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Background: Prescribing inappropriate pill splitting is not rare in clinical practice. To reduce inappropriate pill splitting, we developed an automatic warning system linked to a computerized physician order entry (CPOE) system for special oral formulation drugs in outpatient settings. We examined the impact of the warning system on inappropriate prescribing of pill splitting and assess prescribers' responses to the warnings. Methods: Drugs with extended-release or enteric-coated formulations that were not originally intended to be split were recognized as “special oral formulations”. A hard-stop system which could examine non-integer doses of drugs with special oral formulations, provide warnings to interrupt inappropriate prescriptions was integrated in CPOE in a medical center since June 2010. We designed an intervention study to compare the inappropriate splitting before and after the implementation of the warning system (baseline period 2010 January to May vs. intervention period 2010 June to 2011 August). During the intervention period, prescription changes in response to a warning were logged and analyzed. Results: A total of 470,611 prescribed drug items with 34 different drugs with special oral formulations were prescribed in the study period. During the 15-month intervention period, 909 warnings for 26 different drugs were triggered among 354,523 prescribed drug items with special oral formulations. The warning rate of inappropriate splitting in the late intervention period was lower than those in baseline period (0.16% vs. 0.61%, incidence rate ratio 0.27, 95% CI 0.23–0.31, P<0.001). In respond to warnings, physicians had to make adjustments, of which the majority was changing to an unsplit pill (72.9%). Conclusions: The interruptive warning system could avoid the prescriptions with inappropriate pill splitting. Accordingly, physicians changed their behavior of prescribing special oral formulations regarding inappropriate pill splitting. We suggest the establishment of such system to target special oral formulations with warnings to prevent inappropriate pill splitting. [ABSTRACT FROM AUTHOR]

Highlights: [•] Resonant control on thermoacoustic engines to amplify power rating. [•] Least-action principle of thermoacoustic dynamics to shape engine chamber. [•] Spatiotemporal transfer function into feedback systems. [•] Conservation law of thermoacoustic storage to figure out engine cycles. [•] Robin boundary condition to identify flow leakage. [Copyright &y& Elsevier]

Background: To investigate the nationwide trend of ambulatory prescriptions of short-acting nifedipine on a PRN (pro re nata) order over a fifteen-year period in Taiwan. Methods: The systematic sampling claims datasets (0.2% sampling ratio) of ambulatory care visits within Taiwan's National Health Insurance from 1997 to 2011 were analyzed. The prescriptions of short-acting capsule-form nifedipine on a PRN order were stratified by the patient's age, the prescribing physician's specialty, and the setting of healthcare facility for each year. Results: During the study period, 8,189,681 visits were analyzed. While the utilization rate of calcium channel blockers changed with time from 2.8% (13,767/489,636) in 1997 to 5.1% (31,349/614,719) in 2011, that of short-acting nifedipine were from 1.0% (n = 5,070) to 0.2% (n = 1,246). However, short-acting capsule-form nifedipine on a PRN order still existed (from 447 prescriptions in 1997 to 784 in 2011). More than one half of these PRN nifedipines were prescribed by the internists and to the elderly patients; almost four-fifths of PRN nifedipines were prescribed during non-emergent consultations. Conclusion: The physicians in Taiwan still had the habit of prescribing short-acting nifedipines for PRN use. The reason for such practices and the impact on patients' health deserve attention. [ABSTRACT FROM AUTHOR]

Background: Prescription errors that occur due to the process of pill splitting are a common medication problem; however, available prescription information involving inappropriate pill splitting and its associated factors is lacking. Methods: We retrospectively evaluated a cohort of ambulatory prescriptions involving extended-release or enteric-coated formulations in a Taiwan medical center during a 5-month period in 2010. For this study, those pill splitting prescriptions involving special oral formulations were defined as inappropriate prescriptions. Information obtained included patient demographics, prescriber specialty and prescription details, which were assessed to identify factors associated with inappropriate pill splitting. Results: There were 1,252 inappropriate prescriptions identified in this cohort study, representing a prescription frequency for inappropriate pill splitting of 1.0% among 124,300 prescriptions with special oral formulations. Among 35 drugs with special oral formulations in our study, 20 different drugs (57.1%, 20/35) had ever been prescribed to split. Anti-diabetic agents, cardiovascular agents and central nervous system agents were the most common drug classes involved in inappropriate splitting. The rate of inappropriate pill splitting was higher in older (over 65 years of age) patients (1.1%, 832/75,387). Eighty-seven percent (1089/1252) of inappropriate prescriptions were prescribed by internists. The rate of inappropriate pill splitting was highest from endocrinologists (3.4%, 429/12,477), nephrologists (1.3%, 81/6,028) and cardiologists (1.3%, 297/23,531). Multivariate logistic regression analysis revealed that the strongest factor associated with individual specific drug of inappropriate splitting was particular physician specialties. Conclusion: This study provides important insights into the inappropriate prescription of special oral formulation related to pill splitting, and helps to aggregate information that can assist medical professionals in creating processes for reducing inappropriate pill splitting in the future. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion (I/R) injury is marked by rapid increase in inflammation and not only results in myocardial apoptosis but also compromises the myocardial function. Dunaliella salina (D. salina), a halophilic unicellular microalga, has been used as a provitamin A carotenoid supplement and color additive. Several studies have reported that D. salina extract could attenuate lipopolysaccharides-induced inflammatory effects and regulate the virus-induced inflammatory response in macrophages. However, the effects of D. salina on myocardial I/R injury remain unknown. Therefore, we aimed to investigate the cardioprotection of D. salina extract in rats subjected to myocardial I/R injury that was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion. Compared with the vehicle group, the myocardial infarct size significantly decreased in rats that were pre-treated with D. salina. D. salina significantly attenuated the expressions of TLR4, COX-2 and the activity of STAT1, JAK2, IκB, NF-κB. Furthermore, D. salina significantly inhibited the activation of caspase-3 and the levels of Beclin-1, p62, LC3-I/II. This study is the first to report that the cardioprotective effects of D. salina may mediate anti-inflammatory and anti-apoptotic activities and decrease autophagy through the TLR4-mediated signaling pathway to antagonize myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Abstract: This paper develops game-theoretic LPV control with multiple -gain objectives to manage the trade-off between energy economy and motion dexterousness of electric scooters. Here a second-order LPV modeling from system identification is incorporated with energy and motion objectives contradictory to each other to form a generalized plant, served for game-theoretic feedback synthesis. In the game-theoretic synthesis, both objectives share the same control and estimation storages, thus reducing the conservatism conventionally happened in robust/optimal control with multiple objectives. Moreover, the feedback controller has a definite structure, thus facilitating the iteration of control modeling and control synthesis to reach a sound design. At the stage of pilot run, it is found that the control design can significantly suppress current overshoots with just a little bit of retard in speed, thus fulfilling the energy–motion regulation. [Copyright &y& Elsevier]

Abstract: The present mainstream realizes that non-Fourier phenomena in heat transfer are arisen from the time-delay in heat diffusion; however, in this paper we mathematically prove this realization an untruth. The analysis is based on the construction of 2D transfer function for the parabolic equation with time-delayed Laplacian that governs the assumed non-Fourier heat transfer. There, functional representation of this spatio-temporal dynamics is performed by the composite of Laplace transform and Galerkin projection. With 2D transfer function, the heat-transfer dynamics is further represented by feedback interconnection of thermal capacitance and time-delayed diffusion, which makes it possible for Nyquist to perform stability and bifurcation analyses on this spatio-temporal dynamics. It comes out that the heat-transfer dynamics under investigation is unstable no matter how small the time-delay in heat diffusion is. That is, time-delayed heat diffusion contradicts the first law of thermodynamics and thus cannot be observed. This paper continues to show that the realization of thermal inertia by thermal inductance is supported by the principle of electro-thermal analogy and compatible with experimental observations. [Copyright &y& Elsevier]

Abstract: Dimemorfan (d-3-methyl-N-methylmorphinan), an analogue of dextromethorphan, is commonly used as a non-opioid antitussive. To clarify the contribution of cytochrome P450 (P450) in dimemorfan N-demethylation, effects of selective inducers and inhibitors were studied in ICR mice. Phenobarbital (PB)- and dexamethasone (Dex)-treatments caused 5-fold increases of liver microsomal dimemorfan N-demethylation activity. In untreated mouse liver microsomes, demethylation activity was strongly inhibited by a CYP3A inhibitor, ketoconazole. In PB-and Dex-treated mouse liver microsomes, ketoconazole caused strong inhibition, whereas orphenadrine caused a decrease of less than 20%. Pretreatment of control mouse liver microsomes with anti-CYP3A inhibited demethylation activity, whereas pre-treatment with anti-CYP2B had no effect. In PB-and Dex-treated mouse liver microsomes, the demethylation activity was inhibited by both anti-CYP3A and anti-CYP2B. In control mice, the intrinsic clearance of dimemorfan from N-demethylation was 5.8 μl min− 1mg protein− 1. In PB- and Dex-treated mice, the correlation coefficient of fitting using one-enzyme and two-enzyme models were similar. The intrinsic clearances of induced mouse liver microsomes were similar. These results revealed that CYP3A played a major role in hepatic demethylation in untreated mice. Both CYP3A and CYP2B were involved in this demethylation in PB- and Dex-treated mice. [Copyright &y& Elsevier]

Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end-stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m2 ) still unclear. The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy-five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure (total cardiovascular (CV) event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg had the lowest MACE (11.0%; 13.2%) and total CV event (23.3%; 21.1%). Patients with systolic BP < 120 mm Hg had a higher risk of MACE (HR: 2.01; 95% CI: 1.17-3.46, p = .008) than those with systolic BP 140-149 mm Hg. Patients with systolic BP ≥ 160 mm Hg (HR: 1.84; 95% CI, 3.27-1.04, p = .04) and diastolic blood BP ≥ 90 mm Hg (HR: 2.19; 95% CI: 1.15-4.16, p = .02) had a higher risk of total CV event rate when compared to those with systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg. A J-shaped association between systolic (140-149 mm Hg) and diastolic (80-89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non-Western population. [ABSTRACT FROM AUTHOR]

Background: This study examines the predictive value of a novel systemic immune‐inflammation index (SII, platelet × neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients. Methods: A total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long‐term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure. Results: An optimal SII cut‐off point of 694.3 × 109 was identified for MACE in the CAD training cohort (n = 373) and then verified in the second larger CAD cohort (n = 5602). Univariate and multivariate analyses showed that a higher SII score (≥694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43‐2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09‐1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28‐2.99), MACE (HR: 1.65; 95% CI: 1.36‐2.01) and total major events (HR: 1.53; 95% CI: 1.32‐1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C‐index (P <.001) and reclassification risk categories by significant NRI (P <.05) and IDI (P <.05). Conclusions: SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention. [ABSTRACT FROM AUTHOR]

Hyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined. We enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure. During an average 65.06 ± 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78–3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53–3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52–16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32–5.05), and total major CV events (HR: 2.72, 95% CI: 2.09–3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36–1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38–1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13–1.82), CV death (HR: 1.77, 95% CI: 1.50–2.11), HF (HR: 1.43, 95% CI: 1.29–1.58), and total major CV events (HR: 1.46, 95% CI: 1.34–1.58). High UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI). Image 1 • High uric acid (UA) variability is associated with increased risk of developing future adverse outcome in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI). • Both higher UA variability and average UA value were significantly associated with a higher CV event occurrence. • High UA variability had greater impact than high average UA value in patients with CAD. [ABSTRACT FROM AUTHOR]