Population-Based Observational Study of Adverse Drug Event-Related Mortality in the Super-Aged Society of Japan.

INTRODUCTION: Adverse drug events (ADEs) are a major cause of mortality. OBJECTIVE: We examined long-term trends for ADE-related deaths in Japan. METHODS: This observational study was conducted using the Japanese Vital Statistics from 1999 to 2016. Data for all ADE-related deaths were extracted using International Classification of Diseases, Tenth Revision codes. We analysed ADE-related deaths by age and sex and calculated crude and age-standardised mortality rates (ASMR) per 100,000 people. We used Joinpoint regression analysis to identify significant changing points in mortality trends and to estimate annual percentage change (APC). RESULTS: In total, 16,417 ADE-related deaths were identified. The crude mortality rate for individuals aged ≥ 65 years was higher than that of young individuals. The ASMR per 100,000 people increased from 0.44 in 1999 to 0.64 in 2016. The crude mortality rate increased from 0.44 in 1999 to 1.01 in 2016. The APC of ASMR increased at a rate of 2.8% (95% confidence interval [CI] 1.4-4.2) throughout the study period. In addition, crude mortality increased at a rate of 5.7% (95% CI 4.2-7.3) annually from 1999 to 2016. The ADE-related mortality rate was higher for men than for women during the study period. CONCLUSIONS: The number of and trend in ADE-related deaths increased in Japan from 1999 to 2016, particularly in the older population.

Adverse drug events (ADEs) are a public health issue, but descriptive data on ADEs in Japan are limited. Studies have shown that elderly people have a higher risk of dying from ADEs. Japan has one of the most rapidly aging populations and the highest percentage of older individuals worldwide. Clarifying long-term data trends in Japan is important in the aging world. Here, we aimed to clarify the trend in mortality related to ADEs in Japan. We selected 16,417 deaths that were assigned an underlying cause (i.e., ADEs) in vital statistics based on codes from the International Classification of Diseases, Tenth Revision (ICD-10). The crude mortality rate for both sexes increased from 0.44 per 100,000 in 1999 to 1.01 in 2016. The average annual percentage change (average APC), which numerically shows the change over time, was 5.7% throughout the study period. The age-standardised mortality rate, using the population in the first year, increased from 0.44 per 100,000 in 1999 to 0.64 in 2016. The average APC of the age-standardised mortality rate showed an increasing trend at 2.8%. Even after age standardisation, ADE-associated death showed an increasing trend. In particular, population groups aged ≥65 years showed a continuous increasing trend. These findings suggest that the ADE-related mortality rate in Japan is increasing, especially in elderly individuals.

Trends in hepatitis C virus-associated mortality rates in Japan, 1998-2017.

BACKGROUND AND AIM: The current prevalence of hepatitis C virus infection and hepatitis C virus-associated mortality in Japan falls short of the World Health Organization goal of viral hepatitis elimination by 2030. We aimed to evaluate the trends in hepatitis C virus-associated mortality in Japan. METHODS: This nationwide observational study used the Japanese Vital Statistics from 1998 to 2017 and included all Japanese hepatitis C virus-associated deaths (84 936) of adults aged ≥ 40 years. We calculated the crude and age-standardized mortality rates per 100 000 persons by age and sex. Joinpoint regression analysis was used to identify significant changing points in trends and to estimate the annual percentage changes and the average annual percentage changes for the entire study period. RESULTS: The crude mortality rate per 100 000 persons (annual death number) increased from 5.5 (3548) in 1998 to 7.0 (4843) in 2005 and decreased to 4.0 (3095) in 2017. By 2017, the crude mortality rates per 100 000 persons among men and women had dropped to 3.6 and 4.3, respectively. The age-standardized mortality rate was higher in women than in men. The average annual percentage change was -3.8% (95% confidence interval: -5.0 to -2.5). The declining trend was more rapid in men (-4.5%, 95% confidence interval: -5.3 to -3.6) than in women (-2.7%, 95% confidence interval: -3.8 to -1.6). CONCLUSIONS: Trends in hepatitis C virus-associated mortality rates have declined in an accelerating manner in Japan, especially among men.

Trends in the Nontuberculous Mycobacterial Disease Mortality Rate in Japan: A Nationwide Observational Study, 1997-2016.

BACKGROUND: The incidence of nontuberculous mycobacterial (NTM) infections has been increasing worldwide, becoming a significant healthcare burden especially among elderly people. This study aimed to evaluate the trends in NTM-associated mortality in Japan. METHODS: This study used vital statistics data and data on all NTM-associated deaths (N = 18 814) among individuals aged ≥40 years in Japan from 1997 to 2016. We calculated the crude and age-adjusted mortality rates by age and sex and used joinpoint regression to analyze trends and estimate the average annual percentage change (AAPC). We compared crude NTM- and tuberculosis-associated mortality rates by sex. RESULTS: The overall crude annual mortality rate increased from 0.63/100 000/year in 1997 to 1.93/100 000/year in 2016 and was the highest among individuals aged 80-84 years. The AAPC of the crude mortality rates among men of all ages and women aged 40-59 years were stable but increased among women aged 60-79 years (3.5%; 95% confidence interval [CI], 2.8-4.3) and ≥80 years (4.3%; 95% CI, 3.7-4.9). Among men, the age-adjusted mortality rates did not show a significant trend, while among women, the rates increased over the study period (AAPC, 4.6%; 95% CI, 2.7-6.6). In women, the crude NTM-associated mortality rate exceeded the tuberculosis mortality rate in 2014, 2015, and 2016. CONCLUSIONS: NTM mortality increased in Japan between 1997 and 2016, especially among the elderly female population. Given the increasing NTM-associated mortality and the susceptible aging population, public health authorities in Japan should pay greater attention to NTM infections.

Antibiotic prescriptions for Japanese outpatients with acute respiratory tract infections (2013-2015): A retrospective Observational Study.

OBJECTIVES: Appropriate antibiotic prescriptions for outpatients with acute respiratory tract infections (ARTIs) are urgently needed in Japan. However, the empirical proof of this need is under-documented. Therefore, we aimed to determine antibiotic prescription rates, and the proportions of antibiotic classes prescribed for Japanese patients with ARTIs. METHODS: We analysed health insurance claims data over 2013-2015 among Japanese patients aged <75 years and determined the following indicators: 1) visit rates for patients with ARTIs and antibiotic prescription rates per 1000 person-years, and 2) proportion of visits by antibiotic-prescribed patients with ARTIs. We defined broad-spectrum antibiotics using the WHO Anatomical Therapeutic Chemical classification 4 level codes. RESULTS: Among 8.65 million visits due to ARTIs at 6859 hospitals and 62,024 physicians' offices, the visit rate and antibiotic prescription rate per 1000 person-years were 990.6 (99% confidence interval [CI], 989.4-991.7) and 532.4 (99% CI, 531.6-533.3), respectively. The visit rates for patients aged 0-17, 18-59, and 60-74 years were 2410.0 (99% CI, 2407.2-2412.9), 683.6 (99% CI, 682.7-684.6), and 682.1 (99% CI, 678.2-686.0), and antibiotic prescription rates were 1093.3 (99% CI, 1091.4-1095.2), 434.1 (99% CI, 433.4-434.9), and 353.4 (99% CI, 350.7-356.1), respectively. The overall proportion of antibiotic prescriptions for ARTI visits was 52.7% and 91.3% of the antibiotics prescribed were broad-spectrum. CONCLUSIONS: Both the visit rates and antibiotic prescription rates for ARTIs were high in this Japanese cohort. The proportion of antibiotic prescriptions exceeded that recommended in the clinical guidelines. Thus, there might be a scope for reducing the current antibiotic prescription rate in Japan.

Trends in Place of Death in a Super-Aged Society: A Population-Based Study, 1998-2017.

Background: Globally, the number of deaths is estimated to increase to 74 million per year by 2030. Place of death (PoD) is increasingly being recognized as an important aspect of end-of-life care. However, recent trends in PoD in Japan, one of the super-aged societies, are unknown. Objective: To analyze trends in PoD in Japan over two decades. Design: Population-based retrospective observational study. Setting: All deaths reported in Japan, 1998-2017. PoD was defined as hospital, nursing home, or own home. Results: All Japanese decedents (∼22.6 million) over the past 20 years were analyzed. The proportion of hospital deaths was consistently high (>80%), with a significant decreasing trend from the mid-2000s. Although the proportion of deaths at home decreased in the first half of the study period, they later increased. There was a low proportion of deaths in nursing homes compared to other places of death; however, the proportion increased continually throughout the study period, particularly among women. In 2015, more women died in nursing homes than at home. Although the proportion of hospital deaths declined in the second half of the study period, their overall number continued to increase, reflecting an increase in total deaths in Japan. Conclusions: This study highlighted rapid changes in trends in PoD in Japan, and the need to consider affordable end-of-life care in Japan as well as other countries with aging populations. The findings from this long-term epidemiological study provide important insights on this issue.

Place of death trends among patients with dementia in Japan: a population-based observational study.

Dementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged ≥65 years and died during 1999-2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999-2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.

Fall-related mortality trends in older Japanese adults aged ≥65 years: a nationwide observational study.

OBJECTIVES: Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016. DESIGN: We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare. RESULTS: The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women. CONCLUSIONS: Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required.