An Awareness of Pharmacovigilance Among Healthcare Professionals Due to an Underreporting of Adverse Drug Reactions Issue: A Systematic Review of the Current State, Obstacles, and Strategy.

BACKGROUND: Healthcare professionals play an essential role in reporting adverse drug reactions as part of pharmacovigilance activities. However, adverse drug reactions reported by healthcare professionals remain low. OBJECTIVE: The aim of this systematic review was to investigate healthcare professionals' knowledge, awareness, attitude, and practice on pharmacovigilance and adverse drug reaction reporting, explore the causes of the underreporting issue, and provide improvement strategies. METHODS: This systematic review was conducted using four electronic databases for original papers, including PubMed, Scopus, Google Scholar, and Scholar ID. Recent publications from 1st January 2012 to 31st December 2022 were selected. The following terms were used in the search: "awareness", "knowledge", "adverse drug reaction", "pharmacovigilance", "healthcare professional", and "underreporting factor". Articles were chosen, extracted, and reviewed by the two authors. RESULTS: Twenty-five studies were selected for systematic review. This review found that 24.8%-73.33% of healthcare professionals were unaware of the National Pharmacovigilance Center. Around 20%-95.7% of healthcare professionals have a positive attitude toward pharmacovigilance and adverse drug reaction reporting, while 12%-60.8% of healthcare professionals have experience reporting any adverse drug reaction in their practice. The most frequently highlighted barriers to pharmacovigilance were a lack of awareness and knowledge regarding what, when, and to whom to report. CONCLUSION: Underreporting issues require immediate attention among healthcare professionals due to a lack of awareness and knowledge of pharmacovigilance and adverse drug reaction reporting. Educational and training program interventions have been suggested by most studies to address these issues.

Influence of genetic polymorphisms on pharmacokinetics and treatment response of mycophenolic acid: a scoping review.

This scoping review explores the impact of genetic polymorphisms on the pharmacokinetics and treatment responses of mycophenolic acid (MPA), an immunosuppressant. The study includes 83 articles from 1226 original studies, focusing on transplantation (n = 80) and autoimmune disorders (n = 3). Genetic variants in uridine 5'-diphospho-glucuronosyltransferase (UGT1A9, UGT1A8 and UGT2B7) and transmembrane transporters (ABCC2, SLCO1B1, SLCO1B3 and ABCB1) significantly affected MPA's pharmacokinetics and susceptibility to its adverse effect. Whereas variants in several genes including UGT1A9, UGT2B7, IMPDH1 and IMPDH2 have been associated with a higher risk of transplant rejection. However, there is a lack of studies on MPA's impact on autoimmune disorders and limited research on the Asian population. The findings underscore the need for further research on MPA's impact across different populations and diseases, particularly among other Asian ethnic groups, to advance personalized medicine in MPA therapy.

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The Role of Pharmacists' Interventions in Increasing Medication Adherence of Patients With Epilepsy: A Scoping Review.

OBJECTIVES: Epilepsy is a chronic disease that requires long-term treatment and intervention from health workers. Medication adherence is a factor that influences the success of therapy for patients with epilepsy. Therefore, this study aimed to analyze the role of pharmacists in improving the clinical outcomes of epilepsy patients, focusing on medication adherence. METHODS: A scoping literature search was conducted through the ScienceDirect, PubMed, and Google Scholar databases. The literature search included all original articles published in English until August 2023 for which the full text was available. This scoping review was carried out by a team consisting of pharmacists and neurologists following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews and the Joanna Briggs Institute guidelines, including 5 steps: identifying research questions, finding relevant articles, selecting articles, presenting data, and compiling the results. RESULTS: The literature search yielded 10 studies that discussed pharmacist interventions for patients with epilepsy. Five articles described educational interventions involving drug-related counseling with pharmacists. Two articles focused on similar pharmacist interventions through patient education, both verbal and written. Three articles discussed an epilepsy review service, a multidisciplinary intervention program involving pharmacists and other health workers, and a mixed intervention combining education and training with therapy-based behavioral interventions. CONCLUSIONS: Pharmacist interventions have been shown to be effective in improving medication adherence in patients with epilepsy. Furthermore, these interventions play a crucial role in improving other therapeutic outcomes, including patients' knowledge of self-management, perceptions of illness, the efficacy of antiepileptic drugs in controlling seizures, and overall quality of life.

Development of White Cabbage, Coffee, and Red Onion Extracts as Natural Phosphodiesterase-4B (PDE4B) Inhibitors for Cognitive Dysfunction: In Vitro and In Silico Studies.

Human cognition fundamentally depends on memory. Alzheimer's disease exhibits a strong correlation with a decline in this factor. Phosphodiesterase-4 B (PDE4B) plays a crucial role in neurodegenerative disorders, and its inhibition is one of the promising approaches for memory enhancement. This study aimed to identify secondary metabolites in white cabbage, coffee, and red onion extracts and identify their molecular interaction with PDE4B by in silico and in vitro experiments. Crushed white cabbage and red onion were macerated separately with ethanol to yield respective extracts, and ground coffee was boiled with water to produce aqueous extract. Thin layer chromatography (TLC)-densitometry was used to examine the phytochemicals present in white cabbage, coffee, and red onion extracts. Molecular docking studies were performed to know the interaction of test compounds with PDE4B. TLC-densitometry analysis showed that chlorogenic acid and quercetin were detected as major compounds in coffee and red onion extracts, respectively. In silico studies revealed that alpha-tocopherol (binding free energy (∆Gbind) = -38.00 kcal/mol) has the strongest interaction with PDE4B whereas chlorogenic acid (∆Gbind = -21.50 kcal/mol) and quercetin (∆Gbind = -17.25 kcal/mol) exhibited moderate interaction. In vitro assay showed that the combination extracts (cabbage, coffee, and red onion) had a stronger activity (half-maximal inhibitory concentration (IC50) = 0.12 ± 0.03 µM) than combination standards (sinigrin, chlorogenic acid, and quercetin) (IC50 = 0.17 ± 0.03 µM) and rolipram (IC50 = 0.15 ± 0.008 µM). Thus, the combination extracts are a promising cognitive enhancer by blocking PDE4B activity.

Effect of Mobile Health Applications on Improving Self-Management Knowledge and Seizure Control in Epilepsy Patients: A Scoping Review.

OBJECTIVES: Mobile health app-based interventions are increasingly being developed to support chronic disease management, particularly for epilepsy patients. These interventions focus on managing stress, monitoring drug side effects, providing education, and promoting adherence to medication regimens. Therefore, this scoping review aims to assess how mobile health applications improve epilepsy patients' knowledge and seizure control, and to identify the features of these apps that are frequently used and have proven to be beneficial. METHODS: This scoping review was conducted using scientific databases such as ScienceDirect, PubMed, and Google Scholar, adhering to the Joanna Briggs Institute guidelines. The review framework consisted of five steps: identifying research questions, finding relevant articles, selecting articles, presenting data, and compiling the results. The literature search included all original articles published in English from 2013 to 2023. RESULTS: Among six articles that discussed mobile applications for epilepsy patients, all featured similar functionalities, including education on epilepsy management and seizure monitoring. Four of the articles highlighted behavioral interventions, such as reminder systems, designed to improve medication adherence. The remaining two articles focused on a side-effect reporting system that enabled doctors or health workers to evaluate and regularly monitor adverse effects. CONCLUSIONS: This scoping review reveals that mobile health applications employing a combination of educational and behavioral interventions for epilepsy patients significantly improve knowledge about patient self-management and medication adherence. These interventions can prevent seizures, increase awareness, enable better activity planning, improve safety, and reduce the frequency of seizures and side effects of antiepileptic drugs.

The efficient use of smartphone apps to improve the level of asthma knowledge.

Patient education is one of the important aspects of improving knowledge and quality of asthma control. In this digital era, it can be made with the support of an app - or known as mHealth. Unfortunately, implementing applications for patient education is relatively new among asthmatic patients in Indonesia. This study aimed to determine the efficacy of the educational content of the AsmaDroid® app on the levels of asthma knowledge among asthmatic patients. This study was a randomized controlled trial carried out from December 2019 to March 2020 in the Special Region of Yogyakarta, Indonesia. A quota sampling was employed, resulting in 140 study participants being categorized into control and treatment groups. Before and after the 4-week treatment period, all participants were asked to complete a pre-test and post-test of the Asthma General Knowledge Questionnaire for Adults (AGKQA) questionnaire. All the scores were then compared to determine the efficacy of educational content on the levels of asthma knowledge. The results of descriptive statistics reported that the pretest scores of AGKQA from the control group (minimum, maximum, and mean) were 9, 25, and 19.04±2.56, respectively, and post-test scores were 10, 27, and 18.79±3.59 (p=0.47). Meanwhile, in the treatment group, these were 13, 25, and 19.11±2.87, while post-test scores were 16, 31, 23.6±3.95 (p=0.01). Additionally, there was a difference between the post-test scores of the control and treatment groups, namely 4.81 (p=0.01). The educational content of the app significantly improved the levels of asthma knowledge.

The influence of metformin transporter gene SLC22A1 and SLC47A1 variants on steady-state pharmacokinetics and glycemic response.

Interindividual variation is important in the response to metformin as the first-line therapy for type-2 diabetes mellitus (T2DM). Considering that OCT1 and MATE1 transporters determine the metformin pharmacokinetics, this study aimed to investigate the influence of SLC22A1 and SLC47A1 variants on the steady-state pharmacokinetics of metformin and the glycemic response. This research used the prospective-cohort study design for 81 patients with T2DM who received 500 mg metformin twice a day from six primary healthcare centers. SLC22A1 rs628031 A>G (Met408Val) and Met420del genetic variants in OCT1 as well as SLC47A1 rs2289669 G>A genetic variant in MATE1 were examined through the PCR-RFLP method. The bioanalysis of plasma metformin was performed in the validated reversed-phase HPLC-UV detector. The metformin steady-state concentration was measured for the trough concentration (Cssmin) and peak concentration (Cssmax). The pharmacodynamic parameters of metformin use were the fasting blood glucose (FBG) and glycated albumin (GA). Only SLC22A1 Met420del alongside estimated-glomerular filtration rate (eGFR) affected both Cssmax and Cssmin with an extremely weak correlation. Meanwhile, SLC47A1 rs2289669 and FBG were correlated. This study also found that there was no correlation between the three SNPs studied and GA, so only eGFR and Cssmax influenced GA. The average Cssmax in patients with the G allele of SLC22A1 Met408Val, reaching 1.35-fold higher than those with the A allele, requires further studies with regard to metformin safe dose in order to avoid exceeding the recommended therapeutic range.

The role of Phosphodiesterase-1 and its natural product inhibitors in Alzheimer's disease: A review.

Phosphodiesterase-1 (PDE1) is a versatile enzyme that has surprisingly received considerable attention as a possible therapeutic target in Alzheimer's disease (AD) because it maintains the homeostasis of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) in the brain. 3',5'-cyclic adenosine monophosphate and 3',5'-cyclic guanosine monophosphate are the two key second messengers that regulate a broad range of intracellular processes and neurocognitive functions, specifically memory and cognition, associated with Alzheimer's disease. However, the lack of available selective drugs on the market poses challenges to identifying the beneficial effects of natural products. The present review focuses on Phosphodiesterase-1 and its isoforms, splicing variants, location, distribution, and function; the role of Phosphodiesterase-1 inhibitors in Alzheimer's disease; and the use of vinpocetine and natural products as specific Phosphodiesterase-1 inhibitors. Moreover, it aims to provide ongoing updates, identify research gaps, and present future perspectives. This review indicates the potential role of Phosphodiesterase-1 inhibitors in the treatment of neurodegenerative disorders, such as Alzheimer's disease. Certain clinical trials on the alleviation of Alzheimer's disease in patients are still in progress. Among de novo outcomes, the employment of Phosphodiesterase-1 inhibitors to treat Alzheimer's disease is an important advancement given the absence of particular therapies in the pipeline for this highly prevalent disease. To sum up, Phosphodiesterase-1 inhibition has been specifically proposed as a critical therapeutic approach for Alzheimer's disease. This study provides a comprehensive review on the biological and pharmacological aspects of Phosphodiesterase-1, its role on the Alzheimer's diseases and its significance as Alzheimer's disease therapeutic target in drug discovery from natural products. This review will help clinical trials and scientific research exploring new entities for the treatment and prevention of Alzheimer's disease.

Asthma self-management app for Indonesian asthmatics: A patient-centered design.

BACKGROUND: A proper education on asthma self-management helps asthmatics to improve health outcomes, such as better asthma knowledge and self-efficacy, increased frequency of symptom-free days, reduced unscheduled healthcare visits and absence from school or work days. In this modern digital era, the use of smartphone apps is increasing rapidly and reaching almost all aspects of our life, including health promotion and patient education on asthma self-management. Studies found that the apps make it easier for asthmatics to receive the education. OBJECTIVE: The aim of this study was to describe the systematic design, development, and implementation process of a Google Android OS asthma self-management smartphone app according to the Patient-Centered Design approach. METHODS: The design, development, and implementation process of the app adopted the Patient-Centered Design approach, including: (1) user needs assessment, (2) design of the app prototype, (3) development of the app prototype, (4) usability test, and (5) product launch. For better results, the study involved end-users (asthmatics and health professionals) during the development of the app. RESULTS: The study resulted in a Google Android OS asthma self-management app, namely AsmaDroid. The app was developed to feature 8 contents and functions, namely: asthma education, a list of asthma medications, asthma diary or journal, peak flow record, asthma control test, asthma action plan, a chat box, and a map of nearest local hospitals or health centers. It was also found that the average success rate of the app was as follow: "completed with ease" was 88.15%, "completed with difficulty" was 7.78%, and "failed to complete" was 4.07%. It means that the success rate of app was "very high". CONCLUSION: The implementation of Patient-Centered Design approach has been successfully completed for the development of AsmaDroid. However, additional research into the use of the app in the actual clinical world is highly required to demonstrate its effectiveness in improving the level of asthma knowledge, the quality of asthma control, and other health outcomes.

Patient-factors associated with metformin steady-state levels in type 2 diabetes mellitus with therapeutic dosage.

AIMS: This prospective study aimed to analyze metformin steady-state concentration in repeated constant dosage and the influencing patient-factors as well as to correlate them with glycemic control. METHODS: The validated HPLC-UV method was used to examine metformin steady-state concentration, while FBG and glycated albumin were used as the parameters of glycemic control during metformin administration. RESULTS: A total of 82 type-2 diabetes patients were involved with 32.1% of them having metformin Cssmin and 84.1% having Cssmax of metformin within the recommended therapeutic range. One patient had metformin Css that exceeded minimum toxic concentration despite his normal renal function and administered therapeutic dosage of metformin. Higher Cssmax was found in patients with metformin monotherapy, while patients with longer duration of metformin use had significantly higher Cssmin. CONCLUSIONS: Along with initial hyperglycemia and eGFR, metformin Cssmin became the only parameter that influenced FBG level (P < 0.05). Duration of previous metformin use should be considered in the strategy of optimizing metformin dosage. The type-2 diabetes patients with obesity are more suggested to take shorter interval of metformin administration (or possibly with sustained-release formulation) to keep Cssmin within the therapeutic range.

The importance of ARG513 as a hydrogen bond anchor to discover COX-2 inhibitors in a virtual screening campaign.

Structure-based virtual screening (SBVS) protocols were developed to find cyclooxygenase-2 (COX-2) inhibitors using the Protein-Ligand ANT System (PLANTS) docking software. The directory of useful decoys (DUD) dataset for COX-2 was used to retrospectively validate the protocols; the DUD consists of 426 known inhibitors in 13289 decoys. Based on criteria used in the article describing DUD datasets, the default protocol showed poor results. However, having ARG513 as a hydrogen bond anchor increased the quality of the SBVS protocol. The modified protocol showed results that could be well considered, with a maximum enrichment factor (EF(max)) value of 32.2.

Effects of benzylidenecyclopentanone analogues of curcumin on histamine release from mast cells.

Curcumin reportedly has anti-allergic effects and can inhibit the release of histamine from mast cells. In the present study, fourteen benzylidenecyclopentanone analogues of curcumin were studied for their effects on histamine release from rat basophilic leukemia (RBL-2H3) cells. After screening, four selected compounds: 2,5-bis(4-hydroxybenzylidene)cyclopentanone; 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone; 2,5-bis(4-hydroxy-3,5-dimethylbenzylidene) cyclopentanone; and 2,5-bis(4-hydroxy-3,5-diethylbenzylidene)cyclopentanone were studied for their concentration-dependent effects on histamine release and Ca(2+) uptake. In RBL-2H3 cells and rat peritoneal mast cells stimulated with antigen or compound 48/80, respectively, the methoxy-hydroxy analogue was more potent than curcumin in inhibiting histamine release. In contrast, the inhibitory effects of methyl/ethyl analogues were less potent than those of curcumin. Moreover, these compounds abrogated histamine release induced by increased intracellular Ca(2+) concentrations in response to stimulants such as thapsigargin and ionomycin. These compounds also showed potent inhibitory effects on (45)Ca(2+) uptake in RBL-2H3 cells. The mechanism of the inhibitory effects of these curcumin analogues on histamine release appeared to be related to blockade of Ca(2+) signaling events. These results provide useful information to guide the development of new synthetic compounds for the treatment of allergic and inflammatory diseases related to histamine or mast cells.