones de dosis personalizadas y recoger una gran cantidad de datos farmacocinéticos (PC)/farmacodinámicos (PD). Con el desarrollo de la atención farmacéutica personalizada, el concepto de medicina de precisión se introduce en la atención farmacéutica, combinando la farmacia basada en evidencias, los enfoques PC/PD y los macrodatos (big data), promover técnicas de MTF en medicamentos, y la realización de análisis farmacogenómicos. La MTF y la farmacogenómica se están aplicando de forma gradual en el tratamiento con antimicrobianos, antitumorales, antipsicóticos e inmunosupresores. Sobre la base del concepto de farmacia de precisión, utilizamos métodos de PC/PD, farmacología cuantitativa, farmacocinética poblacional y aprendizaje automático con big data para ofrecer una atención farmacéutica más personalizada, principalmente a pacientes con necesidades especiales, como los pacientes en estado crítico, con riesgo de interacciones farmacológicas múltiples, pacientes con insuficiencia hepática y renal, mujeres embarazadas, niños y ancianos... (AU)
Subject(s)
Humans , Precision Medicine , Pharmacy , Pharmaceutical Services , Pharmacogenetics , China , Drug MonitoringABSTRACT
Pharmacy service is to provide individualized pharmaceutical care for patients, which should follow the current evidence-based pharmacy, and constantly verify the evidence and then produce new evidence. In pharmaceutical care, differences are often found in the efficacy and adverse reactions of drugs among individuals, even within individuals, which are closely related to patients' genetics, liver and kidney functions, disease states, and drug interactions. Back in the 1980s, therapeutic drug monitoring (TDM) has been applied to routinely monitor the blood drug concentration of patients taking antiepileptic drugs or immunosuppressants after transplantation to provide individualized dosage recommendations and accumulate a large amount of pharmacokinetic (PK)/pharmacodynamic (PD) data. As individualized pharmaceutical care proceeds, the concept of precision medicine was introduced into pharmacy services in combination with evidence-based pharmacy, PK/PD theories, and big data to further promote the TDM technology and drugs, and carry out pharmacogenomics analysis. The TDM and pharmacogenomics have been applied gradually to the fields of antimicrobial, antitumor, and antipsychotic drugs and immunosuppressants. Based on the concept of precision pharmacy, we adopted approaches including PK/PD, quantitative pharmacology, population pharmacokinetics, and big data machine learning to provide more personalized pharmacy services, which is mainly for special patients, such as critical patients, patients with interaction risk of multiple drugs, patients with liver and renal insufficiency, pregnant women, children, and elderly patients. As the service pattern of precision pharmacy has been constructed and constantly improved, better evidence in clinical practice will be produced to provide patients with better precision pharmacy service.
Subject(s)
Pharmaceutical Services , Pharmacy , Pregnancy , Child , Humans , Female , Aged , Precision Medicine , Immunosuppressive Agents/therapeutic use , Drug InteractionsABSTRACT
Objetivo: la capecitabina es un fármaco antineoplásico utilizado en el tratamiento del cáncer de mama y de colon que puede dar lugar a una toxicidad grave, llegando a ser mortal en algunos pacientes. La variabilidad interindividual de esta toxicidad es debida en gran medida a las variaciones genéticas en los genes diana y las enzimas de metabolismo de este fármaco, como la timidilato sintasa y la dihidropirimidina deshidrogenasa. La enzima citidin desaminasa (CDA), imprescindible en la activación de la capecitabina, también presenta diversas variantes asociadas con un mayor riesgo de toxicidad al tratamiento, aunque su papel como biomarcador aún no está claramente definido. Por ello, nuestro objetivo principal es estudiar la asociación entre la presencia de las variantes genéticas en el gen CDA, su actividad enzimática y el desarrollo de la toxicidad grave en los pacientes tratados con capecitabina, cuya dosis inicial se haya ajustado con base en el perfil genético del gen de la dihidropirimidina deshidrogenasa (DPYD). Método: estudio de cohortes observacional multicéntrico prospectivo, centrado en el análisis de la asociación genotipo-fenotipo de la enzima CDA. Tras la fase experimental, se desarrollará un algoritmo que permita determinar el ajuste necesario de las dosis para disminuir el riesgo de toxicidad del tratamiento en función del genotipo CDA, elaborando una guía clínica para la dosificación de la capecitabina en función de las variantes genéticas en DPYD y CDA. Con base en esta guía, se creará una herramienta bioinformática que genere el informe farmacoterapéutico de manera automática, facilitando la implementación del consejo farmacogenético en la práctica clínica. Esta herramienta proporcionará un gran respaldo en la toma de decisiones farmacoterapéuticas basadas en el perfil genético del paciente, incorporando la medicina de precisión en la rutina clínica. ... (AU)
Objective: Capecitabine, an antineoplastic drug used in the treatment of breast and colon cancer, can cause severe, even fatal toxicity in some patients. The interindividual variability of this toxicity is largely due to genetic variations in target genes and enzymes of metabolism of this drug, such as thymidylate synthase and dihydropyrimidine dehydrogenase. The enzyme cytidine deaminase (CDA), involved in the activation of capecitabine, also has several variants associated with an increased risk of toxicity to treatment, although its role as a biomarker is not yet clearly defined.Therefore, our main objective is to study the association between the presence of genetic variants in CDA gen, CDA enzymatic activity and the development of severe toxicity in patients treated with capecitabine whose initial dose was adjusted based on the genetic profile of the dihydropyrimidine dehydrogenase gen (DPYD). Method: Prospective multicenter observational cohort study, focused on the analysis of the genotype-phenotype association of the CDA enzyme.After the experimental phase, an algorithm will be developed to determine the dose adjustment needed to reduce the risk of treatment toxicity according to CDA genotype, developing a clinical guide for capecitabine dosing according to genetic variants in DPYD and CDA. Based on this guide, a Bioinformatics Tool will be created to generate the pharmacotherapeutic report automatically, facilitating the implementation of pharmacogenetic advice in clinical practice. This tool will be a great support in making pharmacotherapeutic decisions based on the patient's genetic profile, incorporating precision medicine into clinical routine. Once the usefulness of this tool has been validated, it will be offered free of charge to facilitate the implementation of pharmacogenetics in hospital centers and equitably benefit all patients on capecitabine treatment. (AU)
Subject(s)
Humans , Genetic Variation , Enzyme Assays , Cytidine Deaminase/drug effects , Cytidine Deaminase/pharmacology , Toxicity , Capecitabine/toxicity , Dosage , Pharmacogenetics , Clinical Protocols , Precision Medicine , Cohort Studies , Prospective StudiesABSTRACT
Pharmacy service is to provide individualized pharmaceutical care for patients, which should follow the current evidence-based pharmacy, and constantly verify the evidence and then produce new evidence. In pharmaceutical care, differences are often found in the efficacy and adverse reactions of drugs among individuals, even within individuals, which are closely related to patient's genetics, liver and kidney functions, disease states, and drug interactions. Back in the 1980s, therapeutic drug monitoring (TDM) has been applied to routinely monitor the blood drug concentration of patients taking antiepileptic drugs or immunosuppressants after transplantation to provide individualized dosage recommendations and accumulate a large amount of pharmacokinetic (PK)/pharmacodynamic (PD) data. As individualized pharmaceutical care proceeds, the concept of precision medicine was introduced into pharmacy services in combination with evidence-based pharmacy, PK/PD theories and big data to further promote the TDM technology and drugs, and carry out pharmacogenomics analysis. The TDM and pharmacogenomics have been applied gradually to the fields of antimicrobial, antitumor and antipsychotic drugs and immunosuppressants. Based on the concept of precision pharmacy, we adpoted approaches including PK/PD, quantitative pharmacology, population pharmacokinetics, and big data machine learning to provide more personalized pharmacy services, which is mainly for special patients, such as critical patients, patients with interaction risk of multiple drugs, patients with liver and renal insufficiency, pregnant women, children and elderly patients. As the service pattern of precision pharmacy has been constructed and constantly improved, better evidence in clinical practice will be produced to provide patients with better precision pharmacy service.
Subject(s)
Pharmaceutical Services , Pharmacy , Pregnancy , Child , Humans , Female , Aged , Precision Medicine , Immunosuppressive Agents/therapeutic use , Drug InteractionsABSTRACT
OBJECTIVE: Capecitabine, an antineoplastic drug used in the treatment of breast and colon cancer, can cause severe, even fatal toxicity in some patients. The interindividual variability of this toxicity is largely due to genetic variations in target genes and enzymes of metabolism of this drug, such as Thymidylate Synthase (TS) and Dihydropyrimidine Dehydrogenase (DPD). The enzyme Cytidine Deaminase (CDA), involved in the activation of capecitabine, also has several variants associated with an increased risk of toxicity to treatment, although its role as a biomarker is not yet clearly defined. Therefore, our main objective is to study the association between the presence of genetic variants in CDA gen, CDA enzymatic activity and the development of severe toxicity in patients treated with capecitabine whose initial dose was adjusted based on the genetic profile of the DPD gen (DPYD). METHOD: Prospective multicenter observational cohort study, focused on the analysis of the genotype-phenotype association of the CDA enzyme. After the experimental phase, an algorithm will be developed to determine the dose adjustment needed to reduce the risk of treatment toxicity according to CDA genotype, developing a Clinical Guide for capecitabine dosing according to genetic variants in DPYD and CDA. Based on this guide, a Bioinformatics Tool will be created to generate the pharmacotherapeutic report automatically, facilitating the implementation of pharmacogenetic advice in clinical practice. This tool will be a great support in making pharmacotherapeutic decisions based on the patient's genetic profile, incorporating precision medicine into clinical routine. Once the usefulness of this tool has been validated, it will be offered free of charge to facilitate the implementation of pharmacogenetics in hospital centers and equitably benefit all patients on capecitabine treatment.
Subject(s)
Antimetabolites, Antineoplastic , Fluorouracil , Capecitabine , Antimetabolites, Antineoplastic/therapeutic use , Fluorouracil/adverse effects , Prospective Studies , Genotype , Dihydrouracil Dehydrogenase (NADP)/geneticsABSTRACT
RESUMEN Introducción: La desensibilización farmacológica induce un estado temporal de hiposensibilidad a un medicamento que se realiza a pacientes con reacciones mediadas por Inmunoglobulina E. Reporte de caso: Presentamos el caso de un paciente con exacerbación respiratoria de fibrosis quística que presentó hipersensibilidad inmediata a colistina, un antibiótico esencial para su tratamiento, tanto por la sensibilidad del microorganismo, como la falta de disponibilidad de otros medicamentos. Se realizó el procedimiento en Unidad de Cuidados Intensivos de forma exitosa y el paciente completó el esquema del tratamiento. Conclusión: Actualmente el paciente se encuentra en tratamiento específico para su enfermedad de fondo y no ha presentado nuevos episodios de exacerbación ni neumonías.
ABSTRACT Introduction: Pharmacological desensitization induces a temporary hyposensitivity to the causative drug in patients with Immunoglobulin E-mediated drug reactions. Case of report: We present the case of a patient with respiratory exacerbation of cystic fibrosis who presented immediate hypersensitivity to colistin, an essential antibiotic for its treatment-both due to the sensitivity of the microorganism and the lack of availability of other drugs. The procedure was successfully performed in the Intensive Care Unit, and the patient completed the treatment schedule. Conclusion: Currently, the patient is undergoing specific treatment for his underlying disease and has not presented any new episodes of exacerbation or pneumonia.
ABSTRACT
OBJECTIVE: Capecitabine, an antineoplastic drug used in the treatment of breast and colon cancer, can cause severe, even fatal toxicity in some patients. The interindividual variability of this toxicity is largely due to genetic variations in target genes and enzymes of metabolism of this drug, such as thymidylate synthase and dihydropyrimidine dehydrogenase. The enzyme cytidine deaminase (CDA), involved in the activation of capecitabine, also has several variants associated with an increased risk of toxicity to treatment, although its role as a biomarker is not yet clearly defined. Therefore, our main objective is to study the association between the presence of genetic variants in CDA gen, CDA enzymatic activity and the development of severe toxicity in patients treated with capecitabine whose initial dose was adjusted based on the genetic profile of the dihydropyrimidine dehydrogenase gen (DPYD). METHOD: Prospective multicenter observational cohort study, focused on the analysis of the genotype-phenotype association of the CDA enzyme. After the experimental phase, an algorithm will be developed to determine the dose adjustment needed to reduce the risk of treatment toxicity according to CDA genotype, developing a clinical guide for capecitabine dosing according to genetic variants in DPYD and CDA. Based on this guide, a Bioinformatics Tool will be created to generate the pharmacotherapeutic report automatically, facilitating the implementation of pharmacogenetic advice in clinical practice. This tool will be a great support in making pharmacotherapeutic decisions based on the patient's genetic profile, incorporating precision medicine into clinical routine. Once the usefulness of this tool has been validated, it will be offered free of charge to facilitate the implementation of pharmacogenetics in hospital centers and equitably benefit all patients on capecitabine treatment.
Subject(s)
Antimetabolites, Antineoplastic , Dihydrouracil Dehydrogenase (NADP) , Capecitabine , Antimetabolites, Antineoplastic/therapeutic use , Dihydrouracil Dehydrogenase (NADP)/genetics , Prospective Studies , Genotype , Fluorouracil/adverse effectsABSTRACT
La congestión desempeña un papel fundamental en la patogénesis, la presentación y el pronóstico de la insuficiencia cardiaca y es un objetivo terapéutico importante. Sin embargo, su gravedad y su distribución por órganos y compartimentos varían mucho entre los pacientes, lo que ilustra la complejidad de este fenómeno. Aunque los síntomas y signos clínicos son útiles para evaluar la congestión y controlar el estado del volumen en un paciente individual, tienen poca sensibilidad y no permiten fenotipificar la congestión. Esto conduce a la incertidumbre diagnóstica y dificulta la toma de decisiones terapéuticas. En este artículo se ofrece una visión general actualizada de los biomarcadores circulantes, las modalidades de imagen (es decir, la ecografía cardiaca y extracardiaca) y las técnicas invasivas que podrían ayudar a los clínicos a identificar los diferentes perfiles de congestión y guiar la estrategia de tratamiento para esta población diversa de pacientes de alto riesgo con insuficiencia cardiaca.(AU)
Congestion plays a major role in the pathogenesis, presentation, and prognosis of heart failure and is an important therapeutic target. However, its severity and organ and compartment distribution vary widely among patients, illustrating the complexity of this phenomenon. Although clinical symptoms and signs are useful to assess congestion and manage volume status in individual patients, they have limited sensitivity and do not allow identification of congestion phenotype. This leads to diagnostic uncertainty and hampers therapeutic decision-making. The present article provides an updated overview of circulating biomarkers, imaging modalities (ie, cardiac and extracardiac ultrasound), and invasive techniques that might help clinicians to identify different congestion profiles and guide the management strategy in this diverse population of high-risk patients with heart failure.(AU)
Subject(s)
Humans , Heart Failure , Pulmonary Edema , Biomarkers , Precision Medicine , Ultrasonography , Cardiology , Cardiovascular DiseasesABSTRACT
Congestion plays a major role in the pathogenesis, presentation, and prognosis of heart failure and is an important therapeutic target. However, its severity and organ and compartment distribution vary widely among patients, illustrating the complexity of this phenomenon. Although clinical symptoms and signs are useful to assess congestion and manage volume status in individual patients, they have limited sensitivity and do not allow identification of congestion phenotype. This leads to diagnostic uncertainty and hampers therapeutic decision-making. The present article provides an updated overview of circulating biomarkers, imaging modalities (ie, cardiac and extracardiac ultrasound), and invasive techniques that might help clinicians to identify different congestion profiles and guide the management strategy in this diverse population of high-risk patients with heart failure.