Safety profile of hypnotics or sedatives on community-dwelling older adults aged 75 or older in Japan: A retrospective propensity-matched cohort study.

OBJECTIVE: The purpose of the study is to assess if daily use of hypnotics increases mortality, aspiration pneumonia and hip fracture among relatively healthy individuals aged 75 years or older who lead independent lives in the community. METHOD AND PATIENTS: Of the adults aged 75 years or older residing in Hokkaido prefecture of Japan (n = 705,538), those who did not meet several exclusion criteria were eligible for generating propensity score-matched cohorts (n = 214,723). Exclusion criteria included co-prescribed medications acting on the central nervous system, diagnoses of malignant neoplasm, dementia, depression, etc. We compared 33,095 participants who were prescribed hypnotics for daily use (hypnotic group) with a propensity score-matched cohort without a prescription (control group). Participants were followed for more than 42 months. RESULTS: During the 42-month follow-up period, the incidence of the three outcome measures in the hypnotics group was significantly higher than that in the control group (aspiration pneumonia p < 0.001, hip fracture p = 0.007, and all-cause mortality p < 0.001). Sensitivity analyses utilizing inverse probability weighting demonstrated hazard ratios of 1.083 [1.023-1.146] for mortality, 1.117 [1.014-1.230] for aspiration pneumonia, and 1.720 [1.559-1.897] for hip fracture. Meanwhile, the attribute risk differences were 2.7, 1.5, and 1.0 per 1000 patient-years, respectively. CONCLUSIONS: Although daily use of hypnotics increased the risk of three events, their attribute risk differences were fewer than 3.0 per 1000 patient-years. The results will help provide guidance on whether it is reasonable to prescribe hypnotics to geriatric population aged 75 or older leading independent lives in the community. CLINICAL TRIAL REGISTRATION: UMIN-CTR UMIN000048398.

Independent Factors for In-Hospital Death Following Drug-Eluting Stent Thrombosis From the Japanese Adverse Event Report System.

BACKGROUND: Stent thrombosis (ST) is a serious complication after drug-eluting stents (DES) implantation. To identify the risk factors of mortality following ST, we evaluated adverse event reports used for safety measures after approval.Methods and Results:Between July 2004 and August 2019, 2,887 ST case reports were submitted to the Pharmaceutical and Medical Device Agency. Reports of probable or possible ST (n=604), with insufficient data regarding in-hospital outcome or duration between procedure and ST occurrence (n=37) or duplicate reports (n=191) were excluded. Accordingly, 2,045 reports with definite ST were analyzed. Among the subjects, there were 286 in-hospital deaths (14.0%). Multivariate logistic regression analysis revealed that left main trunk (LMT) (odds ratio [OR]: 4.76, 95% confidence interval [CI]: 3.26-6.96), chronic heart failure (CHF) (OR: 2.88, 95% CI: 1.61-5.14), hemodialysis (OR: 2.69, 95% CI: 1.66-4.36), prior stroke (OR: 2.28, 95% CI: 1.15-4.51), over 70 years old (OR: 1.62, 95% CI: 1.22-2.16), and right coronary artery (OR: 0.41, 95% CI: 0.27-0.63) were independent factors for in-hospital death after DES-ST. CONCLUSIONS: LMT, CHF, hemodialysis, prior stroke, and older age were independently associated with higher risk of in-hospital death following DES-ST. If target patients have these factors, maximum preventive strategies against ST occurrence, including adequate dual-antiplatelet therapy duration and optimal DES deployment procedures, are required.

Influence of Type 2 Endoleaks on Long-Term Outcomes after Endovascular Repair for Abdominal Aortic Aneurysms: A National Hospital Organization Network Study for Abdominal Aortic Aneurysms in Japan.

BACKGROUND: Although endovascular repair (EVAR) is the first-line treatment for abdominal aortic aneurysm, type 2 endoleak (EL), which is associated with late sac enlargement or rupture, remains a concern. The present study aimed to assess the influence of type 2 EL on long-term outcomes after EVAR. METHODS: Among 550 patients who underwent EVAR between 2007 and 2013 at 14 Japanese national hospitals, 135 patients had type 2 EL diagnosed on follow-up computed tomography (CT) within 12 months after EVAR (EL2[+] group) and 415 patients did not have EL within 12 months (EL2[-] group). The cumulative incidences of sac enlargement, late intervention, and aneurysm-related death after EVAR were estimated using the cumulative incidence function method, and prognostic factors were investigated using the Fine-Gray hazard model. RESULTS: The median follow-up period was 5 years, and the 5-year cumulative incidence rates of sac enlargement, late intervention, and aneurysm-related death were 30.7% ± 4.4%, 25.3% ± 4.1%, and 2.6% ± 1.4%, respectively, in the EL2(+) group, and 8.7% ± 1.6%, 7.6% ± 1.4%, and 0.3% ± 0.3%, respectively, in the EL2(-) group. The cumulative incidence rates of sac enlargement (P = 0.002), late intervention (P < 0.001), and aneurysm-related death (P = 0.015) were significantly different between the 2 groups. As the first-line treatment for sac enlargement with type 2 EL, transcatheter coil embolization was performed in 30 patients. Information about sac behavior on CT after coil embolization was available in 20 of the 30 patients. Among these patients, no patients experienced sac shrinkage, and the aneurysmal sac dilated after coil embolization in 18 patients. CONCLUSIONS: Type 2 EL affects the long-term outcomes after EVAR. It is not recommended to observe large aneurysmal sacs conservatively as they tend to dilate in the presence of type 2 EL.

Future development of artificial organs related with cutting edge emerging technology and their regulatory assessment: PMDA's perspective.

Future development of innovative artificial organs is closely related with cutting edge emerging technology. These technologies include brain machine or computer interface, organs made by three dimensional bioprinting, organs designed from induced-pluripotent stem cell for personalized tissue or organ, and xenotransplantation. To bridge the gap between scientific innovation and regulatory product review, Pharmaceuticals and Medical Devices Agency of Japan (PMDA) started the science board to discuss about the new scientific topics regarding medical products including medical device and regenerative products with external experts since 2012. Topics which PMDA raised for science board included cellular and tissue-based products from iPS cells, artificial intelligence and genome editing technology. In addition, PMDA started the horizon scanning to identify a new cutting edge technology which could potentially lead to innovative health technology or product, which has a strong impact on clinical medicine. Although the effectiveness and safety of the medical products must be reasonably assured before clinical use, PMDA introduced Sakigake review assignment (a review partner of device development) and conditional approval system to balance between pre-market and post-market evaluation.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

OBJECTIVE: The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. METHODS: Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. RESULTS: The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. CONCLUSIONS: Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Learning Curve for Transcatheter Aortic Valve Implantation Under a Controlled Introduction System　- Initial Analysis of a Japanese Nationwide Registry.

BACKGROUND: The introduction of transcatheter aortic valve implantation (TAVI) into Japan was strictly controlled to optimize patient outcomes. The goal of this study was to assess if increasing experience during the introduction of this procedure was associated with outcomes.Methods and Results:The initial 1,752 patients registered in the Japanese national TAVI registry were included in the study. The association between operator procedure number and incidence of the early safety endpoint at 30 days (ESE30) as defined in the Valve Academic Research Consortium-2 consensus document was evaluated. Patients were divided into 4 groups by quartiles of procedure count (Groups I-IV in order of increasing number of procedures). Median patient age was 85 years, and 30.5% were male. The 30-day mortality rate was 1.4% (n=24), and 78 patients (7.9%) experienced 95 ESE30. Among the variables included in the model, ESE30 was associated with non-transfemoral approach (P=0.004), renal dysfunction (Cr >2.0 mg/dL) (P=0.01) and NYHA class III/IV (P=0.04). ESE30 incidence was not significantly different between Groups I-III and Group IV. Spline plots demonstrated that experience of 15-20 cases in total was needed to achieve a consistent low risk of ESE30. CONCLUSIONS: Increasing experience was associated with better outcomes, but to a lesser degree than in previous reports. Our findings suggested that the risks associated with the learning curve process were appropriately mitigated.

Design Strategies for Global Clinical Trials of Endovascular Devices for Critical Limb Ischemia (CLI)　- A Joint USA-Japanese Perspective.

For more than 10 years, the Harmonization by Doing (HBD) program, a joint effort by members from academia, industry and regulators from the United States of America (USA) and Japan, has been working to increase timely regulatory approval for cardiovascular devices through the development of practical global clinical trial paradigms. Consistent with this mission and in recognition of the increasing global public health effects of critical limb ischemia (CLI), academic and government experts from the USA and Japan have developed a basic framework of global clinical trials for endovascular devices for CLI. Despite differences in medical and regulatory environments and complex patient populations in both countries, we developed a pathway for the effective design and conduct of global CLI device studies by utilizing common study design elements such as patients' characteristics and study endpoints, and minimizing the effect of important clinical differences. Some of the key recommendations for conducting global CLI device studies are: including patients on dialysis; using a composite primary endpoint for effectiveness that includes 6-month post-procedure therapeutic success and target vessel patency; and using a 30-day primary safety endpoint of perioperative death and major adverse limb events. The proposed approach will be uniquely beneficial in facilitating both the initiation and interpretation of CLI studies and accelerating worldwide CLI device development and innovation.

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

BACKGROUND: The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. CONCLUSIONS: Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

A positive family history of hypertension might be associated with an accelerated onset of type 2 diabetes: Results from the National Center Diabetes Database (NCDD-02).

Type 2 diabetes, which is characterized by a combination of decreased insulin secretion and decreased insulin sensitivity, can be delayed or prevented by healthy lifestyle behaviors. Therefore, it is important that the population in general understands their personal risk at an early age to reduce their chances of ever developing the disease. A family history of hypertension is known to be associated with insulin resistance, but the effect of a family history of hypertension on the onset of type 2 diabetes has not well been examined. We performed a retrospective study examining patient age at the time of the diagnosis of type 2 diabetes by analyzing a dataset of 1,299 patients (1,021 men and 278 women) who had been diagnosed as having type 2 diabetes during a health checkup. The mean ± standard deviation of the patient age at the time of the diagnosis of diabetes was 49.1 ± 10.4 years for patients with a family history of hypertension and 51.8 ± 11.4 years for patients without a family history of hypertension (p < 0.001). A multivariate linear regression analysis showed a significant association between a family history of hypertension and a younger age at the time of the diagnosis of type 2 diabetes, independent of a family history of diabetes mellitus and a male sex, suggesting that a positive family history of hypertension might be associated with the accelerated onset of type 2 diabetes.

Impact of introducing endovascular aneurysm repair on treatment strategy for repair of abdominal aortic aneurysm--National Hospital Organization network study in Japan.

BACKGROUND: The objective of the present study was to assess the hypothesis that the introduction of endovascular aneurysm repair (EVAR) into Japan has expanded the indication of abdominal aortic aneurysm (AAA) repair without increasing surgical mortality. METHODS AND RESULTS: From 10 national hospitals, we registered a total of 2,154 consecutive patients (Open surgery [OS]: n=1,577, EVAR: n=577) over 8 years, divided into 4 time periods: Group I (2005-2006: n=522), Group II (2007-2008: n=475), Group III (2009-2010: n=551), Group IV, (2011-2012: n=606). Mean age increased over the 4 time periods (P<0.0001). The incidences of COPD, smoking history, history of abdominal surgery and concomitant malignancy significantly increased as well, while the numbers of patients with preoperative shock or high ASA status reduced over time. The proportion of EVAR in AAA repair increased from: 0% in Group I, 11.6% in Group II, 41.0% in Group III, to 48.8% in Group IV (P<0.0001). Early mortality was 0.8% in the EVAR and 3.4% in the OS (P<0.001) groups. Survival rates among the 4 groups free of all-cause death and aneurysm-related death at 1 year were 92.1-96.3% (P=0.1555) and 95.5-96.8% (P=0.9891), respectively. Multiple logistic regression analysis for surgical death failed to demonstrate survival advantage of EVAR over OS. CONCLUSIONS: Introduction of EVAR expanded the indication of AAA repair without increasing mortality, while high risk for anesthesia and emergency cases reduced over time. UMIN-CTR (UMIN000008345).

Long-Term Outcomes of Endovascular Aneurysm Repair in Patients Aged ≤70 Years.

Objectives: The efficacy of endovascular aneurysm repair (EVAR) against abdominal aortic aneurysm (AAA) in younger patients remains unknown. Hence, the current study aimed to investigate whether the aneurysm-related mortality rate of EVAR is acceptable among patients aged ≤70 years. Methods: Among 644 patients, 148 underwent EVAR (EVAR group), and 496 received open surgical repair (OSR group). The cumulative incidence rates of aneurysm-related death, any intervention, and serious aneurysm-related events after AAA repair were evaluated using the cumulative incidence function in the presence of competing risks. Results: The EVAR group had higher prevalences of several comorbidities, and overall survival for the EVAR group was significantly inferior to that of the OSR group. The cumulative incidence rates of aneurysm-related death, any intervention, and serious aneurysm-related events at 5 years were 1.5%, 11.7%, and 6.4% in the EVAR group and 1.3%, 5.3%, and 5.9% in the OSR group, respectively. EVAR was not a significant prognostic factor of aneurysm-related mortality and serious aneurysm-related events. However, it was an independent poor prognostic factor of any intervention. Conclusion: EVAR was not a significant prognostic factor of aneurysm-related mortality and serious aneurysm-related events. Therefore, it demonstrated acceptable procedure-related long-term outcomes, at least in high-risk young patients.

Retrospective observational study of a novel smartphone app on the management of patients with mild cognitive impairment or mild dementia.

Introduction: In this study, we aimed to evaluate the feasibility, utility, and potential effects of LQ-M/D App, a smartphone application developed by Life Quest Inc., Tokyo, Japan, for patients with mild cognitive impairment (MCI) and mild dementia. The app incorporates cognitive and physical exercise training, lifestyle habit acquisition features, and a continuity improvement feature added in the post-update version to enhance user engagement. The continuity improvement feature includes the optimization of training content, and disease education, and enables family monitoring via a family app. Methods: A retrospective analysis was conducted on app usage, cognitive and exercise training implementation and interruptions, questionnaire response rates, and cognitive assessments in a single institution. A total of 20 patients used the app, with 10 patients using the pre-update version without the continuity improvement feature, and the other 10 patients using the post-update version with the continuity improvement feature. Results and Conclusion: The results demonstrated that the LQ-M/D App could be effectively used by the study population, and the continuity improvement feature positively influenced app usage in several aspects. Although a potential association between app usage and cognitive ability was suggested, the scatter in the data points warrants cautious interpretation. Limitations of the study included a small sample size, a single institution setting, and the retrospective nature of the study. In the future, a randomized controlled trial design using a larger sample size and multiple institutions to further evaluate the effectiveness of LQ-M/D App in managing MCI and mild dementia should be performed.

Procedure- and age-specific risk stratification of single aortic valve replacement in elderly patients based on Japan Adult Cardiovascular Surgery Database.

BACKGROUND: Successful introduction of trans-catheter aortic valve implantation for selected patients with critical aortic stenosis has raised the question of how to identify appropriate high-risk candidates. METHODS AND RESULTS: To assess the risk profile of patients undergoing single aortic valve replacement (sAVR), multiple logistic regression analysis was applied for open sAVR (n = 7,883) registered in the Japan Cardiovascular Surgery Database to predict surgical mortality. Three subgroup analyses stratified by age, <70 years (young), 70-79 years (middle), and ≥80 years (elderly), were also performed. Preoperative patient characteristics indicated increased prevalence of several variables in the elderly subgroup including New York Heart Association (NYHA) class III/IV, 3-vessel coronary artery disease (3VCAD), respiratory insufficiency, and stroke. The following factors, however, were decreased in the elderly subgroup: dialysis, poor heart function, reoperation, renal dysfunction, and emergency surgery. Mortality was 3.0% in all sAVR patients and 5.2% in the elderly subgroup. Multivariate analysis in all patients produced 16 variables as operative risks (P<0.05) including respiratory insufficiency, dialysis, NYHA class III/IV, and reoperation. The analysis in the elderly subgroup produced 9 variables with more pronounced relative risk (RR), which included dialysis (RR = 5.4), respiratory insufficiency (RR = 3.3), preoperative arrhythmia (RR = 3.0), 3VCAD (RR = 3.6), and emergency surgery (RR = 23.1). CONCLUSIONS: sAVR has produced good surgical results in Japan. Procedure- and age-specific analyses have identified a risk profile that is unique to sAVR patients in the elderly population in Japan.

Associations of coprescribed medications for chronic comorbid conditions in very old adults with clinical dementia: a retrospective cohort study using insurance claims data.

OBJECTIVE: To assess the association of coprescribed medications for chronic comorbid conditions with clinical dementia in older adults, as indicated by the initiation of a new prescription of antidementia medication (NPADM). DESIGN: Retrospective enumeration cohort study. SETTING: A Japanese city in Tokyo Metropolitan Area. PARTICIPANTS: A total of 42 024 adults aged ≥77 years residing in Kashiwa City, a suburban city of Tokyo Metropolitan Area, who did not have any prscription of antidementia medication from 1 April to 30 June 2012. MAIN OUTCOME MEASURE: The primary outcome was NPADM during follow-up period until 31 March 2015 (35 months). Subjects were categorised into four age groups: group 1 (77-81 years), group 2 (82-86 years), group 3 (87-91 years) and group 4 (≥92 years). In addition to age and sex, 14 sets of medications prescribed during the initial background period (from 1 April 2012 and 31 June 2012) were used as covariates in a Cox proportional hazard model. RESULTS: In a follow-up period of 1 345 457 person-months (mean=32.0±7.5 months, median 35 months), NPADM occurred in 2365 subjects. NPADM incidence at 12 months was 1.9%±0.1% (group 1: 0.9%±0.1%, group 2: 2.1%±0.1%, group 3: 3.2%±0.2% and group 4: 3.6%±0.3%; p<0.0001). In addition to older age and female sex, use of the following medications was significantly associated with NPADM: statins (HR: 0.82, 95% CI 0.73 to 0.92; p=0.001), antihypertensives (HR: 0.80, 95% CI 0.71 to 0.85; p<0.0001), non-steroidal bronchodilators (HR: 0.72, 95% CI 0.58 to 0.88; p=0.002), antidepressants (HR: 1.79, 95% CI 1.47 to 2.18; p<0.0001), poststroke medications (HR: 1.45, 95% CI 1.16 to 1.82; p=0.002), insulin (HR: 1.34, 95% CI 1.01 to 1.78; p=0.046) and antineoplastics (HR: 1.12, 95% CI 1.01 to 1.24; p=0.035). CONCLUSIONS: This retrospective cohort study identified the associations of coprescribed medications for chronic comorbid conditions with NPADM in older adults. These findings would be helpful in understanding the current clinical practice for dementia in real-world setting and potentially contribute to healthcare policymaking. TRIAL REGISTRATION NUMBER: UMIN000039040.

Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial.

A number of preclinical studies have indicated the therapeutic potential of endothelial progenitor cells for vascular regeneration in ischemic diseases. A phase I/IIa clinical trial of transplantation of autologous CD34(+) cells, the endothelial and hematopoietic progenitor-enriched fraction, was performed in no-option patients with atherosclerotic peripheral artery disease or Buerger's disease with critical limb ischemia (CLI). CD34(+) cells were isolated from the G-CSF-mobilized apheresis product using a magnetic cell sorting system. CD34(+) cells (10(5)/kg, n = 6; 5 x 10(5)/kg, n = 8; or 10(6)/kg, n = 3) were injected i.m. into the leg with more severe ischemia. The Efficacy Score, representing changes in the toe brachial pressure index (TBPI), Wong-Baker FACES pain rating scale, and total walking distance 12 weeks after cell transplantation, the primary endpoint, was positive, indicating improvement in limb ischemia in all patients, although no significant dose-response relationship was observed. During the 12-week observation after cell therapy, the Wong-Baker FACES pain rating scale, TBPI, transcutaneous partial oxygen pressure, total or pain-free walking distance, and ulcer size serially improved in all patients. No death or major amputation occurred, and severe adverse events were rare, although mild to moderate events relating to G-CSF and leukapheresis were frequent during the 12-week follow-up. In conclusion, the outcomes of this prospective clinical study indicate the safety and feasibility of CD34(+) cell therapy in patients with CLI. Favorable trends in efficacy parameters encourage a randomized and controlled trial in the future.

Endovascular stent-graft repair for spontaneous dissection of infra-renal abdominal aorta.

Abdominal aortic dissection (AAD) is a rare pathology and potentially causes rupture or other serious complications. This case report details our experience in endovascular aneurysm repair for AAD in a patient who had a history of coronary bypass surgery. Circumferential dissection of terminal aorta showed stenosis of true lumen as well as blood flow present in the pseudolumen. Using Zenith AAA endovascular device, the entry site was closed and the pseudolumen was thrombosed successfully. In the present report, published data on AAD were reviewed and endovascular aneurysm repair as a treatment option has been discussed as well.

Patient and lesion characteristics in late/very late stent thrombosis with everolimus-eluting stents from real-world adverse event reporting.

BACKGROUND: Stent thrombosis (ST) is a rare but serious complication after deployment of a drug-eluting stent. The features of ST after implantation of an everolimus-eluting stent (EES) have not been fully elucidated. METHODS: A comprehensive survey of real-world adverse event reporting with conditions for approval under the Pharmaceuticals and Medical Devices Act identified 490 cases of ST with EES. A total of 370 patients with definite ST after EES implantation [287 with early (E)ST (within 30 days), 54 with late (L)ST (31-365 days), and 29 with very late (VL)ST (over 1 year)] were divided into an EST group and an LST/VLST group to compare the patients and lesions characteristics. RESULTS: The frequency of patients with hemodialysis and in-stent restenosis (ISR) lesions were significantly higher in the LST/VLST group than in the EST group (hemodialysis, 22.9% vs 2.7%, p = 0.0001; ISR lesions, 25.9% vs 9.4%, p = 0.0001). Characteristic demographic factors for LST/VLST versus EST identified by multivariable model were hemodialysis and ISR lesions (hemodialysis: odds ratio 7.348, 95% confidence interval 2.458-21.968, p = 0.0001; ISR lesions: odds ratio, 2.490, 95% confidence interval 1.100-5.638, p = 0.027). The in-hospital death rates from ST were not significantly different between the EST group and the LST/VLST group (EST, 15% vs LST/VLST, 21.7%, p = 0.147). CONCLUSIONS: Patient-related and lesion-related characteristics were significantly different between EST and LST/VLST. Data collection from adverse event reporting could be a helpful strategy for evaluation of this serious but rare complication.

Changes in Antidiabetic Drug Prescription and Glycemic Control Trends in Elderly Patients with Type 2 Diabetes Mellitus from 2005-2013: An Analysis of the National Center Diabetes Database (NCDD-03).

Objective To analyze the changes in the pharmacotherapy and glycemic control trends in elderly patients with type 2 diabetes mellitus (T2DM) in Japan. Methods We extracted the data of 7,590 patients (5,396 men and 2,194 women; median year of birth: 1945) with T2DM registered in the National Center Diabetes Database for the years 2005 to 2013, and conducted age-stratified (<65, 65-74, and ≥75 years of age) analyses. Results The hemoglobin A1c (HbA1c) levels declined from 2005 to 2013, and for those who received antihyperglycemic drug prescription, the HbA1c levels were lower in the older age group than in the younger age group. In the ≥75 age group, dipeptidyl peptidase-4 inhibitors (DPP4i) became the most frequently prescribed drug (49.1%) in 2013, and sulfonylureas remained the second-most frequently prescribed drug (37.8%) with decreased prescribed doses. The prescription ratio of oral drugs associated with a risk of hypoglycemia was higher in patients ≥75 years of age than in those <75 years of age (40.5% and 26.4%, respectively in 2013), although it showed a downward trend. The prescription rates of insulin for patients ≥75 years of age increased during the study period. Conclusion The pharmacotherapy trends for elderly patients with T2DM changed dramatically in Japan with the launch of DPP4i in 2009. Glycemic control in a considerable portion of the ≥75 age group in Japan was maintained at the expense of potential hypoglycemia by the frequent, although cautious, use of sulfonylureas, glinides and insulin.

Reoperation for early failure of a freestyle bioprosthesis using a full root technique.

The case is reported of a 65-year-old male who required reoperation for early failure of a Freestyle stentless valve aortic root bioprosthesis implanted using the full root technique. The bioprosthesis had been implanted to treat annuloaortic ectasia associated with severe aortic regurgitation (AR). At 18 months postoperatively, a new diastolic murmur developed, though without complaint by the patient. Transthoracic echocardiography demonstrated severe AR with aneurysmal dilatation of the non-coronary porcine sinus of Valsalva. Pseudoaneurysm formation, associated with perforation of the non-coronary sinus of Valsalva of the bioprosthesis, was observed at surgery. On inspection, the pseudoaneurysm had pushed the commissures inward, and had created severe aortic valve regurgitation. No infection or calcification was detected on the Freestyle valve, and the aortic root was successfully reconstructed using a composite graft.