Study design
A clinical prospective intervention study in end-of-life patients with advanced cancers was conducted. The study protocol was certified and approved by the Institutional Review Board (IRB)/Ethics Committee at Kaohsiung Medical University (KMU) Chung-Ho Memorial Hospital (IRB Number: KMUHIRB-SV(I)-20180050). All patients were admitted in the hospice ward of KMU Hospital between March and August 2019, and informed consent was written by volunteer patients or their primary caregivers. We conducted this study in two phases, and the flow of the study protocol is illustrated in Fig 1.
Phase I (pilot study, n = 30)
Before providing oral care, we defined inclusion and exclusion criteria, established a method for evaluating the quality of care, confirmed the validity and reliability of our evaluation tool (a questionnaire), and calculated the required sample size. We recruited 30 patients in our Phase I pilot study and confirmed the questionnaire’s validity (0.99) and reliability (Cronbach’s α > 0.9). We also calculated the minimum sample size of 12. Only patients who (1) were ≥20 years old, (2) had received a diagnosis of terminal advanced cancers by two specialists, and (3) agreed to accept oral care intervention were included. The patients who (1) were <20 years old, (2) had non–terminal advanced cancers, (3) had oral malignant disorders, (4) were warded more than once, (5) accepted any regular dental treatment within the past 1 year, and (6) were critically ill or with systemic conditions, such as extremely low platelet count, or those who could not withstand the oral care procedure were excluded.
Phase II (n = 27)
We then began the Phase II study by recruiting 30 patients. However, we excluded three patients who survived for >30 days and included only end-of-life patients. The exclusion and inclusion criteria and the intervention of oral care procedures were identical to those of the Phase I pilot study. After carefully anticipating and solving possible problems in the pilot study, we collected data on the oral examinations and physical conditions of 27 terminally ill patients with advanced cancers.
Finally, 27 end-of-life patients with advanced cancers were enrolled; they underwent oral examination on Days 1, 4, and 7 in the intervention period. Professional oral care was administered daily in the morning. Before providing oral care, we performed an oral examination. We recorded the oral conditions on Days 1, 4, and 7. Therefore, subsequent oral care would not affect the initial oral examination data. Power analysis was performed, and the improvement of conditions was evaluated by comparing oral conditions after and before the intervention.
Classification of cancer type
According to International Classification of Diseases for Oncology, Third Edition (ICD-O-3), cancers are coded according to topographic sites. In this study, cancers of various anatomical sites included malignant carcinoma of the colon, rectum, rectosigmoid junction, and anus (C18–C21); the trachea, bronchus, and lungs (C33–C34); the liver and intrahepatic bile ducts (C22); the head and neck (C76); the oesophagus (C15); leukaemia (C42); skin and malignant melanoma (C44); the pancreas (C25); the kidneys (C64); the cervix uteri (C53); the corpus uteri (C54); and the ovary, fallopian tube, and broad ligament (C56, C57.0–C57.4); the female breasts (C50); and the meninges, spinal cord, and other parts of the central nervous system (C70, C72).
Content and sections of the questionnaire
The final questionnaire content for the patients with cancer contained four sections on their (1a) sociodemographic information (gender, age, and education level) and (1b) clinical index (BMI, estimated survival, Eastern cooperative oncology group (ECOG) status, activities of daily living (ADL), Glasgow coma scale, palliative prognosis index, limb oedema index, and bacterial level), (2) oral health (mucosa health, oral moisture, and oral cleanliness), (3) general oral assessment (Oral Health Assessment Tool (OHAT) at examination at different oral sites), and (4) oral function (voice, swallow, modified water swallowing test (MWST), and maximum mouth opening (MMO)). These sections comprised 19 major items, which are detailed subsequently.
Oral examination and data recording
All examinations were conducted by a certified dentist. Our oral examination comprised four major sections. The first section involved extracting patient data from medical records. These data comprised general data on cancer type and cancer treatment prior to being warded in the hospice, sociodemographic data (assessed using three questions, each on gender, age, and education level), and clinical index data (BMI, estimated survival, ECOG status, ADL, Glasgow coma scale, palliative prognosis index, limb oedema index, and bacterial amount level). Furthermore, data of personal habits including oral care habits, record of ECOG, consciousness status (Glasgow coma scale), degree of extremity edema [11], and the nutrition route were collected.
The second section was the oral examination, which was used to gather oral health data on mucosa health, oral cleanliness, moisture, and oral function. To evaluate oral mucositis, we used the mucositis classification of World Health Organization (WHO) [12-14]. In this study, we divided the patients into two groups based on the presence or absence of mucositis: the presence of mucositis (grades I–IV) and absence of mucositis (Grade 0). The description of grades is as follows: Grade 0 (no mucositis): no changes or normal mucosa; Grade I (mild mucositis): oral soreness and erythema; Grade II (moderate mucositis): oral erythema, ulcers, and ability to accept a solid diet; Grade III (severe mucositis): oral ulcers and ability to accept a liquid diet only; and Grade IV (life-threatening mucositis): oral alimentation is impossible [13].
To evaluate oral cleanliness, we determined the tongue coating index (TCI) according to a previously reported method [15]. The TCI separated the tongue surface into nine parts, and the consistency of tongue fur or debris on each part was recorded. The level of bacterial accumulation was assessed using a rapid oral bacteria quantification machine through dielectrophoresis and impedance measurement; higher readings represented the higher levels of bacterial accumulation (level 1 indicated an accumulated bacterial count of <105 CFU/ml; level 2 indicated an accumulated bacterial count between 105 and 106 CFU/ml, level 3 indicated an accumulated bacterial count between 106 and 106.5 CFU/ml, and level 7 indicated an accumulated bacterial count of over 108 CFU/ml) [16]. Therefore, we divided the patients into low (≤106.5 CFU/ml) and high (> 106.5 CFU/ml) groups based on the accumulation of bacteria.
The oral debris, also called the detach mucous film retention in Japan, was classified into three levels according to its amount and consistency. The mild group comprised level 1 (no retention) and level 2 (some retention and white appearance). The severe group comprised level 3 (generalised intraoral retention). Oral moisture was recorded using the Clinical Diagnosis Classification (Grade 0, 1, 2, and 3) of oral dryness and self-reported oral dryness (sensation), according to a previous study [17]. Grade 0 indicated non–dry mouth, Grade 1 viscous saliva in the mouth, Grade 2 saliva with tiny bubbles on the tongue, and Grade 3 dry tongue with either no or less viscous saliva.
Furthermore, oral dryness sensation was assessed by directly asking the patients (scores of 1, 2, and 3 indicated sensations of no, mild, and severe oral dryness [SOD]) by using a questionnaire. A device was used to measure oral moisture to quantify the degree of oral dryness (Mucus®, Life Co., Ltd.) [18].
To verify the effect of the intervention on oral moisture, we used the oral moisture device before and after the oral care. Oral moisture was tested at two sites, namely 1 cm from the tongue tip on the dorsal tongue and on the buccal mucosa (1 cm from the corner of the mouth). Oral moisture was tested was 1–2 hours after the intervention had been administered in the morning.
The third section indicated general oral evaluation conducted using the Oral Assessment Guide (OAG) [19] and Oral Health Assessment Tool (OHAT) [20]. The OHAT has eight categories and includes evaluation of the entire mouth; scores of 0, 1, and 2 represent normal oral conditions, change in conditions, and unhealthy conditions, respectively, and the OHAT is the recommended assessment in dental health examinations [20]. Furthermore, the OAG has eight categories of evaluation; however, the evaluation category is partially different and includes differences in description, such as evaluation of voice and swallowing function, and the ratings range from 1 to 3 [19].
The fourth section evaluated voice function, where the patients were divided into normal and abnormal groups; the normal group was assigned a score of 1. The abnormal group had ratings of 2 and 3, respectively, which indicated that the patients had deeper than normal or raspy voices and experienced difficulty in talking or crying or pain while talking or crying. The four part includes the swallowing function was assessed by determining the swallowing scores of the OHAT, MWST [21]. The fungal infection examination included collection of tongue smears for Candida examination. In most categories, higher scores represented poorer conditions. However, in the MWST, higher scores indicated superior swallowing function. Higher readings on the oral moisture device indicated higher oral moisture.
We considered the first day on which the patients were admitted to the hospice as Day 1. The first oral examination was conducted on Day 1 before any oral care or oral treatment. After the examination, oral care was initiated, and oral hygiene instructions were provided to the patients’ families or caregivers. The oral care procedure we developed combined a wiping technique [22] and oral care protocols suggested by professor Matsuo [10]. Oral examination was performed every 3 days (Days 1, 4, and 7), and professional oral care was provided every morning and three times per day.
Oral care protocol
At the beginning of oral care, a facial massage was provided, including a massage of the masseter muscle and salivary glands. An oral moisture spray and oral moisture jelly were used for increasing mucosal moisture and for protecting the mucosa. Retained plaque and debris on the teeth were removed using a soft dental brush. Then, oral foam sticks were used for mucosa cleaning. The teeth and mucosa were wiped with a moistened gauze. Oral moisture jelly was applied again for maintaining the moisture of the oral mucosa.
Data Analyses
Statistical analysis
All quantitative variables are presented as medium and interquartile range (IQR), and categorical variables are presented as frequencies and percentages. Because these data did not conform to the assumption of normality according to Shapiro–Wilk test, the nonparametric Mann–Whitney U was used to test two independent samples. Furthermore, a Friedman test was used to test any significant difference in the measurements over time. For intragroup comparisons, Cochran’s Q for repeated measures was used to assess bivariate associations. After controlling for gender and age, adjusted odds ratio (AOR), 95% confidence intervals (CI) and exact p values were estimated with an unconditional logistic regression model. To confirm agreement between the examiner’s and senior dentist’ evaluations, Cohen’s kappa statistics (an interrater statistical indicator) and overall percentage agreement were calculated. In this study, two-tailed p < 0.05 was considered statistically significant. All statistical procedures were conducted using SPSS v 20.0 Statistical Package (SPSS Inc., IBM, Armonk, New York, USA).
Sample size calculation and the power of the study
G∗Power (version 3.1.9.4, program written, conceptualised, and designed by Franz, Universitat Kiel, Germany), a freely available windows application software, was used for sample size and power estimation. Our pilot study estimated an effect size of 1.65; the mean ± standard deviation for SOD was 1.87 ± 0.35 and that for nonsevere oral dryness (NOD) was 1.07 ± 0.59. In our pilot study’s nonparametric Mann–Whitney U test, the estimated effect size was 1.65, type I (α) error was 0.05, and type II error (β) was 0.2; a minimum sample size of 12 was required to achieve a power (1-β) of ≥80%. Thus, in total, 27 participants were recruited to this study, and post hoc power analyses indicated that post hoc power was at least 85%, and a type II error (β) of 0.15 was present.