Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

Eficacia de una vía de alta resolución en la evaluación del cólico renoureteral no complicado en un servicio de urgencias hospitalario: un ensayo clínico aleatorizado (Estudio STONE) / Efficacy of a fast-track pathway for managing uncomplicated renal orureteral colic in a hospital emergency department: the STONE randomized clinical trial of Sonography and Testing of a Nephrolithiasis Episode

OBJETIVO: Evaluar una vía de alta resolución (vía POC) que utiliza análisis en el punto de atención (point-of-care testing-POCT-) y ecografía en el punto de atención (point-of-care ultrasonography -POCUS-) en la sospecha del cólico renoureteral (CRU) no complicado y compararla con la vía estándar (vía STD). MÉTODO: Ensayo clínico aleatorizado, controlado, no ciego, realizado en un servicio de urgencias hospitalario (SUH). Incluyó pacientes con sospecha clínica de CRU agudo y se aleatorizaron 1:1 a seguir vía POC o vía STD. Se analizó el tiempo de estancia en el SUH, el tratamiento administrado, la proporción de diagnósticos alternativos a CRU y las complicaciones a 30 días. RESULTADOS: Entre noviembre de 2018 y octubre de 2019, se reclutaron 140 pacientes de los que se analizaron 124.El tiempo de estancia total en el SUH de la vía POC fue de 112 minutos (DE 45) y en la vía STD 244 minutos (DE102) (p < 0,001). No hubo diferencias en el tratamiento administrado en urgencias, en el número de diagnósticos alternativos, ni en las complicaciones a 30 días. CONCLUSIONES: La utilización de una vía de alta resolución del manejo del CRU en un SUH es eficaz, segura y reduce el tiempo de estancia en urgencias

OBJECTIVES: To evaluate a fast-track pathway utilizing point-of-care (POC) testing and sonography as soon as uncomplicated renal or ureteral colic is suspected and to compare the POC clinical pathway to a standard one. METHODS: Unblinded randomized controlled clinical trial in a hospital emergency department (ED). We enrolled patients with suspected uncomplicated renal or ureteral colic and randomized them to a POC or standard pathway(1:1 ratio). Duration of ED stay, treatments, the proportion of diagnoses other than uncomplicated colic, and 30-daycomplications were analyzed. RESULTS: One hundred forty patients were recruited between November 2018 and October 2019; data for 124 were analyzed. The mean (SD) total time in the ED was 112 (45) minutes in the POC arm and 244 (102) in the standard arm (P< .001). Treatments, alternative diagnoses, and complication rates did not differ. CONCLUSION: The use of a fast-track POC pathway to manage uncomplicated colic in the ED is effective and safe. It also reduces the amount of time spent in the ED

Hepatotoxicity induced by acute and chronic paracetamol overdose in children: Where do we stand?

BACKGROUND: There are few data on hepatotoxicity induced by acute or chronic paracetamol poisoning in the pediatric population. Paracetamol poisoning data can reveal the weaknesses of paracetamol poisoning management guidelines. METHODS: We retrospectively studied the patients of less than 18 years old with measurable paracetamol levels, who were brought to the emergency department (ED) of La Paz University Hospital, Madrid, Spain, for suspected paracetamol overdoses between 2005 and 2010. RESULTS: Ninety-two patients with suspected paracetamol poisoning were identified. In 2007, the incidence of paracetamol poisoning in the pediatric population was 0.8 [Poisson-95% confidence interval (CI): 0.03-3.69] per 10 000 inhabitants aged less than 18 years. The incidence in the same year was 1.53 (Poisson-95% CI: 0.24-5.57) per 10 000 patients in the pediatric ED. The most common cause of poisoning was attempted suicide (47.8%) in teenagers with a median age of 15 years, followed by accidental poisoning (42.2%) in babies with a median age of 2.65 years. Difference was seen in the frequency of hepatotoxicity between acute and chronic poisoning cases. Only 1 of 49 patients with acute poisoning showed hepatotoxicity [acute liver failure (ALF)], whereas 7 of 8 patients with chronic poisoning showed hepatotoxicity (3 cases of ALF). The average time to medical care was 6.83 hours for acute poisoning and 52.3 hours for chronic poisoning (P<0.001). CONCLUSIONS: Chronic paracetamol poisoning is a potential risk factor for hepatotoxicity and acute liver failure. Delays in seeking medical help might be a contributing factor. Clinicians should have a higher index of clinical suspicion for this entity.

Conversion from Prograf to Advagraf in adolescents with stable liver transplants: comparative pharmacokinetics and 1-year follow-up.

The recommended dose of Advagraf for conversion from Prograf is considered to be 1:1 on a milligram basis. However, the long-term equivalence of Prograf and Advagraf has been questioned. The relative bioavailability of Advagraf and Prograf was evaluated in a single-center, open-label study of Prograf-to-Advagraf conversion in 20 patients, ranging in age from 12 to 18 years, who had a stable liver transplant and were receiving Prograf. After the supervised administration of Prograf for 7 days, the patients were converted to Advagraf. On days 7 and 14, serial blood samples were obtained for tacrolimus determinations. The pharmacokinetic parameters were calculated with a noncompartmental approach, and the relative bioavailability of both formulations was calculated according to standard statistical methods. Polymorphisms in cytochrome P450 3A5 (rs776746), adenosine triphosphate-binding cassette B1 (rs1045642), POR*28 (rs1057868), and POR (rs2868177) were determined with standard methods. The clinical and analytical data from a 1-year follow-up period were collected for all patients 30, 90, 180, and 360 days after conversion. The mean ratios for Cmax and AUC0-24 were 96.9 (90% confidence interval = 85.37-110.19) and 100.1 (90% confidence interval = 90.8-112.1), respectively. No relationship was found between the patients' genotypes and the pharmacokinetic tacrolimus values. During the follow-up, biochemical parameters (aspartate aminotransferase, alanine aminotransferase, bilirubin, cystatin C, and creatinine) did not change significantly; 3 patients presented with relevant clinical events, but no event was considered to be related to tacrolimus. A decrease in tacrolimus blood levels and an increase in dose/level ratios were observed 3 and 6 months after conversion, but they returned to basal levels by month 12. In conclusion, conversion from Prograf to Advagraf with a 1:1 dose equivalence is appropriate as an initial guideline. Our 1-year follow-up showed a transient decrease in tacrolimus levels, so closer monitoring of tacrolimus levels may be required after conversion.