Safety of mirogabalin and pregabalin in Japanese patients with neuropathic pain: a retrospective cohort study.

BACKGROUND: Few studies have compared the safety risks between the gabapentinoids, pregabalin, and mirogabalin in post-marketing clinical settings. We assessed reported events associated with gabapentinoid use in patients with neuropathic pain. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study between September 2020 and December 2020 using the community pharmacies records in Japan. The pharmacists identified new vs. prevalent users of mirogabalin and pregabalin in September 2020 and reported data regarding baseline and adverse events to the Japan Pharmaceutical Association using web-based questionnaires. The incidence of events and hazard ratio (HR) were consequently compared. RESULTS: New users of mirogabalin and pregabalin were identified (n = 1,650 and 2,244; mean age (SD): 69 (15) and 68 (16) years; women: 59% and 56%, respectively). Although serious events were not reported, a marked difference in HRs of common adverse events, including somnolence (1.6), dizziness (1.3), nausea (2.8), edema (3.1), and acetaminophen (2.0)/antidepressant (2.4) addition, was observed. CONCLUSION: No new serious safety concerns were found for mirogabalin and pregabalin use in patients with neuropathic pain, although the HR of some events indicated increased risk among mirogabalin users. However, further studies are needed as estimates for events occurring in small numbers with wide confidence intervals.

Exploration of Trends in Antimicrobial Use and Their Determinants Based on Dispensing Information Collected from Pharmacies throughout Japan: A First Report.

The purpose of this study was to evaluate the defined daily doses (DDD)/1000 prescriptions/month (DPM) as a new indicator that can be used in pharmacies, and to describe antimicrobial use patterns in pharmacies nationwide in Japan. Dispensing volumes, number of prescriptions received, and facility information were obtained from 2638 pharmacies that participated in a survey. DPM was calculated based on the dispensing volume and number of prescriptions, which are routinely collected data that are simple to use. Use of third-generation cephalosporins, quinolones, and macrolides in pharmacies that received prescriptions primarily from hospitals or clinics decreased from January 2019 to January 2021. In particular, the antimicrobial use was higher in otorhinolaryngology departments than in other departments, despite a decrease in the antimicrobial use. In the linear multiple regression analysis, otorhinolaryngology department was independently associated with the third-generation cephalosporin, quinolone, and macrolide prescription in all periods. This study reveals for the first-time trends in antimicrobial use through a new indicator using the volume of drugs dispensed in pharmacies throughout Japan. Antimicrobial use differed by the medical department, suggesting the need to target interventions according to the department type.

Event Monitoring and Evaluation by Community Pharmacists in Japan: A Pilot Study on Fenofibrate and Pemafibrate.

BACKGROUND: The Japan Pharmaceutical Association has conducted drug event monitoring to detect drug events related to pemafibrate. As there are a few studies on the safety of pemafibrate in clinical settings, a pilot study evaluating the association between drug use and detected events was performed in Japan. AIMS: In this study, the association between detected events and the use of pemafibrate, utilizing pharmacy records maintained by community pharmacists, was investigated. We identified the newuser cohort using a test and active comparison drug and collected the baseline information. An active comparison group comprising new users was used to assess the events. METHODS: A retrospective cohort study using questionnaires regarding baseline and event data was conducted by community pharmacists belonging to the Japan Pharmaceutical Association. The incidence of event and estimated hazard ratio were calculated using the Cox proportional hazards model that was adjusted for confounding factors, such as age and sex. RESULTS: A total of 1294 patients using pemafibrate and 508 patients using fenofibrate were identified as new drug users. The most reported events involving suspected adverse reactions and add-on drugs were increased blood pressure and lipid-lowering effects with pemafibrate use, and nasopharyngitis, pruritus, dizziness, and lipid-lowering effects with fenofibrate use. No significant differences were found in commonly occurring events, except that an add-on anti-hypertensive drug has been used by pemafibrate users compared to fenofibrate users. CONCLUSION: This study conducted by pharmacists can facilitate the safety assessment of newly marketed drugs, as few drug use investigations with a comparator are carried out by the Japanese authority for pharmaceutical companies. However, further research is required.

Factors Associated with Medication Non-Adherence among Patients with Lifestyle-Related Non-Communicable Diseases.

This cross-sectional study explored the association between medication non-adherence and its factors in patients with non-communicable diseases (NCDs) using an online structured questionnaire emailed to 30,000 people (aged over 20 years who lived in Japan at the time of the survey). The questions concerned respondents' characteristics, medication non-adherence, health beliefs, lifestyles, and trouble taking medication. Factors related to non-adherence were analyzed among patients with lifestyle-related NCDs categorized into two age groups: 20-59, and >60 years. Unintentional (p < 0.001) and intentional (p < 0.001) non-adherence were more common among patients aged 20-59 than in older adults. NCD patients aged 20-59 experienced significantly more trouble taking medication than older adults. Multiple regression analysis showed that for patients aged 20-59 with NCDs, unintentional non-adherence was significantly and positively associated with current smoking habits (ß = 0.280, p < 0.001), while intentional non-adherence was significantly and positively associated with alcohol consumption (ß = 0.147, p = 0.020) and current smoking habits (ß = 0.172, p = 0.007). In patients aged 20-59, unhealthy eating habits (ß = -0.136, p = 0.034) and lack of exercise (ß = -0.151, p = 0.020) were negatively associated with intentional non-adherence. In conclusion, factors affecting medication non-adherence in patients with lifestyle-related diseases are related to health awareness, lifestyle, and medication barriers.

[Adherence to Oral Antihyperglycemic Agents (Dipeptidyl Peptidase-4 Inhibitors and Biguanides) and Its Associated Factors in Patients with Type 2 Diabetes].

To investigate medication adherence to oral antihyperglycemic agents and its associated factors in Japanese type 2 diabetic patients, a questionnaire survey was conducted in 983 adult patients receiving once-daily (QD) or twice-daily (BID) dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitor) or BID biguanides (BG) as monotherapy at 502 pharmacies in Japan. The percentage of patients with good adherence (the proportion of days in which patients took all pills as prescribed in the past 7 days ≥80%) was high (≥90%) in any dosing regimen with no significant difference among the groups. The following factors were identified as associating with good adherence: the longer duration of type 2 diabetes (≥1 year) (p=0.002), "Feeling your disease gets worse if you don't take medications" (p=0.031), "Not forgetting to bring along your medicine when you leave home" (p=0.007), "Feeling anxiety on taking medications for long period of time" (p=0.042), "Neither feeling nor not feeling anxiety on taking medications for a long period of time" (p=0.004), "Never run out of your medicine because you get a refill on time" (p=0.035), and the lower MMAS-4 score (p<0.001). Subgroup analyses revealed that adherence of younger patients (<65 years) with BG (BID) was lower than those with DPP-4 inhibitor (QD) (p=0.021). Additionally, around 60% of patients currently prescribed with QD preferred QD regimen, and ≥80% patients prescribed with BID equally preferred once-weekly or QD regimen, suggesting a large discrepancy exists between their preference and the actual regimen in patients on BID.

Hospital-pharmacy cooperative training and drug-taking compliance in outpatients with chronic pain: a case-control study.

Purpose: Chronic pain is a common symptom that is suffered by 20% of the overall population in Japan. Although pharmacotherapy is critical for the treatment of chronic pain, there are no reports on the pharmacies. In the present study, we examined the effect of hospital-community pharmacy cooperative training on improving drug-taking compliance, pain relief, anxiety, insomnia, and motor function in patients with chronic pain. Patients and methods: The subject sample included 87 patients with chronic pain who were examined for the first time at the outpatient services department of Nihon University Itabashi Hospital. Patients were interviewed to obtain information regarding drugs used before and after the treatment, habitually used community pharmacies, presence of cooperative training with Itabashi Hospital, drug-taking compliance, and side effects. We compared treatment outcomes before and after consultation using the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), EuroQol Group measure (EQ-5D) for quality of life, Athens Insomnia Scale, and Locomo 25 scale for motor function. Results: In patients who used community pharmacies that perform training, drug-taking compliance was significantly better, and a significant improvement was observed in the scores of BPI, HADS Anxiety, Athens Insomnia, and Locomo 25. Conclusion: Pharmacotherapy is essential for the treatment of chronic pain. To this end, appropriate drugs with proper drug management guidance are indispensable. In this study, the use of community pharmacies that have undergone cooperative training with hospitals improves pain and anxiety. This is achieved through proper drug management guidance, shared awareness of drug information, and achievement of better drug-taking compliance. To improve the quality of treatment for chronic pain, involvement of community pharmacies such as by providing accurate information is essential. In the future, expanding cooperative training with hospitals may further help reassure patients, facilitate drug-taking, and improve the quality of treatment for chronic pain.

Validation of a Reorganized Training Program Using a Cognitive Behavioral Therapy Approach to Enable Community Pharmacists to Provide Empathic Patient Counseling.

To enable community pharmacists to provide empathic patient counseling, we developed and validated a training program based on the cognitive behavioral therapy approach (CBT-A) in our previous study. The major focus points of the re-structured training program were "inclusion of basic communication skills", "exemplifying correspondence involving CBT-A using pre-recorded video(VTR)", and "approach methods for cases where counter-evidence is unavailable". The training program lasted for 4 h per day, for a total of 8 h. We also performed role-play scenarios on information gathering and medication guidance for simulated patients before and after training, and evaluated patient satisfaction with counseling, patient counseling alliance scores, and the degrees of the psychological distance between patients and pharmacists. Participants had high satisfaction with the discussion and role-play aspects of the training, as in our previous study. Participants also showed high satisfaction with "exemplifying correspondence involving CBT-A using VTR". Counseling time was significantly longer when using CBT-A compared to ordinary information gathering and medication guidance, but patient satisfaction and patient counseling alliance scores were both higher, and the psychological distance between patient and pharmacist was lower. Accordingly, if patients cannot solve their own problems, even when pharmacists provide polite responses and expertise, patients can be guided in their problem solving using CBT-A. It suggested that using CBT-A could solve the problem of patients with anxiety due to problems that cannot be solved only via drug-centered approach.

Prescription surveillance for early detection system of emerging and reemerging infectious disease outbreaks.

Based on prescriptions filled at external pharmacies, prescription surveillance (PS) in Japan has been reporting the estimated numbers of influenza and varicella patients and people prescribed certain drugs since 2009. Every morning, this system estimates the numbers of patients from the numbers of prescriptions filled nationwide for neuraminidase inhibitors, anti-herpes virus drugs, antibiotic drugs, antipyretic analgesics, and multi-ingredient cold medications. Moreover, it can detect "unexplained" infectious diseases that are not explained as infectious diseases monitored by other surveillance systems. Such "unexplained" infectious diseases might be emerging and re-emerging infectious diseases including bioterrorism attacks, which are reportedly difficult to diagnose, at least in early outbreak stages. To ascertain the system's potential benefits, this study examined schemes to detect "unexplained" infectious diseases using PS information. The numbers of patients prescribed the respective drugs are first regressed on the known infectious diseases, time trends, and dummies for day-of-the-week, holidays, and days following a holiday. Known infectious diseases are defined as covered by the National Official Sentinel Surveillance for Infectious Diseases under the Infection Control Law. After the numbers of patients from PS are compared with the predicted numbers of patients, their probabilities of occurrence are calculated. We examined the system's prospective operation from January 2017 through July 2018. The criterion we used to define aberrations varied, from 0.01 to 10-7. For criteria of 0.01 and 10-7 we found 254 and 15 aberrations, respectively. We confirmed its feasibility and effectiveness.

Evaluation of the global action plan on antimicrobial resistance in Japan during its first eighteen months.

Antimicrobial resistance (AMR) has garnered the most attention among public health concerns worldwide. Japan formulated a national action plan for AMR in April 2016. The plan seeks to reduce the amount of antimicrobials used in 2020 to two-thirds of the use recorded in 2013. Prescription surveillance (PS) is being used to monitor trends in the amount of antimicrobials used. PS estimates the number of patients prescribed an antimicrobial each day. The number of patients who were prescribed an antimicrobial under the action plan was analyzed by including dummy variables with other control variables. Data from April 1, 2011 to 30 September 30, 2017 were analyzed. When the number of patients with an infectious disease (1 of 13 specified diseases) served as a dummy variable, estimates indicated that the coefficient of that dummy variable was not significant. If the number of patients with an infectious disease (1 of 13 specified diseases) was excluded as an explanatory variable, then the estimated coefficient was significant. The global action plan in Japan might not reduce the amount of antimicrobials used. The current results indicated that the number of patients who were prescribed an antimicrobial did not decrease significantly after initiation of the action plan. This finding does not exclude the possibility that the average amount of antimicrobials used per patient has decreased.

Welfare analysis of a zero-smoking policy - A case study in Japan.

Smoking cessation efforts in Japan reduce smoking rates. A future zero-smoking policy would completely prohibit smoking (0% rate). We therefore analyzed the social welfare of smokers and non-smokers under a hypothetical zero-smoking policy. The demand curve for smoking from 1990 to 2014 was estimated by defining quantity as the number of cigarettes smoked and price as total tobacco sales/total cigarettes smoked by the two-stage least squares method using the tax on tobacco as the instrumental variable. In the estimation equation (calculated using the ordinary least squares method), the price of tobacco was the dependent variable and tobacco quantity the explanatory variable. The estimated constant was 31.90, the estimated coefficient of quantity was - 0.0061 (both, p < 0.0004), and the determinant coefficient was 0.9187. Thus, the 2015 consumer surplus was 1.08 trillion yen (US$ 9.82 billion) (95% confidence interval (CI), 889 billion yen (US$ 8.08 billion) - 1.27 trillion yen (US$ 11.6 billion)). Because tax revenue from tobacco in 2011 was 2.38 trillion yen (US$ 21.6 billion), the estimated deadweight loss if smoking were prohibited in 2014 was 3.31 trillion yen (US$ 30.2 billion) (95% CI, 3.13 trillion yen (US$ 28.5 billion) - 3.50 trillion yen (US$ 31.8 billion)), representing a deadweight loss about 0.6 trillion yen (US$ 5.45 billion) below the 2014 disease burden (4.10-4.12 trillion yen (US$ 37.3-37.5 billion)). We conclude that a zero-smoking policy would improve social welfare in Japan.

Comparative study of preciseness in the regional variation of influenza in Japan among the National Official Sentinel Surveillance of Infectious Diseases and the National Database of Electronic Medical Claims.

In Japan, national official surveillance for influenza has been performed at about 5,000 sentinel hospitals/clinics by the National Official Sentinel Surveillance of Infectious Diseases (NOSSID). Meanwhile, all electronic medical claims nationwide in the National Database of Electronic Medical Claims (NDBEMC) were recently disclosed by the Ministry of Health, Labour and Welfare of Japan. We compared the regional variation of influenza incidence among prefectures between the NOSSID and NDBEMC. The data were extracted from NOSSID and the NDBEMC for the 2010/2011 through 2013/2014 seasons. We compared the data of both datasets season by season by using Spearman's rank correlation in each season. Spearman's rank correlation values for the four seasons were 0.7823, 0.3907, 0.4961 and 0.4543, and their p-values were less than 0.00005, 0.0066, 0.0004 and 0.0013, respectively. Statistically, regional variation of influenza incidence in NOSSID is not imprecise, but its correlation with the NDBEMC dataset is not so high. It is important to note this fact when interpreting regional variation in NOSSID.

Development and Validation of a Training Program Using a Cognitive Behavioral Therapy Approach with the Purpose of Enabling Community Pharmacists to Provide Empathic Patient Counseling.

To enable community pharmacists to provide empathic patient counseling, we developed and validated a training program based on cognitive reframing, which is one of the cognitive behavioral therapies. We divided 24 community pharmacists into two groups, providing training to the intervention group. The duration of the training program was two hours per session, with a total of eight hours. We conducted a survey of the intervention group to evaluate their training experience. In addition, we performed two role-play scenarios on patient counseling using simulated patients, evaluating the patient counseling alliance scores and the degrees of the psychological distance between the patients and pharmacists. The degree of satisfaction correlated with four training items, including "explanation by comics". When pharmacists felt that the cognitive behavioral therapy approach was successful, no significant differences were found in the patient counseling alliance grades. However, the psychological distance between the patients and pharmacists was smaller. We were able to infer that a cognitive behavioral therapy approach could decrease the psychological distance between patients and pharmacists, thereby enabling empathic patient counseling.

Assessment of Assistance in Smoking Cessation Therapy by Pharmacies in Collaboration with Medical Institutions- Implementation of a Collaborative Drug Therapy Management Protocol Based on a Written Agreement between Physicians and Pharmacists.

This study built a protocol for drug therapy management (hereinafter "the protocol") that would enable continuous support from the decision making of smoking cessation therapy to the completion of therapy through the collaboration of physicians and community pharmacists, after which we evaluated whether the use of this protocol would be helpful to smoking cessation therapy. This study utilized the "On the Promotion of Team-Based Medical Care", a Notification by the Health Policy Bureau as one of the resources for judgment, and referred to collaborative drug therapy management (CDTM) in the United States. After the implementation of this protocol, the success rate of smoking cessation at the participating medical institutions rose to approximately 70%, approximately 28-point improvement compared to the rate before the implementation. In addition to the benefits of the standard smoking cessation program, this result may have been affected by the intervention of pharmacists, who assisted in continuing cessation by advising to reduce drug dosage as necessary approximately one week after the smoking cessation, when side effects and the urge to smoke tend to occur. Additionally, the awareness survey for the intervention group revealed that all respondents, including patients who failed to quit smoking, answered that they were satisfied to the question on general satisfaction. The question about the reason for successful cessation revealed that the support by pharmacists was as important as, or more important than, that by physicians and nurses. This infers that the pharmacists' active engagement in drug therapy for individual patients was favorably acknowledged.

Community pharmacists provided telephone treatment support for patients who received long-term prescribed medication.

PURPOSE: This study was conducted to evaluate whether a community pharmacist's assistance during the treatment of a patient with a chronic illness would help to discover and improve issues regarding the treatment. METHOD: We employed a prospective intervention study with a control group. The patients ranging in age from 60 to 74, were using one of the six selected community pharmacies in the Tokyo metropolitan area. They had been prescribed six or fewer kinds of medications, one of which was amlodipine. The medication dosages covered 1 month or longer. Patients who agreed to participate in the study were randomly assigned to the groups at each pharmacy. For the patients in the intervention group, the pharmacists provided telephone counseling between physician visits, in addition to the time they visited the pharmacies to collect their medications. For the patients in the control group, the pharmacists provided counseling only at their pharmacies. RESULTS AND DISCUSSION: The average days of medication administration were 49.2 days for the 58 patients in the intervention group, and 49.8 days for the 53 patients in the control group, with the average number of medications being 3.4 items per person for both groups. Through the telephone counseling, we were able to collect more information, eg, changes in physical condition and occurrences of side effects, from the intervention group than from the control group. The rate of incident detection in the information from the intervention group was five times that of the control group, making subsequent incident resolutions faster. CONCLUSION: This study suggested that phone counseling between physician visits could enable the identification of more issues regarding patients' conditions.

[Association between Diarrheal Infectious Diseases and Antidiarrheal Drugs Assessed with Prescription Surveillance].

OBJECT: It appears to be possible to measure the outbreak of infectious diseases with accompanying diarrhea by early detection of an outbreak. However, because some diseases are reported weekly from sentinel medical institutions, early detection of outbreaks might be inadequate. In this study, we examined the number of patients with diarrhea assessed with prescription surveillance and validated its association with the number of patients who have infectious diseases with diarrhea. METHODS: The number of patients who were prescribed an antidiarrheal drug or intestinal drug was estimated for each prefecture using the prescription surveillance system from April 1, 2011 through March 31, 2014. Moreover, we examined the association between the prevalence of diarrhea in prescription surveillance and the number of patients with diarrheal infectious diseases. RESULTS: Results showed a positive correlation between the prevalence of diarrhea in prescription surveillance and the number of reported cases per sentinel with gastrointestinal infections. However, no positive correlation was found with the others infectious diseases. CONCLUSION: Estimation of the number of patients with diarrhea in prescription surveillance might facilitate early detection of an outbreak of gastrointestinal infections.

[Evaluation of the Number of Varicella Patients Estimated by Prescription Surveillance].

OBJECT: It is important to know the precise number of varicella patients infected for evaluation of routine immunization and anti-bioterrorism attack using smallpox. Prescription Surveillance (PS) has been providing the estimated number of varicella patients up to the present. However, the estimated number of varicella patients cannot be validated because to date there has been no other comparable precise method of estimation. Recently, all electronic medical claims nationwide (NDB) have been disclosed. In this paper, we compare the number of varicella patients estimated by PS with NDB data, and adjust the number estimated with PS, if necessary. METHOD: For both NDB and PS, we used the monthly data from April, 2010 to March, 2013. The estimation of the number of varicella patients from the PS data was adjusted by the proportion of estimated number based on PS to the one based on NDB in the entire study period. Moreover, we adjusted it month by month, if the former method may not be enough to compensate for the discrepancy between the two datasets. RESULTS: The average discrepancy between NDB and PS was 48.00% in three years. By the adjustment using NDB in the three years, the discrepancy was improved to 11.49%. However, seasonal patterns of overestimation or underestimation were found. Conversely, by the adjustment using NDB month by month, the discrepancy was greatly reduced to 4.33%. Moreover, the seasonal patterns of overestimation or underestimation disappeared. CONCLUSION: The number of patients based on NDB would appear the most precise number, however, there may be a delay of about one year before it becomes available. On the other hand, PS data are updated every day and provide us with the up-to-date situation. This paper found that combining the timeliness of the PS data and preciseness of the NDB data will provide substantial benefit for public health.

Proposition of real-time precise prediction model of infectious disease patients from Prescription Surveillance using the National Database of Electronic Medical Claims.

The incidence of common pediatric infectious diseases has been monitored officially at sentinel medical institutions in Japan. However, the numbers of affected patients are not provided. Prescription Surveillance (PS), which infers the number of patients with influenza, varicella, and gastrointestinal infections from data related to prescriptions at external pharmacies, provides estimates to the public the following morning. This study assessed the prediction ability of the incidence of common pediatric infectious diseases from PS information using the National Database of Electronic Medical Claims (NDBEMC): the number of patients prescribed neuraminidase inhibitors, anti-herpes virus drugs, antibiotic drugs, antipyretic analgesics, and multi-ingredient cold medications. The diseases include RS virus infection, pharyngoconjunctival fever, hand, foot and mouth disease, erythema infectiosum, exanthem subitum, pertussis, herpangina, influenza, varicella, and gastrointestinal infection. For comparison, we used the estimated number of patients who were prescribed neuraminidase inhibitor in PS, which had been confirmed already for precision, and provided estimates to the general public via the internet. The discrepancy rates of all considered diseases between the reported number in NDBEMC and the predicted numbers of patients from PS were less than the value in NI counts and the coefficients of determination in the estimation were from .8109 to .9825. These predictions were sufficiently precise to provide to the general public.

[Outcome of the 6-year curriculum for pharmacy education: "Contribution to medical care and society: how will I act as a pharmacist in the future?"--A report on the 3rd National Student Workshop].

In August 2013, the Pharmaceutical Society of Japan held the Third National Student Workshop in Tokyo. A total of 88 people-70 sixth-year undergraduate students from 70 universities, and 18 alumni who had participated in the First and the Second Workshops-attended this Workshop. The theme of this Workshop was "Contribution to medical care and society: How will I act as a pharmacist in the future?" The first day took the form of a World Café, with participants exchanging information on such topics as, "The purpose for choosing a pharmacy major, and my achievement status", "My favorite aspects of my college", and "My dreams and paths: Painting my future image". Later that day, participants discussed and gave presentations on the ways they would be contributing as pharmacists to society and medical care. On the second day, participants discussed and gave presentations on the efforts they would like to make as pharmacists to contribute to society and medical care. The final session was a general assembly for discussion on the ways they would be contributing as pharmacists to society and medical care. Throughout the two days, attendees participated in discussions with an awareness of their common ground, in that they all had national qualification in spite of different intended paths. In this article, 4 sixth-year students (their status at the time of the symposium) from the Workshop introduce outlines of the discussions and products from each group.