Applicability of tools to identify potentially inappropriate prescribing in elderly during medication review: Comparison of STOPP/START version 2, Beers 2019, EU(7)-PIM list, PRISCUS list, and Amsterdam tool-A pilot study.

Potentially inappropriate prescribing (PIP) is one of the major risk factors of adverse drug events in elderly patients. Pharmacotherapy assessment criteria may help reduce the instances of PIP among geriatric patients. This study aimed to verify the applicability of selected tools designed to assess prescribing appropriateness in elderly and to identify PIP in the study population. Based on pharmacist-led medication reviews that were performed among patients attending senior day-care centers based in Poland, aged 65 years and over, the following tools were applied for assessing the appropriateness of pharmacotherapy: PILA (patient-in-focus listing approach): STOPP/START v.2 and Amsterdam tool, DOLA (drug-oriented listing approach): PRISCUS list, and DOLA+: Beers criteria v.2019 and the EU(7)-PIM list-the criteria oriented on medications requiring indications. Fifty patients participated in the study. The prevalence of prescribing issues in the study population was very high and ranged from 28% to 100%, depending on the criteria applied. The highest number of PIP cases was identified based on the PILA criteria: STOPP/START v.2 (171, a mean of 3.4 PIP cases per patient), and the Amsterdam criteria (124, a mean of 2.5 PIP cases per patient). The lack of protective vaccinations against pneumococci identified using the START criterion was found to be the most common PIP (identified in 96% of the patients). Proton-pump inhibitors (PPIs) were identified as the most problematic group of medications. The STOPP, EU(7)-PIM and Beers criteria revealed cases of inappropriate prolonged PPI use, whereas the Amsterdam tool identified cases where PPIs should have been prescribed but were not. The highest number of PIP cases in the study population were identified with the PILA tools, and on this basis the most comprehensive assessment of pharmacotherapy appropriateness in geriatric patients was conducted. Further studies should be designed, covering a larger group of patients across different healthcare settings (inpatient and outpatient), with access to comprehensive patient data.

Efficacy and safety of BRAF inhibitors and anti-CTLA4 antibody in melanoma patients-real-world data.

PURPOSE: In the management of melanoma, BRAF inhibitors yield fast disease control; however, the duration of response does not last very long. Ipilimumab-an anti-CTLA4 antibody on the other hand-provides longer-lasting results of treatment but achieves less favorable responses. The aim of this study was to assess the efficacy and safety of novel drugs for advanced melanoma in daily routine practice. METHODS: A retrospective observational study was conducted on all Polish patients (1170 patients), diagnosed with advanced metastatic melanoma, treated with the following drugs: vemurafenib, dabrafenib, and ipilimumab. The antitumor efficacy of these agents was retrospectively assessed by Response Evaluation Criteria in Solid Tumors in the case of BRAF inhibitors and by Immune-Related Response Criteria in the case of ipilimumab therapy. Adverse events were assessed in relation to the morphologic parameters of blood, nephrotoxicity, and hepatotoxicity. RESULTS: The overall response to treatment with BRAF inhibitors (vemurafenib and dabrafenib) was similar with a slightly better outcome in the group treated with vemurafenib. Compared to clinical trials, the objective response rate was slightly worse for both BRAF inhibitors (30% and 42% for dabrafenib and vemurafenib, respectively), as well as the immune-related response for ipilimumab (1%). There was no significant difference in patient's response rates regardless of what lines of treatment (first, second, or next) vemurafenib was applied in. A few severe adverse events (mostly anemia and hyperbilirubinemia) were observed during treatment. CONCLUSIONS: The lack of evidence in responses observed regardless of what line of treatment vemurafenib was applied in suggests there is no clinical reason for restricting BRAF inhibitors to only the first line of therapy. Our study confirms that novel agents brought about a major advancement in the management of melanoma. In line with literature, BRAF inhibitors and ipilimumab significantly improved the antitumor response rate with manageable adverse events.

Drug adulteration of food supplements: A threat to public health in the European Union?

Food supplements have been playing an increasingly important role in the consumers' awareness nowadays. They are widespread and - according to popular belief - healthier and safer than synthetic drugs. In the European Union (EU) food supplements are classified as foodstuffs and thus not subjected to any specific safety assessments prior to commercialisation. With the growing popularity of food supplements, there is an increased need for more effective control of their production and distribution. The aim of this study was to examine the food notifications, recorded since 2003 via the EU RASFF database with particular regard to recent years, as well as to evaluate the involvement of different EU state structures in the fight against drug-adulterated food supplements with regard to efficacy and safety. In recent years, the number of RASFF notifications in the category of dietetic foods, food supplements and fortified foods, especially related to unauthorised composition, has increased significantly. The majority of EU Member States authorities, who responded to the study, consider drug-adulterated food supplements to be a public health threat. However, the competences of different official structures within the Member States concerning such products do not appear to be clearly defined. Regulators should thus think of stricter legislative solutions to increase the safety of public health.

SOX10-MITF pathway activity in melanoma cells.

Melanoma is one of the most dangerous and lethal skin cancers, with a considerable metastatic potential and drug resistance. It involves a malignant transformation of melanocytes. The exact course of events in which melanocytes become melanoma cells remains unclear. Nevertheless, this process is said to be dependent on the occurrence of cells with the phenotype of progenitor cells - cells characterized by expression of proteins such as nestin, CD-133 or CD-271. The development of these cells and their survival were found to be potentially dependent on the neural crest stem cell transcription factor SOX10. This is just one of the possible roles of SOX10, which contributes to melanomagenesis by regulating the SOX10-MITF pathway, but also to melanoma cell survival, proliferation and metastasis formation. The aim of this review is to describe the broad influence of the SOX10-MITF pathway on melanoma cells.

Survival of melanoma patients treated with novel drugs: retrospective analysis of real-world data.

PURPOSE: Recently, several new drugs have been licensed for advanced melanoma therapy, significantly changing the therapeutic landscape. Ipilimumab and vemurafenib were the first drugs that demonstrated a survival benefit over the long-standing standard therapy with dacarbazine. However, the comparative efficacy of these novel drugs has not been properly assessed yet. PATIENTS AND METHODS: We conducted a retrospective analysis of all the Polish population treated between January 2012 and October 2016 with one of the following agents: ipilimumab (IPI), vemurafenib (VEM), dabrafenib (DAB), and classic chemotherapy (CTH). The main objective was to assess the overall survival of melanoma patients treated in real-world conditions, taking into account sequences of treatment. RESULTS: We identified 3397 patients with malignant melanoma treated for the first line and the second line. Patients receiving CTH were significantly older than those treated with the novel drugs. At the same time, the population treated with immunotherapy and targeted therapy was well balanced. Overall survival was significantly better for the novel drugs compared to classic chemotherapy in both lines (for the first line, VEM vs CTH HR = 0.72, 95% CI 0.65-0.81; p < .01, and for the second line, VEM vs CTH HR = 0.78, 95% CI 0.62-0.98; p = .03; IPI vs CTH HR = 0.72, 95% CI 0.62-0.86; p < .01). There was no statistically significant difference for IPI vs VEM; however, subgroup analysis revealed superior results in the case of the CTH-IPI over BRAFi-IPI sequence. CONCLUSION: Novel drugs for melanoma provide a significant advantage in survival over classic chemotherapy. Comparative assessment of IPI and VEM indicated no difference, but only immunotherapy-treated patients achieved long-lasting results. Our data on sequential treatment indicate that immunotherapy might be a better option for the first line rather than targeted therapy, but that conclusion requires further studies of the best way to manage the treatment of melanoma patients.

Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer and Normal Cells, and Effects Cisplatin Cytotoxicity.

Uncaria tomentosa is a woody vine with a long history of use in traditional Peruvian medicine and nowadays supplements containing this vine as ingredient are available. Immunomodulating, anti-inflammatory and anticancer properties of Uncaria tomentosa have been suggested and attributed mainly to the presence of tetracyclic or pentacyclic oxindole alkaloids. However, the synergic action of different compounds occurring in extracts and modulation of redox processes may significantly influence the anticancer activity of Uncaria tomentosa. The aim of the present study was to investigate for the first time the cytotoxic effects of the tetracyclic alkaloids free aqueous extract (decoction) of dried Uncaria tomentosa leaf blades in normal and cancer cells, and to assess the effect of the tested extract on cisplatin (CDDP) cytotoxicity. Tested Uncaria tomentosa extract was not cytotoxic for NHDF cells, but demonstrated cytotoxic effect against HepG2 cells. The extract increased ROS production in HepG2 cells, which resulted in decreased GSH level, leading to apoptosis of these cells through activation of caspase-3 and caspase-7. A reduction of NF-κB active form was observed in cancer cells. In normal cells the extract did not affect ROS production, GSH level and NF-κB activity, and maintained cell viability. HepG2 cells incubation with Uncaria tomentosa decoction and simultaneously with CDDP resulted in an increase in CDPP cytotoxic activity against HepG2, while under the same conditions Uncaria tomentosa prevents NHDF cell viability reduction due to CDDP. The results indicate that Uncaria tomentosa leaves decoction modulates differently cancer and normal cells oxidative metabolism and, enhanced cytotoxicity of CDDP against cancer cells and at the same time increased normal healthy cells resistance to cisplatin. Further studies are needed to confirm our observations and to describe underlying molecular mechanism, and the potential usefulness of Uncaria tomentosa decoction in adjuvant therapy for cancer.

Drug Combinations as the New Standard for Melanoma Treatment.

OPINION STATEMENT: Advanced melanoma is related to a very grim prognosis and fast progression. Until recently, there has been no indicated treatment that would affect the disease's outcome. However, the progress in immunotherapy and molecular therapy has significantly changed the unfavourable prognosis of melanoma progression and its short survival rate. Both approaches have improved patients' outcomes and provided renewed hope for successful treatment. Moreover, in order to further enhance patients' outcomes and to avoid mechanisms of tumour resistance, investigators attempted a combined approach. Targeted therapy combinations allowed a better response rate and progression-free survival than monotherapy with one of the agents. Another promising combination, but with limiting toxicities, is a concurrent immuno- and molecular-targeted therapy. It is suspected that complimentary usage of these drugs may lead to synergism, providing robust and quick tumour responses as well as long-lasting effects. Results of currently ongoing clinical trials that investigate combination strategies in melanoma are expected to provide more mature data about the effectiveness and the safety profile of those therapies. Until more robust results of these studies occur, the best management of advanced and metastatic melanoma is immunotherapy with anti-PD1 drugs or targeted therapy with concomitant BRAF and MEK inhibitor. However, which of these two options should be used first is still under discussion.