記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. METHODS: This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography. RESULTS: Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement. CONCLUSION: This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

DOI： 10.1080/03007995.2017.1297931

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Teriparatide is the first anabolic agent shown to reduce the risk of fractures in patients with osteoporosis. In Japan, teriparatide is prescribed to treat patients at high risk of fracture. Given that bisphosphonates are commonly used prior to teriparatide as treatment for osteoporosis, information on the effectiveness and safety of teriparatide with or without previous bisphosphonate treatment is helpful for physicians in clinical practice. This study aims to report the effectiveness and safety of teriparatide in treatment-naive and bisphosphonate-pretreated patients in Japan as real-world evidence. METHODS: A post hoc analysis of a postmarketing surveillance study was conducted in Japanese patients with osteoporosis at high risk of fracture who received 24-month treatment of daily teriparatide. Changes in bone turnover biomarkers and bone mineral density and incidence of new fractures were analyzed in treatment-naive as well as bisphosphonate-pretreated patients. RESULTS: The analysis included 1433 patients (treatment-naive, n = 659; bisphosphonate-pretreated, n = 774). Bone mineral density increased significantly from baseline at 24 months in both treatment-naive (lumbar spine, 13.45%; femoral neck, 5.16%; total hip, 4.46%) and bisphosphonate-pretreated (lumbar spine, 11.20%; femoral neck, 2.22%; total hip, 0.67%) patients. The incidence rates of new vertebral and nonvertebral fractures at 24 months were 1.69% and 3.37%, respectively, in treatment-naive patients and 3.60% and 5.56%, respectively, in bisphosphonate-pretreated patients. The incidence of adverse drug reactions was 6% in treatment-naive patients and 10% in bisphosphonate-pretreated patients. The most common adverse drug reaction in treatment-naive and bisphosphonate-pretreated patients was nausea (0.91%) and hyperuricaemia (1.81%), respectively. CONCLUSIONS: In this post hoc analysis, no new safety concerns and similar effectiveness of teriparatide were observed in Japanese patients with osteoporosis at high risk of fracture, regardless of their previous treatment status with bisphosphonates.

DOI： 10.1016/j.jos.2016.11.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Teriparatide (recombinant 1-34 N-terminal sequence of human parathyroid hormone) for the treatment of osteoporosis should be prescribed with caution in patients with severe stages of chronic kidney disease (CKD). However, in clinical settings, physicians and surgeons who treat such patients have few available options. We sought to further explore the safety and effectiveness of teriparatide for the treatment of osteoporosis in Japanese patients with severe stages of CKD. This was a post hoc analysis of a postmarketing surveillance study that included patients with osteoporosis at high risk of fracture and stage 4 or 5 CKD. Patients received subcutaneous teriparatide 20 μg daily for up to 24 months. Safety profiles were assessed by physician-reported adverse drug reactions (ADRs). Effectiveness was assessed by measuring bone formation (via procollagen type 1 N-terminal propeptide [P1NP]), bone mineral density (BMD), and the incidence of clinical vertebral or nonvertebral fragility fractures. A total of 33 patients with severe stages of CKD (stage 4, n=30; stage 5, n=3) were included. All patients were female, and 81.8% had a history of previous fracture. No serious ADRs were recorded; a total of 4 ADRs were recorded for 4 of 33 patients. Increases in BMD and P1NP levels were observed both overall and in most individual patients. New fractures occurred in 1 patient with stage 5 CKD, but not in patients with stage 4 CKD. In this post hoc analysis conducted in Japan, teriparatide appeared to be effective for the treatment of osteoporosis in elderly female patients with severe stages of CKD, and no new safety concerns were observed.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This postmarketing surveillance study assessed the safety and effectiveness of teriparatide in patients with osteoporosis at high risk of fracture in Japan. The patients received teriparatide 20 μg daily by subcutaneous injection, for a maximum of 24 months. Safety and effectiveness analyses were based on data from 1,847 patients who were predominantly female (92.6%) with a mean age of 75.4 years. A total of 157 adverse drug reactions (ADRs) were reported in 140 (7.58%) patients; the most common ADRs were hyperuricemia, nausea, and dizziness. Only six (0.32%) patients reported serious ADRs, the most common being nausea (two patients; 0.1%). Persistence with teriparatide treatment was 60.8% and 39.1% at 18 and 24 months, respectively. There were significant increases in biomarkers for bone formation (procollagen type I N-terminal propeptide and bone-specific alkaline phosphatase) and bone resorption (collagen type I cross-linked C telopeptide and tartrate-resistant acid phosphatase 5b) throughout the study. These were accompanied by significant increases in bone mineral density and low incidences of new vertebral and nonvertebral fractures. Patient-reported measurements for health-related quality of life revealed significant improvements from baseline in back pain and overall health-related quality of life (Short Form-8™ health survey). The results of this 24-month postmarketing surveillance study imply that teriparatide has a favorable safety profile and is effective in the treatment of patients with osteoporosis at high risk of fracture in Japan. Teriparatide may also be a useful treatment for osteoporosis in other societies with aging populations.

DOI： 10.2147/CIA.S107285

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Long-term safety of medication is a concern for older persons because they may have several comorbidities that can influence drug metabolism, efficacy, and safety. In Japan, raloxifene is an effective and well-tolerated medication for the treatment of osteoporosis in postmenopausal women, but there is little available evidence on whether raloxifene has an acceptable safety profile in older women. The objective of this post hoc analysis was to investigate the safety of raloxifene as a long-term treatment of osteoporosis in Japanese postmenopausal women aged 75 years or older. METHODS: We report a post hoc analysis of a safety dataset (6,960 participants) from a published postmarketing surveillance study (postmenopausal women treated with raloxifene 60 mg/d for ≤3 y). The safety dataset was divided into two groups: (1) women younger than 75 years at baseline (4,522 participants) and (2) women aged 75 years or older at baseline (2,438 participants). Incidence of adverse drug reactions and reactions of note in each age group were compared using Fisher's exact test. RESULTS: Approximately 10% of women in each group reported at least one adverse drug reaction. This analysis did not identify any clinically important differences in the incidence or type of adverse drug reactions reported or in reactions of note between women aged 75 years or older and younger women. CONCLUSIONS: There were no obvious additional safety concerns for women aged 75 years or older who were treated with raloxifene. The findings in this post hoc evaluation suggest no differences in adverse events in the age groups evaluated.

DOI： 10.1097/GME.0000000000000441

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To assess the effect of active vitamin D3 on quality of life (QOL) and pain in raloxifene-treated Japanese women with postmenopausal osteoporosis. RESEARCH DESIGN AND METHODS: This is a post hoc analysis of a previous prospective postmarketing observational study conducted without a comparator group. This study was conducted in 60 Japanese hospitals from September 2007 to February 2009. We compared changes from baseline in QOL and pain in patients receiving raloxifene plus active vitamin D3 with those in patients receiving raloxifene monotherapy at 8 and 24 weeks after treatment. CLINICAL TRIAL REGISTRATION: Japan Pharmaceutical Information Center (JapicCTI-070465). MAIN OUTCOME MEASURES: QOL and pain were assessed using Short Form-8 (SF-8), European Quality of Life Instrument 5 Dimensions (EQ-5D), Japanese Osteoporosis Quality of Life Questionnaire (JOQOL), visual analogue pain scales (VAS pain), and pain frequency scores. RESULTS: A total of 506 patients were included in the post hoc analysis. Both raloxifene monotherapy (RLX, n = 354) and active vitamin D3 cotreatment (COMBI, n = 152) significantly improved QOL and reduced pain from the baseline at Week 8 and Week 24. The COMBI group had significantly greater improvements in JOQOL total score and activity of daily living (total) domain at Week 24 and last observation carried forward (LOCF) than the RLX group. The COMBI group also had significantly greater improvements in SF-8 domains of general health (at Week 8, Week 24, and LOCF), role physical (at Week 24 and LOCF), and mental health (at LOCF) than the RLX group. The COMBI group also had significantly greater reduction in VAS pain at LOCF than the RLX group (mean [SD]: RLX = -0.99 [2.72], COMBI = -1.54 [2.21], P = 0.042). CONCLUSIONS: Active vitamin D3 supplementation to raloxifene treatment for 24 weeks may have additional benefits in improving QOL and relieving pain in Japanese women with postmenopausal osteoporosis.

DOI： 10.1185/03007995.2014.975339

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In addition to impaired physical activity, adult GH deficiency (GHD) can decrease quality of life (QOL). Hence, assessment of QOL is important to evaluate the efficacy of GH replacement therapy. This study aimed to identify factors that may be predictive of long-term improvement in QOL among clinical/laboratory variables during GH replacement therapy. The analysis included 83 Japanese adults with GHD who participated in the Hypopituitary Control and Complications Study (HypoCCS). Correlations between the change from baseline in clinical/laboratory variables at 6 months and the change from baseline in Quality of life (Short-Form 36 [SF-36] component scores) at 12 months were examined. Unexpectedly, all component scores were negatively correlated with the change in fasting plasma glucose concentration (FPG) (physical component summary [PCS], r = -0.456; mental component summary [MCS], r = -0.523; role/social component summary [RCS], r = -0.433). The change in MCS was positively correlated with the change in insulin-like growth factor-1 standard deviation score (IGF-1 SDS) (r = 0.417). The change in PCS was positively correlated with the change in body fat (r = 0.551). The change in RCS was positively correlated with the change in waist circumference (r = 0.528). Short-term changes in several clinical/laboratory variables, most notably FPG and IGF-1 SDS, were correlated with long-term changes in QOL. The clinical importance of these correlations for predicting GH replacement treatment efficacy warrants further investigation.

DOI： 10.1507/endocrj.EJ14-0616

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The Japanese Osteoporosis Quality of Life (JOQOL) questionnaire measures quality of life in Japanese patients with osteoporosis. However, several important aspects of the psychometric properties of individual domains, including responsiveness, have not been addressed to enable valid clinical application. This analysis examined the internal and external responsiveness of the JOQOL questionnaire. METHODS: This was a post hoc analysis of a 24-week prospective postmarketing study of raloxifene (60 mg/day) administered to postmenopausal Japanese women with osteoporosis (JapicCTI-070465). Internal responsiveness was assessed using Standardized Response Mean (SRM) statistics and changes in JOQOL domain scores. Patients were also stratified into those who did or did not achieve a minimal clinically important change (MCIC) in pain, assessed by a visual analogue scale for pain (VAS pain): comparisons were made between treated patients who achieved VAS pain reduction ≥ 20 mm versus VAS pain reduction < 20 mm. External responsiveness was assessed using Pearson's correlation coefficient (r) for changes in JOQOL domain scores with Short Form-8 Health Survey and European Quality of Life Instrument scores. RESULTS: Of 506 patients analyzed, 421 had a baseline value for VAS pain; of these, 152 patients (36.1%) had a MCIC, whereas 264 patients (62.7%) did not. The JOQOL domains pain, overall health, and falls/psychological factors had small to moderate SRM values (0.3-0.5) in all patients, but consistently showed significantly larger changes in patients whose pain score changes exceeded the MCIC. Together, these findings suggest some degree of internal responsiveness for these domains. However, activities of daily living domain had a SRM value as low as 0.2, and recreation/social activities and posture/physique domains had SRM values close to 0. Moderate correlation (defined as r ≥ 0.4 to < 0.6) was noted between the domains pain, activities of daily living, and overall health and some Short Form-8 Health Survey subscales and the European Quality of Life total score, suggesting external responsiveness of these domains. CONCLUSIONS: The inconsistent responsiveness among individual JOQOL domains in treated patients suggests the need for improving several JOQOL domains, especially the activities of daily living, recreation/social activities and posture/physique domains, before application to clinical research.

DOI： 10.1186/s12955-014-0178-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This postmarketing surveillance study assessed the safety and effectiveness of daily teriparatide treatment in patients with osteoporosis in a Japanese clinical setting. In this prospective, multicenter, observational study, patients with osteoporosis at high risk for fracture received subcutaneous injections of teriparatide (20 μg/day) for a maximum of 24 months. For this interim report, data from 1,671 patients were eligible for analysis at the cutoff date. The mean age was 75.3 years; 93% of patients (1,552/1,671 patients) were women. There were 117 adverse drug reactions (ADRs) reported in 101 of 1,671 patients (6.04%); the most common reported ADRs were nausea, dizziness, headache, and palpitations. No clinically significant safety issues were identified, although 5 serious ADRs were reported in 4/1,671 (0.24 %) patients. At 12 months, 71.9% of patients remained on teriparatide treatment. From 1 month, there were rapid increases in the biomarkers of bone formation P1NP and, to a lesser extent, BAP. In contrast, increases in the biomarkers of bone resorption, serum NTX, urinary NTX, and TRACP5b, were smaller. After 12 months of treatment, there was an increase in bone mineral density at the lumbar spine, femoral neck, and total hip, and a decrease in the Visual Analog Scale score for back pain. The incidence of new vertebral and nonvertebral fractures was 1.21% and 3.18%, respectively. In conclusion, the favorable safety profile and effectiveness of teriparatide observed in this population of Japanese patients with osteoporosis were accompanied by relatively high persistence with treatment, which is a key factor in the success of osteoporosis treatment.

DOI： 10.1007/s00774-013-0546-6

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS/INTRODUCTION: Our primary objective was to assess changes in quality of life (QOL) associated with changes in insulin regimen in patients with type 2 diabetes mellitus. Secondary objectives were to assess the reasons for and patterns of changes in insulin regimen, and the effects on glycemic control. MATERIALS AND METHODS: This 12-week, observational study included patients with type 2 diabetes mellitus (n = 625) who planned to change insulin regimen (type of insulin, injection device and/or number of injections). The primary outcome measure was a change from baseline in QOL assessed by the Insulin Therapy-Related (ITR) QOL questionnaire. The secondary outcome measures included change from baseline in plasma glycated hemoglobin (HbA1c) level, the reasons for and pattern of insulin regimen change, and change from baseline in QOL assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ). RESULTS: QOL did not worsen during the study. Improvements were seen in the ITR-QOL 'daily activities' subscale score (baseline: 12.7 ± 2.3; week 12: 12.9 ± 2.3; P = 0.038, n = 568) and the DTSQ 'perceived frequency of hyperglycemia' subscale score (baseline: 3.4 ± 1.6; week 12: 3.0 ± 1.7; P < 0.001, n = 573). Glycemic control improved, as evidenced by decreased plasma HbA1c levels (baseline: 8.21 ± 1.47%; week 12: 7.85 ± 1.31%; P < 0.001, n = 606). CONCLUSIONS: It was suggested that insulin regimen changes might improve glycemic control in Japanese patients with type 2 diabetes mellitus without worsening QOL. This trial was registered with ClinicalTrials.gov (no. NCT01055808).

DOI： 10.1111/jdi.12086

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This large-scale observational study examined the long-term effectiveness and safety of growth hormone (GH) replacement therapy for adult GH deficiency (GHD) in Japanese clinical practice using the Hypopituitary Control and Complications Study database. The study included 402 GHD patients for safety analyses and a subset of 209 patients (149 adult-onset and 60 childhood-onset GHD patients) who had not previously received GH replacement therapy for the efficacy analyses. Data on clinical, metabolic, quality of life (QoL) characteristics, and all adverse events (AEs) were collected at baseline (start of GH treatment), 6 months, 1 year and 2 years. Over the observation period, there were improvements from baseline in insulin-like growth factor-I standard deviation scores (P<0.001), although the changes in metabolic parameters were minimal. QoL (Short Form-36) Z-scores significantly increased from baseline in both onset-type groups for several subscale domains (P<0.05). A total of 145 (36.1%) patients experienced ≥1 AE. Common AEs were hyperlipidaemia (2.7%) and hyperinsulinaemia (2.2%). Some patients experienced recurrent hypothalamic/pituitary tumour (events per 1000 patient-years: 2.78), new benign (0.93), malignant tumour (10.28) or other new tumour (0.93), new diabetes mellitus (7.45), and new stroke (3.71). Seven patients died during the observation period. Our safety findings are inconclusive about the associations between GH replacement and AEs, although the incidence of diabetes mellitus and cardiovascular events are similar to those reported in the Japanese general population. In conclusion, the key beneficial effects of GH replacement therapy for GHD are observed in routine clinical practice in Japan.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The objective of this study was to evaluate the efficacy and safety of stepwise introduction of insulin lispro mix 50 (LM50) from once to 3 times daily in Japanese patients with type 2 diabetes mellitus inadequately controlled by oral therapy. This was a multicenter, open-label, non-randomized trial consisting of three 16-week periods (48 weeks total); all patients were given once-daily injections of LM50 in Period 1. The regimen was intensified to twice daily in Period 2, and 3 times daily in Period 3 if HbA1c was ≥ 6.9% before the start of the period. A total of 135 patients were enrolled, and 116 patients completed the study. Main baseline characteristics of enrolled patients were a mean age of 60.3 years, mean diabetes duration of 11.4 years, mean BMI of 25.2 kg/m(2), and mean HbA1c of 8.71%. The percentages of patients who achieved HbA1c levels <6.9% and <7.4% at endpoint were 18.5% (25/135 patients) and 52.6% (71/135 patients), respectively. Mean HbA1c decreased significantly from 8.70% to 7.44% (p<0.001). The incidence of hypoglycemic episodes over the treatment periods was 65.9% (89/135 patients); severe hypoglycemia occurred in 2.2% (3/135 patients). There were no other clinically significant safety issues related to the study drug. Stepwise introduction of LM50 from once to 3 times daily can be a safe, effective, and simple therapy for Japanese patients with type 2 diabetes mellitus inadequately controlled by oral therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Gemcitabine was approved for the treatment of biliary tract cancer in 2006 in Japan. While biliary tract cancer is usually associated with patients 70 years of age or older and/or those who tend to have underlying liver dysfunction, data on this population were limited in the Japanese Phase II study of gemcitabine. Thus, further evaluation of safety and effectiveness in this population was planned. This special post-marketing surveillance was conducted as an observational study on the use of gemcitabine in a clinical practice setting. METHODS: Gemcitabine-naïve patients with biliary tract cancer were enrolled from 2006 to 2008 and observed over 12 months; one or more doses of gemcitabine were administered during the period. Data such as patient background, treatment details, adverse events occurring during the observational period, laboratory values of liver enzyme and survival status were collected 3 and 12 months after the start of therapy. RESULTS: Of the 285 patients registered for the study, 260 were included in the analysis. The mean age was 66.9 years. There were 120 patients (46.2%) classified as elderly (70 years or older). Haematotoxicities were the most common adverse drug reactions. In the elderly and the non-elderly, adverse drug reactions (serious) occurred in 48.3% (20.8%) and 50.7% (12.9%), respectively. The overall estimated 1-year survival rate was 52.5% (95% confidence interval, 45.9-58.7%). CONCLUSIONS: In line with previous clinical and post-marketing studies conducted in Japan, the results of this study suggest that gemcitabine could be used safely and effectively for biliary tract cancer patients including the elderly.

DOI： 10.1093/jjco/hys149

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To assess changes in quality of life (QOL) and pain in raloxifene-treated Japanese women with postmenopausal osteoporosis. RESEARCH DESIGN AND METHODS: This prospective, postmarketing observational study was conducted at 60 Japanese hospitals from September 2007 to February 2009 and included Japanese women with postmenopausal osteoporosis who were new to standard treatment with raloxifene (60 mg/day). Primary outcome measures (QOL and pain) were assessed using the Short Form-8 (SF-8), European Quality of Life Instrument (EQ-5D), osteoporosis-specific Japanese Osteoporosis Quality of Life Questionnaire (JOQOL), a visual analogue scale (VAS-pain), and a pain frequency survey. Assessments were performed at baseline and 8 (except JOQOL) and 24 weeks after first administration of raloxifene. Adverse drug reactions were recorded. Japan Pharmaceutical Information Center registration number: JapicCTI-070465. RESULTS: A total of 506 participants, mean (±standard deviation [SD]) age = 70.7 ± 8.7 years, completed ≥1 follow-up assessment and were included in the analyses. All QOL scores increased from baseline during follow-up. All SF-8 domain scores increased significantly from baseline after 8 and 24 weeks (P < 0.001). Mean (±SD) EQ-5D scores increased significantly from baseline (0.70 ± 0.17) by 0.05 ± 0.15 after 8 weeks and 0.07 ± 0.17 after 24 weeks (P < 0.001). The mean (±SD) total JOQOL score increased significantly from baseline (66.8 ± 16.5) by 3.8 ± 11.3 after 24 weeks (P < 0.001). The percentage of participants with a ≥20 mm reduction in VAS-pain was 32.6% (120/368) and 39.5% (115/291) after 8 and 24 weeks, respectively. The frequency of pain reported by participants decreased after 8 and 24 weeks. Forty adverse drug reactions were reported by 34 participants. LIMITATIONS: Limitations include the lack of a control group, the possibility of the changes being due to the natural disease course, and potential selection bias. CONCLUSIONS: Our findings suggest that standard treatment with raloxifene improves QOL and relieves pain in Japanese women with postmenopausal osteoporosis in a real-world clinical setting.

DOI： 10.1185/03007995.2012.736860

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This large-scale postmarketing surveillance of raloxifene (60 mg/day) was conducted to assess the safety and effectiveness of raloxifene for long-term use in postmenopausal Japanese women with osteoporosis. The baseline examination included 6,967 women (mean age, 70.4 years). Participants completed observation after 6, 12, 24, and 36 months of therapy. Adverse drug reactions (ADR) were reported in 776 participants (11.14 %), with a total of 87 serious ADR cases occurring in 76 participants (1.09 %). The most frequently reported ADRs were edema peripheral (45/6,967, 0.65 %) and venous thromboembolism (11/6,967, 0.16 %). Of the 6,967 participants, 2,784 were included in the effectiveness analysis. Lumbar spine bone mineral density (BMD) increased significantly (p < 0.001, paired t test) compared with baseline at 6, 12, 24, and 36 months (2.51 %, 2.85 %, 4.76 %, and 3.51 %, respectively). Significant decreases in serum and urinary cross-linked amino-terminal telopeptide of type I collagen (NTX) and urinary deoxypyridinoline levels from baseline were observed at 3 months, followed by a significant decrease of serum bone alkaline phosphatase at 6 months [p < 0.001 for all comparisons except serum NTX (p = 0.011), Wilcoxon signed-rank test]. Early reductions in the biochemical markers of bone turnover (BTM) observed at 3 months with raloxifene treatment correlated negatively with subsequent increases in lumbar spine BMD at 1 year (r = -0.347, p = 0.008). The incidence of any new clinical fractures within 3 years was 1.18 % (82/6,967 participants). In summary, no new signals in safety were observed in the daily use of raloxifene. Moreover, the effectiveness profile of raloxifene was confirmed in practical use by this large-scale, long-term, postmarketing surveillance.

DOI： 10.1007/s00774-012-0365-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/PURPOSE: Complications from biliary drainage in biliary tract cancer (BTC) may influence the relative dose intensity of chemotherapy or increase adverse events during chemotherapy. BT22 was a randomized phase II trial, the results of which were consistent with those of a phase III trial in non-Japanese that demonstrated the effectiveness of gemcitabine plus cisplatin combination therapy (GC) in BTC. The purpose of this exploratory analysis of the BT22 study was to identify the possible effects of biliary drainage on the efficacy and safety of GC or gemcitabine monotherapy (G). PATIENTS AND METHODS: The 83 BTC patients who received GC or G in BT22 were retrospectively analysed in two subgroups dependent upon whether biliary drainage was performed before study entry. Efficacy and safety of treatment (GC vs. G) were compared in these two groups. RESULTS: The GC arm had a higher 1-year survival rate and longer median survival time (MST) than the G arm independent of prior biliary drainage. Patients in the drainage subgroup developed cholangitis more frequently, however, the frequency of grade 3/4 adverse events did not differ between the treatment regimens with/without drainage. CONCLUSIONS: Biliary drainage before chemotherapy did not affect the therapeutic efficacy or tolerability of chemotherapy using G or GC.

DOI： 10.1111/j.1477-2574.2011.00431.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Increased risks of acute pancreatitis in patients with type 2 diabetes mellitus have been reported recently in several countries. We aimed to estimate the risks of acute pancreatitis in Japanese patients with diabetes mellitus. METHODS/FINDINGS: We examined a large-scale hospital administrative database consisting of one million patients in 16 secondary medical care hospitals, from 2003 to 2010. The incidence rates of acute pancreatitis were estimated with cohort design; the odds ratios associated with diabetes mellitus and other comorbid risk factors were estimated with separate case-control analyses. In cohort analysis, the incidence of acute pancreatitis was higher in 14,707 diabetic patients than in 186,032 non-diabetic patients (4.75 vs. 1.65 per 1,000 patient-years) and increased in male patients and as age advanced. The adjusted odds ratio of acute pancreatitis in patients with diabetes mellitus was 1.86 (P<0.001) compared with non-diabetic patients in case-control analysis from 1,372 cases and 5,469 matched controls, which is consistent with the ones reported in previous studies. Alcoholism and gallstones were associated with a large increase in the risk of acute pancreatitis (adjusted odds ratio 13.40 and 14.29, respectively, P<0.001), although dyslipidemia was associated with significant risk reduction (adjusted odds ratio 0.62, P<0.001). CONCLUSIONS: This observational study ascertained the elevated incidence rates and risk of acute pancreatitis in Japanese patients with diabetes. The risk estimates in Japanese patients with diabetes were in agreement with the ones reported in previous studies, and the elevated risk of acute pancreatitis in patients with diabetes would be generalized in different locations/populations.

DOI： 10.1371/journal.pone.0053224

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

To elucidate the detailed profiles of major adverse events associated with gemcitabine hydrochloride, such as myelosuppression and interstitial pneumonitis (IP), we reanalyzed the results from Japanese clinical studies conducted by Eli Lilly Japan K. K. in patients with various types of cancer. Myelosuppression was clearly apparent after starting therapy at 2-3 weeks in the 28- day course monotherapy group, and at 2 weeks in the 21-day course combination therapy group with paclitaxel, cisplatin, or docetaxel. Increases in the number of courses did not necessarily lead to worsening of myelosuppression. IP possibly related to gemcitabine was seen in 6 out of 5 23 monotherapy patients and 5 out of 233 combination therapy patients. Five of these 11 patients were diagnosed in the first course; however, another patient was diagnosed with IP in Course 6. Two of these patients died of IP, one of whom had a past history of interstitial lung disease. These results indicate that ample attention should be paid to myelosuppression 2-3 weeks after the start of therapy, and to IP during the entire course of therapy.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There had been no standard chemotherapy established for advanced biliary tract cancer (BTC) until 2009, when the combination of cisplatin and gemcitabine (GC) was adopted as a first line standard chemotherapy option based on the results from two randomized studies: ABC-02, a UK investigator-initiated trial and the largest randomized phase III study in this tumor type with 410 patients; and BT22, a Japanese, industry-sponsored, randomized phase II study with 83 patients. In this review, investigators from both studies collaborated to compare protocols, patient characteristics, and outcomes of both studies including sub-analyses of study results. Although both studies showed GC combination therapy to be more effective than monotherapy, a detailed comparison revealed disparities between efficacy and safety end-points between the studies, which did not necessarily arise from different populations but from differences in protocol design. This review provides clinicians with insights for advanced BTC clinical study design and interpretation of historical studies.

DOI： 10.1016/j.critrevonc.2010.10.009

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