Background/Aims: Golimumab (GLM) is an anti-tumor necrosis factor-α drug approved for treating moderate-to-severe active ulcerative colitis (UC). A 52-week post-marketing surveillance (PMS) was initiated to evaluate its safety and effectiveness in patients with UC in Japan. We present an interim report of the ongoing PMS. Methods: Patients received 200 mg of subcutaneous GLM at week 0, 100 mg at week 2, and 100 mg 4 weekly thereafter. The safety analysis set included 392 patients with UC, and the effectiveness analysis set 387 patients. Safety and effectiveness were assessed at week 6. Results: Adverse drug reactions (ADRs) were reported in 8.2% (32/392) and serious ADRs in 4.6% (18/392). The most frequent ADRs were infection and infestation (3.3%), with herpes zoster being the most common. ADRs were significantly higher in patients with concomitant corticosteroid use (odds ratio [OR], 3.45; 95% confidence interval [CI], 1.40–9.68). No significant difference in ADR incidence was observed between patients aged ≥65 and <65 years (OR, 1.23; 95% CI, 0.35–3.47). Six-week effectiveness of GLM was confirmed by a decrease in the partial Mayo score (–2.3; 95% CI, –2.6 to –2.1) and C-reactive protein levels (–0.64; 95% CI, –0.92 to –0.36), including in the biologics-experienced population. Conclusions The safety and effectiveness of GLM at week 6 in a real-world setting were demonstrated in patients with UC in Japan. ADR patterns were consistent with previous reports with no new safety signals. Concomitant corticosteroid use may be associated with increased ADR incidence. The final results of the ongoing PMS are necessary for further evaluation.

Objective: The guidance on “what to do when patients missed a dose” is an important item of medication instructions; however, only a small number of prescription drugs contain it. The “Drug Guide for Patients” and “Kusuri-no-Shiori” are documents designed to facilitate medication instructions for patients, having a section on “what to do when patients missed a dose.” Specific descriptions under it differ among medication instruction documents for some drugs, including those containing the same active pharmaceutical ingredients; however, the actual status of such discrepancies has not been clarified. In this study, we conducted a fact-finding survey to clarify such discrepancies using two medication instruction documents for drugs containing the same active pharmaceutical ingredients.Methods: The medication instructions of “Drug Guides for Patients” and “Kusuri-no-Shiori” for 532 active pharmaceutical ingredients used in oral drugs were included in the survey. After reading the descriptions under the “what to do when patients missed a dose” section, we divided them into six groups and determined whether the descriptions for the same ingredient in the documents fell in the same group.Results: For 186 ingredients (35.0%), we identified discrepancies between the documents. Among these, the instructions for 61 ingredients (11.5%) contained contradicting descriptions, such as “take the missed dose as soon as you remember” in one document and “always let go of the missed dose” in another document.Conclusions: A substantial number of discrepancies in descriptions about “what to do when patients missed a dose” were found between the two documents, raising concerns of confusion in medication instructions when the documents used were different. Therefore, the descriptions should be improved to resolve the discrepancies among medication instruction documents. Moreover, it is important for pharmacists or other healthcare professionals to review the descriptions thoroughly before using the document to provide appropriate medication instructions without confusion.

Introduction: The diagnosis of cancer-related neuropathic pain is often difficult for non-pain medicine specialists. We examined whether a Japanese version of a neuropathic pain screening questionnaire (Japan-Q), which was developed for chronic pain, is appropriate for screening cancer-related neuropathic pain. Methods: Our palliative care team screened 104 patients from May 2014 to December 2015 and compared total points of the Japan-Q with diagnosis of the type of cancer pain by specialized pain clinicians. Validity was evaluated using a receiver operating characteristic (ROC) curve. Results: The area under the ROC curve in terms of the total score, sensitivity, and specificity for the Japan Q was 0.82, which indicated a moderate level of diagnostic accuracy. A cut-off value of 3 points was shown to be best (sensitivity: 79%, specificity: 82%). When a cut-off value of 9 points was used as the diagnostic criterion for neuropathic pain, there was greatly reduced sensitivity (sensitivity: 40%, specificity: 97%). Conclusion: Although the Japan-Q shows moderate diagnostic accuracy related to cancer pain, the cut-off value for this tool is lower than that for chronic pain. Cancer-related neuropathic pain should be suspected with a total score of 3 or more in the Japan-Q.

BACKGROUND/AIMS: Inhibition of α4β7 integrin has been shown to be effective for induction and maintenance therapy in patients with ulcerative colitis (UC). We investigated the effects of varying doses of the α4β7 inhibitor abrilumab in Japanese patients with moderate-to-severe UC despite conventional treatments. METHODS: In this randomized, double-blind, placebo-controlled study, 45 UC patients were randomized to abrilumab 21 mg (n=11), 70 mg (n=12), 210 mg (n=9), or placebo (n=13) via subcutaneous (SC) injection for 12 weeks. The double-blind period was followed by a 36-week open-label period, in which all patients received abrilumab 210 mg SC every 12 weeks, and a 28-week safety follow-up period. The primary efficacy variable was clinical remission at week 8 (total Mayo score ≤2 points with no individual subscore >1 point). RESULTS: Clinical remission at week 8 was 4 out of 31 (12.9%) overall in the abrilumab groups versus 0 out of 13 in the placebo group (abrilumab 21 mg, 1/10 [10.0%]; 70 mg, 2/12 [16.7%]; 210 mg, 1/9 [11.1%]). In both the double-blind and open-label periods, fewer patients in the abrilumab groups experienced ≥1 adverse event compared with those in the placebo group. There were no cases of progressive multifocal leukoencephalopathy and no deaths. CONCLUSIONS: Abrilumab 70 mg and 210 mg yielded numerically better results in terms of clinical remission rate at Week 8 than placebo, with the 210 mg dose showing more consistent treatment effects. Abrilumab was well tolerated in Japanese patients with UC.
Asian Continental Ancestry Group ; Colitis, Ulcerative ; Follow-Up Studies ; Humans ; Japan ; Leukoencephalopathy, Progressive Multifocal ; Ulcer

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.
Asian Continental Ancestry Group ; Colectomy ; Colitis, Ulcerative ; Colorectal Neoplasms ; Consensus ; Crohn Disease ; Disease Management* ; Disease Progression ; Early Intervention (Education) ; Epidemiology ; Expert Testimony ; Gastrointestinal Tract ; Hospitalization ; Humans ; Inflammatory Bowel Diseases* ; Japan* ; Prevalence ; Prognosis

PURPOSE: Postoperative pancreatic fistula is a serious and fatal complication of gastrectomy for gastric cancer. Blunt trauma to the parenchyma of the pancreas can result from an assistant's forceps compressing and retracting the pancreas, which in turn may result in pancreatic juice leakage. However, no published studies have focused on blunt trauma to the pancreas during laparoscopic surgery. Our aim was to investigate the relationship between compression of the pancreas and pancreatic juice leakage in a swine model. MATERIALS AND METHODS: Three female pigs were used in this study. The pancreas was gently compressed dorsally for 15 minutes laparoscopically with gauze grasped with forceps. Pancreatic juice leakage was visualized by fluorescence imaging after topical administration of chymotrypsin-activatable fluorophore in real time. Amylase concentrations in ascites collected at specified times was measured. In addition, pancreatic tissue was fixed with formalin, and the histology of the compressed sites was evaluated. RESULTS: Fluorescence imaging enabled visualization of pancreatic juice leaking into ascites around the pancreas. Median concentrations of pancreatic amylase in ascites increased from 46 U/L preoperatively to 12,509 U/L 4 hours after compression. Histological examination of tissues obtained 4 hours after compression revealed necrotic pancreatic acinar cells extending from the surface to deep within the pancreas and infiltration of inflammatory cells. CONCLUSIONS: Pancreatic compression by the assistant's forceps can contribute to pancreatic juice leakage. These findings will help to improve the procedure for lymph node dissection around the pancreas during laparoscopic gastrectomy.
Acinar Cells ; Administration, Topical ; Amylases ; Ascites ; Female ; Formaldehyde ; Gastrectomy* ; Hand Strength ; Humans ; Laparoscopy ; Lymph Node Excision* ; Lymph Nodes* ; Optical Imaging ; Pancreas ; Pancreatic Fistula ; Pancreatic Juice ; Stomach Neoplasms ; Surgical Instruments ; Swine ; Wounds, Nonpenetrating

No abstract available.
Crohn Disease* ; Food, Formulated* ; Humans ; Infliximab*

Since distal femoral varus osteotomy (DFO)
Asian Continental Ancestry Group ; Humans ; Japan ; Knee ; Osteoarthritis ; Osteotomy ; Tibia ; Weight-Bearing

OBJECTIVE: To assess actual rates of late vaginal stenosis and identify predisposing factors for complications among patients with previously untreated cervical cancer following high-dose-rate brachytherapy. METHODS: We performed longitudinal analyses of 57 patients using the modified Dische score at 6, 12, 18, 24, 36, and 60 months after treatment, which consisted of 15 interstitial brachytherapys and 42 conventional intracavitary brachytherapys, with a median follow-up time of 36 months (range, 6 to 144 months). RESULTS: More than half of the patients developed grade 1 (mild) vaginal stenosis within the first year of follow-up, and grade 2 (97.5%, moderate) to grade 3 (severe) stenosis gradually increased with time. Actual stenosis rates for grade 1, 2, and 3 were 97.5% (95% confidence interval [CI], 92.7 to 97.5), 60.7% (95% CI, 42.2 to 79.3), and 7.4% (95% CI, 0 to 18.4) at 3 years after treatment. Pallor reaction grade 2-3 at 6 months was only a statistically significant predisposing factor for grade 2-3 late vaginal stenosis 3 years or later with a hazard ratio of 3.48 (95% CI, 1.32 to 9.19; p=0.018) by a multivariate Cox proportional hazard model. Patients with grade 0-1 pallor reaction at 6 months showed a grade > or =2 vaginal stenosis rate of 53%, whereas the grade 2-3 pallor reaction group achieved a grade > or =2 vaginal stenosis rate at 3 years at 100% (p=0.001). CONCLUSION: High-dose-rate brachytherapy was associated with high incidence of late vaginal stenosis. Pallor reaction grade 2-3 at 6 months was predictive of late grade 2-3 vaginal stenosis at 3 years after treatment. These findings should prove helpful for patient counseling and preventive intervention.
Adult ; Aged ; Aged, 80 and over ; Brachytherapy/*adverse effects/methods ; Constriction, Pathologic/etiology/pathology ; Female ; Humans ; Iridium Radioisotopes/therapeutic use ; Middle Aged ; *Pallor ; Prognosis ; Prospective Studies ; Radiopharmaceuticals/therapeutic use ; Retrospective Studies ; Uterine Cervical Neoplasms/*radiotherapy ; Vaginal Diseases/*etiology/pathology

Objective: Incidents, such as disturbance of consciousness due to adverse reactions of medications during automobile driving, could cause a serious accident.  Although automobile driving is indicated to be “prohibited” in the package inserts of many drugs, no explicit guidelines are available in Japan on specific guidance to patients.  Therefore, we attempted to prepare guidelines for medication guidance regarding automobile driving.
Methods: We investigated the number of incidents involving traffic accidents and the disturbance of consciousness cases reported in “Japanese Adverse Drug Event Report” database by “Pharmaceuticals and Medical Devices Agency (PMDA).”  We also analyzed descriptions regarding automobile driving found in package inserts and guidelines to determine a risk level for each medication.
Results: Guidelines for medication guidance were prepared based on four-level classification of drugs for which “prohibition” of automobile driving was indicated in their package inserts; these levels are “conform to pertinent guidelines,” “strictly prohibited,” “prohibited,” and “conditionally prohibited.”  The contents of the guidance prepared for some drugs were different from their package inserts.
Conclusions: The guidelines prepared in this study can be expected to become a support tool to ensure close attention to cautions regarding automobile driving.  Because some contents of the guidance are different from that described in the package inserts, it is desirable to obtain agreement with physicians in hospitals adopting these guidelines.  In addition, guidelines based on a broader range of information should be prepared in the future.