Machine-learning-derived predictive score for early estimation of COVID-19 mortality risk in hospitalized patients.

The clinical course of COVID-19 is highly variable. It is therefore essential to predict as early and accurately as possible the severity level of the disease in a COVID-19 patient who is admitted to the hospital. This means identifying the contributing factors of mortality and developing an easy-to-use score that could enable a fast assessment of the mortality risk using only information recorded at the hospitalization. A large database of adult patients with a confirmed diagnosis of COVID-19 (n = 15,628; with 2,846 deceased) admitted to Spanish hospitals between December 2019 and July 2020 was analyzed. By means of multiple machine learning algorithms, we developed models that could accurately predict their mortality. We used the information about classifiers' performance metrics and about importance and coherence among the predictors to define a mortality score that can be easily calculated using a minimal number of mortality predictors and yielded accurate estimates of the patient severity status. The optimal predictive model encompassed five predictors (age, oxygen saturation, platelets, lactate dehydrogenase, and creatinine) and yielded a satisfactory classification of survived and deceased patients (area under the curve: 0.8454 with validation set). These five predictors were additionally used to define a mortality score for COVID-19 patients at their hospitalization. This score is not only easy to calculate but also to interpret since it ranges from zero to eight, along with a linear increase in the mortality risk from 0% to 80%. A simple risk score based on five commonly available clinical variables of adult COVID-19 patients admitted to hospital is able to accurately discriminate their mortality probability, and its interpretation is straightforward and useful.

Evaluación del sesgo de género en la revista Farmacia Hospitalaria 2016-2018 / Assessment of Gender Bias in the Farmacia Hospitalaria Journal 2016-2018

No disponible

[Pharmacokinetics and pharmacodynamics of the new oral anticoagulants dabigatran and rivaroxaban]. / Farmacocinética y farmacodinamia de los nuevos anticoagulantes orales.

Dabigatran is the first available oral direct thrombin inhibitor anticoagulant. Absorption of the prodrug, dabigatran etexilate and its conversion to dabigatran is rapid (peak plasma concentrations are reached 4-6 hours following surgery, and a further 2 hours later). Its oral bioavailability is low, but shows reduced interindividual variability. Dabigatran specifically and reversibly inhibits thrombin, the key enzyme in the coagulation cascade. Studies both in healthy volunteers and in patients undergoing major orthopaedic surgery show a predictable pk/pd profile that allows for fixed-dose regimens. The anticoagulant effect correlates adequately with the plasma concentrations of the drug, demonstrating effective anticoagulation combined with a low risk of bleeding. Dabigatran is mainly eliminated by renal excretion (a fact which affects the dosage in elderly and in moderate-severe renal failure patients), and no hepatic metabolism by cytochrome P450 isoenzymes has been observed, showing a good interaction profile. Rivaroxaban will probably be the first available oral factor Xa (FXa) direct inhibitor anticoagulant drug. It produces a reversible and predictable inhibition of FXa activity with potential to inhibit clot-bound FXa. Its pharmacokinetic characteristics include rapid absorption, high oral availability, high plasma protein binding and a half-life of aprox. 8 hours. Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. Although the drug has demonstrated moderate potential to interact with strong CYP3A4 inhibitors, it does not inhibit or induce any major CYP450 enzyme.

Farmacocinética y farmacodinamia de los nuevos anticoagulantes orales / Dabigatran and rivaroxaban, new oral anticoagulants for the treatment of venous thromboembolism

Dabigatran es el primer anticoagulante inhibidor directo de la trombina disponible por vía oral. La absorción del profármaco dabigatran etexilato y su conversión a dabigatran es rápida (concentraciones máximas de 4-6 h tras cirugía y 2 h posteriormente) y, pese a la baja biodisponibilidad oral, presenta escasa variabilidad entre individuos. Inhibe específica y reversiblemente la trombina, la enzima llave de la cascada de la coagulación. Los estudios tanto en voluntarios sanos como en pacientes sometidos a cirugía ortopédica mayor muestran un perfil pk/pd predecible, lo que permite regímenes fijos de dosificación. El efecto anticoagulante se correlaciona bien con las concentraciones plasmáticas del fármaco, lo que aúna una efectiva anticoagulación con un bajo riesgo de hemorragia. La excreción es mayoritariamente renal (lo que condiciona su dosificación en pacientes ancianos y con insuficiencia renal), y no sufre metabolismo hepático por el sistema del citocromo P450, por lo que presenta un perfil de fármaco sin grandes problemas de interacción con otros medicamentos. Rivaroxaban será probablemente el primer fármaco anticoagulante oral inhibidor directo del factor Xa (FXa) disponible. Produce una inhibición reversible y predecible de la actividad del FXa con capacidad de inhibir el FXa ligado al coágulo. Sus características farmacocinéticas incluyen rápida absorción, con elevadas biodisponibilidad y unión a proteínas plasmáticas y semivida de eliminación de, aproximadamente, 8 h. La eliminación es de tipo dual, renal (mayoritaria) y biliar. Aunque ha demostrado tener un potencial moderado de interacción con inhibidores fuertes del citocromo P450-A4, no parece inhibir ni inducir ninguna enzima P450 (AU)

Dabigatran is the first available oral direct thrombin inhibitor anticoagulant. Absorption of the prodrug, dabigatran etexilate and its conversion to dabigatran is rapid (peak plasma concentrations are reached 4-6 hours following surgery, and a further 2 hours later). Its oral bioavailability is low, but shows reduced interindividual variability. Dabigatran specifically and reversibly inhibits thrombin, the key enzyme in the coagulation cascade. Studies both in healthy volunteers and in patients undergoing major orthopaedic surgery show a predictable pk/pd profile that allows for fixed-dose regimens. The anticoagulant effect correlates adequately with the plasma concentrations of the drug, demonstrating effective anticoagulation combined with a low risk of bleeding. Dabigatran is mainly eliminated by renal excretion (a fact which affects the dosage in elderly and in moderate-severe renal failure patients), and no hepatic metabolism by cytochrome P450 isoenzymes has been observed, showing a good interaction profile. Rivaroxaban will probably be the first available oral factor Xa (FXa) direct inhibitor anticoagulant drug. It produces a reversible and predictable inhibition of FXa activity with potential to inhibit clot-bound FXa. Its pharmacokinetic characteristics include rapid absorption, high oral availability, high plasma protein binding and a half-life of aprox. 8 hours. Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. Although the drug has demonstrated moderate potential to interact with strong CYP3A4 inhibitors, it does not inhibit or induce any major CYP450 enzyme (AU)

Estudio observacional y prospectivo del consentimiento informado de los pacientes en ensayos clínicos con medicamentos / No disponible

No disponible

Ertapenem-induced acute pancreatitis in a surgical elderly patient.

Case summary A 78-year old man was given, after surgery, 1 g ertapenem every 24 h intravenously. His clinical evolution was favorable and on day 8 ertapenem was discontinued and the patient was put on a semi-solid diet. On day 9, abdominal distension was seen accompanied by epigastric pain. The laboratory tests on day 8 showed an altered pancreatic profile: amylase = 1823 U/l (normal value: 0-100); lipase = 8045 U/l (normal value: 0-60); C-reactive protein (CRP) = 16.09 mg/dl (normal value: 0-0.5). Full Blood Count (FBC) showed leukocytosis with an increase in neutrophils and eosinophils. The prior pancreatic parameters were normal without leukocytosis. The evolution of clinical symptoms after discontinuing ertapenem was rapid. Between days 11 and 16, the laboratory parameters returned to normal values; the eosinophilia persisted longer, decreasing between days 14 and 16. Conclusions clinicians should include monitoring the development of acute pancreatitis in the safety parameters in patients undergoing treatment with this carbapenem.

Acute cholestatic hepatitis probably associated with risperidone.

OBJECTIVE: Risperidone is an atypical neuroleptic drug widely used due to the lower incidence and severity of hepatic adverse effects in comparison to phenothiazines. Although idiosyncratic reversible hepatotoxicity may occur in association with risperidone, the interaction with fluoxetine might increase the risk of toxic liver injury in a vulnerable patient. METHODS AND RESULTS: We present a case of acute cholestatic hepatitis probably associated with the use of risperidone after only a few days of therapy in a patient also treated with fluoxetine. The patient, a 64-year-old male, developed a rapid increase in liver enzymes after starting treatment with only four doses of risperidone 2 mg/day. CONCLUSIONS: We recommend obtaining baseline liver function tests before starting risperidone and regular monitoring to screen patients for liver damage during therapy whenever a patient is also receiving fluoxetine.

Voriconazole in fungal keratitis caused by Scedosporium apiospermum.

OBJECTIVE: To describe the first case, to the best of our knowledge, of posttraumatic Scedosporium apiospermum (ScA) keratitis successfully treated with systemic and topical voriconazole. CASE SUMMARY: A 19-year-old man was admitted to the hospital with an incisive wound of his left eye and the cornea totally sectioned after trauma with a cutter used in gardening. Initial empirical treatment was followed by systemic and topical voriconazole, and the eye did not have to be enucleated. Five months after the trauma, a penetrating keratoplasty and chamber intraocular lens implantation was performed with a favorable visual outcome. DISCUSSION: ScA keratitis is rare, but it must be suspected if a history of ocular injury with contaminated objects exists. Among the antifungals available to treat ScA keratitis, voriconazole has shown advantages such as the lowest minimum inhibitory concentration and the availability of an oral formulation. CONCLUSIONS: Voriconazole shows promise as an effective alternative to conventional antifungals in the treatment of ScA keratitis. It is available both as oral and intravenous preparations, which is a great advantage in these lengthy infections.