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OBJECTIVE: A diagnosis of epilepsy has been associated with adverse cardiovascular events (CEs), but the extent to which antiseizure medications (ASMs) may contribute to this is not well understood. The aim of this study was to compare the risk of adverse CEs associated with ASM in patients with epilepsy (PWE). METHODS: A retrospective case-control cohort study was conducted using TriNetX, a global health federated network of anonymized patient records. Patients older than 18 years, with a diagnosis of epilepsy (International Classification of Diseases, 10th Revision code G40) and a medication code of carbamazepine, lamotrigine, or valproate were compared. Patients with cardiovascular disease prior to the diagnosis of epilepsy were excluded. Cohorts were 1:1 propensity score matched (PSM) according to age, sex, ethnicity, hypertension, heart failure, atherosclerotic heart disease, atrial and cardiac arrythmias, diabetes, disorders of lipoprotein metabolism, obesity, schizophrenia and bipolar disorder, medications, and epilepsy classification. The primary outcome was a composite of adverse CEs (ischemic stroke, acute ischemic heart disease, and heart failure) at 10 years. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) following 1:1 PSM. RESULTS: Of 374 950 PWE included; three cohorts were established after PSM: (1) carbamazepine compared to lamotrigine, n = 4722, mean age 37.4 years; (2) valproate compared to lamotrigine, n = 5478, mean age 33.9 years; and (3) valproate compared to carbamazepine, n = 4544, mean age 37.0 years. Carbamazepine and valproate use were associated with significantly higher risk of composite cardiovascular outcome compared to lamotrigine (HR = 1.390, 95% CI = 1.160-1.665 and HR = 1.264, 95% CI = 1.050-1.521, respectively). Valproate was associated with a 10-year higher risk of all-cause death than carbamazepine (HR = 1.226, 95% CI = 1.017-1.478), but risk of other events was not significantly different. SIGNIFICANCE: Carbamazepine and valproate were associated with increased CE risks compared to lamotrigine. Cardiovascular risk factor monitoring and careful follow-up should be considered for these patients.
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Anticonvulsivantes , Carbamazepina , Enfermedades Cardiovasculares , Epilepsia , Lamotrigina , Humanos , Femenino , Masculino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/inducido químicamente , Persona de Mediana Edad , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Estudios Retrospectivos , Adulto , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Carbamazepina/efectos adversos , Carbamazepina/uso terapéutico , Lamotrigina/uso terapéutico , Lamotrigina/efectos adversos , Estudios de Casos y Controles , Anciano , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéutico , Salud Global/estadística & datos numéricos , Estudios de CohortesRESUMEN
BACKGROUND AND PURPOSE: Epilepsy is associated with higher morbidity and mortality compared to people without epilepsy. We performed a retrospective cross-sectional and longitudinal cohort study to evaluate cardiovascular comorbidity and incident vascular events in people with epilepsy (PWE). METHODS: Data were extracted from the French Hospital National Database. PWE (n = 682,349) who were hospitalized between January 2014 and December 2022 were matched on age, sex, and year of hospitalization with 682,349 patients without epilepsy. Follow-up was conducted from the date of first hospitalization with epilepsy until the date of each outcome or date of last news in the absence of the outcome. Primary outcome was the incidence of all-cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, ischaemic stroke (IS), new onset atrial fibrillation, sustained ventricular tachycardia or fibrillation (VT/VF), and cardiac arrest. RESULTS: A diagnosis of epilepsy was associated with higher numbers of cardiovascular risk factors and adverse cardiovascular events compared to controls. People with epilepsy had a higher incidence of all-cause death (incidence rate ratio [IRR] = 2.69, 95% confidence interval [CI] = 2.67-2.72), cardiovascular death (IRR = 2.16, 95% CI = 2.11-2.20), heart failure (IRR = 1.26, 95% CI = 1.25-1.28), IS (IRR = 2.08, 95% CI = 2.04-2.13), VT/VF (IRR = 1.10, 95% CI = 1.04-1.16), and cardiac arrest (IRR = 2.12, 95% CI = 2.04-2.20). When accounting for all-cause death as a competing risk, subdistribution hazard ratios for ischaemic stroke of 1.59 (95% CI = 1.55-1.63) and for cardiac arrest of 1.73 (95% CI = 1.58-1.89) demonstrated higher risk in PWE. CONCLUSIONS: The prevalence and incident rates of cardiovascular outcomes were significantly higher in PWE. Targeting cardiovascular health could help reduce excess morbidity and mortality in PWE.
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Isquemia Encefálica , Epilepsia , Paro Cardíaco , Insuficiencia Cardíaca , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Estudios Longitudinales , Isquemia Encefálica/complicaciones , Isquemia Encefálica/epidemiología , Estudios Transversales , Accidente Cerebrovascular/epidemiología , Factores de Riesgo , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Epilepsia/epidemiología , Epilepsia/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Paro Cardíaco/complicacionesRESUMEN
Virtual learning resources such as podcasts and social media are increasingly used in medical education. Podcasts are one example of virtual learning, where prerecorded audio files are available to stream or download from the internet, usually without a fee and at any time. This gives listeners flexibility in when and where they engage with the educational material, enabling learning to be better tailored to individual needs. Podcasts are often enjoyed for their relaxed and conversational style. However, listeners must be aware of the lack of external peer review and incomplete coverage of information. There are also risks inherent to distant learning, including depersonalisation of medical education. We describe the roles that podcasts now play in neurological education, exploring some of the ways that they can be used to enhance neurological training both as a learner and educator and giving our top tips, based on our own experiences, for anyone keen to add to the expanding field of available podcasts.
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Clinical guidelines that support practice and improve care are essential in this era of evidence-based medicine. However, implementing this guidance often falls short in practice. Sharing knowledge and auditing practice are important, but not sufficient to implement change. This article brings together evidence from the study of behaviour, education and clinical practice and offers practical tips on how practising neurologists might bring about change in the healthcare environment. Common themes include the importance of team working, multidisciplinary engagement, taking time to identify who and what needs changing, and selecting the most appropriate tool(s) for the job. Engaging with the challenge is generally more rewarding than resisting and is important for the effective provision of care.
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Neurología , Guías de Práctica Clínica como Asunto , HumanosRESUMEN
OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease that is assumed to occur via a complex interplay of environmental and genetic factors. Rare causes of monogenic SLE have been described, providing unique insights into fundamental mechanisms of immune tolerance. The aim of this study was to identify the cause of an autosomal-recessive form of SLE. METHODS: We studied 3 siblings with juvenile-onset SLE from 1 consanguineous kindred and used next-generation sequencing to identify mutations in the disease-associated gene. We performed extensive biochemical, immunologic, and functional assays to assess the impact of the identified mutations on B cell biology. RESULTS: We identified a homozygous missense mutation in PRKCD, encoding protein kinase δ (PKCδ), in all 3 affected siblings. Mutation of PRKCD resulted in reduced expression and activity of the encoded protein PKCδ (involved in the deletion of autoreactive B cells), leading to resistance to B cell receptor- and calcium-dependent apoptosis and increased B cell proliferation. Thus, as for mice deficient in PKCδ, which exhibit an SLE phenotype and B cell expansion, we observed an increased number of immature B cells in the affected family members and a developmental shift toward naive B cells with an immature phenotype. CONCLUSION: Our findings indicate that PKCδ is crucial in regulating B cell tolerance and preventing self-reactivity in humans, and that PKCδ deficiency represents a novel genetic defect of apoptosis leading to SLE.
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Apoptosis , Linfocitos B/patología , Lupus Eritematoso Sistémico/enzimología , Lupus Eritematoso Sistémico/genética , Mutación Missense , Proteína Quinasa C-delta/deficiencia , Proteína Quinasa C-delta/genética , Adolescente , Adulto , Linfocitos B/inmunología , Linfocitos B/metabolismo , Proliferación Celular , Niño , Femenino , Variación Genética , Homocigoto , Humanos , Hiperplasia , Tolerancia Inmunológica , Lupus Eritematoso Sistémico/patología , Masculino , Polimorfismo de Nucleótido Simple , Proteína Quinasa C-delta/inmunología , Adulto JovenRESUMEN
OBJECTIVE: With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. PATIENTS AND METHODS: A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. RESULTS: The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. CONCLUSION: LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined.
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Encefalopatías/diagnóstico , Calcinosis/diagnóstico , Quistes/diagnóstico , Leucoencefalopatías/diagnóstico , Enfermedades del Sistema Nervioso/diagnóstico , Adolescente , Adulto , Encefalopatías/complicaciones , Calcinosis/complicaciones , Niño , Preescolar , Quistes/complicaciones , Humanos , Lactante , Recién Nacido , Leucoencefalopatías/complicaciones , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomógrafos Computarizados por Rayos X , Adulto JovenRESUMEN
Fusidic acid is an antibiotic used in the treatment of staphylococcal infections. Niraparib is an anticancer drug indicated for the treatment of advanced ovarian cancer. The interaction between these two drugs has not been studied and is not referenced in drug databases. We present the case of a patient with pancytopenia who had been treated with fusidic acid and niraparib. No other treatment was taken by this patient. According to the literature, both substances can cause haematological toxicity. It seems unlikely that this is due to niraparib alone because it had been well tolerated by the patient for over a year before the pancytopenia was diagnosed. It was also perfectly well tolerated when it was reintroduced. We cannot determine whether this pancytopenia is due to fusidic acid alone or to a drug interaction between the two treatments. We therefore recommend caution in patients treated with this combination.
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Ácido Fusídico , Pancitopenia , Humanos , Ácido Fusídico/efectos adversos , Pancitopenia/inducido químicamente , Pancitopenia/diagnóstico , Antibacterianos/efectos adversos , Indazoles/efectos adversosRESUMEN
The risks of cardiovascular events (CVEs) in people with epilepsy (PWE) are not well understood. To establish the short- and long-term burden of CVEs in PWE. Electronic health records from a global federated health research network (TriNetX) were used to establish a cohort of PWE. Primary outcomes were: (1) the proportion of people experiencing a composite outcome of cardiac arrest, acute heart failure (HF), acute coronary syndrome (ACS), atrial fibrillation (AF), severe ventricular arrhythmia or all-cause death within 30 days of a seizure; and (2) the 5-year risk for a composite outcome of ischemic heart diseases, stroke, hospitalization, or all-cause death in the PWE experiencing early CVEs. Cox-regression analyses with propensity score matching was used to produce hazard ratios (HRs) and 95% confidence intervals (CI). In 271,172 PWE (mean age 50 ± 20 years; 52% females), the 30-day risk of CVEs following seizure was: 8.7% for the composite outcome, 0.9% for cardiac arrest, 0.8% for HF, 1.2% for ACS, 4.1% for AF, 0.7% for severe ventricular arrhythmias, and 1.6% for all-cause death. For the 15,120 PWE experiencing CVEs within 30 days of seizure, the 5-year adjusted risks for all composite outcomes measured were significantly increased (overall HR: 2.44, 95% CI 2.37-2.51), ischemic heart diseases HR 3.23 (95% CI 3.10-3.36), stroke HR 1.56 (95% CI 1.48-1.64), hospitalization HR 2.03 (95% CI 1.97-2.10), and all-cause death HR 2.75 (95% CI 2.61-2.89). The large proportions of PWE with active disease that experience CVEs and the poor long-term outcome associated suggest the existence of an "epilepsy-heart syndrome."
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Síndrome Coronario Agudo , Fibrilación Atrial , Epilepsia , Paro Cardíaco , Insuficiencia Cardíaca , Accidente Cerebrovascular , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Masculino , Incidencia , Fibrilación Atrial/complicaciones , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/complicaciones , Epilepsia/complicaciones , Epilepsia/epidemiología , Accidente Cerebrovascular/etiología , Convulsiones/complicaciones , Síndrome Coronario Agudo/complicaciones , Paro Cardíaco/epidemiología , Paro Cardíaco/etiología , Paro Cardíaco/terapia , Factores de RiesgoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ursolic acid (UA), oleanolic acid (OA) and betulinic acid (BA), three hydroxyl pentacyclic triterpenoic acids (HPTAs) naturally found in a large variety of vegetarian foods, medicinal herbs and plants have been investigated for antibacterial activity. AIM OF THE STUDY: To determine the antibacterial activity of UA, OA and BA, as well as the toxic impact on eukaryotic cells. MATERIALS AND METHODS: Minimum inhibitory concentrations were determined against five reference strains (Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 & ATCC 29213, Enterococcus faecalis ATCC 29212 and Pseudomonas aeruginosa ATCC 27853), as well as five antibiotic-resistant clinical isolates. Toxicity was evaluated against MRC-5 and HaCaT cell lines. RESULTS: No antibacterial activity was observed for BA; while OA and more particularly UA, did show a moderate to good antibacterial activity, but limited to Gram-positive bacteria. Nevertheless, OA and UA were devoid of antibacterial activities against clinical isolates. Moreover, viability and cytotoxic assays demonstrated that the three compounds induced a significant cytotoxicity. CONCLUSIONS: Despite of a relative similar chemical structure; UA, OA and BA harboured different antibacterial activities, with more significant ones for UA. However, considering both viability and toxicity values, these compounds seem to have a significant impact on eukaryotic cell viability.
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Antibacterianos/farmacología , Ácido Oleanólico/farmacología , Triterpenos/farmacología , Antibacterianos/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Farmacorresistencia Bacteriana , Células Eucariotas/efectos de los fármacos , Células Eucariotas/metabolismo , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Ácido Oleanólico/toxicidad , Triterpenos Pentacíclicos , Pruebas de Toxicidad , Triterpenos/toxicidad , Ácido Betulínico , Ácido UrsólicoAsunto(s)
Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Meningitis Criptocócica/inducido químicamente , Anciano , Cryptococcus neoformans/aislamiento & purificación , Humanos , Infliximab , Masculino , Rituximab , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Lumbar punctures are essential in the management of suspected CNS infections. However, despite clear guidelines their use can be haphazard. This survey investigated the training, knowledge and experience of UK doctors in training in relation to lumbar punctures.
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Infecciones del Sistema Nervioso Central/diagnóstico , Competencia Clínica , Educación de Postgrado en Medicina , Medicina Hospitalar/educación , Punción Espinal , Toma de Decisiones Clínicas , Humanos , Autoeficacia , Encuestas y Cuestionarios , Reino UnidoRESUMEN
Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.