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.

A retrospective analysis of e-prescriptions for non-communicable diseases on a telehealth platform in Malaysia.

BACKGROUND: The management of non-communicable diseases (NCDs) has benefited from telehealth services. As these services which include teleconsultation services and e-prescriptions are relatively new in Malaysia, the data generated provide an unprecedented opportunity to study medication use patterns for the management of NCDs in the country. We analyze e-prescriptions from a local telehealth service to identify medication use patterns and potential areas to optimize medication use in relation to clinical practice guidelines. METHODS: A cross sectional observational study was conducted by retrieving e-prescription records retrospectively from a telehealth service. 739,482 records from January 2019 to December 2021 were extracted using a designated data collection form. Data cleaning, standardization and data analysis were performed using Python version 3.11. The diagnoses were classified according to the International Classification of Disease 10 (ICD-10), while medications were classified using the Anatomical Therapeutic Chemical (ATC) system. Diagnoses, frequency of use for medication classes and individual medications were analyzed and compared to clinical practice guidelines. RESULTS: The top five NCD diagnoses utilized by the service were hypertension (37.7%), diabetes mellitus (25.1%), ischemic heart disease (24.3%), asthma (14.4%), and dyslipidemia (11.7%). Medications were prescribed mostly in accordance with guideline recommendations. However, angiotensin receptor blockers (ARBs) were significantly more frequently prescribed compared to angiotensin converting enzyme inhibitors (ACEIs). Several medication classes appeared underutilized, including ACEIs in hypertensive patients with diabetes or ischemic heart disease, sodium glucose cotransporter 2 inhibitors in diabetic patients with ischemic heart disease, and metformin in patients with diabetes. CONCLUSIONS: Telehealth services are currently being utilized for the management of NCDs. Medication use for the management of NCDs through these services are mostly in accordance with guideline recommendations, but there exist areas that would warrant further investigation to ensure optimal clinical and economic outcomes are achieved.

The Effects and Mechanisms of Xanthones in Alzheimer's Disease: A Systematic Review.

Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of ß-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.

Prevalence of nocturia among community-dwelling adults: a population-based study in Malaysia.

BACKGROUND: Nocturia is widely prevalent condition with detrimental effects on quality of life and general health. In Malaysia, there is a lack of up-to-date prevalence study on nocturia. This study aimed to investigate the prevalence of nocturia and awareness pertaining to nocturia among Malaysian adults. METHODS: A cross-sectional population-based study was conducted among Malaysian adults aged ≥ 18 years old. The data was collected by mixed mode self-administered questionnaire from May 2019 to September 2019. Nocturia was defined as one or more voids at night. RESULTS: There were a total of 4616 respondents with 74.5% of response rate. The overall prevalence of nocturia among Malaysian adults was found to be 57.3%. In multivariate analysis, respondents aged 31-40 (1.91 [1.52-2.40]) or > 60 years old (2.03 [1.48-2.71]), and those who presented with hypertension (2.84 [2.28-3.53]), diabetes mellitus (1.78 [1.42-2.25]), renal disease (3.58 [1.93-6.63]) or overactive bladder (1.61 [1.10-2.35]) were associated with higher prevalence of nocturia. A significantly lower disease prevalence (p < 0.05) was noted among those aged 41-50 (0.73 [0.59-0.91]), male (0.78 [0.69-0.88]) and Chinese (0.47 [0.30-0.74]) or Indian (0.34 [0.21-0.54]) ethnicities. A total of 37.3% of respondents with nocturia reported that they faced sleeping difficulty about half the time or more after waking up in the middle of night. Those who had ≥ 2 voids per night experienced significantly higher mean bother score than those who had 1 void per night (p < 0.001). Approximately half (56.7%) of all respondents were not aware that night time urination is a medical condition. Only 25.2% of respondents with nocturia had sought medical attention for their nocturia. CONCLUSIONS: The prevalence of nocturia among Malaysian adults is high and strongly influenced by age, sex, race and comorbidities. However, the general awareness pertaining to nocturia being a health issue remains low among Malaysians. The findings also highlighted the impact of nocturia on sleep and the need for nocturia education to better address this disease.

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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Skin lightening properties of zerumbone cream: A placebo-controlled study.

OBJECTIVE: Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) in vitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach. METHODS: Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18. RESULTS: Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream. CONCLUSION: ZER demonstrated significant potential as a skin-lightening agent.

Stimulatory effect of eurycomanone from Eurycoma longifolia Jack roots on dopamine secretion in human neuroblastoma SH-SY5Y cell line.

Eurycomanone has been identified as the major bioactive compound contributing to Eurycoma longifolia (EL) aphrodisiac activity, however, its mechanism of action remains obscured. Presently, eurycomanone was isolated from EL root extract and its molecular structure was identified. The human neuroblastoma SH-SY5Y cell line was differentiated into human dopaminergic neuron-like cells. Exogenous dopamine levels from the differentiated SH-SY5Y cells were quantified following the treatment of 5, 10, 15 µM of eurycomanone and 10 µM clorgyline as positive control. Dopamine secretion was significantly increased in a dose-dependent manner, compared to the vehicle control (p < .01) in differentiated SH-SY5Y cells. Dopamine concentration stimulated by 15 µM eurycomanone was significantly higher than clorgyline (p < .05), an inhibitor of monoamine oxidase A that suppresses dopamine catabolism. In conclusion, eurycomanone stimulated dopamine release of human SH-SY5Y neuron-like cells, which could be one of the mechanisms that underpin the aphrodisiac properties of the plant.

FDA-approved CAR T-cell Therapy: A Decade of Progress and Challenges.

CAR T-cell therapy is a promising approach for cancer treatment, utilizing a patient's own T-cells (autologous cell) or T-cells from a healthy donor (allogeneic cell) to target and destroy cancer cells. Over the last decade, significant advancements have been made in this field, including the development of novel CAR constructs, improved understanding of biology and mechanisms of action, and expanded clinical applications for treating a wider range of cancers. In this review, we provide an overview of the steps involved in the production of CAR T-cells and their mechanism of action. We also introduce different CAR T-cell therapies available, including their implementation, dosage, administration, treatment cost, efficacy, and resistance. Common side effects of CAR T-cell therapy are also discussed. The CAR T-cell products highlighted in this review are FDA-approved products, which include Kymriah® (tisagenlecleucel), Tecartus® (brexucabtagene autoleucel), Abecma® (Idecabtagene vicleucel), Breyanzi® (lisocabtagene maraleucel), and Yescarta® (axicabtagene ciloleucel). In conclusion, CAR T-cell therapy has made tremendous progress over the past decade and has the potential to revolutionize cancer treatment. This review paper provides insights into the progress, challenges, and future directions of CAR T-cell therapy, offering valuable information for researchers, clinicians, and patients.

Novel drug candidates against antibiotic-resistant microorganisms: A review.

Antibiotic resistance is fast spreading globally, leading to treatment failures and adverse clinical outcomes. This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus. Several novel drug candidates have shown promising results from in vitro and in vivo studies, as well as clinical trials. The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small molecules with potential antibacterial effects screened by computational receptor docking. As drug discovery progresses, preclinical and clinical studies should also be extensively conducted on the currently available therapeutic agents to unravel their potential antibacterial effect and spectrum of activity, as well as safety and efficacy profiles.

The effects of school-based hygiene intervention programme: Systematic review and meta-analysis.

Children are susceptible to infections due to frequent participation in school group activities and their often-suboptimal hygiene practices. Frequent infections in children affect school attendance, academic performances, and general health. The effectiveness of school-based hygiene-related intervention programmes need to be informed by updated high-quality synthesised evidence. In this systematic review, we searched PubMed and Cochrane CENTRAL for randomised and non-randomised interventional studies that evaluated school-based hygiene-related interventions. We assessed risk-of-bias (Cochrane risk-of-bias 2 tool), performed random-effect meta-analysis (RevMan 5.4) and rated certainty-of-evidence (GRADE). Thirty-nine trials (41 reports), published from 2011 to 2024 from 22 countries were included. Twenty-three studies contributed data for meta-analysis. All school-based interventions were compared with standard curriculum and demonstrated very low to low certainty-of-evidence due to study methodological limitations and imprecision. Hand-body hygiene interventions may improve knowledge, attitudes and practices (SMD 2.30, 95%CI 1.17 to 3.44, 6 studies, 7301 participants), increase handwashing practices (RR 1.75, 95%CI 1.41 to 2.17, 5 studies, 5479 participants), and reduce infection-related absenteeism (RR 0.74, 95%CI 0.66 to 0.83, 5 studies, 1017852 observations). Genital hygiene interventions may improve attitude (SMD 6.53, 95%CI 2.40 to 10.66, 2 studies, 2644 participants) and practices (RR 2.44, 95%CI 1.28 to 4.68, 1 study, 1201 participants). However, intervention effects on oral hygiene appeared mixed, with worsening of the oral hygiene score (SMD 3.12, 95%CI 1.87 to 4.37, 2 studies, 652 participants) but improved dental hygiene (SMD -0.33, 95%CI -0.53 to -0.13, 3 studies, 4824 participants) and dental caries scores (SMD -0.34, 95%CI -0.52 to -0.16, 4 studies, 2352 participants). Limited evidence suggests that interventions targeting hand-body and genital hygiene practices may improve knowledge, practices, and infection-related absenteeism. However, the effects on oral hygiene intervention appeared mixed. Future research should strengthen randomisation and intervention documentation, and evaluate hygiene-related behaviour, academic performances and health outcomes.

Pharmacogenomics of response to statin treatment and susceptibility to statin-induced adverse drug reactions in Asians: a scoping review.

Background: Statins are the most widely used lipid-lowering agents for patients with hyperlipidemia. However, interindividual variations in efficacy and risk of adverse drug reactions to statin treatment have been widely reported. Ethnicity is well known to be one of the contributing factors to this variation, particularly among Asians. Objectives: To identify genetic variants associated with statin treatment responses among Asian populations with a focus on four commonly prescribed statins: atorvastatin, rosuvastatin, simvastatin, and pravastatin. Methods: A literature search was conducted in Medline and Embase databases. Studies published from 2008 to 2021 were included. The title and abstract of each article were screened by two reviewers and verified by another two reviewers. Data charted include information on authors, year of study, study population, statin studied, gene studied, study findings, and data of significant statistical value. Results: A total of 35 articles were included from the 1,939 original studies related to treatment efficacy and 5 articles out of the 284 original studies related to adverse effects. Genetic variants in transmembrane transporters, cytochrome P450 isoenzymes, and apolipoproteins are the most extensively studied among Asian populations, with a main focus on ethnic Chinese. However, Asia consists of genetically different populations, and the results of this review indicated that there is a paucity of studies on other ethnic groups within Asia. Conclusions: Considering the ethnicity of patients could provide a potential value to personalized medicine in statin therapy.

Exploring the rise of telehealth services in Malaysia: A retrospective study.

Background: Telehealth services have gained popularity in Malaysia, providing convenient consultations during the COVID-19 pandemic. However, there is limited research on their usage, user demographics and prescribed medications. This study aims to fill that gap by investigating telehealth service utilisation in community pharmacies and identifying trends in common diagnoses and medications prescribed. Methods: A retrospective observational study was conducted using a telehealth services database in Malaysian community pharmacies. Consultation records from January 2019 to December 2021 were extracted using a data collection form. The study identified the service usage over time, demographic profiles of users and the most common diagnoses and prescribed medications. Diagnoses were classified using the International Classification of Disease, 10th Revision (ICD-10), and medications were classified using the Anatomical Therapeutic Chemical (ATC) system. Results: The study included 835,826 telehealth service records, with 88.8% being assisted consultations with e-prescriptions and 11.2% direct consultations. The user population consisted of primarily Malaysians (96.9%), with a mean age of 50 ± 21 years. Both telehealth services saw an increase in unique users over the 3-year study period. There was a moderate correlation between active COVID-19 cases and monthly user count. Assisted consultations were more widely used than direct consultations. Conclusion: This study found an increased usage of telehealth services and its potential to remain as a healthcare system feature in community pharmacies. Further investigation into the impact on medication safety, quality and healthcare delivery is warranted.

Pharmacogenomics of Cancer Pain Treatment Outcomes in Asian Populations: A Review.

In advanced cancer, pain is a poor prognostic factor, significantly impacting patients' quality of life. It has been shown that up to 30% of cancer patients in Southeast Asian countries may receive inadequate analgesia from opioid therapy. This significant under-management of cancer pain is largely due to the inter-individual variability in opioid dosage and relative efficacy of available opioids, leading to unpredictable clinical responses to opioid treatment. Single nucleotide polymorphisms (SNPs) cause the variability in opioid treatment outcomes, yet their association in Asian populations remains unclear. Therefore, this review aimed to evaluate the association of SNPs with variability in opioid treatment responses in Asian populations. A literature search was conducted in Medline and Embase databases and included primary studies investigating the association of SNPs in opioid treatment outcomes, namely pharmacokinetics, opioid dose requirements, and pain control among Asian cancer patients. The results show that CYP2D6*10 has the most clinical relevance in tramadol treatment. Other SNPs such as rs7439366 (UGT2B7), rs1641025 (ABAT) and rs1718125 (P2RX7) though significant have limited pharmacogenetic implications due to insufficient evidence. OPRM1 rs1799971, COMT rs4680 and ABCB1 (rs1045642, rs1128503, and rs2032582) need to be further explored in future for relevance in Asian populations.

Optimizing Antimicrobial Therapy by Integrating Multi-Omics With Pharmacokinetic/Pharmacodynamic Models and Precision Dosing.

In the era of "Bad Bugs, No Drugs," optimizing antibiotic therapy against multi-drug resistant (MDR) pathogens is crucial. Mathematical modelling has been employed to further optimize dosing regimens. These models include mechanism-based PK/PD models, systems-based models, quantitative systems pharmacology (QSP) and population PK models. Quantitative systems pharmacology has significant potential in precision antimicrobial chemotherapy in the clinic. Population PK models have been employed in model-informed precision dosing (MIPD). Several antibiotics require close monitoring and dose adjustments in order to ensure optimal outcomes in patients with infectious diseases. Success or failure of antibiotic therapy is dependent on the patient, antibiotic and bacterium. For some drugs, treatment responses vary greatly between individuals due to genotype and disease characteristics. Thus, for these drugs, tailored dosing is required for successful therapy. With antibiotics, inappropriate dosing such as insufficient dosing may put patients at risk of therapeutic failure which could lead to mortality. Conversely, doses that are too high could lead to toxicities. Hence, precision dosing which customizes doses to individual patients is crucial for antibiotics especially those with a narrow therapeutic index. In this review, we discuss the various strategies in optimizing antimicrobial therapy to address the challenges in the management of infectious diseases and delivering personalized therapy.

Diabetes emergencies around Ramadan study (DEARS) - A multi-center study of diabetes emergencies admitted before, during and after Ramadan in Malaysia.

OBJECTIVE: The objective of this study was to determine admissions for diabetes emergencies among patients who fasted or planned to fast one month before, during and one month after Ramadan 2019 in public hospitals in Malaysia. MATERIALS AND METHODS: This was a cross sectional prospective study done in 18 public hospitals in Malaysia from 7/4/2019 to 2/7/2019. Data was collected prospectively with universal sampling. All adult Muslim patients with previous diagnosis of diabetes, who were admitted for hypoglycemia, DKA or HHS were included if they had fasted and had intentions to fast. RESULTS: 295 admissions for diabetes emergencies were analyzed. The pre-Ramadan period recorded the highest number of admissions (119) followed by during (106) and post-Ramadan (70). Admissions for hyperglycemic emergencies accounted for 2/3 of total admissions. 37% of admissions for hypoglycemia occurred during pre-Ramadan period compared to 32.1% during Ramadan. Contributing factors included use of sulphonylurea (59.6%), presence of nephropathy (54.5%) and past history of hypoglycemia (45.5%). Admissions for DKA were more common than HHS (119 versus 77) and highest during Ramadan period (36.1%). Most of the admissions for hyperglycemic emergencies were among those with Type 2 diabetes (75.9% for DKA and 97.4% for HHS). Only 31.5% of patients admitted for diabetes emergencies recalled having received Ramadan advice in the past. DISCUSSION: Admissions for diabetes emergencies were highest during pre-Ramadan period followed by Ramadan and post-Ramadan period. This suggests that fasting during Ramadan does not increase admissions for diabetes emergencies.