Lung immune prognostic index (LIPI) as a prognostic factor in patients with extensive-stage small cell lung cancer treated with first-line chemoimmunotherapy.

INTRODUCTION: The lung immune prognostic index (LIPI) is a biomarker that combines the lactate dehydrogenase (LDH) value and the derived neutrophil/lymphocyte ratio (dNLR). Its prognostic ability has been reported in non-small cell lung cancer (NSCLC) with immunotherapy. In the context of extensive-stage small cell lung cancer (ES-SCLC) with chemoimmunotherapy, its role remains to be determined. METHODS: A retrospective, multicenter study of patients with ES-SCLC who received atezolizumab plus chemotherapy as first-line treatment was conducted. 101 patients were divided into three groups: LIPI good (n = 33), LIPI intermediate (n = 41), and LIPI poor (n = 27). The Kaplan-Meier method was used for analysis of overall survival (OS) and progression-free survival (PFS), using the log-rank test for comparisons. Univariate and multivariate Cox models were developed to assess the LIPI as an independent predictor of survival. RESULTS: The good LIPI group had a significantly longer median PFS than the intermediate and poor LIPI groups: 9.6 vs 5.4 vs 5.2 months, respectively (p < 0.001). Significant differences in OS between good, intermediate, and poor LIPI were also observed, with median OS of 23.4 vs 9.8 vs 6.0 months, respectively (p < 0.001). Multivariate Cox regression analysis for PFS identified liver metastases and intermediate and poor LIPI as worse prognostic factors (p < 0.050). For OS, a worse prognosis was confirmed in both the intermediate LIPI group (HR: 2.18, 95% CI: 1.07-4.41, p = 0.031) and the poor LIPI group (HR: 5.40, 95% CI: 2.64-11.07, p < 0.001). CONCLUSIONS: In patients with ES-SCLC treated with chemoimmunotherapy, an intermediate and poor pretreatment LIPI score was associated with worse PFS and OS prognosis.

Evolución temporal de la terapia antirretroviral (2017-2021): análisis de la modificación del tratamiento y su impacto económico / Temporal evolution of antiretroviral therapy (2017-2021): analysis of treatment change and its economic impact

Objetivos. Analizar las modificaciones de la terapia antirre troviral (TAR) y su impacto económico en la práctica clínica diaria. Material y métodos. Estudio observacional, retrospectivo de los pacientes que iniciaron TAR entre 01/2017-12/2021 (se guimiento hasta 12/2022). Variables recogidas: TAR, duración, motivo del cambio y costes del tratamiento. Resultados. 280 pacientes iniciaron TAR. La mediana de durabilidad de la 1ª línea fue: 19,9 meses en 2017 (IC95% 13,9-25,9), 12,2 meses en 2018 (IC95% 4,7-19,7), 27,4 meses en 2019 (IC95% 6,8-48,1) y no se alcanzó la mediana para los años 2020 y 2021 (p p<0,001). De un total de 541 líneas prescri tas, la triple terapia con inhibidores de la proteasa se modificó en el 63,8% (81/127), seguido de los inhibidores de la integrasa 52,1% (159/305), mientras que, la terapia dual (DTG/3TC) solo en el 8,3% (7/84). De un total de 261 modificaciones, la simpli ficación/optimización 47,5% (124/261) fue el principal motivo, seguido de efectos adversos 21,8% (57/261), siendo el 2017 el único año donde ambos motivos se encontraban al mismo nivel. El impacto económico de los cambios supusieron una re ducción del coste medio de 34,0€ [-391,4 a +431,4] al mes/ paciente. El año 2019 es el único año donde estos cambios se asociaron con un incremento del coste adicional medio (23,4€ [-358,3 a +431,4]). Conclusiones. Dejando atrás el fracaso virológico, la sim plificación a regímenes de un solo comprimido y de mayor tolerancia han marcado la nueva la era TAR. Con un impacto económico que, a pesar del punto de inflexión del 2019, refleja una reducción progresiva de costes mantenida en el tiempo (AU)

Objectives. To analyze the modifications of antiretrovi ral therapy (ART) and their economic impact on daily clinical practice. Material and methods. Observational, retrospective study of patients who started ART between 01/2017-12/2021 (follow-up until 12/2022). Variables collected: prescribed ART, duration, the reason for the change, and treatment costs. Results. A total of 280 patients initiated ART therapy. The median durability of 1st line was: 19.9 months in 2017 (95%CI 13.9-25.9), 12.2 months in 2018 (95%CI 4.7-19.7), 27.4 months in 2019 (95%CI 6.8-48.1) and the median was not reached for the years 2020 and 2021 (p<0.001). Triple therapy with protease inhibitors was changed in 63.8% (81/127) of cases, followed by integrase inhibitors 52.1% (159/305), while dual therapy (DTG/3TC) only in 8.3% (7/84). The main cause of dis continuation was simplification/optimization 47.5% (124/261), followed by adverse effects 21.8% (57/261), with 2017 being the only year where simplification/optimization was at the same level as adverse effects. The economic impact of ART changes resulted in an average cost reduction of 34.0€ [-391.4 to +431.4] per month per patient. The year 2019 stands out as the only year where these changes were associated with an increase in mean additional cost (23.4€ [-358.3 to +431.4]). Conclusions. Optimization/simplification accounts for almost half of the reasons for TAR change, with an econom ic impact that, despite the inflection point of 2019, each year manages to exceed the previous one, achieving a progressive cost reduction maintained over time (AU)

Adecuación de la prescripción de antibióticos antipseudomónicos tras los cambios en los criterios EUCAST 2019 / Adequacy of the consumption of antipseudomonal antibiotics after changes in the 2019 EUCAST criteria

Introducción. En 2019, el Comité Europeo para el estudio de la sensibilidad antibiótica modificó las categorías de los test de sensibilidad antibiótica incluyendo el término “sensible con exposición incrementada”. Tras la difusión de protocolos locales recogiendo estas modificaciones, el objetivo de nuestro estudio fue analizar si los prescriptores se han adecuado a los mismos y el posible impacto clínico en los casos de inadecuación. Material y métodos. Estudio observacional y retrospecti vo de los pacientes con infección por pseudomonas aeruginosa y que hayan recibido antibiótico antipseudomónico desde ene ro a octubre de 2021 en un hospital terciario. Resultados. La inadecuación a las recomendaciones de la guía fueron un 57,6% en planta y un 40,4% en UCI (p<0,05). Tanto en planta como en UCI el grupo con más prescripción no ajustada a las recomendaciones de la guía fueron los amino glucósidos (92,9% y 64,9% respectivamente) por utilizar dosis subóptimas, seguido de los carbapenémicos (89,1% y 53,7% respectivamente) por no administrarlo en perfusión extendida. En planta, la tasa de mortalidad durante el ingreso o a los 30 días en el grupo de terapia inadecuada fue de 23,3% vs 11,5% en los que recibieron los tratamientos de forma adecuada (OR: 2,34; IC 95% 1,14-4,82); en UCI no hubo diferencias estadísti camente significativas. Conclusiones. Los resultados muestran la necesidad de implementar medidas para garantizar una mejor difusión y co nocimiento de los conceptos claves en el manejo de los antibió ticos, con el objetivo de garantizar exposiciones incrementadas y poder ofrecer una mejor cobertura de la infección, así como de evitar la amplificación de cepas resistente (AU)

Introduction. In 2019, the European Committee for the Study of Antibiotic Susceptibility modified the categories of antibiotic susceptibility tests to include the term “susceptible with increased exposure”. Following the dissemination of local protocols reflecting these modifications, the aim of our study was to analyse whether prescribers have adapted to them and the clinical impact in cases of inadequacy. Material and methods. Observational and retrospective study of patients with infection who received antipseudomonal antibiotics from January to October 2021 in a tertiary hospital.Results. Non adherence to the guideline recommendations was 57.6% in the ward and 40.4% in the ICU (p<0.05). In both the ward and ICU, the group with the most prescriptions not by the guideline ecommendations were aminoglycosides (92.9% and 64.9% respectively) for using suboptimal doses, followed by carbapenems (89.1% and 53.7% respectively) for not administering an extended infusion. On the ward, the mortality rate during admission or at 30 days in the inadequate therapy group was 23.3% vs 11.5% in those who received adequate treatment (OR: 2.34; 95% CI 1.14-4.82); in ICU there were no statistically significant differences.Conclusions. The results show the need to implement measures to ensure better dissemination and knowledge of key concepts in antibiotic management, to ensure increased exposures, and to be able to provide better infection coverage, as well as to avoid amplifying resistant strains (AU)

Interacción paradójica entre nirmatrelvir/ritonavir y voriconazol en un paciente con COVID-19 / Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19

Presentamos el caso de una interacción farmacológica entre nirmatrelvir/ritonavir (fármaco aprobado para la infección por COVID-19) y voriconazol, derivada del efecto bidireccional del ritonavir sobre las 2 principales enzimas metabolizadoras del voriconazol (citocromo P450 3A y 2C19) de forma que, ritonavir inhibe la primera e induce la segunda.De acuerdo con las principales bases de datos de información farmacoterapéutica, en la interacción entre ambos fármacos, se espera una disminución en el área bajo la curva del voriconazol por el efecto inductor de su metabolismo, sin embargo, en el caso que presentamos ha ocurrido el efecto opuesto, se dan niveles supraterapéuticos de forma mantenida, lo cual es un efecto paradójico según la literatura.Dado el corto periodo de tratamiento con nirmatrelvir/ritonavir (5 días), no llega a manifestarse el efecto inductor del ritonavir propuesto en los estudios en los que se basan las recomendaciones, donde el tratamiento con ritonavir es más prolongado. (AU)

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolising enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively.According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the.inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole.Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur. (AU)

Recommended doses of endovenous vancomycin are insufficient to achieve therapeutic concentrations in paediatric patients.

OBJECTIVES: Vancomycin therapeutic drug monitoring is challenging, especially in the paediatric population where evidence is scarce. The main objective of this study was to analyse the achievement of therapeutic concentrations of vancomycin in paediatric patients and to evaluate the current monitoring method (trough levels), doses used, and the time required to achieve target concentrations. METHODS: Paediatric patients on treatment and monitored with vancomycin from November 2019 to December 2021 were included. Those with only one determination of serum vancomycin concentration were excluded. Demographic variables, analytical and microbiological parameters and toxicity data were collected. Pharmacokinetic parameters were assessed at baseline and during treatment. RESULTS: 225 patients (40.9% female; 108 neonates, 49 infants and 68 children or adolescents) were included in the study. The main indications for vancomycin treatment were sepsis (33.9%) and fever of unknown origin (29.3%). Microbiological cultures were positive in 71.1%, mostly with Gram-positive bacteria (60.4%). Therapeutic levels of vancomycin were reached in only 20.1% of the participants in the first determination. After pharmacokinetic monitoring, 81.7% of patients reached therapeutic concentrations, requiring a 23% increase in the initial dose, a 2-day lag time and 1-2 dosage adjustments until the therapeutic concentration was reached. Of the total patients, 13 developed nephrotoxicity, nine neutropenia and one patient developed red man syndrome. CONCLUSIONS: In our sample of paediatric patients, the recommended doses of vancomycin were insufficient to achieve therapeutic concentrations. Revision of the recommendations and/or a change in the method of pharmacokinetic monitoring is crucial to optimise treatment in this population.

[Translated article] Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolizing enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Paradoxical interaction between nirmatrelvir/ritonavir and voriconazole in a patient with COVID-19. / Interacción paradójica entre nirmatrelvir/ritonavir y voriconazol en un paciente con COVID-19.

This case is based on a drug interaction between nirmatrelvir/ritonavir (approved drug for COVID-19) and voriconazole is presented, possibly derived from the bidirectional effect of ritonavir on the 2 main voriconazole metabolising enzymes (cytochrome P450 3A and 2C19) ritonavir inhibits the former and induces the latter respectively. According to the main pharmacotherapeutic information databases, in the interaction between both drugs, a decrease in the area under the curve of voriconazole is expected due to the. inducing effect of its metabolism; however, in the case we present, unexpectedly, a paradoxical effect occurs, according to what is described in literature, with the result of sustained supratherapeutic levels of voriconazole. Given the short treatment period with nirmatrelvir/ritonavir (5 days), the induction effect of ritonavir proposed in the studies on which the recommendations are based, where treatment with ritonavir is longer, does not occur.

Assessment of the effectiveness of tocilizumab on mortality and progression to mechanical ventilation or intensive care in patients with COVID-19 admitted to a tertiary hospital.

OBJECTIVES: The evidence for tocilizumab in the treatment of COVID-19 is contradictory, with some clinical trials showing benefits in regard to progression to mechanical ventilation (MV) and/or mortality. The aim of this study is to evaluate in real clinical practice the effectiveness of tocilizumab in treating COVID-19 and to identify prognostic factors for patient outcomes. METHODS: This was an observational, retrospective study of COVID-19 patients treated with tocilizumab between March 2020 and February 2021 in a tertiary hospital. Variables were demographics, comorbidities, vital signs, analytical parameters, COVID-19 treatment, progression to MV, intensive care unit (ICU) admission, hospital stay, and mortality. RESULTS: A total of 685 patients (64.7% men, median 68 years) were included. Overall mortality was 23.4% (14.2% in the first 14 days post-tocilizumab) and 93.3% in patients with MV and/or in the ICU at 14 days post-tocilizumab. In addition, 61.5% of discharges occurred during the same period. In patients who died, statistically significant differences were observed in the baseline analytical parameters of C-reactive protein (CRP), D-dimer and higher lactate dehydrogenase (LDH) (p<0.05). CONCLUSIONS: In most patients the clinical results of tocilizumab were observed at 14 days post-administration and could benefit from earlier administration of treatment. Baseline levels of CRP, D-dimer and LDH could be prognostic factors for the evolution of the COVID-19 patient.