This Italian observational real-world study aims to assess in chronic hepatitis C virus (HCV) patients treated with pangenotypic direct acting agents (pDAAs) glecaprevir/pibrentasvir (GLE/PIB) or sofosbuvir/velpatasvir (SOF/VEL) the potential drug–drug interactions (DDIs) with concomitant medications prescribed, with a focus on cardiovascular and system nervous (CNS) co-medications. Data were collected from administrative databases covering 6.9 million health-assisted individuals. All patients prescribed SOF/VEL or GLE/PIB between 11/2017 and 12/2018 were included. Patients were analyzed while on DAA. DDIs were identified according to the Liverpool University tool. Overall, 3,181 HCV patients were included: 1619 in the GLE/PIB cohort and 1,562 in the SOF/VEL cohort. SOF/VEL patients were generally older than GLE/PIB ones (mean age 58.4 vs. 53.1, p < 0.001) and had more cardiovascular and CNS comorbidities (58% vs. 42%, p < 0.001 and 33% vs. 28%, p = 0.002, respectively). Contraindications due to DDIs in the GLE/PIB cohort affected 9.3% and 3.2% of patients before and on DAA, respectively, while the percentages in the SOF/VEL cohort were 3.2% before and 0.4% after pDAAs initiation. Among GLE/PIB patients, 2.7% had cardiovascular drugs (all statins) contraindicated while on DAA. The potential DDIs between cardiovascular drugs and SOF/VEL were mainly with statins (5%). SOF/VEL was prescribed in patients with older age and with more cardiovascular and CNS comorbidities. Despite this, a proportion of contraindicated drugs lower than that of GLE/PIB was registered.

Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 weeks without ribavirin as part of routine clinical practice were included. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with an available SVR assessment. Secondary outcomes were reasons for not achieving SVR, characteristics of patients with non-virological failures, adherence, and time from HCV RNA diagnosis to SOF/VEL treatment initiation. A total of 1209 patients were included; 142 did not achieve an SVR for non-virological reasons (n = 112; 83 lost to follow-up, 20 early treatment discontinuations) or unknown reasons (n = 30). Of the 1067 patients in the EP, 97.4% achieved SVR. SVR rates in the EP were ≥95% when stratified by type of mental health disorder and other complicating baseline characteristics, including active injection drug use and antipsychotic drug use. Of 461 patients with data available in the EP, only 2% had an adherence level < 90% and 1% had an adherence level < 80%; all achieved SVR. Patients with mental health disorders can be cured of HCV using a well-tolerated, pangenotypic, protease inhibitor-free SOF/VEL regimen. This DAA allows the implementation of a simple treatment algorithm, with minimal monitoring requirements and fewer interactions with central nervous system drugs compared with protease-inhibitor DAA regimens.

En condiciones de invernadero y durante el ciclo de invierno 2004 - 2005, se evaluaron dos híbridos de tomate (Lycopersicon esculentum Mill.) ‘Big Beef’ y ‘Miramar’ en tres sustratos: S1, vermicomposta + arena, en proporción 1:1 (v:v) + micronutrimentos quelatizados; S2, vermicomposta + arena, sin micronutrimentos; y el testigo S3, arena + solución nutritiva inorgánica. Los seis tratamientos se distribuyeron en un diseño completamente al azar con arreglo factorial 3 x 2 con 36 repeticiones, una planta por repetición. Se detectaron diferencias entre sustratos en rendimiento y calidad (P ≤ 0.01). El híbrido ‘Big Beef’ en el S3 presentó el rendimiento comercial más alto con 279 t ha-1, y superó al S1 con el mismo genotipo. En rendimiento de fruto total ambos híbridos crecidos en el S3 superaron al S1; sin embargo, el rendimiento en S1 fue mayor de 200 t ha-1 en ambos genotipos. Además, en S1 se logró mayor contenidode sólidos solubles y espesor del pericarpio en el fruto que en S3 y S2, por lo que el uso de vermicomposta + arena + quelatos puede ser una opción viable para producir tomate orgánico en invernadero.

ABSTRACT. The objective of this study was to determine the proportion of sand, solarized manure, vermicompost and soil capable of increasing tomato fruit yield and lycopene content. The treatments were: T1: 80 % Sand-20 % Vermicompost (SV), T2: 80 % Sand-20 % Solarized manure (SSM1), T3: 80 % Sand -20 % Pelite ?Steiner solution (SPSS), T4: 80 % Sand-5 % Soil -15 % Vermicompost (SSoV), T5: 85 % Sand -15 % Solarized manure (SSM2) and T6: 80 % Sand -5 % Soil -15 % Solarized manure (SSoSM). The organic substrates T5, T4, T1 and the control (T3) obtained larger fruits and yields. The lycopene content in tomato fruits grown in the organic substrates was 26 % higher than that obtained in the control treatment. Organic fertilizers improve the nutraceutical quality of tomato fruits, without signicantly degrading yield.Keywords: organic fertilizers, lycopene, protected agriculture.RESUMEN. El objetivo del trabajo fue determinar la proporción de arena, estiércol solarizado, vermicomposta y suelo, idónea para incrementar el rendimiento y el contenido de licopeno en frutos de tomate. Los tratamientos evaluados fueron T1: 80 % Arena -20 % Vermicomposta (AV), T2: 80 % Arena-20 % Estiércol solarizado (AES1), T3: 80 % Arena -20 % Perlita -solución Steiner (APSS), T4: 80 % Arena -5 % suelo -15 % Vermicomposta (ASV), T5: 85 % Arena -15 % Estiércol solarizado (AES2) y T6: 80 % Arena -5 % Suelo -15 % Estiércol solarizado (ASES). Los tratamientos T5, T4, T1: y el testigo (T3) fueron de mayor rendimiento y tamaño de fruto. El contenido de licopeno en los sustratos orgánicos superó en 26 % al obtenido en el tratamiento testigo. Los abonos orgánicos mejoran la calidad nutracéutica del tomate, sin disminuir el rendimiento.Palabras clave:abonos orgánicos, licopeno, agricultura protegida.

The availability of pangenotypic direct-acting antivirals for treatment of hepatitis C (HCV) has provided an opportunity to simplify patient pathways. Recent clinical practice guidelines have recognised the need for simplification to ensure that elimination of HCV as a public health concern remains a priority. Despite the move towards simplified treatment algorithms, there remains some complexity in the recommendations for the management of genotype 3 patients with compensated cirrhosis. In an era where additional clinical trial data are not anticipated, clinical guidance should consider experience gained in real-world settings. Although more experience is required for some pangenotypic therapeutic options, on the basis of published real-world data, there is already sufficient evidence to consider a simplified approach for genotype 3 patients with compensated cirrhosis. The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to minimise the need for complex patient pathways and clinical practice guidelines need to continue to evolve in order to ensure that patient outcomes remain optimised.