N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.
Moving away from traditional "one-size-fits-all" treatment to precision-based medicine has tremendously improved disease prognosis, accuracy of diagnosis, disease progression prediction, and targeted-treatment. The current cutting-edge of 5G network technology is enabling a growing trend in precision medicine to extend its utility and value to the smart healthcare system. The 5G network technology will bring together big data, artificial intelligence, and machine learning to provide essential levels of connectivity to enable a new health ecosystem toward precision medicine. In the 5G-enabled health ecosystem, its applications involve predictive and preventative measurements which enable advances in patient personalization. This review aims to discuss the opportunities, challenges, and prospects posed to 5G network technology in moving forward to deliver personalized treatments and patient-centric care via a precision medicine approach.
Cannabis-drug interactions have caused significant concerns, mainly due to their role in the cytochrome P450 (CYP) enzyme-mediated metabolic pathway of numerous medications. A systematic review was conducted to gain an overview of the potential interactions of cannabis with different drug classes by extracting pertinent information from published study data. From the inception of the study to October 1, 2023, we performed a systematic search of PubMed, Scopus, clinicaltrials.gov, and Web of Science. We included 54 out of 464 articles, and a total of 20 drug classes were identified to have interactions with medicinal cannabis. The cannabis-drug interactions were assessed and classified according to their probability and severity. The analysis revealed that antiepileptics had the most evidence of interaction with cannabis, followed by clobazam (CLB), warfarin, and tacrolimus. Generally, cannabis-drug interactions result in pharmacokinetic (PK) or pharmacodynamic (PD) changes. Therefore, careful monitoring should be performed to detect any unusual elevations in plasma levels. In addition, dose titrations or treatment withdrawal could help mitigate the adverse effects attributed to cannabis-drug interactions. Nevertheless, novel drugs are constantly emerging, and more research is needed to further identify potential interactions with cannabis.
Lack of pharmacogenomics knowledge among healthcare professionals is the most significant cited barrier to implementing pharmacogenomics in clinical settings. Despite the growth in research initiatives and awareness of pharmacogenomics, healthcare professionals continue to report a lack of knowledge and confidence in practicing pharmacogenomics. This study aims to assess the current pharmacogenomics knowledge gaps and learning needs of healthcare professionals in Malaysia. A modified Delphi with a multidisciplinary expert panel was conducted, and a purposive sampling method was used with predefined selection criteria. Fourteen study sites in Malaysia were included. The cut-off value to approach consensus was predefined as a threshold of 60% or higher, and a quantitative descriptive statistical analysis was performed. The study demonstrated that all experts rated the suggested educational content components as essential/important to be included in the educational intervention. Additionally, experts highlighted the significant barriers and gaps to adopting and practicing pharmacogenomics. To conclude, this multisite Delphi study enabled the development of a tailored, effective, evidence-based, competency-based educational intervention in pharmacogenomics for healthcare professionals in Malaysia. To keep up with the rapid evolution of the pharmacogenomics field, healthcare professionals should be equipped with the necessary competencies required to practice pharmacogenomics for better health outcomes. Future research is needed to determine the feasibility of the proposed educational intervention.