Objective: There are only a few studies evaluating the effects of drug information services on pharmacotherapy.  We, therefore, studied the effects of providing drug information such as the effectiveness and safety of aliskiren on its pharmacotherapeutic efficacy by comparing before versus after drug information provision.
Methods: Pharmacists provided drug information such as the effectiveness and safety of aliskiren coadministered with either ACE-I (angiotensin converting enzyme inhibitor) or ARB (angiotensin receptor blocker) to physicians and other healthcare professionals.  We compared the number of patients for whom aliskiren was prescribed, the proportion of diabetic patients taking both aliskiren and ACE-I (or ARB), the proportion of patients with low eGFR (estimated glomerular filtration rate), and the proportion of patients with hyperkalemia and related conditions, before versus after providing the drug information to the healthcare professionals.
Results: The number of patients for whom aliskiren was prescribed decreased.  The proportion of patients taking both aliskiren and ACE-I (or ARB) decreased significantly after providing the drug information (p=0.007).  The proportion of diabetic patients taking both aliskiren and ACE-I (or ARB), the proportion of patients with low eGFR, and the proportion of patients with hyperkalemia also decreased, after providing the drug information.
Conclusion: This study showed the drug information service to be clinically beneficial, achieving better pharmacotherapy.  Pharmacists should evaluate and provide information on the effectiveness and safety of drugs announced by authorities in a timely manner to achieve optimal patient care.

Background: Globalization urges us to discuss rationale and policy towards establishing a medical education accrediting body in Japan. Experience of General Medical Council （GMC） suggests us some useful lessons.
Method: Based on our visits and investigation into in GMC, we inquire how Quality Assurance （QA） was introduced in UK with what incentives and how QA has brought reforms in the medical schools in UK.
Result: Since 2003, GMC has changed its policy for QA from ‘inspection’ to ‘dialogue’. Dialogical QA asks a medical school to think critically of their education and consider vigorous actions for further improvements.
Discussion: Implications from the experience of GMC are: 1.QA process in GMC makes medical schools take robust steps towards changes, 2. Sharing the rational and policy for QA created the solid base for its effective implementation, 3. There are possible difficulties in establishing structure to do an enormous amount of coordinating work, which is necessary for constructing ‘dialogue with medical schools’.

Background: Prompt awakening and sufficient recovery of psychomotor and equilibrium functions are important for day surgery. Flumazenil accelerates recovery of consciousness after remimazolam anesthesia, but its effects on psychomotor and equilibrium functions are not well known. The purpose of this study was to determine whether flumazenil improves time to recovery, psychomotor, and equilibrium functions in subjects undergoing remimazolam anesthesia. Methods: The design was a single-center, double-blind, randomized, controlled trial. Inclusion criteria were patients aged 18–64 years scheduled for oral surgery under remimazolam anesthesia, with American Society of Anesthesiologists physical status I or II. The predictor variable was the use of a reversal agent (flumazenil group) versus placebo (non-flumazenil group). The primary outcome variable was recovery from sedation measured using the Modified Observer’s Alertness/Sedation (MOAA/S) scale for wakefulness. Secondary outcome variables were psychomotor function measured using the Trieger Dot Test (number of dots missed [NDM], maximum distance of dots missed [MDDM]), and the digit symbol substitution test (DSST), as well as equilibrium function measured using the timed up and go test (TUG), and gravimetric area and speed. Statistical analyses were performed using the Mann-Whitney U test, χ² test, Student’s t-test, two-way ANOVA, and Bonferroni correction. P-values < 0.05 were considered significant. Results: Sixty-eight subjects were included (male: 33, female: 35). The mean time from extubation to an MOAA/S score of 5 (minutes) was 6.5 (1.5–10.5) in the flumazenil group and 13.5 (6.8–19.3) in the non-flumazenil group (P = 0.01). There was no significant difference in the recovery of psychomotor and balance functions between the two groups. However, the following measurements were significantly increased compared to baseline: NDM (P < 0.001) and DSST (P < 0.001) at 30 minutes, MDDM (P < 0.001), TUG (P < 0.001), and gravimetric speed (P < 0.001) at 60 minutes, and gravimetric area (P = 0.03) at 90 minutes. Conclusion Administration of flumazenil after remimazolam anesthesia resulted in faster recovery of consciousness, but it did not affect the recovery of psychomotor and equilibrium functions. The time until patients were safe to return home was 120 minutes. Flumazenil did not improve the time until it was safe for patients to return home.

Background: Prompt awakening and sufficient recovery of psychomotor and equilibrium functions are important for day surgery. Flumazenil accelerates recovery of consciousness after remimazolam anesthesia, but its effects on psychomotor and equilibrium functions are not well known. The purpose of this study was to determine whether flumazenil improves time to recovery, psychomotor, and equilibrium functions in subjects undergoing remimazolam anesthesia. Methods: The design was a single-center, double-blind, randomized, controlled trial. Inclusion criteria were patients aged 18–64 years scheduled for oral surgery under remimazolam anesthesia, with American Society of Anesthesiologists physical status I or II. The predictor variable was the use of a reversal agent (flumazenil group) versus placebo (non-flumazenil group). The primary outcome variable was recovery from sedation measured using the Modified Observer’s Alertness/Sedation (MOAA/S) scale for wakefulness. Secondary outcome variables were psychomotor function measured using the Trieger Dot Test (number of dots missed [NDM], maximum distance of dots missed [MDDM]), and the digit symbol substitution test (DSST), as well as equilibrium function measured using the timed up and go test (TUG), and gravimetric area and speed. Statistical analyses were performed using the Mann-Whitney U test, χ² test, Student’s t-test, two-way ANOVA, and Bonferroni correction. P-values < 0.05 were considered significant. Results: Sixty-eight subjects were included (male: 33, female: 35). The mean time from extubation to an MOAA/S score of 5 (minutes) was 6.5 (1.5–10.5) in the flumazenil group and 13.5 (6.8–19.3) in the non-flumazenil group (P = 0.01). There was no significant difference in the recovery of psychomotor and balance functions between the two groups. However, the following measurements were significantly increased compared to baseline: NDM (P < 0.001) and DSST (P < 0.001) at 30 minutes, MDDM (P < 0.001), TUG (P < 0.001), and gravimetric speed (P < 0.001) at 60 minutes, and gravimetric area (P = 0.03) at 90 minutes. Conclusion Administration of flumazenil after remimazolam anesthesia resulted in faster recovery of consciousness, but it did not affect the recovery of psychomotor and equilibrium functions. The time until patients were safe to return home was 120 minutes. Flumazenil did not improve the time until it was safe for patients to return home.

Background: Prompt awakening and sufficient recovery of psychomotor and equilibrium functions are important for day surgery. Flumazenil accelerates recovery of consciousness after remimazolam anesthesia, but its effects on psychomotor and equilibrium functions are not well known. The purpose of this study was to determine whether flumazenil improves time to recovery, psychomotor, and equilibrium functions in subjects undergoing remimazolam anesthesia. Methods: The design was a single-center, double-blind, randomized, controlled trial. Inclusion criteria were patients aged 18–64 years scheduled for oral surgery under remimazolam anesthesia, with American Society of Anesthesiologists physical status I or II. The predictor variable was the use of a reversal agent (flumazenil group) versus placebo (non-flumazenil group). The primary outcome variable was recovery from sedation measured using the Modified Observer’s Alertness/Sedation (MOAA/S) scale for wakefulness. Secondary outcome variables were psychomotor function measured using the Trieger Dot Test (number of dots missed [NDM], maximum distance of dots missed [MDDM]), and the digit symbol substitution test (DSST), as well as equilibrium function measured using the timed up and go test (TUG), and gravimetric area and speed. Statistical analyses were performed using the Mann-Whitney U test, χ² test, Student’s t-test, two-way ANOVA, and Bonferroni correction. P-values < 0.05 were considered significant. Results: Sixty-eight subjects were included (male: 33, female: 35). The mean time from extubation to an MOAA/S score of 5 (minutes) was 6.5 (1.5–10.5) in the flumazenil group and 13.5 (6.8–19.3) in the non-flumazenil group (P = 0.01). There was no significant difference in the recovery of psychomotor and balance functions between the two groups. However, the following measurements were significantly increased compared to baseline: NDM (P < 0.001) and DSST (P < 0.001) at 30 minutes, MDDM (P < 0.001), TUG (P < 0.001), and gravimetric speed (P < 0.001) at 60 minutes, and gravimetric area (P = 0.03) at 90 minutes. Conclusion Administration of flumazenil after remimazolam anesthesia resulted in faster recovery of consciousness, but it did not affect the recovery of psychomotor and equilibrium functions. The time until patients were safe to return home was 120 minutes. Flumazenil did not improve the time until it was safe for patients to return home.

[Introduction]Recently, in the development of information technology, VDT workers are increasing rapidly. Physical and mental health symptoms associated with working at visual display terminals (VDTs) are controversial. However, there are few studies about the effect of acupuncture treatment on eye fatigue, neck and shoulder stiffness that many VDT workers have.
Therefore, in this prospective study, we examined the effect of acupuncture treatment for complaints of VDT workers.
[Methods]Sixty-one VDT workers participated as subjects (41 males, 20 females). Acupuncture sessions were performed once a week for four weeks. Acupuncture points were decided by the patient's muscleskeletal distress.
Disposable press tack needles were used. Visual Analogue Scale (VAS) was used to determine eye fatigue, neck and shoulder stiffness. Improvements of each VAS were evaluated. Then we analyzed improvement on shoulder and neck stiffness associated with eye fatigue.
[Results]The neck and shoulder distress of patients was reduced in four weeks by acupuncture treatment. A regular correlation between the improvement rate of eye fatigue and neck/shoulder stiffness was observed.
[Conclusion]The neck and shoulder stiffness was improved by acupuncture treatment. According to improved symptoms, eye fatigue was mitigated as well. Thus it was suggested that utility of acupuncture is high in the field of industrial medicine.

Background/Aims: Crohn’s disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn’s disease in real-world settings. Methods: This was a multicenter, single-cohort, observational study of patients with Crohn’s disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remission, mucosal healing, and Work Productivity and Activity Impairment (WPAI). Results: The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malignancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained > 70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years > 2 to ≤ 3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n = 102) at baseline to 26.9 (n = 84) at 4 weeks. Conclusions Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn’s disease in the real-world setting.

Background/Aims: The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet’s disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet’s disease. Methods: This prospective, all-case, post-marketing study was conducted at 254 centers in Japanese patients with intestinal Behçet’s disease receiving adalimumab. The primary endpoint was incidence of adverse drug reactions. Effectiveness endpoints included global improvement rating and change in C-reactive protein levels. Results: Of the 473 registered patients, 462 and 383 included in the safety and effectiveness populations were administered adalimumab for a mean of 515.3 and 579.5 days, respectively. Overall, 395 patients (85.5%) received adalimumab at the recommended dose. Adverse drug reactions and serious adverse drug reactions were reported in 120 (25.97%) and 51 (11.04%) patients, respectively. The incidence of adverse drug reactions was significantly higher in patients with comorbidities (P< 0.0001), patients taking concomitant oral corticosteroids (P< 0.0001), and those not self-administering adalimumab (P= 0.0257). At study end, global improvement rating was “effective” (n = 156, 40.7%) or “markedly effective” (n = 168, 43.9%) in 324 patients (overall effective, 84.6%). Mean C-reactive protein levels (mg/dL) decreased from 1.96 at baseline (n = 324) to 0.58 at week 24 (n = 208) and 0.25 at week 156 (n = 37). Conclusions This large real-world study confirmed the long-term safety and effectiveness of adalimumab in patients with intestinal Behçet’s disease. No new safety concerns were identified. (Clinical trial registration number: NCT01960790)

Background/Aims: The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet’s disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet’s disease. Methods: This prospective, all-case, post-marketing study was conducted at 254 centers in Japanese patients with intestinal Behçet’s disease receiving adalimumab. The primary endpoint was incidence of adverse drug reactions. Effectiveness endpoints included global improvement rating and change in C-reactive protein levels. Results: Of the 473 registered patients, 462 and 383 included in the safety and effectiveness populations were administered adalimumab for a mean of 515.3 and 579.5 days, respectively. Overall, 395 patients (85.5%) received adalimumab at the recommended dose. Adverse drug reactions and serious adverse drug reactions were reported in 120 (25.97%) and 51 (11.04%) patients, respectively. The incidence of adverse drug reactions was significantly higher in patients with comorbidities (P< 0.0001), patients taking concomitant oral corticosteroids (P< 0.0001), and those not self-administering adalimumab (P= 0.0257). At study end, global improvement rating was “effective” (n = 156, 40.7%) or “markedly effective” (n = 168, 43.9%) in 324 patients (overall effective, 84.6%). Mean C-reactive protein levels (mg/dL) decreased from 1.96 at baseline (n = 324) to 0.58 at week 24 (n = 208) and 0.25 at week 156 (n = 37). Conclusions This large real-world study confirmed the long-term safety and effectiveness of adalimumab in patients with intestinal Behçet’s disease. No new safety concerns were identified. (Clinical trial registration number: NCT01960790)

BACKGROUND/AIMS: It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. METHODS: The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. RESULTS: The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. CONCLUSIONS: In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features.
Asian Continental Ancestry Group ; Biological Markers ; Classification ; Diagnosis ; Fatty Liver* ; Fibrosis ; Genetic Variation* ; Genotype ; Humans ; Japan* ; Multivariate Analysis