Opioid use in terminal patients with cancer: comparison between home-based and hospital-based care in Japan

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Recent national policies promoting home-based care have increased deaths at home. However, comparative evidence on care quality across home and hospital-based settings remains limited. This study compares opioid use in patients with terminal cancer receiving home- versus hospital-based care and examines regional variation using real-world data. Methods Patients with cancer who died within 6 months of completing chemotherapy between 2014 and 2023 were identified from the JMDC Claims Database, one of the largest claims-based healthcare databases in Japan. Opioid doses in the last 90 days of life were compared between home-based and hospital-based care groups using a propensity score-matched analysis. In addition, temporal trends in home-based care use and regional variation were assessed. Results Among 8,429 eligible patients (59.9% male; mean age, 58.2 years), 12.2% received home-based care. The median daily opioid dose, expressed as morphine milligram equivalents, during the last 90 days of life was significantly higher in the home-based care group than in the hospital-based care group (29.4 mg/day vs. 17.8 mg/day; P < 0.001). Home-based care utilization increased over time. The proportion of patients receiving home-based care was highest in the Kanto region, including Tokyo, and opioid doses in home-based care were also highest in this region, although these differences were not statistically significant. Conclusions In this real-world cohort study from Japan, home-based care use was associated with higher opioid doses in patients with terminal cancer. patients with cancer opioid dose home-based care hospital-based care regional differences real-world data Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Japan is one of the most rapidly aging societies in the world, with over 29% of its population aged 65 years or older as of 2023 [ 1 ]. This demographic shift has placed increasing strain on the healthcare system, particularly on inpatient bed capacity. Traditionally, Japan has relied heavily on hospital-based care, and home-based care utilization remains relatively low compared with other high-income countries. According to data from around 2020, 68.3% of deaths in Japan occurred in hospitals, whereas this proportion is < 50% in many developed countries [ 2 ]. This discrepancy reflects cultural preferences and structural characteristics of Japan’s healthcare system, including limited availability of home-based services. In anticipation of future shortage of hospital beds and in response to rising social security expenditures, the Japanese government has promoted home-based care as a sustainable alternative to hospital care [ 3 ]. The shift reflects not only logistical and economic considerations but also a growing emphasis on patient-centered care. For patients with terminal illness, especially those with advanced cancer, care setting can substantially influence physical comfort, psychological well-being, and dignity at the end of life [ 4 ]. Despite the expanding availability of home-based care in Japan, evidence on care quality in these settings is limited. One major concern is whether home-based care can match the level of symptom management and clinical oversight in hospital-based care, particularly for patients with advanced cancer who often require complex symptom control. Among these concerns, pain management is particularly critical. In Japan, opioid use remains considerably lower than in other advanced countries, and delays in the development of palliative care services have been repeatedly noted [ 5 ]. Several factors may underlie this pattern. On the patient side, negative perceptions of opioids (e.g., concerns about danger or addiction) may contribute to reluctance to accept them. On the provider side, limited training opportunities and insufficient education in palliative medicine may contribute to opioid underprescription and underuse. This dual barrier suggests that patients receiving home-based care, especially those with advanced cancer, may receive inadequate pain management at the end of life. Given these circumstances, evaluating pain management in patients with terminal cancer receiving home-based care is highly important. In Japan, small-scale studies from a limited number of institutions have compared opioid use between home- and hospital-based care; however, no nationwide database studies have been reported to our knowledge [ 6 ]. Clarifying differences in opioid doses—an indicator of palliative care quality—between home- and hospital-based care may inform clinical practice, policymaking, and resource allocation to improve palliative care quality in Japan. In this study, we conducted a cohort study using the JMDC Claims Database to compare palliative care quality between home- and hospital-based settings in Japan, focusing on opioid doses in the 90 days preceding death among patients with terminal cancer. Patients and Methods Setting and Data This study followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. It was approved by the Institutional Review Board and Ethics Committee of The University of Tokyo (Reference No. 2021076NI). Because the data were anonymized, the requirement for written informed consent was waived by the Institutional Review Board. This study used data from the JMDC Claims Database (JMDC Inc., Tokyo, Japan) [ 7 ]. The JMDC Claims Database is one of the largest and most comprehensive healthcare datasets in Japan, based on data provided by multiple health insurance societies. It primarily includes employees of medium- to large-sized companies and their dependents younger than 75 years covered by participating health insurance associations. The database integrates three main types of information: (1) enrollee registry data, including demographic and insurance-related details such as birth year and month, sex, and insurance status; (2) health insurance claims for inpatient, outpatient, dental, and pharmacy services; and (3) annual health check-up records, including government-mandated specific health examinations for individuals aged 40–74 years. Claims data include detailed information on medical procedures, consultation dates, diagnoses coded according to the International Classification of Diseases, 10th Revision (ICD-10), and prescription records with drug names classified according to the World Health Organization Anatomical Therapeutic Chemical (ATC) system. As of June 2020, approximately 9.8 million individuals were registered in the JMDC database [ 7 ]. Population Patients aged 18 years or older who died between January 2014 and December 2023 and had a registered cancer diagnosis within 6 months before death were identified from the database. Eligible patients were required to: (1) receive chemotherapy (ATC code L01) within 6 months before death; (2) have at least a 6-month look-back period before the last chemotherapy administration; and (3) have a recorded cancer diagnosis (ICD-10 codes C00.x-C96.x) during the look-back period. Patients were excluded if they (1) died in the same month as the last chemotherapy administration or (2) received home-based care during the look-back period. Exposure Patients who initiated home-based care in the month of the last chemotherapy administration or the following month were classified into the home-based care group. Receipt of home-based care was identified using Japanese medical procedure codes C002, C002-2, and C003. All other patients were classified into the hospital-based care group. Outcomes According to Foley’s estimate, about 80% of patients with terminal cancer require 60–75 mg of oral morphine per day during the 90 days before death [ 8 ]. Using this estimate as a reference, we defined the primary outcome as the median daily opioid dose during the last 90 days before death. The secondary outcomes were trends in opioid dose between home-based care and hospital-based care over the last 3 months before death, annual trends in the proportion of patients receiving home-based care, and regional differences in the proportion of patients receiving home-based care and in opioid dose between home-based and hospital-based care. The opioid dose was calculated as the sum of prescribed oral, transdermal, rectal, and injectable opioid formulations, excluding transmucosal fentanyl products. Before summing across formulations, each prescription was converted to morphine milligram equivalents using the morphine equivalence ratios provided by the Japanese Society for Palliative Medicine Guidelines 2020 for Pharmacological Management of Cancer Pain (Online Resource 1) [ 9 – 12 ]. The opioid dose during the last 90 days before death was calculated as follows. The doses prescribed in the month of death, the preceding month, 2 months before death, and 3 months before death were denoted as D 0 , D 1 , D 2 , and D 3 , respectively. For the month of death, a mean survival of 15 days was assumed. Accordingly, opioid dose during 0–30 days before death was calculated as D 0 + D 1 /2. Similarly, opioid dose during 30–60 days before death was calculated as D 1 /2 + D 2 /2, and opioid dose during 60–90 days before death was calculated as D 2 /2 + D 3 /2. Total opioid dose during the last 90 days before death was calculated as (D 0 + D 1 /2) + (D 1 /2 + D 2 /2) + (D 2 /2 + D 3 /2) = D 0 + D 1 + D 2 + D 3 /2. Potential Confounding Variables Potential confounders included demographic factors, cancer type, and receipt of radiation therapy. Variables were selected based on their potential to influence care setting, opioid dose, and prognosis, according to clinical expertise and prior research [ 13 – 16 ]. Covariates included treatment period, sex, age, Charlson Comorbidity Index score, lung cancer, upper gastrointestinal cancer, lower gastrointestinal cancer, pancreatic cancer, and receipt of radiation therapy. Cancer type included the four most frequent cancers in this database. Receipt of radiation therapy was identified from records during the look-back period. The Charlson Comorbidity Index score, which quantifies comorbidity burden, was calculated from ICD-10 codes registered during the look-back period using Quan’s algorithm [ 17 , 18 ]. Statistical Analysis Comparison between home-based care and hospital-based care A propensity score-matched analysis was conducted to adjust for confounding by indication and baseline differences between the home-based care group and the hospital-based care group [ 19 ]. Propensity scores were calculated using a multivariable logistic regression model, with home-based care as the dependent variable. The independent variables included the nine confounders described above. Nearest neighbor matching at a one-to-four ratio was used, with patients in the home-based care group matched to those in the hospital-based care group using estimated propensity scores within a caliper of 0.2 standard deviations of the logit. Covariate balance between groups was assessed using absolute standardized differences, with a value > 0.1 indicating imbalance. Annual trends in the use of home-based care We estimated adjusted annual proportions of patients receiving home-based care using a multivariable logistic regression model. The model included calendar year and eight additional covariates described earlier, excluding the treatment period. Adjusted proportions were calculated as marginal predicted probabilities from the fitted model. Comparison between regions For regional analyses, Japan was divided into seven regions: Hokkaido/Tohoku, Kanto, Chubu, Kansai, Chugoku, Shikoku, and Kyushu/Okinawa, and comparisons were made across regions. Regional differences in the proportion of patients receiving home-based care were estimated using a logistic regression model that included region in addition to the nine covariates described above. Pairwise comparisons between regions were conducted using margins with Bonferroni correction. Adjusted median opioid doses were estimated using a quantile regression with bootstrap standard errors, including the nine independent variables described earlier, as well as region and home-based care status [ 20 , 21 ]. The interaction between region and home-based care status was also included in the model. Pairwise comparisons were adjusted for multiple testing using the Bonferroni method. Subgroup analysis For the subgroup analysis, we recalculated the same opioid use metric using data from patients whose opioid consumption was within the top 80%, consistent with Foley’s estimate. Continuous variables were compared between the groups using the Mann–Whitney U test. Categorical variables were compared between the groups using the chi-square test. Adjustment for multiple comparisons was performed using the Bonferroni method. All reported P-values were two-sided, and P-values of < 0.05 were considered statistically significant. All statistical analyses were conducted using Stata/SE software (version 19.0; StataCorp, College Station, TX, USA). Results We identified 17,115 patients with both a cancer diagnosis and a death record between January 2014 and December 2023 in the database. After applying the exclusion criteria, 8,429 patients were included for analysis (5,052 [59.9%] male; mean age [standard deviation], 58.2 [10.0] years) (Fig. 1 ). Table 1 presents the baseline characteristics of the two groups. One-to-four propensity score matching yielded a final study cohort of 1,028 patients and 4,112 patients in the home- and hospital-based care groups, respectively. After matching, all absolute standardized differences were < 0.1, indicating acceptable matching quality (Table 1 ). Figure 2 presents the primary outcomes in the matched groups. The median daily opioid dose in the last 90 days of life was significantly higher in the home-based care group than in the hospital-based care group (29.4 mg [95% confidence interval (CI), 25.2–32.9] vs 17.8 mg [16.4–18.7]; P < 0.001, Mann–Whitney U test). Figure 3 presents the trends in opioid dose over the last 3 months before death in the two groups. Opioid dose increased as death approached. Online Resources 2 and 3 show daily opioid doses among patients in the top 80% of opioid consumption. Figure 4 shows the annual trends in the utilization of home-based care. Use of home-based care increased gradually over time. Online Resource 4 presents the unadjusted baseline characteristics by region. Figure 5 presents regional differences in the proportion of patients receiving home-based care. After Bonferroni correction, significant differences were observed between the Kanto region (including Tokyo) and the Hokkaido/Tohoku, Chubu, Chugoku, and Kyushu/Okinawa regions, as well as between the Kansai region (including Osaka and Kyoto) and the Hokkaido/Tohoku, Chubu, and Kyushu/Okinawa regions. Figure 6 shows regional differences in opioid doses between the two groups. Significant differences between the home- and hospital-based care groups were observed only in the Kanto region ( P < 0.001) and the Kansai region ( P = 0.035). The adjusted opioid dose in the home-based care group was highest in the Kanto region; however, this difference did not reach statistical significance. Table 1 Baseline patient characteristics in the unmatched and propensity score-matched groups. Unmatched groups Matched groups Home-based care group Hospital-based care group ASD* Home-based care group Hospital-based care group ASD* 1028 7401 1028 4112 Treatment period 2014–2019 239 (23.2) 3425 (46.3) 0.52 239 (23.2) 961 (23.4) < 0.01 2020–2021 339 (33.0) 2027 (27.4) 339 (33.0) 1348 (32.8) 2022–2023 450 (43.8) 1949 (26.3) 450 (43.8) 1803 (43.8) Sex Male 550 (53.5) 4502 (60.8) 0.15 550 (53.5) 2176 (52.9) 0.01 Female 478 (46.5) 2899 (39.2) 478 (46.5) 1936 (47.1) Age, years 56.5 ± 10.8 58.5 ± 9.9 56.5 ± 10.8 56.9 ± 10.0 18–49 242 (23.5) 1252 (16.9) 0.18 242 (23.5) 953 (23.2) 0.04 50–59 353 (34.3) 2503 (33.8) 353 (34.3) 1433 (34.8) 60–69 319 (31.0) 2618 (35.4) 319 (31.0) 1317 (32.0) ≥70 114 (11.1) 1028 (13.9) 114 (11.1) 409 (9.9) Charlson comorbidity index 0–8 291 (28.3) 2196 (29.7) 0.04 291 (28.3) 1165 (28.3) < 0.01 9–10 410 (39.9) 2967 (40.1) 410 (39.9) 1637 (39.8) ≥11 327 (31.8) 2238 (30.2) 327 (31.8) 1310 (31.9) Radiation therapy 244 (23.7) 1608 (21.7) 0.05 244 (23.7) 1002 (24.4) 0.01 Lung cancer 208 (20.2) 1757 (23.7) 0.08 208 (20.2) 753 (18.3) 0.05 Upper gastrointestinal cancer 257 (25.0) 1805 (24.4) 0.01 257 (25.0) 952 (23.2) 0.04 Lower gastrointestinal cancer 253 (24.6) 1974 (26.7) 0.05 253 (24.6) 902 (21.9) 0.06 Pancreatic cancer 222 (21.6) 1402 (18.9) 0.07 222 (21.6) 800 (19.5) 0.05 Categorical variables are presented as n (%), and continuous variables are presented as mean ± standard deviation. *ASD > 0.1 is considered imbalanced. ASD, absolute standardized difference. Discussion In this study, we found that opioid use during the last 90 days before death among patients with terminal cancer was higher in the home-based care group than in the hospital-based care group. This tendency was consistently observed over time and across regions. One possible explanation for the lower opioid use observed in the hospital-based care group is the absence of or inadequate functioning of palliative care teams in hospital settings. As of 2024, there were more than 1,700 acute care hospitals in Japan, of which only 464 were designated as cancer care hospitals as of 2025 [ 22 , 23 ]. Although the establishment of a palliative care team is required for designation as a cancer care hospital, this requirement does not apply to other hospitals. As a result, many patients with cancer in Japan are likely to receive care in settings without access to a dedicated palliative care team. Furthermore, substantial variation exists in the level of clinical activity even among hospitals with palliative care teams. We have previously reported that lower levels of palliative care team activity are associated with poorer patient outcomes, and such low-activity teams may also be associated with insufficient opioid prescribing [ 24 ]. Taken together, both the limited availability of palliative care teams and the presence of teams with low levels of activity may account for the lower levels of opioid prescribing observed in the hospital-based care group. Although opioid use was higher in the home-based care group than in the hospital-based care group, the absolute doses remained low compared with international standards. In this study, the median daily opioid dose during the last 90 days before death was 29.4 mg/day in the home-based care group and 17.8 mg/day in the hospital-based care group. According to Foley’s estimate, approximately 80% of patients with terminal cancer require 60–75 mg of oral morphine per day during the last 90 days before death [ 8 ]. In the subgroup analysis restricted to the top 80% of opioid users to align with Foley’s estimate (Online Resource 2), the opioid dose in the home-based care group was 44.7 mg/day (95% CI, 39.1–49.3), which remained below Foley’s estimate. In the trend analysis (Online Resource 3), the home-based care group reached 61.6 mg/day (95% CI, 55.9–69.5) in the month of death, approaching Foley’s estimate. However, doses at other time points were substantially lower, and the hospital-based care group showed lower doses throughout. The relatively low level of opioid prescribing in Japan may be explained by a combination of cultural and regulatory factors. From a cultural perspective, opioids in Japan are often perceived by the general public not as analgesics, but as illegal psychoactive substances or medications used for end-of-life sedation. As a result, many patients and their families are reluctant to use opioids for pain management. In addition, some healthcare professionals, partly because of limited education and training, may avoid opioid use, believing that opioids should be avoided whenever possible [ 25 ]. From a regulatory perspective, outpatient opioid prescriptions in Japan are limited to 30 days. In addition, regulations governing the handling and storage of opioids in hospitals are highly restrictive, which may further discourage their use in routine clinical practice [ 26 ]. As part of national efforts to promote the appropriate use of opioids, designated cancer care hospitals are required to establish palliative care teams, and physicians on these teams are required to complete designated palliative care training programs on appropriate opioid use [ 27 ]. However, as noted above, hospitals other than designated cancer care hospitals are not required to establish palliative care teams, and many therefore lack such teams; accordingly, the effectiveness of this policy remains unclear. In the present study, opioid use in home-based care in the Kanto region, including Tokyo, was the highest across all care settings, although the difference was not statistically significant. The geographic maldistribution of palliative care specialists, who are concentrated in urban areas, may partly explain the lower opioid use observed in rural regions. In Japan, policy efforts to promote home-based care included enhanced financial incentives for home medical services in 2006. Consistent with these policies, this study showed a temporal trend toward increased home-based care use over time (Fig. 4 ). However, the utilization of home-based care remains lower in rural areas, such as the Hokkaido/Tohoku region and the Kyushu/Okinawa region, than in urban areas (Fig. 5 ). A previous study has also reported lower utilization of home-based care in rural areas than in urban areas [ 28 ]. Low population density, which reduces financial viability, and difficulties in securing hospital admission in the event of acute deterioration, which increase the burden on home-based physicians, may limit the expansion of home-based care services in rural areas. Strengthening incentives for home-based care in rural areas may increase the utilization of home-based care among patients with terminal cancer, thereby promoting appropriate opioid use. This study has some limitations. First, compared with the general Japanese population, the study sample included a smaller proportion of older patients (Online Resource 5), which may have biased the estimated opioid doses. Second, opioid doses in this study were calculated from prescribed amounts, which may not have been fully consumed in clinical practice and may therefore have overestimated opioid use. Third, to approximate a terminal cancer population, we included patients who died within 6 months after their final chemotherapy; however, this approach may have included some patients who were not at the terminal stage. Fourth, as with other propensity score-matched analyses, residual confounding due to unmeasured variables, such as performance status and body mass index, may have resulted in incomplete adjustment between groups. In this study, home-based care was significantly associated with higher opioid consumption among patients with terminal cancer; however, the absolute opioid dose remained low compared with international standards. We also found that the utilization of home-based care has increased over time; however, its use remains relatively low in rural areas. To promote the appropriate use of opioids among patients with terminal cancer, policies aimed at expanding home-based care—particularly in rural regions—may be warranted. Declarations Declaration of financial/other relationship The department to which HA and SN belong is supported by Shionogi & Co., Ltd., Nippon Zoki Pharmaceutical Co., Ltd., Aiwa Hospital, and Yoshida Hospital. MS received funding for this study from Shionogi & Co., Ltd., Nippon Zoki Pharmaceutical Co., Ltd., Aiwa Hospital, and Yoshida Hospital, and payments for lectures from Shionogi & Co., Ltd., Daiichi Sankyo Company, Limited, and GlaxoSmithKline plc. YM is an employee of Shionogi & Co., Ltd. All other authors declare no competing interests. Ethics approval statement : This study was approved by the Institutional Review Board and Ethics Committee of The University of Tokyo (Reference No. 2021076NI). Patient consent statement Due to the anonymized nature of the data, the requirement for obtaining written informed consent was waived by the Institutional Review Board. Funding: Shionogi & Co., Ltd. had a role in the collection of data from the JMDC database and in the publication. Nippon Zoki Pharmaceutical Co., Ltd., Aiwa Hospital, and Yoshida Hospital had no role in the collection, analysis, and interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication. Authors’ contributions: HA, YM, and MS conceived and designed the study. RI, TK, RT, YS, YO, and YY extracted, cleaned, and prepared the data for analysis. HA, SN, and HO conducted the statistical analysis. HA, YM, and MS interpreted the results. HA drafted the manuscript. HA, YM, and MS critically revised the manuscript. All authors are fully responsible for the overall content for the work and the conduct of the study. All authors had access to the data and were involved in the decision to publish the study. All authors reviewed the manuscript and approved the final submitted version. Acknowledgments: We thank Yumi Sato of Shionogi & Co., Ltd. for study planning and data curation for this study. Data availability statement: We cannot provide raw data being freely available because we did not obtain agreements to release the data from the supplier and because our ethical approval did not include the release. Instead, the datasets used and/or analyzed during this study are completely available from the corresponding author for collaborative research purposes upon reasonable request. References Cabinet Office Japan (2024) Annual report on the ageing society [Summary]. FY2024 [Internet]. 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Abe","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYDACCQY2hg9IfAMozYZXC+MMOC+BSC3MPFi04Ab8s5uPPbb5xSDH336ATYLxh42xwfEGxg8/GPjycFpy51i6cW4fg7HEmQQ2CYaENDODMweYJXsY2IpxWnMjx0w6t4chcQPQhdJ/Eg7bGNxIYJAG+iWxAYcO+Rv536QtexjqQVqAtoC1MP/Gp8XgRg6bNMMPhgQDqBYzoBY2vLYY3jlmJtnbIGE440xiswVDWpqx5JmDbZY9Brj9Ine7+ZnEjz828vzthw/eYLCxMew73nz4xo+KYzhDDAwY2yRAJMQlCgdADINjCXi1MPxBYstDdNYQ0DIKRsEoGAUjCAAAlcJPTmIDD8EAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-2493-302X","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":true,"prefix":"","firstName":"Hiroaki","middleName":"","lastName":"Abe","suffix":""},{"id":625847213,"identity":"3f8bfed8-eab5-4cc3-b511-a3a7379ea15a","order_by":1,"name":"Reo Inoue","email":"","orcid":"","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Reo","middleName":"","lastName":"Inoue","suffix":""},{"id":625847214,"identity":"8f55bc8e-7464-4b16-bc32-3b9f41d6655e","order_by":2,"name":"Takamichi Kogure","email":"","orcid":"","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Takamichi","middleName":"","lastName":"Kogure","suffix":""},{"id":625847215,"identity":"1c093300-5d67-49ee-9ad1-1275e7ce3185","order_by":3,"name":"Rikuhei Tsuchida","email":"","orcid":"","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Rikuhei","middleName":"","lastName":"Tsuchida","suffix":""},{"id":625847216,"identity":"8704e7c3-d689-42b5-a4a9-757ee1338d9d","order_by":4,"name":"Saya Nagata","email":"","orcid":"","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Saya","middleName":"","lastName":"Nagata","suffix":""},{"id":625847217,"identity":"879b8fc7-a02e-4f81-8d19-748166a071fa","order_by":5,"name":"Hiroaki Owada","email":"","orcid":"","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Hiroaki","middleName":"","lastName":"Owada","suffix":""},{"id":625847218,"identity":"b0ac51a1-7f85-4e18-a024-882c4ea845c5","order_by":6,"name":"Yoshika Sudo","email":"","orcid":"","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Yoshika","middleName":"","lastName":"Sudo","suffix":""},{"id":625847219,"identity":"6661cd2d-4450-4410-bfda-cb24c0ce6f89","order_by":7,"name":"Yuki Odawara","email":"","orcid":"","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Odawara","suffix":""},{"id":625847220,"identity":"7c5e4edb-1ea7-42b1-99b7-182ea8f4df18","order_by":8,"name":"Yaeko Yokoshima","email":"","orcid":"","institution":"The University of Tokyo Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Yaeko","middleName":"","lastName":"Yokoshima","suffix":""},{"id":625847221,"identity":"8a727c6f-3e31-4484-9eaa-70552c3d085c","order_by":9,"name":"Yasuhide Morioka","email":"","orcid":"","institution":"Shionogi and Co Ltd","correspondingAuthor":false,"prefix":"","firstName":"Yasuhide","middleName":"","lastName":"Morioka","suffix":""},{"id":625847222,"identity":"95a030e0-aee8-469b-a6c7-14a9519214f3","order_by":10,"name":"Masahiko Sumitani","email":"","orcid":"","institution":"Tokyo University Hospital: Tokyo Daigaku Igakubu Fuzoku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Masahiko","middleName":"","lastName":"Sumitani","suffix":""}],"badges":[],"createdAt":"2026-04-18 09:39:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9455777/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9455777/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108009601,"identity":"be8d0966-83b6-485e-916b-f216866afc12","added_by":"auto","created_at":"2026-04-28 13:10:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1851431,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart of patient selection based on the inclusion and exclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e*A minimum 6-month look-back period was required before the last administration of chemotherapy\u003c/p\u003e","description":"","filename":"20260222Fig1600.png","url":"https://assets-eu.researchsquare.com/files/rs-9455777/v1/0752b04e5ce38ad9aef635af.png"},{"id":108009397,"identity":"2d7a4db2-aa31-47e2-86be-d78ddaa11d8c","added_by":"auto","created_at":"2026-04-28 13:10:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5368130,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDaily opioid dose during the last 90 days before death in the two groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are presented as medians with 95% confidence intervals in morphine milligram equivalents. Between-group comparison was performed using the Mann–Whitney U test\u003c/p\u003e","description":"","filename":"20260328Fig2600.png","url":"https://assets-eu.researchsquare.com/files/rs-9455777/v1/3a26ab9f40139d84a0125444.png"},{"id":108010010,"identity":"9274bfa5-7984-4fa9-b721-109841f55a0c","added_by":"auto","created_at":"2026-04-28 13:12:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":7768719,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTrends in opioid dose over the last 3 months before death in the two groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are presented as medians with 95% confidence intervals in morphine milligram equivalents. Between-group comparisons were performed using the Mann–Whitney U test with Bonferroni correction\u003c/p\u003e","description":"","filename":"20260328Fig3600.png","url":"https://assets-eu.researchsquare.com/files/rs-9455777/v1/a5376959c1e47b2333f649c4.png"},{"id":108010459,"identity":"ecee145a-cb10-405c-b7ff-ec43d5a5e29b","added_by":"auto","created_at":"2026-04-28 13:13:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":5546427,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTrends in the utilization of home-based care\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnnual proportions of patients receiving home-based care were estimated using a multivariable logistic regression model. Data are presented as adjusted proportions with 95% confidence intervals.\u003c/p\u003e","description":"","filename":"20260328Fig4600.png","url":"https://assets-eu.researchsquare.com/files/rs-9455777/v1/9ce4fc5b3928a33d7a65c39f.png"},{"id":108010019,"identity":"eb55e1ff-502f-42c9-87d6-cfafa7f4d8c6","added_by":"auto","created_at":"2026-04-28 13:12:16","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":8592158,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRegional differences in the proportion of patients receiving home-based care\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdjusted proportions with 95% confidence intervals were estimated using multivariable logistic regression. Pairwise regional comparisons were conducted using margins with Bonferroni correction. The Kanto (including Tokyo) and Kansai (including Osaka and Kyoto) regions showed significant differences compared with the †- and *-marked regions, respectively\u003c/p\u003e","description":"","filename":"20260328Fig5600.png","url":"https://assets-eu.researchsquare.com/files/rs-9455777/v1/643393de4fb5d7d660270691.png"},{"id":108009405,"identity":"b67bdd49-e0a9-42af-b51d-2d5b5cf38edb","added_by":"auto","created_at":"2026-04-28 13:10:13","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":16401224,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRegional differences in opioid doses between the two groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdjusted median opioid doses with 95% confidence intervals were estimated using a bootstrap quantile regression model. Pairwise comparisons were adjusted for multiple testing using the Bonferroni method.\u003c/p\u003e","description":"","filename":"20260328Fig6600.png","url":"https://assets-eu.researchsquare.com/files/rs-9455777/v1/6eafcce9be313f784e0c8e26.png"},{"id":108012833,"identity":"6a1ae49a-eac7-4476-8e06-cfcc0af88c66","added_by":"auto","created_at":"2026-04-28 13:16:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":39830415,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9455777/v1/ab5e59c8-38a1-4751-851d-2706598896bd.pdf"},{"id":108009650,"identity":"9c21f955-0d8f-4b64-8bf0-e6f2b4535bf5","added_by":"auto","created_at":"2026-04-28 13:10:46","extension":"docx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":577398,"visible":true,"origin":"","legend":"","description":"","filename":"20260411SupplementaryFilever3.1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9455777/v1/fc8cb9049d2853d7c6c0d1ce.docx"}],"financialInterests":"","formattedTitle":"Opioid use in terminal patients with cancer: comparison between home-based and hospital-based care in Japan","fulltext":[{"header":"Introduction","content":"\u003cp\u003eJapan is one of the most rapidly aging societies in the world, with over 29% of its population aged 65 years or older as of 2023 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This demographic shift has placed increasing strain on the healthcare system, particularly on inpatient bed capacity. Traditionally, Japan has relied heavily on hospital-based care, and home-based care utilization remains relatively low compared with other high-income countries. According to data from around 2020, 68.3% of deaths in Japan occurred in hospitals, whereas this proportion is \u0026lt;\u0026thinsp;50% in many developed countries [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This discrepancy reflects cultural preferences and structural characteristics of Japan\u0026rsquo;s healthcare system, including limited availability of home-based services. In anticipation of future shortage of hospital beds and in response to rising social security expenditures, the Japanese government has promoted home-based care as a sustainable alternative to hospital care [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The shift reflects not only logistical and economic considerations but also a growing emphasis on patient-centered care. For patients with terminal illness, especially those with advanced cancer, care setting can substantially influence physical comfort, psychological well-being, and dignity at the end of life [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the expanding availability of home-based care in Japan, evidence on care quality in these settings is limited. One major concern is whether home-based care can match the level of symptom management and clinical oversight in hospital-based care, particularly for patients with advanced cancer who often require complex symptom control. Among these concerns, pain management is particularly critical. In Japan, opioid use remains considerably lower than in other advanced countries, and delays in the development of palliative care services have been repeatedly noted [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Several factors may underlie this pattern. On the patient side, negative perceptions of opioids (e.g., concerns about danger or addiction) may contribute to reluctance to accept them. On the provider side, limited training opportunities and insufficient education in palliative medicine may contribute to opioid underprescription and underuse. This dual barrier suggests that patients receiving home-based care, especially those with advanced cancer, may receive inadequate pain management at the end of life.\u003c/p\u003e \u003cp\u003eGiven these circumstances, evaluating pain management in patients with terminal cancer receiving home-based care is highly important. In Japan, small-scale studies from a limited number of institutions have compared opioid use between home- and hospital-based care; however, no nationwide database studies have been reported to our knowledge [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Clarifying differences in opioid doses\u0026mdash;an indicator of palliative care quality\u0026mdash;between home- and hospital-based care may inform clinical practice, policymaking, and resource allocation to improve palliative care quality in Japan.\u003c/p\u003e \u003cp\u003eIn this study, we conducted a cohort study using the JMDC Claims Database to compare palliative care quality between home- and hospital-based settings in Japan, focusing on opioid doses in the 90 days preceding death among patients with terminal cancer.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSetting and Data\u003c/h2\u003e \u003cp\u003e This study followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. It was approved by the Institutional Review Board and Ethics Committee of The University of Tokyo (Reference No. 2021076NI). Because the data were anonymized, the requirement for written informed consent was waived by the Institutional Review Board.\u003c/p\u003e \u003cp\u003eThis study used data from the JMDC Claims Database (JMDC Inc., Tokyo, Japan) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The JMDC Claims Database is one of the largest and most comprehensive healthcare datasets in Japan, based on data provided by multiple health insurance societies. It primarily includes employees of medium- to large-sized companies and their dependents younger than 75 years covered by participating health insurance associations. The database integrates three main types of information: (1) enrollee registry data, including demographic and insurance-related details such as birth year and month, sex, and insurance status; (2) health insurance claims for inpatient, outpatient, dental, and pharmacy services; and (3) annual health check-up records, including government-mandated specific health examinations for individuals aged 40\u0026ndash;74 years. Claims data include detailed information on medical procedures, consultation dates, diagnoses coded according to the International Classification of Diseases, 10th Revision (ICD-10), and prescription records with drug names classified according to the World Health Organization Anatomical Therapeutic Chemical (ATC) system. As of June 2020, approximately 9.8\u0026nbsp;million individuals were registered in the JMDC database [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePopulation\u003c/h3\u003e\n\u003cp\u003ePatients aged 18 years or older who died between January 2014 and December 2023 and had a registered cancer diagnosis within 6 months before death were identified from the database. Eligible patients were required to: (1) receive chemotherapy (ATC code L01) within 6 months before death; (2) have at least a 6-month look-back period before the last chemotherapy administration; and (3) have a recorded cancer diagnosis (ICD-10 codes C00.x-C96.x) during the look-back period. Patients were excluded if they (1) died in the same month as the last chemotherapy administration or (2) received home-based care during the look-back period.\u003c/p\u003e\n\u003ch3\u003eExposure\u003c/h3\u003e\n\u003cp\u003ePatients who initiated home-based care in the month of the last chemotherapy administration or the following month were classified into the home-based care group. Receipt of home-based care was identified using Japanese medical procedure codes C002, C002-2, and C003. All other patients were classified into the hospital-based care group.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eAccording to Foley\u0026rsquo;s estimate, about 80% of patients with terminal cancer require 60\u0026ndash;75 mg of oral morphine per day during the 90 days before death [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Using this estimate as a reference, we defined the primary outcome as the median daily opioid dose during the last 90 days before death. The secondary outcomes were trends in opioid dose between home-based care and hospital-based care over the last 3 months before death, annual trends in the proportion of patients receiving home-based care, and regional differences in the proportion of patients receiving home-based care and in opioid dose between home-based and hospital-based care.\u003c/p\u003e \u003cp\u003eThe opioid dose was calculated as the sum of prescribed oral, transdermal, rectal, and injectable opioid formulations, excluding transmucosal fentanyl products. Before summing across formulations, each prescription was converted to morphine milligram equivalents using the morphine equivalence ratios provided by the Japanese Society for Palliative Medicine Guidelines 2020 for Pharmacological Management of Cancer Pain (Online Resource 1) [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The opioid dose during the last 90 days before death was calculated as follows. The doses prescribed in the month of death, the preceding month, 2 months before death, and 3 months before death were denoted as D\u003csub\u003e0\u003c/sub\u003e, D\u003csub\u003e1\u003c/sub\u003e, D\u003csub\u003e2\u003c/sub\u003e, and D\u003csub\u003e3\u003c/sub\u003e, respectively. For the month of death, a mean survival of 15 days was assumed. Accordingly, opioid dose during 0\u0026ndash;30 days before death was calculated as D\u003csub\u003e0\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;D\u003csub\u003e1\u003c/sub\u003e/2. Similarly, opioid dose during 30\u0026ndash;60 days before death was calculated as D\u003csub\u003e1\u003c/sub\u003e/2\u0026thinsp;+\u0026thinsp;D\u003csub\u003e2\u003c/sub\u003e/2, and opioid dose during 60\u0026ndash;90 days before death was calculated as D\u003csub\u003e2\u003c/sub\u003e/2\u0026thinsp;+\u0026thinsp;D\u003csub\u003e3\u003c/sub\u003e/2. Total opioid dose during the last 90 days before death was calculated as (D\u003csub\u003e0\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;D\u003csub\u003e1\u003c/sub\u003e/2) + (D\u003csub\u003e1\u003c/sub\u003e/2\u0026thinsp;+\u0026thinsp;D\u003csub\u003e2\u003c/sub\u003e/2) + (D\u003csub\u003e2\u003c/sub\u003e/2\u0026thinsp;+\u0026thinsp;D\u003csub\u003e3\u003c/sub\u003e/2) = D\u003csub\u003e0\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;D\u003csub\u003e1\u003c/sub\u003e + D\u003csub\u003e2\u003c/sub\u003e + D\u003csub\u003e3\u003c/sub\u003e/2.\u003c/p\u003e\n\u003ch3\u003ePotential Confounding Variables\u003c/h3\u003e\n\u003cp\u003ePotential confounders included demographic factors, cancer type, and receipt of radiation therapy. Variables were selected based on their potential to influence care setting, opioid dose, and prognosis, according to clinical expertise and prior research [\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Covariates included treatment period, sex, age, Charlson Comorbidity Index score, lung cancer, upper gastrointestinal cancer, lower gastrointestinal cancer, pancreatic cancer, and receipt of radiation therapy. Cancer type included the four most frequent cancers in this database. Receipt of radiation therapy was identified from records during the look-back period. The Charlson Comorbidity Index score, which quantifies comorbidity burden, was calculated from ICD-10 codes registered during the look-back period using Quan\u0026rsquo;s algorithm [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eComparison between home-based care and hospital-based care\u003c/h2\u003e \u003cp\u003eA propensity score-matched analysis was conducted to adjust for confounding by indication and baseline differences between the home-based care group and the hospital-based care group [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Propensity scores were calculated using a multivariable logistic regression model, with home-based care as the dependent variable. The independent variables included the nine confounders described above. Nearest neighbor matching at a one-to-four ratio was used, with patients in the home-based care group matched to those in the hospital-based care group using estimated propensity scores within a caliper of 0.2 standard deviations of the logit. Covariate balance between groups was assessed using absolute standardized differences, with a value\u0026thinsp;\u0026gt;\u0026thinsp;0.1 indicating imbalance.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\n\u003ch3\u003eAnnual trends in the use of home-based care\u003c/h3\u003e\n\u003cp\u003e We estimated adjusted annual proportions of patients receiving home-based care using a multivariable logistic regression model. The model included calendar year and eight additional covariates described earlier, excluding the treatment period. Adjusted proportions were calculated as marginal predicted probabilities from the fitted model.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComparison between regions\u003c/h2\u003e \u003cp\u003eFor regional analyses, Japan was divided into seven regions: Hokkaido/Tohoku, Kanto, Chubu, Kansai, Chugoku, Shikoku, and Kyushu/Okinawa, and comparisons were made across regions. Regional differences in the proportion of patients receiving home-based care were estimated using a logistic regression model that included region in addition to the nine covariates described above. Pairwise comparisons between regions were conducted using margins with Bonferroni correction. Adjusted median opioid doses were estimated using a quantile regression with bootstrap standard errors, including the nine independent variables described earlier, as well as region and home-based care status [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The interaction between region and home-based care status was also included in the model. Pairwise comparisons were adjusted for multiple testing using the Bonferroni method.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis\u003c/h2\u003e \u003cp\u003eFor the subgroup analysis, we recalculated the same opioid use metric using data from patients whose opioid consumption was within the top 80%, consistent with Foley\u0026rsquo;s estimate.\u003c/p\u003e \u003cp\u003eContinuous variables were compared between the groups using the Mann\u0026ndash;Whitney U test. Categorical variables were compared between the groups using the chi-square test. Adjustment for multiple comparisons was performed using the Bonferroni method. All reported P-values were two-sided, and P-values of \u0026lt;\u0026thinsp;0.05 were considered statistically significant. All statistical analyses were conducted using Stata/SE software (version 19.0; StataCorp, College Station, TX, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWe identified 17,115 patients with both a cancer diagnosis and a death record between January 2014 and December 2023 in the database. After applying the exclusion criteria, 8,429 patients were included for analysis (5,052 [59.9%] male; mean age [standard deviation], 58.2 [10.0] years) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the baseline characteristics of the two groups. One-to-four propensity score matching yielded a final study cohort of 1,028 patients and 4,112 patients in the home- and hospital-based care groups, respectively. After matching, all absolute standardized differences were \u0026lt;\u0026thinsp;0.1, indicating acceptable matching quality (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the primary outcomes in the matched groups. The median daily opioid dose in the last 90 days of life was significantly higher in the home-based care group than in the hospital-based care group (29.4 mg [95% confidence interval (CI), 25.2\u0026ndash;32.9] vs 17.8 mg [16.4\u0026ndash;18.7]; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Mann\u0026ndash;Whitney U test). Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the trends in opioid dose over the last 3 months before death in the two groups. Opioid dose increased as death approached. Online Resources 2 and 3 show daily opioid doses among patients in the top 80% of opioid consumption. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the annual trends in the utilization of home-based care. Use of home-based care increased gradually over time. Online Resource 4 presents the unadjusted baseline characteristics by region. Figure\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e presents regional differences in the proportion of patients receiving home-based care. After Bonferroni correction, significant differences were observed between the Kanto region (including Tokyo) and the Hokkaido/Tohoku, Chubu, Chugoku, and Kyushu/Okinawa regions, as well as between the Kansai region (including Osaka and Kyoto) and the Hokkaido/Tohoku, Chubu, and Kyushu/Okinawa regions. Figure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e shows regional differences in opioid doses between the two groups. Significant differences between the home- and hospital-based care groups were observed only in the Kanto region (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and the Kansai region (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035). The adjusted opioid dose in the home-based care group was highest in the Kanto region; however, this difference did not reach statistical significance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline patient characteristics in the unmatched and propensity score-matched groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnmatched groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eMatched groups\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHome-based\u003c/p\u003e \u003cp\u003ecare group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHospital-based\u003c/p\u003e \u003cp\u003ecare group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASD*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHome-based\u003c/p\u003e \u003cp\u003ecare group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHospital-based\u003c/p\u003e \u003cp\u003ecare group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eASD*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7401\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2014\u0026ndash;2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e239 (23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3425 (46.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e239 (23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e961 (23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2020\u0026ndash;2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e339 (33.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2027 (27.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e339 (33.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1348 (32.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2022\u0026ndash;2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e450 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1949 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e450 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1803 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e550 (53.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4502 (60.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e550 (53.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2176 (52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e478 (46.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2899 (39.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e478 (46.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1936 (47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56.5\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e242 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1252 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e242 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e953 (23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50\u0026ndash;59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e353 (34.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2503 (33.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e353 (34.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1433 (34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60\u0026ndash;69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e319 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2618 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e319 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1317 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1028 (13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e114 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e409 (9.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharlson comorbidity index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e291 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2196 (29.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e291 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1165 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e410 (39.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2967 (40.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e410 (39.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1637 (39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e327 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2238 (30.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e327 (31.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1310 (31.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiation therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e244 (23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1608 (21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e244 (23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1002 (24.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e208 (20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1757 (23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e208 (20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e753 (18.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUpper gastrointestinal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e257 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1805 (24.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e257 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e952 (23.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLower gastrointestinal cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e253 (24.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1974 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e253 (24.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e902 (21.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePancreatic cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222 (21.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1402 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e222 (21.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e800 (19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eCategorical variables are presented as n (%), and continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e*ASD\u0026thinsp;\u0026gt;\u0026thinsp;0.1 is considered imbalanced.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eASD, absolute standardized difference.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we found that opioid use during the last 90 days before death among patients with terminal cancer was higher in the home-based care group than in the hospital-based care group. This tendency was consistently observed over time and across regions.\u003c/p\u003e \u003cp\u003eOne possible explanation for the lower opioid use observed in the hospital-based care group is the absence of or inadequate functioning of palliative care teams in hospital settings. As of 2024, there were more than 1,700 acute care hospitals in Japan, of which only 464 were designated as cancer care hospitals as of 2025 [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Although the establishment of a palliative care team is required for designation as a cancer care hospital, this requirement does not apply to other hospitals. As a result, many patients with cancer in Japan are likely to receive care in settings without access to a dedicated palliative care team. Furthermore, substantial variation exists in the level of clinical activity even among hospitals with palliative care teams. We have previously reported that lower levels of palliative care team activity are associated with poorer patient outcomes, and such low-activity teams may also be associated with insufficient opioid prescribing [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Taken together, both the limited availability of palliative care teams and the presence of teams with low levels of activity may account for the lower levels of opioid prescribing observed in the hospital-based care group.\u003c/p\u003e \u003cp\u003eAlthough opioid use was higher in the home-based care group than in the hospital-based care group, the absolute doses remained low compared with international standards. In this study, the median daily opioid dose during the last 90 days before death was 29.4 mg/day in the home-based care group and 17.8 mg/day in the hospital-based care group. According to Foley\u0026rsquo;s estimate, approximately 80% of patients with terminal cancer require 60\u0026ndash;75 mg of oral morphine per day during the last 90 days before death [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In the subgroup analysis restricted to the top 80% of opioid users to align with Foley\u0026rsquo;s estimate (Online Resource 2), the opioid dose in the home-based care group was 44.7 mg/day (95% CI, 39.1\u0026ndash;49.3), which remained below Foley\u0026rsquo;s estimate. In the trend analysis (Online Resource 3), the home-based care group reached 61.6 mg/day (95% CI, 55.9\u0026ndash;69.5) in the month of death, approaching Foley\u0026rsquo;s estimate. However, doses at other time points were substantially lower, and the hospital-based care group showed lower doses throughout.\u003c/p\u003e \u003cp\u003eThe relatively low level of opioid prescribing in Japan may be explained by a combination of cultural and regulatory factors. From a cultural perspective, opioids in Japan are often perceived by the general public not as analgesics, but as illegal psychoactive substances or medications used for end-of-life sedation. As a result, many patients and their families are reluctant to use opioids for pain management. In addition, some healthcare professionals, partly because of limited education and training, may avoid opioid use, believing that opioids should be avoided whenever possible [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. From a regulatory perspective, outpatient opioid prescriptions in Japan are limited to 30 days. In addition, regulations governing the handling and storage of opioids in hospitals are highly restrictive, which may further discourage their use in routine clinical practice [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. As part of national efforts to promote the appropriate use of opioids, designated cancer care hospitals are required to establish palliative care teams, and physicians on these teams are required to complete designated palliative care training programs on appropriate opioid use [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, as noted above, hospitals other than designated cancer care hospitals are not required to establish palliative care teams, and many therefore lack such teams; accordingly, the effectiveness of this policy remains unclear. In the present study, opioid use in home-based care in the Kanto region, including Tokyo, was the highest across all care settings, although the difference was not statistically significant. The geographic maldistribution of palliative care specialists, who are concentrated in urban areas, may partly explain the lower opioid use observed in rural regions.\u003c/p\u003e \u003cp\u003eIn Japan, policy efforts to promote home-based care included enhanced financial incentives for home medical services in 2006. Consistent with these policies, this study showed a temporal trend toward increased home-based care use over time (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, the utilization of home-based care remains lower in rural areas, such as the Hokkaido/Tohoku region and the Kyushu/Okinawa region, than in urban areas (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). A previous study has also reported lower utilization of home-based care in rural areas than in urban areas [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Low population density, which reduces financial viability, and difficulties in securing hospital admission in the event of acute deterioration, which increase the burden on home-based physicians, may limit the expansion of home-based care services in rural areas. Strengthening incentives for home-based care in rural areas may increase the utilization of home-based care among patients with terminal cancer, thereby promoting appropriate opioid use.\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, compared with the general Japanese population, the study sample included a smaller proportion of older patients (Online Resource 5), which may have biased the estimated opioid doses. Second, opioid doses in this study were calculated from prescribed amounts, which may not have been fully consumed in clinical practice and may therefore have overestimated opioid use. Third, to approximate a terminal cancer population, we included patients who died within 6 months after their final chemotherapy; however, this approach may have included some patients who were not at the terminal stage. Fourth, as with other propensity score-matched analyses, residual confounding due to unmeasured variables, such as performance status and body mass index, may have resulted in incomplete adjustment between groups.\u003c/p\u003e \u003cp\u003eIn this study, home-based care was significantly associated with higher opioid consumption among patients with terminal cancer; however, the absolute opioid dose remained low compared with international standards. We also found that the utilization of home-based care has increased over time; however, its use remains relatively low in rural areas. To promote the appropriate use of opioids among patients with terminal cancer, policies aimed at expanding home-based care\u0026mdash;particularly in rural regions\u0026mdash;may be warranted.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eDeclaration of financial/other relationship\u003c/h2\u003e \u003cp\u003eThe department to which HA and SN belong is supported by Shionogi \u0026amp; Co., Ltd., Nippon Zoki Pharmaceutical Co., Ltd., Aiwa Hospital, and Yoshida Hospital. MS received funding for this study from Shionogi \u0026amp; Co., Ltd., Nippon Zoki Pharmaceutical Co., Ltd., Aiwa Hospital, and Yoshida Hospital, and payments for lectures from Shionogi \u0026amp; Co., Ltd., Daiichi Sankyo Company, Limited, and GlaxoSmithKline plc. YM is an employee of Shionogi \u0026amp; Co., Ltd. All other authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eEthics approval\u003c/h2\u003e \u003cp\u003e\u003cb\u003estatement\u003c/b\u003e: This study was approved by the Institutional Review Board and Ethics Committee of The University of Tokyo (Reference No. 2021076NI).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003ePatient consent statement\u003c/strong\u003e \u003cp\u003e Due to the anonymized nature of the data, the requirement for obtaining written informed consent was waived by the Institutional Review Board.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eShionogi \u0026amp; Co., Ltd. had a role in the collection of data from the JMDC database and in the publication. Nippon Zoki Pharmaceutical Co., Ltd., Aiwa Hospital, and Yoshida Hospital had no role in the collection, analysis, and interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication.\u003c/p\u003e\u003ch2\u003eAuthors\u0026rsquo; contributions:\u003c/h2\u003e \u003cp\u003eHA, YM, and MS conceived and designed the study. RI, TK, RT, YS, YO, and YY extracted, cleaned, and prepared the data for analysis. HA, SN, and HO conducted the statistical analysis. HA, YM, and MS interpreted the results. HA drafted the manuscript. HA, YM, and MS critically revised the manuscript. All authors are fully responsible for the overall content for the work and the conduct of the study. All authors had access to the data and were involved in the decision to publish the study. All authors reviewed the manuscript and approved the final submitted version.\u003c/p\u003e\u003ch2\u003eAcknowledgments:\u003c/h2\u003e \u003cp\u003eWe thank Yumi Sato of Shionogi \u0026amp; Co., Ltd. for study planning and data curation for this study.\u003c/p\u003e\u003ch2\u003eData availability statement:\u003c/h2\u003e \u003cp\u003eWe cannot provide raw data being freely available because we did not obtain agreements to release the data from the supplier and because our ethical approval did not include the release. Instead, the datasets used and/or analyzed during this study are completely available from the corresponding author for collaborative research purposes upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCabinet Office Japan (2024) Annual report on the ageing society [Summary]. FY2024 [Internet]. Accessed 2026 Jan 22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www8.cao.go.jp/kourei/english/annualreport/2024/pdf/2024.pdf\u003c/span\u003e\u003cspan address=\"https://www8.cao.go.jp/kourei/english/annualreport/2024/pdf/2024.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilson DM, Fabris LG, Martins ALB et al (2025) Location of death in developed countries: Are hospitals a primary place of death and dying now? Omega 91:781\u0026ndash;797. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1177/00302228221142430\u003c/span\u003e\u003cspan address=\"10.1177/00302228221142430\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMinistry of Health, Labour and Welfare of Japan (2012) [Internet] Home medical and long-term care security. 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Pain Med 4:125\u0026ndash;134. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1046/j.1526-4637.2003.03020.x\u003c/span\u003e\u003cspan address=\"10.1046/j.1526-4637.2003.03020.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"patients with cancer, opioid dose, home-based care, hospital-based care, regional differences, real-world data","lastPublishedDoi":"10.21203/rs.3.rs-9455777/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9455777/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn Japan, end-of-life care for patients with terminal illness has traditionally been delivered predominantly in hospitals. Recent national policies promoting home-based care have increased deaths at home. However, comparative evidence on care quality across home and hospital-based settings remains limited. This study compares opioid use in patients with terminal cancer receiving home- versus hospital-based care and examines regional variation using real-world data.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients with cancer who died within 6 months of completing chemotherapy between 2014 and 2023 were identified from the JMDC Claims Database, one of the largest claims-based healthcare databases in Japan. Opioid doses in the last 90 days of life were compared between home-based and hospital-based care groups using a propensity score-matched analysis. In addition, temporal trends in home-based care use and regional variation were assessed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 8,429 eligible patients (59.9% male; mean age, 58.2 years), 12.2% received home-based care. The median daily opioid dose, expressed as morphine milligram equivalents, during the last 90 days of life was significantly higher in the home-based care group than in the hospital-based care group (29.4 mg/day vs. 17.8 mg/day; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Home-based care utilization increased over time. The proportion of patients receiving home-based care was highest in the Kanto region, including Tokyo, and opioid doses in home-based care were also highest in this region, although these differences were not statistically significant.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this real-world cohort study from Japan, home-based care use was associated with higher opioid doses in patients with terminal cancer.\u003c/p\u003e","manuscriptTitle":"Opioid use in terminal patients with cancer: comparison between home-based and hospital-based care in Japan","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-28 12:56:09","doi":"10.21203/rs.3.rs-9455777/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-04-21T12:57:13+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-19T22:49:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-18T11:29:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2026-04-18T05:39:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a8fe5082-79b8-4e39-821e-a425ac1f0772","owner":[],"postedDate":"April 28th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T12:56:09+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-28 12:56:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9455777","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9455777","identity":"rs-9455777","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}