Integrating design thinking and implementation science principles in delivering a medication review service in the community pharmacy setting-An implementation testing study.

BACKGROUND: Medication review (MR) services are evidenced-based practices in which a systematic assessment of a patient's medication is conducted, primarily aiming to optimize drug therapy and minimize adverse drug events through pharmacist interventions. Although studies show that MR services are effective, the implementation of MR services in Malaysia has been challenging due to several barriers. An MR services blueprint was developed to be adapted to the Malaysian community pharmacy setting as part of tailoring strategies. OBJECTIVE: Through utilizing the design thinking triple diamond model and implementation science principles, a powerful guide for healthcare researchers and stakeholders to assist with effective service implementation, this study aimed to evaluate the implementation testing and observe the effectiveness of the developed MR service blueprint. METHOD: The study utilizes an effectiveness-implementation Type 3 hybrid implementation science framework conducted from May 2021 to April 2022. Employing a qualitative ethnographic approach, researchers observed pharmacy study sites during the implementation of MR services. Both qualitative and quantitative data were collected across exploration, preparation, testing, and operational phases. Implementation outcomes evaluated include phases, reach, fidelity, acceptability, as well as implementation barriers and strategies. MR intervention outcomes included service characteristics and the number and type of drug-related problems and interventions offered. RESULTS: 17 community pharmacists were invited to pilot the MR service blueprint for six months in their setting. Of this, 78.5% (n = 11) of the pharmacies reached the testing phase, and 36% (n = 4) reached the implementation phase. Fifty-four patients were in the study, giving an implementation reach of 70%. The majority of surveyed patients expressed satisfaction with the service. The total DRP identified was 133, and 64 interventions were provided by the pharmacists. Facilitation strategies such as "Engage stakeholders by creating ownership of the change" and "Equip stakeholders with training" are needed to overcome the barriers. CONCLUSION: This study marked the beginning of successful MR service implementation at Malaysian community pharmacies. Future studies with multi-level partnered strategies are required to reach full implementation and sustainability.

Prevalence, Risk Factors, and Management of Metabolic Acidosis in Chronic Kidney Disease Patients: A Multicenter Retrospective Study in Malaysia.

Background Metabolic acidosis in chronic kidney disease (CKD) patients has lately gained attention due to the growing evidence of its treatment benefits. This study aims to provide baseline data on the prevalence, risk factors, and current management of metabolic acidosis among the pre-dialysis adult Malaysian CKD population. Methodology This multicenter cross-sectional retrospective study involved pre-dialysis CKD patients above 18 years old on regular nephrology clinic follow-up at three Malaysian government hospitals with nephrology subspecialty. Demographic data, clinical information, laboratory data, and a list of concomitant medications were collected. Factors associated with the occurrence of metabolic acidosis were identified via multiple logistic regression. Results Six hundred and fifty-seven CKD patients were screened for this study, in which only 39.4% (n=259) had available bicarbonate levels. From this, a total of 86.1% (n=223) had metabolic acidosis. Higher estimated glomerular filtration rate (odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-1.00, p=0.043) and those with cardiovascular disease (OR 0.33, 95% CI 0.15-0.73; p=0.007) were significantly associated with lower odds of metabolic acidosis. There were 43.0% (n=96) on alkali therapy with sodium bicarbonate solution being the most common (n=91, 94.8%). Among those receiving alkali therapy, only 19.8% (n=19) achieved bicarbonate levels of ≥ 22 mEq/L. Conclusion Our study showed that metabolic acidosis was highly prevalent, although few achieved target levels despite supplementation, supporting the need for focused management of metabolic acidosis in the CKD population.

The Impact of ABCC2 -24C>T Gene Polymorphism on Graft Survival in Kidney Transplant Recipients.

Personalized medicine in kidney transplantation has the potential to improve outcomes and reduce complications. The aim of this study was to investigate the influence of single nucleotide polymorphisms in genes encoding metabolizing enzymes (CYP3A5) and transporters (ABCC2) on clinical outcomes (acute graft failure and/or acute tubular necrosis (ATN)) in kidney transplant recipients (KTR). This was a multicenter, retrospective cohort study where adult KTR who had undergone kidney transplantation between 2020 and 2021 and received tacrolimus-mycophenolate treatment were enrolled in the study. DNA was extracted from collected blood samples using a commercially available kit. CYP3A5*3, ABCC2 -24C>T and ABCC2 3972C>T SNP were determined by polymerase chain reaction. Of the total 39 patients included, nine (23.1%) KTR had an incidence of acute graft failure and/or ATN. A multiple logistic regression showed wildtype ABCC2 -24C>T C allele had a higher risk of developing acute graft rejection and/or ATN compared to the variant allele carriers (adjusted Odd Ratios [aOR]: 27.675, p = 0.038). Recipients who had delayed graft function (aOR: 49.214, p = 0.012) and a history of CMV infection (aOR: 18.097, p = 0.009) were at 49.2 and 18.1-times increased risk for acute graft failure and/or ATN, respectively. The large aOR was inevitable due to the small sample size and required cautious interpretation. This is the first study to determine the effect of the ABCC2 -24C>T genetic polymorphism on clinical outcomes in Malaysian KTR and forms the basis for further work on ABCC2 -24C>T effects in long-term KTR.

Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study.

OBJECTIVES: Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption. METHODS: We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant. RESULTS: Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%). CONCLUSION: Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.

Understanding methiopropamine, a new psychoactive substance: an in-depth review on its chemistry, pharmacology and implications to human health.

Methiopropamine or 1-(thiophen-2-yl)-2-methylaminopropane (MPA) is a thiophene ring-based structural analogue of methamphetamine, first synthesized in 1942 but become popular when it started to be available for purchase on websites selling 'legal highs' since 2010. While it is legally controlled in many countries, it remains readily accessible and frequently encountered in recreational settings. The growing prevalence of MPA use results in new therapeutic challenges. Relatively few studies have focused on its pharmacodynamics and pharmacokinetics, making it important to better understand its potential risks and harmful effects in humans in terms of its toxicity. This review provides a comprehensive profiling of MPA toxicological properties, including its chemical properties, analytical methods, prevalence, patterns of use, and legal status. Additionally, it discusses the drug's effects on the central nervous system, its potential for addiction, and its adverse physical and mental health effects. Improving the understanding of safety aspects of MPA and how it imposes health threats for public health will guide the development of therapeutic approach of its intoxication and guide the authorities in deciding its legal status.

Health-related quality of life in osteoporosis: a systematic review of measurement properties of the QUALEFFO-41.

The 41-item Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) is a widely used and freely available patient-reported outcome measure (PROM). However, data on its reliability, validity, and responsiveness remain unclear. Therefore, this study aimed to systematically review the measurement properties of the QUALEFFO-41. A systematic search of MEDLINE, EBSCOhost, and Cochrane Library from their inception up to December 2022 was performed. Data were extracted, and the methodological quality of each measurement property was evaluated according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. The evidence of the measurement properties was rated against the updated criteria for good measurement properties, and the quality of evidence was graded using the modified GRADE approach. A total of 99 articles were identified, of which eight studies were included in the review. The QUALEFFO-41 is categorized as B as it demonstrated moderate quality evidence for sufficient content validity, moderate-to-high quality evidence for sufficient hypothesis testing for construct validity (except for the social function domain for convergent validity), and very low-quality evidence for sufficient responsiveness. For structural validity and internal consistency, only the domains of pain and general health perception were sufficient with low-quality evidence. For reliability, only the domain of physical function was sufficient with low-quality evidence. None of the studies reported measurement error, cross-cultural validity, and criterion validity. The QUALEFFO-41 may be a promising, valid, and reliable PROM to assess HRQoL in osteoporosis patients with vertebral fractures. However, future studies must focus on good methodological quality to strengthen the evidence of measurement properties, especially on structural validity, reliability, responsiveness, and cross-cultural validity. The systematic review evaluated the measurement properties of the QUALEFFO-41 questionnaire for assessing Health-Related Quality of Life (HRQoL) in osteoporosis patients. The review found moderate-to-high-quality evidence for construct validity but limited evidence for responsiveness and other properties. Future studies should focus on strengthening the evidence, particularly for structural validity, reliability, responsiveness, and cross-cultural validity. The QUALEFFO-41 shows promise as a valid and reliable PROM for HRQoL assessment in osteoporosis patients.

Digital Health in Enhancing Antiretroviral Therapy Adherence: A Systematic Review and Meta-Analysis.

Adherence to antiretroviral therapy (ART) is essential in determining successful treatment of human immunodeficiency virus (HIV). The adoption of digital health is suggested to improve ART adherence among people living with HIV (PLHIV). This study aimed to systematically determine the effect of digital health in enhancing ART adherence among PLHIV from published studies. The systematic search was conducted on Scopus, Web of Science (WoS), PubMed, Ovid, EBSCOHost, and Google Scholar databases up to June 2022. Studies utilized any digital health as an intervention for ART adherence enhancement and ART adherence status as study's outcome was included. Digital health refers to the use of information and communication technologies to improve health. Quality assessment and data analysis were carried out using Review Manager (RevMan) version 5.4. A random-effects model computed the pooled odds ratio between intervention and control groups. The search produced a total of 1864 articles. Eleven articles were eligible for analysis. Digital health was used as follows: six studies used short message service or text message alone, three studies used mobile applications, and two studies used combination method. Four studies showed statistically significant impacts of digital health on ART adherence, while seven studies reported insignificant results. Results showed studies conducted using combination approach of digital health produced more promising outcome in ART adherence compared to single approach. New innovative in combination ways is required to address potential benefits of digital health in promoting ART adherence among PLHIV.

Budget impact of increasing uptake of denosumab for the treatment of postmenopausal osteoporosis in Malaysia.

This study evaluated the financial impact of increasing denosumab usage for managing postmenopausal osteoporosis over a 5-year period from the Malaysian healthcare provider's perspective. A gradual moderate increase in denosumab uptake would have a minimal budget impact, with potential savings in fracture treatment expenses. Optimizing denosumab usage could be a cost-effective and potentially affordable strategy to alleviate the economic burden of osteoporosis in Malaysia. PURPOSE: The study aimed to evaluate the budget impact of increasing the uptake of denosumab for the management of postmenopausal osteoporosis in Malaysia. METHODS: A Markov budget impact model was developed to estimate the financial impact of osteoporosis treatment. We modelled a scenario in which the uptake of denosumab would increase each year compared with a static scenario. A 5-year time horizon from the perspective of a Malaysian MOH healthcare provider was used. Model inputs were based on Malaysian sources where available. Sensitivity analyses were performed to examine the robustness of the modelled results. RESULTS: An increase in denosumab uptake of 8% per year over a 5-year time horizon would result in an additional budget impact, from MYR 0.26 million (USD 0.06 million) in the first year to MYR 3.25 million (USD 0.78 million) in the fifth year. When expressed as cost per-member-per-month (PMPM), these were less than MYR 0.01 across all five years of treatment. In sensitivity analyses, the acquisition cost of denosumab and medication persistence had the largest impact on the budget. CONCLUSION: From the perspective of a Malaysian MOH healthcare provider, moderately increasing uptake of denosumab would have a minimal additional budget impact, partially offset by savings in fracture treatment costs. Increasing the use of denosumab appears affordable to reduce the economic burden of osteoporosis in Malaysia.

Clinical impact of multidisciplinary carbapenem stewardship interventions: a retrospective cohort study.

BACKGROUND: Antimicrobial stewardship (AMS) program aims to optimise antimicrobial utilisation and curb antimicrobial resistance. We investigated the clinical impact of AMS among patients with carbapenem in medical wards of a tertiary hospital. METHODS: A retrospective cohort study was conducted on hospitalised adult patients treated with carbapenem and reviewed by a multidisciplinary AMS team. We compared the clinical outcomes of accepted (n = 103) and not-accepted AMS intervention cases (n = 37). The outcomes evaluated include trends of total white blood cells (TWBC), C-reactive protein (CRP), body temperature at day-7, and clinical status at day-30 post-AMS intervention. RESULTS: The interventions included discontinuation (50%), de-escalation (47.9%) and escalation (2.1%) of antibiotics, where the acceptance rate was 67.1%, 80.6% and 66.7%, respectively. Overall, we found no significant difference in clinical outcomes between accepted and not-accepted AMS interventions at day-7 and day-30 post-interventions. On day-7, 62.0% of patients in the accepted group showed decreased or normalised TWBC and CRP levels compared to 47.4% of the not-accepted group (p = 0.271). The mortality at day-30 (32% versus 35%, p = 0.73), discharge rate (53.4% versus 45.9%, p = 0.437), and median length of hospital stay (36.0 versus 30.0 days, p = 0.526) between the groups were comparable. The predictors of 30-day mortality in the study subjects were Charlson Comorbidity Index > 3 (OR: 2.84, 95% CI 1.28-6.29, p = 0.010) and being febrile at day-7 (OR: 4.58, 95% CI 1.83-11.5, p = 0.001). CONCLUSION: AMS interventions do not result in significant adverse clinical impact and mortality risk.

Publics' Knowledge, Perception and Practice on Management of Minor Ailment in Community Pharmacy in Malaysia.

Introduction: Minor ailments can be defined as medical conditions that can be self-diagnosed, resolve on their own, and be self-managed with over-the-counter (OTC) medications. Nevertheless, minor ailment management was reported to consume much of the health care resources, which may burden the health care system as it increases patient waiting times and the doctors' workload. Purpose: To evaluate the publics' knowledge, perceptions, and practice on the management of minor ailments in community pharmacies in Malaysia and factors that may influence it. Methods: A cross-sectional, self-administered survey was conducted between Dec 2020 and April 2021 among general population in Malaysia. The self-developed and validated survey form consisted of four sections included respondents' demographics, knowledge, perceptions and practices toward minor aliment management in community pharmacy and was distributed using Google Forms via social media platforms. Factors influencing good public practices and perceptions were modeled using binary logistic regression. Results: A total of 562 respondents completed the survey. Majority (n = 354, 63.0%) have good knowledge (score of 9-10), good practice (n = 367, 65.3%) (score 18-30) and good perception score (n = 305, 54.3%) (score 41-60). Variables such as age, those with higher degree (master/PhD), and prior experience and frequency of using community pharmacy had significant influence on respondents' good perceptions, while age and frequency of visit were found to influence respondents' good practice on minor ailment management in community pharmacy. Conclusion: Public in Malaysia have good knowledge on management of minor ailments by community pharmacies. Nevertheless, the publics' perceptions and practice need to be further improved. More advocacy on community pharmacy's roles on minor ailment management among public is need to strengthen the Malaysia's healthcare system resources.

Effects of MDR1 and OPRM1 genetic polymorphisms on the pharmacodynamics of propofol-remifentanil TIVA in pediatrics.

Aims: To investigate the roles of MDR1 (1236C>T, 2677G>T/A, and 3435C>T) and OPRM1 (118A>G) gene polymorphisms on the anesthetic and adverse effects of propofol-remifentanil total intravenous anesthesia in pediatric surgery. Materials & methods: The genotypes were identified through Sanger sequencing. The clinical data including hemodynamics on anesthesia, postanesthesia pain and sedation score and the occurrence of adverse effects were recorded and compared against the genetic data. Results: A total of 72 pediatric patients undergoing surgery were recruited. A weak to no association was found between the genetic polymorphisms of MDR1 and OPRM1 and the anesthetic and adverse effects of propofol-remifentanil. Conclusion: Genetic polymorphisms in OPRM1, but not in MDR1, gene polymorphism, demonstrated plausible association with the effects of propofol-remifentanil.

Seizure severity assessment tools for adult epilepsy patients: A systematic review.

INTRODUCTION: Seizure outcomes from antiseizure medication (ASM) therapy can be measured across various domains using assessment tools. The available tools may contain an array of different components or items. Seizure severity assessment, as opposed to seizure frequency count may have been a more accurate measurement in determining the effectiveness of ASM therapy. This study aimed to review studies developing seizure severity assessment tools for adults with epilepsy, describe the development methods and validation, and compare the list of items in these tools. METHODS: The systematic search utilized established databases such as Scopus, Ovid, Web of Science, Medline, Wiley Online, and Cochrane Library. Studies published from inception to December 15, 2022, were selected. Publications describing the development of tools to measure seizure severity among adult epilepsy patients were included. Outcome measures including the tool's content, development methods, validity, and reliability assessments were compared. RESULTS: The search produced eight publications describing the development of eight seizure severity assessment tools. One of these tools is part of a multidimensional assessment of the overall impact of epilepsy. The frequently used method in the initial development was the qualitative method (n = 6) where two publications reanalyzed the items from previous studies. Face validity was the most common validation test conducted (n = 4). At least one reliability assessment was conducted for each of the tools, most commonly by the test-retest method (n = 6) and inter-rater reliability (n = 5). All of these tools cover the components of pre-ictal (warning/aura), ictal, and postictal (recovery) events. CONCLUSION: The identified tools described the assessment of seizure severity using various subscales. The emergence of new methods in quantifying seizure severity unfolds opportunities in discovering more comprehensive assessments of seizure severity in both clinical trials and daily clinical practice.

Prevalence and predictive factors of tuberculosis treatment interruption in the Asia region: a systematic review and meta-analysis.

INTRODUCTION: Tuberculosis (TB) treatment interruption remains a critical challenge leading to poor treatment outcomes. Two-thirds of global new TB cases are mostly contributed by Asian countries, prompting systematic analysis of predictors for treatment interruption due to the variable findings. METHODS: Articles published from 2012 to 2021 were searched through seven databases. Studies that established the relationship for risk factors of TB treatment interruption among adult Asian were included. Relevant articles were screened, extracted and appraised using Joanna Briggs Institute's checklists for cohort, case-control and cross-sectional study designs by three reviewers. Meta-analysis was performed using the random effect model in Review Manager software. The pooled prevalence and predictors of treatment interruption were expressed in ORs with 95% CIs; heterogeneity was assessed using the I2 statistic. The publication bias was visually inspected using the funnel plot. RESULTS: Fifty eligible studies (658 304 participants) from 17 Asian countries were included. The overall pooled prevalence of treatment interruption was 17% (95% CI 16% to 18%), the highest in Southern Asia (22% (95% CI 16% to 29%)), followed by Eastern Asia (18% (95% CI 16% to 20%)) and South East Asia (16% (95% CI 4% to 28%)). Seven predictors were identified to increase the risk of treatment interruption, namely, male gender (OR 1.38 (95% CI 1.26 to 1.51)), employment (OR 1.43 (95% CI 1.11 to 1.84)), alcohol intake (OR 2.24 (95% CI 1.58 to 3.18)), smoking (OR 2.74 (95% CI 1.98 to 3.78)), HIV-positive (OR 1.50 (95% CI 1.15 to 1.96)), adverse drug reactions (OR 2.01 (95% CI 1.20 to 3.34)) and previously treated cases (OR 1.77 (95% CI 1.39 to 2.26)). All predictors demonstrated substantial heterogeneity except employment and HIV status with no publication bias. CONCLUSION: The identification of predictors for TB treatment interruption enables strategised planning and collective intervention to be targeted at the high-risk groups to strengthen TB care and control in the Asia region.

Perspectives of pharmacists on medication reviews- Exploring implementation research in service establishment in community settings.

BACKGROUND: Pharmacists' roles have been evolving to include more patient-centered care services such as medication reviews that help patients receive the most benefits from their medication. In Malaysia, medication review is yet to be widely implemented in the community pharmacy setting for several reasons, including the non-dispensing separation healthcare system. To establish and implement a feasible medication review service model in Malaysia, it is important to gather community pharmacists' perspectives on such services. AIM: To explore community pharmacists' perceptions of barriers, facilitators, and strategies for the implementation of a medication review service in Malaysia. METHODS: A focus group discussion followed by semi-structured interviews were conducted among purposively sampled community pharmacists with an interest in medication review service. A framework analysis approach using the consolidated framework for implementation research (CFIR) was utilized to generate and analyze the data. After data mapping, the CFIR-ERIC (expert recommendations for implementing change) matching tool was used to generate the strategies according to the barriers identified. RESULTS: Twenty community pharmacists participated in this study. Several barriers and facilitators to service implementation were identified based on the respondent's input. The CFIR-ERIC strategies matching tool analysis reported potential plans that can mitigate the barriers such as: identify and prepare champions, conduct local consensus discussions, conduct educational meetings, alter incentive/allowance structures, and develop a formal implementation blueprint. CONCLUSION: Multifaceted strategies are required to ensure the successful implementation of medication review services in Malaysia. The findings of this study will assist in the development of a sustainable medication review service blueprint for the Malaysian community pharmacy setting.

Drug-Related Problems in Pulmonary Hypertension with Valvular Heart Disease.

Purpose: The occurrence of drug-related problems (DRPs) and their causes specifically among pulmonary hypertension (PH) with valvular heart disease (VHD) has not been evaluated and is unknown. Therefore, this study aimed to determine the percentage of occurrence, types, and causes of DRPs among PH with VHD patients. Patients and Methods: An observational retrospective study was conducted at Cardiology Centre, Hospital Serdang, from 1st January to 30th April 2021. Data were collected from medication charts, medical progress notes, laboratory and operative charts through electronic Health Information System (eHIS). The types and causes of DRPs were identified and classified based on Pharmaceutical Care Network of Europe's (PCNE) classification system V9.02. The data were analyzed using descriptive statistics. Results: All patients (100%) experienced at least one DRP. Total number of DRPs identified was 120 encounters which were associated with 503 causes. The majority of problems were related to treatment effectiveness (59.1%) and treatment safety (33.4%). The causes of DRPs are mainly related to inappropriate monitoring including therapeutic drug monitoring (18.6%), inappropriate combination of drugs, or drugs and dietary/herbal supplement (10.3%), drug dose was too high (8.9%), drug dose was too low (8.2%) and inappropriate timing of administration or dosing intervals (7.7%). Conclusion: The percentage of DRP occurrence was high in the studied population. Treatment effectiveness and treatment safety issues were the main DRPs identified with various preventable causes. The findings may be useful to guide the planning of measures to prevent and solve future DRPs in the population.

Mechanisms of natural products as potential antiepileptic drugs.

The universal epileptogenic cascade remains unknown and most modern treatments focus on the reduction of symptoms and the prevention of seizure recurrence. Experimental studies have demonstrated that herbal medicines may act as antiepileptogenic agents. In this study, the possibilities of plants with antiepileptic properties were reviewed and discussed on their structures and related mechanism of actions. This work constituted a literature review of medicinal plants showing antiepileptic properties by literature searching in Science Direct, PubMed and Wiley Online Library. The keywords of search included epilepsy, antiepileptogenesis, antiepilepsy, natural compounds, extract, herbal medicines and medicinal plants in epilepsy treatment. Only articles published in English were reviewed. Mechanism of action of the natural plants were described according to experimental studies. From the databases, we found 135 natural plants with antiepileptic properties. In this review, the highly studied natural plants were selected. These included Acorus calamus, Bacopa monnieri, Boerhaavia diffusa, Curcuma longa, Gastrodia elata, Ginseng, Uncaria rhynchophylla, Pinellia ternatae, Withania somnifera, Magnolia bark and Resveratrol-related products. From the evidences, natural products may potentially be developed as antiepileptic or antiepileptogenic agents. However, several issues in drug development should be considered such as safety, formulations, pharmacokinetic characteristics and possible interactions.

A systematic review and meta-analysis of dabigatran peak and trough concentration in adults.

Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine dabigatran concentration monitoring is not recommended in clinical practice; however, measurement of dabigatran concentration may be required in several conditions. This study aims to pool the peak and trough dabigatran concentration from real-world studies. A systematic review was performed to identify studies that measured the peak and trough dabigatran concentrations. Observational studies reporting dabigatran peak or trough concentrations and patients' clinical characteristics of either sex, age or weight were included. Random-effect meta-analyses and metaregression were conducted to pool dabigatran concentrations and to identify the correlation between factors affecting dabigatran concentrations. Fifteen studies with a total of 1226 patients were included. The pooled peak dabigatran concentration was 133 ng/mL (95% CI: 113-154, I2  = 86%, n = 655), while the pooled dabigatran trough concentration was 80 ng/mL (95% CI: 69-91, I2  = 93%, n = 1010). Metaregression analyses suggested that age is significantly correlated to trough concentration, while body weight and creatinine clearance significantly correlated to peak concentration. Subgroup results revealed that dabigatran concentration when measured with liquid chromatography-tandem mass spectrometry was higher than haemoclot thrombin inhibitor assay. Several guidelines have proposed dabigatran concentrations target range and the pooled dabigatran concentrations were in line with the suggested range. Further studies to correlate dabigatran concentrations and clinical outcomes is warranted to improve the safety and efficacy monitoring of dabigatran therapy.

Genetic polymorphisms of OPRM1 on the efficacy and safety of anesthetic and analgesic agents: a systematic review.

Aim: This systematic review aimed to outline the outcome of OPRMI (A118G) variants on the effects of anesthetic and analgesic agents used in various procedures. Materials & methods: Literature was obtained from reliable, established databases and reference tracking. Efficacy and side/adverse effects of anesthetic and analgesic drugs intraoperatively or within 48 h postsurgery were the key outcome measures for all populations. Animal studies were excluded. Results: Twenty-nine studies were chosen for inclusion. In association with the efficacy and safety of anesthetic and analgesic agents, gene polymorphism in OPRM1 displayed a strong correlation in reduced analgesic effect and protection against adverse reactions. Conclusion: This systematic review summarized the correlation between genetic polymorphism in the OPRM1 gene and anesthetic/analgesic effects.

Prescribing Practices of Intravenous Immunoglobulin in Tertiary Care Hospitals in Malaysia: A Need for a National Guideline for Immunoglobulin Use.

Rational use of drug involves the use of medicine as per clinical guidelines. Given the steady increase in the clinical utility of intravenous immunoglobulin (IVIG) either as licensed or off-label use, concerns are being raised about the possibility of supply shortages that could significantly impact patient care. Therefore, there is a need to regulate and to promote the rational use of this valuable medication. This cross-sectional chart review study attempts to evaluate the prescribing patterns of IVIG at two tertiary hospitals in Malaysia. Patients' medical files and dispensing records were examined and compared with current guidelines. A total of 348 prescriptions for IVIG were written during the 1-year study period. The highest usage of IVIG was for neurological (47.9%), immunological (27.5%), and hematological conditions (20%). The number of prescriptions with the US Food and Drug Administration (FDA) licensed indications and off-label indications was 148 (42.5%) and 200 (57.5%), respectively. Age (OR: 1.02, 95% CI: 1.01-1.03, p = 0.003) and those admitted to the critical care units (OR: 11.11, 95% CI: 5.60-22.05, p < 0.001) were significant factors for receiving IVIG for an off-label indication. Most prescriptions (79%) had appropriate dosing. Significant factors associated with receiving inappropriate dose of IVIG include age (OR: 0.93, 95% CI: 0.89-0.97, p = 0.001) and those admitted to the critical care units (OR: 10.15, 95% CI: 3.81-27.06, p < 0.001). This study advocates the development and implementation of evidence-based clinical guidelines with prioritization protocol to ensure rational use of IVIG.

Use of Complementary and Alternative Medicine and Adherence to Medication Therapy Among Stroke Patients: A Meta-analysis and Systematic Review.

Purpose: To identify the use patterns of complementary and alternative medicine (CAM) and its impact on medication adherence among patients with stroke. Method: A systematic search through Science Direct, Google Scholar, and PubMed was performed to identify potential studies up to June 2021.The primary outcome was CAM use, and the secondary outcome was medication adherence among patients with stroke. Articles included in the review met the following criteria: 1) patients with stroke ≥18 years old on prescribed medications, and 2) medication adherence reported status. Meta-analyses were conducted to estimate the pooled prevalence of complementary and alternative medicine and adherence in stroke patients using a random-effects model. Results: A total of 1,330 studies were screened, of which 22 were included in the final analysis. The type of studies included were cross-sectional surveys, cohort studies, retrospective studies and prospective survey. The pooled prevalence of CAM usage was at 38% (29-48% CI) and medication non-adherence among stroke patients was at 29% (20-48% CI). The most common reason for inadequate stroke therapy and higher dependence on CAM was the patients' lack of knowledge and the regimen complexity of the medication. Other factors for medication non-adherence were forgetfulness, side effects, cost, and lack of doctor-patient communication. Conclusion: A low prevalence of CAM usage and non-adherence to medications was observed among patients with stroke. Studies investigating the association between CAM usage and medication adherence among patients with stroke are scarce and future researches are needed to explore the influence of CAM use on stroke medication adherence.