Administration of Kampo medicine through a tube at an advanced critical care center.

n emergency and critical care medical centers, tube administration is employed for patients who have difficulty swallowing oral drugs owing to decreased consciousness or mechanical ventilation. However, tube clogging due to drug injection is a concern. We compared the crushing method with the simple suspension method for the passage of amlodipine, an antihypertensive drug, in combination with rikkunshito, which has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux in emergency and critical care medical centers, to ascertain the effect of Kampo products on the passage of other drugs during tube administration. When the crushing method was employed, poorly water-soluble solid products were formed, while a uniformly dispersed suspension was obtained using the simple suspension method. In addition, the passage rate of amlodipine through the tube was 64% and 93% in the crushing and simple suspension methods, respectively, thereby indicating that the simple suspension method provided more favorable than the crushing method. The results of this study suggested that the passage rate of amlodipine for patients who received Kampo products concurrently was higher when the simple suspension method was used, and an appropriate drug amount might well be able to administered to patients using this method. J. Med. Invest. 65:32-36, February, 2018.

Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit.

PURPOSE: Although the 2016 Japanese guidelines for the management of sepsis recommend de-escalation of treatment after identification of the causative pathogen, adherence to this practice remain unknown. The objective of this study was to evaluate the benefits of de-escalating treatment for sepsis patients at an advanced critical care and emergency medical centre. METHODS: Based on electronic patient information, 85 patients who were transported to the centre by ambulance, and diagnosed with sepsis between January 2008 and September 2013 were enrolled and evaluated. Patients were divided into two groups with and without de-escalation, and comparisons were conducted for several variables, including length of hospital stay, and length of antibiotic administration. Two types of subgroup analysis were conducted between patients with septic shock or positive blood cultures. Statistical analysis was conducted using chi-square and Mann-Whitney U tests. RESULTS: The length of hospital stay after diagnosis was significantly shorter for the de-escalation group than for the non-de-escalation group. In the subgroup analysis, de-escalation for blood culture-positive patients was beneficial in terms of the length of hospital stay and length of antibiotic administration. CONCLUSIONS: The findings of this study suggest that sepsis treatment de-escalation is beneficial for treatment efficacy and appropriate use of antibiotics. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Intracranial self-stimulation and immobilization had different effects on neurite extension and the p38 MAPK pathway in PC12m3 cells.

AIM: In mammals, rewarding and aversive states are motivational drivers of behavioral expression. However, it is unclear whether such states affect neuronal functions at the level of individual neurons. In the present study, the neuronal effects of rewarding and aversive states were investigated in using PC12 mutant cells (PC12m3 cells) with low sensitivity to nerve growth factor. MAIN METHODS: The intracranial self-stimulation (ICSS) and immobilization (IMM) methods were used to create rewarding and aversive states, respectively, in rats. Furthermore, experiments involving voluntary running on a wheel and forced running on a rotating rod were used to evaluate the effects of behavioral excitement on neurons. Then, the effects of plasma samples collected from the animals on neurite extension were examined microscopically, and p38 mitogen-activated protein kinase (MAPK) activity was assessed using Western blotting. KEY FINDINGS: Plasma samples from the ICSS and IMM rats facilitated neurite outgrowth to different degrees. However, their effects were not influenced by behavioral excitement. Furthermore, the plasma from the ICSS rats also induced upregulated p38 MAPK activity, whereas that from the IMM rats produced the same or slightly lower levels of MAPK activity to the control plasma. SIGNIFICANCE: These findings indicate that rewarding and aversive states might cause morphological changes, such as neurite extension. As for the effects of these states on p38 MAPK activity, the former state might directly increase p38 MAPK activity, but the latter state might have no effect or cause a slight reduction in p38 MAPK activity.

Evaluation of pharmaceutical lifesaving skills training oriented pharmaceutical intervention.

BACKGROUND: Many pharmacists are participating in team-based medical care in emergency hospitals. Therefore, there is a desperate need to improve the education system. In the present study, we provided a "pharmaceutical lifesaving skills training" to the students in their fifth and sixth year of the pharmaceutical school and evaluated the program's impact on the students' learning and confidence in their ability to perform pharmaceutical interventions for emergency patients. METHODS: We conducted a pharmaceutical lifesaving skills training program with 12 participants who were in their fifth and six year of pharmaceutical school. We prepared a fictional scenario in which a patient with cardiac arrest has been rushed into a hospital. We measured the participants' level of knowledge of pharmaceutical lifesaving procedures and participants' confidence to perform pharmaceutical interventions before and after the training session. Using the data obtained from type II quantification method, we examined what elements in the content of the pharmaceutical lifesaving skill training attended by pharmacy students will affect the students' confidence to perform pharmaceutical interventions. In addition, using the correspondence structural analysis, we examined which sections of the content of the pharmaceutical lifesaving skill training should be improved in the future. RESULTS: When we evaluated the level of knowledge acquired in pharmaceutical lifesaving skills training, the post-training overall correct answer rate was significantly higher than the pre-training overall correct answer rate. And also, level of participants' confidence to perform pharmaceutical interventions similarly increased after pharmaceutical lifesaving skill training. The influence degree graph indicates that the items likely to have a major impact on the participants' confidence to perform pharmaceutical interventions was "Selecting medicine". According to the correspondence structural analysis graph based on the questionnaire survey, one item identified as an improvement required was "Selecting medicine". CONCLUSIONS: Our high-performance patient simulator-based lifesaving skills training program not only increased the participants' understanding of the training content but also increased their confidence in their ability to perform pharmaceutical interventions. Therefore, the pharmaceutical lifesaving skills training program we developed will contribute to the education of emergency care pharmacists who can perform pharmaceutical interventions for emergency patients.

Pharmaceutical Education Focused on Pharmacotherapy in Emergency Medical Care.

Pharmacists are expected to be active members of the healthcare team in emergency medicine, because many pharmaceuticals are administered to patients with life-threatening conditions. However, adequate education for pharmacists and pharmacy students is not provided. The "Emergency Pharmaceutical Sciences" course was introduced for the first time in Japan by the Department of Pharmacy, Okayama University, to offer advanced education in emergency medicine and research related to critical care. We offer an emergency pharmaceutical training program with high-performance simulators and have succeeded in improving the clinical skills and confidence of pharmacy students. In this review, we introduce our activities intended to mold pharmacy students into emergency pharmacists who can contribute to emergency medicine.

[Effects of practical training to increase motivation for learning and related factors].

Under the six-year pharmaceutical education system that was initiated in April 2006, students who had completed the course in March 2012 became the first graduates. The six-year system encourages students to develop a well-rounded personality, a deep sense of ethics, knowledge required for health care professionals, abilities to identify and solve problems, and practical skills required in clinical settings, as well as basic knowledge and skills. Under the new education system based on the "pharmaceutical education model core curriculums" and "practical training model core curriculums", general pharmaceutical education is implemented in each college, and five-month practical training is conducted in clinical settings. Clinical tasks experienced by students for the first time are expected to significantly influence their motivation to learn and future prospects. In the present survey research, students who had completed practical training evaluated the training program, and correspondence and logistic regression analyses of the results were conducted to examine the future effects and influences of the training on the students. The results suggest that the students viewed the practical training program positively. In addition, clinical experience during the training sessions not only influenced their decisions on future careers, but also significantly increased their motivation to learn. Furthermore, their motivation for learning was increased most by the enthusiasm of pharmacists who advised them in clinical settings, rather than the training program itself. To improve pharmaceutical clinical learning, it is important to develop teaching and working environments for pharmacists in charge of advising students in clinical training.

[Education effect of the simple suspension method training for fifth-year medical students].

The clinical training curriculum for fifth-year students of a school of medicine (Department of Medicine) includes training in clinical pharmacy, which is conducted by the Department of Pharmacy. Following training involving the simple suspension method, a survey was conducted to examine its effects to improve medical students' knowledge on the proper use of drugs. Forty-eight 5th-year students of Ehime University School of Medicine, Department of Medicine, underwent training that employed the simple suspension method, and examinations were conducted prior to and following it to assess its effects. Following the training, the questionnaire results were analyzed using Quantification Theory Class II to examine whether knowledge acquired from it had motivated the students to use the simple suspension method. A correspondence structural analysis was also conducted to identify improvements in the training. The correct answer rate increased from 55.2±2.4% before to 83.8±1.7% after training, which supports its learning effects. The presence or absence of changes in disposition and the efficacy of the method for patients with dysphagia strongly motivated the medical students to use the method. As a future improvement, it is necessary to describe differences between the crushing and simple suspension methods during training. The results of a survey on training involving medical students conducted based on the simple suspension method suggested its learning effects and knowledge that motivated them to use the method.

Effect of GBR12909 on affective behavior: distinguishing motivational behavior from antidepressant-like and addiction-like behavior using the runway model of intracranial self-stimulation.

RATIONALE: It was recently demonstrated that the priming stimulation effect (PSE) in the runway model of intracranial self-stimulation (ICSS) can be used as a model system to study the motivational effects of drugs. However, the characteristics of this novel experimental model have not been fully clarified. OBJECTIVE: To elucidate the involvement of dopamine uptake inhibition in motivated behavior and the difference in experimental characteristics between closely related experimental models, we investigated the effects of the dopamine uptake inhibitor GBR12909 in the runway ICSS model, in the forced swimming test (FST), and on conditioned place preference (CPP). In addition, the role of dopamine receptor signaling in the runway model was evaluated using dopamine receptor agonists and antagonists. RESULTS: GBR12909 dose-dependently increased running speed on the runway and decreased immobility time in the FST without affecting the time spent in the drug-associated compartment in CPP tests. The effect of GBR12909 in the runway model was inhibited by pre-treatment with the dopamine receptor antagonists haloperidol and raclopride. The dopamine receptor agonists SKF38393 and quinpirole dose-dependently decreased running speed. CONCLUSIONS: These results demonstrate that GBR12909 displays motivation-enhancing and antidepressant-like effects without place conditioning effects. In addition, the mechanisms of PSE enhancement in the runway ICSS model are different from those underlying closely associated experimental models and are mediated by increases in dopamine signaling.

Differential effects of nomifensine and imipramine on motivated behavior in the runway model of intracranial self-stimulation.

A motivational deficit (the loss of pleasure or interest in previously rewarding stimuli) is one of the core symptoms of major depression, and valid models evaluating the motivational effects of drugs are needed. It was recently demonstrated that the priming stimulation effect in the runway model of intracranial self-stimulation (ICSS) can be used as a model system to study the motivational effects of drugs. However, the characteristics of this novel experimental model have not been fully clarified. In this study, we investigated the effects of nomifensine and imipramine in the runway ICCS model, forced swim tests, and locomotor activity tests to differentiate motivation from affective-like states. Nomifensine dose-dependently increased running speed on the runway and decreased immobility time in the forced swim test. In contrast, imipramine decreased running speed on the runway although it also decreased immobility time in the forced swim test. In addition, the motivation-enhancing effect of nomifesine in the runway model was completely inhibited by pretreatment with the dopamine receptor antagonist haloperidol, although nomifensine-induced increases in locomotion were not affected by haloperidol. These results demonstrate that nomifensine displays motivation-enhancing and antidepressant-like effects. In addition, the motivational effects of nomifensine in the runway ICSS model are primarily mediated by dopamine receptors and enhancements of motivated behavior do not simply reflect hyperlocomotion.

A new method for evaluation of motivational effects of drugs.

Motivation is a process that continuously changes behavior to achieve a goal and can be conceptualized as a series of steps relating to that process. Intracranial self-stimulation (ICSS) behavior is considered to consist of reward and motivational effects. Moreover, priming stimulation of ICSS behavior is known to promote motivational effects. Using the runway method and priming stimulation, rewards and motivational effects of ICSS behavior can be differentiated. We investigated whether the runway method and priming stimulation of ICSS behavior could be used to evaluate motivational effects of a drug. In the ICSS runway model, running speed was considered as a reference of motivational effect. An assessment of pharmacological drugs known to influence motivational states was also undertaken. Using our experimental methods, prominent changes were observed in running speed when animals were administered methamphetamine and nicotine. Based on our results, we conclude that the runway method may be useful for the evaluation of substances that affect motivation. This review introduces 4 types of neuronal processes involved in motivation, reward mechanisms, outlines evaluation methods, and describes motivational properties of psychoactive drugs.

Evaluation of motivational effects induced by intracranial self-stimulation behavior.

In the runway model of intracranial self-stimulation (ICSS) experimentation, the experimental animal is timed in running a fixed distance to depress a lever that releases electrical stimulation to an electrode implanted along its medial forebrain bundle. This ICSS has both a reward and a motivational component. Using the runway method and priming stimulation, we designed an experimental method for directly measuring motivation. An assessment of pharmacological agents that are known to influence motivational states was also undertaken. Using the experimental methods that we created, we observed prominent changes in running speed when animals were exposed to methamphetamine and nicotine. According to these data, the runway method employing intracranial self-stimulation behavior may be useful for the evaluation of substances that act on motivation. We review the underlying neuropharmacological and anatomical functions associated with our experimental methods. We hope that this technique will be used to scientifically evaluate the impact of drugs and/or therapeutic interventions on human motivation.

Nicotinic acetylcholine alpha4beta2 receptor regulates the motivational effect of intracranial self stimulation behavior in the runway method.

Recently, it was demonstrated that the priming stimulation effect (PSE) of intracranial self-stimulation (ICSS) with the runway method can be used as a model system to study the motivation that contributes to specific behaviors. It was postulated that these behaviors could be used to compare the effects of various drugs on the mechanism of motivation. In the present study, the influences of nicotine, methyllycaconitine (alpha7 nicotine-receptor antagonist), and dihydro-beta-erythroidine (alpha4beta2 nicotine-receptor antagonist) on motivation were examined using the runway method for ICSS. Electrodes were implanted into the medial forebrain bundle of Wistar rats. The rats ran to the goal lever to get the reward (50 - 200 microA, 0.2 ms, 60 Hz) and pretrial electric stimulation (priming stimulation) in the medial forebrain bundle was performed. The experiment measured the running time from the start box until the rat pressed the goal lever for the reward stimulation. Under these reward and priming stimulation conditions, nicotine (0.2 mg/kg) induced a significant increase in running speed. The nicotine receptor antagonist alpha4beta2 rather than alpha7 showed a dose-dependent antagonistic action on the effect of nicotine on running speed. These results demonstrate that nicotine enhances the running speed towards the goal lever via alpha4beta2 nicotinic receptors and suggest that alpha4beta2 nicotinic receptors influence the brain mechanism of motivation.

Motivational effects of nicotine as measured by the runway method using priming stimulation of intracranial self-stimulation behavior.

It is well known that priming stimulation promotes the motivational effects of intracranial self-stimulation(ICSS) behavior. An experimental methodology using the runway method could separately study the reward and motivational effects of ICSS behavior. In the present study, we examined the motivational effect of nicotine as measured by the runway method using priming stimulation of ICSS behavior. Electrodes were implanted chronically into the medial forebrain bundle (MFB) in rats. A lever for stimulation of the MFB was set on the opposite side of the start box in the apparatus, and rats were trained to get a reward stimulation (50-200 microA, 0.2 ms, 60 Hz) of MFB when the goal lever was pressed. After the rats were trained to press the lever, a priming stimulation of the MFB was performed. After receiving the priming stimulation, rats were placed at the start box of the runway apparatus, and the running time duration until the goal lever was pressed was measured. Subcutaneous injection of nicotine at a dose of 0.2mg/kg produced an increase in running speed to obtain the reward stimulation, and priming stimulation facilitated the motivational effect to obtain the electrical brain stimulation reward in the rats. These results suggest that nicotine significantly enhanced the motivational effect on ICSS behavior as determined using the runway method. The runway method using priming stimulation of ICSS behavior may become the new experimental methodology with which to measure the motivational effect of some drugs.

Effect of diazepam on the runway method using priming stimulation of intracranial self stimulation behavior.

Intracranial self-stimulation (ICSS) behavior is an experimental methodology to study reward and motivational effects. We have established a paradigm to evaluate enhancing motivation by drugs in the runway method using the priming stimulation of ICSS. In the present study, we investigated the effects of diazepam on the experimental extinction process of non-reinforcing reward and pre-trial electric priming stimulations in lateral hypothalamic self-stimulation. The extinction process in the runway method consisted of these 15 trials. Diazepam, an anti-anxiety drug, at doses of 0.5 and 1 mg/kg (i.p.) delayed the extinction of running behavior when priming stimulation was given. The GABAergic antagonist flumazenil at doses of 5 and 10 mg/kg (i.p.) totally prevented the effect of diazepam. These results demonstrate that diazepam delays the extinction of running behavior on ICSS in the runway method and flumazenil, a GABAergic antagonist, eliminates the delayed effect of diazepam, that is, indicating that the delayed extinction effect of diazepam may be related to facilitation of motivation, which was promoted via the GABAergic system in the ICSS behavior.

Motivational effect of nomifensine in the intracranial self-stimulation behavior using a runway method.

Intracranial self-stimulation (ICSS) behavior is an experimental methodology to study reward and motivational effects. We have established a new paradigm to evaluate enhancing motivation by drugs in the runway method using the priming stimulation of ICSS. In the present study, we investigated the effects of nomifensine on the experimental extinction process of non-reinforcing reward and pre-trial electric priming stimulations in lateral hypothalamic self-stimulation. In this study, the experimental extinction process of the non-reinforcing reward means the experimental method of excluding reward effect in ICSS behavior. The extinction process in the runway method consisted of these 15 trials. Nomifensine, an antidepressant drug, delayed the running speed of the extinction process at doses of 5 and 10 mg/kg (i.p.) compared with the vehicle alone. This result suggests that the delay in the running speed of the extinction process promotes a motivational effect in rats. Previously, priming stimulation in the runway method was found to affect motivational function of ICSS. Therefore, our findings suggest the possible application of nomifensine for improving motivation.

Motivational effects of methamphetamine as measured by the runway method using priming stimulation of intracranial self-stimulation behavior.

Priming stimulation is known to promote the motivational effects of intracranial self-stimulation (ICSS) behavior. The runway method using priming stimulation can experimentally distinguish the reward and motivational effects of ICSS behavior. In this study, we examined the motivational effect of a drug as determined by the runway method using priming stimulation of ICSS behavior. Electrodes were implanted chronically into the medial forebrain bundle (MFB) of the rats. A lever for stimulation of the MFB was set on the opposite side of the start box in the apparatus. The rats were trained to obtain a reward stimulation (50-200 muA, 0.2 ms, 60 Hz) of the MFB by pressing the goal lever, and then priming stimulation of the MFB was applied. After priming stimulation, rats were placed in the start box of the runway apparatus and the time taken by the rat to press the lever was recorded. Priming stimulation frequency was significantly correlated with running speed (r=0.897, p<0.05). Methamphetamine (1, 3 mg/kg) induced an increase in running speed (F(3, 20)=16.257, p<0.01), and was further increased with increase in priming stimulation frequency. In addition, methamphetamine significantly enhanced the motivational effect. These results suggest that the runway method using priming stimulation of ICSS behavior may be an effective way to evaluate the enhancing effect of a drug on motivation.

Selegilin exerts antidepressant-like effects during the forced swim test in adrenocorticotropic hormone-treated rats.

In the present study, we investigated the effect of adrenocorticotropic hormone (ACTH) on the immobilization of rats in the forced swim test after the administration of selegiline, a selective and irreversible monoamine oxidase (MAO)-B inhibitor. Single and repeated administration of selegiline significantly decreased the duration of immobility in normal rats. When selegiline was administered for 15 days, we observed a significant decrease in immobility in rats treated with ACTH for 14 days. The immobility-decreasing effect of selegiline was blocked by nafadotride, a selective dopamine D(3)-receptor antagonist in normal and ACTH-treated rats. Selegiline may be useful in an animal model of depressive conditions resistant to tricyclic antidepressant treatment via the dopamine D(3) receptor.

Effects of imipramine and bupropion on the duration of immobility of ACTH-treated rats in the forced swim test: involvement of the expression of 5-HT2A receptor mRNA.

We examined the effect of chronic administration of imipramine and bupropion, monoamine reuptake inhibitors, on the duration of immobility in the forced swim test and serotonin (5-HT)(2A) receptor function in the form of 5-HT(2A) receptor mRNA levels in rats chronically treated with adrenocorticotropic hormone (ACTH). The immobility-decreasing effect of bupropion without imipramine did not influence the chronic ACTH treatment. The effect on the expression of 5-HT(2A) receptor mRNA of chronic ACTH treatment was decreased by bupropion, but not imipramine. These results suggest that bupropion has the effect of reducing immobility time in the forced swim test in the tricyclic antidepressant-resistant depressive model induced by chronic ACTH treatment in rats, and that decreased 5-HT(2A) receptor mRNA levels may be involved in this phenomenon.

[Comparison of the visual analog scale method and 5-point evaluation in student self-assessment of comprehension and acquisition in a model core curriculum for practical training].

In examining assessment methods used for evaluating training, there have so far been no studies reporting any differences between the visual analogue scale (VAS) evaluation method, based on a rating scale, and evaluation methods based on an ordinal scale. Here we report the findings of an examination into differences and discrepancies between the results of the VAS method and a 5-point evaluation. Following the end of their training period, seven trainees carried out a self-evaluation regarding their level of understanding and performance using the 5-point evaluation and VAS methods. We then compared the average results of both assessment methods and examined the correlation between the two sets of figures. We found no differences between the 5-point evaluation method and VAS method in evaluating training for dispensing drugs, administering injections, pharmacy preparation, and medication management and instruction. There was also a significant correlation between average values for the 5-point evaluation and VAS method in evaluating training for dispensing drugs, administering injections, pharmacy preparation, and medication management and instruction. This led us to the conclusion that both the 5-point evaluation method and VAS method give similar results and outcomes in assessing the results of practical training.