Combination carboplatin and nab-paclitaxel as a first-line treatment for advanced thymic carcinoma.

Thymic carcinoma is a very rare neoplasm for which no optimal chemotherapeutic regimen has been established to date. Hence, we performed this study to investigate the efficacy and safety of carboplatin plus nanoparticle albumin-bound (nab)-paclitaxel as a first-line regimen for patients with advanced thymic carcinoma. We conducted this multi-institutional retrospective cohort study of patients with advanced thymic carcinoma who had received carboplatin plus nab-paclitaxel as a first-line chemotherapy between August 2013 and December 2021. Twelve patients were included in this study and were subjected to efficacy and safety analysis. Their median age was 62 years (range, 47-74 years), and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. After a median follow-up time of 19.7 months, the overall response rate was 50%; the median progression-free and overall survival times were 8.8 months and 23.3 months, respectively. Chemotherapy-related peripheral neuropathy was observed in 2 patients (16%; each with grade 1). Other toxicities were manageable, and there were no treatment-related deaths. Carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen showed good efficacy and safety in patients with advanced thymic carcinoma.

A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

Single oral administration of the novel CXCR4 antagonist, KRH-3955, induces an efficient and long-lasting increase of white blood cell count in normal macaques, and prevents CD4 depletion in SHIV-infected macaques: a preliminary study.

We evaluated the long-term effects of the single oral administration of a new CXCR4 antagonist, KRH-3955, on elevation of white blood cell (WBC), neutrophil and lymphocyte counts in normal cynomolgus monkeys. In the monkeys treated with 0, 2, 20, 200 mg/kg of the compound, WBC, neutrophil and lymphocyte counts increased dramatically at 2 days after treatment. This effect was dose-dependent, and these cell counts remained elevated 15 days after drug treatment. Since neutrophils are the most abundant WBCs in circulation and bone marrow neutrophil exhaustion impairs the response to bacterial infections, it is intriguing to exploit this pharmacological increase of neutrophils as a tool to address its influence on viral infections in vivo. The SHIV infection studies using the SHIV-KS661c/cynomolgus monkey model showed that a single oral administration of KRH-3955 (100 mg/kg) approximately 24 h before virus exposure did not prevent infection, although it did prevent CD4 cell depletion in 3/3 monkeys. Furthermore, single oral administration of the drug 2 weeks before viral exposure rescued CD4 cells in 1/3 monkeys. This prevention of CD4 cell depletion was observed in both blood and lymphoid tissues. These results show that natural course of the SHIV infection is modulated by artificial increase of neutrophils and lymphocytes caused by KRH-3955 in the cynomolgus monkey model.

The cytostatic effects of lovastatin on ACC-MESO-1 cells.

BACKGROUND: Malignant pleural mesothelioma is known to be widely resistant to therapy, and new treatment strategies are needed. Statins are small molecules that suppress the production of multiple hydrophobic substrates in the mevalonate pathway. Although still controversial, statins may decrease the risk of certain cancers such as colon cancer, lung cancer, and prostate cancer. Since the evaluations of the direct effect of statins on malignant mesothelioma are still few, the present study was done to evaluate the effects of lovastatin on ACC-MESO-1 cells in vivo and to investigate the potential mechanisms involved in vitro. MATERIALS AND METHODS: The in vivo effect of lovastatin was evaluated using an NOD/SCID/γnull (NOG) mouse model of human malignant mesothelioma using ACC-MESO-1 cells. Lovastatin was also applied to ACC-MESO-1 cells in vitro and the effects were observed. RESULTS: Lovastatin administration reduced primary tumor and metastasis in the NOG mouse model of human malignant mesothelioma. In vitro studies showed that lovastatin administration induced cytostatic effects as per reduced cell viability and cell migration in ACC-MESO-1 cells. These effects were suggested to be dependent on autophagic changes rather than apoptosis. Furthermore, induction of autophagic changes by lovastatin in ACC-MESO-1 cells was independent of mTOR, and was considered to be dependent at least in part on Rac/phospholipase C/ inositol 1,4,5-triphosphate axis. CONCLUSIONS: These results suggest that it may be possible to utilize statins, or other pharmacological agents that are known to induce mTOR-independent autophagy, as an adjunct to standard treatments in malignant mesothelioma.

[Use of sugammadex in a patient with narrow angle glaucoma].

An 86-year-old woman was scheduled to receive fourth reconstructive surgery for femoral bone fracture under general anesthesia. She had been suspected with narrow angle glaucoma due to headache and bloodshot eyes during gastroscopy. During transfer to our hospital, she fell down and suffered from the right femoral neck fracture. The patient underwent femoral head replacement under spinal anesthesia. Later, she received surgeries twice uneventfully under spinal anesthesia; removal and re-implantation of the femoral bone head due to infection of the implanted head. Six months later, she fell down again and femoral bone was fractured during rehabilitation. Anesthesia was induced with propofol followed by rocuronium 0.9 mg x kg(-1) i.v. Anesthesia was maintained with propofol and remifentanil, and rocuronium was administered to maintain PTC of 10 or less. The surgery was completed in 150 minutes. At the end of surgery, a laryngeal mask was inserted and the tracheal tube was removed. TOF ratio recovered to 80% 8 minutes after sugammadex 2 mg kg(-1) i.v., and increased to 100% 3 minutes after additional 1 mg x kg(-1). Intraocular pressure stayed below 20 mmHg during the intervention. We could achieve full reversal of neuromuscular blockade and suppress increase in intraocular pressure with use of sugammadex.

[A case of valsartan-induced pneumonitis with marked elevation of serum KL-6].

A 64-year-old man, who had been treated with valsartan for hypertension since about 2 months previously, was admitted with exertional dyspnea. A chest X-ray film on admission showed infiltrative shadows in bilateral lower lung fields. Chest computed tomographic images showed diffuse ground-glass opacities, consolidation and traction bronchiectasis. His serum KL-6 level was markedly elevated, to 7,360 U/ml. Despite the withdrawal of valsartan, his symptoms deteriorated, and a drug lymphocyte stimulation test was positive for valsartan. Based on these findings, we diagnosed valsartan-induced pneumonitis. Glucocorticoids were administered, and his symptoms, chest radiograph findings and serum KL-6 level all improved. Currently, angiotensin II receptor blockers (ARBs), including valsartan, are often used as the first drug of choice to treat hypertension, but they can cause drug-induced pneumonitis. It has been previously reported that serum KL-6 levels may reflect the clinical activity of drug-induced pneumonitis. In cases of drug-induced pneumonitis with a high level of serum KL-6, glucocorticolds should be started at an early stage.

[A long-term case of Sjögren's syndrome with pulmonary multiple cystic lesions].

A 68-year-old woman was admitted to our institution's respiratory section because of dyspnea on effort in January, 2007. She had previously received a diagnosis of Sjögren's syndrome because of dryness in her eyes in 1991. Chest radiography and chest CT in 2001 revealed diffuse multiple cystic lesions in both lungs which had progressed gradually for 6 years. Biopsy specimens obtained by video-assisted thoracoscopy showed lymphoid hyperplasia with follicular bronchiolitis and lymphocytic alveolitis. Narrowing of the small airways and obstructive lung disease with multiple bullae were observed and we suspected them to be related to peribronchiolar lymphocytic infiltration. These were lung involvements associated with Sjögren's syndrome. The patient's cystic lesions gradually worsened despite the administration of corticosteroid and cyclophosphamide. Cystic lesions in Sjögren's syndrome may be a treatment-resistant finding.

[Current Status and Development of Drug Information Infrastructure System for the Public in Japan and Overseas].

With the progress of medical treatment, information on drugs, etc. is overflowing on the media and the Internet, and some of them are leading to uncertain information for the purpose of profit, and some of them are wrong information or inaccurate information, and the effect on the patient is regarded as a problem. In Japan, information on public pharmaceuticals for patients and consumers is provided on the Internet, but its utilization is not sufficient. In the Pharmaceuticals and Medical Devices Act, it is stated that "Citizens shall endeavor to use pharmaceuticals, etc., properly and deepen their knowledge and understanding of their efficacy and safety". On the other hand, there is a variety of information available on the Internet, and simply searching does not necessarily lead to reliable information. It is necessary to provide information with a mechanism to ensure that the information is reliable so that it can lead to appropriate medical care. Overseas, medical information infrastructure systems, including highly reliable public pharmaceuticals based on evidence, have been developed. Examples include National Health Service (NHS) in the United Kingdom, MedlinePlus in the United States, and National Prescribing Service (NPS) MedicineWise in Australia. In the era of digital health, it is necessary to discuss issues and prospects for the construction and dissemination of information provision infrastructure that meets the needs of patients and consumers from the perspective of industry, government, academia, and patients.

Evaluation of rapid drug safety communication materials for patients in Japan.

Since 2011, pharmaceutical companies in Japan have been required to issue two types of documents regarding severe adverse drug reactions reported post-marketing, namely the Rapid Safety Communication Materials for Patients and the Related Materials. However, the adequacy of these documents has not yet been systematically assessed. The aim of this study was to evaluate the adequacy of these two types of materials. The Rapid Safety Communications for Patients were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website. The Related Materials were obtained from pharmaceutical companies or the PMDA website. Three assessors independently scored the Rapid Safety Communication for Patients and the Related Materials using the Centers for Disease Control and Prevention Clear Communication Index (CCI). In addition, the contents and descriptions of the materials were analyzed. In total, 13 materials for seven drugs were assessed. Almost all materials contained the "main message" and "call to action". However, the average CCI scores for the Rapid Safety Communication for Patients and Related Materials for Patients were 68.8 and 74.3 (out of 100), respectively. Further, none of the evaluated materials were scored above the CCI threshold score (i.e., ≥ 90%). Descriptions regarding "language", "state of science", and "risk" were not adequate. In particular, the terminology used in materials seemed difficult for patients to understand. In conclusion, the Japanese Rapid Communication Materials for Patients require improvement. Furthermore, a system for evaluating these materials prior to publication should be established.

MDM2 SNP 309 human papillomavirus infection in cervical carcinogenesis.

OBJECTIVE: To investigate the biological significance of single nucleotide polymorphism (SNP) at murine double-minute 2 homolog (MDM2) promoter 309 in cervical carcinogenesis. METHODS: SNP at MDM2 promoter 309 (T/G) together with human papillomavirus (HPV) types was examined in a total of 195 cervical smear samples and 8 human cervical squamous carcinoma cell lines using two independent PCR assays and PCR-RFLP techniques. RESULTS: Forty-one patients with high-grade squamous intraepithelial lesion (HSIL) had higher frequency of high-risk HPV than 102 with low-grade SIL (LSIL) and 52 controls. There was an increased OR (8.88; CI=2.34-33.63; P=0.003) for TG+GG genotype in HSIL cases compared to controls among 68 patients with high-risk HPV. Twenty-one cases with HPV types 16 and/or 18 had significantly higher frequency of the TG+GG genotype and G allele than 47 with other types of high-risk HPV. Seven of 8 cervical carcinoma cell lines also showed TG or GG genotype. CONCLUSION: MDM2-SNP309 (T/G) and high-risk HPV infection may be closely associated with cervical carcinogenesis in a Japanese population.

Vitamin D deficiency in two young adults with biochemical findings resembling pseudohypoparathyroidism type I and type II.

We report two patients with vitamin D deficiency due to unbalanced diet. The patients initially presented with severe hypocalcemia, normophosphatemia and markedly elevated serum PTH levels. Although nutritional vitamin D deficiency was suspected from their history of gastrointestinal problems and dietary restriction, we conducted Ellsworth- Howard test to exclude the possibility of pseudohypoparathyroidism (PHP). Both patients showed no incremental response of urinary phosphate excretion. However, the urinary cAMP response to exogenous PTH was different between the two. Case 1 showed a blunted response (5-fold and 1.54 micro mol/h increase) and case 2 showed a normal response (39-fold and 3.04 micro mol/h increase). According to the criteria of Ellsworth-Howard test, the data of case 1 was compatible with PHP type I, and of case 2 with PHP type II. The final diagnosis of vitamin D deficiency was established in both patients based on very low serum 25-hydroxyvitamin D levels (less than 5 ng/mL) and the effect of treatment. After calcium supplementation with or without vitamin D, their biochemical abnormalities disappeared. They maintained normocalcemia without medication after correction of their unbalanced diet. The present study indicated that patients with vitamin D deficiency occasionally showed biochemical findings suggestive of PHP and that such patients could exhibit not only PHP type II pattern of response to exogenous PTH but also of type I pattern. Thus our clinical observation suggests the complexity of PTH resistance in vitamin D deficiency and underscores the importance of diet to prevent the disorder.

[Spinal anesthesia in a patient with SMON disease].

We report a patient with subacute myelo-optico-neuropathy (SMON) in whom spinal anesthesia was employed to treat fracture of the femur neck. An 87-year-old woman was diagnosed as having SMON at the age of 45. The patient was admitted to our hospital with fracture of the femur neck. Aspiration pneumonia was also suspected with shadow in the right lung on the chest X-P The percutaneous oxygen saturation (Spo2) with room air was 77%. Spinal anesthesia with 5 mg of 0.5% hyperbaric bupivacaine and 20 mcg of fentanyl was performed at L3-4. The level of anesthesia was T4. During surgery, no severe pain in the lower limbs was observed. Three hours after the end of surgery, the level of anesthesia was T9. On the day after surgery, the extent of dysesthesia and reflex were similar to those before surgery. General anesthesia has been chosen in SMON patients, because there was a report of severe pain of the lower limbs after spinal anesthesia with dibucaine. In our patient, general anesthesia was considered inappropriate due to hypoxemia. We used a mixture of bupivacaine and fentanyl for spinal anesthesia, because the neurotoxicity of bupivacaine is weaker than that of dibucaine.

[A case of recurrent invasive thymic cancer showing a stable disease to carboplatin plus paclitaxel].

A 56-year-old man was admitted to our hospital because of increasing chest discomfort and abnormal chest shadow. Computed tomography (CT) of the chest revealed an anterior mediastinal mass, pleural dissemination and lung metastasis. Percutaneus needle biopsy guided by CT showed that the mass was advanced thymic cancer (stage IV b according to the classification proposed by Masaoka). After failure of combination chemotherapy of cisplatin, vincristine, doxorubicin and etoposide (CODE), he received 4 cycles of carboplatin plus paclitaxel and then achieved confirmed stable disease. In terms of toxicity profile, grade 4 anemia, grade 2 leucopenia and neutropenia were observed, and particularly non-severe toxicity was not observed in terms of non-hematologic toxicity. Carboplatin plus paclitaxel can be an active agent against pretreated thymic cancer.

An HIV protease inhibitor, ritonavir targets the nuclear factor-kappaB and inhibits the tumor growth and infiltration of EBV-positive lymphoblastoid B cells.

Epstein-Barr Virus (EBV)-associated immunoblastic lymphoma occurs in immunocompromised patients such as those with AIDS or transplant recipients after primary EBV infection or reactivation of a preexisting latent EBV infection. In the present study, we evaluated the effect of ritonavir, an HIV protease inhibitor, on EBV-positive lymphoblastoid B cells in vitro and in mice model. We found that it induced cell-cycle arrest at G1-phase and apoptosis through down-regulation of cell-cycle gene cyclin D2 and antiapoptotic gene survivin. Furthermore, ritonavir suppressed transcriptional activation of NF-kappaB in these cells. Ritonavir efficiently prevented growth and infiltration of lymphoma cells in various organs of NOD/SCID/gammacnull mice at the same dose used for treatment of patients with AIDS. Our results indicate that ritonavir targets NF-kappaB activated in tumor cells and shows anti-tumor effects. These data also suggest that this compound may have promise for treatment or prevention of EBV-associated lymphoproliferative diseases that occur in immunocompromised patients.

Fluctuating liver functions in siblings with MPV17 mutations and possible improvement associated with dietary and pharmaceutical treatments targeting respiratory chain complex II.

BACKGROUND/AIMS: To describe the clinical and biological findings of two Japanese siblings with novel MPV17 gene mutations (c.451insC/c.509C > T) manifesting hepatic mitochondrial DNA depletion syndrome. METHODS: We observed these brothers and sought to determine the efficacy of treatment targeting respiratory chain complex II for the younger brother. RESULTS: A 3-month-old boy had presented with profound liver dysfunction, failure to thrive, and watery diarrhea. Although he was then placed on a carbohydrate-rich diet, his liver function thereafter fluctuated greatly in association with viral infections, and rapidly deteriorated to liver failure. He underwent liver transplantation at 17 months of age but died at 22 months of age. The younger brother, aged 47 months at the time of this writing, presented with liver dysfunction from 8 months of age. His transaminase levels also fluctuated considerably fluctuations in association with viral infections. At 31 months of age, treatment with succinate and ubiquinone was initiated together with a lipid-rich diet using ketone milk. Thereafter, his transaminase levels normalized and never fluctuated, and the liver histology improved. CONCLUSIONS: These cases suggested that the clinical courses of patients with MPV17 mutations are greatly influenced by viral infections and that dietary and pharmaceutical treatments targeting the mitochondrial respiratory chain complex II may be beneficial in the clinical management of MPV17 mutant patients.

Effect of gefitinib on warfarin antithrombotic activity.

BACKGROUND: Despite the literature indicating adverse interactions between warfarin and cytotoxic agents, whether such an interaction occurs when warfarin and gefitinib are used concomitantly is unknown. We analyzed the prevalence of the concomitant use of warfarin and gefitinib, and the incidence of prothrombin time-international normalized ratio (PT-INR) alterations or adverse interactions in concomitant users of warfarin and gefitinib. METHODS: We conducted a retrospective study of patients with non-small cell lung cancer treated at the Kitasato University Hospital who received concomitant warfarin and gefitinib between September 2002 and January 2007. Medical information, including the indication for warfarin use, warfarin dosing and dosing changes, and exposure to gefitinib were collected from computerized databases and medical records. RESULTS: Twelve (4.1%) of 296 patients treated with gefitinib received warfarin. PT-INR elevation occurred in 6 patients (50.0%). Two (16.7%) of the 12 patients had liver metastases. Liver dysfunction was associated with PT-INR elevation (P = 0.0100). CONCLUSION: As there is a possibility of PT-INR abnormalities occurring during the concomitant use of gefitinib and warfarin, clinicians should be aware of this interaction. Because of the potentially severe consequences of this interaction, close monitoring of PT-INR and warfarin dose adjustment are recommended for patients receiving warfarin and gefitinib, especially during the first 2 weeks in the beginning of warfarin therapy.

Difference in autologous blood transfusion-induced inflammatory responses between acute normovolemic hemodilution and preoperative donation.

PURPOSE: The inflammatory response triggered by transfusion is implicated in the pathophysiology of transfusion-related immunomodulation. The authors hypothesized that two distinctive autotransfusion methods, acute normovolemic hemodilution (ANH) and preoperative donation (PD), have different influences on both inflammatory mediator generation during storage and the inflammatory response after a transfusion. The purpose of this study was to compare the plasma concentrations of neutrophil elastase (NE), interleukin (IL)-6, IL-8, and IL-10 in patients who underwent either of these two autologous transfusion methods. METHODS: With institutional review board approval, the plasma concentrations of the above inflammatory mediators were determined in 23 patients with ANH and 8 patients with PD at the following time points: after anesthetic induction, at the end of the operation, and the morning of postoperative day 1. The concentrations of these inflammatory mediators were also measured in the donated blood obtained by either ANH or PD before retransfusion. RESULTS: The mean storage durations were 3.7 h and 6.1 days for ANH and PD, respectively. Higher concentrations of NE and IL-10 were detected in the PD blood than in the ANH blood. Long duration of storage and/or low temperature may have been responsible for the increased NE and IL-10 concentrations in the PD blood. However, the difference between the two groups in the extent of increased plasma concentrations of these inflammatory mediators was not statistically significant. CONCLUSION: Inflammatory mediators were significantly increased in PD blood during storage compared to the blood obtained by ANH. However, their effects on the inflammatory response elicited in the recipients were not significantly different.

[Parental presence is a useful method for smooth induction of anesthesia in children: a postoperative questionnaire survey].

BACKGROUND: Parental presence during induction of anesthesia (PPIA) is widely practiced to prevent preoperative anxiety in children. However, some previous studies described parental presence is less effective than sedative premedication. The purpose of this investigation is to determine whether PPIA is not an effective prevention of preoperative anxiety using a postoperative questionnaire survey to parents. METHODS: PPIA was performed for 72 children (aged 1-15 years old) during one year. No patients received sedative premedication before surgery. We evaluated degree of anxiety before induction of anesthesia with four-point scale, 1: exciting and crying before entering surgical room, 2: exiting and crying on a surgical bed, 3: agitated, crying, not exciting, 4: calm. After surgery, we executed a questionnaire survey to parents concerning degree of anxiety and satisfaction. RESULTS: Ninty percent of parents accepted PPIA and all parents wanted PPIA next time if their children undergo surgery again. Younger age and frequency of surgery were associated with anxiety during induction in children (P<0.05). On the other hands, children above ten years of age did not want PPIA so much. CONCLUSIONS: PPIA has beneficial effects against preoperative anxiety in both children and parents.

[Activities of Choosing Wisely and Role of Pharmacists].

Choosing Wisely (CW) is a pharmaceutical campaign activity that is spreading rapidly internationally. Briefly, it is an activity "aiming for appropriate medical care by reviewing the medical practice that is practiced despite lack of evidence from the viewpoint of evidence based medicine (EBM)". Here, healthcare workers and patients, through dialogue, are aiming to be able to carry out medical practices (examinations, treatment) that are scientifically validated, truly necessary, and have few side effects. In 2012, the American Institute of Internal Medicine listed five topics (Top Five Lists) and presented the medical practices and reasons that should be reconsidered. Based on this, many academic societies and medical professional organizations around the world presented five unique lists from their respective standpoints. And, in 2016, CW Japan was established in our country. The ultimate goal of this activity is to encourage dialogue and share decision-making with the patients so that healthcare workers can "select wisely" appropriate medicine for their patients based on professionalism. In Japan, recent attention has also been paid to problems concerning proper use of polypharmacy and antibiotics, especially for elderly people. To support a sustainable medical system in the future, it is desirable to promote efforts to realize "high-value care" for patients, paying particular attention to limit unnecessary medical care. Under such circumstances, I will introduce some issues and activities that overseas pharmacists are working on in the context of CW, and discuss roles and tasks to be taken by pharmacists in Japan.

[Significance and Role of Academic Detailing for Optimal Medication].

"Academic detailing" is used to clearly explain scientific issues. In the field of clinical practice, "academic detailing" is a form of interactive educational outreach to physicians in order to provide unbiased, non-commercial, evidence-based information about medications and other therapeutic modalities, with the goal of improving patient care. It is necessary to provide proper information about prescription drugs for their appropriate use in clinical practice. However, this requires of physicians significant time and labor to comprehensively collect and summarize all necessary information for the proper clinical application of pharmaceutical products, a task which may be both difficult and prohibitive to a busy physician. However, if clinical experience and other pharmaceutical or treatment information is derived solely from the commercial entities, this may lead to improper prescription practices. In western countries, public funds are used to support universities and other research institution programs. In Canada, clinical pharmacists act as "detailers". Their mission and role is to listen to the needs of the physician or health care professional, to provide objective, evidence-based drug information on selected drug therapy topics, to educate physicians on the optimal use of medications, to provide practical alternatives, and to extend the physician's usable knowledge base. The importance of this "academic detailing" activity is also recognized in Japan, and pharmacists can be expected to act as detailers in the future. We hope that this will lead to improvement in the quality of medical care.