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Our aim was to describe the incidence and characteristics of immune-related adverse events (irAEs) in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and to evaluate their impact on outcome. All cases of NSCLC patients treated with ICIs in the second-line setting between December 2015 and May 2018 were evaluated. Seventy patients were included. Mean age was 65.9 years, and the majority of male (n = 53, 75.7%), with PS of 0-1 (n = 62, 88.6%) treated with nivolumab (n = 51; 72.9%). Thirty-one patients (44.3%) experienced an AE, 5 (7.1%) were grades 3-4. Median OS in patients with AE was 30.1 months (95% CI, 16.7-43.5) compared with 5.1 months (95% CI, 1.2-9.0) in cases without AE (log-rank test: p = 0.010). The adjusted HR for OS was 0.46 (95% CI, 0.25-0.86) for the irAE occurrence and 3.60 (95% CI, 1.56-8.32) for PS 2-3 group. The development of irAEs was associated with improved patient outcome.

BACKGROUND An increasing trend in opioid consumption has been observed worldwide in last decades. However, data related to opioid utilization in hospital settings are scarce. The aim of this study was to determine the evolution of use of strong opioids and pain intensity in a tertiary hospital during 6 years. METHODS Consumption of strong opioid analgesics used at the hospital at any time between 2012 and 2017 was collected. Data were expressed on oral morphine equivalents (OMEs) per 100 bed-days. Pain intensity was measured by the numerical rating scale (NRS) and the percentage of patients who experienced a NRS value ≥3 and ≥7 were calculated. Case mix index (CMI) was also collected. Data were quantified in medical and surgical area separately. RESULTS Consumption of opioids varied from 812.4 to 1,038.8 OMEs/100 bed-days and from 967.3 to 1,023.7 in medical and surgical area. The percentage of patients that experienced a value of NRS ≥ 3 and ≥7 in medical area increased from 24.2% and 5.5% to 31.7% and 7.5%, (p = .038, p = .040). It was observed a correlation between the percentage of patients that experienced a NRS ≥ 7 in two consecutive determinations and opioid prescription in medical area (p = .039).The CMI increased from 1.05 and 0.91 to 1.18 and 1.04 in medical and surgical area (p = .020, p = .004). CONCLUSIONS Consumption of strong opioids has remained stable, both in medical and surgical area, during last years. A correlation between prescription of opioids and pain intensity is observed in case of repeated and severe pain in medical departments. SIGNIFICANCE This study shows a stable consumption of strong opioid analgesics in a hospital setting in contrast to what appears to be the extrahospitalary trend during last years. The association between consumption of opioids and pain intensity seems to indicate a good control of pain in the clinical setting, showing a significant correlation between the consumption of opioids and repeated and severe pain in medical departments.

BACKGROUND AND AIM Patients with chronic hepatitis C (CHC) frequently associated comorbidities and concomitant medication. Sustained virological response (SVR12) has been related to an increase in cholesterol serum levels and in peripheral vascular resistance. Our aim was to evaluate the impact of SVR12 on the use of concomitant medication and serum lipid profile. METHODS Prospective study including patients treated with direct-acting antivirals who had achieved the SVR12. Clinical data and concomitant drugs were analysed at baseline and at least 1 year after SVR12. Differences from baseline to follow-up in the concomitant medication were evaluated by Stuart-Maxwell test and lipid profile by Wilcoxon signed-rank test. Patients were categorized according to the increase/decrease in the number of drugs included in each class (Anatomical Therapeutic Chemical classification system). RESULTS Two hundred twenty-six patients with SVR12 were included, 73.5% were receiving concomitant drugs (49.6% with antihypertensive effect, 30.5% antacids, 16.4% anti-diabetic drugs, and 7.1% lipid-lowering agents). One year after SVR12, total cholesterol serum levels increased from 161 to 179 mg/dl (P < 0.001) and, after a median time of 25.7 months, the use of lipid-lowering drugs increased from 7.8 to 11.5% (P = 0.009). In addition, we observed a trend to use more antihypertensive drugs in older patients (P = 0.06), especially in those with cirrhosis. Anxiolytics decreased after SVR12 from 13.7 to 10.6% (P = 0.035). CONCLUSION CHC cure is associated with a significant increase in cholesterol serum levels and the use of lipid-lowering agents, as well as the use of drugs with antihypertensive effect in older patients.

Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy, however, not all patients benefit. Here, we hypothesized that the heterogeneity in the response seen in patients is partly explained by the levels of human epidermal growth factor receptor 2 gene (ERBB2) mRNA. We analyzed ERBB2 expression using a clinically applicable assay in formalin-fixed paraffin-embedded (FFPE) tumors (primary or metastatic) from a retrospective series of 77 patients with advanced HER2+ BC treated with T-DM1. The association of ERBB2 levels and response was further validated in 161 baseline tumors from the West German Study (WGS) Group ADAPT phase II trial exploring neoadjuvant T-DM1 and 9 in vitro BC cell lines. Finally, ERBB2 expression was explored in 392 BCs from an in-house dataset, 368 primary BCs from The Cancer Genome Atlas (TCGA) dataset and 10,071 tumors representing 33 cancer types from the PanCancer TCGA dataset. High ERBB2 mRNA was found associated with better response and progression-free survival in the metastatic setting and higher rates of pathological complete response in the neoadjuvant setting. ERBB2 expression also correlated with in vitro response to T-DM1. Finally, our assay identified 0.20&ndash, 8.41% of tumors across 15 cancer types as ERBB2-high, including gastric and esophagus adenocarcinomas, urothelial carcinoma, cervical squamous carcinoma and pancreatic cancer. In particular, we identified high ERBB2 mRNA in a patient with HER2+ advanced gastric cancer who achieved a long-lasting partial response to T-DM1. Our study demonstrates that the heterogeneity in response to T-DM1 is partly explained by ERBB2 levels and provides a clinically applicable assay to be tested in future clinical trials of breast cancer and other cancer types.

Our objective was to evaluate the prevalence of discrepancies between primary care electronic medication records (EMR) and patient reported medication (PRM) in ambulatory patients starting a hospital dispensing treatment (HDT) at a hospital-based ambulatory care pharmacy (HACPh). Our secondary aims were to analyse factors associated with the presence of discrepancies and their impact on the prevalence of potential drug-drug interactions (DDIs) with the HDT.Retrospective study including 230 patients starting a HDT at the HACPh. Pharmacists interviewed patients and PRM was compared with EMR. Discrepancies were classified as omissions (medication in the PRM not present in the EMR) and commissions (medication active in the EMR that the patients were not taking). Potential DDIs with the HDT were screened, and univariate and multivariate analyses were performed to detect factors associated with the presence of discrepancies.We identified 221 discrepancies in 116 (50.4%) patients. Being visited by three or more medical specialties (OR 1.93, 95% CI 1.11 to 3.37) and attending private healthcare (OR 4.36, 95% CI 1.14 to 16.72) in the 12 months before the study inclusion were the factors independently associated with the presence of discrepancies. Among patients with commissions (n=91), 15.4% had a potential DDI between the HDT and one medication from the EMR that they were not taking at that moment. Among patients with omissions (n=45), 11.1% had a potential DDI between the HDT and a medication in the PRM not present in the EMR.About 40% of patients had one or more medications in the EMR which they were not taking and one fifth used medications that were not listed in the EMR. EMR should not be used as the only source of information when screening for DDIs, especially in patients followed by different medical specialties or combining private and public healthcare.

Background Integrase inhibitors (INSTIs) are recommended as firstline antiretroviral treatment (ART) in HIV patients. However, several factors such as toxicity, virological failure or a low adherence can lead to a switch of ART. Purpose To assess the frequency and compare the reasons for switching among the INSTIs in a HIV unit in a tertiary hospital. Material and methods A retrospective study including all patients who switched from INSTIs to other ART (January 2014–September 2016) in our cohort of 1750 HIV infected patients was conducted. Switches involving ART other than INSTIs were not included. Data collected: demographics, hepatitis C virus coinfection, previous and new ART. Reasons for switching were classified as: adverse events (neuropsychiatric toxicity, dermatologic, gastrointestinal and others), schedule optimisation (convenience, simplification or food restrictions), drug–drug interactions, pregnancy and low level viraemia (LV). Results 733 patients were treated with INSTIs during this period: 223 (30.4%) raltegravir, 159 (21.7%) elvitegravir and 351 (47.9%) dolutegravir. The INSTI was switched in 133 patients (7.2% of total patients): 101 (75.9%) men, age 47.0±13.2 years, HCV 39 (29.3%). New ART treatment included INSTIs in 97 (72.9%) (6% raltegravir; 24.8%elvitegravir; 42.1% dolutegravir); non-nucleoside reverse transcriptase inhibitors in 11 (8.3%); protease inhibitors in 20 (15.0%); and others ART in 5 (3.8%) patients. Conclusion In more than 50% of patients, the INSTIs were switched in order to optimise the ART schedule. Raltegravir was the INSTI more frequently switched, because of schedule optimisation and presence of LV (due to poor adherence in almost all patients). Drug interactions leading to an INSTI switch were exceptional and were only seen with elvitegravir, probably related to its coformulation with cobicistat. The most common reason for stopping dolutegravir was adverse events, mostly gastrointestinal, while none of the patients experienced LV. No conflict of interest