An estimate of the economic impact of immunotherapy relative to PD-L1 expression in Brazil - An update with brazilian costs

Delivering high quality cancer care at an affordable cost is one of the main challenges for health care professionals and policy makers, especially in lowand middle-income countries. The objective of our study is to assess the economic impact of nivolumab and pembrolizumab with and without the use of PD-L1 as a biomarker in Brazil.info:eu-repo/semantics/publishedVersio

Communities of practice and QFD method for green logistics in the cosmetics industry: a suggested review

The Cosmetics, Personal Hygiene and Perfumery industry has significant importance in Brazil and seeks to adopt concepts and technologies of sustainable development to generate competitive advantages that can be achieved by companies in the industry. In this context, this research proposes to identify the perception of sustainability in recycling, mainly plastic packaging, and to suggest the use of Green Logistics and Cradle-to-Cradle concepts and the use of Communities of Practice. The research has a qualitative nature, using the methodology of multiple case studies with several companies in the industry, the data collection was performed through interviews with semi-structured questionnaire and documentary analyzes. The results were the identification of the companies' perceptions regarding sustainability and a suggestion of the application of the QFD method in the systematic unfolding between the needs of the consumer and the quality characteristics of the product that can be applied in these cooperatives to determine, with the presentation of their aspects and the generation of a quality matrix with the requirements raised

Main degradation products of dabigatran etexilate evaluated by LC-UV and LC-ESI-MS, degradation kinetics and in vitro cytotoxicity studies

The present study reports the stability profile of an antithrombotic drug: dabigatran etexilate (DAB). The drug was subjected to thermal degradation at 60 °C and products formed were investigated by liquid chromatography-UV (LC-UV) and liquid chromatography-mass spectrometry (LC-ESI-MS). Chromatographic separation of the degradation products was performed on a GL Sciences Inc. Inertsil ODS-2 column (250 mm × 4.6 mm i.d., with a particle size of 5 µm and pore size of 110 Å) with mobile phase consisting of acetonitrile and ammonium acetate buffer (pH 5.5; 10 mmol L−1 ) (65:35, v/v) pumped at 1.0 mL min−1 flow rate. Column temperature was set at 30 °C and detection at 225 nm using a UV detector. LC-UV method previously validated was extended to LC-ESI-MS for the characterization of the degradation products (DP-01 and DP-02) formed, without complicated isolation or purification processes, based on retention times and confirmation of molecular weight. Degradation kinetics of DAB was also evaluated and could be described as a first-order process (R2 = 0.9900). Furthermore, no evidence of cytotoxicity in human mononuclear cells was observed for DAB degraded samples

New target therapies in advanced non-small cell lung cancer: a review of the literature and future perspectives

Lung cancer (LC) is the most common neoplasm worldwide, and 85% of these tumors are classified as non-small cell lung cancer (NSCLC). LC treatment was initially restricted to cytotoxic chemotherapy-platinum compounds associated with 3rd generation cytotoxic agents (paclitaxel, gemcitabine, pemetrexed) and, more recently, with monoclonal antibodies (bevacizumab, ramucirumab). Advancements in treatment are correlated with prolonged overall survival (OS). Current advances are focused on target therapies. Target agents: Anti-epidermal growth factor receptor (EGFR) therapy consists of 1st and 2nd generation tyrosine kinase inhibitors (TKIs such as erlotinib, afatinib). In 60% of cases, resistance to these TKIs occurs due to T790M mutation in EGFR, which is overcome 3rd generation drugs (osimertinib). Anaplastic lymphoma kinase (ALK) is the target for drugs such as crizotinib, alectinib, ceritinib. Programmed death 1 (PD-1) and its ligand serve as targets for immunotherapy agents such as pembrolizumab, nivolumab, atezolizumab.info:eu-repo/semantics/publishedVersio

Immunotherapy in patients with advanced non-small cell lung cancer lacking driver mutations and future perspectives

From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI.info:eu-repo/semantics/publishedVersio

Preemptive use of intravenous ibuprofen to reduce postoperative pain after lower third molar surgery: a systematic review of randomized controlled trials

This study aimed to systematically review the literature to assess the effect of preemptive intravenous ibuprofen on pain reduction after lower third molar surgery. Nine databases (PubMed, Scopus, LILACS, SciELO, Embase, Web of Science, Cochrane, Open Gray, and Open Thesis) were used as sources of research, including “grey literature.” The protocol was registered in PROSPERO. Only randomized clinical trials evaluating the effects of preemptive intravenous ibuprofen on pain during and immediately after the extraction of lower third molars were included, without restrictions of year and language. Two reviewers independently performed the study selection, data extraction, and assessment of the risk of bias. The “Joanna Briggs Institute for Randomized Controlled Trials” tool was used to assess the risk of bias. Each study was categorized according to the percentage of positive responses to the questions corresponding to the assessment instrument. The results were measured narratively/descriptively. The initial search resulted in 3,257 records, of which only three studies (n=150 participants) met the eligibility criteria and were included in the qualitative analysis. All studies were published in 2019. The risk of bias ranged from low to moderate. Two studies found significant pain reduction within 48 h after the procedure. In conclusion, the use of preemptive intravenous ibuprofen for extracting third molars reduces pain and analgesic consumption after the surgical procedure

Screening for colorectal cancer leading into a new decade: the “Roaring ‘20s” for epigenetic biomarkers?

Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: “Screening”, “Diagnosis”, and “Biomarkers for CRC”. American and European clinical trials in progress were included as well.info:eu-repo/semantics/publishedVersio

Current and future aspects of TIM-3 as biomarker or as potential targeted in non-small cell lung cancer scope: is there a role in clinical practice?

Lung cancer is an aggressive disease with a high rate of mortality (1). Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all histology types (2). In the 1990’s, chemotherapy was the standard of care for the treatment of metastatic NSCLC (3). Since 2005, targeted therapies have emerged as a new cornerstone in the treatment of NSCLC. These include epidermal growth factor receptor tyrosine kinase inhibitors (EGFRTKI) such as gefitinib, erlotinib, afatinib, osimertinib, and dacomitinib (4) as well as the anaplastic lymphoma kinase (ALK) inhibitors crizotinib, alectinib, ceritinib, brigatinib and lorlatinib (5,6). Improving our understanding of tumor biology has therefore become a fundamental issue among oncologists to optimize these novel treatment strategies (7). In 2018, James P. Allison and Tasuku Honjo (8) won the Nobel prize for their research on the mechanisms of the tumor immune escape, which led to the first immunotherapy drugs to be utilized in clinical practice: nivolumab and ipilimumab (3,9). The Karolinska Institute Nobel Prize Committee declared that Allison and Honjo’s findings constituted the fourth cornerstone of cancer treatment, alongside surgery, radiotherapy and chemotherapy (1,9).National Council for Scientific and Technological Development (CNPq) 402621/2016-6info:eu-repo/semantics/publishedVersio