This document reports the results of a questionnaire survey conducted among pharmaceutical companies that are members of the Japan Pharmaceutical Manufacturers Association as part of a collaborative research project within the AMED Research on Regulatory Science of Pharmaceuticals and Medical Devices ‘Research for the promotion of the utilization of real-world evidence in the pharmaceutical regulatory system and the harmonization of international regulations, and for the proposal of an ideal system in Japan’ (Principal Investigator： Harumasa Nakamura, National Center of Neurology and Psychiatry). This survey is the first domestic attempt to clarify the current state of development and utilization of data for companion applications (CPs) in pharmaceuticals. It is expected that the widespread development and use of pharmaceutical CPs will enhance the collection of patient-reported outcomes (PROs), which in turn will foster the utilization of real-world data (RWD) under pharmaceutical regulations. In anticipation that the results of this survey will contribute to this promotion, we are publishing the entire questionnaire results in this report.

This document reports the results of a questionnaire survey conducted among pharmaceutical companies that are members of the Japan Pharmaceutical Manufacturers Association as part of a collaborative research project within the AMED Research on Regulatory Science of Pharmaceuticals and Medical Devices ‘Research for the promotion of the utilization of real-world evidence in the pharmaceutical regulatory system and the harmonization of international regulations, and for the proposal of an ideal system in Japan’ (Principal Investigator： Harumasa Nakamura, National Center of Neurology and Psychiatry). This survey is the first domestic attempt to clarify the current state of development and utilization of data for companion applications (CPs) in pharmaceuticals. It is expected that the widespread development and use of pharmaceutical CPs will enhance the collection of patient-reported outcomes (PROs), which in turn will foster the utilization of real-world data (RWD) under pharmaceutical regulations. In anticipation that the results of this survey will contribute to this promotion, we are publishing the entire questionnaire results in this report.

Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%).Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions The present study demonstrated that ca-4F12-E6 was well-tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

A 77-year-old woman underwent endovascular abdominal aortic repair (EVAR) for an abdominal aortic aneurysm (AAA)．Five years after surgery, she visited the hospital with the chief complaint of a fever. Enhanced computed tomography (CT) showed enlargement of the AAA around the stent-graft and a mass, which was suspected to be an abscess, outside the aneurysm. A blood test revealed a high level of inflammatory response. The patient was diagnosed with infectious AAA. She received antibiotics; however, the inflammatory response did not completely improve. A second CT scan revealed that the suspected abscess had a spreading tendency. The patient was referred to our hospital for a highly suspected stent-graft infection. We performed Y-graft replacement using a rifampicin-immersed graft, and as much as possible of the wall around the aortic aneurysm was removed. The inflammatory response improved rapidly after the operation, and the patient was discharged 15 days later. According to the results of a pathological examination, a diagnosis of xanthogranulomatous inflammation and fibrosis was made. Here, we report a rare case of xanthogranulomatous inflammation of the aortic aneurysm wall after EVAR.

Objective: Histological verification of epithelioid cell granuloma is important in diagnosing sarcoidosis; tissue sampling is a worldwide requirement. In 2006, to reduce medical expenses and avoid invasive procedures, diagnostic criteria without histological verification were permitted by the Japanese government. In 2015, new diagnostic criteria, allowed clinical diagnoses based on only respiratory, ocular, and cardiac systems with at least a two-system involvement, increasing the need to sample tissue from clinically unevaluable organs in suspected sarcoidosis. This study aimed to compare the characteristics of patients who were diagnosed with sarcoidosis according to the 2006 and 2015 criteria.Materials and Methods: Using the 2015 version, we re-evaluated the characteristics of 264 patients with diagnosed or suspected sarcoidosis according to the 2006 criteria, at Jichi Medical University Hospital between 2004 and 2012 (clinical diagnosis, 84; histological diagnosis, 117; suspected sarcoidosis 63).Results: Thirty-nine patients were diagnosed with suspected sarcoidosis due to the absence of at least a two-system involvement; two patients had insufficient laboratory data suggestive of sarcoidosis. Six patients moved from suspected sarcoidosis to a histological diagnosis because of a greater leniency in the criteria for supportive findings. The 2015 diagnostic criteria excluded patients with organ involvement without a requirement for systemic steroids from the clinical diagnosis group. A case of schwannoma, erroneously placed in the clinical diagnosis group by the 2006 criteria, was reclassified according to the 2015 criteria.Conclusion: The 2015 version is preferable for clinically diagnosing sarcoidosis, even without histological specimens, and provides guidance for indications for systemic treatment.

BACKGROUND: Estimates of daily sodium (Na) and potassium (K) excretion were explicitly biased when using equations for adults. We aimed to develop equations to estimate them using overnight urine from Japanese children and adolescents. METHODS: The subjects comprised 70 students aged 10.49-15.76 years: validation group, n = 34; and verification group, n = 36. Each subject performed two operations of overnight spot urine (U RESULTS: In validation, we formulated Na excretion (mg d CONCLUSION We obtained validated equations to estimate daily Na and K excretion with accessible variables such as Na, K, and Cr concentrations of overnight urine, body height and weight, and age for children and adolescents. When using the obtained equations, caution should be paid to small but definite biases and measurement errors.
Adolescent ; Child ; Creatinine/urine* ; Female ; Humans ; Japan ; Male ; Potassium/urine* ; Sodium/urine*

Chinese Medicine Questionnaire (CCMQ-J) consists of sixty independent questionnaires and 9 physical constitutions called subscales. One type is balanced constitution (i.e., gentleness), and the following eight types represent unbalanced constitution: Qi-deficiency constitution, Yang-deficiency constitution, Yin-deficiency constitution, Phlegm-dampness constitution, Damp-heat constitution, Stagnant Blood constitution, Stagnant Qi constitution, and Inherited Special constitution. In this study, we proposed to determine optimal number of groups in 851 participants recruited from crowdsourcing answered CCMQ-J questionnaire consisting of 60 questions. In the present study, we applied k-means clustering with gap statistics to the questionnaire data and the number of optimal groups was estimated by five. The five groups are mainly characterized by 3 subscales in CCMQ-J, i.e. (i) two subscales corresponding to Yang-deficiency and Qi-depress, (ii) three subscales corresponding to gentleness, Yang-deficiency and Qi-depress (iii) Yang-deficiency, (iv) gentleness, and (v) Qi-depress. In the crowdsourcing survey, two subscales, Yang-deficient and Qi-depress are the most frequently occurred in current Japanese people.

PURPOSE: The difficulty of femoral preparation with supine-position hip hemi-arthroplasty (HA) often leads to intra-operative fractures (IOFs). We aimed to clarify the incidence and types of IOFs in HA for hip fractures performed in the supine and lateral positions. MATERIALS AND METHODS: We retrospectively investigated cases of HA for acute femoral neck fractures from June 2013 to May 2018. We examined the incidence and types of IOFs according to different approaches. We defined supine-position in HA as the supine and hip-hyperextended (over-range) femoral preparation position, and lateral position as the lateral and hip-flexed femoral preparation position. We used a short tapered wedged stem. RESULTS: Supine-position HA was used in 46 patients (23.7%) and lateral-position HA in 148 patients (76.3%). IOFs in supine-position HA occurred in 8 patients (17.4%) and included five Vancouver AGT and three Vancouver B2 fractures. IOFs in lateral-position HA occurred in 3 patients (2.0%) and included one Vancouver AGT and two Vancouver B fractures. Supine-position HA was a risk factor for IOFs (adjusted odds ratio, 9.71; 95% confidence interval, 2.37–39.8; P < 0.01) CONCLUSION: Supine-position in HA is an IOF risk factor and significantly increases the incidence of great trochanter fractures of Vancouver type A.
Arthroplasty, Replacement, Hip ; Femoral Neck Fractures ; Femur ; Hemiarthroplasty ; Hip Fractures ; Hip ; Humans ; Incidence ; Minimally Invasive Surgical Procedures ; Odds Ratio ; Periprosthetic Fractures ; Retrospective Studies ; Risk Factors

PURPOSE: Since oncological outcomes of transanal colorectal tube (TCT) placement, an endoscopic treatment for colorectal cancer (CRC) with acute colorectal obstruction (ACO), remain unknown, this study analyzed long-term outcomes of TCT placement for stage II/III CRC with ACO. MATERIALS AND METHODS: Data were retrospectively reviewed from consecutive patients with distal stage II/III CRC who underwent surgery between January 2007 and December 2011 at two Japanese hospitals. One hospital conducted emergency surgery and the other performed TCT placement as the standard treatment for all CRCs with ACO. Propensity score (PS) matching was used to adjust baseline characteristics between two groups. RESULTS: Among 754 patients with distal stage II/III CRC, 680 did not have ACO (non-ACO group) and 74 had ACO (ACO group). The PS matching between both hospitals identified 234 pairs in the non-ACO group and 23 pairs in the ACO group. In the non-ACO group, the surgical quality was equivalent between the two institutions, with no significant differences in overall survival (OS) and disease-free survival (DFS). In the ACO group, the rate of primary resection/anastomosis was higher in the TCT group than in the surgery group (87.0% vs. 26.1%, p < 0.001). No significant differences were noted between the surgery and the TCT groups in OS (5-year OS, 61.9% vs. 51.5%; p=0.490) and DFS (5-year DFS, 45.9% vs. 38.3%; p=0.658). CONCLUSION: TCT placement can achieve similar long-term outcomes to emergency surgery, with a high rate of primary resection/anastomosis for distal stage II/III colon cancer with ACO.
Asian Continental Ancestry Group ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Disease-Free Survival ; Emergencies ; Humans ; Propensity Score ; Retrospective Studies

OBJECTIVE: Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. METHODS: Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m² day 1) and paclitaxel (135 mg/m² day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0–13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0–120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. RESULTS: The CC rate in the overall phase was significantly higher in the rikkunshito group than in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints: the CC rate in the delayed phase (24–120 hours), and the complete response (CR) rates (no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time to treatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to be superior in the rikkunshito group from day 2 through day 6. CONCLUSION: Rikkunshito provided additive effect for the prevention of CINV and anorexia.
Administration, Oral ; Anorexia* ; Antiemetics ; Appetite ; Cisplatin* ; Drug Therapy ; Dyspepsia ; Eating ; Herbal Medicine* ; Humans ; Japan ; Nausea* ; Paclitaxel* ; Time-to-Treatment ; Vomiting*