Cost-Effectiveness Analysis of Neoadjuvant Chemotherapy with Zoledronic Acid for HER2-Negative Breast Cancer in Japan: The JONIE1 Study

Objective: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption. Adding ZOL to neoadjuvant chemotherapy has been shown to have potential anticancer benefits in women with HER2-negative breast cancer. The objective of the present study was to investigate ZOL’s cost-effectiveness from the perspective of health care payers in Japan. Methods: A Markov model was developed to evaluate the costs and effectiveness associated with ZOL + chemotherapy (CTZ) and chemotherapy (CT) alone over a 10-year time horizon. Monthly transition probabilities were estimated according to JONIE1 (Japan Organization of Neoadjuvant Innovative Expert) Study data and an extrapolated Weibull model. Health outcomes were measured in quality-adjusted life years (QALYs). Costs were calculated using year-2018 Japanese yen (JPY) (1.00 US dollars (USD) = 110.4 JPY). Model robustness was addressed through one-way and probabilistic sensitivity analysis. The costs and QALYs were discounted at a rate of 2% per year. Results: In the base case, the use of CTZ was associated with a gain of 3.94 QALYs. The incremental cost per QALY of the CTZ gain was 681,056.1 JPY (6168.99 USD) per QALY. Conclusion: It is convincing that neoadjuvant CTZ for patients with breast cancer would be expected to have statistically significant clinical efficacy. Addition of ZOL to CT might be a cost-effective option compared with CT alone.

Factors predicting aggressiveness of non-hypervascular hepatic nodules detected on hepatobiliary phase of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging

AIM: To establish a prognostic formula that distinguishes non-hypervascular hepatic nodules(NHNs) with higher aggressiveness from less hazardous one. METHODS: Seventy-three NHNs were detected in gadolinium ethoxybenzyl diethylene-triamine-pentaaceticacid magnetic resonance imaging(Gd-EOB-DTPA-MRI) study and confirmed to change 2 mm or more in size and/or to gain hypervascularity. All images were interpreted independently by an experienced, board-certified abdominal radiologist and hepatologist; both knew thatthe patients were at risk for hepatocellular carcinoma development but were blinded to the clinical information. A formula predicting NHN destiny was developed using a generalized estimating equation model with thirteen explanatory variables: age, gender, background liver diseases, Child-Pugh class, NHN diameter, T1-weighted imaging/T2-weighted imaging detectability, fat deposition, lower signal intensity in arterial phase, lower signal intensity in equilibrium phase, α-fetoprotein, des-γ-carboxy prothrombin, α-fetoprotein-L3, and coexistence of classical hepatocellular carcinoma. The accuracy of the formula was validated in bootstrap samples that were created by resampling of 1000 iterations. RESULTS: During a median follow-up period of 504 d, 73 NHNs with a median diameter of 9 mm(interquartile range: 8-12 mm) grew or shrank by 68.5%(fifty nodules) or 20.5%(fifteen nodules), respectively, whereas hypervascularity developed in 38.4%(twenty eight nodules). In the fifteen shrank nodules, twelve nodules disappeared, while 11.0%(eight nodules) were stable in size but acquired vascularity. A generalized estimating equation analysis selected five explanatories from the thirteen variables as significant factors to predict NHN progression. The estimated regression coefficients were 0.36 for age, 6.51 for lower signal intensity in arterial phase, 8.70 or 6.03 for positivity of hepatitis B virus or hepatitis C virus, 9.37 for des-γ-carboxy prothrombin, and-4.05 for fat deposition. A formula incorporating the five coefficients revealed sensitivity, specificity, and accuracy of 88.0%, 86.7%, and 87.7% in the formulating cohort, whereas these of 87.2% ± 5.7%, 83.8% ± 13.6%, and 87.3% ± 4.5% in the bootstrap samples. CONCLUSION: These data suggest that the formula helps Gd-EOB-DTPA-MRI detect a trend toward hepatocyte transformation by predicting NHN destiny.

A Questionnaire Survey in Kidney Transplant Outpatients: Factors Associated with Good Self-Management

It is very important for outpatients who have had a kidney transplant to take care of themselves after discharge. However, outpatients have limited access to medical care by hospital staff after discharge;therefore, medical staff are unaware of the patient’s living conditions, and the uncertainties and problems that they encounter related to self-management. We conducted a questionnaire survey among 161 of 200 outpatients who received kidney transplants to investigate their recognition and actual practice of daily self-management. To determine the characteristics of adherent outpatients, we divided patients into two groups (the adherent and non-adherent group) and compared them. The Chi-squared test was conducted to test the equality of proportions among the groups, and then multiple logistic regression analysis was used to explore the factors significantly associated with regularly taking medicine or failing to take medicine. As a result of the logistic regression model using demographic factors as independent factors, the periods after transplantation (2 - 5 and 5 - 10 years) and living-donor kidney transplantation or cadaveric kidney transplantation were selected as significant factors associated with good self-management. As a whole, 68.3% of the 145 patients were correctly predicted using the model. The results of this study suggest that in the short period after transplantation (2 - 5 years), cadaveric kidney transplantation and that the patient has a job are significant factors associated with good self-management. Behind these results, a unique Japanese concept, “amae”, could be found. Therefore, medical knowledge and techniques as well as cultural background should be studied.

Analysis of Hospital Characteristics Affecting the Choice of Management Strategy Types: A Cross-Sectional Survey of Private Hospitals in Japan

The hospital environment in Japan has changed drastically lately. Its unpredictability has increased the need for hospitals to select management strategies to clarify their course. However, research on Japanese hospitals’ management strategies has only recently begun with too few studies in this area. Hence, this study clarifies the management strategies of Japanese private hospitals. It explores the hospital characteristics that affect strategy selection. A questionnaire was mailed to 5682 private medical institutions in 2013, and 459 responses with no missing data were used for analysis. Factor analysis yielded four factors: “bed conversion and downsizing (Factor 1),” “diversification of medical and nursing care (Factor 2),” “expansion in business scale (Factor 3),” and “expansion of income from non-insured medical care (Factor 4)”. Logistic regression analysis revealed that Year Founded (before 1965), Hospital Location (municipalities with populations smaller than 100,000), Hospital Type (psychiatric hospitals and mixed-care hospital), and Hospital Income and Expenditure (deficit) had significant positive impacts on the choice of Factor 1. For Factor 2, Hospital Type (sanatorium ward and mixed-care hospitals) and Hospital Income and Expenditure (constant surplus) had positive impacts. For Factor 3, Hospital Type (general hospital) and Bed Counts (more than 200) had positive impacts. For Factor4, Hospital Type (general hospital) had positive impacts. In other words, older hospitals, hospitals in rural areas, psychiatric hospitals, mixed-care hospitals, and hospitals with deficits tended to choose bed conversion and downsizing. Sanatorium ward hospitals, mixed-care hospitals, and hospitals with a constant surplus tended to choose diversification of medical and nursing care. General hospitals and large hospitals tended to choose expansion in scale, and general hospitals tended to choose expansion into non-insured medical care. The planning of mid- to long-term management strategies suitable for each hospital and their steady execution are required.

Association of social distance toward schizophrenia with help-seeking among mothers of adolescents in Japan

Negative maternal attitudes toward schizophrenia may be linked with delayed treatment of their children. We investigated the relation between negative attitudes toward schizophrenia and help-seeking among mothers of junior and senior high school students in Japan. The participants were 1309 Japanese mothers of junior and senior high school students. Social distance was evaluated by using the Social Distance Scale-Japanese version (SDS-J). In addition, mothers were asked about help-seeking for a child with sleeplessness, social withdrawal, and strange behavior. One-way analysis of variance and Student’s t-test were used to evaluate associations between social distance toward schizophrenia and help-seeking. Most (76.4%) participants were aged 40 - 49 years. Maternal demographic characteristics significantly associated with social distance were employment and participation in welfare activities for people with mental illness. In responding to a child with sleeplessness, social withdrawal, and strange behavior, the level of maternal social distance was not significantly associated with the likelyhood of seeking psychiatric help. However, mothers with greater social distance were less likely to seek help at a psychiatric clinic. Maternal social distance toward schizophrenia was not significantly associated with seeking psychiatric help;however, it did affect the type of facility selected among those would seek such help.

Social distance toward schizophrenia among parents of adolescents

Social distance toward schizophrenia is a reason for delays in receiving early treatment for the disorder. This study attempted to identify the factors underlying social distance. The participants were 2690 parents of adolescents. Factor analysis using a social distance scale identified two factors: private relationship and social relationship. Regression analysis revealed that gender, age, and participation in welfare activities for people with mental illnesses had independent effects on the factor private relationship (p < 0.05). These results suggest that women aged 40 - 49 years should be targeted for activities that attempt to counteract social distance and that they would benefit from taking part in public welfare activities for individuals with mental illnesses.

Schizophrenia knowledge and attitudes toward help-seeking among Japanese fathers and mothers of high school students

The prodromal symptoms of schizophrenia are nonspecific and include social withdrawal, sleeplessness, decreased desire, and loss of concentration. Schizophrenia outcomes might be improved if greater therapeutic effort was focused on people with prodromal symptoms. To hasten help-seeking for schizophrenia, we developed a schizophrenia education program for families of patients. Help-seeking and schizophrenia attitudes and knowledge were analyzed among Japanese parents (666 fathers and 613 mothers) of high school students by using the Social Distance Scale-Japanese version, the Link Devaluation-Discrimination Measure and our own questions on help-seeking and schizophrenia knowledge. Statistical analysis included cross-tabulation, the χ2 test, and multiple regression analysis. Most (97.5%) fathers were aged 40 - 59 years;most (78.3%) mothers were aged 40 - 49 years. There was a significant difference between fathers and mothers in basic knowledge of schizophrenia (P < 0.001);however, fathers and mothers did not significantly differ in their attitudes toward schizophrenia (P > 0.05). When asked what treatment they would seek for a child with sleeplessness or social withdrawal, fathers and mothers significantly differed in seeking help medical care at a department of psychosomatic medicine (P < 0.05) and in seeking help from the nurse at their child’s school (P < 0.001). Fathers and mothers also differed in relation to the decision not to seek help (P < 0.001). Multiple regression analysis revealed that basic knowledge significantly differed between fathers and mothers (P = 0.001). In an analysis of parental response to a child with sleepiness and social withdrawal, multiple regression analysis revealed that fathers and mothers significantly differed in the likelihood of seeking help at a department of psychosomatic medicine and from a school nurse and in the likelihood of not seeking help (P < 0.05, P = 0.001 and P = 0.001, respectively). In conclusion, help-seeking behavior differed between Japanese fathers and mothers. These findings should assist in developing schizophrenia education programs that aim to hasten intervention.