Selection of and Retention in Surgical Specialty during Early Career in Japan.

The number of surgeons is decreasing in Japan. We investigated the trend and factors influencing surgeons' selection of and retention in surgical specialty. In 2016, we obtained data of biennial surveys conducted by the government, and analyzed the annual data of doctors up to the latest available survey at that time (survey, 1994-2014; medical license acquisition, 1993-2014). The rate of selecting surgery by male and female doctors during early career (first three surveys after acquiring medical license) decreased from 28.1% in 1994 to 21.3% in 2010 (first to nineth survey). Female surgeons increased from 7.8% in 1993 to 12.4% in 2003, but decreased from 12.5% in 2006 to 10.7% in 2010. Total number of surgeons declined throughout the period. In females, the rate of selecting surgery tended to increase at the beginning of the new training system in 2004, but declined slightly thereafter. The retention rate in those who selected surgery at least once by the third survey (1998) after acquiring medical license in 1993 showed a downward trend. The retention rate in females declined continuously to 48.4% in 2002, stabilized thereafter, and then increased from 47.6% in 2006 to 50.8% in 2014. The retention rate after 10 years (1993-2003) was almost stable (72.4%) in males, but increased to 57.5% in females, and the gender difference tended to decrease. Younger doctors tend to value their private life, and may not choose or continue to practice surgery unless working conditions in surgery improve and income is commensurate with their work.

[Comparison of the Cost-Effectiveness of the SOX and COX Regimens in Patients with Unresectable Advanced and Recurrent Colorectal Cancer Using a Clinical Decision Analysis Approach].

Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

Apixaban for the Treatment of Japanese Subjects With Acute Venous Thromboembolism (AMPLIFY-J Study).

BACKGROUND: Anticoagulation is recommended as standard of care for venous thromboembolism (VTE) (pulmonary embolism [PE]/deep vein thrombosis [DVT]), for which unfractionated heparin (UFH) and warfarin are used in Japan. In the multi-regional AMPLIFY study, a fixed-dose regimen of apixaban alone was non-inferior to conventional therapy for treatment of PE/DVT and was associated with significantly fewer bleeding events. METHODS AND RESULTS: Japan phase 3 study (AMPLIFY-J), randomized, active-controlled, open-label study in Japanese subjects with acute PE/DVT, was designed based on AMPLIFY. Key objectives were to investigate safety and efficacy of apixaban in symptomatic PE/DVT subjects during 24-week treatment. UFH/warfarin was used as control treatment. Apixaban was initiated at 10 mg twice daily for 7 days, followed by 5 mg twice daily for 23 weeks. All endpoints and imaging for thrombotic burden were assessed by an event adjudication committee. Eighty subjects were randomized, 33 subjects (41.3%) were aged <65 years. Proportion of major/clinically relevant non-major bleeding was lower in apixaban (7.5%) compared with well-controlled UFH/warfarin (28.2%; median TTR, 70.4%). [corrected]. Recurrent VTE occurred in no subjects in apixaban and in 1 subject in UFH/warfarin. Thrombotic burden results were similar in both groups. Proportions of subjects with adverse events was generally similar in both groups. CONCLUSIONS: Apixaban was well-tolerated and had a favorable safety profile. No clinically important efficacy difference compared with UFH/warfarin was observed.

[Is Atrial Fibrillation a Pre-Thrombotic State?].

Atrial fibrillation (AF) is said to be a pre-thrombotic state. In patients with AF, the left atrium is usually dilated and blood flow is sluggish, which enables the formation of a thrombus within the left atrium. This is consistent with two of Virchow's Triad, stasis of blood flow and endothelial injury, but the last of the Triad, hypercoagulability of blood, is difficult to explain in AF. There are reports that von Willebrand Factor (vWF), FVIII, fibrinogen, D-dimer, and Fragment 1+2 are elevated in AF patients. The important thing in the daily clinical setting is to identify high-risk AF patients who are prone to stroke and treat them with oral anticoagulants. Over the last 15 years, two well known criteria to predict the risk have been proposed. The first one is called CHADS2 and the second one is the CHA2DS2-VASc score. The CHADS2 score is a clinical prediction rule for estimating the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). A high CHADS2 score corresponds to a greater risk of stroke, while a low CHADS2 score corresponds to a lower risk. The CHA2DS2-VASc score was proposed to complement the CHADS2 score by the inclusion of additional risk factors. These prediction rules are important because not all NVAF patients require oral anticoagulant therapy. There are disadvantages to taking oral anticoagulants, primarily bleeding complications. Therefore, even prediction rules of bleeding risks have been proposed to screen NVAF patients. In conclusion, it is difficult to predict a high-risk pre-thrombotic state among NVAF patients based only on laboratory findings. Practically, prediction rules will play a major role in the decision to start oral anticoagulant therapy.

[Clinical evaluation of lapatinib therapy in metastatic breast cancer using the Bayes meta-analysis].

The efficacy of treatments involving lapatinib for patients with metastatic breast cancers was evaluated in a Bayesian metaanalysis of published data from randomized controlled clinical trials. Four randomized controlled trials including 2,708 patients met the inclusion criteria. Among these patients, 568 were positive for the human epidermal growth factor receptor 2(HER2). The clinical benefit rate(CBR)for HER2-positive patients was the primary outcome of the analysis, and the overall survival(l OS) and the number needed to treat(NNT)were the secondary outcomes of the reported meta-analysis. The Bayesian metaanalysis was conducted according to the Markov-chain Monte-Carlo technique in WinBUGS. The CBR for HER2-positive patients was significantly improved(odds ratio[OR]: 2.281, 95% confidence interval[CI]: 1.490-3.628), whereas no statistically significant improvement was seen in the overall patient CBR(OR: 1.559, 95% CI: 0.768-3.238). The OS hazard ratio (HR)and NNT for the CBR were also estimated for HER2-positive patients. The difference in the OS HR was not statistically significant(HR: 0.789, 95% CI: 0.556-1.086)for HER2-positive patients. The improvement in the NNT for the CBR was statistically significant(NNT 5.164, 95% CI: 3.803-8.723)for HER2-positive patients.

[Study on medical economic evaluation methods for metastatic brain tumors therapy].

INTRODUCTION: Treatment design for metastatic brain tumors is required to firstly care about the life and function for which the patient hopes because it is terminal care. Therefore, to discuss the value of the therapy, a viewpoint of the QOL and the socioeconomic factors other than the survival rate is important. However, examination that applies these factors to the therapy needs to be carried out more thoroughly. With this in mind, we discuss cost effectiveness of therapy for metastatic brain tumor, through a pilot study on gamma knife therapy. MATERIALS AND METHOD: We studied 18 patients (mean age 61.6 years old) undergoing therapy for metastatic brain tumors. The health rate QOL was assessed by the profile-type measure SF-36 (Short-Form 36-Item Ver1.2) and the preference-based measure EQ-5D (EuroQoL-5D), before and six months after gamma knife therapy. Cost-utility-analysis (yen/Qaly) was carried out from quality adjusted life years (Qalys) and medical fee claims. In addition, we made a correlation analysis of the irradiation procedure and the gains attained. RESULTS: The observation by SF-36 for six months was useful for metastatic brain tumor. As a result, the QOL indicators showed increased mental health (MH: p=0.040) and role emotional (RE: p=0.029) with significant difference. In the measurement of EQ-5D, it was added only for one month based on the significant difference (p=0.022) from the pre-therapy QOL. The utilities that were analyzed became 0.052+/-0.175SD (score), and Qalys were 0.135. Because the cost was 721.4+/-5.2SD (thousand yen), the performance of cost-utility-analysis was estimated as 5, 330, 000 (yen/Qaly). In addition, positive correlation (r=0.845/p=0.034) was found between the EQ-5D utility score and the tumor irradiation energy (mJ), etc. CONCLUSION: We established a new value over and above mere survival rate concerning metastatic brain tumor therapy. The socioeconomics and efficacy of therapy are more difficult to discuss in this disease than in other diseases. We did this by clarifying the measurement and analysis of QOL as compared with the cost factor. We found that quantitatively, the mental health rate involved in the QOL, had improved. We established that it is appropriate to cover this disease by public insurance, because cost-utility-analysis showed that it was under the threshold line. Our study also suggested that, when guessing the QOL of the prognosis, there should be grades of sensitivity according to the irradiation element involved in the therapy.

Clinical characteristics of hospitalized heart failure patients with preserved, mid-range, and reduced ejection fractions in Japan.

AIMS: There are regional differences in the patient characteristics, management, and outcomes of hospitalized patients with heart failure (HF). The aim of this study was to evaluate the clinical characteristics and outcomes of Japanese patients who are hospitalized with HF on the basis of the left ventricular ejection fraction (LVEF) stratum. METHODS AND RESULTS: We retrospectively conducted a multicentre cohort study of 1245 hospitalized patients with decompensated HF between 2013 and 2014. Of these patients, 36% had an LVEF < 40% [HF with reduced ejection fraction (HFrEF), median age 72 years, 71% male], 21% had an LVEF 40-49% [HF with mid-range EF (HFmrEF), 77 years, 56% male], and 43% had an LVEF ≥ 50% [HF with preserved EF (HFpEF), 81 years, 44% male]. The primary outcome was death from any cause, and the secondary outcomes were cardiac death and re-hospitalization due to worsened HF after hospital discharge. There were high proportions of non-ischaemic cardiomyopathy (32%) in HFrEF patients, coronary artery disease (44%) in HFmrEF patients, and valvular disease (39%) in HFpEF patients. The frequencies of intravenous diuretic and natriuretic peptide administration during hospitalization were 66% and 30%, respectively. The median hospital stay for the overall population was 19 days, and the length of stay was >7 days for >90% of patients. In-hospital mortality was 7%, but was not different among the LVEF groups (HFrEF 7%, HFmrEF 6%, and HFpEF 8%). After a median follow-up of 19 months (range, 3-26 months), 192 (17%) of the 1156 patients who were discharged alive died, and 534 (46%) were re-hospitalized after hospital discharge. There were no significant differences in mortality after hospital discharge among the three LVEF groups (HFrEF 18%, HFmrEF 16%, and HFpEF 16%). There were no differences in cardiac death or re-hospitalization due to worsened HF after hospital discharge among the LVEF groups (cardiac death: HFrEF 8%, HFmrEF 7%, and HFpEF 7%; re-hospitalization due to worsened HF: HFrEF 19%, HFmrEF 16%, and HFpEF 17%). Multivariable-adjusted analyses showed that the HFmrEF and HFrEF groups, compared with the HFpEF group, were not associated with an increased risk for in-hospital death or death after hospital discharge. Non-cardiac causes of death and re-hospitalization after hospital discharge accounted for 35% and 38%, respectively. CONCLUSIONS: Our results revealed different clinical characteristics but similar mortality rates in the HFrEF, HFmrEF, and HFpEF groups. The most common cause of death and re-hospitalization after hospital discharge was HF, but non-cardiac causes also contributed to their prognosis. Integrated management approaches will be required for HF patients.

Pharmacoeconomics of antiviral therapy for influenza in a Japanese hospital setting.

OBJECTIVES: We constructed a cost-effectiveness decision model to determine a hypothetical 'best treatment' pathway for patients presenting at our institution with influenza virus infection when the choice of treatment was either oseltamivir, zanamivir or a control therapy not active against influenza. METHODS: The decision model was constructed using DATA 3.5 for evaluating the cost-effectiveness analysis of neuraminidase inhibitors from the perspective of the healthcare payer. The time horizon was set at 14 days based on the general duration of influenza infection in Japan. Clinical outcomes were mainly derived from reports and guidance published by the National Institute for Clinical Excellence in the UK. Japan-specific cost parameters incorporated into the decision model were taken from the Medical Fee Point Survey conducted at St Luke's International Hospital in accordance with medical fee receipts kept at our institution. The study included four professionals and a supporter who gathered information required for the analysis. RESULTS: In otherwise healthy adults, cost savings of yen831.6 (approximately $US6.72; 2002 values) in the oseltamivir group and an increment in cost of yen40.5 (approximately $US0.33) in the zanamivir group were achieved in comparison with the control group. In contrast, an incremental cost of yen288.4 (approximately $US2.33) was incurred in the oseltamivir group versus the control group when at-risk patients were assessed, but cost savings of yen159.8 (approximately $US1.29) were achieved in the zanamivir group. As a result of cost-effectiveness and cost-utility analyses in otherwise healthy adults, oseltamivir dominated the control therapy because cost savings in the oseltamivir group were made. In the zanamivir group the cost was incremental and the Incremental Cost-Utility Ratio (ICUR) compared with the control group was about yen13 000 (approximately $US107.34)/quality-adjusted life-year (QALY) gained. As a result of cost-effectiveness and cost-utility analyses in at-risk patients, in the oseltamivir group the cost was incremental and the ICUR compared with the control group was about yen230 000 (approximately $US2138.77)/QALY gained. As cost savings were made, zanamivir dominated the control therapy. CONCLUSION: While the cost effectiveness (from the perspective of a healthcare payer) of the neuraminidase inhibitors was superior to that of the control group in the treatment of otherwise healthy adults with influenza in our study, it seemed necessary to take other factors into consideration before recommending one agent over the other as a first-line therapy. On the other hand, we suggest that zanamivir is the drug of choice for use in at-risk patients, and we recommend, in the light of our results, that if zanamivir is not available another therapy should be given rather than oseltamivir. Since with influenza infections deaths and hospitalisations of at-risk patients impact on the Japanese community, decision-making on the appropriate therapy should take into account the particular patient group involved.

[Introduction patient analysis from the medical institution in Shinjuku].

The number of introduction patients from July 22, 2003 to the end of December was 10,329 persons. The introduction from the medical institution in Shinjuku was 2,175 persons (21.1%). We investigated 2,175 persons for man and woman, age, the department of medical examination, the address ground, etc. Shinjuku-ku is special area; there is much population of daytime. We analyzed the present condition and analyzed needs this time.

Pharmacoeconomic analysis of cilostazol for the secondary prevention of cerebral infarction.

BACKGROUND: The antiplatelet agent, cilostazol, is known to reduce the risk of subsequent cerebral infarction. However, the cost effectiveness of such treatment in comparison to aspirin has not been studied. METHODS AND RESULTS: A Markov model was developed to calculate the health outcomes and associated costs for 65-year-old patients with cerebral infarction who were treated with 200 mg/day cilostazol or 81 mg/day aspirin. Cilostazol was more effective, but also more expensive than aspirin. Cilostazol would extend quality-adjusted life years (QALY) by 0.64, while increasing life-time costs by approximately Yen 1.1 million. The incremental cost-effectiveness ratio of cilostazol in comparison with aspirin was estimated to be Yen 1.8 million per QALY. CONCLUSIONS: The use of cilostazol to prevent recurrence of cerebral infarction appears to be cost effective.

Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy.

Phospholamban is an endogenous inhibitor of sarcoplasmic reticulum calcium ATPase and plays a prime role in cardiac contractility and relaxation. Phospholamban may be a candidate gene responsible for cardiomyopathy. We investigated genome sequence of phospholamban in patients with cardiomyopathy. PCR-based direct sequence was performed for the promoter region and the whole coding region of phospholamban in 87 hypertrophic, 10 dilated, and 2 restricted cardiomyopathic patients. We found a heterozygous single nucleotide transition from A to G at -77-bp upstream of the transcription start site in the phospholamban promoter region of one patient with familial hypertrophic cardiomyopathy. This nucleotide change was not found in 296 control subjects. Using neonatal rat cardiomyocytes, the mutation, -77A-->G, increased the phospholamban promoter activity. No nucleotide change in the phospholamban coding region was found in 99 patients with cardiomyopathy. We suspect that the mutation plays an important role in the development of hypertrophic cardiomyopathy.