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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)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rangsit University (the primary institution of all the authors except CP and SW) had research collaboration with Naree Pharma Group Co., Ltd., the owner of the combined plant extracts used in this study. The company had no role in the study design, conduct, analysis and interpretation of the data, writing of the manuscript, or dissemination of the trial results. The authors declare no conflict of interest. This study was funded by RSU Research Institute (Grant number 51/2565), Rangsit University. The funder had no role in the study design, conduct, analysis and interpretation of the data, writing of the manuscript, or dissemination of the trial results. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: CYP2C19 plays a major role in the metabolism of various drugs. The most common genetic variants were the CYP2C19*2 and *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*2 (681G > A) and CYP2C19*3 (636G > A)., Results: In the Thai population, the CYP2C19*1 allele was the most prevalent at 70.14%, while the CYP2C19*2 and *3 alleles were found at frequencies of 25.36% and 4.50%, respectively. Conversely, the CYP2C19*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 *1/*2 (36.02%) and *1/*3 (6.63%). Likewise, poor metabolizers (PMs) with genotypes *2/*2 (6.16%), *2/*3 (2.37%), and *3/*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., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest or financial conflict with the subject matter or materials discussed in this manuscript., (© 2024 Nakhonsri et al.)

Stenotrophomonas maltophilia is a multidrug-resistant bacterium that is difficult to treat in hospitals worldwide, leading to high mortality. Published data describing the use of monotherapy or combination therapy and which one is better is still unclear. We aimed to investigate the efficacy of monotherapy and combination therapy in the treatment of S. maltophilia infections. We performed a systematic review of combination therapy and additionally a systematic review and meta-analysis to determine the effects of monotherapy versus combination therapy on mortality in S. maltophilia infections. Electronic databases: Cochrane Library, PubMed, Embase, ClinicalTrials.gov, Scopus, and OpenGrey were accessed. Of the 5030 articles identified, 17 studies were included for a systematic review of combination therapy, of which 4 cohort studies were finally included for meta-analysis. We found there is a trend of favorable outcomes with respect to mortality in the use of combination therapy to treat complex or severe S. maltopholia infections. A meta-analysis of monotherapy showed a statistical significance in the decreasing rate of mortality in hospital-acquired pneumonia (hazard ratio 1.42; 95% confidence interval, 1.04-1.94) compared to combination therapy, but not significant in bacteremia (hazard ratio 0.76; 95% confidence interval, 0.18-3.18). Further studies should continue to explore this association.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sirichayanugul, Srisawat, Thummakomut, Prawang, Huynh, Saokaew, Phisalprapa and Kanchanasurakit.)

Few studies have analyzed community hospital-based parenteral anti-infective therapy (CohPAT). We aimed to assess the clinical impact of a pharmacist-led implementation of a clinical practice guideline (CPG) for CohPAT, and to determine the pharmacist's role in CohPAT medication management. The prospective-period patients (post-implementation group) were compared with the historical control-period patients (pre-implementation group) for receiving a continuous antimicrobial parenteral injection. A CPG was used for laboratory testing for efficacy and safety, the monitoring of adverse drug events during admission, microbiology results coordination, and dosage adjustment. For any antimicrobial drug-related problems, the pharmacist consulted with the clinicians. Over 14 months, 50 participants were included in each group. In the pre-implementation period, 7 (14%) and 4 (8%) out of 50 patients received an inappropriate dosage and nonlaboratory monitoring for dose adjustment, respectively. The patients received the proper dosage of antimicrobial agents, which increased significantly from 78% pre- to 100% post-implementation ( p = 0.000). The pharmacist's interventions during the prospective-period were completely accepted by the clinicians, and significantly greater laboratory monitoring complying with CPG was given to the postimplementation group than the pre-implementation group (100% vs. 60%; p = 0.000). Significantly less patients with unfavorable outcomes (failure or in-hospital mortality) were observed in the post-implementation than in the pre-implementation (6% vs. 26%; p = 0.006) group. For the logistic regression analysis, lower respiratory infection (adjusted OR, aOR 3.68; 95%CI 1.13-12.06) and the post-implementation period (aOR 0.21; 95%CI 0.06-0.83) were significant risk factors that were associated with unfavorable outcomes. Given the better clinical outcomes and the improved quality of septic patient care observed after implementation, pharmacist-led implementation should be adopted in healthcare settings.