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Brolucizumab (Beovu) for Age-Related Macular Degeneration
Prucalopride (Motegrity) for Chronic Idiopathic Constipation
Design, synthesis and preliminary bioactivity studies of indomethacin derivatives as Bcl-2/Mcl-1 dual inhibitors
Publication date: 1 July 2019
Source: Bioorganic & Medicinal Chemistry, Volume 27, Issue 13
Author(s): Chen Chen, Yiming Nie, Guangsen Xu, Xinying Yang, Hao Fang, Xuben Hou
Abstract
Bcl-2 family proteins, which divides into pro-apoptosis proteins and anti-apoptosis proteins, are involved in cell apoptosis progression. As numerous studies illustrated, targeting Bcl-2 family proteins is more and more attractive and practicable to cancer treatment. In this work, we designed and synthesized a series of indomethacin derivatives as new inhibitors for Bcl-2 family proteins. Our results of binding assay to Bcl-2 proteins, MTT assay and apoptotic assay indicated that some compounds had potent binding affinity to Bcl-2/Mcl-1 but not Bcl-XL. Furthermore, compound 8j showed improved anti-proliferative activity than known Bcl-2 inhibitor WL-276.
Graphical abstract

Evaluation of patient satisfaction and experience towards pharmacist-administered vaccination services in Western Australia
Abstract
Background Pharmacist-administered vaccination services have been available in various countries for several years. In 2014, Western Australian (WA) legislation was introduced to allow pharmacist immunisers to administer the influenza vaccine to consumers 18 years and older. Objective To determine consumer satisfaction with pharmacist-administered influenza vaccination services in WA and identify factors associated with opinions to extend the service to include other vaccines. Setting Thirteen WA community pharmacies. Method In 2015, 133 pharmacies in WA offered pharmacist-administered influenza vaccinations. Of the 133 pharmacies, a purposive sample of 10% (13) were invited to participate in this 2016 study. Following vaccination, consumers were given a questionnaire and asked to evaluate the service and if they would support expansion of the service to include other vaccinations. Main outcome measure Consumer satisfaction with aspects of the service using a 5-point Likert scale. Results A total of 434 (66.8%) questionnaires were completed at the 13 pharmacies and returned. The majority of consumers (99.5%) were satisfied with the service overall, and 97.2% advised they would receive a vaccination from a community pharmacist in the future. Over 60% would like vaccinations to expand to other conditions. Women and those who would again have their influenza vaccine from the pharmacist were particularly supportive of this expansion. Conclusion Consumer satisfaction with pharmacist-administered vaccinations was high. Consumers found the service convenient, comfortable and professional. The majority of respondents supported expansion of pharmacist-administered vaccination services to a wider range of vaccines.
Signal detection of benzodiazepine use and risk of dementia: sequence symmetry analysis using South Korean national healthcare database
Abstract
Background Benzodiazepine use can potentially cause confusion and delays in mental processes. These well-known side effects appear to be linked to an increased risk of being diagnosed with dementia. Objective To evaluate the possibility of an association between benzodiazepine and dementia. Setting Korean healthcare database from 2002 to 2013. Methods Sequence symmetry analysis was conducted to investigate whether benzodiazepine use increases the risk of dementia or not. We defined exposure as new benzodiazepine users and outcome as new diagnosis of dementia (ICD-10: F00-03, G30, and G318). Benzodiazepines were categorized into two groups (long-acting and short-acting) based on the duration of action. Antidepressants, opioid analgesic, and statin were used as active comparators to rule out any possible non-causal interpretations of our results. The time-trend adjusted sequence ratio (ASR) with 95% confidence intervals (CI) was measured to identify possible associations. Main outcome measure Adjusted sequence ratio. Results Benzodiazepine users were shown to be associated with dementia [benzodiazepine: 4212 pairs, ASR = 2.27 (95% CI 2.11–2.44)]. In addition, long-acting benzodiazepines had a higher ASR than that of short-acting benzodiazepines [long-acting: 3972 pairs, ASR = 2.22 (95% CI 2.06–2.39] and [short-acting: 5213 pairs, ASR = 1.88 (95% CI 1.77–2.00)]. However, our SSA found no duration-response relationship. Conclusion Our signal detection suggests that there is a possible association between benzodiazepines and dementia. Additionally, it proposes that persons receiving long-acting benzodiazepines are at a higher risk of developing dementia than those receiving short-acting benzodiazepines. Further studies are recommended to confirm whether this epidemiological association is a causal effect or not.


