Is use of a long-term proton pump inhibitor or histamine-2 receptor antagonist a risk factor for iron-deficiency anaemia in Taiwan? A neglected clinical drug-drug interaction.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists change the gastric pH and reduce the intestinal absorption of nonheme iron. Case reports and case-control studies have demonstrated that absorption of iron is affected by gastric acidity, but the clinical importance of these drug-drug interactions has remained uncertain. OBJECTIVES: The present case-control study employed 2 million longitudinal claims in 2011-2018 in the Taiwan National Health Insurance Research Database to investigate the impact of PPIs/H2 antagonists on the occurrence of iron-deficiency anaemia (IDA). METHODS: The present study retrospectively compared exposure to PPIs/H2 antagonists for 1 year among 5,326 cases with IDA and 21,304 matched controls. The postdiagnosis prescribing pattern was also calculated to understand current practice. RESULTS: Long-term (≥2 month) use of PPIs/H2 antagonists resulted in a higher risk of developing IDA than noncontinuous use/nonuse of those drugs (adjusted odds ratio [aOR] = 2.36, 95% confidence interval [CI] = 1.94-2.86, P < 0.001). There were significant changes in the postdiagnosis prescribing patterns of PPIs/H2 antagonists. The risk of developing IDA remained significant in the female subgroup (aOR = 2.16, 95% CI = 1.73-2.70, P < 0.001) and was even more prominent in those aged ≥ 50 years (aOR = 2.68, 95% CI = 1.94-3.70, P < 0.05). CONCLUSIONS: This study found that long-term use of PPIs/H2 antagonists increased the risk of developing IDA, and there was strong evidence of prescription pattern adjustments postdiagnosis. Physicians and pharmacists should be aware of this risk when patients are expected to take or have been taking PPIs/H2 antagonists for the long term.

Proton pump inhibitors (PPIs) and histamine-2 receptor (H2) antagonists, 2 kinds of gastric suppressants commonly used for gastroesophageal reflux disease, decrease iron absorption in the gut and thus increase the risk of developing iron-deficiency anaemia (IDA). We constructed a retrospective matched case-control study within the Taiwan National Health Insurance Research Database. The longer period of PPIs/H2 antagonists used, the higher risk of IDA was, with the highest risk in female elderly groups (adjusted odds ratio = 2.68 in females aged ≥ 50). PPI users had a higher risk than H2 antagonist users during the 1-year follow-up. The prescription patterns postdiagnosis of IDA witnessed considerable drops for both groups, with less than a 10th of original users remaining the usages (1.72% and 9.85% taking PPIs and H2 antagonists within 90 days after receiving a diagnosis, respectively). Physicians and pharmacists should be aware of the risk of developing IDA in patients currently undergoing or expected to take long-term gastric acid suppressants.

A Computer-Based Interactive Narrative and a Serious Game for Children With Asthma: Development and Content Validity Analysis.

BACKGROUND: Nonadherence to medications, failure to prevent exposure to asthma triggers, lack of knowledge about using medications, and fixed mindsets contribute to poor asthma control in children. Digital learning could provide a new strategy for improving health-related outcomes in children with asthma. OBJECTIVE: The aim of this study is to develop and design a digital educational program, titled Module of Inhaler and Asthma Triggers for Children (MIRACLE), for Indonesian children with asthma. The program comprises an interactive narrative and a serious game. It was proposed to increase the understanding of asthma self-management, instruct on proper inhaler techniques, improve asthma control, and promote a growth mindset for children with asthma. METHODS: Two phases of research were conducted to develop the program. In the first phase, a literature search and two rounds of the Delphi technique were conducted to obtain agreement from an expert panel regarding elements of asthma self-management and the design of interactive narratives and a serious game. The expert panel item statements were evaluated using the content validity index (CVI). In the second phase, the SERES framework, Norma Engaging Multimedia Design, and Psychological Theory of Growth Mindset were applied to create a storyline, learn objectives, and game challenges. RESULTS: In the first phase, 40 experts were invited to participate in Delphi round 1. Forty responses were collected to generate 38 item statements that consisted of part 1, elements of asthma self-management (25 items), and part 2, design of an interactive narrative and a serious game (13 items); 38 experts were involved in Delphi round 2. In total, 24 statements in part 1 and 13 items in part 2 had item-CVI values >0.80. The average CVI was 0.9, which was considered acceptable. Four narrative plots and five game sessions were developed during the second phase. Challenges with the scenario, scoring, and feedback on asthma difficulties were designed to promote a growth mindset for learners. CONCLUSIONS: We developed a culture-specific, computer-based asthma program containing an interactive narrative and a serious game to deliver asthma self-management and promote a growth mindset among Indonesian children.

A novel preventive mechanism of gentamicin-induced nephrotoxicity by atorvastatin.

Atorvastatin (ATO) inhibits the synthesis of nonsteroidal isoprenoid compounds and possesses a pleiotropic effect. However, the detailed mechanism of ATO in preventing gentamicin (GM)-induced renal injury remains obscure. Although underlying multifaceted mechanisms involving GM-induced nephrotoxicity were well known, further work on elucidating the essential mechanism was needed. Using a fluorogenic derivatization-liquid chromatography tandem mass spectrometry proteomic method (FD-LC-MS/MS method), we investigated the effects and mechanisms of ATO treatment on GM-induced nephrotoxicity in rats. Consequently, 49 differentially expressed proteins were identified. The most significant mechanisms of nephrotoxicity caused by GM were mitochondrial dysfunction, fatty acid metabolism and oxidative stress. Their upstream regulator was found to be PPARα. The proteins involved in GM nephrotoxicity were sodium-hydrogen exchanger regulatory factor (SLC9A3R1), cathepsin V (CTSV), macrophage migration inhibitory factor (MIF) and RhoGDP dissociation inhibitor alpha (ARHGDIA). After ATO intervention, we observed a reversed enrichment pattern of their expression, especially in CTSV and SLC9A3R1 (P-value<0.05). We predicted that ATO may improve abnormal phospholipid metabolism and phospholipidosis caused by GM and also alleviate cell volume homeostasis and reverse the interference of GM with the transporter. Furthermore, proteomic results also provided clues as to GM-induced nephrotoxicity biomarkers such as CTSV and transthyretin.

The association between urbanization and rheumatoid arthritis in Taiwan.

OBJECTIVES: To investigate the association between rheumatoid arthritis (RA) and urbanization and compare the medication selection for RA patients in urban vs. rural areas. METHODS: RA patients were identified among 1,000,000 random individuals from a 23-million-person nationwide health insurance database, and controls were matched at a 1 : 10 ratio. Taiwan's 359 townships were grouped into 7 urbanization levels. Geographic region and monthly income were also analyzed. Medication use in the most urbanized and less-urbanized areas were also compared. RESULTS: Rural dwellers had lower odds of having an RA diagnosis. The odds ratio (OR) for level 5 area residents of having an RA diagnosis was 0.62 (95% confidence interval (CI) 0.46 - 0.85; p = 0.002), and they were both 0.76 for level 6 - 7 area residents (95% CI, 0.61 - 0.95 for level 6; p = 0.017 and 0.60 - 0.96 for level 7; p = 0.021) compared to level 1 (the most urban dwellers). The ORs of having a new RA diagnosis were 0.57 (95% CI 0.41 - 0.79, p = 0.001) in eastern Taiwan and 0.33 (95% CI 0.15 - 0.69, p = 0.004) on offshore islands compared to northern Taiwan. No association was found between monthly income and RA. Urban-dwelling RA patients used more tumor necrosis factor-α antagonists (level 1 urbanization; n = 24; 2.3%) than RA patients in less-urbanized areas (level 2 - 7 urbanization n = 30; 1.3%; p = 0.038). CONCLUSION: Results of this study suggested that an RA diagnosis and treatment are associated with urbanization.

Clinical evaluation of tigecycline in the treatment of nosocomial infection in a hospital in Taiwan.

OBJECTIVE: Clinical information on tigecycline use in serious nosocomial infections is limited, and the efficacy is uncertain. The aim of this retrospective study was to assess the utilization pattern and the effectiveness of tigecycline in a tertiary medical center in Taiwan. METHODS: A retrospective study of the clinical and microbiological outcome of all patients treated with tigecycline for at least 72 hours over a 2-year period was conducted in a 730-bed teaching hospital. RESULTS: Data from 133 patients with 149 cases of nosocomial infection were analyzed in this assessment. The mean APACHE II score at the initiation of tigecycline therapy was 22.5 ± 8.8, and the mean duration of treatment was 11.4 ± 5.6 days. Pneumonia was the most frequently diagnosed clinical indication for tigecycline use (113 cases, 76%). An overall positive clinical outcome was observed in 75 cases (50%). Multidrug-resistant Acinetobacter baumannii (MDRAB) is the most common organism for tigecycline therapy (n = 59), with a positive clinical outcome of 38% in tigecycline monotherapy, 66% in dualtherapy, and 17% in triple-therapy (p = 0.031). The most commonly used combining agents with tigecycline to treat MDRAB infections were intravenous colistin, inhaled colistin, and cepoferazone/sulbactam, with positive clinical outcome rates of 53%, 100%, and 80%, respectively. Admission to intensive care unit was identified as a predictive factor for negative clinical outcome. CONCLUSION: Our pneumonia-dominated study population demonstrated a lower clinical improvement rate of tigecycline compared to previous published data. Tigecycline monotherapy is not recommended for MDRAB infection, but colistin or cephoperazone/ sulbactam combined with tigecycline seemed to yield a good clinical outcome for MDRAB infection.

Clinical and economic impact of a pharmacist-managed i.v.-to-p.o. conversion service for levofloxacin in Taiwan.

OBJECTIVE: A pharmacist-managed antibiotic intravenous to oral (i.v.-top. o.) conversion program has been incorporated to minimize unnecessary i.v. antibiotic usage. This study evaluated the clinical and economical impacts of a pharmacist-directed i.v.-to-p.o. conversion program for levofloxacin in Taiwan. METHODS: Data was retrospectively collected by chart review during the pre-intervention period (PIP). During the intervention proactive conversion period (PCP), pharmacists reviewed and intervened on all levofloxacin orders. The detailed reimbursements for medications and inpatient expenses from the Bureau of National Health Insurance (NHI), Taiwan were calculated. The clinical impacts during the PIP and PCP were compared with the duration of the i.v. levofloxacin therapy, total used i.v./p.o. ratio levofloxacin, and total length of hospital stay. The financial impact was compared with medication costs and total inpatient expenditures. RESULTS: The mean length of hospital stay was significantly decreased from 27.2 days to 16.1 days (p = 0.001) after the conversion program was implemented. The i.v. over p.o. ratio for DDD was 3.0 ± 0.6 vs. 2.1 ± 0.6 for PIP vs. PCP group (p = 0.032). The cost of the levofloxacin was significantly decreased ($ 568.9 ± 262.9 vs. $ 449.0 ± 266.4, PIP vs. PCP, p = 0.044). The total inpatient expenditures were also significantly reduced ($ 6,096 ± 5,164.0 vs. $ 3,649.6 ± 3, 740.4, PIP vs. PCP, p = 0.017). CONCLUSIONS: The pharmacist-managed i.v.-to-p.o. conversion service not only decreased the length of hospital stays, but also produced significant cost savings, both on medication costs and the total inpatient expenditures. This represents strong evidence for implementing the i.v.-to-p.o. conversion service in Taiwan.

Ocular Disease Therapeutics: Design and Delivery of Drugs for Diseases of the Eye.

The ocular drug discovery field has evidenced significant advancement in the past decade. The FDA approvals of Rhopressa, Vyzulta, and Roclatan for glaucoma, Brolucizumab for wet age-related macular degeneration (wet AMD), Luxturna for retinitis pigmentosa, Dextenza (0.4 mg dexamethasone intracanalicular insert) for ocular inflammation, ReSure sealant to seal corneal incisions, and Lifitegrast for dry eye represent some of the major developments in the field of ocular therapeutics. A literature survey also indicates that gene therapy, stem cell therapy, and target discovery through genomic research represent significant promise as potential strategies to achieve tissue repair or regeneration and to attain therapeutic benefits in ocular diseases. Overall, the emergence of new technologies coupled with first-in-class entries in ophthalmology are highly anticipated to restructure and boost the future trends in the field of ophthalmic drug discovery. This perspective focuses on various aspects of ocular drug discovery and the recent advances therein. Recent medicinal chemistry campaigns along with a brief overview of the structure-activity relationships of the diverse chemical classes and developments in ocular drug delivery (ODD) are presented.

Cultural Sensitivity and Global Pharmacy Engagement in Asia: China, Japan, South Korea, and Taiwan.

Interest in global engagement among schools and colleges of pharmacy in the United States and Asian countries is growing. To develop fruitful relationships and engage in mutually enriching experiences, the cultural aspects of these countries need to be understood and respected. The aim of this paper is to facilitate culturally sensitive interactions between practitioners, faculty members, and students in the United States and those in Asian countries when they engage in health care practice and/or education. This paper introduces general information about China (including Macau and Hong Kong), Japan, South Korea, and Taiwan. Unique characteristics of the health care system and pharmacy education are described for each country. Stereotypes and misconceptions are discussed. Recommendations are included for initiating interactions and developing learning programs and scholarly collaborations while promoting culturally sensitive engagement. These recommendations are provided for US scholars, health care professionals, and students traveling to these countries as well as for those hosting visitors from these countries in the United States.

The effect of medication therapy management service combined with a national PharmaCloud system for polypharmacy patients.

BACKGROUND: This study evaluated a medication therapy management service using the Taiwan National Health Insurance Administration's PharmaCloud system in a medical center in Taiwan. The new PharmaCloud System, launched in 2013, links a complete list of prescribed and dispensed medication from different hospitals, clinics, and pharmacies for all insured patients. METHOD: The study included patients with polypharmacy (≥5 drugs) at a medication therapy management service from March 2013 to March 2014. A structured questionnaire was designed to collect patients' baseline data and record patients' knowledge, attitudes, and practice scores before and after the service intervention. Phone follow-ups for practice and adherence scores on medication use were performed after 3 months. RESULTS: There were 152 patients recruited in the study. Scores for medication use attitudes and practice significantly increased after the service (attitudes: 40.06 ± 0.26 to 43.07 ± 0.19, p <0.001; practice: 33.42 ± 0.30 to 40.37 ± 0.30, p <0.001). The scores for medication adherence also increased from 3.02 ± 0.07 to 3.92 ± 0.02 (p <0.001). CONCLUSIONS: The PharmaCloud system facilitates accurate and efficient medication reconciliation for pharmacists in the medication therapy management service. The model improved patients' attitudes and practice of the rational use of medications and adherence with medications. Further studies are warranted to evaluate human resources, executing costs, and the cost-benefit ratio of this medication therapy management service with the PharmaCloud system.

HPLC assay for albendazole and metabolites in human plasma for clinical pharmacokinetic studies.

A sensitive and selective HPLC chromatography method using UV detection (295 nm) was developed for the determination of albendazole, albendazole sulfoxide (ABZSO), and albendazole sulfone (ABZSO2) in human plasma. Albendazole, ABZSO, ABZSO2, and the internal standard, oxibendazole, were extracted from human plasma by loading onto a conditioned C(18) SPE cartridge, rinsing with 15% methanol, and eluting with 90% methanol. Samples were evaporated under a stream of nitrogen, reconstituted with mobile phase, 1.25% triethylamine in water-methanol-acetonitrile (72:15:13, v/v/v) (pH* 3.1), and injected onto a Waters muBondapak Phenyl 3.9 x 300 mm HPLC column. Mobile phase flow rate was 1.0 ml/min. The retention times of albendazole, ABZSO, ABZSO2, and the internal standard were approximately 24.4, 7.9, 13.4, and 11.3 min, respectively. Total run time was 30 min. The assay was linear for concentration ranges in human plasma of 20-600 ng/ml for albendazole, 20-1000 ng/ml for ABZSO, and 20-300 ng/ml for ABZSO2. The analysis of quality control samples demonstrated excellent precision. Coefficients of variation for albendazole (20, 400, 600 ng/ml) were 6.7, 8.1 and 7.0%; ABZSO (20, 400, 800 ng/ml) were 6.0, 8.5 and 5.9%; ABZSO2 (20, 150, 300 ng/ml) were 3.1, 3.9 and 2.3%, respectively. The method appears to be robust and has been applied to a pharmacokinetic study of albendazole in healthy volunteers.

Evaluating an online pharmaceutical education system for pharmacy interns in critical care settings.

Incorporating electronic learning (eLearning) system into professional experimental programs such as pharmacy internships is a challenge. However, none of the current systems can fully support the unique needs of clinical pharmacy internship. In this study we enhanced a commercial eLearning system for clinical pharmacy internship (The Clinical Pharmacy Internship eLearning System, CPIES). The KAP questionnaire was used to evaluate the performance of group A with the traditional teaching model and group B with the CPIES teaching model. The CPIES teaching model showed significant improvement in interns' knowledge and practice (p = 0.002 and 0.031, respectively). The traditional teaching model only demonstrated significant improvement in practice (p = 0.011). Moreover, professionalism, such as attitudes on cooperating with other health professionals, is developed by learning from a good mentor. The on-line teaching and traditional teaching methods should undoubtedly be blended in a complete teaching model in order to improve learners' professional knowledge, facilitate correct attitude, and influence good practice.

Comparison of the pharmacokinetics of moxidectin and ivermectin after oral administration to beagle dogs.

This study compares plasma disposition kinetics of ivermectin and moxidectin after oral administration to beagle dogs experimentally infected with the filarial parasite, Brugia pahangi. Sixteen dogs were selected and randomly allocated into two groups of eight dogs each. Animals in each group received either ivermectin or moxidectin by oral route at a dose of 250 microg/kg. Blood samples were collected from 0.5 h up to 56 days post-treatment and the plasma was analysed by high performance liquid chromatography (HPLC). The obtained data were analysed by compartmental and non-compartmental pharmacokinetic techniques. Peak plasma concentrations (C(max)) of 234.0 +/- 64.3 ng/ml (mean +/- SD) were obtained for moxidectin and 132.6 +/- 43.0 ng/ml for ivermectin. The terminal elimination half-life was significantly (p<0.01) longer in the moxidectin treated group (621.3 +/- 149.3 h) than for ivermectin treated group (80.3 +/- 29.8 h). A significantly (p< 0.01) larger V(ss)/F was obtained for moxidectin (19.21 +/- 3.61 l/kg) compared with ivermectin (5.35 +/- 1.29 l/kg). The mean estimates of CL/F of moxidectin and ivermectin were 0.0220 +/- 0.00381 and 0.0498 +/- 0.0179 l/h/kg, respectively. The comparative plasma disposition kinetics of ivermectin and moxidectin in dogs is reported for the first time.