Significance of pharmacist intervention to oral antithrombotic therapy in the pharmaceutical outpatient clinic of cardiovascular internal medicine: a retrospective cohort study.

BACKGROUND: Optimised antithrombotic therapy requires clinical experience and an understanding of the current guidelines. This retrospective study aimed to evaluate whether pharmacist interviews and interventions with patients taking oral antithrombotic drugs in the pharmaceutical outpatient cardiology clinic had favourable clinical outcomes including decreased bleeding. METHODS: The participants included patients visiting the outpatient clinic of cardiovascular internal medicine at the Kobe University Hospital from January-December 2017, and were taking oral antithrombotic medication. The observation period was from the first visit to the outpatient clinic to October 2021 or death. Patients who received pharmacist intervention more than twice were defined as the pharmacist intervention group. Two control patients per one pharmacist intervention group individual were selected from the non-intervention pool matched for age, gender and antithrombotic medication type. RESULTS: Of the 895 eligible patients, 132 were in the pharmacist intervention group and 264 were selected for the matched non-intervention group. Bleeding events according to the Bleeding Academic Research Consortium criteria over type 2 were significantly lower in the pharmacist intervention group compared with the non-intervention group (17.4% versus 28.4%, P = 0.019). There were no significant differences in mortality and heart failure hospitalisation frequency, stroke, or cardiovascular events between the groups. Multivariate analysis identified age (≥ 65 years) and pharmacist intervention as factors associated with bleeding (odds ratio = 2.29 and 0.51, respectively). CONCLUSION: Pharmacist intervention in the outpatient clinic of cardiovascular internal medicine was effective in reducing the risk of bleeding in patients undergoing antithrombotic therapy.

Enhancing Study Motivation and Efficacy among First-year Students Using Minute Papers in the Interdisciplinary Subject of Yakugaku Nyumon.

Active learning in higher education is important for learning efficacy and motivation. Accordingly, lectures that integrate strategies toward active learning, such as minute papers, debates, and collaborative learning, have become widely adopted. Minute papers facilitate communication among both teachers and students, and can be used as a tool for reviewing lectures. In the present study, we examined the effect of using minute papers on learning efficacy and motivation. To enhance the curriculum of the interdisciplinary course Yakugaku Nyumon, which consists of an omnibus lecture series and problem-based learning, minute papers with exercises were provided to applicants. In a follow-up questionnaire, students who used minute papers (S-USE) responded that they had a better understanding of the relationships, ranging from basic to clinical subject matter, than students who did not use such papers (S-NON). Using the Attention, Relevance, Confidence, and Satisfaction (ARCS) model questionnaire to measure study motivation, S-USE scored higher for some questionnaires than S-NON. This finding indicates that minute papers promoted learning motivation among students taking the Yakugaku Nyumon course. In regular examinations, the average score of S-USE was also statistically higher than that of S-NON. These results demonstrate that minute papers possibly encouraged students to actively review the lectures, thereby increasing both learning efficacy and motivation. This study shows that through promoting active, self-learning, minute papers are suitable for improving curricular strategies in subjects that rely on passive learning methods.

Interdisciplinary Subject "Yakugaku Nyumon" for First-year Students Constructed with Lectures and Problem-based Learning.

In 2013, Kobe Pharmaceutical University established "Yakugaku Nyumon", an interdisciplinary course, which consists of omnibus lectures and problem-based learning (PBL) on topics ranging from basic to clinical subjects. The themes of the PBL were original ones; "Study from package inserts of aspirin", which aimed to reinforce the contents of the interdisciplinary lectures, and "Let's think about aspirin derivatives (super-aspirin)", which aimed to engender an interest in studying pharmacy. The PBL featured questions from teachers to help with study and was therefore referred to as "question-led PBL" (Q-PBL). The Q-PBL regarding aspirin derivatives began with preparing answers to the questions for a small group discussion (SGD) as an assignment, followed by a SGD, a presentation, and peer-feedback. From an analysis of the questionnaire survey, it was found that students considered the Q-PBL satisfying and that they had achieved the 4 aims: (1) to increase the motivation to study, (2) to enhance an understanding of the relations and significance of basic and clinical sciences, (3) to comprehend the learning content, and (4) to recognize the importance of communication. The Q-PBL with assignments has two favorable points. One is that the first-year students can challenge difficult and high-level questions when they are given these as assignments. The other is that students, who are unfamiliar with SGD can engage in discussions with other students using the knowledge gained from the assignment. The introduction of omnibus lectures and Q-PBL, along with these improvements in theme, application, and review process, promises increased learning efficacy at the university.

Energy evaluation of a bio-inspired gait modulation method for quadrupedal locomotion.

We have proposed a bio-inspired gait modulation method, by means of which a simulated quadruped model can successfully perform smooth, autonomous gait transitions from a walk to a trot to a gallop, as observed in animals. The model is equipped with a rhythm generator called a central pattern generator (CPG) for each leg. The lateral neighbouring CPGs are mutually and inhibitorily coupled, and the CPG network is hardwired to produce a trot. Adding only the simple feedback of body tilt to each CPG, which was based on input from the postural reflex, led to the emergence of un-programmed walking and galloping at low and high speeds, respectively. Although this autonomous gait transition was a consequence of postural adaptation, it coincidentally also resulted in the minimization of energy consumption, as observed in real animals. In simulations at a variety of constant speeds the energy cost was lower for walking at low speeds and for galloping at high speeds than it was for trotting. Moreover, each gait transition occurred at the optimal speed, such that the model minimised its energy consumption. Thus, gait transitions in simulations that included the bio-inspired gait modulation method were similar to those observed in animals, even from the perspective of energy consumption. This method should therefore be a preferred choice for motion generation and control in biomimetic quadrupedal locomotion.

A simple rule for quadrupedal gait generation determined by leg loading feedback: a modeling study.

We discovered a specific rule for generating typical quadrupedal gaits (the order of the movement of four legs) through a simulated quadrupedal locomotion, in which unprogrammed gaits (diagonal/lateral sequence walks, left/right-lead canters, and left/right-lead transverse gallops) spontaneously emerged because of leg loading feedbacks to the CPGs hard-wired to produce a default trot. Additionally, all gaits transitioned according to speed, as seen in animals. We have therefore hypothesized that various gaits derive from a trot because of posture control through leg loading feedback. The body tilt on the two support legs of each diagonal pair during trotting was classified into three types (level, tilted up, or tilted down) according to speed. The load difference between the two legs led to the phase difference between their CPGs via the loading feedbacks, resulting in nine gaits (3(2): three tilts to the power of two diagonal pairs) including the aforementioned.

Comparison of the effects of azole antifungal agents on the anticoagulant activity of warfarin.

The package insert of the antithrombotic agent warfarin warns users of its interaction with azole antifungals. However, information on the frequency or degree of these interactions is limited. In particular, the time to onset of azole-mediated prothrombin time prolongation, expressed as the international normalized ratio (INR), is poorly characterized. Therefore, we retrospectively examined the INR in 29 patients administered warfarin with fluconazole (FLCZ), voriconazole (VRCZ), or itraconazole (ITCZ). INRs in 18 patients taking FLCZ and in 5 patients taking VRCZ significantly increased from 1.40 to 2.94 and from 1.95 to 2.89, respectively. The warfarin sensitivity index (WSI), calculated as INR/daily warfarin dose, also significantly increased from 1.06 to 1.89 with FLCZ and showed an upward trend from 1.13 to 2.23 with VRCZ. ITCZ had no influence on the INR or WSI in 6 patients. The INRs observed when warfarin was coadministered with azoles (Y) correlated significantly with those observed in the absence of azoles (X): FLCZ, Y=4.94X-3.96, r(2)=0.80; VRCZ, Y=2.13X-1.27, r(2)=0.93. Moreover, in all 8 patients with closely monitored INRs, the WSI increased within 1 week of FLCZ or VRCZ coadministration. In conclusion, FLCZ and VRCZ augmented the anticoagulant activity of warfarin. The INR should be closely monitored within 1 week of initiating FLCZ or VRCZ coadministration with warfarin, especially in patients with high INRs.

Analysis of the gait generation principle by a simulated quadruped model with a CPG incorporating vestibular modulation.

This study aims to understand the principles of gait generation in a quadrupedal model. It is difficult to determine the essence of gait generation simply by observation of the movement of complicated animals composed of brains, nerves, muscles, etc. Therefore, we build a planar quadruped model with simplified nervous system and mechanisms, in order to observe its gaits under simulation. The model is equipped with a mathematical central pattern generator (CPG), consisting of four coupled neural oscillators, basically producing a trot pattern. The model also contains sensory feedback to the CPG, measuring the body tilt (vestibular modulation). This spontaneously gives rise to an unprogrammed lateral walk at low speeds, a transverse gallop while running, in addition to trotting at a medium speed. This is because the body oscillation exhibits a double peak per leg frequency at low speeds, no peak (little oscillation) at medium speeds, and a single peak while running. The body oscillation autonomously adjusts the phase differences between the neural oscillators via the feedback. We assume that the oscillations of the four legs produced by the CPG and the body oscillation varying according to the current speed are synchronized along with the varied phase differences to keep balance during locomotion through postural adaptation via the vestibular modulation, resulting in each gait. We succeeded in determining a single simple principle that accounts for gait transition from walking to trotting to galloping, even without brain control, complicated leg mechanisms, or a flexible trunk.

Restored expression and activity of organic ion transporters rOAT1, rOAT3 and rOCT2 after hyperuricemia in the rat kidney.

We previously reported that in hyperuricemic rats, renal impairment occurred and organic ion transport activity decreased, accompanied with a specific decrease in the expression of rat organic anion transporters, rOAT1 and rOAT3, and organic cation transporter, rOCT2. In the present study, we investigated the reversibility of the organic ion transport activity and expression of organic ion transporters (slc22a) during recovery from hyperuricemia. Hyperuricemia was induced by the administration of a chow containing uric acid and oxonic acid, an inhibitor of uric acid metabolism. Four days after discontinuance of the chow, the plasma uric acid concentration returned to the normal level, and renal functions such as creatinine clearance and BUN levels were restored, although the recovery of tubulointerstitial injury was varied in sites of the kidney. Basolateral uptake of p-aminohippurate (PAH) and tetraethylammonium (TEA), and both protein and mRNA levels of rOAT1, rOAT3 and rOCT2 in the kidney gradually improved during 14 days of recovery from hyperuricemia. Basolateral PAH transport showed a higher correlation with the protein level of rOAT1 (r(2)=0.80) than rOAT3 (r(2)=0.34), whereas basolateral TEA transport showed a strong correlation with rOCT2 protein (r(2)=0.91). The plasma testosterone concentration, which is a dominant factor in the regulation of rOCT2, was gradually restored during the recovery from hyperuricemia, but the correlation between the plasma testosterone level and rOCT2 protein expression in the kidney was not significant. These results suggest that the regulation of organic ion transporters, rOAT1, rOAT3 and rOCT2, by hyperuricemia is reversible, and the organic ion transport activity restores according to the expression levels of these transporters.

Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney: roles of organic ion transporters, rOAT1, rOAT3 and rOCT2.

We investigated organic anion and cation transport activity and the expression of several organic ion transporters in hyperuricemic rat kidney. Feeding oxonic acid, an inhibitor of uric acid metabolism, and uric acid for 10 days significantly increased plasma uric acid level. Plasma creatinine and blood urea nitrogen concentrations also increased in hyperuricemic rats, indicating impaired renal function. The accumulation of organic anions, p-aminohippurate (PAH) and methotrexate, and cations, tetraethylammonium (TEA) and cimetidine, into renal slices was markedly decreased, suggesting decreased transport activity for organic anions and cations at the basolateral membrane in the kidney. The expression levels of basolateral organic anion transporters rOAT1 and rOAT3, and organic cation transporter, rOCT2, significantly decreased in hyperuricemic rat kidney as assessed by mRNA and protein levels. In contrast, the expression of rOCT1 was unaltered by hyperuricemia at both mRNA and protein levels. Moreover, the mRNA expression of kidney-specific organic anion transporters, OAT-K1 and OAT-K2, and organic anion transporting polypeptide (oatp) 1, which localize at the brush-border membrane in the kidney, was unchanged in hyperuricemic rats. In conclusion, we showed decreased basolateral organic anion and cation transport activity, accompanied by a specific decrease in rOAT1, rOAT3 and rOCT2 expression in hyperuricemic rat kidney. These phenomena partly contribute to the changed renal disposition of organic anions and cations in hyperuricemia.

p-Aminohippurate transport at the apical membrane in the OK kidney epithelial cell line.

PURPOSE: We investigated the characteristics of transport of an organic anion, p-aminohippurate (PAH), at the apical membrane in a kidney epithelial cell line OK. METHODS: Efflux and uptake of [14C]PAH across the apical membrane were measured using OK cell monolayers grown on microporous membrane filters. RESULTS: PAH efflux to the apical side was greater than that to the basolateral side and significantly inhibited by probenecid. Diethyl pyrocarbonate (DEPC), an inhibitor of potential-sensitive organic anion transport, significantly decreased PAH efflux to the apical side. Moreover, PAH efflux to the apical side was significantly decreased on incubation with high potassium buffer, as compared with control condition. Extracellular pH and Cl- had no effect on PAH efflux across the apical membrane. PAH uptake from the apical side was inhibited by various organic anions, and the inhibition patterns of PAH uptake from the apical and basolateral sides by various dicarboxylates were similar. CONCLUSIONS: These results suggested that PAH efflux to the apical side in OK cells was mediated by a potential-sensitive transport system, but not by an anion exchanger. Moreover, PAH uptake from the apical side was mediated by a specific transport system, which interacts with various organic anions and dicarboxylates.