Discovery of aurones bearing two amine functionalities as SHIP2 inhibitors with insulin-sensitizing effect in rat myotubes.

Pharmacological inhibition of the SH2 domain-containing inositol 5-phosphatase 2 (SHIP2) by small-molecule compounds presents an attractive approach to modulate insulin sensitivity. Few drug-like SHIP2 inhibitors have been discovered to date. A series of aurones incorporating key motifs from known SHIP2 inhibitors were synthesized and evaluated for SHIP2-inhibiting activity against a recombinant SHIP2 protein in vitro. Three aurones that inhibited SHIP2 at 15-50 µM were identified. These aurone inhibitors required two amine functionalities, one at ring A and a second at ring B for good inhibitory activity as exemplified by 12a. Mechanistically, molecular dynamics simulations revealed 12a to preferably bind to an allosteric site, restricting the motion of the flexible L4 loop required for SHIP2 phosphatase activity. Additionally, a basic piperidine moiety of 12a interacted with an aspartate residue proximal to the site. At 20-40 µM, 12a significantly enhanced glucose uptake in rat myotubes via increased Akt phosphorylation. 12a showed good permeability across the Caco-2 cell monolayer supporting the aurone chemotype as a new lead to develop drug-like, oral insulin sensitizers.

Assessing the impact of direct-acting antivirals on hepatitis C complications: a systematic review and meta-analysis.

Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.

Development and validation of patient diabetes knowledge questionnaire (PDKQ).

BACKGROUND: Evaluation of diabetes knowledge plays a pivotal role in identifying and addressing patients' knowledge gaps. The implementation of a standardized diabetes knowledge assessment tool is important to ensure consistent scoring and facilitating the development of effective and standardized education programs. AIM: To develop and validate a patient diabetes knowledge questionnaire (PDKQ) to assess knowledge of diabetes mellitus patients. METHODS: The development of the PDKQ questionnaire involved three phases: item development, content validation, and reliability testing. In the item development phase, the initial draft of the PDKQ, comprising a multiple-choice answer questionnaire was developed. The content validation phase comprised two stages. Firstly, ten experts participated in the expert validation process, followed by face validation involving six patients. In the final phase, test-retest analysis was performed among diabetes mellitus patients to assess reliability. RESULTS: The first draft of PDKQ consisted of 11 patient characteristics items and 37 items of multiple choices questions. During the expert validation, three items were eliminated due to low clarity, and an additional six items were removed as they were deemed irrelevant or unimportant. During the face validation, three patients' characteristic items and eight multiple-choice questions were excluded due to a content validity index of less than 0.83. In the test-retest phase, 36 subjects responded to 8 items pertaining to patients' characteristics and 20 multiple-choice questions. The test-retest analysis yielded an intraclass correlation coefficient of 0.88, indicating good reliability. CONCLUSION: The 20-item PDKQ is a reliable and robust tool in assessing the knowledge of diabetes mellitus patients in Malaysia. Its implementation allows standardized assessment of diabetic patients' knowledge levels, enabling targeted interventions to empower patients and optimize diabetes care practices.

The impact of pharmacist interventions, follow-up frequency and default on glycemic control in Diabetes Medication Therapy Adherence Clinic program: a multicenter study in Malaysia.

BACKGROUND: Pharmacist's involvement in optimizing medication adherence among diabetic patients has been implemented for over a decade. Diabetes Medication Therapy Adherence Clinic (DMTAC) was set up to educate diabetic patients, monitor treatment outcomes, and manage drug-related problems. While evidence shows that pharmacist-led DMTAC was effective in reducing HbA1c, there was limited data regarding the impact of different intervention types and default to follow-up on glycemic control. AIM: To assess the impact DMTAC on glycemic control and the difference in glycemic control between hospital and health clinic settings as well as defaulter and non-defaulter. In addition, the impact of pharmacist's interventions, DMTAC follow-up frequencies, and duration of diabetes on glycemic control were also determined. METHODS: A retrospective study was conducted among diabetes patients under DMTAC care between January 2019 and June 2020 in five hospitals and 23 primary health clinics. Patients' demographics data, treatment regimens, frequencies of DMTAC visits, defaulter (absent from DMTAC visits) and types of pharmacists' intervention were retrieved from patients' medical records and electronic database. HbA1c was collected at baseline, 4-6 months (post-1), and 8-12 months (post-2). RESULTS: We included 956 patients, of which 60% were females with a median age of 58.0 (IQR: 5.0) years. Overall, the HbA1c reduced significantly from baseline (median: 10.2, IQR: 3.0) to post-1 (median: 8.8, IQR: 2.7) and post-2 (median: 8.3, IQR: 2.6%) (p < 0.001). There were 4317 pharmacists' interventions performed, with the majority being dosage adjustment (n = 2407, 55.8%), followed by lab investigations (849, 19.7%), drugs addition (653, 15.1%), drugs discontinuation (408, 9.5%). Patients treated in hospitals received significantly more interventions than those treated in primary health clinics (p < 0.001). We observed significantly less reduction in HbA1c in DMTAC follow-up defaulters than non-defaulters after 1 year (- 1.02% vs. - 2.14%, p = 0.001). Frequencies of DMTAC visits (b: 0.19, CI: 0.079-0.302, p = 0.001), number of dosage adjustments (b: 0.83, CI: 0.015-0.151, p = 0.018) and number of additional drugs recommended (b: 0.37, CI: 0.049-0.691, p = 0.024) had positive impact on glycemic control whereas duration of diabetes (b: - 0.0302, CI: - 0.0507, - 0.007, p = 0.011) had negative impact. CONCLUSION: Glycemic control improved significantly and sustained up to one year among patients in pharmacists-led DMTAC. However, DMTAC defaulters experienced poorer glycemic control. Considering more frequent visits and targeted interventions by pharmacists at DMTAC resulted in improved HbA1c control, these strategies should be taken into account for future program planning.

Comparing the efficacy of tocilizumab with corticosteroid therapy in treating COVID-19 patients: a systematic review and meta-analysis.

PURPOSE: Tocilizumab has shown equivocal outcomes in reducing mortality in COVID-19. The corticosteroids appear to be an affordable alternative to tocilizumab. This study aims to estimate the efficacy of tocilizumab and the corticosteroids particularly dexamethasone and methylprednisolone and to identify possible determinants of their efficacy. METHODS: Five electronic databases were searched for studies involving tocilizumab, dexamethasone, and methylprednisolone in treating COVID-19. We included case-control and randomized or partially randomized trials. Meta-regression for patient baseline characteristics, co-medications, and tocilizumab dose regimens was performed to identify contributing factors to drug efficacy. RESULTS: Thirteen randomized controlled trials (RCTs) and twenty-four case-control studies were included in our meta-analysis involving 18,702 patients. Meta-analysis among the RCTs showed that a summary estimate favoring mortality reduction (OR 0.71, 95%CI 0.55 - 0.92) contributed mainly by tocilizumab and dexamethasone. Among case-control studies, meta-analysis showed mortality reduction (OR 0.52, 95%CI 0.36 - 0.75) contributed by tocilizumab and tocilizumab-methylprednisolone combination. Methylprednisolone alone did not reduce mortality except for one study involving high dose pulse therapy. Meta-analysis also found that all three drugs did not significantly reduce mechanical ventilation (OR 0.72, 95%CI 0.32 - 1.60). CONCLUSION: Tocilizumab and dexamethasone emerge as viable options in reducing mortality in severe COVID-19 patients. A tocilizumab-corticosteroid combination strategy may improve therapeutic outcome in cases where single therapy fails.

Systematic Review and Meta-Analysis of Diabetes Knowledge among Type 2 Diabetes Patients in Southeast Asia.

OBJECTIVE: Recognition of patient baseline knowledge is important in educating patients with type 2 diabetes mellitus (T2D) to manage their disease effectively. The purpose of this study is to review current evidence on the level of diabetes knowledge among T2D patients and determine factors affecting their knowledge. METHODS: A systematic search of English language articles published between 1990 and June 2019 was conducted using six electronic databases. Only quantitative studies that assessed knowledge of T2D patients in Southeast Asian countries were included. Data were extracted and a meta-analysis was conducted. RESULTS: A total of 6210 articles were retrieved; seven articles met the inclusion criteria, comprising 1,749 T2D patients. The calculated mean knowledge score was 55.6% (95% CI: 7.6 to 103.6). Five types of assessment tools were identified ranging from five to 41 questions that focused on disease specifics, treatment, and nutrition. Age, education level, and glycemic control were the most common factors impacting knowledge. CONCLUSIONS: The level of knowledge among T2D patients in Southeast Asia was unsatisfactory, especially in older patients with low education levels and poor glycemic control. Hence, an appropriate educational plan should be prioritized to these groups.

Comparing the cost, glycaemic control and medication adherence of utilizing patients' own medicines (POMs) versus usual dispensing among diabetic patients in an outpatient setting.

BACKGROUND: Millions worth of unused drugs particularly those indicated for chronic diseases such as diabetes were returned and disposed leading to substantial wastage. Use of patients' own medications (POMs) in the inpatient setting has reduced wastage and saved cost. The impact of utilizing POMs in the outpatient setting has hitherto not been determined. PURPOSE: This study aims to compare the cost, medication adherence and glycaemic control of utilizing POMs versus usual dispensing. METHODS: Prospective randomized controlled study was conducted among diabetic patients that required monthly medication refill in the Outpatient Pharmacy in 2017. Patients who consented were equally divided into POMs and control groups. Both groups brought excess medications from home at week-0 and week-12. Patients in the POMs group brought excess medications monthly and sufficient amount of drugs were added until the next refill date. Drugs were dispensed as usual in the control group. Total cost consisting of the cost of drugs, staff and building was calculated. Glycosylated haemoglobin (HbA1c) was measured at baseline and week-12. Adherence was measured based on pill counting. RESULTS: Thirty patients aged 56.77 ± 14.67 years with 13.37 ± 7.36 years of diabetes participated. Baseline characteristics were similar between the groups. POMs minimized the total cost by 38.96% which translated to a cost saving of USD 42.76 ± 6.98, significantly different versus USD 0.02 ± 0.52 in the control group, p = 0.025. Mean HbA1c reduced significantly (-0.79%, p = 0.016) in the POMs group but not significant in the control group (-0.11%, p = 0.740). Medication adherence improved significantly in both groups at week-12 (p < 0.010). Nevertheless, patients in the POMs group were more adherent, 87.20% vs. 66.32%, p = 0.034. CONCLUSION: Utilizing POMs resulted in cost saving, improved adherence and better glycaemic control. Use of POMs should be practiced in the outpatient pharmacy to reduce wastage and cost.

Study investigating the impact of pharmacist involvement on the outcomes of diabetes medication therapy adherence program Malaysia.

Involvement of pharmacists in improving medication adherence among diabetic patients is recognized globally. In Malaysian healthcare system, pharmacists are also operating health services i.e. Diabetes Medication Therapy Adherence Clinic (DMTAC). This study aimed to assess the clinical outcomes of patients managed by pharmacists (DMTAC), in a Malaysian hospital setting. This was an open labelled randomised study. Type 2 diabetes patients with HbA1c ≥8% were recruited and arbitrarily divided into the intervention group (usual care plus DMTAC) and the non-intervention group (usual care only). Those enrolled in the intervention group were scheduled for follow-up for eight consecutive visits. Improvements in lab results were compared longitudinally (pre and post analysis) between the groups. Data analysis was done using PASW 18® version. A total of 76 patients were enrolled, with 39 patients in the intervention group and 37 patients in the non-intervention group. Mean HbA1c (-0.90% vs. -0.08%, p=0.011) and fasting blood glucose levels (-3.45 mmol.l vs. +0.79 mmol/l, p=0.002) reduced significantly between the intervention group vs. non-intervention group. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were also significantly reduced in the intervention group (TC -0.34 mmol/l, p=0.018) (LDL -0.45 mmol/l, p=0.001). In conclusion, pharmacists managed DMTAC significantly improved glycaemic control and lipid profile of diabetic patients.

Evaluation of a pharmacist-managed diabetes medication therapy adherence clinic / Evaluación de una clínica farmacéutica para el cumplimiento del tratamiento en diabetes

Patient adherence to prescribed medication regimens is important in diabetes care to prevent or delay microvascular and macrovascular complications such as retinopathy, nephropathy and myocardial infarction. In Penang Hospital, Malaysia, pharmacists collaborate with physicians in diabetes care through a pharmacist-managed Diabetes Medication Therapy Adherence Clinic (DMTAC) in the Endocrine Clinic, in operation since 2006. Objective: To evaluate the effectiveness of the pharmacist-managed DMTAC program in improving glycaemic control, lipid parameters and patients´ medication adherence. Method: A retrospective study among patients enrolled in the DMTAC program was conducted between September 2007 and December 2008. Data was included from patients with a glycosylated haemoglobin (HbA1c) >8% and who had completed eight visits with the pharmacists. Medical records and DMTAC forms that provided patients´ demographics, medication regimens, adherence and laboratory parameters as well as pharmacists´ interventions were reviewed. HbA1c, fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL), triglycerides (TG) and high-density lipoprotein cholesterol (HDL) were evaluated. Documented data of patients´ adherence to medication regimen [Modified Morisky Medication Adherence Score (MMMAS); high adherence if score >8, medium adherence if score 6 to <8 and low adherence if score <6] was also evaluated. Results: A total of 43 patients (53.5% females; 46.5% Malays, 44.2% Chinese and 9.3% Indians) were included in the analysis. A mean reduction in HbA1c of 1.73% (p<0.001), mean reduction in FBG of 2.65mmol/l (p=0.01) and mean reduction in LDL cholesterol of 0.38mmol/l (p=0.007) were achieved. The difference in TG and HDL cholesterol were not significant. Patients´ adherence to medication regimens improved significantly with an increase in the mean MMMAS score from 7.00 to 10.84 (p<0.001) after completion of the DMTAC program. Conclusion: The pharmacist-managed DMTAC program resulted in significant improvements in HbA1c, glucose and LDL cholesterol levels as well as medication adherence in patients with diabetes (AU)

El cumplimiento de la medicación en los pacientes diabéticos es importante para prevenir o retrasar complicaciones micro y macrovasculares tales como retinopatía, neuropatía e infarto de miocardio. En el Hospital de Penang, Malasia, los farmacéuticos colaboran con los médicos en diabetes a través de una clínica farmacéutica para el cumplimiento del tratamiento en diabetes (DMTAC) en la clínica endocrinológica, operando desde 2006. Objetivo: Evaluar la efectividad del programa de la DMTAC en la mejora del control glucémico, de parámetros lipídicos y de cumplimiento de la medicación por los pacientes. Métodos: Entre septiembre 2007 y diciembre 2008 se realizó un estudio retrospectivo entre los pacientes atendidos en el programa de la DMTAC. Se incluyeron datos de pacientes con hemoglobina glicosilada (HbA1c) >8% y que habían completado 8 visitas con el farmacéutico. Se revisaron los historiales médicos y los formularios de la DMTAC que proporcionaron datos demográficos de los pacientes, medicación, cumplimiento y parámetros de laboratorio, así como las intervenciones de los farmacéuticos. La HbA1c, glucemia en ayuno, colesterol de lipoproteínas de baja densidad (LDL), triglicéridos (TG) y colesterol de lipoproteínas de alta densidad (HDL). También se evaluaron los datos de cumplimiento de los pacientes [Modified Morisky Medication Adherence Score (MMMAS); alto cumplimiento si la puntuación >8, cumplimiento medio si puntuación de 6 a 8 y bajo cumplimiento si puntuación <6]. Resultados: Se incluyó en el análisis un total de 43 pacientes (53,5% mujeres; 46.5% Malayos, 44.2% Chinos and 9.3% Indios). Se obtuvo una reducción media de HbA1c de 1,73% (p<0,001), de glucemia de 2,65 mmol/l (p=0,01) y de colesterol LDL de 0.38 mmol/l (p=0,007). La diferencia en TG y colesterol HDL no fue significativa. Después de completar el programa de la DMTAC, el cumplimiento de los pacientes de su medicación mejoró significativamente con un aumento en la puntuación del MMMAS de 7,00 a 10,84 (p<0,001). Conclusión: el programa farmacéutico de la DMTAC produjo mejorías significativas en los niveles de HbA1c, glucosa y colesterol LDL, así como en el cumplimiento de la medicación de los pacientes con diabetes (AU)

Evaluation of a pharmacist-managed diabetes medication therapy adherence clinic.

UNLABELLED: Patient adherence to prescribed medication regimens is important in diabetes care to prevent or delay microvascular and macrovascular complications such as retinopathy, nephropathy and myocardial infarction. In Penang Hospital, Malaysia, pharmacists collaborate with physicians in diabetes care through a pharmacist-managed Diabetes Medication Therapy Adherence Clinic (DMTAC) in the Endocrine Clinic, in operation since 2006. OBJECTIVE: To evaluate the effectiveness of the pharmacist-managed DMTAC program in improving glycaemic control, lipid parameters and patients' medication adherence. METHOD: A retrospective study among patients enrolled in the DMTAC program was conducted between September 2007 and December 2008. Data was included from patients with a glycosylated haemoglobin (HbA1c) >8% and who had completed eight visits with the pharmacists. Medical records and DMTAC forms that provided patients' demographics, medication regimens, adherence and laboratory parameters as well as pharmacists' interventions were reviewed. HbA1c, fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL), triglycerides (TG) and high-density lipoprotein cholesterol (HDL) were evaluated. Documented data of patients' adherence to medication regimen [Modified Morisky Medication Adherence Score (MMMAS); high adherence if score >8, medium adherence if score 6 to <8 and low adherence if score <6] was also evaluated. RESULTS: A total of 43 patients (53.5% females; 46.5% Malays, 44.2% Chinese and 9.3% Indians) were included in the analysis. A mean reduction in HbA1c of 1.73% (p<0.001), mean reduction in FBG of 2.65mmol/l (p=0.01) and mean reduction in LDL cholesterol of 0.38mmol/l (p=0.007) were achieved. The difference in TG and HDL cholesterol were not significant. Patients' adherence to medication regimens improved significantly with an increase in the mean MMMAS score from 7.00 to 10.84 (p<0.001) after completion of the DMTAC program. CONCLUSION: The pharmacist-managed DMTAC program resulted in significant improvements in HbA1c, glucose and LDL cholesterol levels as well as medication adherence in patients with diabetes.