Evaluation of medication use and pharmacy services for visually impaired persons: Perspectives from both visually impaired and community pharmacists.

BACKGROUND: Visual impairment poses various challenges to individuals in taking their medications, but there is a lack of studies on visually impaired population and their use of medications and pharmacy services. OBJECTIVES: In this study, we aimed to examine (1) the usage pattern of medications and pharmacy services in visually impaired persons and (2) the status of medication counseling conducted to the visually impaired persons by the community pharmacists. METHODS: This was a cross-sectional study conducted both to visually impaired and community pharmacists. After pilot testing, survey questionnaires were prepared for each group. Visually impaired participants were recruited from two institutions for visually impaired in South Korea. Pharmacists working at 47 community pharmacies that were selected for braille sticker distribution by the Seoul Metropolitan Government were recruited. SPSS Statistics 23 was used for statistical analysis. RESULTS: One hundred and fourteen visually impaired and 36 pharmacies participated in this study. Majority of the visually impaired participants reported experiencing challenges in identifying medications at home but were using their own methods, such as the use of different storage containers or locations to distinguish medications. While the visually impaired preferred more detailed counseling and use of various tools for medication counseling, the majority of the pharmacists performed counseling to the patients' family members or caretakers. CONCLUSIONS: For challenges in managing medications by the visually impaired persons, community pharmacists can play a role by putting efforts to understand their impairment and utilize tools available to guide them.

Evaluation of pharmacokinetic, pharmacodynamic, efficacy, and safety data of low-dose ticagrelor versus standard dose in East Asians: a systematic review.

East Asians are prone to higher systemic exposure and increased risk of bleeding compared to other races after administration of antiplatelet agent(s). The aim of this systematic review was to compare and evaluate the appropriateness of a lower dose versus standard dose of ticagrelor in East Asians. A systematic search was conducted in PubMed, EMBASE, and Cochrane databases for studies comparing low versus standard doses of ticagrelor in East Asian populations; a total of seven studies were included in the review. Pharmacokinetic (PK), pharmacodynamic (PD), clinical efficacy, and safety data were collected. PK data demonstrated that the Cmax and area under the curve (AUC) of ticagrelor increased dose-proportionally. PD data indicated that while the low dose of ticagrelor resulted in less antiplatelet activity in three of the five PD studies, in the other studies, there were no differences between low and standard doses. There were two clinical studies included in this review, which showed that the efficacy was similar between the low and standard doses, but both studies were limited by the number of patients included. While there were generally greater incidence of adverse events observed in the standard ticagrelor dose, the magnitude or actual difference between the two doses is difficult to determine due to lack of consistent data. In East Asians, the appropriateness of the low-dose ticagrelor cannot be determined based on the currently available evidence. Additional large-scale and longer duration studies are warranted.

Early assessment of response to induction therapy in acute myeloid leukemia using 18F-FLT PET/CT.

BACKGROUND: We evaluated the suitability of 18F-fluorodeoxythymidine (18F-FLT) positron emission tomography (PET)/computed tomography (CT) for assessment of the early response to induction therapy and its value for predicting clinical outcome in patients with acute myeloid leukemia (AML). Adult patients who had histologically confirmed AML and received induction therapy were enrolled. All patients underwent 18F-FLT PET/CT after completion of induction. PET/CT images were visually and quantitatively assessed. Cases with intensely increased bone marrow uptake in more than one third of the long bones and throughout the central skeleton were interpreted as PET-positive for resistant disease (RD). PET results were compared to the clinical response and outcome. RESULTS: In visual PET analysis of 10 eligible patients (7 male, 3 female; median age 58 years), 5 patients were interpreted as being PET-positive and 5 as PET-negative. Standardized uptake values were significantly different between PET-positive and PET-negative groups. Eight of 10 patients achieved clinical complete remission (CR)/CR with incomplete blood count recovery (CRi). Five CR/CRi patients had PET-negative findings, but 3 CR patients had PET-positive findings. Both of the RD patients had PET-positive findings. During follow-up, 2 CR patients with PET-positive findings relapsed, or were strongly suspected of relapse, 4 months after consolidation. CONCLUSION: 18F-FLT PET/CT after induction therapy showed good sensitivity and negative-predictive value for evaluating RD in patients with AML. This preliminary study suggests that 18F-FLT PET/CT may be valuable as a noninvasive tool for early assessment of the response to treatment and may provide prognostic value for survival in patients with AML.

Marmesin-mediated suppression of VEGF/VEGFR and integrin ß1 expression: Its implication in non-small cell lung cancer cell responses and tumor angiogenesis.

In the present study, we investigated the effects and molecular mechanism of marmesin, a natural coumarin compound isolated from Broussonetia kazinoki, on non-small cell lung cancer (NSCLC) cell responses and tumor angiogenesis. Marmesin abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type A549 and p53-deficient H1299 NSCLC cells. These antitumor activities of marmesin were mediated by the inactivation of mitogenic signaling pathways and downregulation of cell signaling-related proteins including vascular endothelial growth factor receptor-2 (VEGFR-2), integrin ß1, integrin-linked kinase and matrix metalloproteinases-2. Furthermore, marmesin suppressed the expression and secretion of VEGF in both NSCLC cells, leading to inhibition of capillary-like structure formation in human umbilical vein endothelial cells. Collectively, these findings demonstrate the pharmacological roles and molecular targets of marmesin in regulating NSCLC cell responses and tumor angiogenesis.

Clinical impact of induction treatment modalities and optimal timing of radiotherapy for the treatment of limited-stage NK/T cell lymphoma.

This study retrospectively investigated the optimal timing of radiotherapy (RT) in patients with limited-stage extranodal NK/T-cell lymphoma (ENTKL). Among 158 patients with newly diagnosed stage I/II ENKTL, 61 patients were treated with sequential chemotherapy followed by radiotherapy (SCRT), 55 with concurrent chemoradiotherapy followed by non-anthracycline-based chemotherapy (CCRT/CT), and 42 with chemotherapy (CT) only. The 5-year overall survival (OS) rate did not differ between SCRT (77.7±5.5%) and CCRT/CT (68.9±6.8%; p=0.234). In the SCRT group, 18 patients (29.5%) relapsed within the RT field and 6 (9.8%) at systemic sites, while in the CCRT/CT group, 9 patients (16.4%) relapsed at the primary site and 14 (25.5%) at systemic sites. The 5-year cumulative incidence of relapse (CIR) at primary sites was 26.3% and 19.2% after SCRT and CCRT/CT (p=0.308), while the 5-year CIR of systemic sites was 8.7% and 26.5% after SCRT and CCRT/CT, respectively (p=0.010). In the multivariate analysis, NK/T-cell Prognostic Index score and CR achievement were the most important prognostic factors for survival. Although up-front RT had limitations in systemic disease control and was associated with an increased risk of systemic relapse during RT compared to SCRT, timing of RT did not significantly affect survival outcomes.

Role of high-dose melphalan with autologous stem cell transplantation in multiple myeloma patients receiving botezomib-containing induction therapy.

To examine the role of high-dose melphalan therapy with autologous stem cell transplantation (HDM/ASCT) in the final outcomes of multiple myeloma (MM) patients receiving bortezomib-containing induction therapy (IT), we analyzed relationships between quality of response after IT including bortezomib or HDM/ASCT and survival. In total, 92 MM patients who received IT with bortezomib followed by HDM/ASCT were enrolled. The median follow-up was 28.0 months. Three-year progression-free survival (PFS) and overall survival (OS) were 41.1 and 72.0 %, respectively. A complete response (CR) after HDM/ASCT was a strong prognostic factor for PFS and OS (p = 0.002 and 0.001, respectively). Additionally, out of 67 patients who failed to achieve CR after IT, 36 (53.7 %) patients achieved CR after HDM/ASCT. PFS and OS in patients with CR after additional HDM/ASCT were similar to those in patients who had already achieved CR after IT. However, achievement of at least very good partial response following IT with bortezomib failed to improve PFS and OS (p = 0.35 and 0.11, respectively). Thus, we conclude that post-HDM/ASCT CR is the best prognostic factor for both PFS and OS regardless of response to bortezomib. Therefore, HDM/ASCT remains an important therapy in MM patients even after introduction of bortezomib IT.

Therapeutic potential of Gastrodia elata Blume for the treatment of Alzheimer's disease.

Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide (Aß)-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer's disease, we established a rat model of Alzheimer's disease by injecting Aß25-35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer's disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while Ellman method showed significant decrease in the activity of acetylcholinesterase in all three regions (prefrontal cortex, medial septum and hippocampus). These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer's disease.

Gastrodia elata Blume and its pure compounds protect BV-2 microglial-derived cell lines against ß-amyloid: the involvement of GRP78 and CHOP.

OBJECTIVES: Gastrodia elata (GE) Blume (Orchidaceae) has been previously known for its therapeutic benefits against neurodegenerative diseases. Microglial activation and death have been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease. In this study, GE and its pure components, gastrodin and 4-hydroxybenzyl alcohol (4HBA), were applied to ß-amyloid-induced BV2 mouse microglial cells. MATERIALS AND METHODS: Cell viability was assessed by the MTT assay and Western blotting was also performed. RESULTS: ß-amyloid-induced cell death was shown to be induced time- and dose-dependently. To examine the cell death mechanism, we confirmed the involvement of ER stress signaling. C/EBP homologous protein (CHOP), a pro-apoptotic ER stress protein, was expressed at high levels but glucose-regulated protein 78 (GRP78), an anti-apoptotic ER stress protein with chaperone activity, was only slightly affected by treatment with ß-amyloid. However, pretreatment with GE and its components inhibited the expression of CHOP but increased that of GRP78 in ß-amyloid-treated cells. This study also showed that a single treatment with GE extracts, gastrodin, or 4HBA induced the expression of GRP78, a marker for enhanced protein folding machinery, suggesting a protective mechanism for GE against ß-amyloid. CONCLUSIONS: This study reveals the protective effects of GE against ß-amyloid-induced cell death, possibly through the enhancement of protein folding machinery of a representative protein, GRP78, and the regulation of CHOP in BV2 mouse microglial cells.