ABSTRACT
BACKGROUND: Proper identification of patients at risk of developing serious disease in the context of SARS-CoV-2 infection, as well as the initiation of early treatment, is one of the fundamental elements for successful management of COVID-19. The main objective of this study was to evaluate the usefulness of serum biomarkers (neutrophils, lymphocytes, C-reactive protein, lactate dehydrogenase, D-dimer, ferritin, and interleukin-6) to predict the early response to immunosuppressant therapy in COVID-19 patients. METHODS: This is a case-control study nested in a retrospective cohort, which included hospitalized patients with interstitial pneumonia and with elevation of some proinflammatory parameters. Each of the individuals who died during the 28-day follow-up was defined as a case. For each case, 4 controls were selected, matched by age, gender, and comorbidities. RESULTS: The initial cohort included 856 patients. The incidence of therapeutic failure in the cohort was 14%, thus we identified a total of 120 cases. After the application of a Cox regression model, high serum concentrations of LDH (> 451 IU/L), ferritin (> 1,014 ng/mL) and D-Dimer (> 1,300 ng/mL) were identified as predictors of poor response to treatment. Highly-specific cut-off points could not be established for any of these biomarkers. CONCLUSIONS: Some inflammatory biomarkers, such as LDH, ferritin, and D-dimer, may be helpful in identifying patients for whom an early immunomodulatory therapeutic intervention should be considered in the treatment of COVID-19 patients with pneumonia.
Subject(s)
COVID-19 Drug Treatment , Biomarkers , C-Reactive Protein/analysis , Case-Control Studies , Ferritins , Humans , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Interleukin-6 , L-Lactate Dehydrogenase , Retrospective Studies , SARS-CoV-2ABSTRACT
Avapritinib is a protein kinase inhibitor designed to selectively inhibit oncogenic KIT and platelet-derived growth factor receptor alpha (PDGFRA) mutants by targeting the active conformation of the kinase. On 24 September 2020, a marketing authorisation valid through the European Union was issued for avapritinib as treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the PDGFRA D842V mutation. The drug was evaluated in an open-label, phase I, first-in-human, dose-escalation, open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of avapritinib in adults with unresectable or metastatic GIST. The benefit of avapritinib was observed in patients with GIST harbouring the PDGFRA D842V mutation. The overall response rate was 95% (95% confidence interval 82.3%-99.4%), with a median duration of response of 22.1 months (95% confidence interval 14.1-not estimable months). The most common adverse events were nausea, fatigue, anaemia, periorbital and face oedema, hyperbilirubinaemia, diarrhoea, vomiting, increased lacrimation, and decreased appetite. Most of the reported cognitive effects were mild memory impairment. Rarer events were cases of severe encephalopathy and intracranial or gastrointestinal bleeding. The aim of this manuscript is to summarise the scientific review of the application leading to regulatory approval in the European Union.
Subject(s)
Gastrointestinal Stromal Tumors , Adult , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/genetics , Humans , Mutation , Pyrazoles , Pyrroles , Receptor, Platelet-Derived Growth Factor alpha/genetics , TriazinesABSTRACT
INTRODUCTION: Angelman syndrome is a neurodevelopmental disorder of genetic origin, with important clinical motor, behavioural, communicative and electroencephalographic manifestations, with particular relevance as regards the presence of epileptic seizures. AIMS: To describe the electroencephalographic characteristics (qualitatively and quantitatively) of patients diagnosed with Angelman syndrome and to determine the electroencephalographic profile according to age and genetic alteration. PATIENTS AND METHODS: A retrospective observational study in which the demographic, clinical and electroencephalographic characteristics of 51 patients with Angelman syndrome were analysed. RESULTS: A higher delta power was evident in all brain regions, with a maximum peak in the frontopolar and temporal regions, and a lower power in the alpha and beta frequency range in all regions, with a greater preponderance in younger patients, and a trend that decreases with age. The coherence showed a predominance of delta and theta in the frontopolar region, which was higher for all frequencies in the deletion group, where delta was predominant, especially in the frontopolar region. CONCLUSION: The electroencephalogram could be a useful biomarker as a qualitative and quantitative tool in the investigation of Angelman syndrome and in measuring the response to possible therapies under investigation.
TITLE: Análisis descriptivo del electroencefalograma en el síndrome de Angelman.Introducción. El síndrome de Angelman es un trastorno del neurodesarrollo de origen genético, con importantes manifestaciones clínicas motoras, conductuales, comunicativas y electroencefalográficas, con especial relevancia en lo que concierne a la presencia de crisis epilépticas. Objetivos. Describir las características electroencefalográficas (cualitativa y cuantitativamente) de los pacientes con diagnóstico de síndrome de Angelman y determinar el perfil electroencefalográfico según la edad y la alteración genética. Pacientes y métodos. Estudio observacional retrospectivo donde se analizaron las características demográficas, clínicas y electroencefalográficas de 51 pacientes con síndrome de Angelman. Resultados. Se evidenció una mayor potencia delta en todas las regiones cerebrales, con un pico máximo en las regiones frontopolar y temporal, y una menor potencia en el rango de frecuencias alfa y beta en todas las regiones, con mayor preponderancia en los pacientes más jóvenes, con tendencia decreciente con la edad. La coherencia mostró un predominio delta y theta en la región frontopolar, que fue mayor para todas las frecuencias en el grupo de deleción, con predominio delta, especialmente en la región frontopolar. Conclusión. El electroencefalograma podría ser un biomarcador útil como herramienta cualitativa y cuantitativa en la investigación del síndrome de Angelman y en la medición de la respuesta a eventuales terapias en investigación.
Subject(s)
Angelman Syndrome/diagnosis , Electroencephalography , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective StudiesABSTRACT
El procedimiento de registro de medicamentos centralizado implica una evaluación conjunta por todas las Agencias Reguladoras de los Estados miembros de la Unión Europea que es coordinada por la Agencia Europea de Medicamentos. Desde su implantación en 1995, la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) ha contribuido de forma activa al Comité de medicamentos de uso humano. Las áreas terapéuticas en las que la AEMPS tiene más presencia son cardiovascular, órganos de los sentidos (fundamentalmente oftalmología) y genitourinario-hormonas sexuales. A esta labor contribuyen con sus conocimientos y su extensa experiencia los técnicos de la propia AEMPS así como profesionales del sistema sanitario español que actúan en calidad de expertos externos aportando su visión clínica y acercando la práctica diaria a la evaluación de medicamentos. Como sucede con otros espacios de decisión europeos, la participación del conjunto de Estados miembro no es homogénea siendo todavía una minoría de países los que lideran la mayoría de las evaluaciones del Comité de medicamentos de uso humano, aunque todos los países toman parte en la opinión final (AU)
The centralized procedure for registering medicinal products involves a joint assessment by all regulatory agencies of European Union member states, which are coordinated by the European Medicines Agency. Since its implementation in 1995, the Spanish Agency for Medicines and Healthcare Products (AEMPS) has actively contributed to the committee on medicinal products for human use. The therapeutic areas in which AEMPS has the greatest presence are cardiovascular, sensory organs (mainly ophthalmology) and genitourinary/sexual hormones. The technical staff of AEMPS contributes their expertise and extensive experience to this task, as do the practitioners of the Spanish healthcare system who act as external experts, providing their clinical vision and bringing the daily clinical practice to the evaluation of medicinal products. As with other European decision spaces, the joint participation of the member states is not homogeneous, with a minority of countries still heading the majority of assessments for the committee on medicinal products for human use, although all member countries take part in the final decision (AU)
Subject(s)
Humans , Drug Approval , Drug Evaluation , Drug and Narcotic Control/organization & administration , Pharmaceutical TradeABSTRACT
The centralized procedure for registering medicinal products involves a joint assessment by all regulatory agencies of European Union member states, which are coordinated by the European Medicines Agency. Since its implementation in 1995, the Spanish Agency for Medicines and Healthcare Products (AEMPS) has actively contributed to the committee on medicinal products for human use. The therapeutic areas in which AEMPS has the greatest presence are cardiovascular, sensory organs (mainly ophthalmology) and genitourinary/sexual hormones. The technical staff of AEMPS contributes their expertise and extensive experience to this task, as do the practitioners of the Spanish healthcare system who act as external experts, providing their clinical vision and bringing the daily clinical practice to the evaluation of medicinal products. As with other European decision spaces, the joint participation of the member states is not homogeneous, with a minority of countries still heading the majority of assessments for the committee on medicinal products for human use, although all member countries take part in the final decision.
