Exploring the impact of pharmacogenetics on personalized medicine: A systematic review. / [Artículo traducido] Exploración del impacto de la farmacogenética en la medicina personalizada: una revisión sistemática.

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.

Factors Contributing to Negative Outcomes Associated with Medications and Drug-Related Problems in Kidney Replacement Therapy-A Hospital-Based Prospective Observational Study.

BACKGROUND: Negative outcomes associated with medications (NOM) and drug-related problems (DRP) significantly impact individuals with kidney replacement therapy (KRT) given the complexities of managing kidney disease and associated comorbidities. The present study aims to assess the frequency of NOMs/DRPs among KRT patients and identify contributing factors. METHODS: A cross-sectional study was conducted at Virgen de las Nieves University Hospital (Granada, Spain), involving 117 outpatient adults with KRT. Data were collected from February 2021 to July 2023 using electronic records, semi-structured interviews (Dáder Method), and discussions with nephrology specialists. NOMs/DRPs were identified following treatment guidelines. Binary logistic regression was used to determine associated factors (p-value < 0.05). RESULTS: Across 117 patients, 2436 NOMs and 3303 DRPs were identified, averaging 20.82 NOMs and 28.23 DRPs per patient. Prevalent NOMs included untreated conditions (58.95%), quantitative ineffectiveness (35.43%), and non-quantitative safety problems (5.13%). Dominant DRPs were undertreated conditions (37.63%), wrong dose/posology/length (33.00%), risk of adverse drug reactions (ADR) (16.14%), and non-adherence (6.87%). Patients with ADR, undertreated conditions, and anemia were associated with quantitative ineffectiveness. Risk of ADR and vitamin D deficiency/insufficiency correlated with non-quantitative safety problems. CONCLUSIONS: KRT patients exhibited a substantial prevalence of NOMs/DRPs. Further research is needed to deepen our understanding of these complexities for improved patient care.

Exploring the impact of pharmacogenetics on personalized medicine: A systematic review.

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.

Recomendaciones de consenso para el tratamiento de la prevención de la migraña / Consensus recommendations for the treatment of migraine prevention

Objetivo los objetivos son conocer la opinión de neurólogos y farmacéuticos hospitalarios sobre aquellos aspectos aún en el debate respecto al papel de los anticuerpos monoclonales anti-CGRP en el tratamiento preventivo de la migraña. Identificar aquellas controversias aún existentes. Proponer recomendaciones consensuadas de mejora asistencial. Y promover el acceso de los clínicos y los pacientes a estos nuevos tratamientos en la prevención de la migraña con fármacos biológicos, a fin de mejorar la atención y seguimiento del paciente. Métodos se identificaron y valoraron recomendaciones para la utilización de fármacos biológicos en la prevención de la migraña a través de la metodología de consenso Delphi, proponiendo 88 aseveraciones agrupadas en 3 temas: un módulo de clínica que trata sobre el manejo de los tratamientos biológicos en la migraña, un módulo de pacientes que trata sobre las estrategias de educación al paciente y mejora de la adhesión y un módulo de coordinación que incluye las aseveraciones relacionadas con las estrategias para mejorar el trabajo conjunto entre los 2 colectivos. Se empleó la escala ordinal de Likert de 9 puntos para puntuar dichas recomendaciones y, posteriormente, los datos se analizaron estadísticamente a través de diferentes métricas. Resultados tras las 2 rondas de consulta, se alcanzó consenso en el acuerdo en 71 aseveraciones (80,7%) y consenso en el desacuerdo en una de ellas (1,1%), quedando como indeterminadas 16 aseveraciones (18,2%) de las 88 debatidas. Conclusiones el alto grado de consenso indica que la opinión de neurólogos y farmacéuticos hospitalarios sobre el papel de los anticuerpos monoclonales anti-CGRP en el tratamiento de la migraña es muy similar y permite identificar aquellas controversias aún existentes, para mejorar la atención y seguimiento del paciente con migraña. (AU)

Objective The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-CGRP monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. Methodology Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into three themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analyzed through different metrics. Results After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving one statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). Conclusions The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-CGRP monoclonal antibodies in the treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine. (AU)

Lista de comprobación para la atención farmacéutica del paciente con enfermedad pulmonar intersticial (CheckEPID): un consenso basado en el método Delphi / Checklist for Pharmaceutical Care of the Patient with interstitial lung disease (CheckEPID): A Delphi-based consensus

Objetivo desarrollar una lista de comprobación para facilitar la atención farmacéutica al paciente con enfermedad pulmonar intersticial que requieren o están en tratamiento con antifibróticos. Método 5 especialistas en farmacia hospitalaria desarrollaron un listado inicial de 37 ítems divididos en 4 bloques: 1) primera visita del paciente, que incluía datos generales del paciente y datos del primer tratamiento; 2) visitas de seguimiento, valorando aspectos del seguimiento del tratamiento con nintedanib o pirfenidona; 3) telefarmacia, consistente en la evaluación de la inclusión de pacientes en un programa de este tipo, evolución de la enfermedad e identificación del contacto con el servicio de farmacia y 4) tratamiento no farmacológico e información al paciente. Para decidir su potencial inclusión en el listado de comprobación se realizaron 2 rondas del Delphi en las que los panelistas tenían que valorar de cada ítem propuesto su grado de acuerdo con su «utilidad», que fue el criterio determinante para su inclusión y su «aplicabilidad». Resultados se contactó con 48 farmacéuticos hospitalarios, 30 (63%) aceptaron por escrito participar, 28 (58%) completaron la primera ronda del Delphi y 27 (56%) completaron la segunda ronda. Después de la primera ronda el cuestionario se modificó y quedó constituido por 40 ítems. De los 40 ítems evaluados tras las 2 rondas del Delphi, hubo 2 que, basados en la utilidad, los participantes del Delphi no alcanzaron el consenso para su inclusión en el listado: el referido a «Antecedentes de intervención quirúrgica, específicamente cirugía abdominal en las últimas 4 semanas» (finalmente mantenido en el listado por su implicación en la indicación de nintedanib) y el de realizar recomendaciones sobre «Relajación». En 2 de los ítems no se alcanzó consenso sobre su aplicabilidad: «Estratificación del paciente según el modelo del paciente crónico de la SEFH» y «Recogida de resultados comunicados por el paciente». Conclusiones... (AU)

Objective To develop a checklist to facilitate pharmaceutical care for patients with interstitial lung disease who require or are undergoing treatment with antifibrotic drugs. Method Five hospital pharmacists developed an initial list of 37 items divided into 4 blocks: 1) First visit, which included general patient data and data from the first treatment; 2) Follow-up visits, assessing aspects of the follow-up of the treatment with nintedanib or pirfenidone; 3) Telepharmacy, consisting of the evaluation of the inclusion of patients in a program of this type, course of the disease, and identification of the contact with the pharmacy service; 4) Non-pharmacological treatment and patient information. To decide its potential inclusion in the checklist, two rounds of the Delphi were carried out in which the panelists had to assess the degree of agreement of each proposed item according to its “utility”, which was the determining criterion for its inclusion, and its “applicability”. Results 48 hospital pharmacists were contacted, 30 (63%) agreed in writing to participate, 28 (58%) completed the first round of the Delphi, and 27 (56%) completed the second round. After the first round of the Delphi the questionnaire was amended and comprised 40 items. Of the 40 items evaluated after the two rounds of the Delphi, there were two that, based on utility, the participants did not reach consensus for inclusion in the checklist: The one referring to “History of surgical intervention, specifically abdominal surgery in the last 4 weeks” (finally kept on the checklist due to its involvement in the indication of nintedanib) and to make recommendations on “Relaxation”. No consensus was reached on their applicability for two of the items: “Patient stratification according to the Spanish Society of Hospital Pharmacy (SEFH) chronic patient model” and “Collection of Results Reported by the Patient”. Conclusions ... (AU)

[Translated article] Checklist for the pharmaceutical care of patients with interstitial lung disease (CheckEPID): A Delphi-based consensus.

OBJECTIVE: To develop a checklist to facilitate pharmaceutical care for patients with interstitial lung disease who require or are undergoing treatment with antifibrotic drugs. METHOD: Five hospital pharmacists developed an initial list of 37 items divided into 4 blocks: (1) First visit, which included general patient data and data from the first treatment; (2) follow-up visits, assessing aspects of the follow-up of the treatment with nintedanib or pirfenidone; (3) telepharmacy, consisting of the evaluation of the inclusion of patients in a program of this type, course of the disease, and identification of the contact with the pharmacy service; (4) non-pharmacological treatment and patient information. To decide its potential inclusion in the checklist, 2 rounds of the Delphi were carried out in which the panelists had to assess the degree of agreement of each proposed item according to its "utility", which was the determining criterion for its inclusion, and its "applicability". RESULTS: Forty-eight hospital pharmacists were contacted, 30 (63%) agreed in writing to participate, 28 (58%) completed the first round of the Delphi, and 27 (56%) completed the second round. After the first round of the Delphi, the questionnaire was amended and comprised 40 items. Of the 40 items evaluated after the 2 rounds of the Delphi, there were 2 that, based on utility, the participants did not reach consensus for inclusion in the checklist: the one referring to "History of surgical intervention, specifically abdominal surgery in the last 4 weeks" (finally kept on the checklist due to its involvement in the indication of nintedanib) and to make recommendations on "Relaxation". No consensus was reached on their applicability for 2 of the items: "Patient stratification according to the Spanish Society of Hospital Pharmacy (SEFH) chronic patient model" and "Collection of Results Reported by the Patient". CONCLUSIONS: The management of patients with ILD and/or pulmonary fibrosis is complex and requires a multidisciplinary approach where the hospital pharmacist plays a key role, especially, although not only, in monitoring drug treatment. We believe that this checklist can contribute from pharmaceutical care to improving the integrated care of patients with ILD who require or are undergoing treatment with antifibrotic drugs.

[Translated article] Consensus recommendations on the preventive treatment of migraine.

OBJECTIVE: The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. METHODOLOGY: Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into 3 themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analysed through different metrics. RESULTS: After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving 1 statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). CONCLUSIONS: The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Medication Review with Follow-Up for End-Stage Renal Disease: Drug-Related Problems and Negative Outcomes Associated with Medication-A Systematic Review.

BACKGROUND: This article reviews the available scientific literature on drug-related problems and negative outcomes associated with medications identified by medication review with follow-up for end-stage renal disease and discussed with the physicians. METHODS: A systematic review was conducted of the scientific literature retrieved from the following databases: MEDLINE (via PubMed), Web of Science, SCOPUS, Cochrane Library: The Cochrane Central Register and Control Trials (CENTRAL) and Literatura Latinoamericana y del Caribe (LILACS), Medicina en Español (MEDES), and the SciELO bibliographic database (a collection of scientific journals). The following terms were used as descriptors and searched in free text: "end-stage renal disease", "medication review", "drug-related problems", and "negative outcomes associated with medication". The following limits were applied: "humans" and "adults (more than 18 years)". RESULTS: A total of 59 references were recovered and, after applying inclusion/exclusion criteria, 16 articles were selected. Of these selected articles, 15 provided information on drug-related problems and only 1 on negative outcomes associated with medications. CONCLUSIONS: It can be concluded that drug-related problems and negative outcomes associated with medications affect patients with end-stage renal disease, mainly those receiving renal replacement therapy. More evidence is needed, especially on negative outcomes associated with medication.

Clinical Outcomes of First-line Therapies for Advanced Non-Small Cell Lung Cancer: A Systematic Review of Trials Published Between 2010 and 2020.

OBJECTIVES: To analyze the evolution of clinical outcomes derived from clinical trials on first-line therapies for advanced or metastatic non-small cell lung cancer (NSCLC) published between 2010 and 2020, focusing on how these outcomes impact survival rates and management of patients. METHODS: A systematic review of phase III and pivotal phase II clinical trials was conducted by a structured search on Medline and Embase. A comprehensive set of variables was collected to assess their influence on survival rates. We also estimated the clinical benefit by applying the ESMO-MCBS v1.1 and extracted the authors' conclusions. RESULTS: Sixty-six studies involving 34,951 patients were included. Best survival outcomes were found for nonsquamous non-small cell lung cancer (OS and progression-free survival medians: 19.4 and 10.2 mo) and for those expressing molecular targets (OS and progression-free survival medians: 23.8 and 11.0 mo). No significant influence on survival rates was observed for industry funding and disease stage (IIIB/IV vs. IV). ESMO-MCBS v1.1 was applied in 45 positive studies and resulted in a meaningful clinical benefit score in 37.8%. Quality of life (QoL) was reported in 57.6% of the original publications and showed statistical significance favoring the experimental arm in 33.3%. Positive authors' conclusions (75.7% of trials) were based on OS and/or QoL in 34% and on surrogate endpoints in 66%. CONCLUSIONS: Extended survival times and a steady improvement in QoL have been observed. However, there were more than twice as many studies reporting positive authors' conclusions as studies meeting the ESMO threshold for meaningful clinical benefit.

Checklist for Pharmaceutical Care of the Patient with interstitial lung disease (CheckEPID): A Delphi-based consensus. / Lista de comprobación para la atención farmacéutica del paciente con enfermedad pulmonar intersticial (CheckEPID): un consenso basado en el método Delphi.

OBJECTIVE: To develop a checklist to facilitate pharmaceutical care for patients with interstitial lung disease who require or are undergoing treatment with antifibrotic drugs. METHOD: Five hospital pharmacists developed an initial list of 37 items divided into 4 blocks: 1) First visit, which included general patient data and data from the first treatment; 2) Follow-up visits, assessing aspects of the follow-up of the treatment with nintedanib or pirfenidone; 3) Telepharmacy, consisting of the evaluation of the inclusion of patients in a program of this type, course of the disease, and identification of the contact with the pharmacy service; 4) Non-pharmacological treatment and patient information. To decide its potential inclusion in the checklist, two rounds of the Delphi were carried out in which the panelists had to assess the degree of agreement of each proposed item according to its "utility", which was the determining criterion for its inclusion, and its "applicability". RESULTS: 48 hospital pharmacists were contacted, 30 (63%) agreed in writing to participate, 28 (58%) completed the first round of the Delphi, and 27 (56%) completed the second round. After the first round of the Delphi the questionnaire was amended and comprised 40 items. Of the 40 items evaluated after the two rounds of the Delphi, there were two that, based on utility, the participants did not reach consensus for inclusion in the checklist: The one referring to "History of surgical intervention, specifically abdominal surgery in the last 4 weeks" (finally kept on the checklist due to its involvement in the indication of nintedanib) and to make recommendations on "Relaxation". No consensus was reached on their applicability for two of the items: "Patient stratification according to the Spanish Society of Hospital Pharmacy (SEFH) chronic patient model" and "Collection of Results Reported by the Patient". CONCLUSIONS: The management of patients with ILD and/or pulmonary fibrosis is complex and requires a multidisciplinary approach where the hospital pharmacist plays a key role, especially, although not only, in monitoring drug treatment. We believe that this checklist can contribute from pharmaceutical care to improving the integrated care of patients with ILD who require or are undergoing treatment with antifibrotic drugs.

Consensus recommendations for the treatment of migraine prevention. / Recomendaciones de consenso para el tratamiento de la prevención de la migraña.

OBJECTIVE: The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-CGRP monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. METHODOLOGY: Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into three themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analyzed through different metrics. RESULTS: After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving one statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). CONCLUSIONS: The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-CGRP monoclonal antibodies in the treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Contribution of cabotegravir + rilpivirine long-acting for the treatment of HIV-1 infection.

OBJECTIVE: To determine the value contribution of cabotegravir + rilpivirine, the first injectable every two months long-acting antiretroviral  regimen, using multi-criteria decision analysis. METHOD: The study was developed in two phases. After a small pilot, a field  ork study with a larger number of multidisciplinary experts was carried out.  Seven single-tablet regimens, currently recommended by the GeSIDA  guidelines, were selected as comparators. EVIDEM methodology was followed,  with a framework composed by 12 quantitative and 5 contextual criteria. Mean  and standard deviations were calculated for quantitative criteria (1 to 5 scale;  comparative criteria -5 to +5), whereas qualitative criteria were analyzed as  percentages of experts that considered a positive, neutral or negative impact  for the National Health System. RESULTS: 35 experts participated in the study. Human immunodeficiency virus- 1 infection was considered severe (mean ± standard deviation: 3.0 ± 1.0),  with moderate size of affected population (2.7 ± 1.2) and unmet needs (2.8 ±  1.0). Minimal differences were found in comparative efficacy/effectiveness (0.1  ± 0.5), safety/tolerability (-0.5 ± 0.7), and cost criteria: cost of the  intervention (0.5 ± 2.0), other medical costs (0.2 ± 1.8) and non- medical/indirect costs (0.5 ± 1.6). Experts perceived an improvement with  cabotegravir + rilpivirine long-acting, compared  to current daily oral single-tablet regimens, in patient-reported outcomes (2.7 ± 1.4). Therapeutic benefit  of the long-acting regimen was considered moderate-to-high (3.5 ± 1.2).  Experts considered the evidence provided by cabotegravir + rilpivirine long- actingrobust (4.3 ± 0.8), with elevated consensus on its future  recommendation in guidelines (3.2 ± 1.0). In contextual criteria, most experts  considered positive the impact on population priorities and access (91%),  common goal and specific interests (63%) and political, historical, and cultural  context criteria (60%). Impact was neutral in system capacity and appropriate  use (40%), and opportunity costs and affordability criteria (51%). Result of the  weighted global value contribution of cabotegravir + rilpivirine long-acting  was 0.34 (-1 to +1 scale), with Patient Reported Outcomes comparative  criterion bringing the highest added value. CONCLUSIONS: Cabotegravir + rilpivirine long-acting provides added value  contribution to human immunodeficiency virus-1 management in Spain  compared to daily oral single-tablet regimens. Patient Reported Outcomes and  therapeutic benefit of cabotegravir + rilpivirine long-acting were highly valued  by experts, as the expected benefit in adherence and stigma-related issues  would improve overall quality of life for people living with human  immunodeficiency virus-1.

OBJETIVO: Determinar la contribución de valor de cabotegravir + rilpivirina, el  primer tratamiento antirretroviral inyectable de acción prolongada, utilizando  metodología de análisis de decisión multicriterio.Método: El estudio se desarrolló en dos fases: una prueba piloto y una fase de  extensión, con un grupo multidisciplinar más grande. Se seleccionaron siete regímenes de comprimido único orales diarios  recomendados en las guías GeSIDA como comparadores. Se utilizó el marco  EVIDEM, compuesto por 12 criterios cuantitativos y 5 contextuales. Los  criterios cuantitativos se analizaron calculando la media y desviación estándar,  y los cualitativos se analizaron mediante el porcentaje de expertos que  consideraron el impacto positivo, neutro o negativo para el Sistema Nacional de Salud. RESULTADOS: Un total de 35 expertos participaron en el estudio. La infección  por virus de la inmunodeficiencia humana 1 se consideró grave (media ±  desviación estándar: 3,0 ± 1,0), con un tamaño de población afectada (2,7 ±  1,2) y unas necesidades no cubiertas (2,8 ± 1,0) moderadas. Las diferencias  fueron mínimas en los criterios comparativos de eficacia/efectividad (0,1 ±  0,5), seguridad/tolerabilidad (­0,5 ± 0,7) y coste: coste del tratamiento (0,5 ±  2,0), otros costes médicos (0,2 ± 1,8) y costes no-médicos/indirectos (0,5  ± 1,6). Los expertos observaron una emtrimejora con cabotegravir + rilpivirina  de acción prolongada en los resultados reportados por los pacientes  (2,7 ± 1,4). El beneficio terapéutico (3,5 ± 1,2) se consideró moderado-alto.  La evidencia de cabotegravir + rilpivirina de acción prolongada fue considerada  robusta (4,3 ± 0,8), con elevado consenso sobre su futura  recomendación en las guías (3,2 ± 1,0). En los criterios contextuales, el  impacto fue positivo en los criterios de prioridades de acceso (91%), objetivo  común (63%) y contexto político (60%). El impacto fue neutro en la capacidad  del sistema (40%) y los costes de oportunidad (51%). El resultado  promedio de la contribución del valor global de cabotegravir + rilpivirina de  acción prolongada fue de 0,34 (escala de ­1 a +1), siendo el criterio de  resultados reportados por el paciente el que proporcionó la mayor contribución de valor (0,04). CONCLUSIONES: Cabotegravir + rilpivirina de acción prolongada aporta un valor  añadido en el manejo del virus de la inmunodeficiencia humana 1 en  España en comparación con los regímenes de comprimido único utilizados  actualmente. Los expertos valoraron positivamente los resultados reportados  por los pacientes y el beneficio terapéutico de cabotegravir + rilpivirina de  acción prolongada, considerando que el beneficio esperado en la adherencia y  los problemas relacionados con el estigma produciría una mejora en la calidad  de vida de las personas con virus de la inmunodeficiencia humana 1.

Contribución de cabotegravir + rilpivirina de acción prolongada al tratamiento de la infección por VIH-1 / Contribution of cabotegravir + rilpivirine long-acting for the treatment of HIV-1 infection

Objetivo: Determinar la contribución de valor de cabotegravir + rilpivirina, el primer tratamiento antirretroviral inyectable de acción prolongada,utilizando metodología de análisis de decisión multicriterio.Método: El estudio se desarrolló en dos fases: una prueba piloto y unafase de extensión, con un grupo multidisciplinar más grande. Se seleccionaron siete regímenes de comprimido único orales diarios recomendadosen las guías GeSIDA como comparadores. Se utilizó el marco EVIDEM,compuesto por 12 criterios cuantitativos y 5 contextuales. Los criterioscuantitativos se analizaron calculando la media y desviación estándar, ylos cualitativos se analizaron mediante el porcentaje de expertos que consideraron el impacto positivo, neutro o negativo para el Sistema Nacionalde Salud.Resultados: Un total de 35 expertos participaron en el estudio. Lainfección por virus de la inmunodeficiencia humana 1 se consideró grave(media ± desviación estándar: 3,0 ± 1,0), con un tamaño de poblaciónafectada (2,7 ± 1,2) y unas necesidades no cubiertas (2,8 ± 1,0) moderadas. Las diferencias fueron mínimas en los criterios comparativos deeficacia/efectividad (0,1 ± 0,5), seguridad/tolerabilidad (–0,5 ± 0,7) ycoste: coste del tratamiento (0,5 ± 2,0), otros costes médicos (0,2 ± 1,8)y costes no-médicos/indirectos (0,5 ± 1,6). Los expertos observaron una mejora con cabotegravir + rilpivirina de acción prolongada en los resultados reportados por los pacientes (2,7 ± 1,4). El beneficio terapéutico(3,5 ± 1,2) se consideró moderado-alto. La evidencia de cabotegravir+ rilpivirina de acción prolongada fue considerada robusta (4,3 ± 0,8),con elevado consenso sobre su futura recomendación en las guías(3,2 ± 1,0). En los criterios contextuales, el impacto fue positivo en loscriterios de prioridades de acceso (91%), objetivo común (63%) y contextopolítico (60%). (AU)

Objective: To determine the value contribution of cabotegravir + rilpivirine, the first injectable every two months long-acting antiretroviral regimen, using multi-criteria decision analysis.Method: The study was developed in two phases. After a small pilot,a field work study with a larger number of multidisciplinary experts wascarried out. Seven single-tablet regimens, currently recommended by theGeSIDA guidelines, were selected as comparators. EVIDEM methodology was followed, with a framework composed by 12 quantitative and5 contextual criteria. Mean and standard deviations were calculated forquantitative criteria (1 to 5 scale; comparative criteria –5 to +5), whereasqualitative criteria were analyzed as percentages of experts that considered a positive, neutral or negative impact for the National Health System.Results: 35 experts participated in the study. Human immunodeficiencyvirus-1 infection was considered severe (mean ± standard deviation:3.0 ± 1.0), with moderate size of affected population (2.7 ± 1.2) andunmet needs (2.8 ± 1.0). Minimal differences were found in comparative efficacy/effectiveness (0.1 ± 0.5), safety/tolerability (–0.5 ± 0.7),and cost criteria: cost of the intervention (0.5 ± 2.0), other medical costs(0.2 ± 1.8) and non-medical/indirect costs (0.5 ± 1.6). Experts perceived an improvement with cabotegravir + rilpivirine long-acting, compared to current daily oral single-tablet regimens, in patient-reported outcomes(2.7 ± 1.4). Therapeutic benefit of the long-acting regimen was considered moderate-to-high (3.5 ± 1.2). (AU)

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

Adverse events reported after administration of BNT162b2 and mRNA-1273 COVID-19 vaccines among hospital workers: a cross-sectional survey-based study in a Spanish hospital.

BACKGROUND: The World Health Organization declared COVID-19 a pandemic in March 2020. The first vaccine became available in December, with practically no post-marketing data. METHODS: An analytical cross-sectional survey-based study was conducted in a third-level hospital in Spain between March and April 2021 to describe the difference in adverse events with the BNT162b2 and mRNA-1273 COVID-19 vaccines. The participants were hospital workers who completed a survey voluntarily at least 14 days after the last vaccine. The STROBE checklist was followed. RESULTS: One thousand two hundred and forty-nine respondents completed the survey; 48% (599) received mRNA-1273 and 52% (650) BNT162b2. Fourteen thousand four hundred and two adverse reactions were recorded, 6896 local (3939 with mRNA-1273 and 2957 with BNT162b2 (6.6 vs 4.4 reactions per patient)) and 7506 systemic (4460 with mRNA-1273 and 3046 with BNT162b2 (7.4 vs 4.7 per patient)). Local reactions were more frequent after the first dose, while systemic reactions were higher after the second, for both vaccines and in a higher percentage with mRNA-1273 compared to BNT162b2 (p-value<0.05). CONCLUSIONS: Licensed mRNA vaccines were highly safe when administered under post-marketing conditions among working-age adults. The main adverse events were mild, although they occurred in most patients, especially after the mRNA-1273 vaccine.

Effectiveness and safety of topical 15% resorcinol in the management of mild-to-moderate hidradenitis suppurativa: A cohort study.

Antibiotics remain one of the main treatment alternatives in mild-to-moderate hidradenitis suppurativa. The use of topical 15% resorcinol reduces antibiotic pressure and the generation of resistance. However, knowledge on its efficacy and safety is limited. This single-center, prospective, follow-up cohort study evaluated topical 15% resorcinol every 12-h response at 16 weeks. Those individuals with mild-to-moderate hidradenitis suppurativa (Hurley I-II) who started treatment with topical resorcinol monotherapy between April 2019 and May 2020 were eligible for follow-up. The primary endpoint for effectiveness was the proportion of patients who achieved an overall clinical response (complete or partial response) at week 16, evaluated as intention-to-treat. Responses were measured according to the Hidradenitis Suppurativa Clinical Response index. Target lesion size was measured clinically and by ultrasonography. Quality of life was assessed through the Dermatology Life Quality Index (DLQI) questionnaire. Safety was measured by recording the adverse events reported during the follow-up period. A total of 32 patients were enrolled (mean age, 40.1 years [95% confidence interval, 35.7-44.4]; women, 20 [62.5%]; Hurley I, 17 [53.1%]). Under the intention-to-treat analysis, 68.8% (n = 22) of the patients achieved a clinical response. A ≥50% reduction in the size of the main lesion was observed in 56.3% of the patients (n = 18). Some 65.6% (n = 21) of the patients had a ≥50% reduction (improvement) in their baseline DLQI score. Fifty percent of patients who completed the follow-up period experienced adverse events, all of which were local, mild, and transient and did not lead to discontinuation of resorcinol. To conclude, in this cohort study, topical 15% resorcinol was shown to be effective for mild-to-moderate hidradenitis suppurativa and to have a positive impact on quality of life with an acceptable safety profile.

Discontinuation of cholinesterase inhibitor treatment in institutionalised patients with advanced dementia.

OBJECTIVE: To evaluate the impact of discontinuation of treatment with cholinesterase inhibitors (ChEIs) on cognitive, behavioural and functional outcomes in patients with severe dementia. METHODS: A prospective observational study in which the prescribing physician decides, depending on multidisciplinary assessment and following the recommendations of the clinical practice guidelines, whether to withdraw or continue ChEI treatment in institutionalised patients, with a follow-up of 3 months. Cognitive abilities were measured using the Mini-Mental State Examination (MMSE) and Reisberg's Global Deterioration Scale (GDS). Other measures were the behavioural and psychological symptoms of dementia (BPSD) according to the Neuropsychiatric Inventory (NPI), the activities of daily living using the Barthel index, the pharmacological and the non-pharmacological measures to treat the BPSD. RESULTS: ChEI treatment was discontinued in 23 of 43 patients. After 3 months there were no differences in MMSE (p=0.441), GDS (p=0.976), NPI (p=0.882) or Barthel index (p=0.080) scores, or the establishing of new pharmacological measures (p=0.919) or non-pharmacological measures (p=0.832). CONCLUSIONS: ChEI discontinuation in advanced stage dementia was not related to clinical deterioration in terms of cognitive function, BPSD, or functional status. Discontinuing ChEI treatment according to a multidisciplinary assessment and the recommendation of the guidelines appears to be a possible way of optimising pharmacotherapy without altering the main clinical evaluation scales.

Formulation, long-term physicochemical and microbiological stability of 15% topical resorcinol for hidradenitis suppurativa.

OBJECTIVES: Topical resorcinol 15% is a self-treatment for painful hidradenitis suppurativa nodules and abscesses with good results in reducing pain and lesion duration. The aim of this study is to establish a 15% topical resorcinol formula, to develop a physicochemical and microbiological stability study and to further determine the compounding shelf-life in different package conditions following the European Pharmacopoeia (Ph. Eur.) specifications. METHODS: Physicochemical and microbiological stability studies of the formulation were conducted for 12 months at room temperature (25°C±2°C) in different package conditions: aluminium tubes (aluminium A7-99.7% varnish DF-6172), plastic tubes (low density polyethylene) and amber plastic containers (polyethylene terephthalate). High performance liquid chromatography (HPLC) was developed as a method of indicating the stability of the resorcinol formulation. A microbiological growth assay was also validated according to the Ph. Eur. Physical properties were inspected to determine parameters such as odour, colour, pH, emulsion phase and extensibility index and its evolution. RESULTS: The HPLC method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. At day 365, visual inspection remained unchanged only for preparations packaged in aluminium tubes. The pH did not vary by more than 0.3 units in all conditions. The extensibility index decreased in the preparations packaged in plastic and amber plastic containers. HPLC analysis conducted over 1 year did not show a degradation greater than 7% of resorcinol in the preparation in plastic and aluminium packages. The ability of ATCC strains to grow in resorcinol formulation was confirmed under the suitability test. Resorcinol packed in aluminium tubes achieved microbiological stability at day 365. CONCLUSIONS: Only the formulation package in aluminium tubes showed physicochemical and microbiological stability of resorcinol for 12 months at room temperature (25°C±2°C).

Switch to subcutaneous infliximab during the SARS-CoV-2 pandemic: preliminary results.

A new subcutaneous formulation of the infliximab biosimilar CT-P13 has recently been developed for the treatment of inflammatory bowel disease (IBD), providing response rates similar to intravenous treatment. The use of this new formulation was requested, in an effort to limit patient attendance at intravenous infusion centers and to maintain biological treatment during the COVID-19 pandemic. The objective of this observational, retrospective and descriptive study was to assess CT-P13 efficacy and safety after switching from intravenous to a subcutaneous formulation in patients with IBD receiving maintenance therapy. This article shows preliminary results after six months of follow-up.