Development of a Consensus Syllabus of Palliative Medicine for Physicians in Japan Using a Modified Delphi Method.

CONTEXT: Although palliative care is rapidly being disseminated throughout Japan as a result of government policy, a systematic syllabus of palliative medicine for physicians has not been developed. AIMS: This study aimed to develop a Japanese national consensus syllabus of palliative medicine for physicians. DESIGN: We used a modified Delphi method to develop the consensus syllabus. METHODS AND SETTING: We created a Delphi panel by selecting 20 expert eligible panelists consisting of Diplomate or Faculty of the Specialty Board of Palliative Medicine and certified by the Japanese Society for Palliative Medicine. We inducted external reviewers from 11 palliative care-related organizations. RESULTS: Among 20 experts surveyed, 20 (100%) responded over all rounds. Ten (50%) participated in a panel meeting. In the first round, 179 of 179 (100%) learning objectives were judged to be appropriate and 5 of 179 (3%) learning objectives were judged to be too difficult. In the panel meeting, 25 learning objectives were excluded, three new learning objectives were added, and 15 learning objectives were reworded. In the second round, 18 of 18 (100%) learning objectives were judged to be appropriate. The final version of the syllabus developed consists of 157 specific behavioural objectives and 22 general instructional objectives across 22 courses. CONCLUSIONS: We have developed the first national consensus syllabus of palliative medicine for physicians in Japan. Based on this syllabus, a training program on palliative medicine will be established by training facilities in Japan, and physicians will be able to practice specific palliative care.

The distress and benefit to bereaved family members of participating in a post-bereavement survey.

BACKGROUND: Few studies have simultaneously collected quantitative data regarding the positive and negative effects of participating in post-bereavement surveys. METHODS: We conducted a cross-sectional postal questionnaire survey in October 2013. Potential participants were caregivers for family members who had died in four inpatient palliative care units, two home hospices, and a general hospital. We collected opinions regarding the distress and benefit of completing a post-bereavement survey. After collecting data, we provided feedback to participating institutions in the form of study results and de-identified open-ended comments. RESULTS: Of 692 potential participants, 596 were sent questionnaires; 393 returned questionnaires were valid and analyzed. Of the respondents, 62% reported being distressed by completing the questionnaire. Female participants and those who were mentally ill during the caregiving period reported more distress. However, 86% of respondents reported they found the questionnaire beneficial. Better quality of end-of-life care and respondent depression were associated with more benefit. Major benefits were: contributing to the development of end-of-life care as a family (63%); expressing gratitude to the hospital and medical staff (60%); and looking back and reflecting on the end-of-life period (40%). Feeling benefit was not correlated with feeling distressed (P = -0.02). CONCLUSION: In this large-scale study on the effects of post-bereavement surveys in Japan, many bereaved family members reported that completing the survey was beneficial. In addition to possibly having feelings of distress, post-bereavement surveys might also be beneficial to end-of-life care facilities.

Development the Care Evaluation Scale Version 2.0: a modified version of a measure for bereaved family members to evaluate the structure and process of palliative care for cancer patient.

BACKGROUND: The Care Evaluation Scale (CES1.0) was designed to allow bereaved family members to evaluate the structure and process of care, but has been associated with a high frequency of misresponses. The objective of this study was to develop a modified version of CES1.0 (CES2.0) that would eliminate misresponses while maintaining good reliability and validity. METHODS: We conducted a cross-sectional questionnaire survey by mail in October 2013. The participants were bereaved family members of patients who died from cancer in seven institutions in Japan. All family members were asked to complete CES2.0, the short form CES1.0, items on overall care satisfaction, the Family Satisfaction with Advanced Cancer Care (FAMCARE) Scale, the Patient Health Questionnaire-9 (PHQ-9) and the Brief Grief Questionnaire (BGQ). To examine test-retest reliability, all participants were asked to complete a second CES2.0. RESULTS: Of 596 questionnaires sent, 461 (77%) were returned and 393 (66%) were analyzed. In the short form CES1.0, 17.1% of the responses were identified as misresponses. No misresponses were found in CES2.0. We identified 10 CES2.0 subscales similar to those in CES1.0 using exploratory factor analysis. Cronbach's alpha was 0.96, and the intraclass correlation coefficient was 0.83. Correlations were found between CES2.0 and overall satisfaction (r = 0.83) and FAMCARE (r = 0.58). In addition, total CES2.0 scores were negatively correlated with the PHQ-9 (r = -0.22) and BGQ (r = -0.10). CONCLUSION: These results suggest that CES2.0 eliminated misresponses associated with CES1.0 while maintaining good reliability and validity and greatly improving test-retest reliability.

Potential utility of peripherally applied loperamide in oral chronic graft-versus-host disease related pain.

Four patients with oral chronic graft-versus-host disease pain were treated with loperamide oral-rinse solution. Two-week continued use of the drug solution improved not only the pain scores but also the pain-causing disabilities associated with eating, drinking and sleeping, with no noticeable side effects. Current results suggest that the mu-opioid agonist, loperamide, has a potential analgesic effect that could be clinically used as a peripheral analgesic agent for stomatitis pain. However, these observations will need to be further confirmed in a randomized-controlled trial.

DNA methylation of genes linked with retinoid signaling in gastric carcinoma: expression of the retinoid acid receptor beta, cellular retinol-binding protein 1, and tazarotene-induced gene 1 genes is associated with DNA methylation.

BACKGROUND: Hypermethylation of CpG islands has been associated with silencing of various tumor suppressor genes, and the retinoid acid receptor beta (RARbeta), cellular retinol-binding protein 1 (CRBP1), and tazarotene-induced gene 1 (TIG1) genes have been associated with retinoic acid signaling. To the authors' knowledge, little is known regarding the involvement of these three genes in gastric carcinoma (GC). In this study, the authors investigated the methylation status of these genes and analyzed the role of their DNA methylation in GC. METHODS: DNA methylation of 3 retinoic acid-associated genes was analyzed in 42 samples of GC from 42 patients and in 8 GC cell lines by methylation-specific polymerase chain reaction (PCR) analysis. The mRNA expression levels for these three genes were measured by quantitative reverse transcription-PCR. RESULTS: In 7 of 8 GC cell lines, the CRBP1 gene was hypermethylated, and CRBP1 transcription was inactive. In 6 of 8 GC cell lines, the TIG1 gene was hypermethylated, and TIG1 transcription was inactive. Treatment with demethylating agent 5-aza-2'-deoxycytidine restored both CRBP1 and TIG1 transcription. DNA methylation of the RARbeta, CRBP1, and TIG1 genes was detected in 15 of 42 GC samples (36%), 14 of 42 GC samples (33%), and 4 of 42 GC samples (10%), respectively, and in 6 of 30 samples (20%), 0 of 30 samples (0%), and 1 of 30 samples (3%) of corresponding nonneoplastic mucosa. None of the 10 normal gastric mucosa samples from young, healthy individuals demonstrated hypermethylation of any of these genes. DNA methylation of each gene was associated significantly with low mRNA expression of the respective gene. Twenty-four of 42 GC samples (57%) demonstrated hypermethylation of at least 1 of the 3 genes. However, no significant, concordant hypermethylation of these genes was observed. CONCLUSIONS: The results suggested that gastric carcinogenesis involves transcriptional inactivation by aberrant DNA methylation of genes related to retinoid signaling.

Molecular-pathological prognostic factors of gastric cancer: a review.

Invasion and metastasis are critical determinants of cancer morbidity. Genes and molecules participating in these steps must be regarded as potential prognostic factors. Growth factors and their receptors, cell-cycle regulators, cell-adhesion molecules and matrix-degrading enzymes are those to be used as prognostic factors, including epidermal growth factor (EGF), EGF receptor, K-sam, HER-2, interleukin (IL)-8, vascular endothelial growth factor (VEGF), cyclin E, p27, E-cadherin, CD44v6, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Alterations in epigenetics, such as aberrant DNA methylation and histone modification that are, in part, associated with the tumor progression of gastric cancer, can be candidate prognostic factors. The number of methylated genes may serve as a marker of tumor progression. Genetic polymorphism not only affects cancer susceptibility but also influences malignant phenotype; examples include single-nucleotide polymorphism in the HER-2 and MMP-9 genes. Comprehensive gene expression analyses are useful to search for novel genes related to invasion and metastasis and potential prognostic factors. Serial analysis of gene expression (SAGE) has identified several these genes, such as CDH17, APOE, FUS, COL1A1, COL1A2, GW112, and MIA. Overexpression of MIA is found to be associated with poor prognosis. Microarray analysis has great potential for identifying the characteristics of individual cancers, from the view point of gene expression profiles. A combination of these examinations can not only foretell a patient's prognosis but can also give information directly connected with personalized cancer medicine and prevention.