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• Hypertension may be a significant risk factor for dementia. • The use of antihypertensive medications could lower the risk of progression of newly diagnosed dementia in hypertensive patients. • CCBs and ARBs are recommended first-line AHMs for hypertensive patients that could significantly reduce the risk of getting dementia. • The use of traditional Chinese medicine could reduce the development of newly diagnosed dementia after hypertension. The claim between hypertension and dementia needs more evidence due to limited data. We aim to examine the risk of dementia in patients with hypertension, and determine whether the use of antihypertensive medications (AHMs) could decrease the incidence of dementia diagnosed following the onset of hypertension. We employed the Taiwan National Health Insurance Research Database from 2000 to 2016 and performed a retrospective cohort study. We also carried out a case-control study to see if AHMs could reduce the incidence of newly diagnosed dementia in hypertensive patients. In the retrospective cohort study, we selected 587,762 participants with age and gender matched in experimental and control groups. The hypertension group had significantly higher adjusted hazard ratios (aHRs) of getting newly diagnosed dementia, including all-cause dementia, Alzheimer's disease, and vascular dementia (aHR, 2.86; 95 % confidence interval (CI), 2.74–2.99) than the control group. Three kinds of specific AHMs, namely, angiotensin II receptor blockers (aHR, 0.55; 95 % CI, 0.53–0.57), calcium channel blockers (aHR, 0.76; 95 % CI, 0.73–0.80), and diuretics (aHR,0.93; 95 % CI, 0.89–0.97) could significantly decrease the incidence of getting newly diagnosed dementia. Also, the application of traditional Chinese medicine (TCM) significantly associates with the lower aHRs of newly diagnosed dementia in hypertensive patients compared to patients without TCM (aHR, 0.90; 95 % CI, 0.81–1.00). Hypertension may be a significant risk factor for dementia. Both AHMs and TCM significantly associate with the lower incidence of newly diagnosed dementia in hypertensive patients. [ABSTRACT FROM AUTHOR]

Background/purpose: With an increasing geriatric population, the need for effective management of chronic conditions and medication use in the elderly is growing. Medication use in the elderly presents significant challenges due to changes in pharmacodynamic and pharmacokinetic profiles. We aimed to examine the impact of a collaborative physician-pharmacist medication therapy management (MTM) program for polypharmacy elderly patients.Methods: Elderly patients with multiple chronic conditions on polypharmacy were enrolled in this prospective, randomized, and controlled study over 16 months of implementation. The intervention group consisted of patients randomized to a collaborative pharmacist-physician MTM program. They were monitored continuously by a clinical pharmacist, while patients in the control group received only usual care with follow-up assessment. Primary outcome was economic differences, measured in total medical expenditure. Secondary outcomes of clinical and humanistic effects were compared between the two groups.Results: The total number of enrolled patients was 87 and 91 in the MTM and usual groups, respectively. The difference-in-difference estimate on medical expenditure during the 16-month implementation period was $3,758,373 New Taiwan Dollars ($127,015 US Dollars) less than the usually care group. Impact was also seen in humanistic outcomes while lipid profiles and mortality trended toward improvement.Conclusion: The pharmacist-physician collaborative MTM program for polypharmacy elderly had significant cost savings and improvement in humanistic measures, demonstrating the importance of clinical pharmacists and MTM programs for elderly patients in Taiwan. The results suggest the possibility of clinical benefits, but the study was not substantially powered to find a statistical difference. [ABSTRACT FROM AUTHOR]

Background: The issue of multidrug resistance (MDR) cancer is one of the major barriers to successful chemotherapy treatment. The ATP-binding cassette (ABC) efflux transporters play an important role in the chemotherapeutic failure. Several generations of ABC efflux transporter inhibitors have been developed, however, none of them could provide better clinical outcome due to systemic toxicities and significant drug-drug interactions. Therefore, the present study focused on identifying the effect of the natural carotenoid on ABC transporters and may provide a safer choice to defeat MDR cancer. Purpose: The aim of the present study was to evaluate the inhibitory potency of β-carotene on the ABC efflux transporters, as well as the reversal effect of β-carotene toward MDR cancers. The underlying molecular mechanisms and inhibitory kinetics of β-carotene on the major ABC efflux transporter, P-glycoprotein, were further investigated. Methods: The human P-gp (ABCB1/Flp-In(TM)-293), MRP1 (ABCC1/Flp-In(TM)-293) and BCRP (ABCG2/Flp-In(TM)-293) stable expression cells were established by using the Flp-In(TM) system. The cytotoxicity of β-carotene was evaluated by MTT assay in the established cell lines, sensitive cancer cell lines (HeLaS3 and NCI-H460) and resistant cancer cell lines (KB-vin and NCI-H460/MX20). Surface protein detection assay and eFluxx-ID Green Dye assay were applied for confirmation of surface expression and function of the transporters. The transporter inhibition potency of β-carotene was evaluated by calcein-AM uptake assay and mitoxantrone accumulation assay. Further interaction kinetics between β-carotene and P-gp were analyzed by rhodamine123 and doxorubicin efflux assay. The influence of β-carotene on ATPase activity was evaluated by Pgp-Glo(TM) Assay System. Results: Among the tested ABC efflux transporters, β-carotene significantly inhibited human P-gp efflux function without altering ABCB1 mRNA expression. Furthermore, β-carotene stimulated both P-gp basal ATPase activity and the verapamil-stimulated P-gp ATPase activity. In addition, β-carotene exerted partially inhibitory effect on BCRP efflux function. The combination of β-carotene and chemotherapeutic agents significantly potentiated their cytotoxicity in both cell stably expressed human P-gp (ABCB1/Flp-In(TM)-293) and MDR cancer cells (KB-vin and NCI-H460/MX20). Conclusion: The present study indicated that β-carotene may be considered as a chemo-sensitizer and regarded as an adjuvant therapy in MDR cancer treatment. [ABSTRACT FROM AUTHOR]

• A total of 252 patients with bacteraemia caused by Staphylococcus aureus , comprising 118 in the iAMS group and 134 in the non-iAMS group, were assessed. • The iAMS group demonstrated a 5.2% increase in the 1-year survival rate (from 55.2% to 50.0%; P = 0.96). • Within the iAMS group, the 1-year survival rate rose by 17.6% (from 70.9% to 53.3%; P = 0.41) and 7.0% (from 52.3% to 45.3%; P = 0.57) for patients with MRSA and MSSA infections, respectively. • The intervention led to a significant 97.3% relative decrease in near-miss medication incidents reported by pharmacists (P = 0.013). This study aimed to investigate the clinical impact of the Intelligent Antimicrobial System (iAMS) on patients with bacteraemia due to methicillin-resistant (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). A total of 1008 patients with suspected SA infection were enrolled before and after the implementation of iAMS. Among them, 252 with bacteraemia caused by SA, including 118 in the iAMS and 134 in the non-iAMS groups, were evaluated. The iAMS group exhibited a 5.2% (from 55.2% to 50.0%; P = 0.96) increase in the 1-year survival rate. For patients with MRSA and MSSA compared to the non-iAMS group, the 1-year survival rate increased by 17.6% (from 70.9% to 53.3%; P = 0.41) and 7.0% (from 52.3% to 45.3%; P = 0.57), respectively, both surpassing the rate of the non-iAMS group. The iAMS intervention resulted in a higher long-term survival rate (from 70.9% to 52.3%; P = 0.984) for MRSA patients than for MSSA patients. MRSA patients experienced a reduced length of hospital stay (from 23.3% to 35.6%; P = 0.038), and the 45-day discharge rate increased by 20.4% (P = 0.064). Furthermore, the intervention resulted in a significant 97.3% relative decrease in near miss medication incidents reported by pharmacists (P = 0.013). Implementation of iAMS platform improved long-term survival rates, discharge rates, hospitalization days, and medical cost (although no significant differences were observed) among patients with MRSA bacteraemia. Additionally, it demonstrated significant benefits in ensuring drug safety. [Display omitted] [ABSTRACT FROM AUTHOR]

• Combination of the Rapid Sepsityper Kit and a machine learning (ML)-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) approach for the rapid prediction of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Klebsiella pneumoniae (CRKP) from positive blood culture bottles. • In total, 47 S. aureus isolates comprising 406 MALDI-TOF MS files and 132 K. pneumoniae isolates comprising 1249 MALDI-TOF MS files were evaluated. • Accuracy, area under the curve, and F1 score for MRSA/MSSA were 0.875, 0.898 and 0.904, respectively; these values for CRKP/CSKP were 0.766, 0.828 and 0.795, respectively. • The novel ML-based MALDI-TOF MS approach enables rapid identification of MRSA and CRKP from flagged blood cultures within 1 h. This enables earlier initiation of targeted antimicrobial therapy, reducing deaths due to sepsis. This study investigated combination of the Rapid Sepsityper Kit and a machine learning (ML)-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) approach for rapid prediction of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Klebsiella pneumoniae (CRKP) from positive blood culture bottles. The study involved 461 patients with monomicrobial bloodstream infections. Species identification was performed using the conventional MALDI-TOF MS Biotyper system and the Rapid Sepsityper protocol. The data underwent preprocessing steps, and ML models were trained using preprocessed MALDI-TOF data and corresponding labels. The interpretability of the model was enhanced using SHapely Additive exPlanations values to identify significant features. In total, 44 S. aureus isolates comprising 406 MALDI-TOF MS files and 126 K. pneumoniae isolates comprising 1249 MALDI-TOF MS files were evaluated. This study demonstrated the feasibility of predicting MRSA among S. aureus and CRKP among K. pneumoniae isolates using MALDI-TOF MS and Sepsityper. Accuracy, area under the receiver operating characteristic curve, and F1 score for MRSA/methicillin-susceptible S. aureus were 0.875, 0.898 and 0.904, respectively; for CRKP/carbapenem-susceptible K. pneumoniae , these values were 0.766, 0.828 and 0.795, respectively. In conclusion, the novel ML-based MALDI-TOF MS approach enables rapid identification of MRSA and CRKP from flagged blood cultures within 1 h. This enables earlier initiation of targeted antimicrobial therapy, reducing deaths due to sepsis. The favourable performance and reduced turnaround time of this method suggest its potential as a rapid detection strategy in clinical microbiology laboratories, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

• Rapid prediction method developed for carbapenem-resistant (CRKP) and colistin-resistant (ColRKP) Klebsiella pneumoniae. • MALDI–TOF mass spectrometry results were used to formulate a suitable and rapid treatment strategy. • Accuracy and AUC for differentiating CRKP and carbapenem-susceptible K. pneumoniae were 0.8869 and 0.9551, respectively. • Accuracy and AUC for differentiating ColRKP and ColIKP were 0.8361 and 0.8447, respectively. • Mortality rate lower in patients who received antibiotic regimen adjustment based on preliminary ML prediction (4/14, 28.6%). The objective of this study was to develop a rapid prediction method for carbapenem-resistant Klebsiella pneumoniae (CRKP) and colistin-resistant K. pneumoniae (ColRKP) based on routine MALDI–TOF mass spectrometry (MS) results in order to formulate a suitable and rapid treatment strategy. A total of 830 CRKP and 1462 carbapenem-susceptible K. pneumoniae (CSKP) isolates were collected; 54 ColRKP isolates and 1592 colistin-intermediate K. pneumoniae (ColIKP) isolates were also included. Routine MALDI-TOF MS, antimicrobial susceptibility testing, NG-Test CARBA 5, and resistance gene detection were followed by machine learning (ML). Using the ML model, the accuracy and area under the curve for differentiating CRKP and CSKP were 0.8869 and 0.9551, respectively, and those for ColRKP and ColIKP were 0.8361 and 0.8447, respectively. The most important MS features of CRKP and ColRKP were m/z 4520–4529 and m/z 4170–4179, respectively. Of the CRKP isolates, MS m/z 4520–4529 was a potential biomarker for distinguishing KPC from OXA, NDM, IMP, and VIM. Of the 34 patients who received preliminary CRKP ML prediction results (by texting), 24 (70.6%) were confirmed to have CRKP infection. The mortality rate was lower in patients who received antibiotic regimen adjustment based on the preliminary ML prediction (4/14, 28.6%). In conclusion, the proposed model can provide rapid results for differentiating CRKP and CSKP, as well as ColRKP and ColIKP. The combination of ML-based CRKP with preliminary reporting of results can help physicians alter the regimen approximately 24 h earlier, resulting in improved survival of patients with timely antibiotic intervention. [ABSTRACT FROM AUTHOR]