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Background: Previous studies have implicated inherited mutations in mitochondrial DNA (mtDNA) in sensorineural hearing loss (SNHL). However, the definitive association between mitochondrial 12S rRNA (MT-RNR1) variants and hearing loss in the population has not been well established, particularly in Asia. The objective of this retrospective cohort study was to assess the association between MT-RNR1 variants and the risk of SNHL in patients in Taiwan. Methods: The cohort included 306,068 participants from Taiwan between January 2003 and December 2020. Participants were classified based on genetic variants, particularly mitochondrial mutations (rs267606618, rs267606619, rs267606617). MT-RNR1 variant cases were matched 1:10 with non-mutant patients by age, gender, and visit year, excluding those with pre-existing hearing loss. The primary endpoint was SNHL, identified using specific ICD-TM codes with a 90% positive predictive value. Medication exposure history was determined via self-report or electronic medical records in the hospital. Cox proportional hazard regression models were used to assess the association between MT-RNR1 variants and hearing loss, adjusting for various covariates. Kaplan-Meier survival curves and log-rank tests compared hearing loss incidence between groups. Results: The mean age of the mtDNA variants group is 32.4 years, with a standard deviation of 19.2 years. The incidence density of hearing loss for the mutation group was 36.42 per 10,000 person-years (95% Confidence Interval [CI], 27.21–47.73), which was higher than the 23.77per 10,000 person-years (95% CI, 21.32–26.42) in the wild-type group (p = 0.0036). Additionally, diabetes mellitus was associated with an increased risk of developing SNHL in individuals with MT-RNR1 variants (adjusted hazard ratio = 1.76 [95% CI, 1.00-3.09], p < 0.05). Conclusion: This study highlights the increased risk of hearing loss in patients carrying MT-RNR1 variants, particularly those with diabetes mellitus. Future research that integrates genetic and clinical data is crucial for developing more precise interventions to monitor and treat hearing loss in this vulnerable population. [ABSTRACT FROM AUTHOR]

Prescribing cascade is a significant clinical problem but is often overlooked. We explore the incidence of the prescribing cascades of antigout medications related to thiazide treatment in gout-naïve hypertensive adults newly exposed to the pharmacological treatment. This population-based, retrospective cohort study used the Taiwan National Health Insurance Registry Database. Gout-naïve hypertensive adults who were newly dispensed first-line antihypertensive drugs between January 1, 2000, and December 31, 2016, were enrolled. Patients were divided into the thiazide group (n = 4192) and the non-thiazide group (n = 81,083). The non-thiazide group included patients who received an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, or beta-blocker. The study utilized propensity score matching and multivariable Cox regression models to investigate the prescribing cascade of antigout agents following antihypertensive treatment, adjusting for factors like age, sex, comorbidities, and concurrent medications. After propensity score matching, each group consisted of 4045 patients, with the thiazide group exhibiting a higher risk of being prescribed antigout medications across different time intervals post-treatment initiation. Specifically, adjusted hazard ratios (aHRs) for the thiazide group were 2.23, 2.07, and 2.41 for < 30 days, 31–180 days, and > 180 days, respectively, indicating a sustained and significant risk over time. Comparative analyses revealed thiazide diuretics were associated with a higher risk of antigout medication prescriptions compared to other antihypertensive classes, particularly evident after 180 days. Subgroup analyses across various demographics and comorbidities consistently showed an increased risk in the thiazide cohort. Gout-naïve hypertensive adults newly dispensed thiazide had a higher risk of subsequently adding antigout agents than those taking other first-line antihypertensive medications. The awareness and interruption of these prescribing cascades are critical to improving patient safety. [ABSTRACT FROM AUTHOR]

Background: Several case reports have indicated that tamoxifen induced acute pancreatitis (AP); but no pharmacoepidemiological data support the claim. Therefore, we investigated whether tamoxifen use is correlated with the risk of AP in patients with breast cancer. Methods: This population-based cohort study used the Taiwan National Health Insurance Research Database. A cohort of 22 005 patients aged ≥20 years with breast cancer from January 1, 2000 to December 31, 2009 was identified and the date of cancer diagnosis was set as the index date. The end point was developing AP during the follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated to determine the correlation between the risk of AP and tamoxifen use. Because the drug use varied over time, it was measured as a time-dependent covariate in the Cox proportional hazard model. The same approaches were applied in PS-matched cohorts. Results: After adjustment for covariates and medication use including fluorouracil and doxorubicin, the risk of AP was not significant between tamoxifen users and tamoxifen nonusers (adjusted HR = 0.94, 95% CI = 0.74–1.19) in the non-matching cohorts. The results revealed no dose–response trend between tamoxifen use and the risk of AP (adjusted HR = 0.98, 95% CI = 0.96–1.00). The comorbidities DM and gallstones were associated with a significantly increased risk of AP. Similar trends were observed in PS-matched cohorts. Conclusions: No significant correlation was observed between tamoxifen use and the risk of AP in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Background 5-alpha-reductase inhibitors (5 ARIs) are the potent androgen responsible for the development and enlargement of the prostate gland by decreasing dihydrotestosterone ( DHT). This results in inhibition of the conversion of testosterone to dihydrotestosterone and markedly suppresses serum dihydrotestosterone levels. Testosterone replacement therapy improves bone density in men with hypogonadal osteoporosis. This study explores the possible association between the use of two typical 5 ARIs (finasteride and dutasteride) and the subsequent risk of osteoporosis diagnosis. Methods We identified 1352 osteoporosis diagnosis cases and 5387 control cases without osteoporosis diagnosis from the claims data for patients with benign prostate hyperplasia ( BPH), which are collected in the Taiwanese National Health Insurance Research Database ( NHIRD). Four controls were frequency matched to each case according to age (every 5 years) and diagnosis date. We measured the effect of 5 ARIs and determined the adjusted odds ratios ( ORs) with 95% confidence intervals ( CIs). Results We observed a 1·52-fold increase in osteoporosis diagnosis among patients with BPH using finasteride (95% CI, 1·01-2·30). Furthermore, a dosage analysis showed that higher doses of finasteride were associated with higher osteoporosis diagnosis risk ( OR = 1·68; 95% CI, 1·01-2·81), relative to the patients not using 5 ARIs. Conclusion This population-based nested case-control study suggests that the use of finasteride can increase the risk of osteoporosis diagnosis among patients with BPH. The effects were more prominent in patients using higher doses of finasteride. [ABSTRACT FROM AUTHOR]

Indoxyl sulfate (IS), a highly protein-bound nephro-cardiovascular toxin, was poorly removed by hemodialysis. IS exists as anions in the body and the renal excretion is mediated by organic anion transporter 1 (OAT1) and OAT3. Acidic antibiotics such as cephalosporins and fluoroquinolones were putative substrates/inhibitors of OATs. We hypothesized that cephalosporins and fluoroquinolones might compete with IS for OAT1- and/or OAT3-mediated renal excretions. This study investigated the effects of ciprofloxacin, cefuroxime, cefotaxime, cefazolin and ofloxacin on the intravenous pharmacokinetics of IS in rats. IS was intravenously injected with and without each individual antibiotics, and the concentrations of IS in serum and lysate were determined by HPLC. The results showed that ciprofloxacin significantly increased AUC0-t and T1/2 of IS by 272% and 491%, respectively, and decreased the clearance by 71%. However, ofloxacin, cefuroxime, cefotaxime and cefazolin did not alter the pharmacokinetics of IS. Furthermore, cell line study showed that ciprofloxacin inhibited the OAT3-mediated transport of IS. This study indicates 30 mg/kg of ciprofloxacin decreased the clearance of IS through inhibition on the OAT3-mediated transport, whereas 50 mg/kg of ofloxacin, cefuroxime, cefotaxime and cefazolin did not show significant influence. [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]

The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan's herbal medicines adverse reaction database and facilitate epidemiological analysis. [ABSTRACT FROM AUTHOR]

Valproic acid (VPA), an anti-epileptic drug with a narrow therapeutic index, is a substrate of the monocarboxylate transporter (MCT). In this study, we investigated the effect of Gegen-Qinlian-Tang (GQT), a Chinese Medicine prescription containing Puerariae Radix (PR), Scutellariae Radix (SR), Coptidis Rhizoma (CR) and Glycyrrhizae Radix (GR), on the pharmacokinetics of VPA, as a probe drug of MCT, in rats and the underlying mechanism. Sprague-Dawley rats were orally administered VPA with and without GQT in crossover design. The serum concentrations of VPA were determined by a fluorescence polarization immunoassay. The results showed that coadministration with 2.0 and 4.0 g/kg of GQT remarkably decreased the Cmax of VPA by 72% and 74% and reduced the 0-t by 63% and 53%, respectively. The mechanism study using Caco-2 cells revealed that the uptake function of MCT was inhibited by GQT and each component herb. In conclusion, the MCT-mediated absorption of VPA was significantly decreased by GQT and its component herbs. [ABSTRACT FROM AUTHOR]

The role of allopurinol usage in colorectal cancer (CRC) has no definite conclusion. The aim of this study was to explore the correlation between allopurinol usage and CRC risk in Taiwan. Using the National Health Insurance Database, we conducted a case‐control study of cases who were ≥20 years old and had newly diagnosed CRC for the period from 2000 to 2013. The controls were matched to cases by age, sex, index year, comorbidities, and socioeconomic status using propensity scores. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were measured by the conditional logistic regression model. We examined 4372 cases and 4372 matched controls. A statistically significant correlation was noted between allopurinol usage and CRC risk (OR, 0.79; 95%CI, 0.69‐0.90). We used the cumulative‐defined daily doses (cDDDs) in a further subgroup analysis, the ORs decreased from tertile 1 (T1; low dose, <12 cDDDs), T2 (medium dose, 12 to 88.5 cDDDs), to T3 (high dose, >88.5 cDDDs). These values were 0.85 (95%CI, 0.69‐1.06), 0.77 (95%CI, 0.62‐0.95), to 0.76 (95%CI, 0.61‐0.94). The results indicated a dose‐response relationship between allopurinol usage and CRC risk (P for trend <.001). We thus inferred that patients with medium and high doses of allopurinol (≥12 cDDDs) had a statistically significantly decreased CRC risk. [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]

Resveratrol (RVT) has various beneficial bioactivities and popularly used as a dietary supplement. RVT showed inhibitions on CYP1A2/2C9/3A4, breast cancer resistance protein (BCRP), and some conjugated metabolites of RVT also inhibited BCRP. (±)Warfarin, an anticoagulant for cardiovascular disease but with narrow therapeutic window, were substrates of CYP1A2/3A4(R-form), 2C9(S-form) and BCRP. We hypothesized that the concurrent use of RVT might affect the metabolism and excretion of warfarin. This study investigated the effect of RVT on the pharmacokinetics and anticoagulation effect of (±)warfarin. Rats were orally given (±)warfarin (0.2 mg/kg) without and with RVT (100 mg/kg) in a parallel design. The results showed that RVT significantly increased the AUC0−t of S-warfarin and international normalized ratio. Mechanism studies showed that both RVT and its serum metabolites (RSM) inhibited BCRP-mediated efflux of R- and S-warfarin. Moreover, RSM activated CYP1A2/3A4, but inhibited CYP2C9. In conclusion, concomitant intake of RVT increased the systemic exposure of warfarin and enhanced the anticoagulation effect mainly via inhibitions on BCRP and CYP2C9. [ABSTRACT FROM AUTHOR]

Background: Issuing of correct prescriptions is a foundation of patient safety. Medication errors represent one of the most important problems in health care, with 'look-alike and sound-alike' (LASA) being the lead error. Existing solutions to prevent LASA still have their limitations. Deep learning techniques have revolutionized identification classifiers in many fields. In search of better image-based solutions for blister package identification problem, this study using a baseline deep learning drug identification (DLDI) aims to understand how identification confusion of look-alike images by human occurs through the cognitive counterpart of deep learning solutions and thereof to suggest further solutions to approach them.Methods: We collected images of 250 types of blister-packaged drug from the Out-Patient Department (OPD) of a medical center for identification. The deep learning framework of You Only Look Once (YOLO) was adopted for implementation of the proposed deep learning. The commonly-used F1 score, defined by precision and recall for large numbers of identification tests, was used as the performance criterion. This study trained and compared the proposed models based on images of either the front-side or back-side of blister-packaged drugs.Results: Our results showed that the total training time for the front-side model and back-side model was 5 h 34 min and 7 h 42 min, respectively. The F1 score of the back-side model (95.99%) was better than that of the front-side model (93.72%).Conclusions: In conclusion, this study constructed a deep learning-based model for blister-packaged drug identification, with an accuracy greater than 90%. This model outperformed identification using conventional computer vision solutions, and could assist pharmacists in identifying drugs while preventing medication errors caused by look-alike blister packages. By integration into existing prescription systems in hospitals, the results of this study indicated that using this model, drugs dispensed could be verified in order to achieve automated prescription and dispensing. [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]

Chronic kidney disease (CKD) is a health problem worldwide. Indoxyl sulfate (IS) is a nephro-cardiovascular toxin accumulated in CKD patients and cannot be removed through hemodialysis. The renal excretion of IS was mediated by organic anion transporters (OATs) OAT 1 and OAT 3. Because a number of nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to inhibit OATs, we hypothesize that NSAIDs might inhibit the renal excretion of IS. Rats were intravenously injected IS with and without diclofenac, ketoprofen or salicylic acid, individually. Blood samples were collected at predetermined time points and the concentrations of IS were determined by HPLC method. The results showed that diclofenac and ketoprofen at 10.0 mg/kg significantly decreased the systemic clearance of IS by 71% and 82%, and increased the MRT of IS by 106% and 105%, respectively, whereas salicylic acid did not exhibit significant effects. Cell studies indicated that diclofenac and ketoprofen inhibited the uptake of IS mediated by OAT 1 and OAT 3. In conclusion, diclofenac and ketoprofen inhibited the excretion of IS through inhibition on OAT 1 and OAT 3. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess a possible correlation between zolpidem use and acute pyelonephritis (APN) in women in Taiwan. Therefore, we performed a case-control study involving the Taiwan's National Health Insurance Research Database between 2000 and 2011. This study included 3151 female participants aged 20 to 84 years who experienced the first bout of APN (case group) and 6015 randomly selected female participants without APN (control group). Zolpidem use was defined as 'current,' 'early,' or 'late,' if the last remaining 1 tablet for zolpidem was detected within 7 days, between 8 and 14 days, or ≥15 days before the date of APN diagnosis, respectively. The multivariable unconditional logistic regression model was used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the correlation between zolpidem use and APN. After adjusting for confounders, the multivariable analysis yielded an adjusted APN OR of 2.2 for participants with current zolpidem use (95%CI 1.7-2.8) compared with participants who never used zolpidem. The adjusted ORs gradually decreased to 1.4 for participants with early zolpidem use (95%CI 0.8-2.5) and 1.1 for participants with late zolpidem use (95%CI 0.9-1.2), but without statistical significance. Only patients with current zolpidem use had a significantly increased relative risk of APN. Additional large confirmatory studies are needed to illustrate a causal relationship. Meanwhile, physicians and pharmacists should be more cautious about the risk of APN when prescribing and dispensing zolpidem in women. [ABSTRACT FROM AUTHOR]

Methadone is a widely used substitution therapy for opioid addiction. Large inter-individual variability has been observed in methadone maintenance dosages and P-glycoprotein (P-gp) was considered to be one of the major contributors. To investigate the mechanism of P-gp’s interaction with methadone, as well as the effect of genetic variants on the interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established in the present study. The RNA and protein expression levels of human P-gp were confirmed by real-time quantitative RT-PCR and western blot, respectively. Utilizing rhodamine 123 efflux assay and calcein-AM uptake study, methadone was demonstrated to be an inhibitor of wild-type human P-gp via non-competitive kinetic (IC50 = 2.17±0.10 µM), while the variant-type human P-gp, P-gp with 1236T-2677T-3435T genotype and P-gp with 1236T-2677A-3435T genotype, showed less inhibition potency (IC50 = 2.97±0.09 µM and 4.43±1.10 µM, respectively) via uncompetitive kinetics. Methadone also stimulated P-gp ATPase and inhibited verapamil-stimulated P-gp ATPase activity under therapeutic concentrations. These results may provide a possible explanation for higher methadone dosage requirements in patients carrying variant-type of P-gp and revealed the possible drug-drug interactions in patients who receive concomitant drugs which are also P-gp substrates. [ABSTRACT FROM AUTHOR]

Folium Sennae (FS), a popular laxative (Senna), contains polyphenolic anthranoids, whose conjugation metabolites are probable modulators of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). We suspected that the combined use of FS might alter the pharmacokinetics of various medicines transported by MRPs or BCRP. This study investigated the effect of FS on the pharmacokinetics of methotrexate (MTX), an anticancer drug and a probe substrate of MRPs/BCRP. Rats were orally administered MTX alone and with two dosage regimens of FS in a parallel design. The results show that 5.0 g/kg of FS significantly increased the AUC0–2880, AUC720–2880 and MRT of MTX by 45%, 102% and 42%, and the seventh dose of 2.5 g/kg of FS significantly enhanced the AUC720–2880 and MRT by 78% and 42%, respectively. Mechanism studies indicated that the metabolites of FS (FSM) inhibited MRP 2 and BCRP. In conclusion, the combined use of FS increased the systemic exposure and MRT of MTX through inhibition on MRP 2 and BCRP. [ABSTRACT FROM AUTHOR]

Antihypertensive drugs have been linked to new-onset diabetes (NOD); however, data on the effect of these drugs on the development of NOD in hypertensive patients has not been well determined in a clinical setting. The aim was to investigate the association between antihypertensive drugs and NOD in Taiwan. We conducted a retrospective study of hypertensive Taiwanese patients receiving antihypertensive drugs treatment between January 2006 and December 2011. Clinical information and laboratory parameters were collected by reviewing the medical records. We estimated the odds ratios (ORs) of NOD associated with antihypertensive drug use; nondiabetic subjects served as the reference group. A total of 120 NOD cases were identified in 1001 hypertensive patients during the study period. The risk of NOD after adjusting sex, age, baseline characteristics, and lipid profiles was higher among users of thiazide diuretics (OR, 1.65; 95% confidence interval (CI), 1.12-2.45) and nondihydropyridine (non-DHP) calcium channel blockers (CCBs) (OR, 1.96; 95% CI, 1.01-3.75) than among nonusers. Other antihypertensive drug classes were not associated with risk of NOD. Our results show that patients with hypertension who take thiazide diuretics and non-DHP CCBs are at higher risk of developing NOD than those who take other classes of antihypertensive drugs in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Medication adherence is critical for patient treatment. This study involved evaluating how implementing Short Message Service (SMS) reminders affected patient medication adherence and related factors.Methods: We used a structured questionnaire to survey outpatients at three medical centers. Patients aged 20 years and older who were prescribed more than 7 days of a prescription medication were randomized into SMS intervention or control groups. The intervention group received daily messages reminding them of aspects regarding taking their medication; the control group received no messages. A phone follow-up was performed to assess outcomes after 8 days. Data were collected from 763 participants in the intervention group and 435 participants in the control group.Results: After participants in the intervention group received SMS reminders to take medication or those in the control group received no messages, incidences of delayed doses were decreased by 46.4 and 78.8% for those in the control and intervention groups, respectively. The rate of missed doses was decreased by 90.1% for participants in the intervention group and 61.1% for those in the control group. We applied logistic regression analysis and determined that participants in the intervention group had a 3.2-fold higher probability of having a decrease in delayed doses compared with participants in the control group. Participants in the intervention group also showed a 2.2-fold higher probability of having a decrease in missed doses compared with participants in the control group.Conclusions: Use of SMS significantly affected the rates of taking medicine on schedule. Therefore, daily SMS could be useful for reminding patients to take their medicine on schedule. [ABSTRACT FROM AUTHOR]