Acute mycophenolate overdose: case series and systematic literature analysis

Background: Literature regarding acute human toxicity of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) is limited. Objectives: Our objectives were to describe all cases of overdose with MMF or EC-MPS reported to the Swiss Toxicological Information Centre (STIC) or in the literature between 1995 and 2013. Therefore, we performed an observational case-series and systematic literature search to determine circumstances, magnitude, management and outcome of overdose with MMF or EC-MPS. Results: Of 152,762 reports to STIC, 15 (7 pediatric) involved overdose with MMF (n = 13) or EC-MPS (n = 2). Three cases from other centers were identified from a systematic literature search. The magnitude of overdose ranged from 1.2 to 16.7 (median 2.9) times usual dose. Six (33%) MMF overdoses had attributable symptoms, which included abdominal pain, vomiting, headache and dizziness. The majority of findings were minor, although a 9-fold MMF overdose caused hypotension 8 h after ingestion and a 12.5-fold overdose caused leukopenia after 5 days. Symptoms did not occur in patients who took 2.5 times or less of their usual MMF dose. Gastrointestinal decontamination measures with activated charcoal were undertaken in one-third of cases. Conclusions: Acute MMF and EC-MPS overdoses had a favorable outcome in all cases reported to STIC and in the literature

Medication wrong route administration: a poisons center-based study

OBJECTIVES: To describe clinical effects, circumstances of occurrence, management and outcomes of cases of inadvertent administration of medications by an incorrect parenteral route. METHODS: Retrospective single-center consecutive review of parenteral route errors of medications, reported to our center between January 2006 and June 2010. We collected demographic data and information on medications, route and time of administration, severity of symptoms/signs, treatment, and outcome. RESULTS: Seventy-eight cases (68 adults, 10 children) were available for analysis. The following wrong administration routes were recorded: paravenous (51%), intravenous (33%), subcutaneous (8%), and others (8%). Medications most frequently involved were iodinated x-ray contrast media (11%) and iron infusions (9%). Twenty-eight percent of the patients were asymptomatic and 54% showed mild symptoms; moderate and severe symptoms were observed in 9% and 7.7%, respectively, and were mostly due to intravenous administration errors. There was no fatal outcome. In most symptomatic cases local nonspecific treatment was performed. CONCLUSIONS: Enquiries concerning administration of medicines by an incorrect parenteral route were rare, and mainly involved iodinated x-ray contrast media and iron infusions. Most events occurred in adults and showed a benign clinical course. Although the majority of exposures concerned the paravenous route, the occasional severe cases were observed mainly after inadvertent intravenous administration

Clinical subtypes of obsessive-compulsive disorder based on the presence of checking and washing compulsions Subtipos clínicos do transtorno obsessivo-compulsivo com base na presença de compulsões de checagem e lavagem

OBJECTIVE: We aimed at examining the utility of checking and washing compulsions as markers of valid subtypes of obsessive-compulsive disorder (OCD). METHODS: One hundred and six patients with obsessive-compulsive disorder were evaluated with a socio-demographic and clinical questionnaire, the Structured Clinical Interview for DSM-IV, the Yale-Brown Obsessive-Compulsive Scale, the Clinical Global Impression, the Beck Depression Inventory, the Hamilton Rating Scale for Depression, and the Global Assessment of Functioning. These individuals were allocated in one of four subgroups [checkers (OCD-Ch; n = 20), washers (OCD-Wa; n = 13), checkers and washers (OCD-CW; n = 48), and non-checkers and non-washers (OCD non-CW = 25)] on the basis of the presence and the clinical relevance of checking and/or washing compulsive behaviors across their lifetime. Socio-demographic and clinical variables were compared and contrasted between the groups by means of ANOVA followed by post-hoc Least Significant Difference or Dunnett's tests for continuous variables and chi-square tests followed by partitioned chi-square tests for categorical variables. RESULTS: OCD-Ch and OCD-Wa did not differ on most demographic and clinical features, the only exception being the number of different types of obsessions, which were significantly higher in the former group. The OCD-CW group was more likely to exhibit an insidious onset of obsessive-compulsive symptoms, to manifest itself as a mixed subtype of obsessive-compulsive disorder and to display obsessions with contamination themes. On the other hand, the OCD non-CW group was more likely to exhibit an acute onset, a shorter duration of illness, obsessions with religious themes, an episodic course, and less severe obsessive-compulsive symptoms. CONCLUSIONS: In our sample, the probing of the presence of checking and/or washing compulsions has provided significant empirical support to establish valid subtypes of obsessive-compulsive disorder.<br>OBJETIVO: Nós investigamos a utilidade das compulsões de verificação e de lavagem como marcadores de subtipos válidos do transtorno obsessivo-compulsivo (TOC). MÉTODOS: Cento e seis pacientes com transtorno obsessivo-compulsivo foram avaliados com um questionário sociodemográfico e clínico e com a entrevista clínica estruturada para o DSM-IV, a escala de sintomas obsessivo-compulsivos de Yale-Brown, a escala de impressão clínica global, o inventário de depressão de Beck, a escala para avaliação de depressão de Hamilton e a avaliação global de funcionamento. Estes indivíduos foram incluídos em um dos seguintes subgrupos: verificadores (TOC-Ver; n = 20), lavadores (TOC-Lav; n = 13), verificadores e lavadores (TOC-VL; n = 48) e não-verificadores e não-lavadores (TOC-NVL = 25). Esta classificação foi realizada com base na presença e relevância clínica de compulsões de verificação e de lavagem ao longo da vida dos pacientes. As variáveis sociodemográficas e clínicas foram comparadas e contrastadas entre os subgrupos através de uma ANOVA seguida pelos testes LSD ou Dunnett para variáveis contínuas e do teste do qui-quadrado seguido pelo qui-quadrado particionado para variáveis categóricas. RESULTADOS: Os pacientes com TOC-Ver e os pacientes com TOC-Lav não diferiram significativamente entre si na maioria das variáveis incluídas no estudo, com exceção do número de diferentes tipos de obsessões, significativamente maior nos primeiros. Os pacientes com TOC-VL exibiram, com maior freqüência, um início insidioso, o subtipo misto de TOC segundo a CID-10 e obsessões de contaminação. Pacientes com TOC-NVL apresentaram, com maior freqüência, um início súbito, menor duração de sintomas, obsessões de conteúdo religioso, curso episódico e sintomas obsessivo-compulsivos menos graves. CONCLUSÕES: A investigação quanto à presença de compulsões de verificação e lavagem sugeriu que estes sintomas podem contribuir para validar subtipos de transtorno obsessivo-compulsivo

Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology

Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics