Utilización terapéutica de los anticuerpos monoclonales

La utilización de terapias basadas en anticuerpos monoclonales ha supuesto un gran avance en la práctica clínica. Tienen un ámbito de utilización muy diverso, incluyendo aplicaciones diagnósticas y terapéuticas principalmente. En cuanto a su uso como tratamiento, las áreas más beneficiadas con su descubrimiento han sido la oncología y las enfermedades del sistema inmune. Se trata de un área en continuo crecimiento, tanto por la aparición de nuevos fármacos, como por la ampliación de indicaciones de los ya existentes. Esta revisión resume las características farmacológicas más importantes de los anticuerpos monoclonales comercializados en nuestro país. Se centra principalmente en la utilidad terapeútica, dosificación, eventos adversos de gran relevancia clínica y consideraciones importantes para su correcta administración. También se realiza un breve apunte de las indicaciones de los anticuerpos monoclonales autorizados por la agencia europea del medicamento (EMEA) y que se encuentran en distintas fases del proceso de comercialización.The utilization of therapies based on monoclonal antibodies has supposed a great advance in the clinical practice. They have a diverse field of use, including diagnostic and therapeutic applications. As treatment, the most benefited has been the oncology and immune system diseases. This is an area in continuous growth, so much for the appearance of new medicaments, since for the extension of indications of the already existing ones. This review summarizes the most important pharmacological characteristics of the monoclonal antibodies commercialized in our country. It centres principally on the authorized indications, dosing, adverse events of great clinical relevancy and important considerations for his correct administration. Also there is realized a brief note of the indications of the monoclonal antibodies authorized by the European agency of the medicine (EMEA) and that are in different phases of the process of commercialization

Prescribing Patterns of Codeine and Alternative Medicines in Children in Europe

INTRODUCTION: Concerns over serious respiratory depression in children led to two European Union (EU) referral procedures (in 2013 and 2015) to review the benefit–risk balance of codeine in this population when used for pain relief, cough or cold. Consequently, codeine should no longer be used in children aged < 12 years and restrictions were introduced for treatment in children ≥ 12 years. OBJECTIVE: This multinational collaborative study aimed to assess the effectiveness of these risk minimisation measures by evaluating changes in prescribing of codeine and alternative treatments. METHOD: Children under 12 and 12–18 years old were followed between 2010 and 2017 to analyse quarterly trends in prescribing of codeine and alternative treatments in electronic health records from France, Germany, Norway, Spain and the United Kingdom using interrupted time series analysis. RESULTS: Overall prescribing of codeine in children decreased in all five countries, reaching near zero prevalence in children under 12 years of age. This was accompanied by an increase in use of other opioid analgesics in France (from 0.15 to 0.56 prevalence per 100 person-years immediately after the first referral), Norway (from 0.0006 to 0.0013 at the end of the study), the United Kingdom (from 0.018 to 0.05 at the end of the study), and an increase in non-opioid analgesics in Norway (from 0.045 to 0.075 at the end of the study) after the referral on pain relief indication. The referral on cough/cold indication led to a decrease in use of opioid and non-opioid antitussives in children aged < 12 years in France (from 10 to 7 and 20 to 16, respectively) and had no impact in other countries. Overall prescribing trends for codeine and alternatives were similar across both age groups within each country. CONCLUSION: The decrease in use of codeine shows that healthcare professionals followed the adopted measures and switched prescribing practices for pain management in children aged < 18 years towards opioid or non-opioid analgesics depending on national clinical and reimbursement settings. Whist the magnitude of the first referral on pain differed between countries, the second referral on cough/cold had only a minimal impact on the use of codeine and antitussives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40264-022-01214-y

Actualización en terapéutica de anticuerpos monoclonales

Objetivos: La terapéutica basada en anticuerpos monoclonales es un área en continuo crecimiento, motivo por el cual hemos considerado necesario realizar una actualización sobre la revisión que hicimos hace dos años. Material y métodos: Se efectuó una revisión narrativa de las modificaciones efectuadas en ficha técnica en lo relativo a ampliación y/o modificación de las indicaciones de los anticuerpos monoclonales comercializados en nuestro país. También se detallan todos los nuevos anticuerpos monoclonales comercializados para los que se describen sus puntos más importantes. Asimismo se exponen las alertas más relevantes en relación a estas moléculas mediante la revisión de los informes mensuales de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) y de las notas publicadas por distintas agencias reguladoras. Por último se han incluidolas moléculas empleadas fuera de indicación a partir de nuestro propio registro hospitalario y de aquéllas en distintas fases de investigación clínica a través del registro web clinicaltrials. Resultados: Se han registrado 22 ampliaciones/modificaciones en las indicaciones de los anticuerpos monoclonales comercializados hasta el año 2011. En relación a dichas moléculas se han publicado 12 alertas por parte de las agencias reguladoras y de los laboratorios fabricantes. Igualmente son 12 los anticuerpos monoclonales que han sido comercializados en nuestro país desde entonces. Los usos fuera de indicación de estas moléculas son muy variados destacando dermatología y enfermedades del sistema inmune como servicios solicitantes. Existen multitud de anticuerpos monoclonales en investigación clínica, algunos de ellos como nuevas moléculas y en otros casos para la ampliación del repertorio de indicaciones de los mismos. Conclusión: El conocimiento en la terapéutica basada en anticuerpos monoclonales precisa de actualizaciones periódicasdebido a la investigación de nuevas moléculas, cambios o ampliación de las indicaciones en las moléculas ya comercializadas y aparición de alertas durante la fase de farmacovigilancia.Aim: The monoclonal antibody-based therapeutics is a continuously growing area, which is why we found it necessary to perform an update on the review we did two years ago. Materials and methods: They conducted a narrative review of the technical changes made regarding expansion and / or modification of monoclonal antibodies directed marketed in our country. It also details all new monoclonal antibodies marketed for describing its main points. It also presents the most relevant alerts in relation to these molecules by reviewing the monthly reports of the Agencia Española de Medicamentos y ProductosSanitarios (AEMPS)and notes issued by various regulatory agencies. Finally, we have included the molecules used off label from our own hospital registry and those in various stages of clinical research through clinical trials web log. Results: There have been 22 additions / modifications in monoclonal antibodies directed marketed until 2011. In relation to these molecules it has been published 12 alerts by regulatory agencies and laboratories manufacturers. Also there are 12 monoclonal antibodies that have been marketed in our country since then. The off-label uses of these molecules are varied highlighting dermatology and immune system diseases such as requesting services. There are plenty of monoclonal antibodies in clinical research, some of them as new molecules and in other cases to expand the repertoire of indications thereof. Conclusion: The knowledge in monoclonal antibody-based therapeutics requires regular updates because of the research of new molecules, changes or expansion of indications in the molecules already on the market and appearance of alerts during the pharmacovigilance

Topography of activation deficits in schizophrenia during P300 task related to cognition and structural connectivity

Background The study of cerebral underpinnings of schizophrenia may benefit from the high temporal resolution of electromagnetic techniques, but its spatial resolution is low. However, source imaging approaches such as low-resolution brain electromagnetic tomography (LORETA) allow for an acceptable compromise between spatial and temporal resolutions. Methods We combined LORETA with 32 channels and 3-Tesla diffusion magnetic resonance (Dmr) to study cerebral dysfunction in 38 schizophrenia patients (17 first episodes, FE), compared to 53 healthy controls. The EEG was acquired with subjects performing an odd-ball task. Analyses included an adaptive window of interest to take into account the interindividual variability of P300 latency. We compared source activation patters to distractor (P3a) and target (P3b) tones within- and between-groups. Results Patients showed a reduced activation in anterior cingulate and lateral and medial prefrontal cortices, as well as inferior/orbital frontal regions. This was also found in the FE patients alone. The activation was directly related to IQ in the patients and controls and to working memory performance in controls. Symptoms were unrelated to source activation. Fractional anisotropy in the tracts connecting lateral prefrontal and anterior cingulate regions predicted source activation in these regions in the patients. Conclusions These results replicate the source activation deficit found in a previous study with smaller sample size and a lower number of sensors and suggest an association between structural connectivity deficits and functional alterations.Postprint (author's final draft

Mindfulness dirigido a estudiantes de Educación Social: programa de formación y su impacto en entidades socio-educativas

Mindfulness conocida también como “atención plena” o “conciencia plena” (e.g. Baer, 2003; Kabat-Zinn, 1990, 2003a, 2003b; Mañas, 2009; Miró, 2006; Simón, 2006; Vallejo, 2006) es una técnica de meditación “centrada en el presente, no elaborativa ni condenatoria, en la cual cada pensamiento, sentimiento o sensación que surge en el campo atencional es reconocido y aceptado tal y como es” (e.g. Kabat-Zinn, 2003a, 2003b; Shapiro y Schwartz, 2000; Segal et al., 2002). Así la meditación tiene como componente principal la concentración y la capacidad de mantener la atención de manera consciente en la mente, de ahí, que su práctica continua permita al cuerpo adquirir altos niveles de relajación. El proyecto de innovación se ha diseñado bajo dos objetivos generales dirigidos principalmente a estudiantes de Educación Social. El primero, centrado en la formación y el segundo, en la aplicación del Mindfulness en las prácticas curriculares que realizan dichos estudiantes: 1.Diseñar y evaluar la eficacia de un programa formativo introductorio de entrenamiento en Mindfulness dirigido a estudiantes de Educación Social, para reducir el nivel de estrés percibido y aumentar el bienestar psicológico, la atención plena y la compasión. 2.Valorar intervenciones en Mindfulness llevadas a cabo por estudiantes de Educación Social quienes han recibido formación en atención plena, en las entidades en donde realizan sus prácticas. Los resultados del programa señalan una disminución del estrés percibido y un incremento en el bienestar bienestar, atención plena y compasión

Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P &lt;0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39-49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed

Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert

La enfermedad de Steinert o distrofia miotónica tipo 1 (DM1), (OMIM 160900) es la miopatía más prevalente en el adulto. Es una enfermedad multisistémica con alteración de prácticamente todos los órganos y tejidos y una variabilidad fenotípica muy amplia, lo que implica que deba ser atendida por diferentes especialistas que dominen las alteraciones más importantes. En los últimos anos ˜ se ha avanzado de manera exponencial en el conocimiento de la enfermedad y en su manejo. El objetivo de la guía es establecer recomendaciones para el diagnóstico, el pronóstico, el seguimiento y el tratamiento de las diferentes alteraciones de la DM1. Esta guía de consenso se ha realizado de manera multidisciplinar. Se ha contado con neurólogos, neumólogos, cardiólogos, endocrinólogos, neuropediatras y genetistas que han realizado una revisión sistemática de la literatura. Se recomienda realizar un diagnóstico genético con cuantificación precisa de tripletes CTG. Los pacientes con DM1 deben seguir control cardiológico y neumológico de por vida. Antes de cualquier cirugía con anestesia general debe realizarse una evaluación respiratoria. Debe monitorizarse la presencia de síntomas de disfagia periódicamente. Debe ofrecerse consejo genético a los pacientes con DM1 y a sus familiares. La DM1 es una enfermedad multisistémica que requiere un seguimiento en unidades especializadas multidisciplinares

Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis

Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use

Impact of the 2018 revised Pregnancy Prevention Programme by the European Medicines Agency on the use of oral retinoids in females of childbearing age in Denmark, Italy, Netherlands, and Spain: an interrupted time series analysis

Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women.Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription.Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12–55 years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs.Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9–22.2 years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in &gt;95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively.Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use