Comparative analysis of medical costs after hepatectomy versus radiofrequency ablation in patients with hepatocellular carcinoma in real-world clinical practice.

AIM: To compare the total medical costs and treatment outcomes in patients with primary hepatocellular carcinoma (HCC) according to their initial treatment, that is, hepatectomy or radiofrequency ablation (RFA), in real-world clinical practice in Japan. METHODS: This retrospective observational study was conducted using a medical claims database. Patients who underwent hepatectomy or RFA for primary HCC were matched using propensity score matching methods for available baseline characteristics. The average per-patient total medical costs from the date of initial treatment to up to 3 years were estimated. The 3-year survival and recurrence rates were estimated using the Kaplan-Meier method. RESULTS: Data of 1726 patients (863 in each group) were analyzed. The average 3-year medical costs were USD 8000 lower in the RFA group than in the hepatectomy group (USD 35,000 vs. USD 43,000). Patients in the RFA group had comparable 3-year overall survival to those in the hepatectomy group (87.6% vs. 90.4%). However, the 3-year recurrence rate was significantly higher in the RFA group than in the hepatectomy group (41.5% vs. 30.8%; hazard ratio = 1.56, 95% confidence interval: 1.31-1.87). CONCLUSIONS: In this 3-year study, patients achieved similar survival rates irrespective of initial treatment, but the RFA group had a lower total medical cost burden than the hepatectomy group. If both treatments are equally feasible, RFA may be a preferable initial curative treatment for primary HCC. However, careful consideration and adequate treatment should be given due to its higher recurrence risk.

Treatment patterns and medical costs after hepatectomy in real-world practice for patients with hepatocellular carcinoma in Japan.

AIM: To examine the treatment patterns and medical costs in real-world practice among patients who received hepatectomy for hepatocellular carcinoma (HCC) in Japan. METHODS: Data of patients who underwent hepatectomy as an initial therapy for primary HCC were extracted from a Japanese medical claims database from April 2008 to December 2019. The types of additional treatments for recurrent HCC and medical costs for up to 3 years from the first hepatectomy were analyzed. The average cumulative cost per patient starting on the date of the first hepatectomy was calculated using the Kaplan-Meier sample-average method. RESULTS: Data from 2 342 patients (median age, 71 years) were analyzed. Overall, 35.6% of patients received at least one HCC treatment within 3 years of the first hepatectomy. The total average cumulative 3-years medical cost was JPY 4 993 300 (95% confidence interval [CI]: 4 804 100 to 5 220 500). Surgical procedures were the most costly components in the first month after hepatectomy, whereas the costs of drugs, which mainly included antiviral and antineoplastic medications, increased thereafter. Patients with advanced stage HCC, hepatitis C, or a higher Charlson Comorbidity Index at hepatectomy, or those who required additional treatment, especially with antineoplastic drugs for recurrent HCC, incurred higher medical costs. CONCLUSIONS: Patients with HCC after hepatectomy experienced a large economic burden, which was more serious for those with advanced stage HCC, higher comorbidities, and hepatitis at baseline and for patients treated with antineoplastic drugs. A treatment selection that considers its medical cost burden would help to reduce some of these economic burdens.

Effectiveness and safety of eribulin in Japanese patients with HER2-negative, advanced breast cancer: a 2-year post-marketing observational study in a real-world setting.

Background Data on eribulin as the first- or second-line treatment in a clinical setting, especially the overall survival (OS) of patients, are scarce. Therefore, we assessed the effectiveness and safety of eribulin as the first-, second-, and third- or later-line treatments in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in Japan. Methods This multicenter, prospective, post-marketing, observational study enrolled patients from September 2014 to February 2016 in Japan and followed them for 2 years. Patients were categorized by eribulin use into the first-, second-, and third- or later-line treatment groups. Results Of 651 registered patients, 637 patients were included in the safety and effectiveness analysis. In all, first-, second-, and third or later-line treatment groups, median OS (95% confidence interval) were 15.6 (13.8-17.6), 22.8 (17.3-31.0), 16.3 (12.4-19.9), and 12.6 (11.2-15.1) months and time to treatment failure (TTF) (95% confidence interval) were 4.2 (3.7-4.4), 5.2 (3.7-5.9), 4.2 (3.7-5.1), and 3.8 (3.5-4.2) months, respectively. Prolonged TTF was associated with complications of diabetes and the development of peripheral neuropathy after eribulin treatment, according to multivariate Cox regression analysis. Grade ≥ 3 adverse drug reactions (ADRs) were reported in 61.7% of the patients. Neutropenia (49.5%) was the most common grade ≥ 3 ADR in all groups. Conclusions The effectiveness and safety results of eribulin as the first- or second-line treatment were favorable. Thus, these suggest eribulin may be a first-line treatment candidate for patients with HER2-negative advanced breast cancer in Japan.

Pharmacodynamic analysis of eribulin safety in breast cancer patients using real-world postmarketing surveillance data.

Postmarketing surveillance is useful to collect safety data in real-world clinical settings. In this study, we applied postmarketing real-world data on a mechanistic model analysis for neutropenic profiles of eribulin in patients with recurrent or metastatic breast cancer. Demographic and safety data were collected using an active surveillance method from eribulin-treated recurrent or metastatic breast cancer patients. Changes in neutrophil counts over time were analyzed using a mechanistic pharmacodynamic model. Pathophysiological factors that might affect the severity of neutropenia were investigated, and neutropenic patterns were simulated for different treatment schedules. Clinical and laboratory data were collected from 401 patients (5199 neutrophil count measurements) who had not received granulocyte colony-stimulating factor and were eligible for pharmacodynamic analysis. The estimated mean parameters were as follows: mean transit time = 104.5 h, neutrophil proliferation rate constant = 0.0377 h-1 , neutrophil elimination rate constant = 0.0295 h-1 , and linear coefficient of drug effect = 0.0413 mL/ng. Low serum albumin levels and low baseline neutrophil counts were associated with severe neutropenia. The probability of grade ≥3 neutropenia was predicted to be 69%, 27%, and 27% for patients on standard, biweekly, and triweekly treatment scenarios, respectively, based on virtual simulations using the developed pharmacodynamic model. In conclusion, this is the first application of postmarketing surveillance data to a model-based safety analysis. This analysis of safety data reflecting authentic clinical settings will provide useful information on the safe use and potential risk factors of eribulin.

Pharmacological effects of lysozyme on COPD and bronchial asthma with sputum: A randomized, placebo-controlled, small cohort, cross-over study.

BACKGROUND: Mucolytic agents are often used in Japan to ease excessive mucus production in patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma (BA); the treatment ameliorates dyspnea and improves quality of life (QOL). AIM: Efficacy and safety of lysozyme hydrochloride (LYS), an oral mucolytic enzyme preparation, for patients with COPD or BA were investigated. PATIENTS AND METHODS: This study was a placebo-controlled, double-blind, randomized, cross-over design. Twenty-four patients with COPD and twenty-four patients with BA were enrolled. LYS or placebo was administered for 28 days in each treatment period, with a 28-day washout between the first and second treatment periods. The results of spirometry, impulse oscillometry system (IOS) examination, fractional exhaled nitric oxide (FeNO) measurement, as well as the changes in the subjective symptoms, were evaluated after the treatment period. RESULTS: On spirometry, airway function (FEV1) improved in patients with COPD after administration of LYS (LYS vs placebo: 0.08 L vs 0.029 L, p = 0.030). Similar trends were also found in %FEV1 in COPD patients. On IOS examination, resistance of the respiratory system at 5 Hz levels was significantly improved only in patients with COPD (LYS vs placebo: -0.455 cm H2O/L/s vs 0.095 cmH2O/L/s, p = 0.012). Similar trends were found in terms of the resistance of the respiratory system at 20 Hz, and of the reactance area. In the COPD assessment test, subjective symptoms also significantly improved in patients with COPD during the LYS treatment period (improvement rates-LYS vs. placebo: 69.6% vs. 39.1%; p = 0.022). A similar effect of LYS was not seen in BA patients. CONCLUSION: LYS, a mucolytic agent, has capability to improve the function of peripheral airways in patients with COPD, which leads to improvements of the patients' symptoms and QOL.

Disease state changes and safety of long-term donepezil hydrochloride administration in patients with Alzheimer's disease: interim results from the long-term, large-scale J-GOLD study in Japan.

BACKGROUND: There have been very few long-term studies involving a large study population; existing studies usually have no more than a few hundred patients with Alzheimer's disease. For these reasons, there are no detailed investigations regarding changes in activities of daily living evaluated by the Functional Assessment Staging Test (FAST). METHODS: A long-term, large-scale observational study of donepezil hydrochloride (Aricept(®); Eisai Co., Ltd, Tokyo, Japan) is currently in progress. Its objective is to investigate disease state changes associated with the long-term administration of this drug and its safety in patients with Alzheimer's disease. In this report, data collected over a maximum of 24 months were compiled. Efficacy was assessed using FAST and a cognitive function test (Mini-Mental State Examination or the Hasegawa's Dementia Scale-Revised). RESULTS: The percentages of patients whose FAST stage improved or remained the same compared to at the start of donepezil hydrochloride administration (baseline) were 91.1% at 6 months, 83.0% at 12 months, 79.5% at 18 months, and 74.8% at 24 months. Multivariate logistic regression analysis was conducted to investigate factors that affect the improvement and maintenance or exacerbation of FAST at 24 months. 'Independence level in the daily life of elderly with dementia' and 'duration of illness' were identified as variables that affected the improvement and maintenance or exacerbation of FAST. Cognitive function improved significantly at 12 weeks and at 6 months compared to baseline, maintained baseline levels at 12 months and at 18 months, and decreased significantly at 24 months compared to baseline. CONCLUSIONS: This is the largest prospective study involving Alzheimer's disease patients in Japan, and we believe it is an important study that shows the reality of daily clinical practice.

Correction to: Prevalence, incidence, and medications of narcolepsy in Japan: a descriptive observational study using a health insurance claims database.

[This corrects the article DOI: 10.1007/s41105-022-00406-4.].

Linguistic and Psychometric Validation of the Cognition Bolt-On Version of the Japanese EQ-5D-5L for the Elderly.

BACKGROUND: The need for a cognition bolt-on version of the EQ-5D, which would capture cognitive impairment by adding a dimension to the generic instrument assessing health status, has been increasing in Japan. OBJECTIVE: To develop a cognition bolt-on version of the 5-level EQ-5D (EQ-5D-5L+C), we linguistically validated a cognition dimension and psychometrically validated the EQ-5D-5L+C. METHODS: Following linguistic validation of the cognition dimension, psychometric validation of the EQ-5D-5L+C proxy version utilized anonymized data collected from nursing home residents between October 2021 to April 2022. The validity, reliability, and sensitivity to change were evaluated. RESULTS: Data from 254 participants, including the finalized Japanese EQ-5D-5L+C proxy version, were analyzed for the psychometric validation. Mean (±standard deviation) age and Mini-Mental State Examination (MMSE) scores were 87.14±7.29 years and 15.76±8.46, respectively. The correlation was strongest between the cognition dimension and MMSE scores (rs = -0.640). Test-retest reliability was good in the cognition dimension in both baseline and two-time points (3 months: k = 0.644; 6 months: k = 0.656). Although a correlation between changes in the cognition dimension and those in the MMSE score from baseline was weak (3 months: rs = -0.191; 6 months: rs = -0.267), a correlation with changes in the MMSE score was higher when the cognition dimension was added compared to the EQ-5D alone (3 months: rs = -0.142 versus rs = -0.074). CONCLUSION: The Japanese EQ-5D-5L+C proxy version developed is a valid tool that captures health status including cognitive function, with a consideration for an over-time assessment. The benefits in adding the cognition dimension to the EQ-5D-5L to assess health state were suggested.

Prevalence, incidence, and medications of narcolepsy in Japan: a descriptive observational study using a health insurance claims database.

The objectives of this study were to describe prevalence, incidence, and medications among patients who were diagnosed with narcolepsy in Japan using a claims database. Patients diagnosed with narcolepsy were identified from January 2010 to December 2019 using an employment-based health insurance claims database compiled by JMDC Inc. The prevalence and incidence of narcolepsy were estimated annually in the overall population and by age and sex among employees and their dependents aged < 75 years. Medications, examined for each quarter in the overall population, were modafinil, methylphenidate, pemoline, tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors. We identified 1539 patients with narcolepsy. The overall annual prevalence increased from 5.7 to 18.5/100,000 persons in 2010 and 2019, respectively. Large increases were found from 2010 to 2019 in patients aged 20-29 years and 10-19 years, with the highest prevalence in 2019 (9.7-37.5/100,000 persons and 5.0-27.1/100,000 persons). The overall incidence slightly increased from 3.6 to 4.3/100,000 person-year from 2010 to 2019, and the highest incidence was found in patients aged 20-29 years and 10-19 years (5.8-11.3/100,000 person-year, and 3.8-7.4/100,000 person-year from 2010 to 2019, respectively). Methylphenidate and modafinil were commonly prescribed in 2010 (27.3-38.9% and 17.5-45.5%, respectively). Methylphenidate prescriptions declined during the 10 years, whereas modafinil prescriptions increased (15.6-17.1% and 43.8-45.8% in 2019, respectively). The estimated prevalence and incidence of narcolepsy appeared to increase from 2010 to 2019, especially in teenagers and 20-year olds. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00406-4.

Long-term effectiveness of Gliadel implant for malignant glioma and prognostic factors for survival: 3-year results of a postmarketing surveillance in Japan.

BACKGROUND: Adjuvant treatment with Gliadel wafers may prolong overall survival (OS) for malignant glioma patients without increasing toxicity. In Japan, the long-term OS of these patients treated with Gliadel 7.7 mg implants has not been studied. We evaluated OS and prognostic factors that might affect OS in Japanese patients with malignant glioma who received the Gliadel 7.7 mg implant. METHODS: This observational, long-term, postmarketing surveillance was an extension of a previous surveillance. Data were collected through case report forms at 2 and 3 years after Gliadel implant. Up to 8 Gliadel wafers (61.6 mg of carmustine) were placed over the tumor resection site. Primary endpoints were OS and prognostic factors that may influence OS. RESULTS: Among the 506 patients analyzed, 62.6% had newly diagnosed disease, and 37.4% had recurrent disease; 79.1% had glioblastoma histological type and 79.6% had World Health Organization Grade IV disease. Patients received a median of 8 wafers. The median OS was 18.0 months; OS rates were 39.8% and 31.5% at 2 and 3 years, respectively. Age ≥65 years (hazard ratio [HR]: 1.456; P = .002), lower resection rate (HR: 1.206; P < .001), recurrence (HR: 2.418; P < .001), and concomitant radiotherapy (HR: 0.588; P < .001) were identified as significant prognostic factors. CONCLUSIONS: This study confirmed the 2- and 3-year OS of Japanese malignant glioma patients with varied backgrounds after Gliadel implant. With a careful interpretation of indirect comparisons with previously reported data, the results suggest that prognosis could be improved with Gliadel implants. CLINICAL TRIAL REGISTRATION: NCT02300506.

Safety of Gliadel Implant for Malignant Glioma: Report of Postmarketing Surveillance in Japan.

Clinical trial data of Carmustine implant (Gliadel Wafer) in Japanese patients with malignant glioma are limited; thus, we conducted a postmarketing surveillance study to evaluate the safety of Gliadel in real-world clinical practice in Japan. In this postmarketing surveillance study, all patients who received Gliadel placement for malignant glioma surgeries from its market launch (January 9, 2013) to July 10, 2013 were enrolled from 229 institutions using a central registration system. Up to eight wafers of Gliadel (containing 61.6 mg of carmustine) were used to cover the site of brain tumor resection intraoperatively according to the size and shape of the tumor resection cavity. The observation period lasted 3 months after Gliadel placement. Patients were followed up for 1 year postoperatively. Safety was assessed by the incidence of adverse events (AEs) and adverse drug reactions (ADRs). In total, 558 patients were included. Most patients (66.7%) received eight Gliadel wafers. The percentage of patients with ADRs was 35.7% (365 ADR episodes in 199 patients). Of the AEs of special interest, the most common were cerebral edema (22.2%, 124/558 patients), convulsion (9.9%, 55/558 patients), impaired healing (4.8%, 27/558 patients), and infection (3.4%, 19/558 patients). This first all-case postmarketing surveillance report of the safety of Gliadel in real-world clinical practice in Japan suggests that the risk of toxicity with Gliadel placement is relatively tolerable. The survival benefits of Gliadel placement should be evaluated and considered carefully by the clinician taking into account possible toxicities.

Impact of the Severity of Alzheimer's Disease on the Quality of Life, Activities of Daily Living, and Caregiving Costs for Institutionalized Patients on Anti-Alzheimer Medications in Japan.

BACKGROUND: Alzheimer's disease (AD) increases societal costs and decreases the activities of daily living (ADL) and quality of life (QoL) of the affected individuals. OBJECTIVE: We assess the impact of AD severity on ADL, QoL, and caregiving costs in Japanese facilities for the elderly. METHODS: Patients with AD in facilities for the elderly were included (47 facilities, N = 3,461). The QoL, ADL, and disease severity of patients were assessed using Barthel Index (BI), EuroQoL-5D-5L (EQ-5D-5L), and Mini-Mental State Examination (MMSE), respectively. Annual caregiving costs were estimated using patients' claims data. The patients were subcategorized into the following three groups according to the MMSE score: mild (21≤MMSE≤30), moderate (11≤MMSE≤20), and severe (0≤MMSE≤10). Changes among the three groups were evaluated using the Jonckheere-Terpstra test. RESULTS: Four hundred and one participants were on anti-AD medicines, of whom 287 (age: 86.1±6.4 years, 76.7% women) in the mild (n = 53, 84.0±6.9 years, 71.7%), moderate (n = 118, 86.6±5.9 years, 76.3%), and severe (n = 116, 86.6±6.5 years, 79.3%) groups completed the study questionnaires. The mean BI and EQ-5D-5L scores for each group were 83.6, 65.1, and 32.8 and 0.801, 0.662, and 0.436, respectively. The mean annual caregiving costs were 2.111, 2.470, and 2.809 million JPY, respectively. As AD worsened, the BI and EQ-5D-5L scores decreased and annual caregiving costs increased significantly. CONCLUSION: AD severity has an impact on QoL, ADL, and caregiving costs.

Indices of peripheral leukocytes predict longer overall survival in breast cancer patients on eribulin in Japan.

BACKGROUND: It was reported that eribulin regulates the tumor microenvironment, including the immune system, by inducing vascular remodeling. Lymphocyte counts are a critical index of immune response in patients. The non-Asian, global EMBRACE study has suggested that baseline absolute lymphocyte count (ALC) may be a predictor of the survival benefit of eribulin in breast cancer patients. We examined whether the baseline ALC is a potential predictor of overall survival (OS) in Japanese patients with HER2-negative advanced breast cancer treated with eribulin. METHODS: This was a post hoc analysis of data from a post-marketing observational study of eribulin in Japan. The OS by baseline ALC was estimated using the Kaplan-Meier method, with the cut-off value of 1500/µL for ALC. The OS by baseline neutrophil-to-lymphocyte ratio (NLR), a general prognostic index in breast cancer patients, was also estimated, with the cut-off value of 3. RESULTS: The median OS was longer in patients with an ALC of ≥ 1500/µL than in those with an ALC of < 1500/µL (19.4 vs. 14.3 months; hazard ratio [HR]: 0.628; 95% confidence interval [CI]: 0.492, 0.801). Patients with an NLR of ≥ 3 showed shorter OS than those with an NLR of < 3 (13.2 vs. 18.8 months; HR: 1.552; 95% CI 1.254, 1.921), and NLR also separated OS in patients with an ALC of < 1500/µL. CONCLUSIONS: Consistent with the findings of a previous study involving a non-Asian, Western population, our study suggested that baseline ALC may be a predictive factor for the survival benefit of eribulin in Japanese patients.

Safety and Effectiveness of Lenvatinib in 594 Patients with Unresectable Thyroid Cancer in an All-Case Post-Marketing Observational Study in Japan.

INTRODUCTION: Lenvatinib is approved in Japan for treating patients with all histological subtypes of unresectable thyroid cancer, including differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC), and anaplastic thyroid cancer (ATC). However, safety and effectiveness data are limited in Japanese patients. Therefore, this prospective, post-marketing observational study evaluated, in daily clinical practice, the safety and effectiveness of lenvatinib in Japanese patients with unresectable thyroid cancer. METHODS: All patients with unresectable thyroid cancer first treated with lenvatinib between May and November 2015 were registered. Patients were orally administered lenvatinib and followed up for 12 months. The endpoints included adverse drug reactions (ADRs), overall survival (OS), overall response rate (ORR), and time-to-treatment failure. Post hoc Cox multivariate analyses were performed to assess prognostic factors associated with the 12-month OS rate. RESULTS: Of 629 registered patients, 594 were included in the analysis. A total of 442 patients (74.4%) had DTC, 28 (4.7%) had MTC, and 124 (20.9%) had ATC. Hypertension, proteinuria, and palmar-plantar erythrodysesthesia syndrome were the most frequently reported ADRs across all histological subtypes. The median OS was 101.0 days in patients with ATC which was not reached in patients with DTC and patients with MTC, with 12-month OS rates of 15.6%, 75.7%, and 83.0%, respectively. The ORRs were 59.2%, 45.0%, and 43.8% among 368 patients with DTC, 20 with MTC, and 105 with ATC, respectively. Multivariate analyses revealed that Eastern Cooperative Oncology Group performance status (ECOG PS), tumor size, the presence of tumor invasion, and body weight were baseline prognostic factors affecting OS in patients with DTC, while ECOG PS and the presence of liver metastasis were prognostic factors in patients with ATC. CONCLUSION: Lenvatinib demonstrated an acceptable safety profile for patients with thyroid cancer in a real-world setting in Japan. The safety profile and effectiveness findings for lenvatinib in this study were consistent with those from previous clinical trials, irrespective of histological subtype.

Chemotherapy-induced peripheral neuropathy in breast cancer patients treated with eribulin: interim data from a post-marketing observational study.

BACKGROUND: Few studies have examined chemotherapy-induced peripheral neuropathy (CIPN) following the administration of eribulin as first- or second-line therapy in patients with breast cancer. We therefore assessed CIPN incidence by severity and risk factors for CIPN in patients treated with eribulin for HER2-negative inoperable or recurrent breast cancer, regardless of line therapy status. METHODS: This multicenter, prospective, post-marketing observational study enrolled patients from September 2014 in Japan and followed them for 2 years. For this interim analysis, the data cut-off point was in November 2017. CIPN severity was assessed based on the Japanese version of the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Among 634 patients included in the safety analysis, 374 patients did not have existing CIPN at baseline. CIPN was observed in 105 patients (28.1%), including 67 (17.9%), 34 (9.1%), and 4 (1.1%) patients with grade 1, 2, and 3 severity, respectively. Of the 105 patients, 85.7% patients continued, 7.6% reduced, interrupted or postponed, and 6.7% discontinued eribulin. The median time (min‒max) from baseline to CIPN onset was 60 (3‒337) days. Multivariate logistic regression identified a significant association between CIPN and hemoglobin level at baseline, starting dose of eribulin, and history of radiotherapy. CONCLUSIONS: Our findings indicate that, with respect to CIPN, eribulin is well-tolerated, as approximately one-quarter of patients developed CIPN, most cases were grade 1 or 2, and the majority of patients continued eribulin after CIPN onset.

Use of a Healthcare Claims Database for Post-Marketing Safety Assessments of Eribulin in Japan: A Comparative Assessment with a Prospective Post-Marketing Surveillance Study.

BACKGROUND: To understand the extent to which a large-scale healthcare claims database (DB) captures the safety profile of eribulin mesylate (Halaven®, Eisai Co., Ltd., Japan), we compared patient characteristics, drug use, and adverse events (AEs) between data for patients treated with eribulin retrieved from a DB and data for metastatic breast cancer patients from a conventional prospective post-marketing surveillance (PMS). METHODS: We descriptively summarized patient characteristics and AEs of 551 and 951 patients retrieved from DB and PMS, respectively, during 2011‒2013. Using 2814 patient data from the DB during 2011‒2016, the drug use and AE incidence over time were assessed. RESULTS: In both datasets, 99.8% were females, and the mean age was 57.8 ± 10.7 years. The mean number of eribulin administration was 11.1 ± 10.9 and 10.1 ± 7.8 in DB and PMS, respectively. Although, overall, the difference in AE incidence between the two datasets was moderate, gaps were larger for nausea (DB: 73.32% vs. PMS: 15.77%), neutropenia (20.87% vs. 66.67%), stomatitis (37.39% vs. 10.94%), and alopecia (0.36% vs. 12.09%). During 2011‒2016, the observed incidence of anemia or pyrexia significantly decreased (trend test, p = 0.0009 for both). CONCLUSION: Generally, patient characteristics, drug use, and AE incidence between the DB and PMS were comparable; however, AEs such as neutropenia may require defining based on the laboratory data to achieve more comparable results in DBs. Besides the usefulness of healthcare claims DBs for long-term assessments, they may also serve as a good complementary to PMS in the pharmacovigilance of eribulin.

Pharmacotherapy decision-making among patients with breast cancer in Japan: results of an online survey.

BACKGROUND: Although communication between patients with breast cancer and physicians is central to treatment decision-making for patients and the concept of shared decision-making has been increasingly advocated worldwide, little is known about decision-making and perceptions among the population in Japan. Therefore, this cross-sectional study aimed to clarify the status of pharmacotherapy decision-making among patients with breast cancer in Japan and assess factors associated with patient satisfaction with patient-physician communication. METHODS: Data for women previously treated with pharmacotherapy agents for breast cancer in Japan were collected in July 2017 using an online survey. Respondents were categorized by their decision-making role (active, shared, passive). Characteristics, decisional conflict level, and satisfaction with communication with their physician at the time of pharmacotherapy selection were stratified by decision-making roles. Stepwise multivariate logistic regression was performed to assess factors associated with satisfaction. RESULTS: Of 486 women that responded, nearly half played an active decision-making role (48.4%) and 26.0% played a shared role. The lowest decisional conflict and higher satisfaction were observed among those who played a shared role. The highest decisional conflict and lower satisfaction were observed in passive decision-makers. Shared decision-making, a longer consultation time with the physician, and multiple treatment options provided by the physician were significantly associated with satisfaction with communication with the physician. CONCLUSIONS: Our findings suggest that among patients with breast cancer, a shared role in treatment decision-making, longer consultation time at treatment selection, and having multiple treatment options are important for higher patient satisfaction with communication with their physician.

Prevention of COPD exacerbation by lysozyme: a double-blind, randomized, placebo-controlled study.

BACKGROUND/AIM: Lysozyme (mucopeptide N-acetyl-muramyl hydrolase) is widely used as a mucolytic and anti-inflammatory agent in Japan. We evaluated the effects of long-term lysozyme administration on COPD exacerbation. METHODS: In a 1-year, randomized, double-blind, placebo-controlled, parallel trial, patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected. Lysozyme (270 mg) or placebo was administered orally for 52 weeks as an add-on to the standard therapies such as bronchodilators. COPD exacerbation, pulmonary function, and COPD assessment test scores were analyzed. An exacerbation was defined as worsening of more than one symptom of COPD (cough, sputum volume, purulent sputum, or breathlessness) leading to a change in medication. The primary endpoint was exacerbation rate. RESULTS: A total of 408 patients were randomly assigned to the lysozyme and placebo groups. The baseline characteristics were similar between the two groups. The exacerbation rate was not significantly different between the two groups (1.4 vs 1.2; P=0.292, Poisson regression). However, a subgroup analysis showed that lysozyme might reduce exacerbation rate in patients with airway-dominant phenotype (1.2 vs 1.6). Moreover, the median time to first exacerbation was longer in patients with airway-dominant phenotype in the lysozyme group than that in the placebo group. The levels of improvement in forced expiratory volume in 1 second and COPD assessment test scores were not statistically different between the groups, but were always greater in the lysozyme group than in the placebo group over the 52 weeks of the study. CONCLUSION: The effects of using lysozyme as an add-on to standard COPD therapy were not significantly different compared with placebo and were insufficient to prevent COPD exacerbation.

A multicenter prospective observational study of triple therapy with rabeprazole, amoxicillin and metronidazole for Helicobacter pylori in Japan.

OBJECTIVE: Triple therapy with rabeprazole (RPZ), amoxicillin (AMPC) and metronidazole (MNZ) (RPZ+AMPC+MNZ therapy: RAM therapy) has been approved by the Japanese Ministry of Health, Labour and Welfare as a second-line therapy for Helicobacter pylori-positive gastric and duodenal ulcers in Japan. The present multicenter prospective observational study aimed to investigate the safety and efficacy of RAM therapy in clinical practice. METHODS: Patients with H. pylori-positive gastric or duodenal ulcers (including ulcer scars) in whom first-line therapy was unsuccessful were administered 10 mg of RPZ, 750 mg of AMPC and 250 mg of MNZ twice daily for seven days (total: 14 doses) based on an approved dose and regimen. Patient background factors, including complications, previous medical history, concomitant drugs, eradication results and adverse events were recorded by the investigator. RESULTS: The incidence of adverse drug reactions was 2.21% and the H. pylori eradication rate was 92.8%. Subgroup analyses performed to investigate the patient background factors affecting safety and efficacy revealed no factors that significantly affected the incidence of adverse drug reactions or the H. pylori eradication rate. CONCLUSION: Amid reports of decreased eradication rates with clarithromycin-based first-line therapy, the >90%H. pylori eradication rate achieved in the present study demonstrates the clinical efficacy of RAM therapy in subjects in whom first-line therapy is unsuccessful.