Palliative Care Unit at Home: Impact on Quality of Life in Cancer Patients at the End of Life in a Rural Environment.

INTRODUCTION: Advanced cancer is accompanied by a substantial burden of symptoms, and palliative care (PC) plays an essential role, especially at the end of life (EOL). In fact, a comprehensive PC through Home Palliative Care Units (HPCU) has been associated with reducing potentially aggressive care at the EOL. We aim to study the impact of HPCU on the quality of assistance of cancer patients at Alcoy Health Department. METHODS: A retrospective study was conducted including patients diagnosed with terminal cancer at the Medical Department of Hospital Virgen de los Lirios who died between January 2017 and December 2018. The Multivariate Cox regression model was used to assess the impact of HPCU assistance on the quality of life indicators. RESULTS: 388 patients were included. The median age was 71 years; 65% patients were male, and 68% presented with a 0-2 score on the ECOG scale. On the multivariate analysis, a lack of assistance by HPCU was associated with a higher risk of consulting in the emergency department (OR = 1.29, 95% CI: 1.02-1.67), of hospital admissions (OR = 4.72, 95% CI: 2.45-9.09), a higher probability of continuing active treatment (OR = 2.59, 95% CI: 1.44-4.67), and a greater probability of dying in hospital (OR = 6.52, 95% CI: 3.78-11.27). CONCLUSIONS: Patients receiving HPCU assistance have a lower number of emergency room visits and hospital admissions, and are more likely to die at home. Taken together, these results support the relevance of HPCU providing a high quality attention of cancer patients.

Impact of Age on Inflammation-Based Scores among Patients Diagnosed with Stage III Non-Small Cell Lung Cancer.

BACKGROUND: Inflammatory and nutritional indexes are prognostic factors in non-small cell lung cancer (NSCLC). Furthermore, a low grade of chronic inflammation has been described in the older population (inflammaging). We aimed to evaluate the neutrophil-to-lymphocyte ratio (NLR), the Prognostic Nutritional Index (PNI), the advanced lung cancer inflammation index (ALI), the platelet-to-lymphocyte ratio (PLR), and the Glasgow Prognostic Score (GPS) in young and older patients diagnosed with locally advanced NSCLC to determine if significant differences between these groups exist. METHODS: We conducted a retrospective study analyzing the impact of age on the NLR, PNI, ALI, PLR, and GPS among patients diagnosed with stage III NSCLC at Hospital Universitario Doctor Peset between 2010 and 2015. RESULTS: We included 124 patients (84 young, 40 older patients). The median hemoglobin level and leukocyte count were lower in the older patients (p = 0.0158 and p = 0.001, respectively). A higher median C-reactive protein level was also found in this group (p = 0.0095). Regarding specific inflammatory indexes, the PNI, comprising inflammatory and nutritional parameters, was lower among the older patients (p = 0.0463). The median NLR, ALI, and PLR were similar in both age groups. Moreover, no differences between the age groups were found in the percentage of patients showing high versus low NLR (cutoff point, 5) or ALI (cutoff point, 18) or in the different GPS groups. CONCLUSIONS: The baseline PNI, hemoglobin level, and lymphocyte count were lower among the older patients; furthermore, CRP was higher, possibly, because of a more prominent inflammatory status in older patients with lung cancer. No other immunological or nutritional analytical variables were different between the age groups.

Cognitive impairment is related to a reduced count of T-lymphocytes in older patients diagnosed with non-small cell lung cancer (NSCLC).

BACKGROUND: Aging is a risk factor for cancer and cognitive impairment, and both have been related to changes in the immune system (immunosenescence) and chronic inflammation (inflammaging) of elderly individuals. Therefore, it would be interesting to know if there is a connection between immunological variations and cognitive function in oncologic patients, especially in lung cancer, in which, inflammation plays a crucial role in tumor development and progression. Our objective is to assess, in older patients diagnosed with non-small cell lung cancer (NSCLC), differences in parameters of the immune system depending on their cognitive status. METHODS: We retrospectively analyzed patients ≥70 years diagnosed with NSCLC with evaluated cognitive function, from January 2017 to April 2019. Lymphocyte count was gathered at baseline and checked for differences in lymphocyte counts between patients with a Pfeiffer result of 0-2 vs. 3-10 mistakes. Multiple regression models were used to assess the impact of clinical parameters on lymphocyte count. RESULTS: Seventy patients were analyzed. Sixty had a normal cognitive function, while ten had an impaired cognitive status; these were significantly older. Multivariate analysis showed that patients with cognitive impairment had lower levels of total, T and CD8+ T-lymphocytes (P=0.011, 0.011 and 0.019, respectively). Older age was only correlated to higher level of CD8+ T-lymphocytes (P=0.0390). Odds ratio for the risk of cognitive impairment depending on the level of T-lymphocytes was 0.996 (95% CI: 0.995-0.998), P=0.037. CONCLUSIONS: T-lymphocyte count is lower in patients diagnosed with lung cancer and cognitive impairment. These findings suggest that clinical features are closely related to immunological status in older patients with NSCLC. Therefore, age cannot always explain immunosenescence, and geriatric assessment could help.

Real-World Data of the Correlation between EGFR Determination by Liquid Biopsy in Non-squamous Non-small Cell Lung Cancer (NSCLC) and the EGFR Profile in Tumor Biopsy.

EGFR-mutated non-small cell lung cancer (NSCLC) has significant improved outcomes when treated with EGFR-tyrosine kinase inhibitors (TKI). Thus, EGFR-mutational status should be assessed at diagnosis and in the course of treatment with TKI. However, tissue samples are not always evaluable, and molecular profiling has been increasingly performed in cell-free tumor DNA (ctDNA) from blood samples. Our objective is to evaluate the reliability of ctDNA profiling in plasma samples in a real-world setting. We retrospectively analyzed the patients diagnosed with non-squamous NSCLC from May 2016 to December 2017 at Hospital Universitario Doctor Peset who had been tested for EGFR mutations in tissue and plasma samples. Both samples were sent to an external laboratory to perform the analysis by the cobas® EGFR assay. Percentage of agreement and concordance were calculated by kappa statistic. Of 102 patients reviewed, 89 were eligible. The overall EGFR mutation frequency was 18.6% for the evaluable tissue samples and 19.6% for evaluable plasma samples. Mutation status concordance between matched samples was 87.4%. Cohen's kappa index (κ) = 0.6 (sensitivity 70.6%, specificity 91.7%, positive predictive value 66.7%, negative predictive value 93%). When concordance was stablished only in stage IV tumors κ = 0.7, suggesting a higher agreement in advanced disease. This real-world data suggest that plasma is a feasible sample for ctDNA EGFR mutation assessment. Results of ctDNA molecular profiling are reliable when using a validated technique such as the cobas® EGFR assay, especially in patients that cannot undergo a tissue biopsy.

Deprescribing of non-antiretroviral therapy in HIV-infected patients.

PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.

The effects of Maraviroc on liver fibrosis in HIV/HCV co-infected patients.

INTRODUCTION: The fibrogenesis analysis in quimeric CCR1 and CCR5 mice revealed that CCR5 mediates its pro-fibrogenic effects in hepatic cells and promoting stellate cells. The blockage of co-receptors could preserve the progression of hepatic fibrosis in HIV/HCV co-infected patients. OBJECTIVE: To evaluate the beneficial effects on hepatic fibrosis in HIV/HCV co-infected patients that are on antiretroviral therapy (ART) with CCR5 co-receptor antagonists. METHOD AND MATERIALS: A multicentre, retrospective pilot study of the evaluation of hepatic fibrosis at mid- and long-term by non-invasive methods in a HIV/HCV co-infected patients cohort in the Valencian Community (Spain) that received ART with a CCR5 co-receptor antagonist. The cut-off points of serum marker tests of hepatic fibrosis were: AST to Platelet Ratio Index (APRI)<0.5 (F0-F1); >1.5 F2; >2 Cirrhosis and Forns Index<4.2 excludes fibrosis; >6.9>F2 fibrosis. Inclusion criteria was established for HIV/HCV co-infected patients on ART with CCR5 co-receptor antagonists that had no previous history of interferon and ribavirin treatment or those who were null-responders and received CCR5 co-receptor antagonist treatment in the previous year. Patients with HBV infection were excluded. RESULTS: A total of 71 male patients (69%) were reported. A CD4 nadir <100 cells/uL was observed in 42% of patients and 62% (44/71) had a basal CD4 level >350 cells/uL. According to genotypes, 50% were G-1a, 14% G-1b, 11% G-3 and 25% G-4. The median duration of treatment with Maraviroc (MVC) was the following: 45% took it over a year, 41% over two years and 14% over three years. Before starting treatment with MVC, we observed an initial fibrosis of F0-F1 in 49% of patients, F2-F3 in 24% and F4 in 27%. The medium follow-up was of 18.45 months. Progression to a higher fibrosis level was observed in five patients, 11 patients improved at least one stage and the others were stable over time. There were 38 patients taking MVC over two years, 27 patients in this group (59.38%) did not modify their fibrosis, 3 patients (11%) progressed and 8 (29.62%) showed regression of liver fibrosis in one stage. CONCLUSIONS: The data above shows a benefit over fibrosis progression with MVC, expressed by fibrosis serum marker tests in HIV/HCV co-infected patients with CCR5 tropism. The prolong treatment with MVC (over two years) has a better effect on liver fibrosis.

Alternation of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study.

INTRODUCTION: Alternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection. However, some concerns persist regarding antiviral efficacy, adherence, toxicity and resistance evolution in the long term. METHODS: A total of 161 antiretroviral-naive HIV-1-infected patients were randomized to receive stavudine/didanosine/efavirenz (group A) or zidovudine/lamivudine/ nelfinavir (group B) or to alternate between the two regimens every 3 months starting with regimen A (group C). Antiviral efficacy, adherence, safety and tolerability were analysed every 12 weeks. RESULTS: After 96 weeks, time to virological failure was significantly delayed in the alternating regimen compared with the standards of care regimens. Virological suppression was seen in 46%, 48% and 58% of patients in groups A, B and C, respectively, in the intention-to-treat analysis and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014; B vs C: P=0.016; A vs B: P=0.849). At the end of the study, 94% of patients in group A and 92% in groups B and C reported an adherence greater than 95%. Alternating therapy was associated with a similar impact on CD4+ counts in comparison with the standards of care regimens, as well as a lower mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the mitochondrial substudy performed on 37 patients. The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles. DISCUSSION: Our results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations. Moreover, the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups. The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in standard regimens.