研究者業績
基本情報
- 所属
- 藤田医科大学 橋渡し研究シーズ探索センター 准教授
- 学位
- 社会健康医学 修士(2002年3月 京都大学)
- J-GLOBAL ID
- 201801012345530637
- researchmap会員ID
- B000306689
研究キーワード
2論文
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Respiratory investigation 62(2) 277-283 2024年3月BACKGROUND: Secondary pneumothorax, which occurs most commonly in the elderly, is caused by underlying diseases. Cardiac dysfunction and other organ inefficiencies may render surgical repair impossible. Such non-operative and poor-risk cases are targets for pleurodesis, which involves the instillation of chemicals or irritants to the thoracic cavity through injection, bronchoscopic bronchial occlusion, or other procedures. Sterile graded talc has been used for pleurodesis mainly in Europe and the United States; however, only a few studies and case series investigating this topic have been published. This study evaluates the efficacy and safety of talc slurry pleurodesis. METHODS: Patients with inoperable secondary intractable pneumothorax, who were not candidates for surgical repair, were recruited. Four grams of sterilized talc was suspended in 50 mL of physiological saline and injected through a tube into the pleural cavity. Additional 50 mL of saline was subsequently injected through the same channel to clean the residual saline in the injection tube. Another additional talc instillation was allowed to control persistent air leakage. The primary endpoint was the proportion of drainage tube removal within 30 days after talc pleurodesis. RESULTS: Thirty-one patients were included in this study. In 23 out of 28 patients, the drainage tube could be removed within 30 days of talc instillation (82.1 %, 95 % CI = 63.1-93.9), exceeding the threshold of 36.0 % (p < 0.0001). The most common event was pain (11/28 patients, 39.3 %). CONCLUSIONS: Talc slurry pleurodesis is effective for intractable secondary pneumothorax, with minor side effects.
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European journal of haematology 2023年12月19日BACKGROUND: The benefit of adding rituximab to standard lymphomes malins B (LMB) chemotherapy for children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL) has previously been demonstrated in an international randomized phase III trial, to which the Japanese Pediatric Leukemia/Lymphoma Study Group could not participate. METHODS: To evaluate the efficacy and safety of rituximab in combination with LMB chemotherapy in Japanese patients, we conducted a single-arm multicenter trial. RESULTS: In this study, 45 patients were enrolled between April 2016 and September 2018. A total of 33 (73.3%), 5 (11.1%), and 6 (13.3%) patients had Burkitt lymphoma/leukemia, diffuse large B-cell lymphoma, and aggressive mature B-NHL, not otherwise specified, respectively. Ten (22.2%) and 21 (46.7%) patients had central nervous system disease and leukemic disease, respectively. The median follow-up period was 47.5 months. Three-year event-free survival and overall survival were 97.7% (95% confidence interval, 84.9-99.7) and 100%, respectively. The only event was relapse, which occurred in a patient with diffuse large B-cell lymphoma. Seven patients (15.6%) developed Grade 4 or higher non-hematologic adverse events. Febrile neutropenia was the most frequent Grade 3 or higher adverse event after the pre-phase treatment, with a frequency of 54.5%. CONCLUSION: The efficacy and safety of rituximab in combination with LMB chemotherapy in children with high-risk mature B-NHL was observed in Japan.
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JTO clinical and research reports 4(6) 100514-100514 2023年6月INTRODUCTION: In the CAPITAL study, a randomized phase 3 study, wherein carboplatin plus nab-paclitaxel treatment was compared with docetaxel treatment for older patients with squamous-cell lung cancer, the former became the new standard of care for such patients. Our study aimed to evaluate whether the efficacy of second-line immune checkpoint inhibitors (ICIs) affected the primary analysis of overall survival (OS). METHODS: Herein, we performed a post hoc analysis of the impact of second-line ICIs on OS, safety in each group of participants aged more than 75 years, and intracycle nab-paclitaxel skip status. RESULTS: Patients were randomly allocated to the carboplatin plus nab-paclitaxel (nab-PC) arm (n = 95) or the docetaxel (D) arm (n = 95). Of these patients, 74 of 190 (38.9%) were transferred to ICIs for second-line treatment (nab-PC arm: 36, D arm: 38). A survival benefit was numerically observed only for patients for whom first-line therapy was terminated owing to disease progression (median OS [nab-PC arm]: with and without ICIs, 321 and 142 d, respectively; median OS [D arm]: with and without ICIs, 311 and 256 d, respectively). The OS among patients who received ICI after adverse events was similar in the two arms. In the D arm, a significantly higher frequency of grade greater than or equal to 3 adverse events was observed among patients aged more than or equal to 75 years (86.2%) than among those aged less than 75 years (65.6%, p = 0.041), including a significantly higher frequency of neutropenia (84.6% versus 62.5%, p = 0.032); no such differences were observed in the nab-PC arm. CONCLUSIONS: We found that second-line ICI treatment seemed to have a little impact on OS.
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BMJ Open 13(4) e068642-e068642 2023年4月10日Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan. Design Retrospective study. Setting Six hundred and thirty-one primary care institutions in Japan. Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database. Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points). Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality. Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.
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Scientific Reports 12(1) 2022年12月<title>Abstract</title>To determine whether increasing thrombectomy-capable hospitals with moderate comprehensive stroke center (CSC) capabilities is a valid alternative to centralization of those with high CSC capabilities. This retrospective, nationwide, observational study used data from the J-ASPECT database linked to national emergency medical service (EMS) records, captured during 2013–2016. We compared the influence of mechanical thrombectomy (MT) use, the CSC score, and the total EMS response time on the modified Rankin Scale score at discharge among patients with acute ischemic stroke transported by ambulance, in phases I (2013–2014, 1461 patients) and II (2015–2016, 3259 patients). We used ordinal logistic regression analyses to analyze outcomes. From phase I to II, MTs increased from 2.7 to 5.5%, and full-time endovascular physicians per hospital decreased. The CSC score and EMS response time remained unchanged. In phase I, higher CSC scores were associated with better outcomes (1-point increase, odds ratio [95% confidence interval]: 0.951 [0.915–0.989]) and longer EMS response time was associated with worse outcomes (1-min increase, 1.007 [1.001–1.013]). In phase II, neither influenced the outcomes. During the transitional shortage of thrombectomy-capable hospitals, increasing hospitals with moderate CSC scores may increase nationwide access to MT, improving outcomes.
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Pediatric Blood & Cancer 2022年4月11日
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DEN open 2(1) e102 2022年4月OBJECTIVES: This study aimed to evaluate the efficacy and safety of apixaban replacement (AR) as an alternative to heparin bridging (HB) in patients taking warfarin and scheduled for endoscopic mucosal resection (EMR) in the colorectum. METHODS: This trial was conducted at seven institutes in Japan between May 2016 and May 2018. Enrolled patients had been taking oral warfarin and were diagnosed within 3 months with colorectal polyps for which EMR was indicated. Patients were randomly assigned to receive HB or AR. The primary endpoint was the incidence of postoperative bleeding. Secondary endpoints were the length of hospital stay, therapeutic endoscopy outcomes, and adverse events. RESULTS: The planned sample size was 160 patients, but due to a decrease in the number of patients taking warfarin, the target number of cases could not be achieved within the case enrollment period, 44 cases were enrolled. They were divided into HB and AR groups. The incidence of postoperative bleeding was 15% (3/20) in HB and 0% in AR (P = 0.199). The total number of postoperative bleeding events was five in HB and none in AR. The length of hospital stay was significantly shorter in AR than in HB (median: 3.0 vs. 13.5 days, p < 0.001). There were no serious adverse events and no cerebral infarction/systemic embolism events. CONCLUSION: AR for colorectal EMR may prove safe and has the potential to shorten hospital stay and reduce medical costs, though we were unable to evaluate the primary endpoint due to insufficient sample size.
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NAGOYA JOURNAL OF MEDICAL SCIENCE 84(1) 80-90 2022年2月More than 40% of Japanese patients with multiple myeloma (MM) are over 75 years of age at diagnosis. Regardless of the treatment benefits, complications and relapses obstruct long-term survival. We conducted a phase II, open-label, single-arm, multicenter clinical trial to assess the efficacy and safety of alternating bortezomib-dexamethasone (Bd) and lenalidomide-dexamethasone (Ld) (Bd/Ld) treatment in MM patients aged over 75 years (MARBLE trial). Patients received Bd therapy from days 1 to 35 and IA therapy from days 36 to 63. For Bd therapy, patients were administered bortezomib 1.3 mg/m(2) and oral dexamethasone 20 mg on days 1, 8, 15, and 22. For Ld therapy, they were administered lenalidomide 15 mg from days 36 to 56 and dexamethasone 10 mg on days 36, 43, 50, and 57. They underwent six treatment cycles in total, each consisting of a 63-day regimen. In total, 10 patients were enrolled, with a median age of 81 years. Efficacy was not evaluated because the patients were fewer than planned. The overall response rate was 80.0% and complete response rate 40.0%. Seventy percent of patients completed the study treatment. Progression-free survival and overall survival at 2 years were 40.0% and 80.0%, respectively. Adverse events of grade 3 or higher, including anemia, decreased lymphocyte count, neutropenia, and hypokalemia, were observed in eight patients. Alternating chemotherapy with Bd/Ld might he feasible, but its efficacy should be verified further.
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Epileptic disorders : international epilepsy journal with videotape 24(1) 82-94 2022年2月1日 査読有りOBJECTIVE: To examine the current medical and psychosocial status of patients with epilepsy, aiming to facilitate appropriate application of the Intractable/Rare Diseases Act of Japan. METHODS: By analysing the cross-sectional data of patients registered in the tertiary hospital-based Epilepsy Syndrome Registry of Japan, we investigated the proportion of patients who met the severity criteria as defined by the Act (seizure frequency of at least once a month, or presence of intellectual/neurological/psychiatric symptoms, or both) and whether there are candidate syndrome/diseases to be added to the existing list in the Act. RESULTS: In total, 2,209 patients were registered. After excluding self-limited/idiopathic epilepsies, 1,851 of 2,110 patients (87.7%) met the severity criteria. The patients were classified into eight main epilepsy syndromes (594 patients), 20 groups based on aetiology (1,078 patients), and three groups without known aetiology (427 patients). Most of the groups classified by syndrome or aetiology had high proportions of patients satisfying the severity criteria (>90%), but some groups had relatively low proportions (<80%) resulting from favourable outcome of surgical therapy. Several small groups with known syndrome/aetiology await detailed analysis based on a sufficiently large enough number of patients registered, some of whom may potentially be added to the list of the Act. SIGNIFICANCE: The registry provides data to examine the usefulness of the severity criteria and list of diseases that are operationally defined by the Act. Most epilepsy patients with various syndromes/diseases and aetiology groups are covered by the Act but some are not, and the list of designated syndromes/diseases should be complemented by further amendments, as suggested by future research.
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Annals of clinical and translational neurology 9(2) 181-192 2022年2月OBJECTIVE: To determine whether sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, reduces epileptic seizures associated with focal cortical dysplasia (FCD) type II. METHODS: Sixteen patients (aged 6-57 years) with FCD type II received sirolimus at an initial dose of 1 or 2 mg/day based on body weight (FCDS-01). In 15 patients, the dose was adjusted to achieve target trough ranges of 5-15 ng/mL, followed by a 12-week maintenance therapy period. The primary endpoint was a lower focal seizure frequency during the maintenance therapy period. Further, we also conducted a prospective cohort study (RES-FCD) in which 60 patients with FCD type II were included as an external control group. RESULTS: The focal seizure frequency reduced by 25% in all patients during the maintenance therapy period and by a median value of 17%, 28%, and 23% during the 1-4-, 5-8-, and 9-12-week periods. The response rate was 33%. The focal seizure frequency in the external control group reduced by 0.5%. However, the background characteristics of external and sirolimus-treated groups differed. Adverse events were consistent with those of mTOR inhibitors reported previously. The blood KL-6 level was elevated over time. INTERPRETATION: The reduction of focal seizures did not meet the predetermined level of statistical significance. The safety profile of the drug was tolerable. The potential for a reduction of focal seizures over time merit further investigations.
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The Lancet Healthy Longevity 2(12) e791-e800 2021年12月
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Genes 12(10) 2021年9月28日 査読有りThe genotypes of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) can influence therapeutic warfarin doses. Conversely, nongenetic factors, especially renal function, are associated with warfarin maintenance doses; however, the optimal algorithm for considering genes and renal dysfunction has not been established. This single-center prospective cohort study aimed to evaluate the factors affecting warfarin maintenance doses and develop pharmacogenetics-guided algorithms, including the factors of renal impairment and others. To commence, 176 outpatients who were prescribed warfarin for thromboembolic stroke prophylaxis in the stroke center, were enrolled. Patient characteristics, blood test results, dietary vitamin K intake, and CYP2C9 and VKORC1 (-1639G>A) genotypes were recorded. CYP2C9 and VKORC1 (-1639G>A) genotyping revealed that 80% of the patients had CYP2C9 *1/*1 and VKORC1 mutant AA genotypes. Multiple linear regression analysis demonstrated that the optimal pharmacogenetics-based model comprised age, body surface area, estimated glomerular filtration rate (eGFR), genotypes, vitamin K intake, aspartate aminotransferase levels, and alcohol intake. eGFR exercised a significant impact on the maintenance doses, as an increase in eGFR of 10 mL/min/1.73 m2 escalated the warfarin maintenance dose by 0.6 mg. Reduced eGFR was related to lower warfarin maintenance doses, independent of VKORC1 and CYP2C9 genotypes in Japanese patients.
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Pharmaceutical Statistics 2021年9月21日
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Pharmaceutical statistics 21(2) 309-316 2021年9月21日Restricted mean survival time (RMST) is one measure now used to summarize time-to-event type data, but it has been pointed out that the distribution of differences in RMST deviates markedly from a normal distribution for controlled clinical trials with small sample sizes. Therefore, we conducted a numerical simulation of the RMST in which the one-sample survival time follows a Weibull distribution, comparing eight different confidence intervals combining two types of variance with four types of variable transformations, including no transformation. The evaluation items were the coverage probability and the above and below error probabilities for the true value. The variance types were based on Greenwood's formula and its Kaplan-Meier correction. The arcsine square root transformation, logit transformation, and complementary log-log transformation were used as the variable transformations. When the sample size was small and the event rate was low, the confidence interval of the untransformed RMST tended to have a small coverage probability and to be overestimated. Variance by Kaplan-Meier correction improved the coverage. The problems of coverage and overestimation were also improved by variable transformations, and in particular, applying the logit transformation and the complementary log-log transformation both resulted in substantial improvements. Our study suggested that it is preferable to construct the confidence intervals of RMST using the logit transformation for variances based on Greenwood's formula in small sample size trials. The SAS code to replicate the analyses is available at https://github.com/HiroyaHashimoto/SAS-Programs.
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Annals of Oncology 32 S1020-S1021 2021年9月
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Infectious diseases and therapy 10(4) 2353-2369 2021年8月8日INTRODUCTION: The administration of systemic corticosteroids is a key strategy for improving COVID-19 outcomes. However, evidence is lacking on combination therapies of antiviral agents and systemic corticosteroids. The objective of this study was to investigate the efficacy and safety of the combination therapy of favipiravir and methylprednisolone in preventing respiratory failure progression in patients with COVID-19 and non-critical respiratory failure. METHODS: We conducted a multicenter, open-label, single-arm phase II study. The patients received favipiravir 3600 mg on the first day, followed by 1600 mg for a total of 10-14 days. Methylprednisolone was administered intravenously at 1 mg/ideal body weight (IBW)/day from days 1 to 5, followed by 0.5 mg/IBW/day from days 6 to 10 if clinically indicated. The primary endpoint was the proportion of patients requiring mechanical ventilation (MV) (including noninvasive positive pressure ventilation) or those who met the criteria for tracheal intubation within 14 days of the study treatment initiation (MVCTI-14). RESULTS: Sixty-nine patients were enrolled and underwent the study treatment. Of them, the MVCTI-14 proportion was 29.2% (90% confidence interval 20.1-39.9, p = 0.200). The proportion of patients who required MV or who died within 30 days was 26.2%, and 30-day mortality was 4.9%. The most significant risk factor for MVCTI-14 was a smoking history (odds ratio 4.1, 95% confidence interval 1.2-14.2). The most common grade 3-4 treatment-related adverse event was hyperglycemia, which was observed in 21.7%. CONCLUSION: The MVCTI-14 proportion did not reach a favorable level in the clinical trial setting with the threshold of 35%. However, the proportion of MV or death within 30 days was 26.6%, which might be close to the findings (28.1%) of the RECOVERY trial, which showed the efficacy of dexamethasone for patients with COVID-19 and non-critical respiratory failure. Further evaluation of this combination therapy is needed. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier jRCTs041200025.
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Epileptic disorders : international epilepsy journal with videotape 23(4) 579-589 2021年8月1日 査読有りOBJECTIVE: To unveil current medical and psychosocial conditions of patients with West syndrome in Japan. METHODS: A cross-sectional analysis was performed in patients with West syndrome registered in the Rare Epilepsy Syndrome Registry (RES-R) of Japan. Furthermore, new-onset patients registered in the RES-R were observed prospectively and their outcomes after one and two years of follow-up were compared with data at onset. RESULTS: For the cross-sectional study, 303 patients with West syndrome were included. Seizures (such as spasms, tonic seizures and focal seizures) occurred daily in 69.3% of the patients at registration. Seizure frequency of less than one per year was observed in cases of unknown etiology (22.6%), genetic etiology (23.8%) and malformation of cortical development (MCD; 19.1%). Neurological findings were absent in 37.0%, but a high rate of abnormality was seen in patients with Aicardi syndrome, hypoxic-ischemic encephalopathy (HIE), genetic etiology and MCD other than focal cortical dysplasia, accompanied by a >50% rate of bedridden patients. Abnormal EEG was found in 96.7%, and CT/MRI was abnormal in 62.7%. Treatments included antiepileptic drug therapy (94.3%), hormonal therapy (72.6%), diet therapy (8.3%) and surgery (15.8%). Intellectual/developmental delay was present in 88.4%, and was more severe in patients with Aicardi syndrome, genetic etiology and HIE. Autism spectrum disorder was found in 13.5%. For the longitudinal study, 27 new-onset West syndrome patients were included. The follow-up study revealed improved seizure status after two years in 66.7%, but worsened developmental status in 55.6%, with overall improvement in 51.9%. SIGNIFICANCE: The study reveals the challenging neurological, physical and developmental aspects, as well as intractable seizures, in patients with West syndrome. More than a half of the children showed developmental delay after onset, even though seizures were reduced during the course of the disease.
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The Kurume medical journal 66(2) 115-120 2021年7月21日Epileptic seizures are core symptoms in focal cortical dysplasia (FCD), a disease that often develops in infancy. Such seizures are refractory to conventional antiepileptic drugs (AED) and temporarily disappear in response to AED in only 17% of patients. Currently, surgical resection is an important option for the treatment of epileptic seizures in FCD. In 2015, Korean and Japanese groups independently reported that FCD is caused by somatic mosaic mutation of the MTOR gene in the brain tissue. Based on these results we decided to test a novel treatment using sirolimus, an mTOR inhibitor, for epileptic seizures in patients with FCD type II. A single arm open-label clinical trial for FCD type II patients is being conducted in order to evaluate the efficacy and safety of sirolimus. The dose of sirolimus is fixed for the first 4 weeks and dose adjustment is achieved to maintain a blood level of 5 to 15 ng/mL during 8 to 24 weeks after initiation of administration, and it is kept within this level during a maintenance therapy period of 12 weeks. Primary endpoint is a reduction in the rate of incidence of focal seizures (including focal to bilateral tonic-clonic seizures) per 28 days during the maintenance therapy period from the observation period. To evaluate the frequency of epileptic seizures, registry data will be used as an external control group. We hope that the results of this trial will lead to future innovative treatments for FCD type II patients.
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Circulation reports 3(7) 368-374 2021年7月9日Background: The 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend that comatose patients with return of spontaneous circulation after cardiac arrest have targeted temperature management (TTM). However, the duration of TTM remains to be elucidated. Methods and Results: We conducted a cluster randomized trial in 10 hospitals to compare 12-24 vs. 36 h of cooling in patients with cardiac arrest who received TTM. The primary outcome was the incidence, within 1 month, of complications including bleeding requiring transfusion, infection, arrhythmias, decreasing blood pressure, shivering, convulsions, and major adverse cardiovascular events. Secondary outcomes were mortality and favorable neurological outcome (Cerebral Performance Categories 1-2) at 3 months. Random-effects models with clustered effects were used to calculate risk ratios (RR). Data of 185 patients were analyzed (12- to 24-h group, n=100 in 5 hospitals; 36-h group, n=85 in 5 hospitals). The incidence of complications within 1 month did not differ between the 2 groups (40% vs. 34%; RR 1.04, 95% confidence interval [CI] 0.67-1.61, P=0.860). Favorable neurological outcomes at 3 months were comparable between the 2 groups (64% vs. 62%; RR 0.91, 95% CI 0.72-1.14, P=0.387). Conclusions: TTM at 34℃ for 12-24 h did not significantly reduce the incidence of complications. This study did not show superiority of TTM at 34℃ for 12-24 h for neurologic outcomes.
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Circulation journal : official journal of the Japanese Circulation Society 85(2) 201-209 2021年1月25日BACKGROUND: In Japan there is no consensus on how to efficiently measure quality indicators (QIs), defined as a standard of care, for acute ischemic stroke (AIS). Using information from a health insurance claims database and electronic medical records, we evaluated the feasibility and validity of measuring QIs for AIS patients who received intravenous recombinant tissue plasminogen activator (IV rt-PA) or endovascular therapy (EVT).Methods and Results:AIS patients receiving rt-PA or EVT between 2013 and 2015 were identified. We selected 17 AIS QI measures for primary stroke centers (PSCs) and 8 for comprehensive stroke centers (CSCs). Defined QIs were calculated for each hospital and then averaged. In total, the data of 8,206 patients (rt-PA 83.7%, EVT 34.9%) from 172 hospitals were obtained. Median National Institute of Health Stroke Scale score at admission was 14, and 37.7% of the patients were functionally independent at discharge. All target QIs were successfully measured with fewer missing values, and the accuracy of preset data was about 90%. Adherence rates were low (<50%) in 5 QI measures among PSCs, including door-to-needle time ≤1 h, and in 1 QI measure among CSCs (door-to-brain and vascular imaging time ≤30 min). CONCLUSIONS: Measuring QIs for AIS by this novel approach was feasible and reliable in the provision of a national benchmark.
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Cancer science 111(12) 4540-4547 2020年12月Anaplastic lymphoma kinase (ALK) inhibition is expected to be a promising therapeutic strategy for ALK-positive malignancies. We aimed to examine the efficacy and safety of alectinib, a second-generation ALK inhibitor, in patients with relapsed or refractory ALK-positive anaplastic large cell lymphoma (ALCL). This open-label, phase II trial included patients (aged 6 years or older) with relapsed or refractory ALK-positive ALCL. Alectinib 300 mg was given orally twice a day (600 mg/d) for 16 cycles, and the duration of each cycle was 21 days. Patients who weighed less than 35 kg were given a reduced dose of alectinib of 150 mg twice a day (300 mg/d). Ten patients were enrolled, and the median age was 19.5 years (range, 6-70 years). Objective responses were documented in eight of 10 patients (80%; 90% confidence interval, 56.2-95.9), with six complete responses. The 1-year progression-free survival, event-free survival, and overall survival rates were 58.3%, 70.0%, and 70.0%, respectively. The median duration of therapy was 340 days. No unexpected adverse events occurred. The most common grade 3 and higher adverse event was a decrease in neutrophil count in two patients. Alectinib showed favorable clinical activity and was well tolerated in patients with ALK-positive ALCL who had progressed on standard chemotherapy. Based on the results of the current study, the Ministry of Health, Labour and Welfare of Japan approved alectinib for the treatment of recurrent or refractory ALK-positive ALCL in February 2020.
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European heart journal. Cardiovascular pharmacotherapy 8(2) 108-117 2020年11月11日AIMS: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated. METHODS AND RESULTS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (1) patients aged 20 years or older and (2) those with left ventricular ejection fraction of ≤ 40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group (hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855). In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure (HF) within 6 months was 0.55 (95% CI: 0.213 to 1.434). The safety profile for eplerenone was as expected. CONCLUSION: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.
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EJHaem 1(2) 507-516 2020年11月High-dose chemotherapy and autologous stem cell transplantation (ASCT) are too toxic for elderly patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Therefore, effective and tolerable regimens for elderly patients are urgently needed. The present phase II study assessed the efficacy and safety of dose-adjusted therapy with gemcitabine, dexamethasone, cisplatin, and rituximab (GDP-R) in this population. ASCT-ineligible elderly patients with relapsed or refractory DLBCL received dose-adjusted GDP-R in each 28-day cycle for up to six cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete response (CR) rate, progression-free survival (PFS), and safety. Thirty-three patients were enrolled and received dose-adjusted GDP-R. The median age was 75 years (range: 68-87 years). The ORR was 82.8% (90% confidence interval [CI], 67.1-93.0%), with a CR rate of 58.6% (90% CI, 41.7-74.1%). At a median follow-up of 20.9 months, the 2-year PFS rate was 46.8% (90% CI, 30.7-61.5%) and the 2-year overall survival rate was 63.2% (90% CI, 45.8-76.3%). The most frequently observed grade 4 adverse events were neutropenia (63.6%), thrombocytopenia (57.6%), and lymphocytopenia (39.4%). Dose-adjusted GDP-R is a promising salvage regimen for ASCT-ineligible elderly patients with relapsed DLBCL after rituximab-containing chemotherapy and warrants further investigation.
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Anesthesia and analgesia 131(3) 893-900 2020年9月BACKGROUND: Airway stenting is a procedure in which a stent is inserted into a stenotic site of the airway. The safest method of ventilation for airway stenting is controversial. A prospective randomized interventional study was conducted on airway stenting. We conducted this study to investigate whether controlled ventilation with muscle relaxants (MR) during airway stenting reduces the incidence of desaturation events (percutaneous oxygen saturation [SpO2] <95%) in comparison with spontaneous respiration (SP). METHODS: Sixty-four patients were enrolled at our hospital between April 2016 and August 2018, and were randomly assigned to the controlled ventilation with MR group or SP group. For anesthesia, total intravenous anesthesia with propofol target-controlled infusion and remifentanil was performed. In the SP group, SP was maintained. In the MR group, a rigid bronchoscope was inserted after the administration of MR to perform controlled ventilation. The incidence of desaturation events was analyzed by logistic regression adjusted by the preoperative respiratory state and stenotic site of the airway. RESULTS: The incidence of desaturation events in the SP and MR groups was 75.0% (24/32) and 9.7% (3/31), respectively, with an odds ratio of 0.04 (95% confidence interval, 0.01-0.16, reference = SP group; P < .001). In the SP group, the mean intraoperative pH was lower than that in the MR group (7.2 ± 0.1 vs 7.4 ± 0.1, respectively; P < .001). In this group, the mean partial pressure of arterial carbon dioxide (PaCO2) was higher (70.2 ± 17.0 mm Hg vs 40.5 ± 8.0 mm Hg, respectively; P < .001) and the mean partial pressure of oxygen in the arterial blood/fraction of the inspiratory oxygen ratio was lower (263.1 ± 64.2 mm Hg vs 396.4 ± 69.4 mm Hg, respectively; P < .001). CONCLUSIONS: Controlled ventilation with MR during airway stenting reduced the incidence of desaturation events, maintaining a favorable respiratory status.
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BMJ Open 10(8) e033055-e033055 2020年8月 査読有り<sec><title>Objectives</title>Comprehensive stroke centre (CSC) capabilities are associated with reduced in-hospital mortality due to acute stroke. However, it remains unclear whether there are improving trends in the CSC capabilities or how hospital-related factors determine quality improvement. This study examined whether CSC capabilities changed in Japan between 2010 and 2018 and and whether any changes were influenced by hospital characteristics. </sec><sec><title>Design</title>A hospital-based cross-sectional study. </sec><sec><title>Setting</title>We sent out questionnaires to the training institutions of the Japan Neurosurgical Society and Japan Stroke Society in 2010, 2014 and 2018. </sec><sec><title>Participants</title>749 hospitals in 2010, 532 hospitals in 2014 and 786 hospitals in 2018 participated in the J-ASPECT study, a nationwide survey of acute stroke care capacity for proper designation of a comprehensive stroke centre in Japan. </sec><sec><title>Main outcome measures</title>CSC capabilities were assessed using the validated scoring system (CSC score: 1–25 points) in 2010, 2014 and 2018 survey. The effect of hospital characteristics was examined using multiple logistic regression analysis. </sec><sec><title>Results</title>Among the 323 hospitals that responded to all surveys, the implementation of 13 recommended items increased. The CSC score (median and IQR) was 16 (13–19), 18 (14–20) and 19 (15–21) for 2010, 2014 and 2018, respectively (p<0.001). There was a ≥20% increase in six items (eg, endovascular physicians, stroke unit and interventional coverage 24/7), and a ≤20% decrease in community education. A lower baseline CSC score (OR: 0.82, 95% CI 0.75 to 0.9), the number of beds≥500 (OR: 3.9, 95% CI 1.2 to 13.0) and the number of stroke physicians (7–9) (OR: 2.6, 95% CI 1.1 to 6.3) were associated with improved CSC capabilities, independent of geographical location. </sec><sec><title>Conclusions</title>There was a significant improvement in CSC capabilities between 2010 and 2018, which was mainly related to the availability of endovascular treatment and multidisciplinary care. Our findings may be useful to determine which hospitals should be targeted to improve CSC capabilities in a defined area. </sec>
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The Kurume medical journal 66(1) 37-42 2020年7月1日High-dose chemotherapy and autologous stem cell transplantation is too toxic for elderly patients with relapsed or refractory (DLBCL). Therefore, tolerable and efficient salvage regimens for elderly patients are greatly needed. In this study, therapy with rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) will be performed every 4 weeks, and an interim evaluation will be performed after the completion of the 3rd course. If a complete response (CR) is achieved at the time of interim evaluation, 1 course of R-GDP therapy and 2 courses of monotherapy with rituximab will be additionally performed. If a partial response (PR) is achieved, 3 courses of R-GDP therapy will be additionally conducted. In patients without a PR or CR by the time of the interim evaluation, treatment will be discontinued. Treatment will also be discontinued at any point if disease progression is observed during protocol treatment. After the completion of the final course of R-GDP therapy, final effects of the regimen will be evaluated. A primary endpoint is the efficacy of R-GDP therapy (CR and response rates). This is the first multicenter phase II clinical study of R-GDP therapy to examine post-treatment activities of daily living in addition to the safety and efficacy of treatment in elderly patients with relapsed or refractory transplantineligible DLBCL.
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International journal of hematology 111(5) 711-718 2020年5月 査読有りData on the treatment of pediatric patients with brentuximab vedotin are limited. The aims of the present study were to assess the safety and tolerability of brentuximab vedotin in Japanese children with relapsed or refractory Hodgkin's lymphoma (HL) or systemic anaplastic large-cell lymphoma (sALCL). Pediatric patients, aged 2-17 years, with relapsed or refractory HL or sALCL were recruited. Brentuximab vedotin were administered at 1.8 mg/kg via intravenous infusion once every 3 weeks. Primary endpoints were dose-limiting toxicity and safety. Between September 2016, and March 2018, six patients (median age 11.5, range 5-14 years), four with relapsed or refractory HL and two with relapsed or refractory sALCL were enrolled. Dose limiting toxicity was not observed in any of the six patients. Although three of six patients (50%) experienced at least one grade ≥ 3 adverse event, no patient experienced a serious adverse event. The pharmacokinetic profile of brentuximab vedotin in pediatric patients was comparable to that reported in adults. The proportion of patients who achieved overall response was 60% (95% confidence interval 14.7-94.7). Brentuximab vedotin at 1.8 mg/kg once every 3 weeks was considered tolerable in children with relapsed or refractory HL or sALCL.
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Journal of Neurosurgery 134(3) 1-11 2020年3月 査読有り<sec><title>OBJECTIVE</title>Improved outcomes in patients with subarachnoid hemorrhage (SAH) treated at high-volume centers have been reported. The authors sought to examine whether hospital case volume and comprehensive stroke center (CSC) capabilities affect outcomes in patients treated with clipping or coiling for SAH. </sec><sec><title>METHODS</title>The authors conducted a nationwide retrospective cohort study in 27,490 SAH patients who underwent clipping or coiling in 621 institutions between 2010 and 2015 and whose data were collected from the Japanese nationwide J-ASPECT Diagnosis Procedure Combination database. The CSC capabilities of each hospital were assessed by use of a validated scoring system based on answers to a previously reported 25-item questionnaire (CSC score 1–25 points). Hospitals were classified into quartiles based on CSC scores and case volumes of clipping or coiling for SAH. </sec><sec><title>RESULTS</title>Overall, the absolute risk reductions associated with high versus low case volumes and high versus low CSC scores were relatively small. Nevertheless, in patients who underwent clipping, a high case volume (> 14 cases/yr) was significantly associated with reduced in-hospital mortality (Q1 as control, Q4 OR 0.71, 95% CI 0.55–0.90) but not with short-term poor outcome. In patients who underwent coiling, a high case volume (> 9 cases/yr) was associated with reduced in-hospital mortality (Q4 OR 0.69, 95% CI 0.53–0.90) and short-term poor outcomes (Q3 [> 5 cases/yr] OR 0.75, 95% CI 0.59–0.96 vs Q4 OR 0.65, 95% CI 0.51–0.82). A high CSC score (> 19 points) was significantly associated with reduced in-hospital mortality for clipping (OR 0.68, 95% CI 0.54–0.86) but not coiling treatment. There was no association between CSC capabilities and short-term poor outcomes. </sec><sec><title>CONCLUSIONS</title>The effects of case volume and CSC capabilities on in-hospital mortality and short-term functional outcomes in SAH patients differed between patients undergoing clipping and those undergoing coiling. In the modern endovascular era, better outcomes of clipping may be achieved in facilities with high CSC capabilities. </sec>
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International journal of hematology 111(3) 388-395 2020年3月 査読有り
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PloS one 15(4) e0230953 2020年OBJECTIVE: We sought to examine whether the effect of treatment modality and drugs for cerebral vasospasm on clinical outcomes differs between elderly and non-elderly subarachnoid hemorrhage (SAH) patients in Japan. METHODS: We analyzed the J-ASPECT Study Diagnosis Procedure Combination database (n = 17,343) that underwent clipping or coiling between 2010 and 2014 in 579 hospitals. We stratified patients into two groups according to their age (elderly [≥75 years old], n = 3,885; non-elderly, n = 13,458). We analyzed the effect of treatment modality and anti-vasospasm agents (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, eicosapentaenoic acid [EPA], and edaravone) on in-hospital poor outcomes (mRS 3-6 at discharge) and mortality using multivariable analysis. RESULTS: The elderly patients were more likely to be female, have impaired levels of consciousness and comorbidity, and less likely to be treated with clipping and anti-vasospasm agents, except for ozagrel sodium and statin. In-hospital mortality and poor outcomes were higher in the elderly (15.8% vs. 8.5%, 71.7% vs. 36.5%). Coiling was associated with higher mortality (odds ratio 1.43, 95% confidence interval 1.2-1.7) despite a lower proportion of poor outcomes (0.84, 0.75-0.94) in the non-elderly, in contrast to no effect on clinical outcomes in the elderly. A comparable effect of anti-vasospasm agents on mortality was observed between non-elderly and elderly for fasudil hydrochloride (non-elderly: 0.20, 0.17-0.24), statin (0.63, 0.50-0.79), ozagrel sodium (0.72, 0.60-0.86), and cilostazol (0.63, 0.51-0.77). Poor outcomes were inversely associated with fasudil hydrochloride (0.59, 0.51-0.68), statin (0.84, 0.75-0.94), and EPA (0.83, 0.72-0.94) use in the non-elderly. No effect of these agents on poor outcomes was observed in the elderly. CONCLUSIONS: In contrast to the non-elderly, no effect of treatment modality on clinical outcomes were observed in the elderly. A comparable effect of anti-vasospasm agents was observed on mortality, but not on functional outcomes, between the non-elderly and elderly.
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International journal of hematology 110(5) 627-634 2019年11月Outcomes of children treated for relapsed acute lymphoblastic leukemia (ALL) remain poor. Bortezomib (BZM), a proteasome inhibitor, has shown promising activity against lymphoid malignancies. We conducted a phase I study to evaluate the safety and tolerability of multidrug chemotherapy including BZM in Japanese children with relapsed ALL. Three of five children with relapsed ALL enrolled in the study between November 2014 and April 2016 were evaluated. BZM (1.3 mg/m2) was administered on days 8, 11, 15, and 18 of multidrug induction chemotherapy. Pharmacokinetic studies were performed. Age at study entry was 5, 7, and 7 years old, respectively. Two patients had hyperdiploid B-precursor ALL, and one had T cell ALL. Although all patients experienced grade 3-4 hematologic toxicity and grade 3 elevation of aminotransferases, no dose-limiting toxicities were observed. The maximum tolerated dose was defined as 1.3 mg/m2. Peripheral neuropathy and respiratory complications were not observed. Complete remission was achieved in all three patients. The mean maximum plasma concentration and area under the concentration-time curve was 74.0 ng/mL and 73.9 ng h/mL, respectively. Thus, adding BZM to 5-drug induction chemotherapy appears safe and well-tolerated in Japanese children with relapsed ALL.
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Circulation Journal 83(11) 2292-2302 2019年10月25日 査読有りBACKGROUND: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. METHODS AND RESULTS: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. CONCLUSIONS: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.
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International Journal of Stroke 174749301988452-174749301988452 2019年10月25日<sec><title>Background</title> Limited national-level information on temporal trends in comprehensive stroke center capabilities and their effects on acute ischemic stroke patients exists. </sec><sec><title>Aims</title> To examine trends in in-hospital outcomes of acute ischemic stroke patients and the prognostic influence of temporal changes in comprehensive stroke center capabilities in Japan. </sec><sec><title>Methods</title> This retrospective study used the J-ASPECT Diagnosis Procedure Combination database and identified 372,978 acute ischemic stroke patients hospitalized in 650 institutions between 2010 and 2016. Temporal trends in patient outcomes and recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy usage were examined. Facility comprehensive stroke center capabilities were assessed using a validated scoring system (comprehensive stroke center score: 1–25 points) in 2010 and 2014. The prognostic influence of temporal comprehensive stroke center score changes on in-hospital mortality and poor outcomes (modified Rankin Scale: 3–6) at discharge were examined using hierarchical logistic regression models. </sec><sec><title>Results</title> Over time, stroke severity at admission decreased, whereas median age, sex ratio, and comorbidities remained stable. The median comprehensive stroke center score increased from 16 to 17 points. After adjusting for age, sex, comorbidities, consciousness level, and facility comprehensive stroke center score, proportion of in-hospital mortality and poor outcomes at discharge decreased (from 7.6% to 5.0%, and from 48.7% to 43.1%, respectively). The preceding comprehensive stroke center score increase (in 2010–2014) was independently associated with reduced in-hospital mortality and poor outcomes, and increased rt-PA and mechanical thrombectomy use (odds ratio (95% confidence interval): 0.97 (0.95–0.99), 0.97 (0.95–0.998), 1.07 (1.04–1.10), and 1.21 (1.14–1.28), respectively). </sec><sec><title>Conclusions</title> This nationwide study revealed six-year trends in better patient outcomes and increased use of rt-PA and mechanical thrombectomy in acute ischemic stroke. In addition to lesser stroke severity, preceding improvement of comprehensive stroke center capabilities was an independent factor associated with such trends, suggesting importance of comprehensive stroke center capabilities as a prognostic indicator of acute stroke care. </sec>
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ACTA MEDICA OKAYAMA 73(5) 469-474 2019年10月Romidepsin is an important therapeutic option for patients with peripheral T-cell lymphoma (PTCL). However, the timing of romidepsin administration remains controversial. Romidepsin was launched in Japan as a consolidation therapy agent after conventional salvage chemotherapy with gemcitabine, dexamethasone, and cisplatin (GDP). GDP therapy will be administered every 3 weeks. If complete response, partial response, or stable disease is confirmed after 2-4 GDP cycles, romidepsin will be administered every 4 weeks. The primary endpoint is a 2-year progression-free survival rate. Patients participating in this study and undergoing treatment can expect results similar to or better than those of conventional therapies.
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Psychiatry and Clinical Neurosciences 73(10) 660-661 2019年10月
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World neurosurgery 130 e26-e46 2019年10月BACKGROUND: The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients. METHODS: Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients. RESULTS: Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P < 0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at >7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P < 0.001), and incidence of acute subdural hematoma (OR, 1.89; P < 0.001) were associated with in-hospital mortality in elderly patients with TBI. CONCLUSIONS: Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.
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Contemporary Clinical Trials Communications 14 100316 2019年6月 査読有り© 2019 Background: In cluster randomized controlled trials (RCTs) for emergency medical services (EMS) system, we encounter the situation that the actual cluster size and ratio of allocated patients between two groups eventually differ from those used for sample size estimation because of the nature of patient enrollment. In such trials, estimations of effect size of test intervention and intra-cluster correlation coefficient (ICC) used for sample size estimation are also difficult. To improve efficient management on clinical cluster RCTs, we need to understand the effect of such inconsistencies of the design parameters on the type I error rate and statistical power of testing. Methods: We planned the trial which evaluated the 1-month favorable neurological survival of out-of-hospital cardiac arrest patients with or without real-time feedback, debriefing, and retraining system by EMS personnel. Under the conditions that we possibly encountered in this trial, we examined the effect of inconsistencies in the actual ICC, cluster size, and ratio of patient allocation with those expected for sample size estimation on the type I error rate and power, using simulation studies. We further investigated the contribution of incorporating sample size re-estimation, based on the results of interim analysis of the trial, on the power increase. Results: This simulation study showed that the inconsistencies of cluster size and patient allocation ratio decreased the power by 5–10% in some cases. In addition, the power decreased by 3–4% when the actual ICC was larger than that expected for sample size estimation. Furthermore, the use of a generalized estimating equation method to evaluate the difference in the 1-month favorable neurological survival between two groups caused inflation of type I error rate. Finally, the increase in power by incorporating sample size re-estimation was limited. Conclusions: We identified remarkable effects of sample size estimation and re-estimations in a cluster RCT for real-time feedback, debriefing, and retraining system of cardiopulmonary resuscitation for out-of-hospital cardiac arrests. The estimation of design parameters for sample size estimation is generally challenging in cluster RCTs for EMS system; therefore, it is important to conduct a trial simulation that assesses the statistical performances under sample sizes based on the various expected values of the design parameters before beginning the trial.
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Cancer medicine 8(7) 3359-3369 2019年5月 査読有り
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In vivo (Athens, Greece) 33(2) 477-482 2019年3月 査読有り
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PSYCHIATRY AND CLINICAL NEUROSCIENCES 73(2) 90-91 2019年2月 査読有り
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Kurume Medical Journal 66(3) 161-168 2019年Although approximately 70% of pediatric hematological malignancies are curable, approximately 30% remain fatal. No standard treatment is available in patients showing relapse and those with refractory disease. Although different methods are adopted in different hospitals, its efficacy is extremely limited. In recent years, haploidentical stem cell transplantation, involving high-dose cyclophosphamide administration post-transplanta-tion, has been used, mainly in adults however, its application is limited to removal of alloreactive T cells. Multicenter single-arm clinical trials of T-cell replete haploidentical stem cell transplantation (TCR-haplo-SCT) will be conducted in children with relapsed and refractory acute leukemia. After myeloablative conditioning using total body irradiation or busulfan, intensive graft versus host disease prophylaxis is administered, consisting of low-dose rabbit anti-human thymocyte globulin, tacrolimus, methotrexate, and prednisolone. An external control group is set up for the study. The treatment period is around 3 months, and the follow-up period is 2 years from transplantation completion. The aim of this study is to verify the efficacy and safety of TCR-haplo-SCT and present it as a new immune cell therapy for improving survival rate in children with relapsed and refractory acute leukemia.
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In Vivo 33(5) 1641-1644 2019年Background: An open-label, single-arm study was conducted to assess the safety of a cryosurgery unit named CRYO2 for debulking at the site of obstruction or stenosis. Patients and Methods: In order to treat central airway tumor-related stenosis, debulking at the stenotic site of the airway was performed using CRYO2 under general or local anesthesia. The primary endpoint was the incidence of moderate to massive hemorrhage. Results: Incidence of moderate to massive hemorrhage during surgery was 3.8% (1/26) (95% confidence interval(CI)=0.1-19.6%). Technical success was 96.2% (25/26), with a 95% confidence interval of 80.4-99.9%. Conclusion: CRYO2 for debulking at the site of obstruction or stenosis can be performed safely.
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The Kurume medical journal 65(1) 11-16 2018年12月 査読有り
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Acta medica Okayama 72(6) 611-614 2018年12月 査読有り
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The Laryngoscope 128(11) 2593-2599 2018年11月 査読有りOBJECTIVES/HYPOTHESIS: Vocal fold polyps and nodules are common benign laryngeal lesions. Currently, the Japanese health insurance system covers surgical interventions. However, the establishment of more cost-effective conservative methods is required, because healthcare costs are viewed as a major concern, and the government and taxpayers are demanding more economical, effective treatments. In this situation, more suitable vocal hygiene education may be important for the success of cost-effective conservative treatment. In this study, we developed a novel reinforced vocal hygiene education program and compared the results of this program with those of previous methods of teaching vocal hygiene. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Patients who visited a National Hospital Organization (NHO) hospital for the surgical indication of hoarseness were included in the study. Before undergoing surgery, 200 patients with benign vocal fold lesions (vocal fold polyps/nodules) were enrolled and randomly allocated to the NHO-style vocal hygiene educational program (intervention group) or control education program (control group). Two months after enrollment, the patients in both groups underwent laryngeal fiberscopic examinations to determine whether the benign lesions had resolved or whether surgery was indicated for the vocal fold polyps/nodules. RESULTS: After 2 months, in the intervention group, the proportion of lesion resolution (61.3%) was significantly greater than that in the control group (26.3%) (P < .001, Fisher exact test). CONCLUSIONS: Our results clearly indicate that the quality and features of the education program could affect the outcome of the intervention. We found that a reinforced vocal hygiene education program increased the rate of the resolution of benign vocal fold polyps and nodules in a multicenter randomized clinical trial. LEVEL OF EVIDENCE: 1b Laryngoscope, 2593-2599, 2018.
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Trials 19(1) 510 2018年9月20日 査読有り© 2018 The Author(s). Background: The quality of cardiopulmonary resuscitation (CPR) performed by emergency medical services (EMS) personnel affects patient outcomes after cardiac arrest. A CPR feedback device with an accelerometer mounted on a defibrillator can monitor the motion of the patient's sternum to display and record CPR quality in real time. To evaluate the utility of real-time feedback, debriefing, and retraining using a CPR feedback device outside of the hospital, an open-label, cluster randomized controlled trial will be conducted in five municipalities of Osaka Prefecture, Japan. Methods: Each EMS station within a fire department will be randomly assigned to: 1) the treatment group with real-time feedback, debriefing, and retraining using the CPR feedback device (intervention group); or 2) the conventional treatment group without real-time feedback, debriefing, and retraining (control group). This trial will include 2850 to 3020 patients over about 4 years. The primary outcome of the trial is 1-month favorable neurological survival, defined as cerebral performance category scale score 1 or 2. Secondary outcomes are 1-month survival, survival to hospital discharge, return of spontaneous circulation, and quality of CPR including fraction, depth, tempo, and ventilation rate. Discussion: The trial will assess whether treatment monitored by the CPR feedback device, which allows for real-time feedback, debriefing, and retraining using CPR quality data, outperforms conventional treatment without real-time feedback, debriefing, and retraining in terms of 1-month favorable neurological survival in cardiac arrest patients receiving CPR outside the hospital. Trial registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000021431. Registered on 11 March 2016.
MISC
51講演・口頭発表等
1共同研究・競争的資金等の研究課題
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日本学術振興会 科学研究費助成事業 2023年4月 - 2026年3月
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日本学術振興会 科学研究費助成事業 2019年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 2018年4月 - 2022年3月
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日本学術振興会 科学研究費助成事業 2015年4月 - 2019年3月
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日本学術振興会 科学研究費助成事業 2013年4月 - 2017年3月