Real-world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab.

BACKGROUND: There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011. OBJECTIVE: To evaluate ipilimumab and postipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain, following regulatory approval. METHODS: Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death. RESULTS: Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another antimelanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received postipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders. CONCLUSION: During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received postipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options.

Histopathological and Ultrastructural Changes after Electroporation in Pig Liver Using Parallel-Plate Electrodes and High-Performance Generator.

Irreversible electroporation (IRE) has gained attention as a new non-thermal therapy for ablation with important benefits in terms of homogeneous treatment and fast recovery. In this study, a new concept of high voltage generator is used, enabling irreversible electroporation treatment in large tissue volume using parallel plates. Unlike currently available generators, the proposed versatile structure enables delivering high-voltage high-current pulses. To obtain homogeneous results, 3-cm parallel-plates electrodes have also been designed and implemented. IRE ablation was performed on six female pigs at 2000 V/cm electric field, and the results were analysed after sacrifice three hours, three days and seven days after ablation. Histopathological and ultrastructural studies, including transmission and scanning electron microscopy, were carried out. The developed high-voltage generator has proved to be effective for homogeneous IRE treatment using parallel plates. The destruction of the membrane of the hepatocytes and the alterations of the membranes of the cellular organelles seem incompatible with cell death by apoptosis. Although endothelial cells also die with electroporation, the maintenance of vascular scaffold allows repairing processes to begin from the third day after IRE as long as the blood flow has not been interrupted. This study has opened new direction for IRE using high performance generators and highlighted the importance of taking into account ultrastructural changes after IRE by using electron microscopy analysis.

Prevalence and incidence of hyperkalaemia in the Spanish population with heart failure with reduced ejection fraction: a systematic review and populational relevance. / Prevalencia e incidencia de hiperpotasemia en población española con insuficiencia cardiaca con fracción de eyección deprimida: revisión sistemática y relevancia poblacional.

BACKGROUND AND OBJECTIVES: Hyperkalaemia (K+ levels≥5.5mmol/L) is a severe ion imbalance that occurs in patients who have heart failure (HF) with reduced ejection fraction (HFrEF) and increases the risk of ventricular fibrillation. Given that there are no estimates on the number of patients with this complication, the aim of this study was to estimate the prevalence and incidence of hyperkalaemia in patients with HFrEF in Spain. MATERIAL AND METHODS: Based on a systematic literature search and through a meta-analysis, we calculated an HFrEF prevalence of ≤40% in the European and U.S. POPULATION: Based on another systematic literature search, we calculated the prevalence of hyperkalaemia in patients with HF and its annual incidence rate. Considering the previous values and the Spanish population pyramid in 2016, we estimated the number of individuals with HFrEF who currently have hyperkalaemia and those who develop it each year in Spain. RESULTS: Approximately 17,100 (10,000 men and 7100 women) of the 508,000 patients with HFrEF in Spain have hyperkalaemia. Furthermore, approximately 14,900 patients with HFrEF (9500 men and 5400 women) develop hyperkalaemia each year. CONCLUSIONS: Approximately 1 of every 30 patients with HFrEF has plasma potassium values >5.5 mmol/L.

The dilemmas of chronicity: the transition of care policies from the authoritarian state to the welfare state in Spain.

In this article, the constitution of the population of chronic mental patients is examined for the period 1885 to 1975 as well as its influence on the design of reform programmes in the crisis of the Franco-ist state. Then follows an assessment of state reforms and regional policies with effect from 1980. Reference is made to the theoretical models utilised in this last period and to the tension and contradictions between professionals of bio-medical orientation and sectors sympathetic to community models sustained from the perspective of social psychiatry.