The nocebo effect is defined as the incitement or the worsening of symptoms induced by any negative attitude from non-pharmacological therapeutic intervention, sham, or active therapies. When a patient anticipates a negative effect associated with an intervention, medication or change in medication, they may then experience either an increase in this effect or experience it de novo. Although less is known about the nocebo effect compared with the placebo effect, widespread interest in the nocebo effect observed with statin therapy and a literature review highlighting the nocebo effect across at least ten different disease areas strongly suggests this is a common phenomenon. This effect has also recently been shown to play a role when introducing a medication or changing an established medication, for example, when switching patients from a reference biologic to a biosimilar. Given the important role biosimilars play in providing cost-effective alternatives to reference biologics, increasing physician treatment options and patient access to effective biologic treatment, it is important that we understand this phenomenon and aim to reduce this effect when possible. In this paper, we propose three key strategies to help mitigate the nocebo effect in clinical practice when switching patients from reference biologic to biosimilar: positive framing, increasing patient and healthcare professionals’ understanding of biosimilars and utilising a managed switching programme.

Selective elimination of metastatic stem cells (MetSCs) promises to block metastatic dissemination. Colorectal cancer (CRC) cells overexpressing CXCR4 display trafficking functions and metastasis‐initiating capacity. We assessed the antimetastatic activity of a nanoconjugate (T22‐GFP‐H6‐FdU) that selectively delivers Floxuridine to CXCR4+ cells. In contrast to free oligo‐FdU, intravenous T22‐GFP‐H6‐FdU selectively accumulates and internalizes in CXCR4+ cancer cells, triggering DNA damage and apoptosis, which leads to their selective elimination and to reduced tumor re‐initiation capacity. Repeated T22‐GFP‐H6‐FdU administration in cell line and patient‐derived CRC models blocks intravasation and completely prevents metastases development in 38–83% of mice, while showing CXCR4 expression‐dependent and site‐dependent reduction in foci number and size in liver, peritoneal, or lung metastases in the rest of mice, compared to free oligo‐FdU. T22‐GFP‐H6‐FdU induces also higher regression of established metastases than free oligo‐FdU, with negligible distribution or toxicity in normal tissues. This targeted drug delivery approach yields potent antimetastatic effect, through selective depletion of metastatic CXCR4+ cancer cells, and validates metastatic stem cells (MetSCs) as targets for clinical therapy.

High SERPINE1 expression is a common event in head and neck squamous cell carcinoma (HNSCC); however, whether it plays a role in determining clinical outcome remains still unknown. We studied SERPINE1 as a prognostic marker in two HNSCC patient cohorts. In a retrospective study (n = 80), high expression of SERPINE1 was associated with poor progression-free (p = 0.022) and cancer-specific (p = 0.040) survival. In a prospective study (n = 190), high SERPINE1 expression was associated with poor local recurrence-free (p = 0.022), progression-free (p = 0.002) and cancer-specific (p = 0.006) survival. SERPINE1 expression was identified as an independent risk factor for progression-free survival in patients treated with chemo-radiotherapy or radiotherapy (p = 0.043). In both patient cohorts, high SERPINE1 expression increased the risk of metastasis spread (p = 0.045; p = 0.029). The association between SERPINE1 expression and survival was confirmed using the HNSCC cohort included in The Cancer Genome Atlas project (n = 507). Once again, patients showing high expression had a poorer survival (p < 0.001). SERPINE1 over-expression in HNSCC cells reduced cell proliferation and enhanced migration. It also protected cells from cisplatin-induced apoptosis, which was accompanied by PI3K/AKT pathway activation. Downregulation of SERPINE1 expression had the opposite effect.We propose SERPINE1 expression as a prognostic marker that could be used to stratify HNSCC patients according to their risk of recurrence.

IntroductionAbout 50% of patients do not take their long-term therapy for chronic conditions as prescribed. Many studies have centered on patients’ adherence to a specific treatment or single conditions, but few have taken all chronic conditions into consideration from a patient’s perspective. This study aims to explore factors that impact on drug compliance and to identify strategies to improve this from the perspective of patients with at least one chronic condition.MethodsPatients were recruited by healthcare professionals from a hospital pharmacy, four community pharmacies, patient associations, and a primary care center in Barcelona. Five focus groups were conducted (N = 36). Conversations were audiotaped and transcribed verbatim to allow qualitative analysis.ResultsStudy subjects were aged 39–90 years (mean 65 years) and the mean number of comorbidities per patient was 2.3 (range 1–7). The main modifiers of therapeutic conduct were: patients’ health beliefs, patient–prescriber relationships, and patients’ motivation and perception of illness control. Study participants wanted greater participation in decision-making concerning their health and increased education about their illness and medication. They also wanted individualized healthcare that took their preferences and personal and emotional issues into account.ConclusionOur results highlight how the patient–prescriber’s relationship and factors such as health beliefs, motivation and perception of illness control impact on medication adherence in chronic patients. Future interventions to optimize adherence to treatment should focus on shared decision-making and more extensive health education.FundingCelgene Corporation.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0394-6) contains supplementary material, which is available to authorized users.

BackgroundThe resolution of potential drug-related problems is a priority of pharmaceutical care programmes.ObjectivesTo assess the clinical impact on drug-related negative outcomes of a pharmaceutical care programme focusing on the resolution of potential drug-related problems, initiated in the emergency department for patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD).MethodsControlled trials, in which older adults (≥65 years) receiving four or more medications admitted to the emergency department for ≥12 hours for worsening of HF and/or COPD were randomised (1:1) to either a pharmaceutical care programme focusing on resolving potential drug-related problems initiated at the emergency department (intervention group (IG)) or standard care (control group). Comparisons between the groups were made for the proportion of patients with drug-related negative outcomes, number of drug-related negative outcomes per patient, mean stay, patients readmitted within 180 days and 180-day mortality.Results118 patients were included, 59 in each group. Fewer patients in the IG had drug-related negative outcomes (37 (62.7%) vs 47 (79.7%) in the control group (p=0.042)). Fewer drug-related negative outcomes per patient occurred in the IG (56 (0.95 per patient) vs 85 (1.44 per patient) in the control group (p=0.01)). The mean stay was similar between groups (194.7 hours in the IG vs 242.5 hours in the control group (p=0.186)). No difference in revisits within 180 days was found (32 (54.24%) in the IG vs 22 (37.3%) in the control group (p=0.065)). 180-Day mortality was detected in 11 (18.6%) patients in the IG compared with 13 (22%) in the control group (p=0.647).ConclusionA pharmaceutical care programme focusing on resolving potential drug-related problems initiated at the emergency department has a favourable clinical impact, as it reduces the number and prevalence of drug-related negative outcomes. No difference was found in other outcome variables.Trial registration number NCT02368548.

The purpose of this study was to identify molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We studied the expression profile of 63 pre-treatment tumor biopsies obtained from locally advanced HNSCCs treated with standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) (P<0.001), progression free-survival (PFS) (P<0.009) and overall survival (OS) (P<0.004). Tumor subtype 1, associated with short LRFS, PFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes involved in cell adhesion, NF-κB and integrin signalling. Tumor subtype 3, associated with longer LRFS, PFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosomal regions 19q13 and 1q21. Tumor subtype 2, which had an intermediate clinical outcome between subtype 1 and subtype 3, overexpressed genes involved in branching morphogenesis. Finally, we validated the association between gene cluster classification and patient survival using Gene Set Enrichment Analysis and two HNSCC data sets obtained from two independent patient cohorts. In conclusion, we generated a gene prognostic signature associated with survival in locally advanced patients using the expression profile of the pre-treatment tumor biopsy. Independent prospective studies would be necessary to assess if the proposed survival signature could help to guide clinical management of HNSCC.

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