Does Urinary Catheterization Affect the Quality of Death in Patients with Advanced Cancer? A Secondary Analysis of a Multicenter Prospective Cohort Study

Abstract

Background:

Patients with life-limiting illnesses frequently experience urinary difficulties, and urinary catheterization is one of the interventions for managing them. However, evidence supporting the effects of urinary catheters on the quality of death (QoD) is lacking in this population.

Objectives:

To investigate whether urinary catheterization affects QoD in patients with advanced cancer in palliative care units.

Design:

A secondary analysis of a multicenter, prospective cohort study.

Setting/Subjects:

The study enrolled consecutive patients with advanced cancer admitted to palliative care units in Japan between January and December 2017. Those who were not catheterized on admission and who died while in a palliative care unit were analyzed.

Measurements:

QoD was evaluated at death using the Good Death Scale (GDS).

Results:

Of 885 patients, 297 (33.6%) were catheterized during their palliative care unit stay. Females and patients with a long palliative care unit stay were more likely to be catheterized. In inverse probability-weighted propensity score analysis, patients with urinary catheterization during their palliative care unit stay had higher total GDS scores than those without catheterization (coefficient 0.410, 95% confidence interval 0.068–0.752). In subgroup analyses stratified by sex, age, and length of palliative care unit stay, urinary catheterization was associated with higher total GDS scores in patients younger than 65 years of age and those who died after a palliative care unit stay of 21 days or fewer.

Conclusions:

This study suggested that urinary catheterization during a palliative care unit stay may have a positive impact on overall QoD in patients with advanced cancer. This study was registered in the UMIN Clinical Trials Registry (UMIN000025457).

Introduction

Patients with life-limiting illnesses frequently experience urinary difficulties.¹ Above all, urinary incontinence can be extremely distressing and can affect patients' dignity.² To achieve a good death, management of urinary incontinence at the end of life should be as much a priority as managing symptoms such as pain and nausea. However, there is no professional guidance regarding the management of urinary difficulties in patients with life-limiting illnesses.²

Urinary catheterization is one of the interventions for managing urinary difficulties. When using a urinary catheter, it is necessary to balance the problems of catheterization with the potential benefits to each patient.² Patients with life-limiting illnesses are catheterized not only for urinary retention and urinary incontinence³ but also for various indications, including the following: pain, dyspnea, or discomfort on movement; difficulty in moving safely; quality time with family; restlessness or agitation; and dignity.^1,4

Long-term indwelling urinary catheters increase the risk of urinary tract infection⁵ and cause longer hospital stays and greater risk of mortality in hospitalized elderly patients.^6,7 Evidence-based guidelines on the management of patients with long-term indwelling urinary catheters recommend that clinicians consider removing or changing the catheter in patients who have a catheter-associated urinary tract infection.⁸ However, this does not necessarily apply to patients with life-limiting illnesses because their quality of life (QoL) and quality of death (QoD) achieved, in part, by relieving embarrassment and distress related to urinary continence may outweigh the treatment of infection and even their survival time.⁹

Thus far, few studies have examined whether urinary catheterization affects QoL and QoD in patients with life-limiting illnesses. A previous study in multiple sclerosis patients showed that the majority of patients utilizing urinary catheterization reported a positive impact of catheter use on their QoL,¹⁰ and another study in an intensive care unit (ICU) reported that the QoD of patients with life-limiting illnesses catheterized during ICU stays was better than that of patients who were not catheterized.¹¹

This study primarily investigated whether urinary catheterization affected QoD in patients with advanced cancer in palliative care units. It was hypothesized that urinary catheterization would have a positive impact on QoL through reducing physical and psychological burden of urination, resulting in better QoD in patients with advanced cancer. The secondary purpose of this study was to determine which patients with advanced cancer would show the greatest effect in QoD as a result of urinary catheterization.

Materials and Methods

Design

This was a secondary analysis of the East-Asian collaborative cross-cultural Study to Elucidate the Dying process (EASED), a multicenter, prospective cohort study that clarified the dying process and end-of-life practices in patients with advanced cancer. Details on EASED have been documented in previously published articles.^4,12,13

Setting/subjects

This study enrolled consecutive patients with advanced cancer admitted to the 23 palliative care units in Japan between January and December 2017 and followed them for six months from baseline because some may survive for months in the palliative care units. Eligible patients were (1) aged ≥18 years, (2) diagnosed with cancer exhibiting local invasion or metastasis, and (3) discharged dead from palliative care units. Patients missing data necessary for analysis were excluded.

All participating centers received ethical approval for the primary study, the protocol of which had assumed future secondary analyses of de-identified data of the study. Review of such secondary analyses by the Institutional Review Boards was waived as per the Ethics Board of the central study site, Seirei Mikatahara General Hospital (No. 16-22). Since Japanese law does not require individual informed consent from participants in a noninvasive observational trial such as the present study, an opt-out method was used rather than acquiring informed consent; all patients could receive the information of the study through the instructions posted on the ward or institutional website, and they had the opportunity to decline participation.

Measurements

In this secondary analysis, participating palliative care physicians collected all patient data both on admission and at discharge. On admission, the following data were recorded: sex; age; primary cancer site; metastasis to brain, lung, liver, or bone; marital status; persons living with the patient, including minor children; and presence of a urinary catheter, nephrostomy, cystostomy, or ureterostomy. Physicians rated pain, fatigue, and dyspnea on the Integrated Palliative care Outcome Scale (IPOS) (0 = not at all, 4 = overwhelming).¹⁴

In addition, this study evaluated the Palliative Performance Scale (PPS), oral intake, edema, dyspnea at rest, and delirium to score the Palliative Prognostic Index (PPI) for patient prognosis on admission.¹⁵ The PPI is a scoring system for predicting survival in patients with advanced cancer and does not require any invasive examinations such as blood sampling.¹⁵ The severity of delirium was assessed using the Japanese version of Memorial Delirium Assessment Scale (MDAS) item 9 (0 = normal, 3 = severe).¹⁶ At discharge due to death, participating physicians recorded the length of the palliative care unit stay, the presence of catheterization during the palliative care unit stay, and the presence of catheter removal before they died.

Following the death of each patient, QoD was measured with the Japanese version of the Good Death Scale (GDS).¹⁷ The GDS is an instrument that evaluates QoD in patients receiving palliative care in a hospice or hospital, and its internal consistency, reliability, and validity have been confirmed in Asian culture.^18–24 The Quality of Dying and Death (QODD) is the most widely used and best-validated instrument completed by informal caregivers to evaluate the QODD,^25–27 whereas the GDS was developed as a QoD measurement instrument to be completed by health care providers.²⁴

Based on Weisman's definition of a good death, the GDS consists of five domains: awareness that one is dying (“Awareness,” 0 = complete ignorance, 3 = complete awareness), acceptance of death peacefully (“Acceptance,” 0 = complete unacceptance, 3 = complete acceptance), honoring of the patient's wishes (“Propriety,” 0 = no reference to the patient's wishes, 1 = following the family's wishes alone, 2 = following the patient's wishes alone, and 3 = following the wishes of the patient and the family), death timing (“Timeliness,” 0 = no preparation, 1 = the family alone had prepared, 2 = the patient alone had prepared, and 3 = both the patient and the family had prepared), and the degree of physical comfort three days before death (“Comfort,” 0 = a lot of suffering, 1 = suffering, 2 = a little suffering, and 3 = no suffering).²³ As in previous studies,^{18,19,21–23} the outcome was the score in each domain and its total score. The total GDS score was calculated to summarize the extent to which the patient was considered to have had a good death.¹⁸

Statistical analysis

Of the patients whose GDS could be evaluated by the participating physicians, those whose catheters were removed before they died were excluded because the catheter removal made it challenging to treat the patients as either group if their catheters were indwelled for only a short period. Patients with and without catheterization were compared in terms of categorical variables using Pearson's chi-square test. To reduce confounding by contextual patient characteristics on admission, propensity score analysis was applied to test the effect of catheterization on GDS scores in patients with and without catheterization during their palliative care unit stay.

At the beginning of the analysis, a multiple logistic regression model was used to estimate the propensity score of choosing urinary catheterization during the palliative care unit stay for each patient at admission. This model included sex, age (continuous), marital status (married/remarried or single/widowed/divorced), PPI on admission (continuous), pain on admission (IPOS), and fatigue on admission (IPOS) as covariates. “Not assessable” on IPOS was incorporated into the reference. Sex,²⁵ age,^20,21,25,26 marital status,²⁶ and PPI on admission, but not length of hospital stay,²⁰ were hypothesized to be associated with GDS scores based on previous studies regarding QoD. Pain and fatigue on admission were clinically predicted to be associated with both urinary catheterization and GDS scores. All six variables met the following guidelines: (1) do not include variables associated only with urinary catheterization, (2) do not include variables affected by urinary catheterization, and (3) do not include variables that perfectly predict urinary catheterization.²⁸

Second, individual weights were calculated using the estimated propensity score: 1/propensity score for patients with catheterization and 1/(1 − propensity score) for patients without it. Third, the standardized difference was used to measure covariate balance, where an absolute standardized difference above 0.1 represents meaningful imbalance. Finally, the difference in GDS scores between the two groups was tested using a generalized linear model based on inverse probability-weighted propensity score analysis.

In a subgroup analysis to identify patients in whom QoD was particularly impacted by urinary catheterization, total GDS scores were compared, as in all patients, after stratifying by possible interacting factors (sex, age, and length of palliative care unit stay).^20,21,25 A multiplicative interaction term was included in the generalized linear model to test how the interactions between these factors and urinary catheterization affected total GDS scores. A two-tailed p-value of <0.05 was considered significant. All analyses were conducted using STATA version 16.0 (Stata Corp., College Station, TX, USA).

Results

Of 1896 patients included in this study, patients who were discharged alive from institutions (n = 256) and those missing data necessary for analysis (n = 15) were ineligible. Of the remaining 1625 patients, 740 were excluded from the analysis as follows: those who were already catheterized on admission (n = 411), those with catheter removal after catheterization (n = 19; 5% of 382 patients catheterized during the palliative care unit stay), and those whose GDS scores could not be evaluated at discharge (n = 316). The final study group comprised 885 patients from 22 palliative care units throughout Japan.

Characteristics of the study patients

During the palliative care unit stay, 297 (33.6%) patients underwent catheterization, and 588 (66.4%) patients did not (Table 1). The distribution of PPI scores was not significantly different between patients with and without catheterization, but more patients with catheterization were hospitalized for longer than 21 days. Females were catheterized more frequently during the palliative care unit stay than males, whereas marital status and presence or absence of persons living with the patient were not significantly associated with catheterization.

Table 1.

Characteristics of Patients with and without Catheterization during Palliative Care Unit Stay

	No catheterization	Catheterization during PCU stay	p
	n = 588, n (%)	n = 297, n (%)	p
Female	234 (39.8)	179 (60.3)	<0.001
Age, year
<65	139 (23.6)	71 (23.9)	0.930
≥65	449 (76.4)	226 (76.1)
Primary sites
Liver/gall bladder/pancreas	130 (22.1)	56 (18.9)	0.617
Lung	109 (18.5)	43 (14.5)
Colon/rectum	71 (12.1)	41 (13.8)
Gastric	68 (11.6)	38 (12.8)
Breast	32 (5.4)	23 (7.7)
Uterus/ovary	36 (6.1)	19 (6.4)
Head and neck/thyroid	27 (4.6)	14 (4.7)
Kidney/urinary tract/bladder	23 (3.9)	14 (4.7)
Esophagus	18 (3.1)	12 (4.0)
Blood	14 (2.4)	5 (1.7)
Prostate	12 (2.0)	2 (0.7)
Brain	2 (0.3)	3 (1.0)
Skin	3 (0.5)	2 (0.7)
Other	43 (7.3)	25 (8.4)
Metastasis
Brain	77 (13.1)	32 (10.8)	0.321
Lung	219 (37.2)	126 (42.4)	0.136
Liver	244 (41.5)	129 (43.4)	0.581
Bone	129 (21.9)	74 (24.9)	0.320
Pain, IPOS
0	169 (28.7)	84 (28.3)	0.700
1–2	345 (58.7)	183 (61.6)
3–4	61 (10.4)	29 (9.8)
Not assessable	13 (2.2)	1 (0.3)
Fatigue, IPOS
0	75 (12.8)	42 (14.1)	0.945
1–2	404 (68.7)	204 (68.7)
3–4	95 (16.2)	50 (16.8)
Not assessable	14 (2.4)	1 (0.3)
Dyspnea, IPOS
0	321 (54.6)	163 (54.9)	0.696
1–2	210 (35.7)	106 (35.7)
3–4	44 (7.5)	27 (9.1)
Not assessable	13 (2.2)	1 (0.3)
PPS
≥60	54 (9.2)	32 (10.8)	0.002
30–50	449 (76.4)	246 (82.8)
10–20	85 (14.5)	19 (6.4)
PPI
≤3.5	214 (36.4)	109 (36.7)	0.130
3.5–6.5	138 (23.5)	86 (29.0)
≥6.5	236 (40.1)	102 (34.3)
PCU stay, days
≤21	366 (62.2)	143 (48.2)	<0.001
>21	222 (37.8)	154 (51.9)
Marital status
Single	59 (10.0)	37 (12.5)	0.685
Married/remarried	358 (60.9)	174 (58.6)
Widowed	132 (22.5)	64 (21.6)
Divorced	39 (6.6)	22 (7.4)
Live alone	160 (27.2)	82 (27.6)	0.900
Live with minor children	23 (3.9)	17 (5.7)	0.220

IPOS, Integrated Palliative care Outcome Scale; PCU, palliative care unit; PPI, Palliative Prognostic Index; PPS, Palliative Performance Scale.

GDS in patients with and without urinary catheterization

In inverse probability-weighted propensity score analysis, patients with urinary catheterization during the palliative care unit stay had higher total GDS scores at death than those without catheterization (coefficient 0.410, 95% confidence interval [CI] 0.068–0.752, p = 0.019; Table 2). This result was consistent even when dyspnea on admission (IPOS) and the severity of delirium on admission (MDAS) were added as covariates (coefficient 0.376, 95% CI 0.020–0.732, p = 0.038, data not shown).

Table 2.

Propensity Score Analysis of Good Death Scale Scores in Patients with and without Catheterization during Palliative Care Unit Stay

	Propensity score-weighted comparison
	No catheterization (n = 588), mean (SD)	Catheterization (n = 297), mean (SD)	Coefficient	95% CI	p
Awareness	2.51 (0.59)	2.59 (0.57)	0.082	–0.001 to 0.164	0.052
Acceptance	2.21 (0.60)	2.30 (0.64)	0.085	–0.005 to 0.176	0.065
Propriety	2.69 (0.69)	2.73 (0.65)	0.041	–0.056 to 0.137	0.411
Timeliness	2.38 (1.04)	2.55 (0.89)	0.173	0.037 to 0.309	0.013
Comfort	2.05 (0.84)	2.08 (0.83)	0.029	–0.092 to 0.151	0.637
Total score	11.84 (2.50)	12.25 (2.33)	0.410	0.068 to 0.752	0.019

CI, confidence interval; SD, standard deviation.

Among the five GDS subscales, “Timeliness” scores were significantly higher in patients with catheterization (coefficient 0.173, 95% CI 0.037–0.309, p = 0.013). Covariate balance between the two groups was achieved in this analysis (Table 3). Subgroup analysis revealed that total GDS scores were higher in patients with catheterization than in those without it in individuals younger than the age of 65 years and in those with a palliative care unit stay of 21 days or fewer (Fig. 1). In addition, the interaction between length of palliative care unit stay and urinary catheterization significantly affected GDS total scores (p = 0.031).

FIG. 1.

Weighted subgroup analysis of total Good Death Scale scores in patients with and without urinary catheterization during PCU stay. CI, confidence interval; MD, mean difference; PCU, palliative care unit.

Table 3.

Covariate Balance in Propensity Score Analysis of Good Death Scale Scores in Patients with and without Catheterization during Palliative Care Unit Stay

	Propensity score-weighted comparison		Absolute standardized difference
	No catheterization (n = 588)	Catheterization (n = 297)	Absolute standardized difference
Female, %	46.7	46.7	0.002
Age, years, mean (SD)	71.95 (11.90)	71.81 (11.72)	0.012
PPI, mean (SD)	5.75 (3.18)	5.72 (2.99)	0.009
Married/remarried, %	59.9	59.2	0.014
Pain, IPOS
1–2, %	59.4	58.9	0.009
3–4, %	10.3	10.4	0.003
Fatigue, IPOS
1–2, %	68.7	68.0	0.015
3–4, %	16.0	15.7	0.009

Discussion

This is the first study showing that urinary catheterization during their palliative care unit stay may lead to better QoD in patients with advanced cancer. However, this study could not clarify the theories for better QoD because this study did not evaluate QoL and QoD before catheter insertion.

The most important finding is that patients who underwent urinary catheterization during a palliative care unit stay had higher total GDS scores at death than those who did not. Interestingly, patients with and without urinary catheterization showed no significant difference in scores on the “Comfort” subscale of the GDS, whereas patients who underwent catheterization scored higher on the “Timeliness” subscale, which assessed whether the patient and family members are ready to accept the patient's death. However, it is unclear whether this means that urinary catheterization helps patients with life-limiting illnesses prepare for their deaths or that patients with life-limiting illnesses ready to accept their death are likely to opt for urinary catheterization.

On the contrary, the potentially negative impact of urinary catheterization on QoD in patients with advanced cancer must also be considered. A previous study in patients with a long-term urinary catheter reported that catheters use not only caused pain and discomfort but also negatively impacted patients' personal hygiene and sense of independence.²⁹ Although few studies have evaluated these factors in patients with advanced cancer, a urinary catheter should be used in patients for whom catheter insertion may lead to enhanced QoL and QoD based on the indications for insertion and patients' and caregivers' intentions, not in all patients with advanced cancer.

In addition, the subgroup analysis identified age younger than 65 years and a palliative care unit stay of 21 days or fewer as predictive factors for higher GDS scores following urinary catheterization. With regard to patient age, its association with QoD in patients with advanced cancer was controversial in previous studies.^{18,20,25,30,31} A study in Taiwan found that older patients with advanced cancer usually suffer from more physical/mental distress than younger patients, which often leads to the close involvement of their families in medical decisions.¹⁸ Involvement of family in decision making might interfere with the achievement of their good death.¹⁸ Another study in Taiwan showed that older patients had significantly lower scores than younger patients in both “respect for autonomy” and “decision-making participation” because of a lack of truth-telling.³⁰ A review regarding managing urinary incontinence at the end of life suggested that managing the urinary incontinence should be based on the needs and preferences of individual patients in relationship to it as well as the experiential knowledge of nurses.² With reference to these reports, younger patients with less physical/mental distress and higher autonomy may make a decision of urinary catheterization by adequately considering the risks and benefits of it and achieve better QoD through the use of indwelling urinary catheters.

Regarding the length of palliative care unit stay, a previous study identified longer stay (>7 days) as positively related to improvement in total GDS scores.²⁰ In this study, similar results were seen in patients with and without catheterization during their palliative care unit stay. From the finding of higher GDS scores following urinary catheterization in patients with a palliative care unit stay of 21 days or fewer, not in those with a stay longer than 21 days, a longer stay may lead to a diminished effect of catheterization on QoL and QoD. Further verification is warranted for this inference.

Regarding sex, males can easily excrete urine in a handheld urinal even when sitting or lying down, while it is difficult for females to manage urination using options other than an indwelling urinary catheter. The finding in this study that females were more likely to use catheters reflected these facts, but there was no sex difference in the effect of urinary catheterization on total GDS scores.

Our study has several limitations. First, it was carried out in Japan only. Therefore, its results should be cautiously applied to other countries and races that may differ in terms of values regarding a good death. Second, this study evaluated QoD in patients with advanced cancer using the GDS, which is a physician-reported outcome rather than a patient- or caregiver-reported outcome. Although a previous study demonstrated the validity of proxy assessment of patients by physicians and main caregivers,²² the results of the present study should be interpreted with caution. In addition, while the Japanese version of the GDS has been linguistically validated, it still requires verification in terms of reliability and content validity in a Japanese population. Third, this study was limited to inpatients admitted to palliative care units and did not include home care patients or inpatients who were already catheterized on admission. Further studies are necessary to confirm the generalizability of the study results to these patients. Fourth, the effect of catheterization on GDS scores may have been biased by the patient's choice to undergo catheterization. Patients with advanced cancer who are ready to accept their death (as evaluated by the “Timeliness” subscale of the GDS) may have been more likely to opt for catheterization. Finally, this study lacked data on total GDS scores before catheter insertion and the timing of catheterization, which may have impacted the effect of catheterization on GDS scores. To adjust for these factors, further cohort studies should compare total GDS scores in patients with advanced cancer before catheter insertion and at death, including the duration of urinary catheterization into the analysis.

Conclusion

This study suggested that urinary catheterization during a palliative care unit stay may have a positive impact on overall QoD in patients with advanced cancer, especially those younger than the age of 65 years and those with a palliative care unit stay of 21 days or fewer. These results suggest that urinary catheterization is an intervention that can help achieve a good death in some patients with advanced cancer. Further studies are needed to elucidate the association between urinary catheterization and QoD and develop strategies to identify patients with advanced cancer suitable for urinary catheterization.

Footnotes

Acknowledgments

This study was performed in the East-Asian collaborative cross-cultural Study to Elucidate the Dying process (EASED). The participating study sites and site investigators in Japan were as follows: Satoshi Inoue, MD (Seirei Hospice, Seirei Mikatahara General Hospital); Kengo Imai, MD (Seirei Hospice, Seirei Mikatahara General Hospital); Hiroaki Tsukuura, MD, PhD (Department of Palliative Care, TUMS Urayasu Hospital); Toshihiro Yamauchi, MD (Seirei Hospice, Seirei Mikatahara General Hospital); Akemi Shirado Naito, MD (Department of Palliative Care, Miyazaki Medical Association Hospital); Isseki Maeda, MD, PhD (Department of Palliative Care, Senri-Chuo Hospital); Yu Uneno, MD (Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University); Akira Yoshioka, MD, PhD (Department of Oncology and Palliative Medicine, Mitsubishi Kyoto Hospital); Shuji Hiramoto, MD (Department of Oncology and Palliative Medicine, Mitsubishi Kyoto Hospital); Ayako Kikuchi, MD (Department of Oncology and Palliative Medicine, Mitsubishi Kyoto Hospital); Tetsuo Hori, MD (Department of Respiratory Surgery, Mitsubishi Kyoto Hospital); Yosuke Matsuda, MD (Palliative Care Department, St. Luke's International Hospital); Hiroyuki Kohara, MD, PhD (Hiroshima Prefectural Hospital); Keiko Tanaka, MD, PhD (Department of Palliative Care, Tokyo Metropolitan Cancer & Infectious Diseases Center, Komagome Hospital); Kozue Suzuki, MD (Department of Palliative Care, Tokyo Metropolitan Cancer & Infectious Diseases Center, Komagome Hospital); Tina Kamei, MD (Department of Palliative Care, NTT Medical Center Tokyo); Yukari Azuma, MD (Home Care Clinic Aozora Shin-Matsudo); Koji Amano, MD (Department of Palliative Medicine, Osaka City General Hospital); Teruaki Uno, MD (Department of Palliative Medicine, Osaka City General Hospital); Jiro Miyamoto, MD (Department of Palliative Medicine, Osaka City General Hospital); Hirofumi Katayama, MD (Department of Palliative Medicine, Osaka City General Hospital); Hideyuki Kashiwagi, MD, MBA (Department of Transitional and Palliative Care, Aso Iizuka Hospital); Eri Matsumoto, MD (Department of Transitional and Palliative Care, Aso Iizuka Hospital); Kiyofumi Oya, MD (Department of Transitional and Palliative Care, Aso Iizuka Hospital); Takeya Yamaguchi, MD (Department of Palliative Care, Japan Community Health care Organization, Kyushu Hospital); Tomonao Okamura, MD, MBA (Department of Transitional and Palliative Care, Aso Iizuka Hospital); Hoshu Hashimoto, MD, MBA (Department of Internal Medicine, Inoue Hospital); Shunsuke Kosugi, MD (Department of General Internal Medicine, Aso Iizuka Hospital); Nao Ikuta, MD (Department of Emergency Medicine, Osaka Red Cross Hospital); Yaichiro Matsumoto, MD (Department of Transitional and Palliative Care, Aso Iizuka Hospital); Takashi Ohmori, MD (Department of Transitional and Palliative Care, Aso Iizuka Hospital); Takehiro Nakai, MD (Immuno-Rheumatology Center, St. Luke's International Hospital); Takashi Ikee, MD (Department of Cardiology, Aso Iizuka Hospital); Yuto Unoki, MD (Department of General Internal Medicine, Aso Iizuka Hospital); Kazuki Kitade, MD (Department of Orthopedic Surgery, Saga-Ken Medical Centre Koseikan); Shu Koito, MD (Department of General Internal Medicine, Aso Iizuka Hospital); Nanao Ishibashi, MD (Environmental Health and Safety Division, Environmental Health Department, Ministry of the Environment); Masaya Ehara, MD (Toshiba); Kosuke Kuwahara, MD (Department of General Internal Medicine, Aso Iizuka Hospital); Shohei Ueno, MD (Department of Hematology/Oncology, Japan Community Health care Organization, Kyushu Hospital); Shunsuke Nakashima, MD (Oshima Clinic); Yuta Ishiyama, MD (Department of Transitional and Palliative Care, Aso Iizuka Hospital); Akihiro Sakashita, MD, PhD (Department of Palliative Medicine, Kobe University School of Medicine); Ryo Matsunuma, MD (Department of Palliative Medicine, Kobe University Graduate School of Medicine); Hana Takatsu, MD (Division of Palliative Care, Konan Medical Center); Takashi Yamaguchi, MD, PhD (Division of Palliative Care, Konan Medical Center); Satoko Ito, MD (Hospice, The Japan Baptist Hospital); Toru Terabayashi, MD (Hospice, The Japan Baptist Hospital); Jun Nakagawa, MD (Hospice, The Japan Baptist Hospital); Tetsuya Yamagiwa, MD, PhD (Hospice, The Japan Baptist Hospital); Akira Inoue, MD, PhD (Department of Palliative Medicine, Tohoku University School of Medicine); Takuhiro Yamaguchi, PhD (Professor of Biostatistics, Tohoku University Graduate School of Medicine); Mitsunori Miyashita, RN, PhD (Department of Palliative Nursing, Health Sciences, Tohoku University Graduate School of Medicine); Saran Yoshida, PhD (Graduate School of Education, Tohoku University); Yusuke Hiratsuka, MD, PhD (Department of Palliative Medicine, Tohoku University School of Medicine); Keita Tagami, MD, PhD (Department of Palliative Medicine, Tohoku University School of Medicine); Hiroaki Watanabe, MD (Department of Palliative Care, Komaki City Hospital); Takuya Odagiri, MD (Department of Palliative Care, Komaki City Hospital); Tetsuya Ito, MD, PhD (Department of Palliative Care, Japanese Red Cross Medical Center); Masayuki Ikenaga, MD (Hospice, Yodogawa Christian Hospital); Keiji Shimizu, MD, PhD (Department of Palliative Care Internal Medicine, Osaka General Hospital of West Japan Railway Company); Akira Hayakawa, MD, PhD (Hospice, Yodogawa Christian Hospital); Takeru Okoshi, MD, PhD (Okoshi Nagominomori Clinic); Tomohiro Nishi, MD (Kawasaki Municipal Ida Hospital, Kawasaki Comprehensive Care Center); Yasuhiro Shibata, MD (Kawasaki Municipal Ida Hospital, Kawasaki Comprehensive Care Center); Satoshi Miyake, MD, PhD (Department of Clinical Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University); Junko Nozato, MD (Department of Internal Medicine, Palliative Care, Medical Hospital, Tokyo Medical and Dental University); Hiroto Ishiki, MD (Department of Palliative Medicine, National Cancer Center Hospital); Tetsuji Iriyama, MD (Department of Internal Medicine, Palliative Care, Medical Hospital, Tokyo Medical and Dental University); Keisuke Kaneishi, MD, PhD (Department of Palliative Care Unit, JCHO Tokyo Shinjuku Medical Center); Tomofumi Miura, MD, PhD (Department of Palliative Medicine, National Cancer Center Hospital East); Yoshihisa Matsumoto, MD, PhD (Department of Palliative Medicine, National Cancer Center Hospital East); Kazuhiro Kosugi, MD (Department of Palliative Medicine, National Cancer Center Hospital East); Ayumi Okizaki, PhD (Department of Palliative Medicine, National Cancer Center Hospital East); Yuki Sumazaki Watanabe, MD (Department of Palliative Medicine, National Cancer Center Hospital East); Yuko Uehara, MD (Department of Palliative Medicine, National Cancer Center Hospital East); Eriko Satomi, MD (Department of Palliative Medicine, National Cancer Center Hospital); Kaoru Nishijima, MD (Department of Palliative Medicine, Kobe University Graduate School of Medicine); Ryoichi Nakahori, MD (Department of Palliative Care, Fukuoka Minato Home Medical Care Clinic); Takeshi Hirohashi, MD (Eiju General Hospital); Natsuki Kawashima, MD (Department of Palliative Medicine, Tsukuba Medical Center Hospital); Takashi Kawaguchi, PhD (Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences); Megumi Uchida, MD, PhD (Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences); Ko Sato, MD, PhD (Hospice, Ise Municipal General Hospital); Yoichi Matsuda, MD, PhD (Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine); Yutaka Hatano, MD, PhD (Hospice, Gratia Hospital); Sayaka Maeda, MD (Department of Palliative Medicine, Kyoto University Hospital); and Hiroyuki Otani, MD (Palliative Care Team and Palliative and Supportive Care, National Kyushu Cancer Center).

Funding Information

This work was supported by JSPS KAKENHI Grant Number JP20K18842 (Grant-in-Aid for Early Career Scientists) and, in part, by a Grant-in-Aid from the Japanese Hospice Palliative Care Foundation.

Author Disclosure Statement

No competing financial interests exist.

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