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Modern regenerative medicine research has expanded well past the development of traditional drugs and medical devices with many promising new therapies encompassing an increasingly diverse range of substances, notably cell-based therapies. These substantial recent developments and the progress in the health care and therapeutics fields necessitate a new regulatory framework agile enough to accommodate these unique therapies and acknowledge their differences with traditional pharmaceuticals. In the United States, recent proposed changes in the regulatory framework for autologous human cells, tissues, and cellular and tissue-based products (HCT/Ps) and their perceived risk-benefit analysis for patients remain controversial in the scientific field. To provide perspective on of the current status of the most recent attempts to redefine and conceptualize these changes in the United States, we will examine 4 draft guidance documents implemented by the Food and Drug Administration in interpreting relevant concepts and terminology pertaining to HCT/Ps: the Bipartisan Policy Center think tank report, "Advancing Regenerative Cellular Therapy: Medical Innovation for Healthier Americans," the proposed REGROW Act for HCT/Ps, and the current 24 Food and Drug Administration-approved HCT/Ps and related products in the United States., (© 2018 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.)

Legislation for expedited-approval pathways and programmes for drugs, biologics or medical devices has been enacted for rapid commercialization of innovative products in the United States of America (USA) and the European Union (EU). However, less innovative products are increasingly benefitting from these expedited-approval pathways, and obligations to collect and report post-marketing data on approved products are being bypassed frequently. The Japanese government recently enacted legislation for a new conditional and time-limited approval pathway dedicated to regenerative medicine products. The current study examines this new legislation and compares it with existing US and EU regulatory frameworks, with a particular focus on how it addresses the limitations of existing systems. Regulations, guidance documents and approval information were gathered from the websites of the respective authorities in the USA, the EU and Japan, and the systems were categorized through qualitative analysis. The pathways and programmes from each region were categorized into four groups, based on the requirement of pre- or post-marketing clinical data. Expedited-approval pathways in the USA and the EU provide similar qualification criteria, such as severity of target disease; however, such criteria are not specified for the new pathway in Japan. Only the Japanese pathway stipulates a time limitation on exceptional approval, requiring post-marketing study for conditional and time-limited products. Continuous improvement is necessary to solve previously addressed issues within the expedited-approval pathways and programmes and to ensure that innovative medical products are rigourously screened, but also readily available to patients in need. The time limitation of conditional approval could be a potential solution to some of these problems. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd., (Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd.)

The current definition of biomaterials differs vastly from it of just a decade ago. According to advancing technologies, it encompasses unpredictable materials such as engineered human cells and tissue. These biomaterials also have to be approved to use in health care business by regulatory authority, which are defined as drug, medical device, or biologics in the regulation. This Leading Opinion Paper addresses the regulatory issues of engineered human cells and tissue products using allogeneic cells that should have a great possibility to develop therapeutics for life-threating diseases or orphan diseases. Six allogeneic human cells and tissue products derived from neonatal or infant fibroblasts and/or keratinocytes were approved as medical devices or biologics in the United States as well as a hematopoietic cell product. For five of the seven products, well-controlled comparative clinical trials were conducted as pre-approval evaluation followed by post-approval evaluation. Although these products avoid a sterilization process usually used for medical devices, no serious malfunction that would lead to class 1 recall was reported. This article would provide insight for development of the engineered human cells and tissue., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.

Objective: To compare the prevalence of diabetes according to the American Diabetes Association (ADA) and World Health Organization (WHO) classifications in a sample of elderly Japanese-American men; to examine the association with total and cardiovascular mortality by diabetes status using both classifications; and to determine whether the fasting or 2-h glucose measurement is a stronger predictor of adverse outcomes., Research Design and Methods: Examinations given from 1991 to 1993 in the Honolulu Heart Program were used as baseline for these analyses. Subjects were 71-93 years of age at that time and were followed for total and cardiovascular disease mortality for up to 7 years., Results: A total of approximately 66% of individuals who had diabetes by WHO criteria were missed when the ADA definition was used. The relative risks of total and cardiovascular mortality for those with versus those without diabetes were similar for both definitions; however, when fasting and postload glucose measures were analyzed as continuous variables, the 2-h measurement was a superior predictor and was independent of fasting glucose. In contrast, fasting glucose was not an independent predictor of these outcomes in the presence of the 2-h measurement., Conclusions: The prevalence of glucose metabolism abnormalities was very high among elderly Japanese-American men. The WHO classification was superior to the ADA classification in identification of subjects at high risk for adverse outcomes. Therefore, we conclude that the 2-h glucose measurement is valuable and should be retained in epidemiologic studies.

Recent nosocomial infections, such as HCV and tuberculosis, have stimulated interest in infection control practices in health care setting. Therefore, Infection Control Doctors (ICDs) have already started to make best strategies for infection prevention and safe practice. However, many obstacles lie ahead of them, with the cost as the most important. It has been believed that it takes a lot of money for the improvement of infection control. But, this aspect has been changed completely by introduction of EBM because EBM can point out and quite unnecessary practices, resulting in saving money. CDC has been published many guidelines which is evidence based. Therefore, it might be best strategy to introduce CDC guideline into the infection control in Japanese hospitals.

Peripheral vascular disease as measured by the ankle/brachial blood pressure index (ABI) is associated with increased risk of mortality and morbidity. Few sources of data on the relationship of risk factors to ABI are available for the elderly, especially those > 80 years of age, and minority populations. ABI measurements from the Honolulu Heart Program's fourth reexamination of 3450 ambulatory, elderly Japanese American men indicate that the prevalence of an abnormal ABI, defined as a ratio of < 0.9, was 13.6%, increasing from 8.0% in those 71 to 74 years of age to 27.4% in those 85 to 93 years. Associations that were U or J shaped were present for a number or risk factors (higher rates of abnormality [ABI < 0.9] in those in the lowest and highest risk factor quintiles) in a cross-sectional analysis. Risk factors measured at baseline were also predictive of an abnormal ABI 25 years later, even after adjustment for multiple risk factors. The odds ratio (OR) for an ABI < 0.9 at the 80th percentile of cholesterol compared with that at the 20th percentile was 1.4; the OR for 1-hour postload glucose was 1.3, and for alcohol intake 1.2. The OR associated with hypertension was 1.8 and that for smoking, 2.9 (P < .05 for all ORs). These findings are consistent with ABI being a marker for generalized atherosclerotic disease in old and very old Japanese American men.

Clinical and epidemiological studies consistently indicate that elevations in plasma fibrinogen concentration are associated with the presence and development of coronary heart disease (CHD). These elevations are strongly correlated with smoking behavior and may play a significant role in mediating a relation of smoking to CHD. This cross-sectional survey of 3571 elderly Japanese-American men, aged 71 through 93 years, represents survivors of the Honolulu Heart Program cohort. Active smokers are almost twice as likely to be represented in the highest quintile of the fibrinogen distribution compared with the lowest quintile (9.8% versus 5.3%, respectively). The highest prevalence of CHD (34%) was noted in past and current smokers who were in the highest quintile of fibrinogen. The age-adjusted relative odds of prevalent CHD comparing the average fibrinogen levels in the first and fifth quintiles were 1.36 (95% confidence interval, 1.13 to 1.64). After adjustment for smoking status, blood pressure, total and HDL cholesterol, diabetes status, hematocrit, and white cell count, the association between fibrinogen and CHD was changed slightly and remained statistically significant (P < .05). These findings in an elderly cohort of Japanese-American men are consistent with previous studies among middle-aged adults demonstrating fibrinogen to be associated with indicators of clinical CHD and CHD risk factors. Because of the cross-sectional nature of this study, it is not possible to distinguish whether the observed relation of fibrinogen to prevalent CHD is causal or whether it represents a marker of active and progressive disease.

Hip fracture incidence rates among men and women of Japanese ancestry living on Oahu, Hawaii, from 1979 to 1981 were compared with rates for Japanese living on Okinawa, Japan, from 1984 to 1985. Both rates were further compared with those for various American Caucasian populations, including that of Rochester, Minnesota, from 1978 to 1982. Age-specific and cumulative (age 50-84 years) hip fracture rates among persons of Japanese ancestry were approximately half that of Caucasians for both sexes. Although diet and other cultural attributes of the Oahu group have become more westernized than the Okinawan population, there were no detectable differences in hip fracture rates between Oahu and Okinawa Japanese. Additional studies are needed to determine whether the observed differences in fracture rates between Caucasians and Japanese might be related to differences in bone mass, body size, frequency of falls, or other factors.

Electrocardiographic patterns of left axis deviation and left anterior hemiblock, defined by a frontal plane QRS axis of minus 30 degrees to minus 44 degrees and minus 45 degrees to minus 90 degrees, respectively, with normal QRS duration, were found to be fairly common (2.6 and 1.5 percent, respectively) in a community population of 8,000 Japanese-American men aged 45 to 69 years. More than 60 percent of men with these electrocardiographic patterns had no other cardiovascular abnormalities, and the incidence of fatal or nonfatal coronary heart disease and stroke in this group during observation periods of 3 to 6 years was not significantly different from that of control normal men. A significant association was found between these electrocardiographic patterns and the prevalence of hypertension, myocardial infarction and stroke. However, the association of myocardial infarction with left anterior hemiblock appeared to be coincidental and was attributed largely to the similarity of the electrocardiographic manifestations of left anterior hemiblock and inferior wall myocardial infarction. Men with left axis deviation were fatter and had higher blood pressure than the control population. No such difference could be demonstrated for men with left anterior hemiblock although this group was significantly older than control subjects and men with left axis deviation. The results of our study suggest that there are qualitative differences between the causative mechanisms and clinical features of left axis deviation and those of left anterior hemiblock.

The importance of electrocardiographic (ECG) abnormalities at baseline examination for subsequent risk of stroke was analyzed in a 12-year follow-up of 7,560 men in the Honolulu Heart Program, aged 45-68 years, who were free of coronary heart disease and stroke at baseline. Age-adjusted univariate analysis showed that men with major ST depression, left ventricular strain, left ventricular hypertrophy, major T wave inversion, and overall major ECG abnormalities had considerably higher (2.5-5.4 times) incidence rates of both thromboembolic and hemorrhagic stroke than those with normal baseline ECG. When blood pressure, age, cigarette smoking, alcohol consumption, fat intake, serum glucose concentration, serum uric acid concentration, years of education, and years lived in Japan were taken into consideration through multivariate analysis, the ECG abnormalities retained a significant relation with stroke. Our study demonstrates that resting ECG abnormalities are independent predictors of both thromboembolic and hemorrhagic stroke.