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Drug budget and prescription control measures are implemented regionally in Germany, meaning that the uptake of pharmaceuticals, including biosimilars, can vary by region. learn more We examine regional market dynamics of tumor necrosis factor alpha (TNFα) inhibitor originators and biosimilars in Germany and studied the influence of biosimilar policies on these dynamics. This study is based on (1) a literature review in which German biosimilar policies are identified, (2) the analysis of dispensing data (2010-2018) for the class of TNFα inhibitors, and (3) ten semi-structured interviews investigating prescribers’ and insurers’ views on factors potentially influencing biosimilar uptake. The analysis of biosimilar market shares of infliximab and etanercept revealed wide variations across the 17 German Regional Associations of Statutory Health Insurance Accredited Physicians (PA regions). Quantitative analyses indicated that biosimilar market shares for infliximab and etanercept were significantly lower in former East Germany when compared to former West Germany regions. Through qualitative interview analyses, this study showed that the use of infliximab and etanercept biosimilars across Germany is primarily influenced by (1) the regional-level implementation of biosimilar quotas and the presence of monitoring/sanctioning mechanisms to ensure adherence to these quotas, (2) the different insurer-manufacturer discount contracts, and (3) gainsharing arrangements established at the insurer-prescriber level.Esophageal cancer is among the most aggressive diseases, and circulating tumor cells (CTCs) have been recognized as novel biomarkers for various cancers over the past two decades, including esophageal cancer. CTCs might provide crucial clinical information for predicting cancer prognosis, monitoring therapeutic responses or recurrences, or elucidating the mechanism of metastasis. The isolation of CTCs is among the applications of a “liquid biopsy”. There are various technologies for liquid biopsies, and they are classified into two main methods cytometric or non-cytometric techniques. Here, we review a total of 57 eligible articles to summarize various technologies for the use of a liquid biopsy in esophageal cancer and perform a meta-analysis to assess the clinical utility of liquid biopsies as a prognostic and diagnostic biomarker technique. For prognostic evaluation, the pooled hazard ratio in the cytometric assay is relatively higher than that of the non-cytometric assay. On the other hand, a combination of multiple molecules, using a non-cytometric assay, might be a favorable biomarker technique for the early diagnosis of esophageal cancer. Although determining strong evidence for a biomarker by using a liquid biopsy is still challenging, our meta-analysis might be a milestone for the future development of liquid biopsies in use with esophageal cancer.Influenza virus infections represent a major public health issue by causing annual epidemics and occasional pandemics that affect thousands of people worldwide. Vaccination is the main prophylaxis to prevent these epidemics/pandemics, although the effectiveness of licensed vaccines is rather limited due to the constant mutations of influenza virus antigenic characteristics. The available anti-influenza drugs are still restricted and there is an increasing viral resistance to these compounds, thus highlighting the need for research and development of new antiviral drugs. In this work, two semisynthetic derivatives of digitoxigenin, namely C10 (3β-((N-(2-hydroxyethyl)aminoacetyl)amino-3-deoxydigitoxigenin) and C11 (3β-(hydroxyacetyl)amino-3-deoxydigitoxigenin), showed anti-influenza A virus activity by affecting the expression of viral proteins at the early and late stages of replication cycle, and altering the transcription and synthesis of new viral proteins, thereby inhibiting the formation of new virions. Such antiviral action occurred due to the interference in the assembly of viral polymerase, resulting in an impaired polymerase activity and, therefore, reducing viral replication. Confirming the in vitro results, a clinically relevant ex vivo model of influenza virus infection of human tumor-free lung tissues corroborated the potential of these compounds, especially C10, to completely abrogate influenza A virus replication at the highest concentration tested (2.0 µM). Taken together, these promising results demonstrated that C10 and C11 can be considered as potential new anti-influenza drug candidates.

In obsessive-compulsive disorder (OCD), symptom content and severity appear to fluctuate over the course of the life cycle in accordance with stressful life events. The objective of this paper was to compare OCD patients with and without reported stressful life events (SLEs) in terms of the sociodemographics of patients and the clinical characteristics of OCD.

This was a cross-sectional study involving 1001 patients with OCD. Data concerning SLEs were collected via the Yale OCD Natural History Questionnaire, while for OCD symptoms, the Dimensional Yale-Brown Obsessive-Compulsive Scale was used.

Of the 1001 OCD patients, 605 (60.5%) reported experiencing at least one SLE in their lifetime. Self-declared nonwhite skin color (odds ratio (OR) = 1.51), the presence of a sensory phenomenon (OR = 1.47), and comorbidity with post-traumatic stress disorder (PTSD) (OR = 2.38) were some of the logistic regression variables related to the reported SLEs with relevant statistical significance and risk (i.e., OR) values.

Our results indicate that SLEs may make Brazilian OCD patients vulnerable to the onset or exacerbation of obsessive-compulsive symptoms. The positive association of the occurrence of SLEs and sensory phenomena in this population could corroborate that environmental influences impact the neurobiology associated with OCD, and likely with other psychiatric disorders as well.

Our results indicate that SLEs may make Brazilian OCD patients vulnerable to the onset or exacerbation of obsessive-compulsive symptoms. The positive association of the occurrence of SLEs and sensory phenomena in this population could corroborate that environmental influences impact the neurobiology associated with OCD, and likely with other psychiatric disorders as well.