The role of genetic polymorphism and other factors on clopidogrel resistance (CR) in an Asian population with coronary heart disease (CHD)

Clopidogrel is a widely-used antiplatelet drug. It is important for the treatment and prevention of coronary heart disease. Clopidogrel can effectively reduce platelet activity and therefore reduce stent thrombosis. However, some patients still have ischemic events despite taking the clopidogrel due to the alteration in clopidogrel metabolism attributable to various genetic and non-genetic factors. This review aims to summarise the mechanisms and causes of clopidogrel resistance (CR) and potential strategies to overcome it. This review summarised the possible effects of genetic polymorphism on CR among the Asian population, especially CYP2C19 *2 / *3 / *17, where the prevalence rate among Asians was 23.00%, 4.61%, 15.18%, respectively. The review also studied the effects of other factors and appropriate strategies used to overcome CR. Generally, CR among the Asian population was estimated at 17.2–81.6%. Therefore, our overview provides valuable insight into the causes of RC. In conclusion, understanding the prevalence of drug metabolism-related genetic polymorphism, especially CYP2C19 alleles, will enhance clinical understanding of racial differences in drug reactions, contributing to the development of personalised medicine in Asia

The management of myocardial injury related to SARS-CoV-2 pneumonia

The global evolution of the SARS-CoV-2 virus is known to all. The diagnosis of SARS-CoV-2 pneumonia is expected to worsen, and mortality will be higher when combined with myocardial injury (MI). The combination of novel coronavirus infections in patients with MI can cause confusion in diagnosis and assessment, with each condition exacerbating the other, and increasing the complexity and difficulty of treatment. It would be a formidable challenge for clinical practice to deal with this situation. Therefore, this review aims to gather literature on the progress in managing MI related to SARS-CoV-2 pneumonia. This article reviews the definition, pathogenesis, clinical evaluation, management, and treatment plan for MI related to SARS-CoV-2 pneumonia based on the most recent literature, diagnosis, and treatment trial reports. Many studies have shown that early diagnosis and implementation of targeted treatment measures according to the different stages of disease can reduce the mortality rate among patients with MI related to SARS-CoV-2 pneumonia. The reviewed studies show that multiple strategies have been adopted for the management of MI related to COVID-19. Clinicians should closely monitor SARS-CoV-2 pneumonia patients with MI, as their condition can rapidly deteriorate and progress to heart failure, acute myocardial infarction, and/or cardiogenic shock. In addition, appropriate measures need to be implemented in the diagnosis and treatment to provide reasonable care to the patient

Antihypertensive Medications for Severe Hypertension in Pregnancy: A Systematic Review and Meta-Analysis

Background: Hypertension in pregnancy causes significant maternal and fetal mortality and morbidity. A comprehensive assessment of the effectiveness of antihypertensive drugs for severe hypertension during pregnancy is needed to make informed decisions in clinical practice. This systematic review aimed to assess the efficacy and safety of antihypertensive drugs in severe hypertension during pregnancy. Methods: A systematic review using the electronic databases MEDLINE (PubMed) and Cochrane Library was performed until August 2021. The risk-of-bias 2 tool was used to assess the risk-of-bias in each study included. Meta-analysis was conducted to assess heterogeneity and to estimate the pooled effects size. Results: Seventeen studies fulfilled the inclusion criteria and 11 were included in the meta-analysis. Nifedipine was estimated to have a low risk in persistent hypertension compared to hydralazine (RR 0.40, 95% CI 0.23–0.71) and labetalol (RR 0.71, 95% CI 0.52–0.97). Dihydralazine was associated with a lower risk of persistent hypertension than ketanserin (RR 5.26, 95% CI 2.01–13.76). No difference was found in the risk of maternal hypotension, maternal and fetal outcomes, and adverse effects between antihypertensive drugs, except for dihydralazine, which was associated with more adverse effects than ketanserin. Conclusions: Several drugs can be used to treat severe hypertension in pregnancy, including oral/sublingual nifedipine, IV/oral labetalol, oral methyldopa, IV hydralazine, IV dihydralazine, IV ketanserin, IV nicardipine, IV urapidil, and IV diazoxide. In addition, nifedipine may be preferred as the first-line agent. There was no difference in the risk of maternal hypotension, maternal and fetal outcomes, and adverse effects between the drugs, except for adverse effects in IV dihydralazine and IV ketanserin

Association between CYP3A4/CYP3A5 genetic polymorphisms and treatment outcomes of atorvastatin worldwide: is there enough research on the Egyptian population?

Abstract Introduction Atorvastatin is regarded as the most frequently prescribed statin worldwide for dyslipidemia. However, clinical response and risk of adverse effects to statin therapy are associated with genetic variations. Numerous research linked statins pharmacokinetics (PK) variations to genetic polymorphisms in cytochromes P450 (CYPs) metabolic enzymes. Objective This article reviews the association between CYP3A4/5 genetic variations and response to atorvastatin therapy globally, which includes atorvastatin PK, and the risk for adverse reactions, with a hint to the Egyptians. Methods Up to March 30, 2022, electronic medical databases like PubMed, Web of Science, MEDLINE, and Egyptian Knowledge Bank (EKB) were searched. All articles that highlighted the relationship between CYP3A4/5 genetic polymorphisms and atorvastatin efficacy/safety profile were included in this review. Results Initially, 492 articles were retrieved after an exhaustive search. There were 24 articles included according to the inclusion criteria. Findings of association studies of CYP3A4/5 genetic polymorphisms with response to atorvastatin varied among different ethnicities. CYP3A4*1B was associated with better therapeutic outcomes after atorvastatin therapy in Chileans and vice versa in Americans. Caucasians with myalgia while using atorvastatin were at significant risk of suffering severe muscle damage if they were carriers of CYP3A5*3/*3. As far as we can report for the Egyptian population, the impact of CYP3A4/5 genetic variations on the response to atorvastatin therapy was understudied. Conclusion More pharmacogenetic studies amongst diverse populations worldwide, like the Egyptian population, are necessary to detect further atorvastatin-gene interactions. Graphical Abstrac

Physicians' perceived barriers and enablers for deprescribing among older patients at public primary care clinics: a qualitative study

Background Increased harmful effects of medication resulting from polypharmacy, especially among older patients, is a significant concern globally. Hence, continuous medication review and withdrawal of inappropriate medications are essential to improve patient safety. Objective To explore physicians’ perceived barriers and enablers of deprescribing among older patients in the public primary healthcare setting. Setting Public primary care clinics in the northern states of Malaysia. Methods A semi-structured, face-to-face interview was conducted among physicians working in eight primary care clinics in northern Malaysia using a purposive sampling approach. Interviews were conducted using validated topic guides. All the responses were recorded, transcribed verbatim, validated, and analysed for the emerging themes using thematic analysis. Main outcome measure Physicians perceived barriers and enablers of deprescribing among geriatric patients. Results A total of eleven physicians were interviewed. Seven emerging themes were identified, which are categorised under barriers and enablers of deprescribing. The barriers were patient-specific, prescriber-specific, and healthcare provision and system. Prescriber deprescribing competencies, medication-specific outcomes, availability of empirical evidence, and pharmacist’s role were the enablers identified. Conclusion Patient-specific barriers were identified as a significant challenge for deprescribing. Improving competencies on deprescribing was the repeatedly adduced enabler by physicians. The development of targeted educational training can help to reduce the obstacles faced by prescribers

The effectiveness of menstrual education module for children and adolescent refugees: a pilot study

Objectives: Females across low- to middle-income countries have limited knowledge and understanding about menstruation prior to reaching menarche. One of the marginalised populations prone to this challenge is the female refugees in Malaysia. The objective of this pilot study is to evaluate the effectiveness of a menstrual health module developed for children and adolescent refugees. Methods: This is a pilot intervention study among children and adolescents aged 9 to 17 years old attending a school for refugees and stateless children located in Selayang, Selangor. A menstrual health module was developed containing basic knowledge on reproductive organs, changes during menstruation, menstruation cycle, and menstrual hygiene management. Activities were carried out during this program to engage the participants. A set of 20 quiz questions were given, pre- and post-intervention. Scores from the quiz were compared using paired T-test to evaluate the effectiveness of the module. Results: A total of 11 children participated in the program (mean age: 12.8 + 1.3 years). All of the participants are Muslims and the majority of them are Myanmar refugees (n=10, 90.9%). The majority stayed with their parents (n=9, 81.8%). About half of the participants have fathers who are without any education (n=6, 54.5%), while most of the fathers were working full time (n=9, 81.8%). The majority of the participants had a monthly household income of less than RM2500 (n=10, 90.9%). The post-intervention mean score for the quiz questions was significantly higher than the pre-intervention mean score (15.9 + 2.3 and 6.3 + 4.9 for postand pre-intervention, respectively) (p<0.001). Conclusion: The menstrual education module was shown to be effective in increasing the knowledge of menstruation and menstrual hygiene among children and adolescent refugees. Rooms for improvements were identified for further revision of the menstrual health module

A cross-sectional study on menstrual health practice and needs among female Rohingya residing in Malaysia: an interim analysis

Objectives: Not much is known about the menstrual practices and needs among Rohingya females residing in Malaysia. This knowledge gap needs to be addressed, in line with the efforts toward family planning. The objectives of the study are to describe menstrual practices among female Rohingya and to assess whether their menstrual needs are met during their last period. Methods: This is a cross-sectional study involving Rohingya females aged 18 to 55 years old attending QFFD Clinic run by IMARET in Selayang, Selangor between April to July 2022. Menstrual practices and needs were assessed using self-administered questionnaires; the Menstrual Practices Questionnaire (MPQ) and the Menstrual Practice Needs Scale (MPNS-36), respectively. Results: A total of 40 respondents have completed the questionnaire. Only 42.5% (n=17) of respondents have good experiences during their past menstrual cycle despite most of the respondents were able to meet their materials and home environment needs (n=27, 67.5%) and are less concerned when managing the disposal of their menstrual materials (n=25, 62.5%). Though, only 12.5% (n=5) of respondents have their transportation and school environment needs were met during their past menstrual cycle and 37.5% (n=15) of the respondents have concerns with the quality of their menstrual materials. The most common menstrual materials used by respondents at home and while away from home are disposable sanitary pads (n=35, 87.5% and n=36, 90.0% respectively). Many of the respondents prefer to dispose them inside the household rubbish bin which is inside the latrine when at home (n=36, 90.0 %) while the bin in the public latrine or toilet is used when disposing menstrual materials while away from home (n=32, 80.0%). Conclusion: Most of the female Rohingya refugees were able to practice safe and clean menstrual management. Though, some of their needs were not met, especially during transportation and away from home. It is important for non-government organizations like UNHCR to fight for their legal status in Malaysia so that they can feel safe and secure without it impacting their health negativel

A simple PCR-SSP method for detection of HLA-B*15:02, *15:13, and *15:21

This study aims to develop a simple polymerase chain reaction (PCR) sequence-specific primer method, which will be used to genotype HLA-B*15:02, HLA-B*15:13, and HLA-B*15:21

Serotonin reuptake inhibitors (SRIs) and the risk of fetal congenital heart anomalies (CHA): An exploratory pharmacogenetics study

Introduction: Several studies reported the risk of CHA associated with prenatal use of SRIs, but the results have been inconsistent. Objective: To explore whether pharmacogenetics play a role in this teratogenicity using a gene-environment interaction study. Patients and methods: A total of 33 case-mother dyads and 2 mother-only (children deceased) registered in EUROCAT Northern Netherlands were included in a case-only study. Five case-mother dyads and two mothers-only were exposed to SRIs in the first trimester of pregnancy. The remaining 28 case-mother dyads were not exposed to SRIs. Ten genes that encode the enzymes or proteins important in determining fetal exposure to SRIs or its mechanism of action were selected: CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6), ABCB1 (placental P-glycoprotein), SLC6A4 (serotonin transporter) and serotonin receptor genes (HTR1A, HTR1B, HTR2A, and HTR3B). All included subjects were genotyped for 58 genetic variations. Logistic regression analyses were performed to determine the interaction odds ratio (OR) between genetic variations and SRIs exposure on the risk of CHA. Results: Due to low phenotype frequencies of CYP450 poor metabolizers among exposed cases, the OR cannot be calculated. For ABCB1, there was no indication of changes in the risk of CHA with any of the ABCB1 SNPs in the children and their mothers. Several genetic variations of the serotonin transporter and receptors (SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 & rs6298, HTR3B rs1176744) were associated with an increased risk of CHA, but with too limited sample size to reach statistical significance. For SLC6A4 genetic variations, the mean genetic scores of the exposed case-mothers tended to be higher than the unexposed mothers (2.5 ± 0.8 and 1.88 ± 0.7, respectively; p=0.061). For SNPs of the serotonin receptors, the mean genetic score for exposed cases (children) tended to be higher than the unexposed cases (3.4 ± 2.2, and 1.9 ± 1.6, respectively; p=0.065). Conclusion: This study was the first to explore the potential gene-environment interaction between pharmacogenetic determinants and SRIs use on the risk of CHA. With small sample sizes, it was not possible to find a significant interaction. However, the role of serotonin receptor polymorphisms in fetuses exposed to SRIs warrants further investigation