In Japan there are concerns that there will be a surge in social insurance costs such as medical and nursing care expenses as a result of the baby boom generation reaching the late stages of old age (75 years old and beyond) around 2025 (“The 2025 Problem”). In 2012, the “Outline on Social Insurance and Tax Reform” was approved by the Japanese cabinet and government, including “construction of regional comprehensive care”. To promote participation in home medical care by pharmacists, this article presents the roles demanded of pharmacists in regional comprehensive care from the standpoint of physicians, and the discussion of case studies bridging the gap from knowledge learned in lectures to practical applications. In the field of medical education, “The 2023 Problem”, regarding standards of education on a global level, caused medical schools across Japan to scramble for curriculum reform, specifically in the demand for increased time spent in clinical training and the expansion of community-based medical education. The current state of community-based medical education will be reviewed. In light of these developments, “the working group to create home clinical cases for education” was developed by clinical pharmacists in the field and university faculty members at Daiichi University of Pharmacy.
In the pharmaceutical education model core curriculums revision, “basic qualities required as a pharmacist” are clearly shown, and “the method based on learning outcomes” has been adopted. One of the 10 qualities (No. 7) is “Practical ability of the health and medical care in the community”. In the large item “F. Pharmaceutical clinical” of the model core curriculums, “participation in the home (visit) medical care and nursing care” is written in “participation in the health, medical care, and welfare of the community”, and it is an important problem to offer opportunities of home medical care education at university. In our university, we launched a working group to create “home clinical cases for education” from the educational point of view to pharmacy students to learn home medical care, in collaboration with university faculty members and pharmacists, who are practitioners of home care. Through its working group activities, we would like to organize the present conditions and problems of home care education in pharmaceutical education and to examine the possibility of using “home clinical case studies” in home care education at university.
The rapidly aging population in Japan led to the revision of the dispensing fees, with reviews of the system for added fees on prescriptions for home-bound patients by one-pharmacist pharmacies. However, given the current situation, it is difficult for pharmacies to be engaged in home care, so there are few small pharmacies that are willing to do so. This situation led to a decrease in the number of pharmacists who are experienced in home care. Pharmacists are requesting that practical training in home care be included in the Model Core Curriculum. It is difficult for all students to receive Sample Practical Training, so I joined a working group that created case studies that demonstrate simulated experiences of home care. I believe that case studies are an instructional tool that offers essential points for acquiring practical knowledge. Case studies can reduce the anxiety of inexperienced pharmacists to engage in home care, and I expect that this educational approach will contribute to the promotion of business related to home care for pharmacists.
Due to the progression of aging in Japan, pharmacists need to participate in home medical care. To enable pharmacists with no previous experience to participate in home medical care of patients with various diseases in the home environment, it is necessary to adopt an approach of training them in advance. It is thought useful for such clinical training to include patient case studies, which may facilitate the training of pharmacists for home medical care through simulated experience. “The working group to create home clinical cases for education” was launched by a group of university faculty, who have educational knowledge, and trained pharmacists who work with the patients at home. The home care cases were compiled by the university faculty members and the home care practice pharmacists. Working pharmacists and students at pharmaceutical college studied the same case studies of home medical care, and their self-evaluations were compared. They showed that the students rated themselves higher than the pharmacists. One of the reasons was the systematic education of the case studies. The clinical case studies are a good educational tool to promote home care medicine in pharmacies and university pharmaceutical colleges.
Peroxisome proliferator-activated receptor γ (PPARγ) antagonist is a molecular target to create drug for the treatment of not only type 2 diabetes and obesity, but also cancer. However, few rational drug design strategies and concepts are available. Here, we utilized the nuclear receptor helix12-folding inhibition hypothesis, in combination with structural biology data of our PPARγ agonist (5) complexed with the PPARγ ligand-binding domain. We found a potent phenylalkynyl amide-type PPARγ antagonist 18i, based on pinpoint structural modification of the acidic head part of 5. Although 18i exhibited potent PPARγ antagonistic activity, it retained very weak, but distinct PPARγ agonistic activity. We then modified the distal benzene ring of 18i, to delete the residual PPARγ agonistic activity. Introduction of a chlorine atom at the 2-position of the distal benzene ring afforded 18p, which exhibited potent, PPARγ-selective antagonistic activity without any detectable PPARγ agonistic activity. We realized that 18p stabilized the corepressor-PPARγ complex and suppressed basal PPARγ activity. This compound showed potent anti-adipogenesis activity at the cellular level.
We investigated the preparation of a gelling tablet that swells and forms a gel upon absorbing water, and hence would be easy for patients to swallow. We prepared naked tablets and compressed coated tablets by the direct tableting or wet granule-compression methods, using the commonly prescribed drug acetaminophen (AA) and sodium alginate (AG) as a thickening agent. The tablets quickly absorbed water, had favorable gelling properties, low adhesiveness, appropriate drug dissolution profile, and at the same time, were easy to swallow. In the case of naked tablets, water absorption increased upon granulation, but gelling of AG interfere when AA and AG were present together. There was no change in the adhesiveness, and more than 30 min were required to achieve a 25% dissolution ratio. Compressed coated tablets that were made with AA in the inner layer and granulated AG in the outer layer showed improved dissolution behavior, it was about 90% dissolution ratio in 30 min, owing to the water absorption property of AG, and decreased adhesiveness. In this case, there was a difference in the outer layer thickness. As the outer layer amount increased, dissolution slowed, but it did not depend on the compression pressure. Our gelling tablet can be prepared by using AA (main drug) in the inner layer and an appropriate thickness of granulated AG in the outer layer of compressed coated tablets.
Tocopheryl phosphoric acid (TPA, a hydrophilic vitamin E derivative) loaded liposome and glycerin containing phospholipid nanoparticles (GPLNP) were prepared using the film rehydration and extrusion method. Nanoparticle formulations were evaluated for size, zeta potential, and in vitro permeation across hairless mouse skin, and 31P NMR spectral analysis was performed. The prepared formulations were stable for 2 weeks, and their mean nanoparticle size varied between 90 and 140 nm. Although glycerin did not affect the particle size of the empty (no TPA) system, TPA-loading resulted in the reduction of particle size and conferred a negative charge. The 31P NMR spectral analysis showed that the presence of glycerin in the formulation changed the nanoparticle structure from a bilayer to a nonbilayer. Moreover, it was suggested that TPA molecules interacted with phospholipid by entrapping nanoparticles in the formulations. TPA did not permeate across the hairless mouse skin after 48 h. However, the TPA concentration in the hairless mouse skin after permeation study increased in the nanoparticle systems and the 30% GPLNP formulation was the best formulation for the accelerated TPA permeation in the hairless mouse skin. These results demonstrate that 30% GPLNP improved TPA permeation in the hairless mouse skin model. And it was strongly suggested that glycerin has an important role for changing the structure of nanoparticles and enhancing the skin permeation of TPA.
This study evaluated the effect of an evidence-based medicine (EBM) educational program on EBM-related knowledge and skills of pharmacists and pharmacy students. Our preliminary educational program included the following four sessions: 1) ice breaker, 2) formulation of answerable clinical questions from virtual clinical scenario using the PICO criteria, 3) critical appraisal of the literature using a checklist, and 4) critical appraisal of the results and integrating the evidence with experience and patients values. Change in knowledge and skills related to EBM were evaluated using pre- and post-seminar 4-point scale questionnaires comprising of 14 questions. A total of 23 pharmacists, 1 care manager, and 5 pharmacy students participated in our EBM educational seminar. Knowledge and skills related to several variables improved significantly post-seminar (pre-seminar 2.80 versus 3.26 post-seminar; p<0.001). Specifically, the skills of formulating answerable clinical questions from virtual clinical scenario and critical appraisal of the literature using a checklist improved. Our findings suggested that EBM educational program using problem-based learning was effective in improving EBM-related knowledge and skills of pharmacists and pharmacy students.
Several case studies have reported a possible drug interaction between warfarin and tramadol where tramadol coadministration enhanced the antithrombotic effects of warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after tramadol coadministration were investigated in patients receiving warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with warfarin for deep vein thrombosis, atrial fibrillation, arteriosclerosis obliterans, congestive heart failure, and other vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of tramadol (1.81±0.56 vs. 2.47±1.10, p<0.01). Twenty-eight patients (PT-INR increased group) with PT-INR elevation of greater than 0.5 or dose reduction of warfarin after coadministration of tramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that tramadol coadministration enhanced the antithrombotic effects of warfarin in patients with higher PT-INR, lower albumin levels and decreased renal function as the risk factors for this drug interaction.
We developed a new inhalation exposure method to evaluate effects of synthetic cannabimimetics that are being distributed as new, unregulated drugs in the Tokyo area. We selected the commercial product “SOUTOU” containing AB-CHMINACA and 5F-AMB as the test drug and dried marshmallow (Althaea officinalis) leaves as the negative control. A half cigarette packed with dried marshmallow leaves or SOUTOU was ignited, then mainstream smoke from each was delivered to five mice in an exposure box. After the cigarettes were fully consumed, neurobehavioral observations and a catalepsy test were performed at 15, 30 and 60 min after exposure. The effluent air from the exposure box was poured into impingers containing acetonitrile (first impinger) and dimethyl sulfoxide (second impinger). The resulting solutions were analyzed to assess decomposition of the synthetic cannabimimetics. Mice exposed to SOUTOU smoke showed many excitement behaviors and some suppressive behaviors at 15, 30 and 60 min. These clearly included cannabimimetic specific pharmacological actions. Negative control mice also showed some suppressive behaviors at 15 min but these were attenuated at later times, nearly disappearing at 60 min. In addition, the behavioral effects observed in controls were less pronounced than those in SOUTOU exposed mice. The inhalation exposure method developed in our study would be effective for determining cannabinoid specific pharmacological effects of illegal drugs, as well as for assessing the presence of active compound(s) by comparing the test substance with a negative control.
The aim of the present study was to develop a method for grinding tablets with a mortar and pestle while reducing drug loss because grinding tablets is known to be associated with reductions in tablet weight and loss of the active drug. Seven kinds of tablets were subjected to grinding. The proportion (%) of the amount of the active drug in the powder remaining on the surfaces of the mortar and pestle relative to the total amount of the drug recovered (the recovery percent) was calculated. The recovery percent of the 7 kinds of tablets ranged from 17.2-35.9%, and the tablets' recovery percent decreased as the tablet weight increased. When the grinding was performed with 1 g of lactose monohydrate or 1 g of D-mannitol moistened with water, the recovery percent of the tablets decreased to 2.6-9.9% and 3.8-9.9%, respectively. The effects of the weight of lactose monohydrate on the recovery percent of Allegra® 60 mg tablets were examined. It was found that at least 0.6 g of lactose monohydrate was required to have a sufficient effect on drug recovery. Therefore, additives that have stronger effects at lower amounts were sought. As a result, calcium monohydrogen phosphate was found to have the strongest effect on drug recovery. The addition of 0.4 g calcium monohydrogen phosphate resulted in the recovery percent of 5.1%, which was significantly lower than that of 15.0% observed after the addition of 0.4 g lactose monohydrate, and lower than the 6.8% of 1 g lactose monohydrate.
Anticancer drug-induced stomatitis develops in 30% to 40% of cancer cases that undergo chemotherapy. However, medications for this condition are not commercially available in Japan. Upon obtaining approval of the ethics committee, a mouthwash containing rebamipide as the active ingredient (rebamipide mouthwash) was administered to one inpatient and four outpatients, who had developed stomatitis caused by cancer chemotherapy. Starting from 14 d after the administration of the rebamipide mouthwash, the patients scored a stomatitis survey on oral state, pain level, and diet and recorded the number of times they gargled, as well as any stomatitis observations, in a stomatitis diary. The total scores for the points for each of the three types of survey sections were classified into Grades 0 to 4 and evaluated as a stomatitis evaluation score (SES). The SES became “0” in three out of the five patients within 14 d of treatment. No change in SES was found in one patient. In the remaining patients, SES became “0” once but increased again later. Using image analysis software (ImageJ), the area at which the stomatitis was observed was measured. When comparing SES and change in the area in patients who agreed to participate, gradual reductions in the extent of stomatitis was observed even during the period when SES did not change. Having patients fill in an observation chart was effective for grasping changes in symptoms in outpatients.
It is important to ingest just proportions of minerals to prevent disease, but these minerals are also secreted into the hair. Meanwhile, the number of hay fever patients in Japan is increasing, causing an increase in national medical expenses. In this study, we investigated the relationship between hay fever and mineral concentrations in hair to obtain findings on the risk of developing pollen allergies. A questionnaire survey was conducted for 275 men and 977 women on their lifestyle habits and ten kinds of mineral concentrations present in their hair were measured with subsequent analysis using nominal logistic regression analysis. The results indicated that half the patients in each age group had hay fever, with no significant difference between hay fever and aging, exercise habits, sleep and dietary rhythms. On the other hand, there was a significant difference between hay fever and mineral concentrations in the hair, and in men with hay fever, iron (odds ratio: 0.55, p<0.05) was low, while in women calcium (odds ratio: 0.67, p<0.05), chromium (odds ratio: 0.46, p<0.001), cadmium (odds ratio: 0.68, p<0.01) were low and selenium (odds ratio: 1.78, p<0.01) was high. These results, suggest that measurements mineral concentrations in hair are indicators of hay fever risk.
In our previous research, there was no collaboration between care workers and pharmacists, for the most part. As a result, it was discovered that in some cases, problems concerning medication of nursing home residents had not been resolved. To solve this issue, we brought together care workers and pharmacists for a workshop we conducted. We assigned 12 care workers with at least two years of experience and 12 pharmacists to four mixed groups and guided them in the management of in-home long-term medical care and conducted small group discussions (SGD) using the KJ method. In the pre-survey before the workshop, all 12 care workers replied “yes” to having experienced “concerns over medication” and nine (75%) replied “no” to having experienced “discussions (consultations) with pharmacists regarding the medication of residents”. As a result of the SGD, “information sharing among professionals” was revealed as a problem common to all groups. Furthermore, common countermeasures for this issue included communication notes and holding collaborative meetings. In the post-survey after the workshop, 67% of the participants replied that their thoughts concerning countermeasures were “coherent”, and everyone replied that their “awareness was increased”. In a follow-up survey after the workshop, 82% of the participants replied that they were using some form of what they had learned and discovered in the workshop in their actual work.