Factors associated with mortality in patients hospitalized for COVID-19 in Spain. Data from the RERFAR registry.

OBJECTIVE: To determine the baseline characteristics associated with higher  mortality at 42 days in patients hospitalized for COVID-19 in Spain. METHOD: The study analyzed a prospective cohort of hospitalized COVID-19  patients. The dependent variable was 42-day mortality. Data on the subjects'  demographic and clinical characteristics, comorbidities, usual therapy and  supportive interventions and treatments was collected within 48 hours from  admission. To determine the potential association of the data with mortality, a  multivariate analysis was performed using logistic regression. RESULTS: 15,628 patients were included, 18.2% of whom (n = 2,806) died  during the study period. According to the multivariate analysis, the variables  that were significantly associated (p < 0.05) with mortality upon admission  were: being referred from a nursing home (OR 1.9); having a high respiratory  rate (OR 1,5); having moderate (OR 1.7) or severe (OR 2.9) pneumonia  (CURB-65); aspartate aminotransferase transaminase ≥ 100 IU/l (OR 2.1);  lactate dehydrogenase ≥ 360 IU/L (OR 1.6); procalcitonin > 0.5 ng/mL (OR  1.8); creatine kinase ≥ 294 U/L (OR 1.5); D-dimer > 3,000 ng/mL (OR 1.5);  hemoglobin < 11.6 g/dL (OR 1.4) and C-reactive protein > 120 mg/L (OR 1.2;  requiring respiratory support within the first 48 hours (oxygen therapy [OR  2.0], non-invasive ventilation [OR 2.8], and mechanical ventilation [OR 3.5]);  and being treated with interferon-beta (OR 1.5). On the contrary, being under  80 years of age was associated with lower mortality. CONCLUSIONS: The analysis, based on the data in the RERFAR registry, showed that the factors associated with poorer prognosis were older age,  assessed using the CURB-65 scale, level of respiratory support required,  severe pneumonia (CURB-65), hypertransaminasemia, elevated creatine  kinase, lactate dehydrogenase, and D-dimer levels, anemia, and elevated  respiratory rate.

OBJETIVO: Determinar las características basales que se asocian a una mayor  mortalidad a los 42 días en aquellos pacientes hospitalizados por COVID-19 en  España.Método: Cohorte prospectiva de pacientes COVID-19 hospitalizados. La  variable dependiente fue la mortalidad a los 42 días. Además, se recogieron  características demográficas, clínicas, comorbilidades, tratamiento habitual,  intervenciones de soporte y tratamientos en las primeras 48 horas del ingreso.  Para determinar la asociación con la mortalidad, se realizó un análisis  multivariante mediante regresión logística. Resultados: Se incluyeron 15.628 pacientes, de ellos falleció el 18,2% (n =  2.806). El análisis multivariante mostró que las variables asociadas significativamente (p < 0,05) con la mortalidad al ingreso fueron:  proceder de un centro sociosanitario (odds ratio OR 1,9), frecuencia  respiratoria (odds ratio 1,5), gravedad de neumonía (CURB-65) moderada  (odds ratio 1,7) o alta (odds ratio 2,9), transaminasa aspartato  aminotransferasa ≥ 100 UI/l (odds ratio 2,1), lactato-deshidrogenasa ≥ 360  UI/l (odds ratio 1,6), procalcitonina > 0,5 ng/ml (odds ratio 1,8), creatina- quinasa ≥ 294 U/l (odds ratio 1,5), dímero D > 3.000 ng/ml (odds ratio 1,5),  hemoglobina < 11,6 g/dl (odds ratio 1,4) y proteína C reactiva > 120 mg/l  (odds ratio 1,2), necesidad de soporte respiratorio en las primeras 48 horas  (odds ratio 2,0 de oxigenoterapia; odds ratio 2,8 ventilación no invasiva y odds ratio 3,5 ventilación mecánica) y tratamiento con interferón-beta (odds ratio  1,5). Por el contrario, ser menor de 80 años se asoció a una menor mortalidad. Conclusiones: El análisis del Registro Español de Resultados de  farmacoterapia frente a COVID-19 muestra que los factores asociados a peor pronóstico son: mayor edad, valoración mediante la escala CURB­65, el nivel de requerimiento de soporte respiratorio, neumonía grave (CURB­65), hipertransaminasemia, elevación de creatina-quinasa, lactato- deshidrogenasa, y dímero-D, anemia y elevación de la frecuencia respiratoria.

Cost-utility of talazoparib monotherapy treatment for locally advanced or metastatic breast cancer in Spain.

Breast cancer is one of the most frequent malignancies. The aim of the article is to analyse the cost-utility ratio and budgetary impact of talazoparib treatment for patients with locally advanced or metastatic gBRCA + breast cancer from the perspective of the Spanish National Health System. Analyses were based on the EMBRACA clinical trial and the model was constructed according to "partitioned survival analysis". Two scenarios were considered in order to compare talazoparib with the alternatives of capecitabine, vinorelbine and eribulin: 1. Chemotherapy in patients pre-treated with anthracyclines/taxanes and, 2. A second- and subsequent-line treatment option. Treatment types following relapse were recorded in the mentioned clinical trial. The effectiveness measure used was quality-adjusted life years (QALY). The average health cost of patients treated at 43 months with talazoparib was 84,360.86€, whilst current treatment costs were 26,683.90€. The effectiveness of talazoparib was 1.93 years of survival (1.09 QALY) relative to 1.58 years (0.83 QALY) in the treatment group. The incremental cost-utility ratio was 252,420.04€/QALY. This represents the additional cost required to earn an additional QALY when changing from regular treatment to talazoparib. Regarding budgetary impact, the number of patients susceptible to receiving treatment with between 94 and 202 talazoparib was estimated, according to scenario and likelihood. The 3-year cost difference was between 6.9 and 9 million euros. The economic evaluation conducted shows an elevated incremental cost-utility ratio and budgetary impact. Taking these results into account, the price of talazoparib would have to be lower than that taken as a reference to reach the cost-utility thresholds.

Recent Research in Ocular Cystinosis: Drug Delivery Systems, Cysteamine Detection Methods and Future Perspectives.

Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs. Although renal damage prevails during initial stages, the deposition of cystine crystals in the cornea causes severe ocular manifestations. At present, cysteamine is the only topical effective treatment for ocular cystinosis. The lack of investment by the pharmaceutical industry, together with the limited stability of cysteamine, make it available only as two marketed presentations (Cystaran® and Cystadrops®) and as compounding formulations prepared in pharmacy departments. Even so, new drug delivery systems (DDSs) need to be developed, allowing more comfortable dosage schedules that favor patient adherence. In the last decades, different research groups have focused on the development of hydrogels, nanowafers and contact lenses, allowing a sustained cysteamine release. In parallel, different determination methods and strategies to increase the stability of the formulations have also been developed. This comprehensive review aims to compile all the challenges and advances related to new cysteamine DDSs, analytical determination methods, and possible future therapeutic alternatives for treating cystinosis.

Hepatitis C virus core antigen in the management of patients treated with new direct-acting antivirals.

We evaluated the utility of Architect core antigen assay® Abbott Diagnostics (HCVAg) for monitoring patients with HCV infection and compared to HCV-RNA quantification (Cobas Ampliprep TaqMan-Roche Diagnostics). Samples from 262 patients were studied. Mean baseline HCV RNA and HCVAg levels were similar for responders (6.2 log IU/mL and 3.4 log fmol/L) and non-responders (6.1 log IU/mL and 3.2 log fmol/L), respectively. Only 10 patients failed to achieve SVR12 and all were detected by both assays. To evaluate HCVAg quantification as a tool for the detection of failure to DAAs, we performed a retrospective study of 132 non-responder patients. Mean HCV RNA and HCVAg levels at the time of detection of therapeutic failure were 5.88±0.97 log IU/mL and 3.19±0.79 log fmol/L, respectively. HCVAg (>3 fmol/L) was detected in 130/132 patients (98.5%). HCVAg assay was useful for patient selection and for evaluating virological response to DAAs in the real world.