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Vorthunju Nakhonsri,1 Shobana John,2,3 Hathaichanok Panumasmontol,4,5 Manassanan Jantorn,4,5 Pongpipat Chanthot,4,5 Nuntachai Hanpramukkun,6 Supaporn Meelarp,7 Chonlaphat Sukasem,2,3 Sissades Tongsima,1 Sukhontha Hasatsri,4 Abhisit Prawang,8 Thanawat Thaingtamtanha,9,10 Natchaya Vanwong,11,12 Chalirmporn Atasilp,13 Monpat Chamnanphon,14 Pimonpan Jinda,2,3 Patompong Satapornpong4,5 1National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand; 2Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand; 4Division of General Pharmacy Practice, Department of Pharmaceutical Care, College of Pharmacy, Rangsit University, Pathum Thani, Thailand; 5Excellence Pharmacogenomics and Precision Medicine Centre, College of Pharmacy, Rangsit University, Pathum Thani, Thailand; 6Division of Pharmaceutical Technology, Department of Industrial Pharmacy, College of Pharmacy, Rangsit University, Pathum Thani, Thailand; 7Ounjai Medical Clinic, Bangsue, Bangkok, Thailand; 8Division of Pharmacy Practice, Department of Pharmaceutical Care, College of Pharmacy, Rangsit University, Pathum Thani, Thailand; 9Department of Chemistry and Biology, University of Siegen, Siegen, Germany; 10Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, Canada; 11Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand; 12Department of Clinical Chemistry, SYstems Neuroscience of Autism & PSychiatric Disorders (SYNAPS) Research Unit, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand; 13Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand; 14Department of Pathology, Faculty of Medicine, Srinakharinwirot University, Nakornnayok, ThailandCorrespondence: Patompong Satapornpong, Director of Excellence Pharmacogenomics and Precision Medicine Centre, College of Pharmacy, Rangsit University, Pathum Thani, Thailand, Tel +66- 2-791-6000 1420, Fax +66- 2-791-6000 1403, Email patompong.s@rsu.ac.thIntroduction: CYP2C19 plays a major role in the metabolism of various drugs. The most common genetic variants were the CYP2C19&ast;2 and &ast;3 alleles (rs4244285 and rs4986893, non-functional variants). In previous studies, we found that genetic polymorphisms in CYP2C19 variants influenced the active metabolites of clopidogrel and caused major adverse cardiovascular and cerebrovascular effects. However, the distribution of CYP2C19 varies among ethnic groups and according to adverse drug reactions. This study aimed to investigate the frequency of CYP2C19 genetic polymorphisms in the Thai population and analyze the differences in the frequency of CYP2C19 genetic polymorphisms between Thai and other populations.Methods: This study enrolled 211 unrelated healthy Thai individuals in total. We performed a real-time polymerase chain reaction to genotype CYP2C19&ast;2 (681G > A) and CYP2C19&ast;3 (636G > A).Results: In the Thai population, the CYP2C19&ast;1 allele was the most prevalent at 70.14%, while the CYP2C19&ast;2 and &ast;3 alleles were found at frequencies of 25.36% and 4.50%, respectively. Conversely, the CYP2C19&ast;3 allele was not detected in Caucasian, Hispanic, African, Italian, Macedonian, Tanzanian, or North Indian populations. The phenotypic profile of this gene revealed that the frequency of intermediate metabolizers (IMs) is nearly equal to that of extensive metabolizers (EMs), at 42.65% and 48.82% respectively, with genotypes &ast;1/&ast;2 (36.02%) and &ast;1/&ast;3 (6.63%). Likewise, poor metabolizers (PMs) with genotypes &ast;2/&ast;2 (6.16%), &ast;2/&ast;3 (2.37%), and &ast;3/&ast;3 (< 1%) are more prevalent in our population as well.Conclusion: The distribution of CYP2C19 genotype and phenotype influenced by non-functional alleles has potential as a pharmacogenomics biomarker for precision medicine and is dependent on an ethnic-specific genetic variation database.Keywords: CYP2C19 gene, genetic diversity, Thai population, interethnic differences

Background: Long COVID have posed a global health burden since the COVID-19 pandemic. This study aimed to evaluate the efficacy and safety of a combined plant extract (CPE) formulation, containing Citrus aurantifolia, Tiliacora triandra, Cannabis sativa, Alpinia galanga, and Piper nigrum, in participants with long COVID. A newly developed long COVID symptom questionnaire was used to evaluate outcomes. Methods: This randomized, double-blinded, placebo-controlled trial was conducted at the College of Pharmacy, Rangsit University, Thailand. Participants were randomly assigned to receive either a CPE supplement (4500 mg/day) or a placebo for 7 days. Primary outcomes were changes in C-reactive protein (CRP) levels and the total symptom score (ranging from 0 to 57 points). Secondary outcomes included full recovery/improvement of long COVID symptoms, health-related quality of life (HRQOL), and adverse events. Results: A total of 66 participants were enrolled, with 33 in each group. The CPE supplement did not significantly reduce CRP levels, with a median difference (MD) (95 % CI) of −0.05 (−0.49, 0.39) mg/L compared to placebo. However, the CPE group showed a reduction in the total symptom score [MD (95 % CI) of −4.00 (−7.58, −0.42)], and a reduction in overall moderate to severe symptoms [RR (95 % CI) of 0.57 (0.35, 0.91)], moderate to severe fatigue [RR (95 % CI) of 0.25 (0.08, 0.81)], and moderate to severe post-exertional malaise (PEM) [RR (95 % CI) of 0.35 (0.16, 0.78)]. Changes in HRQOL scores did not differ significantly between groups. Adverse events were mostly mild and resolved by the end of the follow-up period. Conclusions: Our study suggests potential benefits of the CPE in alleviating moderate to severe long COVID symptoms, particularly fatigue and PEM, with an acceptable safety profile. However, larger-scale trials are necessary to validate these findings, and assessing the reliability of the long COVID symptom questionnaire is essential before its application in future studies. Trial registration number:: TCTR20230131004 (Registration date: 2023–01–31, Thai Clinical Trials Registry).

Background: Mortality from multidrug-resistant (MDR) pathogens is an urgent healthcare crisis worldwide. At present we do not have any simplified screening tools to predict the risk of mortality associated with MDR infections. The aim of this study was to develop a screening tool to predict mortality in patients with multidrug-resistant organisms.Methods: A retrospective cohort study to evaluate mortality risks in patients with MDR infections was conducted at Phrae Hospital. Univariable and multivariable analyses were used to classify possible risk factors. The model performance was internally validated utilizing the mean of three measures of discrimination corrected by the optimism using a 1000-bootstrap procedure. The coefficients were transformed into item scores by dividing each coefficient with the lowest coefficient and then rounding to the most adjacent number. The area under the receiver operating characteristic curve (AuROC) was used to determine the performance of the model.Results: Between 1 October 2018 and 30 September 2020, a total of 504 patients with MDR infections were enrolled. The ICU-SEPSA score composed of eight clinical risk factors: 1) immunocompromised host, 2) chronic obstructive pulmonary disease, 3) urinary tract infection, 4) sepsis, 5) placement of endotracheal tube, 6) pneumonia, 7) septic shock, and 8) use of antibiotics within the past 3 months. The model showed good calibration (Hosmer-Lemeshow χ2 = 19.27; p-value = 0.50) and good discrimination after optimism correction (AuROC 84.6%, 95% confidence interval [Cl]: 81.0%–88.0%). The positive likelihood ratio of low risk (score ≤ 5) and high risk (score ≥ 8) were 2.07 (95% CI: 1.74–2.46) and 12.35 (95% CI: 4.90–31.13), respectively.Conclusion: A simplified predictive scoring tool wad developed to predict mortality in patients with MDR infections. Due to a single-study design of this study, external validation of the results before applying in other clinical practice settings is warranted.

Long COVID have posed a global health burden since the COVID-19 pandemic. This study aimed to evaluate the efficacy and safety of a combined plant extract (CPE) formulation, containing Citrus aurantifolia , Tiliacora triandra , Cannabis sativa , Alpinia galanga , and Piper nigrum , in participants with long COVID. A newly developed long COVID symptom questionnaire was used to evaluate outcomes. This randomized, double-blinded, placebo-controlled trial was conducted at the College of Pharmacy, Rangsit University, Thailand. Participants were randomly assigned to receive either a CPE supplement (4500 mg/day) or a placebo for 7 days. Primary outcomes were changes in C-reactive protein (CRP) levels and the total symptom score (ranging from 0 to 57 points). Secondary outcomes included full recovery/improvement of long COVID symptoms, health-related quality of life (HRQOL), and adverse events. A total of 66 participants were enrolled, with 33 in each group. The CPE supplement did not significantly reduce CRP levels, with a median difference (MD) (95 % CI) of −0.05 (−0.49, 0.39) mg/L compared to placebo. However, the CPE group showed a reduction in the total symptom score [MD (95 % CI) of −4.00 (−7.58, −0.42)], and a reduction in overall moderate to severe symptoms [RR (95 % CI) of 0.57 (0.35, 0.91)], moderate to severe fatigue [RR (95 % CI) of 0.25 (0.08, 0.81)], and moderate to severe post-exertional malaise (PEM) [RR (95 % CI) of 0.35 (0.16, 0.78)]. Changes in HRQOL scores did not differ significantly between groups. Adverse events were mostly mild and resolved by the end of the follow-up period. Our study suggests potential benefits of the CPE in alleviating moderate to severe long COVID symptoms, particularly fatigue and PEM, with an acceptable safety profile. However, larger-scale trials are necessary to validate these findings, and assessing the reliability of the long COVID symptom questionnaire is essential before its application in future studies. TCTR20230131004 (Registration date: 2023–01–31, Thai Clinical Trials Registry). • This randomized controlled trial evaluated the efficacy and safety of a combined plant extracts (CPE) formulation in alleviating long COVID symptoms. • CPE-treated participants showed significant total symptom score reduction in moderate to severe symptoms, with good safety profile. • CPE offers potential benefits in alleviating moderate to severe long COVID symptoms, especially fatigue and post-exertional malaise. [ABSTRACT FROM AUTHOR]