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Tricotilomanía/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Estudios Transversales , Conjuntos de Datos como Asunto , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/epidemiología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Distribución por Sexo , Tricotilomanía/tratamiento farmacológico , Tricotilomanía/psicología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The FDA maintains the Adverse Event Reporting System (CAERS) database, which contains product complaint reports for foods, dietary supplements, and cosmetics. Product line perception and subsequent adverse event reporting may be impacted by negative media attention. METHODS: The purpose of this analysis was to use the CAERS database to analyze temporal trends in adverse event reporting before and after media coverage of alleged health effects, using WEN by Chaz Dean (WCD) cleansing conditioners as a case study. WCD cleansing conditioner adverse event reports from January 2005 to December 2018 were abstracted from the CAERS database. Zero-inflated negative binomial regression models were used to analyze the rate of adverse events (WCD events/10,000 WCD cleansing conditioner units sold/month), adjusted for temporal trends in CAERS. RESULTS: There was a statistically significant higher rate of adverse event reporting after negative media coverage in December 2015 (IRR 16.71 [95% CI: 7.89-35.39]) when compared to the rate of adverse event reporting before December 2015. CONCLUSIONS: This analysis highlights the importance of assessing potential external factors, such as negative news media coverage, that may alter reporting behaviors due to societal shifts in product-specific risk perception. Consideration of these factors in post-market surveillance programs would result in more comprehensive safety evaluations.
Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Suplementos Dietéticos , Comunicación , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMEN
SMAD4 encodes a member of the SMAD family of proteins involved in the TGF-ß signaling pathway. Potentially heritable, autosomal dominant, gain-of-function heterozygous variants of SMAD4 cause a rare developmental disorder, the Myhre syndrome, which is associated with a wide range of developmental and post-developmental phenotypes that we now characterize as a novel segmental progeroid syndrome. Whole-exome sequencing of a patient referred to our International Registry of Werner Syndrome revealed a heterozygous p.Arg496Cys variant of the SMAD4 gene. To investigate the role of SMAD4 mutations in accelerated senescence, we generated cellular models overexpressing either wild-type SMAD4 or mutant SMAD4-R496C in normal skin fibroblasts. We found that cells expressing the SMAD4-R496C mutant exhibited decreased proliferation and elevated expression of cellular senescence and inflammatory markers, including IL-6, IFNγ, and a TGF-ß target gene, PAI-1. Here we show that transient exposure to TGF-ß, an inflammatory cytokine, followed by chronic IFNγ stimulation, accelerated rates of senescence that were associated with increased DNA damage foci and SMAD4 expression. TGF-ß, IFNγ, or combinations of both were not sufficient to reduce proliferation rates of fibroblasts. In contrast, TGF-ß alone was able to induce preadipocyte senescence via induction of the mTOR protein. The mTOR inhibitor rapamycin mitigated TGF-ß-induced expression of p21, p16, and DNA damage foci and improved replicative potential of preadipocytes, supporting the cell-specific response to this cytokine. These findings collectively suggest that persistent DNA damage and cross-talk between TGF-ß/IFNγ pathways contribute to a series of molecular events leading to cellular senescence and a segmental progeroid syndrome.
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Senescencia Celular , Daño del ADN , Senescencia Celular/genética , Criptorquidismo , Daño del ADN/genética , Facies , Trastornos del Crecimiento , Deformidades Congénitas de la Mano , Humanos , Discapacidad Intelectual , Mutación , Proteína Smad4/genética , Factor de Crecimiento Transformador beta/genéticaAsunto(s)
Alopecia Areata/epidemiología , Alopecia Areata/psicología , Corticoesteroides/uso terapéutico , Adulto , Distribución por Edad , Alopecia Areata/tratamiento farmacológico , Ansiedad/epidemiología , Comorbilidad , Estudios Transversales , Depresión/epidemiología , Dermatitis Seborreica/epidemiología , Femenino , Humanos , Masculino , Prevalencia , Estrés Psicológico/epidemiología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Sorafenib is an oral multikinase inhibitor approved by the United States Food and Drug Administration for the treatment of advanced hepatocellular and renal cell carcinoma. Cases of sorafenib-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome have been reported in the literature. DRESS syndrome is a potentially fatal, drug-induced hypersensitivity reaction that occurs 2-8 weeks after drug exposure. DRESS syndrome presents with generalized morbilliform eruption, facial edema, eosinophilia, and end-organ damage. We present the first reported case of sorafenib toxicity mimicking DRESS syndrome in a patient with metastatic adrenocortical carcinoma presenting with fever, morbilliform rash, and transaminitis in the absence of eosinophilia three days following initiation of sorafenib therapy. It is critical that clinicians are equipped to accurately diagnose DRESS syndrome due to its high mortality rate and the morbidity associated with prolonged steroid therapy. J Drugs Dermatol. 2019;18(5):468-469.
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Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Antineoplásicos/toxicidad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Sorafenib/toxicidad , Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/secundario , Diagnóstico Diferencial , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
Vemurafenib is an inhibitor of BRAF and is used to treat patients with metastatic melanoma who carry a V600E BRAF mutation. Recently, four patients have been described in the literature who developed a neutrophilic panniculitis following treatment with a BRAF inhibitor. We present an additional case and review the clinical findings of the cases reported to date.
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Indoles/efectos adversos , Melanoma/tratamiento farmacológico , Melanoma/patología , Paniculitis/inducido químicamente , Paniculitis/patología , Sulfonamidas/efectos adversos , Sustitución de Aminoácidos , Femenino , Humanos , Indoles/administración & dosificación , Melanoma/enzimología , Melanoma/genética , Persona de Mediana Edad , Mutación Missense , Metástasis de la Neoplasia , Paniculitis/enzimología , Paniculitis/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Sulfonamidas/administración & dosificación , VemurafenibRESUMEN
Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by null mutations at the WRN locus, which codes for a member of the RecQ family of DNA helicases. Since 1988, the International Registry of Werner syndrome had enrolled 130 molecularly confirmed WS cases from among 110 worldwide pedigrees. We now report 18 new mutations, including two genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and two rare missense mutations. We also review evidence for founder mutations among various ethnic/geographic groups. Founder WRN mutations had been previously reported in Japan and Northern Sardinia. Our Registry now suggests characteristic mutations originated in Morocco, Turkey, The Netherlands and elsewhere.