Objective:The objectives were to assess regional differences in the safety outcomes of telaprevir-based triple therapy(T/PR) in Japan and evaluate a suitable generalized linear mixed model for estimating regional differences.

Design and Methods:This study targeted individuals infected with genotype 1 chronic hepatitis C virus registered in a nationwide Japanese interferon database from December 2009 to August 2015. The rate of dropout from treatmentattributable to adverse events was calculated in every prefecture where ≥ 20 cases were reported. We constructed the following four models and evaluated the best-fit model based on Akaike information criterion (AIC) and Bayesian information criterion (BIC):1)prefecture as a fixed-effect,2)prefecture and identified confounding factors as fixed-effects,

3)prefecture as a random-effect,and 4)prefecture as a random-effect and identified confounding factors as fixed-effects.

Results:A total of 25,989 individuals from 38 prefectures were registered during the study period;among them,1,591 from

18 prefectures were included as the study population. The dropout rate ranged from 7.0 to 23.1%among 17 prefectures.

The model considering prefecture as a random-effect and confounding factors as fixed-effects showed the best-fit for the databased on both the AIC (1,108.06)and BIC (1,113.41).

Conclusion:It is difficult to determine if regional differences exist in the safety outcomes of T/PR in Japan because of the limited number of cases. However, the model using prefecture as a random-effect and other confounding factors as fixed-effects would be suitable for estimating parameters that reflect the influence of the prefecture. Further studies using the model would help inform chronic hepatitis C treatment.

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Objective: We have developed an automatic vigilance system (AVS) that automatically reports adverse drug reactions (ADR) based on laboratory finding abnormalities and symptom keywords in electronic medical records.　In this study, we aimed to evaluate the impact of detecting ADR using AVS on medical treatment.

Methods: In AVS, drugs and their ADR signals, which would be detected and reported by AVS to pharmacists, were defined.　Pharmacists evaluated the severity of these signals to identify whether these signals should be discussed with the doctor, continued to be followed up, or ignored.　We investigated detection of ADR at University of Fukui Hospital between April 2016 and March 2017 along with whether prescriptions were modified because of ADR and the contribution of AVS.　Assuming that ADR had worsened without appropriate treatment, medical expenses needed for treating severe ADR were calculated.

Results: In total, 325 signals were defined for 146 drugs.　There were 9,103 ADR signals confirmed by pharmacists for 8,531 subjects.　Of these, 12 and 164 signals were discussed with the doctor and continuously observed, respectively.　The pharmacist's suggestions based on AVS led to prescription modifications in 10 cases, corresponding to a reduction of 2.56 million yen in medical expenses in the event that these cases become severe.

Conclusion: AVS assisted prescription revisions because of ADR and is thought to contribute to the prevention of worsening of ADR and reduction of medical expenses.

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Objectives: The aim of this study was to investigate both the time‐to‐onset and the onset‐pattern of drug‐induced blood disorders (DIBD) following the administration of monoclonal antibody agents through the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report （JADER) database.

Methods: Data in the JADER database from April 2004 to October 2017 were downloaded from the Pharmaceuticals and Medical Devices Agency website.　The DIBD dataset for monoclonal antibody agents was constructed based on the data for the drug information and adverse drug reactions.　The information for the adverse drug reactions was categorized in accordance with the preferred terms of the Medical Dictionary for Regulatory Activities and included thrombocytopenia, platelet count decreased, neutropenia, neutrophil count decreased, leukopenia, white blood cell count decreased, pancytopenia, anaemia, agranulocytosis, granulocyte count decreased, granulocytopenia, and bone marrow failure.　This dataset was then used to calculate the median onset times for the DIBD and the Weibull distribution parameters.

Results: The median onset times of the DIBD for gemtuzumab ozogamicin, cetuximab, ramucirumab, trastuzumab, panitumumab, bevacizumab, infliximab, rituximab, trastuzumab, and ibritumomab tiuxetan (⁹⁰Y) were 4, 10, 13, 14, 14, 14, 16, 16, 27, and 28 days, respectively.　The Weibull distributions for cetuximab, trastuzumab, bevacizumab, infliximab, and tocilizumab were estimated to fit the early failure type profile, while those for gemtuzumab ozogamicin, ramucirumab, rituximab, and ibritumomab tiuxetan (⁹⁰Y) were estimated to fit the wear out failure type profile.　The Weibull distributions for panitumumab were estimated to fit the random failure type profile.

Conclusions: The results of the present study clarified both the most likely time period and the onset‐pattern of DIBD that can occur in patients after the administration of monoclonal antibody agents.

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Background: With the marked changes occurring in the medical field, such as rapid population aging, the frequency of one‐dose package use by medication‐dispensing services is increasing.　Pharmaceutical companies promote the development of pharmaceutical products that can be identified based on their color, size, and imprinted information to reduce one‐dose packaging errors and difficulties in tablet identification.　However, there have not been any studies about the effectiveness of such measures for aiding the identification of tablets in the clinical setting.　Therefore, we examined the effects of imprinting on the ease of identification of tablets and capsules.

Methods: The study was conducted over a 3‐month period and involved 39 pharmacists aged under 40.　The times they needed to transcribe the characters imprinted on each tablet/capsule were measured.

Results: The time needed to identify a tablet was significantly shortened by kana printing (p<0.01), whereas more time was required to identify a capsule when the text color was similar to that of the capsule.　The observed transcription errors included ‘inaccurately transcribing alphanumeric characters' and ‘omitting units or other information.'

Discussion: These results suggest that kana printing is effective at increasing the ease of tablet/capsule identification, which is also affected by the color of the printed text.

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Objective: An evaluation index for drug release was measured in 25 currently used non‐steroidal anti‐inflammatory drugs (NSAIDs) for external use (4 components: indomethacin, diclofenac sodium, ketoprofen, and suprofen).

Methods: All release tests were performed using the Franz diffusion cell with phosphate buffered saline (PBS) as the receptor phase and an artificial membrane to maintain uniform measurement conditions.　The receptor phase was collected over time and measured using high performance liquid chromatography (HPLC) to calculate the release rate.　The measurement time points were set over 0-4 h based on clinical use.　Furthermore, the additives were compared among the products.

Results: The release profile of diclofenac sodium was similar among all 8 products.　On the other hand, the release rate of IN‐E (15.0% after 4 h) from indomethacin was higher than that from the other 6 products (6.2-9.1% after 4 h).　The release rate of KE‐D (39.2% after 4 h) from ketoprofen was higher than that from the cream, KE‐C (30.6 % after 4 h).　For suprofen, the release rate of SU‐E from the cream (18.1% after 4 h) was 1.6-1.7‐times higher than that of the other 2 products (10.9-11.3 %).　No release was detected from 3 suprofen ointments.

Conclusion: Differences in the additives may have been a cause of the observed differences in release over 0-4 h.　This study may serve as a useful index for pharmacists to propose and select appropriate drugs.

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Objective: Difficulty in extracting tablets from a press through pack (PTP) is believed to reduce prescription drug compliance.　This is a particularly serious issue for the elderly or for those who have physical disabilities affecting the fingers.　In this study, the squeezing force necessary to extract tablets from PTPs was measured for 33 commercial tablet products using a force gauge (FG).　Additionally, a sensory test was conducted to determine the degree of difficulty in extracting tablets from PTPs by squeezing, and the correlation between the difficulty measure and squeezing force was evaluated.

Methods: The squeezing force for 33 products was measured by FG.　The sensory test was conducted with 64 subjects.　Four products, each with a different squeezing force, were used for the sensory test.　In the test, each subject ranked the products in order according to the amount of force required to extract the tablets.　Each product's total score was used in the statistical analysis.

Results: The average squeezing force of the 33 products was 33.1 ± 6.9 〔N〕, and significant differences were observed among the products.　The sensory test revealed that each subject could significantly distinguish the amount of force required to extract the tablets from each product.

Conclusion: A positive correlation was observed between the squeezing force obtained using FG and the results from the sensory test.　This suggests that squeezing force can be used as an indicator for the usability of the product.　Therefore, the degree of difficulty in extracting tablets from PTPs should be considered when selecting drugs for the elderly.

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Objective:After the start of the Foods with Function Claims system started in April 2015, the number of Foods with Function Claims has increased every year. As such,the health food market in Japan is expanding and the health foods used by consumers has been changing. To clarify the influence by which Foods with Function Claims has affected people’s eating habits and improved their health, we surveyed people’s recognition and motivations to the Foods with Function Claims.

Methods:Our survey was conducted with 238 consumers attending a sports club in the Tama area in western Tokyo,Japan.

Results:In response to the question recognition of the word “Foods with Function Claims,”43 people(18.1%) responded “I know well,”141 people(59.2%)responded “I have heard it,but I do not know the meaning,”54 people(22.7%)responded “I do not know. I have never heard of it.” In response to the question whether to buy the Foods with Function Claims, 77 people (32.4%) responded “I buy if the price is a little higher than not the Foods with Function Claims,”126 people (52.9%) responded “I buy if the price is equal to not the Foods with Function Claims.” In response to the question, 182 people(76.5%)responded“I go to the hospital,”40 people(16.8%)responded“I do not go to the hospital and I use the Foods with Function Claims.”

Conclusion: Our results revealed that the recognition of Foods with Function Claims was low. However consumers recognized that the Foods with Function Claims is worth using. Education to improve recognition for the Foods with Function Claims is necessary.

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Objective:The topic model is a well-known method used in the field of natural language processing (NLP)that defines adocument as constructed of topics that combine specific t erms. This method is used to model topic co-occurrencemathematically. In this study,we extracted topics from featu re vectors of explicit documents called medical package insertsby using cluster analysis. Methods:We counted the terms(nouns)recognized by the morphological analysis engine MeCab and created a documentterm matrix. A value of“tf・idf”was calculated in this matrix for term weighting to avoid the effect of term frequency. We reduced the dimensionality of the matrix using singular v alue decomposition,which removed unnecessary data,and weextracted feature vectors attributed to each medical package insert. The distance between feature vectors was calculatedusing cosine distance,and cluster analysis was performed based on the distance between the vectors.

Results:Cluster analysis on our document-term matrix show ed that medical package inserts of drugs that have the sameefficacy or active ingredient were included in the same cl uster. Moreover, using term weighting and dimensionalityreduction,we could extract topics from medical package inserts.

Conclusion:We obtained a foothold to apply our findings t o the recommendation of similar drugs. Cluster analysis ofmedical package inserts using NLP can contribute to the pro per application of drugs. In addition,our study revealed thesimilarities of drugs and suggested possibilities for new applications from several points of view.

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In Japan, the National Health Insurance (NHI) prices of new drugs are set according to the NHI Drug Price Standard (NHI Price Standard).　The NHI Price Standard was notified by the Ministry of Health, Labour, and Welfare based on the ”Drug Price Calculation Criteria” proposed by the Central Social Insurance Medical Council (Chuikyo) in Japan.　The NHI Price Standard affects the research and development strategy of pharmaceutical companies.　In order to discover undetected relationships, the factors influencing the ”drug price” were evaluated through the association rule mining technique.　We surveyed the Chuikyo‐documents about NHI price listing over the period October 27, 2006 to February 8, 2007.　The number of approved new drugs was 874, while that of drugs completed (”drug price per day”) was 314.　The numbers of new compounds corresponding to a drug price per day of ”below 200 yen,” ”between 200 yen and 1,000 yen,” ”between 1,000 and 10,000 yen,” and ”above or equal to 10,000 yen” were 87 (27.7%), 91 (29.0%), 79 (25.2%), and 57 (18.2%), respectively.　In the association rule mining method, we observed high lift values of the combined items ”above or equal to 30,000 patients expected to be administrated” and ”drugs affecting sensory organs” in the group of drug price per day below 200 yen.　The lift values of the combinations of ”biological preparations” and ”similar efficacy comparison‐based price setting (Ⅱ)” or ”below 30,000 patients expected to be administrated” and ”antineoplastic drug” in the group of ”above or equal to 10,000 yen of drug price per day” were high.　These results provide a basis for the development and application of new drugs in Japan.

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Objective: Along with the increase in the number of foreign visitors to Japan, the number of inquiries in foreign languages at the time of OTC drug sales has increased.　To clarify the current status of responses to foreign language inquiries when selling OTC drug, we surveyed the frequency of foreign language response, languages used, trouble experienced, and preparation useful in responding to foreign language inquiries when selling OTC drug.

Methods: Our survey was conducted with 694 registered salesclerks of drugs at an external training seminar in Tokyo, Japan.

Results: Of the 649 respondents, 337 (51.9%) had experience in responding to inquiries in a foreign language when selling OTC drug.　The languages used were as follows: ”English,” 86.4%; ”Chinese,” 70.0%; ”Korean,” 25.8%.　Of the respondents who had experience in responding to inquiries in a foreign language when selling OTC drug, 107 (31.8%) responded ”I experienced trouble because I could not understand what was being said,” and 228 (67.7%) responded ”I could not respond and experienced trouble.”　When asked about preparation/tools useful for selling OTC drug, 434 (66.9%) responded ”multilingual written correspondence table,” 359 (55.3%) responded ”smartphone or tablet‐based correspondence multilingual table,” 299 (46.1%) responded ”marks and illustrations,” and 253 (39.0%) responded ”I would like to be taught how to respond in a foreign language (simple conversation).”

Conclusions: Our results revealed that when selling OTC drug, response to inquiries in a foreign language occurred frequently and trouble was experienced in listening comprehension and speaking a foreign language.　Therefore, urgent countermeasures such as preparing a multilingual correspondence table of symptoms, usage, and dosage, and lectures on methods of responding through simple foreign language conversations are necessary.　In addition, efforts such as creation of multilingual drug package inserts by pharmaceutical companies were considered to be an effective measure.

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