Study participants
This is a secondary analysis of an international multicenter cohort study conducted in three East Asian countries including Japan, Korea and Taiwan. The original study was the East Asian collaborative cross-cultural Study to Elucidate the Dying Process (EASED), which investigated the dying process and end-of-life care of inpatients with far advanced cancer in palliative care units (PCUs) in three East Asian countries. Eligible, newly admitted inpatients in the participating PCUs during the study period were consecutively enrolled in the study. All observations were performed in the course of routine clinical practice. The inclusion criteria were as follows: (1) adults (age > = 18 years in Japan and Korea and > = 20 years in Taiwan), (2) suffering from locally extensive or metastatic cancer, and (3) admitted to a participating PCU. The exclusion criteria were: (1) scheduled discharge within 1 week and (2) refusal by patients or their families to participate in the study.
Data collection
The attending palliative care physicians and nurses recorded all demographic data on admission, and symptoms in the last 3 days of life based on the structured questionnaire. The questionnaire was developed through discussions among EASED investigators and the results of both western and eastern studies analyzing “impending death” and “good communication practices” involving dying patients and their families in PCUs [10-15].
We obtained and analyzed the following data: patient demographics and clinical characteristics on admission, and symptoms and signs in the last 3 days of life. Symptoms were defined as observations of patients because subjective assessment was difficult in the last 3 days of life. Symptoms included fatigue, dry mouth, drowsiness, dyspnea, delirium and hallucination. We used the Integrated Palliative Outcome Scale (IPOS) to objectively measure patients’ symptoms including fatigue, dry mouth and drowsiness: 0, not at all; 1, slightly; 2, moderately; 3, severely; 4, overwhelmingly; 5, cannot assess because of unconsciousness. The Japanese version of IPOS is a valid and reliable tool for assessing physical, psychological, social, and spiritual symptoms and measuring the outcomes of adult cancer patients in Japan [16]. The IPOS is currently undergoing validation in Korea. Taiwanese investigators have completed the validation of the IPOS and reported the results at an international symposium (Tohoku Forum for Creativity 2020). Dyspnea was scored as follows: 0, normal; 1, exertional only; and 2, at rest. We assessed delirium using the 10-item Memorial Delirium Assessment Scale (MDAS), based on item # 9 (psychomotor activity): 0, normal or psychomotor hypoactivity; 1, mild; 2, moderate; and 3, severe [17]. Hallucination was evaluated using the Delirium Rating Scale-revised-98 (DRS-R-98), with respect to item # 2 (perceptual disturbances and hallucinations): 0, not present; 1, mild perceptual disturbance; 2, illusions present; and 3, hallucinations present [18]. Respiratory secretion was scored as: 0, not audible; 1, only audible at the head of the bed; 2, clearly audible at the foot of the bed; and 3, clearly audible 6 m away from the foot of the bed [19]. The severity of leg edema was determined by measuring the depth upon pressing the skin for a sufficient amount of time in the area between the upper and the lower joints and was categorized as follows: 0, none; 1, mild (< 5 mm); 2, moderate (5–10 mm); and 3, severe (> 10 mm) [20, 21]. Ascites was scored as follows: 0, physically undetectable; 1, physically detectable but asymptomatic; or 2, symptomatic based on physician examination. We evaluated myoclonus based on five levels of jerking frequency per 10 s at rest: 0, none; 1, ≤ 1 jerk; 2, 2–3 jerks; 3, 4–9 jerks; and 4, ≥ 10 jerks.
Statistical analysis
All analyses were performed using JMP version 14 for Windows (SAS, Cary, NC, USA).
First, we classified study participants into 3 groups according to the type of primary cancer prevailing in East Asia: digestive tract, lung and others. Digestive tract cancer includes gastroesophageal, colorectal, hepatobiliary, and pancreatic cancer. Lung cancer includes small-cell and non-small cell types. Other cancers include breast, gynecological, urological, head and neck, bone and soft tissue, skin, brain cancer and hematological malignancies.
Second, we performed descriptive analyses to summarize baseline characteristics of study participants according to the type of primary cancer.
Third, descriptive analyses were summarized as the prevalence of physical and psychological symptoms and signs according to the type of primary cancer in patients at admission, 1 week after admission and in the last 3 days of life. We defined ‘present symptoms’ as having more than one point of score of the response scale.
Fourth, we compared the severity of physical and psychological symptoms and signs in the last 3 days of life according to the type of primary cancer using one-way analysis of variance (ANOVA). Post hoc analysis was conducted using Tukey-Kramer test for multiple comparisons of each symptom according to the type of primary cancer.
Ethics
In accordance with the ethical guidelines for human research of Japan’s Ministry of Health, Labor, and Welfare, informed patient consent was waived in Japan because of the completely observational nature of the study. In Korea and Taiwan, informed consent was obtained from the patients or their families (if the patient lacked the capacity to make decisions). The study was approved by the local Institutional Review Boards of all participating institutions. Also, the independent ethics committee of Tohoku University School of Medicine (approval no. 2016-1-689) approved this study.