Costs associated with febrile neutropenia in Japanese patients with primary breast cancer: post-hoc analysis of a randomized clinical trial.

BACKGROUND: Febrile neutropenia (FN), a decrease in blood neutrophils accompanied by fever, is a major adverse event (AE) associated with cancer chemotherapy. We aimed to estimate the direct medical costs associated with FN management in breast cancer patients within a clinical trial with pegfilgrastim, a pegylated form of recombinant granulocyte colony-stimulating factor (G-CSF). METHODS: We obtained data from 346 Japanese breast cancer patients in a randomized, placebo-controlled clinical trial comparing FN incidence due to TC adjuvant chemotherapy (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) between pegfilgrastim-treated and placebo groups. We estimated mean costs for chemotherapy drugs, drugs for all AEs and FN, and hospitalization for all AEs and FN. We also calculated mean costs associated with drugs and hospitalization for FN specifically for patients who developed FN in the placebo group. RESULTS: For the pegfilgrastim and placebo groups, the total cost during the first cycle of chemotherapy was ¥189 135 and ¥98 106. This difference is associated with prophylactic use of pegfilgrastim. Our analysis clarified in the placebo group that FN incidents of 119/173 (68.6%), the mean drug cost related to all AEs and hospitalization caused by the first cycle of chemotherapy were ¥14 411and ¥11 180, respectively. The cost of each for FN treatment was ¥16 429 for the placebo group. The mean treatment cost for patients who developed FN in placebo group, was ¥11 145 for drugs and ¥28 420 for drugs and hospitalization. CONCLUSIONS: Pegfilgrastim reduced the costs incurred for both drugs and hospitalization for AEs as well as FN, although the total medical cost during the chemotherapy increased. Our study constitutes baseline data for further health economic evaluations of pegfilgrastim.

Healthcare resource utilization and clinical outcomes associated with acute care and inpatient rehabilitation of stroke patients in Japan.

OBJECTIVE: To investigate healthcare resource utilization and changes in functional status in stroke patients during hospitalization in an acute hospital and a rehabilitation hospital. DESIGN: Retrospective cohort study. SETTING: One acute and one rehabilitation hospital in Japan. PARTICIPANTS: Patients who were admitted to the acute hospital due to stroke onset and then transferred to the rehabilitation hospital (n = 263, 56% male, age 70 ± 12 years). MAIN OUTCOME MEASURES: Hospitalization costs and functional independence measure (FIM) were evaluated according to stroke subtype and severity of disability at discharge from the acute hospital. RESULTS: Median (IQR) costs at the acute hospital were dependent on the length of stay (LOS) and implementation of neurosurgery, which resulted in higher costs in subarachnoid hemorrhage [$52 413 ($49 166-$72 606) vs $14 129 ($11 169-$19 459) in cerebral infarction; and vs $15 035 ($10 920-$21 864) in intracerebral hemorrhage]. The costs at the rehabilitation hospital were dependent on LOS, and higher in patients with moderate disability than in those with mild disability [$30 026 ($18 419-$39 911) vs $18 052 ($10 631-$24 384)], while those with severe disability spent $25 476 ($13 340-$43 032). Patients with moderate disability gained the most benefits during hospitalization in the rehabilitation hospital, with a median (IQR) total FIM gain of 16 (5-24) points, compared with a modest improvement in patients with mild (6, 2-14) or severe disability (0, 0-5). CONCLUSIONS: The costs for in-hospital stroke care were substantial and the improvement in functional status varied by severity of disability. Our findings would be valuable to organize efficient post-acute stroke care.

Cost-Effectiveness of Proton Pump Inhibitor Co-Therapy in Patients Taking Aspirin for Secondary Prevention of Ischemic Stroke.

BACKGROUND: Low-dose aspirin (ASA) is effective for secondary prevention of ischemic stroke but can increase the risks of hemorrhagic stroke, upper gastrointestinal bleeding (UGIB), and dyspepsia. Prophylactic administration of proton pump inhibitors (PPIs) reduces the risks of these digestive symptoms. We investigated the cost effectiveness of adding a PPI to ASA therapy for ischemic stroke patients in Japan. METHODS: A Markov state-transition model was developed to compare the cost effectiveness of ASA monotherapy with ASA plus PPI co-therapy in patients with histories of upper gastrointestinal ulcers and ischemic stroke. The model takes into account ASA adherence rate and adverse effects due to ASA, including hemorrhagic stroke and UGIB. The analysis was performed from the perspective of healthcare payers in 2013. RESULTS: In the base case, total life-years by PPI co-therapy and monotherapy were 16.005 and 15.932, respectively. The difference in duration of no therapy (no ASA or PPI) between the therapies was 558.5 days, which would prevent 30.3 recurrences of ischemic stroke per 1000 person-years. The incremental cost-effectiveness ratio of PPI co-therapy relative to monotherapy was ¥1,191,665 (US$11,458) per life-year gained. In a one-way sensitivity analysis, PPI co-therapy was consistently cost effective at a willingness to pay of ¥5,000,000 (US$48,077) per life-year gained. In a probabilistic sensitivity analysis, the probability that PPI co-therapy was cost effective was 89.74% at the willingness to pay. CONCLUSIONS: Co-therapy with ASA plus PPI appears to be cost-effective compared with ASA monotherapy. The addition of PPI also appeared to prolong the duration of ASA therapy, thereby reducing the risk of ischemic stroke.

The changing patterns of dispensing branded and generic drugs for the treatment of gastroesophageal reflux disease between 2006 and 2011 in Japan: a retrospective cohort study.

BACKGROUND: Despite rising healthcare costs, generic drugs are less frequently dispensed in Japan compared with other developed countries. This study aimed to describe changes in dispensing of branded and generic drugs and to explore possible factors that promote the use of generic drugs. METHODS: We conducted a retrospective cohort study using a Japanese medical and pharmacy claims database. All proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) with indications for gastroesophageal reflux disease (GERD) described on Japanese labels were included. Patterns of dispensing branded and generic drugs for the treatment of GERD between 2006 and 2011 were analyzed. Multivariate logistic regression was applied to investigate factors associated with receiving generic drugs. RESULTS: The study cohort included 14,590 patients (male: 50.2%, mean age: 43.1 years). Branded drugs for GERD were still frequently dispensed despite an increase in the share of generic drugs. Only 4.3% of patients who initially received branded drugs switched to generic drugs. The percentage of patients who received only generic drugs increased over time (6.5% to 22.1%). The frequency of generic drug dispensing was the highest in the setting where both prescription and dispensing were implemented in clinics (43.3%), while the lowest in the setting where both prescription and dispensing were implemented in hospitals (11.5%). Factors associated with receiving generic drugs included year of dispensing (adjusted OR 2.22, 95% CI 1.94 to 2.55 for 2009-11 v 2006-8), prescription and dispensing setting (OR 1.81, 95% CI 1.44 to 2.26 for prescription in hospitals and dispensing in community pharmacies; OR 2.21, 95% CI 1.80 to 2.72 for prescription in clinics and dispensing in community pharmacies; and OR 4.55, 95% CI 3.68 to 5.62 for prescription and dispensing in clinics v prescription and dispensing in hospitals) and H2RAs (OR 1.64, 95% CI 1.49 to 1.81 compared to PPIs). CONCLUSIONS: The share of generic drugs for the treatment of GERD increased over time although branded drugs for GERD were still dispensed frequently. The use of generic drugs for GERD was influenced not only by government policies but also by changes in treatment approach and the setting of prescription and dispensing.

Public attitudes toward practice by medical students: a nationwide survey in Japan.

BACKGROUND: It is essential for medical students to interact directly with patients. However, patients may be reluctant to be seen by medical students in settings in which they may also be seen by senior staff. PURPOSES: To understand patients' attitudes toward practice by medical students and consider the factors involved in obtaining patients' cooperation, we conducted a nationwide cross-sectional survey. METHODS: We randomly selected 2,400 adult participants from all over Japan. Trained research assistants inquired about participants' experiences and attitudes toward practice by medical students using a questionnaire. We compared differences in attitudes between participants who were accepting of practice by medical students and those who were not, as well as differences between participants who had experienced practice by a medical student versus those who had not. RESULTS: A total of 1,109 (46%) participants were included in the study. Eleven percent (117/1109) of the participants had experienced practice by a medical student. One fourth of participants were accepting of practice by medical students, and experienced participants were significantly more likely to be accepting of practice by medical students than inexperienced participants (45% vs. 24%, p<.001). Impressions of practice by medical students among accepting participants with previous experiences included "polite," "kind," and "hard-working." Fifty-nine percent (637/1088) of participants indicated that they would request a senior staff member's supervision when being seen by a medical student. CONCLUSIONS: The present nationwide survey suggests that education emphasizing bedside manner may be effective in promoting patients' cooperation of medical students. In addition, providing information to patients about medical students and efforts to increase supervision during clinical clerkship should be emphasized to foster the public's cooperation.

Time dilation of a bound half-fluxon pair in a long Josephson junction with a ferromagnetic insulator.

The fluxon dynamics in a long Josephson junction with a ferromagnetic insulating layer is investigated. It is found that the Josephson phase obeys a double sine-Gordon equation involving a bound pi fluxon solution, and the internal oscillations of the bound pair acting as a clock exhibit Lorentz reductions in their frequencies regarded as a relativistic effect in the time domain, i.e., time dilation. This is the complement to the Lorentz contraction of fluxons with no clock. A possible observation scheme is also discussed.

Protective effect of crocin against blue light- and white light-mediated photoreceptor cell death in bovine and primate retinal primary cell culture.

PURPOSE: The present study was performed to investigate the effect of crocin on blue light- and white light-induced rod and cone death in primary retinal cell cultures. METHODS: Primary retinal cell cultures were prepared from primate and bovine retinas. Fifteen-day-old cultures were exposed to blue actinic light or to white fluorescent light for 24 hours. Cultures were treated by the addition of different concentrations of crocin for 24 hours before light exposure or for 8 hours after light exposure. Cultures kept in the dark were used as controls. Green nucleic acid stain assay was used to evaluate cell death. Rods and cones were immunolabeled with specific antibodies and counted. TUNEL labeling was used to detect fragmented DNA in fixed cells after light exposure. RESULTS: Primary retinal cell cultures contained a mixture of retinal cells enriched in photoreceptors, bipolar cells, and Müller cells. Twenty-four-hour exposure to blue and white light induced death in 70% to 80% of the photoreceptors in bovine and primate retinal cell cultures. Crocin protected the photoreceptors against blue light- or white light-mediated damage in a concentration-dependent manner with an EC50 of approximately 30 microM. TUNEL assays confirmed that crocin protected photoreceptors from light damage. CONCLUSIONS: These results show that blue and white light selectively induce rod and cone cell death in an in vitro model. Crocin protects retinal photoreceptors against light-induced cell death.