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. 2024 Feb 28;19(2):e0299700. doi: 10.1371/journal.pone.0299700

Changes in the place of death before and during the COVID-19 pandemic in Japan

Masashi Shibata 1, Yuki Otsuka 2,*, Hideharu Hagiya 2, Toshihiro Koyama 3, Hideyuki Kashiwagi 4, Fumio Otsuka 2
Editor: Mihajlo Jakovljevic5
PMCID: PMC10901324  PMID: 38416759

Abstract

Background

In the global aging, the coronavirus disease 2019 (COVID-19) pandemic may have affected the place of death (PoD) in Japan, where hospital deaths have dominated for decades. We analyzed the PoD trends before and during the COVID-19 pandemic in Japan.

Methods

This nationwide observational study used vital statistics based on death certificates from Japan between 1951 and 2021. The proportion of PoD; deaths at home, hospitals, and nursing homes; and annual percentage change (APC) were estimated using joinpoint regression analysis. Analyses were stratified by age groups and causes of death.

Results

After 2019, home deaths exhibited upward trends, while hospital death turned into downward trends. By age, no significant trend change was seen in the 0–19 age group, while hospital deaths decreased in the 20–64 age group in 2019. The trend change in home death in the ≥65 age group significantly increased since 2019 with an APC of 12.3% (95% confidence interval [CI]: 9.0 to 15.7), while their hospital death trends decreased by −4.0% (95% CI: −4.9 to −3.1) in 2019−2021. By cause of death, home death due to cancer and the old age increased since 2019 with an APC of 29.3% (95% CI: 25.4 to 33.2) and 8.8% (95% CI: 5.5 to 12.2), respectively.

Conclusion

PoD has shifted from hospital to home during the COVID-19 pandemic in Japan. The majority of whom were older population with cancer or old age.

Introduction

With the increase in life expectancy, the global population is aging rapidly. Japan is one of the most super-aged countries in the world, and end-of-life care for older population has been a pressing issue [1]. Since the 1950s, medical services and technology have developed sharply during the period of rapid economic growth and the bubble economy in Japan. Consequently, we benefited from the increased number of inpatient beds, leading to a change in the place of death (PoD), i.e., an increase in hospital deaths over the 21st century [2]. However, with the establishment of a long-term care insurance system in 2000 and the institutionalization of home care support clinics in 2006, home deaths have increased in Japan [3]. In fact, in 2005, we observed a decreasing trend in hospital deaths and an inverse increase in home deaths in Japan [4]. However, previous efforts have revealed that the decreasing trend of hospital deaths differs greatly depending on the cause of death (CoD) [5, 6], and the details of this trend need to be examined individually.

The coronavirus disease 2019 (COVID-19) pandemic occurred amid this trend in PoD. Facing the disease outbreak, the world has witnessed various changes in people’s access to and utilization of healthcare services [7]. Although Japan recorded fewer COVID-19-related deaths than other countries [8], the provision of medical services for non-COVID-19 diseases, including emergency care, surgery, and hospitalization, is considerably limited [9–12]. Moreover, family visits to hospitalized patients were severely regulated from the perspective of infection prevention and control; thus, some people might refuse hospitalization. These direct and indirect changes could have contributed to the changing trend of PoD in Japan. In order to be prepared for the upcoming pandemic, the governments and health care providers need to know how the COVID-19 pandemic has changed the demographics of mortality, including PoD. However, studies on this topic are limited. Thus, this study aimed to determine the PoD and CoD trends before and during the COVID-19 pandemic in Japan, a country with a super-aged society.

Materials and methods

Data source

This population-based observational study was conducted in Japan using vital statistics. Data on the number of deaths by location and cause were obtained from vital statistics based on death certificates collected by the Japanese Ministry of Health, Labor, and Welfare from 1951 to 2021 [13]. In the Japanese death certificate database, the direct and underlying CoD and PoD are recorded based on information from death certificates completed by doctors within one week of death. The underlying CoD is published in the vital statistics, based on death certificates. Since 1995, it has been classified based on the International Classification of Diseases Tenth Revision (ICD-10) codes. Determining the underlying cause of death from death certificates consists of an auto-coding system, a rule-based process with manual review. Manual review is performed when the auto-coding system cannot assign an ICD-10 code or when ancillary information is included, which accounts for approximately 40% of the approximately 100,000 death certificates per month [14].

Data processing

PoD was classified as hospital (hospital or physician’s office), nursing home (care home or nursing care home), or home. Data were stratified by age as follows: 0–19 years, 20–64 years, and ≥65 years. The top five CoDs were redefined based on ICD-10 codes as follows: pneumonia (J12–J18), cerebrovascular disease (I60–I69), heart disease (I01–I02, I05–I09, I20–I25, I27, and I30–I52), cancer (C00–97), and old age (R54). In 2021, the major causes of death were 26.5% from cancer, 14.9% from heart disease, 10.6% from old age, 7.3% from cerebrovascular disease, and 5.1% from pneumonia [13]. In the Japanese manual on completing a death certificate, old age is defined as the death of an old person from natural causes without an apparently describable CoD.

Statistical analysis

Firstly, we analyzed the proportion of PoD from 1951 to 2021, then by age group or by the top five CoDs from 2001 to 2021. The percentage of PoDs was calculated by dividing the number of deaths that occurred at each hospital, nursing home, and home by the total number of deaths that occurred in one year. To estimate PoD trends, a joinpoint regression model was applied using the Joinpoint Regression Program version 4.9.1.0 (April 2022; National Cancer Institute). This study used the permutation test as the model selection method in the Joinpoint regression analysis. The year was the independent variable.

The annual percent change (APC) characterizes trends in the proportion of deaths by PoD over time. This method defines the percentage of deaths by PoD as a constant percentage change relative to the previous year’s percentage. A single APC can accurately characterize the trend across a set of data. The Joinpoint model uses statistical criteria to determine when and how often an APC changes. Average Annual Percent Change (AAPC) summarizes trends over the entire study period. This allows the average AAPC over multiple years to be represented by a single number; the AAPC is useful when the joinpoint model shows a change in trend over those years. Additionally, it is calculated as a weighted average of the APCs from the joinpoint model, with the weight equal to the length of the APC interval. Data analysis was performed independently by M. Shibata and Y. Otsuka for validation. Statistical significance was set at p < 0.05.

Ethics approval

The Japanese Ministry of Health, Labour, and Welfare and the Statistics Bureau of the Ministry of Internal Affairs and Communications provided the data for this study. The Okayama University Hospital Ethics Committee determined that a formal ethics review was unnecessary because the data were anonymous and accessible to the general public.

Results

In 1951, hospital, home, and nursing home deaths accounted for 11.6%, 82.5%, and 0% of all deaths, respectively; in 2021, the percentages changed to 67.4%, 17.2%, and 13.5%, respectively. Trends in the number of PoDs over the past 70 years in Japan are presented in Fig 1. Since the 1950s, hospital deaths have steadily increased, whereas home deaths have gradually declined until the mid-2000s; however, they have gradually increased after that. The number of deaths in nursing homes has increased since the late 2000s. These trends indicated apparent shifts between 2019 and 2020: hospital deaths demonstrated a downward trend, whereas home deaths exhibited upward trends.

Fig 1. Trends in the place of death since 1951 in Japan.

Fig 1

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The number of counted deaths in hospitals, nursing homes, and homes are demonstrated. The number of hospital deaths decreased and that of other deaths increased after 2019 when the COVID-19 pandemic began.

The number and the proportion of PoD were different by age in 2001 and 2021 (S1 Table). The PoD trend during this period was calculated by age group and represented in Table 1. The pediatric population aged ≤19 years demonstrated a monotonic trend, with an APC of 3.0% (95% CI: 2.6 to 3.5) increase in home deaths and 0.4% (95% CI: −0.7 to −0.2) decrease in hospital deaths. No trend change points were observed. In contrast, in young- and middle-aged adults (20–64 years), the proportion of home deaths remained slightly increasing trends by 2019 and indicated an upsurge thereafter with an APC of 12.2% (95% CI: 8.9 to 15.6). Meanwhile, hospital deaths decreased suddenly from 2019 to 2021 with an APC of −5.0% (95% CI: −9.2 to −0.5). The older population aged ≥65 years initially demonstrated a decreasing trend in the early 2000s (APC, −4.1% 95% CI: −5.4 to −2.8), then rising trends from 2005 to 2019, and finally a big surge since 2019 with an APC of 12.3% (95% CI: 9.0 to 15.7). In the inverse proportion, hospital deaths in the older population decreased, resulting in an APC of −4.0% (95% CI: −4.9 to −3.1) in 2019–2021.

Table 1. Trends in the place of death by age group in Japan in 2001–2021.

Age/facility Period 1 Period 2 Period 3 Period 4 Average APC (%)
(95% CI)
Years APC (%) Years APC (%) Years APC (%) Years APC (%)
0–19 years
    Home 2001–2021 3.0* 3.0*
(2.6 to 3.5)
    Hospital 2001–2021 −0.4* −0.4*
(−0.7 to −0.2)
    Nursing
home† 		– –
20–64 years
    Home 2001–2005 2.0* 2005–2008 4.1* 2008–2019 2.6* 2019–2021 12.2* 3.6*
(3.0 to 4.2)
    Hospital 2001–2019 −0.5* 2019–2021 −5.0* −1.0*
(−1.4 to −0.5)
    Nursing
home		 2001–2003 −12.1 2003–2021 15.8* 12.6*
(9.3 to 16.1)
≥65 years
    Home 2001–2005 −4.1* 2005–2015 0.3 2015–2019 2.2* 2019–2021 12.3* 0.9*
(0.4 to 1.4)
    Hospital 2001–2005 0.5* 2005–2009 −0.6* 2009–2019 −1.1* 2019–2021 −4.0* −1.0*
(−1.1 to −0.9)
    Nursing
home		 2001–2003 −0.9 2003–2007 6.7* 2007–2013 12.7* 2013–2021 7.6* 8.0*
(7.3 to 8.8)
Open in a new tab

*Significantly different from zero (p < 0.05).

† Data were not available for this age group. APC, annual percentage change; CI, confidence interval.

The trends in the proportions of PoD by CoD over the past two decades are depicted in Fig 2, and the results of the joinpoint regression analysis are summarized in Table 2. Regarding cancer-related deaths, the largest inflection point was observed in 2019. Proportion of home deaths had a significant increase since 2005, which further escalated between 2019 and 2021 with an APC of 29.3% (95% CI: 25.4 to 33.2). By contrast, that of hospital death started to decrease in 2005, and declined greatly in 2019 with an APC of −6.3% (95% CI: −6.9 to −5.8). No significant changes in heart disease were observed during the study period. The proportion of home deaths due to cerebrovascular disease initially demonstrated a decreasing trend and has increased since 2016 (APC, 3.4% 95% CI: 2.0 to 4.8). Hospital deaths followed an inverse trend and had an APC of −2.5% from 2019 to 2021. The proportion of pneumonia-related deaths indicated a trend similar to that of deaths related to cerebrovascular diseases. A remarkable increase in home deaths was observed from 2017 to 2021, with an APC of 5.9% (95% CI: 2.2 to 9.8), Finally, the proportion of home deaths due to old age initially followed significant decreasing trends, but indicated a great increase since 2019 (APC, 8.8% 95% CI: 5.5 to 12.2). Inversely proportional to this, the proportion of hospital deaths started to decline in 2005, with an APC of −0.8% (95% CI: −1.1 to −0.4) in 2005–2012, −2.8% (95% CI: −3.1 to −2.6) in 2012–2019, and −5.8% (95% CI: −7.1 to −4.5) in 2019–2021. The AAPC of all the categories for nursing home deaths demonstrated significant increases, ranging from 5.2% (95% CI: 4.5 to 5.9) for pneumonia to 12.4% (95% CI: 11.3 to 13.5) for cancer.

Fig 2. Trends in the place of death by cause of death in Japan in 2001–2021.

Fig 2

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The percentage of place of death among the top five CoD in Japan was determined. Statistically significant trend shifts in 2019 were observed for cancer and old age.

Table 2. Trends in the place of death by cause of death in Japan in 2001–2021.

Age/facility Period 1 Period 2 Period 3 Period 4 Average APC (%)
(95% CI)
Years APC (%) Years APC (%) Years APC (%) Years APC (%)
Cancer
    Home 2001–2005 −0.4 2005–2019 5.7* 2019–2021 29.3* 6.5*
(6.0 to 7.1)
    Hospital 2001–2005 0.1 2005–2011 −0.7* 2011–2019 −1.0* 2019–2021 −6.3* −1.3*
(−1.3 to −1.2)
    Nursing
home		 2001–2004 2.9 2004–2015 15.9* 2015–2019 9.5* 2019–2021 14.1* 12.4*
(11.3 to 13.5)
Heart disease
    Home 2001–2013 −0.1 2013–2017 −2.1* 2017–2021 0.9* −0.3
(−0.3 to 0)
    Hospital 2001–2006 0 2006–2013 −0.6* 2013–2017 0.1 2017–2021 −1.0* −0.4*
(−0.5 to −0.2)
    Nursing
home		 2001–2005 1.1 2005–2013 8.7* 2013–2021 5.8* 6.0*
(5.4 to 6.6)
Cerebrovascular disease
    Home 2001–2004 −5.2* 2004–2016 −1.4* 2016–2021 3.4* −0.8*
(−1.3 to −0.3)
    Hospital 2001–2006 0.5* 2006–2019 −0.8* 2019–2021 −2.5* −0.7*
(−0.8 to −0.5)
    Nursing
home		 2001–2006 2.5* 2006–2013 12.2* 2013–2019 4.5* 2019–2021 8.4* 7.0*
(6.1 to 8.0)
Pneumonia
    Home 2001–2006 −10.2* 2006–2017 −0.6 2017–2021 5.9* −1.9*
(−2.7 to −1.0)
    Hospital 2001–2006 0.5* 2006–2021 −0.4* −0.2*
(−0.2 to −0.1)
    Nursing
home		 2001–2006 −1.4 2006–2014 9.7* 2014–2018 3.2* 2018–2021 7.5* 5.2*
(4.5 to 5.9)
Old age
    Home 2001–2014 −7.6* 2014–2019 −2.0* 2019–2021 8.8* −4.7*
(−5.1 to −4.3)
    Hospital 2001–2005 4.4* 2005–2012 −0.8* 2012–2019 −2.8* 2019–2021 −5.8* −1.0*
(−1.2 to −0.8)
    Nursing
home		 2001–2011 8.6* 2011–2016 5.4* 2016–2021 2.7* 6.3*
(6.0 to 6.6)
Open in a new tab

*Significantly different from zero (p < 0.05). APC, annual percentage change; CI, confidence interval.

Discussion

This study revealed a significant increase in home deaths after 2019 in Japan. This period coincides with the time of the COVID-19 pandemic. The first case of COVID-19 was identified in Japan on January 16, 2020, and the first emergency declaration was issued on April 7, 2020. Since then, the country has experienced waves 1 to 5 through 2021. The fifth wave (7/1/2021 to 9/30/2021), a delta strain (B.1.617), which tended to cause severe illness, was epidemic. This resulted in a sharp increase in the number of critical cases and caused the collapse of the medical system [15].

Based on the study result, the majority of the increase in home deaths was attributed to elderly individuals with cancer or old age, whereas COVID-19 did not constitute a large proportion of deaths at home. No change in the trend was observed in younger or older patients without malignancies. Thus, the shift in the PoD from hospital to home, recognized over the global outbreak of emerging infectious diseases, varied greatly by patient age and CoD. A multicenter web-based survey of the directors of home visit facilities in Japan has reported an increase in home visits for patients with cancer during the pandemic [16]. Additionally, a study using Japanese vital statistics data has reported an increase in excess deaths at home among patients with cancer since the early stages of the pandemic [17]. The present data reflect the results of previous studies.

Several reports on changes in the PoD during the COVID-19 pandemic have been published in the UK. A population-based modeling study has suggested a 220% increase in elderly care facility deaths during the first 10 weeks of the pandemic [18]. Additionally, from March 2020 to March 2021, a descriptive analysis of mortality data from England, Wales, Scotland, and Northern Ireland has reported a 41% increase in home deaths and a 11% increase in hospital deaths, whereas hospice deaths decreased by 15% [19]. The UK has a significant number of COVID-19 deaths, with 130.1 deaths per 100,000 people [8]. Meanwhile, the mortality rate in Japan is 7.3 deaths per 100,000 people, with comparatively lower overall excess mortality [19]. Thus, the data between the two countries cannot be simply compared.

The changes in the PoD in Japan, where the direct impact of COVID-19 was minimal, may have been influenced by the following reasons. First, the pandemic severely limited hospital capacity. The pandemic’s restrictions on access to hospital beds increased the number of cases in which hospitals could not accept emergency transports [20] and in cases where transport to hospitals providing intensive care was difficult [21]. This may have prevented patients who should have received care at the hospital from accessing it. Second, the intentions of the patient’s family changed due to the restriction of visits. Although it is important to have family support in end-of-life care, hospital visitation restrictions were implemented to prevent hospital outbreaks during the pandemic. This may have increased the number of patients requesting home-based palliative care, and a multicenter web-based survey of home visit facilities in Japan during the pandemic supports this [16]. Furthermore, disease-specific differences in the prevalence of palliative care may explain why the impact of this shift varies by age and cause of death. Palliative care in Japan has a history of being developed mainly for patients with cancer under the Cancer Control Act [22] and home care and palliative care for patients without cancer is still developing. Therefore, it is possible that a system to provide home palliative care to the potential demand of patients without cancer, during the pandemic was not yet in place.

Strength of the present study is that it used the vital statistics and thus enabled us to clarify the nationwide trend of PoD in Japan. While, several limitations of this study should also be considered. First, this was a descriptive study, and the causal relationship between the COVID-19 pandemic and changes in the PoD is inconclusive. PoD may be affected by both environmental and individual variables, such as changes in patient preferences for care settings caused by the pandemic or the discharge of patients from medical institutions to secure hospital beds. However, the present findings cannot be directly used to assess causal correlations. Second, other unmeasured confounding factors that could potentially influence the choice of end-of-life care location in addition to age, sex, and CoD were not considered. Hence, other parameters identified in previous studies should be verified in future studies. However, PoD changes since the pandemic have occurred in only three years, and the impact of factors that occur over a longer period, such as population aging, is expected to be limited. Third, the CoDs on death certificates may have been misclassified. For example, in old age, any disease including COVID-19 present may be misclassified. Thus, the apparent increase in home deaths of old age may suggest an underdiagnosis of COVID-19. Nonetheless, the accuracy of CoD is rather high, particularly for patients with cancer whose changes in PoD were the most pronounced [23]. Finally, this study covered data from 2019 to 2021, including the first five waves of the COVID-19 pandemic in Japan. Depending on the viral variants and hospital capacity, the mortality rate of COVID-19 may change. Thus, the effects of the sixth and subsequent waves after 2022 are unknown. Future studies incorporating longer-term data are needed to determine the clinical significance of this trend change.

Conclusions

In conclusion, the dying situation of Japanese patients with cancer or old age has changed during the COVID-19 pandemic. The rapid shift of PoD from hospital to home since the pandemic may require greater expansion of home palliative care to accommodate the growing number of terminally ill homebound patients. Also, whether this trend is preferable for patients and their families and whether it will persist after the end of the pandemic remain debatable. Therefore, further studies focusing on the quality of end-of-life care during COVID-19 pandemic are suggested. At the very least, physicians are expected to continue to pursue a good death for patients.

Supporting information

S1 Table. Number and proportion of deaths by place and age group in 2001 and 2021.

(DOCX)

pone.0299700.s001.docx (14.7KB, docx)

Acknowledgments

We would like to thank Editage (www.editage.jp) for the English language editing.

Data Availability

The minimal dataset necessary to replicate our study findings can be accessed directly through the Ministry of Health, Labour and Welfare's website (https://www.mhlw.go.jp/english/database/db-hw/outline/index.html). This link leads to the comprehensive database which contains the data we have utilized.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

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23 Oct 2023

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The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study addresses a very pertinent and timely issue, especially in the context of global aging and the challenges the COVID-19 pandemic has posed on health systems worldwide.

The findings are of significant importance as they illustrate the changing dynamics of the PoD in Japan, particularly during the pandemic years. The shift from hospital deaths to home deaths, especially in the older population with cancer or old age, is a trend that needs to be comprehensively understood for potential policy implications and healthcare planning. I find this manuscript to be of high quality and relevance. It sheds light on a topic that warrants immediate attention, especially in the current global health scenario.

Reviewer #2: I have reviewed the manuscript titled "Changes in the Place of Death During COVID-19 Pandemic in Japan." While the authors have made an attempt to explore the effects of the COVID-19 pandemic on the location of deaths in Japan, I have several major concerns regarding the methodology and the scientific significance of the study, which need to be addressed before considering publication.

The primary concern is the limited timeframe after COVID-19 pandemic in the study. The COVID-19 pandemic only spanned two years. To effectively evaluate the impact of COVID-19, it is desirable to have data covering both pre-pandemic (2019) and pandemic (2020) periods, with at least five years of data on each side [International Journal of Epidemiology, 2017, 348–355]. The short observation period may introduce bias, making it challenging to draw robust conclusions about the impact of COVID-19 on the changes observed. Furthermore, while the results may indicate APC, it is essential to consider whether these changes are clinically significant and meaningful absolute difference in the context of a 70-year timeframe.

The manuscript reports changes in the place of death, particularly an increase in home deaths due to cancer and old age. However, it lacks an in-depth analysis of the underlying reasons for these changes. A significant portion of the discussion relies on findings from other studies, which may not directly correlate with the data presented in this study. The discussion, therefore, appears to be speculative and lacking a scientific foundation.

The clinical implications of the study's findings remain unclear. It is challenging to ascertain what actionable insights or recommendations can be derived from this research, especially for future pandemic.

Reviewer #3: The paper analyzes the variation in the place of death (PoD) according to major causes of death during the COVID-19 pandemic in Japan using nationwide death certificate data. The results are interesting and contribute to the analysis of the effect of the pandemic on general and cause-specific mortality. The paper is well written and the results are clearly described. However, some clarifications in the methods section and some revisions of the results would improve the paper.

My comments and suggestions for the authors:

Materials and Methods

1) Line 73. Since the analysis concerns also cause-specific mortality data a more detailed description of death certificates data processing is required. In particular, specify whether death certificates are entirely processed through an automatic coding system (for the coding of the single entries and the selection of the underlying cause) or they are in part manually reviewed by experts (in this case, please report the percentage of certificates manually reviewed). In addition, since you are investigating long-time series data, you should specify whether the same coding system was adopted all over the study period, and whether there have been any change/update in the classification of causes of death (for example from ICD9 to ICD10). Lastly, it should specified that the analysis refers to underlying cause-of-death data (I suppose so).

2) Line 84, Statistical analysis. Please add details on the Jointpoint regression analysis, for instance minimum/maximum number of joinpoints tested, model used and regressor (calendar year). In addition, as some readers might not be familiar with this kind of analysis, I recommend to explain that the APC indicates the annual percent change in the proportion (?) of deaths by PoD and that it has been estimated for different time periods.

Results

3) Lines 100-101: “Trends in the number of PoDs over the past 70 years in Japan are presented in Fig. 1. Since the 1950s, hospital deaths have steadily increased, whereas home deaths have gradually declined”. From Fig.1 I would say that home deaths have gradually declined until mid 2000s, being gradually increasing thereafter.

4) lines 100-104: Please cite in the text the proportion of deaths by each single PoD on total deaths at the beginning and at the end of the study period. I would also suggest to include a table (in the main text or in the supplementary material) reporting the frequencies of deaths by PoD and their proportion in each age stratum, for the first year and the last year considered in the analysis i.e. 2001 and 2021 (see a proposal below), and to briefly comment on them before the presentation of the results of the joinpoint analysis.

2001 2021

no. of deaths % no. of deaths %

0-19 yrs

home

hospital

nursing home

20-64 yrs

home

hospital

nursing home

≥65 yrs

home

hospital

nursing home

5) Lines 111-112: “In order to detect the impact of COVID-19 more sensitively, the results of the trend analysis of the proportion of PoDs focused on the last 20 years in the 21st century”. This sentence expresses a methodological choice, therefore it should be moved to the methods section (Statistical analysis).

6) line 118: “ hospital deaths decreased suddenly in 2019…” it would be more appropriate to say “from 2019 to 2021” than “in 2019”

7) How much do the top five causes of death account on total mortality in Japan? This proportion should be explicitly mentioned in the text

Discussion

The change in time-trends of home deaths due to cancer or old age among the elderly population from 2019 is the main finding of the study.

8) Could the increase in home deaths due to old age be in part attributable to the possible under-diagnosis of SARS-CoV-2 infection, especially during the early pandemic phase? This aspect should be briefly discussed

9) I think the analysis of results could benefit from a brief description of the pandemic phases in Japan during 2020 and 2021

10) In the assessment of time-trends (in particular the increase in home/nursing home deaths) did you evaluate also the possible role of population aging? Although this effect is expected to be limited, this aspect should be discussed

**********

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Reviewer #1: No

Reviewer #2: Yes: Hiroyuki Ohbe

Reviewer #3: No

**********

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PLoS One. 2024 Feb 28;19(2):e0299700. doi: 10.1371/journal.pone.0299700.r002

Author response to Decision Letter 0

15 Jan 2024

Reviewer #1

Comment: The study addresses a very pertinent and timely issue, especially in the context of global aging and the challenges the COVID-19 pandemic has posed on health systems worldwide.

The findings are of significant importance as they illustrate the changing dynamics of the PoD in Japan, particularly during the pandemic years. The shift from hospital deaths to home deaths, especially in the older population with cancer or old age, is a trend that needs to be comprehensively understood for potential policy implications and healthcare planning. I find this manuscript to be of high quality and relevance. It sheds light on a topic that warrants immediate attention, especially in the current global health scenario.

Response: We thank Reviewer #1 for the time and effort spent reviewing our manuscript and providing positive feedback. We are grateful for your assessment of our manuscript as high quality and relevant.

________________________________________

Reviewer #2

Comment: I have reviewed the manuscript titled "Changes in the Place of Death During COVID-19 Pandemic in Japan." While the authors have made an attempt to explore the effects of the COVID-19 pandemic on the location of deaths in Japan, I have several major concerns regarding the methodology and the scientific significance of the study, which need to be addressed before considering publication.

Response: We thank Reviewer #2 for the time and effort spent reviewing our manuscript and for providing positive feedback and suggestions, which have helped us improve our manuscript considerably. We have answered each question below and hope that our responses and revisions address all your comments.

Comment: The primary concern is the limited timeframe after COVID-19 pandemic in the study. The COVID-19 pandemic only spanned two years. To effectively evaluate the impact of COVID-19, it is desirable to have data covering both pre-pandemic (2019) and pandemic (2020) periods, with at least five years of data on each side [International Journal of Epidemiology, 2017, 348–355]. The short observation period may introduce bias, making it challenging to draw robust conclusions about the impact of COVID-19 on the changes observed. Furthermore, while the results may indicate APC, it is essential to consider whether these changes are clinically significant and meaningful absolute difference in the context of a 70-year timeframe.

Response: Thank you for the comment. First, we applied Joinpoint analysis instead of ITS analysis. Your recommendation on covering “at least five years of data on each side” seems to be cited from the ITS analysis tutorial [International Journal of Epidemiology, 2017, 348–355], and we could not find a clear number of data points to be applied for that. The Joinpoint software we used takes the trend data and fits it to the simplest joinpoint model that allows all of its data points. In this case, we did not use 2019 as the split point but rather calculated the change points derived from the optimal model. However, this study only included the first five pandemic waves of COVID-19 in Japan, as you indicated. We have added a note in the Limitations section that future studies incorporating longer-term data are needed to determine clinical significance. (Lines 251‐252) In addition, as you pointed out, this study could not directly estimate the COVID-19 effects on PoD trends. We modified the title (Line 1), abstract (Lines 24 and 37), objectives (Lines 64-65) and discussion from this perspective (Lines 188-189, 256-258).

Comment: The manuscript reports changes in the place of death, particularly an increase in home deaths due to cancer and old age. However, it lacks an in-depth analysis of the underlying reasons for these changes. A significant portion of the discussion relies on findings from other studies, which may not directly correlate with the data presented in this study. The discussion, therefore, appears to be speculative and lacking a scientific foundation.

Response: Thank you for the suggestion. The paragraph discussing the potential reasons for the change in the PoD observed in this study has been revised. (Lines 216-231)

Comment: The clinical implications of the study's findings remain unclear. It is challenging to ascertain what actionable insights or recommendations can be derived from this research, especially for future pandemic.

Response: We thank the reviewer for the insightful comments. The following information has been added to the conclusion: (Lines 256-258)

________________________________________

Reviewer #3

Comment: The paper analyzes the variation in the place of death (PoD) according to major causes of death during the COVID-19 pandemic in Japan using nationwide death certificate data. The results are interesting and contribute to the analysis of the effect of the pandemic on general and cause-specific mortality. The paper is well-written, and the results are clearly described. However, some clarifications in the methods section and some revisions of the results would improve the paper.

Response: We thank Reviewer #3 for the time and effort review our manuscript and for providing positive feedback and suggestions, which have considerably helped us improve the manuscript. We have answered all the questions below and hope that our responses and revisions address all your comments.

Comment: Line 73. Since the analysis concerns also cause-specific mortality data a more detailed description of death certificates data processing is required. In particular, specify whether death certificates are entirely processed through an automatic coding system (for the coding of the single entries and the selection of the underlying cause) or they are in part manually reviewed by experts (in this case, please report the percentage of certificates manually reviewed).

Response: Thank you for your insightful comments. In Japan, the process of determining the underlying cause of death from death certificates comprises an autocoding system, which is a rule-based process, and a manual review. A manual review is performed when an ICD-10 code cannot be assigned by the autocoding system or when ancillary information is included, which accounts for approximately 40% of 100,000 death certificates per month. This information was added to the Methods section. (Lines 76-80)

Comment: In addition, since you are investigating long-time series data, you should specify whether the same coding system was adopted all over the study period and whether there have been any change/update in the classification of causes of death (for example from ICD9 to ICD10).

Response: Thank you for the comment. ICD10 has been used in Japanese Vital Statistics since 1995. Therefore, the same coding system was used in this study for PoD analysis based on the cause of death from 2001 to 2021. This information was added to the Methods section. (Lines 75-76)

Comment: Lastly, it should specified that the analysis refers to underlying cause-of-death data (I suppose so).

Response: Thank you for the comment. In Vital Statistics, the underlying CoD is published based on death certificates. This sentence has been added to the Methods section regarding the data sources. (Lines 74-75)

Comment: 2) Line 84 Statistical analysis. Please add details on the Jointpoint regression analysis, for instance minimum/maximum number of joinpoints tested, model used and regressor (calendar year). In addition, as some readers might not be familiar with this kind of analysis, I recommend to explain that the APC indicates the annual percent change in the proportion (?) of deaths by PoD and that it has been estimated for different time periods.

Response: Thank you for the comment. As you indicated, we have added detailed information on the selected model and variables, as well as the meaning of APC, to the Methods section. (Lines 99-110)

Comment: 3) Lines 100-101: “Trends in the number of PoDs over the past 70 years in Japan are presented in Fig. 1. Since the 1950s, hospital deaths have steadily increased, whereas home deaths have gradually declined”. From Fig.1 I would say that home deaths have gradually declined until mid 2000s, being gradually increasing thereafter.

Response: Thank you for the comment. As you have pointed out, this is correct. We have revised the sentence accordingly. (Lines 123-124)

Comment: 4) lines 100-104: Please cite in the text the proportion of deaths by each single PoD on total deaths at the beginning and at the end of the study period. I would also suggest to include a table (in the main text or in the supplementary material) reporting the frequencies of deaths by PoD and their proportion in each age stratum for the first year and the last year considered in the analysis i.e. 2001 and 2021 (see a proposal below), and to briefly comment on them before the presentation of the results of the joinpoint analysis.

2001 2021

no. of deaths % no. of deaths %

0-19 yrs

home

hospital

nursing home

20-64 yrs

home

hospital

nursing home

≥65 yrs

home

hospital

nursing home

Response: Thank you for the comment. We added the proportion of deaths by each PoD to the total deaths in 1951 and 2021. We have also created a new table as supplementary material, which reports the number and proportion of deaths by place and age group in 2001 and 2021, and briefly commented on them before presenting the results of the joinpoint analysis. (Table S1, Line 134)

Comment: 5) Lines 111-112: “In order to detect the impact of COVID-19 more sensitively, the results of the trend analysis of the proportion of PoDs focused on the last 20 years in the 21st century.””. This sentence expresses a methodological choice, therefore it should be moved to the methods section (Statistical analysis).

Response: Thank you for the comment. We moved this sentence to the Methods section and revised it accordingly. (Lines 94-95)

Comment: 6) line 118: “ hospital deaths decreased suddenly in 2019…” it would be more appropriate to say “from 2019 to 2021” than “in 2019”

Response: Thank you for the comment. We have revised the sentence accordingly. (Line 141)

Comment: 7) How many ofmuch do the top five causes of death account on total mortality in Japan? This proportion should be explicitly mentioned in the text.

Response: Thank you for the comment. We have shown that the proportion of the top five CoDs accounts for the total mortality in the Methods section. (Lines 87-89).

Comment: 8) Could the increase in home deaths due to old age be in part attributable to the possible underdiagnosis of SARS-CoV-2 infection, especially during the early pandemic phase? This aspect should be briefly discussed

Response: Thank you for the comment. We have mentioned the possibility of misclassifying the cause of death in the Limitations section and added your insightful perspective. (Lines 244-246)

Comment: 9) I think the analysis of results could benefit from a brief description of the pandemic phases in Japan during 2020 and 2021.

Response: Thank you for the comment. We added a brief description of the phases of the COVID-19 pandemic in Japan in 2020 and 2021 to the Discussion section. (Lines 189-194)

Comment: 10) In the assessment of time trends (in particular, the increase in home/nursing home deaths), did you evaluate also the possible role of population aging? Although this effect is expected to be limited, this aspect should be discussed

Response: Thank you for the comment. We have added your insightful perspective to the Limitations section. (Lines 242-243)

Decision Letter 1

Mihajlo Jakovljevic

15 Feb 2024

Changes in the place of death before and during the COVID-19 pandemic in Japan

PONE-D-23-28375R1

Dear Dr. Otsuka,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Mihajlo Jakovljevic, MD, PhD, MAE

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: The authors have properly addressed the comments and they have revised the manuscript accordingly.

The paper has improved and I suggest to accept it for publication

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #3: No

**********

Acceptance letter

Mihajlo Jakovljevic

19 Feb 2024

PONE-D-23-28375R1

PLOS ONE

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. Number and proportion of deaths by place and age group in 2001 and 2021.

    (DOCX)

    pone.0299700.s001.docx (14.7KB, docx)

    Data Availability Statement

    The minimal dataset necessary to replicate our study findings can be accessed directly through the Ministry of Health, Labour and Welfare's website (https://www.mhlw.go.jp/english/database/db-hw/outline/index.html). This link leads to the comprehensive database which contains the data we have utilized.

    Articles from PLOS ONE are provided here courtesy of PLOS

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