Early Detection and Prediction of Anthracycline-Induced Cardiotoxicity　- A Prospective Cohort Study.

BACKGROUND: In the present study, we aimed to investigate whether early cardiac biomarker alterations and echocardiographic parameters, including left atrial (LA) strain, can predict anthracycline-induced cardiotoxicity (AIC) and thus develop a predictive risk score.Methods and Results: The AIC registry is a prospective, observational cohort study designed to gather serial echocardiographic and biomarker data before and after anthracycline chemotherapy. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) ≥10 percentage points from baseline and <55%. In total, 383 patients (93% women; median age, 57 [46-66] years) completed the 2-year follow-up; 42 (11.0%) patients developed cardiotoxicity (median time to onset, 292 [175-440] days). Increases in cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) and relative reductions in the left ventricular global longitudinal strain (LV GLS) and LA reservoir strain [LASr] at 3 months after anthracycline administration were independently associated with subsequent cardiotoxicity. A risk score containing 2 clinical variables (smoking and prior cardiovascular disease), 2 cardiac biomarkers at 3 months (TnT ≥0.019 ng/mL and BNP ≥31.1 pg/mL), 2 echocardiographic variables at 3 months (relative declines in LV GLS [≥6.5%], and LASr [≥7.5%]) was generated. CONCLUSIONS: Early decline in LASr was independently associated with subsequent cardiotoxicity. The AIC risk score may provide useful prognostication in patients receiving anthracyclines.

Ectodermal factor restricts mesoderm differentiation by inhibiting p53.

During gastrulation of the amphibian embryo, specification of the three germ layers, endo-, ecto-, and mesoderm, is regulated by maternal and zygotic mechanisms. Although it is known that mesoderm specification requires the cooperation between TGF-beta signaling and p53 activity and requires maternal factors, essential zygotic factors have been elusive. Here, we report that the Zn-finger protein XFDL156 is an ectodermal, zygotic factor that suppresses mesodermal differentiation. XFDL156 overexpression suppresses mesodermal markers, and its depletion induces aberrant mesodermal differentiation in the presumptive ectoderm. Furthermore, we find that XFDL156 and its mammalian homologs interact with the C-terminal regulatory region of p53, thereby inhibiting p53 target gene induction and mesodermal differentiation. Thus, XFDL156 actively restricts mesodermal differentiation in the presumptive ectoderm by controlling the spatiotemporal responsiveness to p53.

The effect of palliative care team intervention and symptom improvement using patient-reported outcomes: a multicenter prospective observational study.

PURPOSE: Hospital-based palliative care teams (HPCTs) are widespread internationally, but multicenter studies about their effectiveness, using patient-reported outcomes (PROs), are limited to Australia and a few other countries. We conducted a multicenter, prospective observational study in Japan to explore the effectiveness of the HPCTs using PROs. METHODS: Nationwide, eight hospitals participated in the study. We included newly referred patients for one month in 2021 and followed them for one month. We asked the patients to complete the Integrated Palliative Care Outcome Scale or the Edmonton Symptom Assessment System as PROs at the time of the intervention, three days later, and weekly after the intervention. RESULTS: A total of 318 participants were enrolled, of whom 86% were patients with cancer, 56% were undergoing cancer treatment, and 20% received the Best Supportive Care. After one week, the following 12 symptoms showed more than a 60% improvement from severe to moderate or less: vomiting (100%), shortness of breath (86%), nausea (83%), practical problems (80%), drowsiness (76%), pain (72%), poor sharing of feelings with family or friends (72%), weakness (71%), constipation (69%), not feeling at peace (64%), lack of information (63%), and sore or dry mouth (61%). Symptoms with improvement from severe/moderate to mild or less were vomiting (71%) and practical problems (68%). CONCLUSION: This multicenter study showed that HPCTs effectively improved symptoms in several severe conditions, as assessed by PROs. This study also demonstrated the difficulty of relieving symptoms in patients in palliative care and the need for improved care.

Improved knowledge of and difficulties in palliative care among physicians during 2008 and 2015 in Japan: Association with a nationwide palliative care education program.

BACKGROUND: Palliative care education for health care professionals is a key element in improving access to quality palliative care. The Palliative Care Emphasis Program on Symptom Management and Assessment for Continuous Medical Education (PEACE) was designed to provide educational opportunities for all physicians in Japan. As of 2015, 57,764 physicians had completed it. The objective of this study was to estimate the effects of the program. METHODS: This study was an analysis of 2 nationwide observational studies from 2008 and 2015. We conducted 2 questionnaire surveys for representative samples of physicians. The measurements used were the Palliative Care Knowledge Test (range, 0-100) and the Palliative Care Difficulties Scale (range, 1-4). Comparisons were made with the unpaired Student t test and with a multivariate linear regression model using 2 cohorts and a propensity score-matched sample. RESULTS: This study analyzed a total of 48,487 physicians in 2008 and a total of 2720 physicians in 2015. Between 2008 and 2015, physicians' knowledge and difficulties significantly improved on the Palliative Care Knowledge Test with total scores of 68 and 78, respectively (P < .001; effect size, 0.40) and on the Palliative Care Difficulties Scale with total scores of 2.65 and 2.49, respectively (P < .001; effect size, 0.29). Propensity-score matching resulted in 619 untrained physicians matched to 619 trained physicians, and physicians who trained with the PEACE program had a higher knowledge score (74 vs 86; P < .001; effect size, 0.64) and a lower difficulties score (2.6 vs 2.3; P < .001; effect size, 0.42). CONCLUSIONS: Physicians' knowledge of and difficulties with palliative care improved on a national level. The PEACE program may have contributed to these improvements. Cancer 2018;124:626-35. © 2017 American Cancer Society.

One-year follow-up of an educational intervention for palliative care consultation teams.

OBJECTIVE: This study explored how an educational intervention affects interdisciplinary palliative care consultation teams. METHODS: A pre-post questionnaire survey conducted before the intervention, as well as immediately, 3, 6 and 12 months later. The outcome measurements were behavior (four domains-17 items) and confidence (one domain-6 items). RESULTS: Of the 252 workshop participants (63 teams), 248 submitted a pre-intervention response, 240 responded immediately after, 198 after 3 months, 197 after 6 months and 184 after 12 months. The behavior domain score significantly increased from pre- to 12 months post-intervention, as follows: 'regional partnership and consultation availability from medical personnel in region', from 15.0 to 17.8 (P < 0.001, effect size = 0.59); 'direct practice or care by member', from 12.8 to 13.4 (P < 0.001, effect size = 0.26); 'provision of information to patient and family', from 11.4 to 12.5 (P < 0.001, effect size = 0.42). The confidence score for palliative care consultation teams activities significantly increased from 18.5 pre-intervention to 20.2 at 12 months later (P < 0.001, effect size = 0.37). By the analysis according to the profession of the team member, the score changes for physicians and psychiatrists were larger than that for nurses and pharmacists. CONCLUSIONS: Participant behavior and confidence scores significantly increased after the educational intervention for the interdisciplinary team. In particular, physicians and psychiatrists showed the largest change. Future studies are needed to confirm the findings.

Dying Patients' Quality of Care for Five Common Causes of Death: A Nationwide Mortality Follow-Back Survey.

Background: The importance of high-quality care for terminal patients is being increasingly recognized; however, quality of care (QOC) and quality of death and dying (QOD) for noncancer patients remain unclear. Objectives: To clarify QOC and QOD according to places and causes of death. Design, Subjects: A nationwide mortality follow-back survey was conducted using death certificate data for cancer, heart disease, stroke syndrome, pneumonia, and kidney failure in Japan. The questionnaire was distributed to 115,816 bereaved family members between February 2019 and February 2020. Measurements included QOC, QOD, and symptoms during the last week of life. Analyses used generalized estimating equations adjusting for age, sex, and region. Results: Valid responses were returned by 62,576 (54.0%). Family-reported QOC and QOD by the place of death were significantly higher at home than in other places across all causes of death (for all combinations with hospital p < 0.01). In stroke syndrome and pneumonia, QOD significantly differed between hospital and home (stroke syndrome: 57.1 vs. 72.4, p < 0.001, effect size 0.77; pneumonia: 57.3 vs. 71.1, p < 0.001, effect size 0.78). No significant differences were observed in QOC and QOD between cancer and noncancer. The prevalence of symptoms was higher for cancer than for other causes of death. Conclusions: QOC and QOD were higher at home than in other places of death across all causes of death. The further expansion of end-of-life care options is crucial for improving QOC and QOD for all terminal patients.

Enhancing end-of-life care quality and achieving a good death for the elderly in Japan.

BACKGROUND: In the context of an aging populations, there is an escalating need for palliative care tailored to the needs of the elderly. This study aimed to assess differences in symptoms and good death among the elderly, along with the structures and processes involved in end-of life care, and to explore the impact of age on achieving a good death. METHODS: We conducted a questionnaire survey for bereaved family members of patients with cancer, heart disease, stroke, pneumonia, and kidney failure in 2019 and 2020. The study population was categorized into the following age groups: ≤64, 65-74, 75-84, and ≥85. The outcomes included symptom intensity, achievement of a good death, and receipt of quality care. RESULTS: In total, 62,576 bereaved family members agreed to participate in the survey (response rate; 54.0 %). The weighted percentages of 'severe' and 'very severe' symptoms decreased with age. These trends were observed across age groups, even among the elderly. The strongest effect of age on achieving a good death was found for 'feeling that life is complete' with reference to those aged ≤64 years: 65-74 years (odds ratio [OR]; 2.09, 95 % CI; 1.94 to 2.25), 75-84 years (OR; 4.86, 95 % CI; 4.52 to 5.22) and ≥85 years (OR; 12.8, 95 % CI; 11.9 to 13.8). CONCLUSION: Age-specific differences were observed in quality of death, quality of care, and symptom intensity. It is important to provide individualized consideration for each age group rather than categorizing them broadly as the elderly when caring for them.

Long-Term Prognosis of Patients with Polypoidal Choroidal Vasculopathy Treated with Photodynamic Therapy.

We evaluated the long-term prognosis of the eyes of patients with polypoidal choroidal vasculopathy (PCV) treated with photodynamic therapy (PDT). In total, 60 eyes of 57 patients diagnosed with PCV and treated with PDT were reviewed retrospectively in real-world settings. The best-corrected visual acuity (BCVA), central retinal thickness (CRT), anatomical findings (vision-threatening findings), and treatment history were assessed. In total, 38 eyes underwent PDT as the initial treatment (initial PDT group) and 22 eyes underwent PDT as a rescue treatment (rescue PDT group). In the initial PDT group, 11 eyes (29%) did not require additional therapy throughout the observation period and maintained good BCVA. A total of 27 eyes (71%) underwent additional treatments and the mean BCVA was only stabilized for 2 years; thereafter, decreased vision occurred even with additional treatments. In the rescue PDT group, 22 eyes (95%) required additional treatment. Hard exudate, serous pigment epithelial detachment, and the total vision-threatening score were related to worse BCVA. Initial PDT may be effective in about 30% of cases with preservation of good vision and no need for additional treatment. However, patients with received rescue PDT needed additional treatment in most cases and the vision decreased in many cases.

The current status and issues regarding hospital-based specialized palliative care service in Japanese Regional Cancer Centers: a nationwide questionnaire survey.

OBJECTIVE: Palliative care consultation teams have become part of all Japanese regional cancer centers. However, the current status and issues regarding specialized palliative care service in the cancer centers have yet to be clarified. Therefore, we conducted a nationwide survey of the current status of palliative care service in all Japanese regional cancer centers in 2007. METHODS: A self-reported cross-sectional survey questionnaire was mailed to all regional cancer centers in Japan. The structure and process of activities of palliative care service were included in the survey questions. RESULTS: A total of 242 of 288 institutions (84%) returned the questionnaires. Responses indicated that 99% had palliative care consultation teams. For the structure of palliative care consultation service, there were 73 ± 133 (mean ± standard deviation) referred patients per year and ∼ 90% had discharge and home care support for patients who needed palliative care; 31% had no available consultation service during the daytime on weekdays. For the process of palliative care consultation service, 90% defined the palliative care consultation request methods, 92% implemented seminars about palliative care for health-care workers in the hospital and 31% had joint meetings with the clinics and home nursing station in the community. CONCLUSIONS: Palliative care services have rapidly been developed and implemented in Japan. However, to improve the quality of palliative care services and provide more specialized palliative care within the limits of resources, it will be necessary to review the system in the future.

The neurotrophin-receptor-related protein NRH1 is essential for convergent extension movements.

Early spherical Xenopus laevis embryos are transformed into a streamlined shape through convergent extension movements. Here we report that a p75(NTR)-related transmembrane protein, NRH1, has an essential function in the regulation of these movements. NRH1 was expressed in marginal zone tissues of the gastrula and in the posterior ectoderm of the neurula. Attenuation of the NRH1 function inhibited convergent extension movements in the embryo and in activin-treated animal caps. NRH1 activated downstream effectors of the Wnt/planar cell polarity pathway: small GTPases and the cascade of MKK7-JNK. Furthermore, gain- and loss-of-function phenotypes of NRH1 were rescued by co-injection of dominant-negative and constitutively active forms of these downstream effectors, respectively, suggesting that NRH1 functions as a positive modulator of planar cell polarity signalling. Interestingly, NRH1 does not require Dishevelled (Xdsh) for the activation of these downstream effectors or translocation of Xdsh to the membrane, suggesting that NRH1 signalling interacts with planar cell polarity signalling downstream of Xdsh. This demonstrates an essential role for p75(NTR)-related signalling in early embryonic morphogenesis.

Growth and Challenges in Hospital Palliative Cancer Care Services: An Analysis of Nationwide Surveys Over a Decade in Japan.

CONTEXT: The development of palliative care services is a public health priority. The Japanese Cancer Control Act has been promoting palliative care services nationwide for over 10 years. OBJECTIVES: To evaluate long-term changes in the structure and processes of hospital palliative cancer care services nationwide. METHODS: This was an observational study using three representative questionnaire surveys between 2008 and 2018. The questionnaire consisted of domains on the structure and process regarding hospital palliative cancer care services. The changes over time were assessed using the MacNemar test. The differences between groups, namely community hospitals and designated cancer hospitals, were determined using χ2 tests. RESULTS: We analyzed changes over time from 281 designated cancer hospitals and compared the services between 1395 community hospitals and 380 designated cancer hospitals. The development of the structure and processes for designated cancer hospital's palliative cancer care services was greater for 10 years including the number of Palliative Care Consultation Teams (PCTs) with more than 50 patient referrals annually (from 2010 to 2018: 76.2% to 85.4%, P < 0.001). The palliative cancer care services of community hospitals were poorly prepared compared with designated cancer hospitals in 2018, such as the "direct medical care by any member of the Palliative Care Consultation Team at least 3 times a week (41.7% vs. 81.3%; P < 0.001). CONCLUSION: Hospital palliative cancer care services in designated cancer hospitals have developed significantly from 2008 to 2018. Building a system to promote palliative care services in community hospitals is a challenge for the next decade.

A Population-Based Mortality Follow-Back Survey Evaluating Good Death for Cancer and Noncancer Patients: A Randomized Feasibility Study.

CONTEXT: Evaluation of end-of-life care is a key element in quality improvement, and population-based mortality follow-back designs have been used in several countries. This design was adapted to evaluate a good death in Japan. OBJECTIVES: This study aimed to explain the scientific background and rationale for assessing the feasibility of a mortality follow-back survey using a randomized design. DESIGN: We used a cross-sectional questionnaire survey to assess feasibility using response rate, sample representativeness, effect on response rate with two methods, and survey acceptability. SETTING/PARTICIPANTS: The subjects were 4812 bereaved family members of patients who died from the major five causes of death: cancer, heart disease, cerebrovascular disease, pneumonia, or kidney failure, using mortality data. RESULTS: Overall, 682 (14.2%) questionnaires could not be delivered, and 2294 (55.5%) family members agreed to participate in the survey. There was little difference in the distribution of characteristics between the study subjects and the full population, and sample representativeness was acceptable. Sending the questionnaire with a pen achieved a higher response rate than without (weighted: 48.2% vs. 40.8%; P < 0.001). In follow-up contact, there was no difference in response rate between resending the questionnaire and a reminder letter alone (weighted: 32.9% vs. 32.4%; P = 0.803). In total, 84.8% (weighted) of the participants agreed with improving quality of care through this kind of survey. CONCLUSION: This study demonstrated the feasibility of conducting a population-based mortality follow-back survey using a randomized design. An attached pen with the questionnaire was effective in improving the response rate.

Rationale, Design, and Feasibility of a Prospective Multicenter Registry Study of Anthracycline-Induced Cardiotoxicity (AIC Registry).

As the number of cancer survivors increases, cardiac management in anthracycline-treated patients has become more important. We planned to conduct a prospective multicenter registry study for comprehensive echocardiographic and biomarker data collection and an evaluation of the current practice in terms of diagnosis and management of anthracycline-induced cardiotoxicity (AIC registry). To examine the feasibility of this registry study, we analyzed the 1-year follow-up data of 97 patients registered during the first year of this registry. The AIC registry was launched in July 2016. Data on echocardiographic parameters (e.g., two-and three-dimensional [(2- and 3-D) left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and biomarkers (e.g., troponin T and brain natriuretic peptide) were collected before anthracycline treatment, every 3 months during the first year after starting anthracycline, and every 6 months during the second year. Eighty-three patients (86%) completed a 1-year follow-up. The measurable rates of 2D LVEF, 3D LVEF, and GLS on each visit were nearly optimal (100%, 86-93%, and 84-94%, respectively). During the 1-year follow-up, 5 patients (6.0%) developed cardiotoxicity (a reduction in LVEF ≥ 10 percentage points from baseline and <55%). The AIC registry study is feasible and will be the first study to collect sizable echocardiographic and biomarker data on cardiotoxicity in Japanese patients treated with anthracycline in a real-world setting.

Hypoxia and CD11b+ Cell Influx Are Strongly Associated With Lymph Node Metastasis of Oral Cancer.

BACKGROUND/AIM: Treatment failure in oral cancer is mainly caused by uncontrolled cervical lymph node (LN) metastasis. We previously reported that CD11b+ cells are recruited into tumor hypoxic areas following radiation, leading to re-vascularization and relapse. Since lymphatic vessel formation has similarities with vascular formation, we examined whether surgery induces hypoxia and stimulates lymphangiogenesis. MATERIALS AND METHODS: The recruitment of CD11b+ cells and the formation of lymphatic vessels were examined using orthotopic tongue cancer mouse models with glossectomy. RESULTS: Surgery on OSC-19 tumor induced LN metastases and hypoxia, followed by CD11b+ cell influx. These phenomena were not observed in the no tumor or SAT tumor models. Stimulation of lymphangiogenesis was observed in the CD11b+ cell influx area, as the tumor grew. The localization of CD11b+ cells was changed from the lymph nodules to the medullary sinuses. CONCLUSION: Surgery-induced hypoxia in oral tumors leads to CD11b+ cell infiltration, lymphangiogenesis, and LN metastasis.

A Self-Check Program Targeting Quality Improvement in a Hospital-Based Palliative Care Consultation Team, Japanese Society for Palliative Medicine: Issues Regarding Team Activities Identified through the Plan-Do-Check-Act Cycle.

Background: The number of hospital-based palliative care consultation teams (PCCTs) has increased in Japan, and quality improvement (QI) of PCCTs is an issue. The Japanese Society for Palliative Medicine is building a framework for continuous QI of PCCT activities. Objective: The objective of this study was to develop a program to support QI for PCCTs, and to describe the initial experience with the program. Design: The report details the development of a self-check program, followed by a one-year follow-up observational survey. Methods: We developed a self-check program using the concept of the Plan-Do-Check-Act (PDCA) cycle and a multidisciplinary expert panel. A total of 114 PCCTs entered the program in the first year. Results: We developed three forms for the CHECK, ACT-PLAN, and DO phases aligned with the PDCA cycle. The forms consisted of 34 items across 8 domains. A total of 83 PCCTs (729 members) returned the CHECK, ACT-PLAN forms, and 41 PCCTs returned the DO forms after one year. Overall, 213 high priority issues were identified in the ACT phase. The issues of many PCCTs were "Sharing goals of care is inadequate within the PCCT (33%)" and "Sharing goals of care is inadequate between patient/family or primary team and the PCCT (28%)." Improvements in identified issues were: "achieved" 23% and "almost achieved" 48% after one year. Conclusions: We developed a self-check program to support QI efforts for hospital-based PCCTs. The priority issues among PCCTs and improvement goals with examples were identified. These results will support ongoing efforts to develop a continuous improvement model for QI of PCCTs.

Changes in Nurses' Knowledge, Difficulties, and Self-reported Practices Toward Palliative Care for Cancer Patients in Japan: An Analysis of Two Nationwide Representative Surveys in 2008 and 2015.

CONTEXT: The Cancer Control Act was passed in Japan in 2007, and various additional programs on palliative care have been implemented to improve quality of life and relieve pain and suffering in patients with cancer. However, how clinical settings have changed remains unclear. OBJECTIVES: The primary aim of the present study was to determine changes in nurses' palliative care knowledge, difficulties, and self-reported practices between 2008 and 2015. METHODS: This study was an analysis of two nationwide observational studies from 2008 to 2015. We conducted two questionnaire surveys for representative samples of nurses in designated cancer hospitals, community hospitals, and district nurse services. The measurements used the Palliative Care Knowledge Test (PCKT, range 1-100), the Palliative Care Difficulties Scale (PCDS, range 1-5), and the Palliative Care Self-Reported Practice Scale (PCPS, range 1-5). Comparisons were made using the nonpaired Student t-test and a multivariate linear regression model using two cohorts. RESULTS: We analyzed survey results for 2707 nurses in 2008 and 3649 nurses in 2015. Significant improvements were seen in PCKT, PCDS, and PCPS total scores for nurses in every work location over the seven-year study period, with PCKT total scores of 53 vs. 65 (P < 0.001; effect size = 0.60), 47 vs. 55 (P < 0.001; effect size = 0.40), and 52 vs. 55 (P = 0.118; effect size = 0.13), PCDS total scores of 3.0 vs. 2.5 (P < 0.001; effect size = 0.76), 3.4 vs. 2.8 (P < 0.001, effect size = 0.91), and 3.2 vs. 2.9 (P < 0.001; effect size = 0.53), and PCPS total scores of 3.7 vs. 4.0 (P < 0.001; effect size = 0.13), 3.5 vs. 3.8 (P < 0.001; effect size = 0.42), and 3.8 vs. 4.0 (P < 0.011; effect size = 0.21) in designated cancer hospitals, community hospitals, and district nurse services, respectively. CONCLUSION: Nurses' palliative care knowledge, difficulties, and self-reported practices improved over the seven-year study period, especially in terms of expert support in designated cancer hospitals and knowledge among nurses in designated cancer hospitals.

Development of a Standard for Hospital-Based Palliative Care Consultation Teams in Japan Using a Modified Delphi Method.

CONTEXT: Hospital-based palliative care consultation teams (PCCTs) are rapidly being disseminated throughout Japan. The roles of PCCTs have changed during the past decade, particularly with the introduction of a modified national cancer care act to promote early palliative care and integrated oncology and palliative care. OBJECTIVES: This study aimed to develop a consultation team standard for hospital-based palliative care in Japan. METHODS: We developed a provisional standard based on literature review and used a modified questionnaire-based Delphi method. Our Delphi panel comprises 20 experts selected from all relevant disciplines. RESULTS: All experts selected responded to the surveys over all rounds, and 14 of the 20 participated in the panel meeting. In the first round, 79 of 109 statements were judged to be appropriate, and 30 of 109 statements led to disagreements. About 16 of those 30 statements underwent minor revision, 1 was divided into two statements, and 13 remained unchanged. We then added six statements based on a discussion among participants and authors. In addition, based on comments from an external reviewer, we revised the standard, resulting in four statements being combined into two for a new total of 114 statements. In the second round, 108 of 114 statements were judged to be appropriate, and in the third round, none of the six controversial statements were judged to be appropriate. The final version comprises 108 statements. CONCLUSION: We developed a standard for PCCTs in Japanese cancer hospitals. This standard provides a useful guide for clinical activities and a tool to evaluate quality of palliative care.

Gene disruption/knock-in analysis of mONT3: vector construction by employing both in vivo and in vitro recombinations.

We report the isolation, spatial/temporal expression and gene disruption phenotype of the mouse ONT3 (mONT3) gene, which encodes a novel secreted signaling protein belonging to the Olfactomedin/Noelin/Tiarin family. During early embryogenesis, mONT3 is detected in the proximal region of the allantois on embryonic day (E) 7.25, in the lateral plate mesoderm on E 8.0 and in the CNS and heart on E 8.5. The homozygous mutant is born normal and fertile. For the expression pattern and loss-of-function analyses, we have successfully generated the LacZ-knock-in targeting vector directly from BACs carrying mouse genomic fragments by combining in vivo and in vitro recombination techniques. This approach enables rapid and reproducible construction of the fully functional vectors within two weeks without the use of restriction enzyme digestion and ligation, or the use of PCR-amplification of large genomic fragments. In addition, this method is applicable to rapid generation of transgenic vectors, demonstrating its versatility in reverse genetic studies.

Population-Based Quality Indicators for Palliative Care Programs for Cancer Patients in Japan: A Delphi Study.

CONTEXT: Cancer control programs in Japan strongly endorse the dissemination of palliative care, and various policy measures have been implemented; however, indicators for evaluating palliative care programs have not been defined. OBJECTIVES: The aim of this study was to develop quality indicators for palliative care programs taking a population-based view to meet the challenge of cancer control in the Japanese population. METHODS: We conducted a modified Delphi survey. The panelists rated a list of indicators over three iterative rounds according to four perspectives: 1) consistency with the policy target, 2) relevance to the problem, 3) clarity of expression, and 4) measurement feasibility. The criterion for adoption of candidate indicators was set at a total mean score of 7 or more. Finally, the most relevant and important indicators were selected; consensus was defined by agreement of panelists at the panel meeting. RESULTS: Among 49 panelists surveyed, 48 (98%), 39 (80%), and 43 (88%) responded over the three rounds, respectively. The 15 indicators were identified from 11 domains: patient-reported quality of life, bereaved family-reported quality at the end of life, family care, place of death, bereaved family-reported quality of palliative care, specialized palliative care services, opioid utilization, public perceptions about palliative care, palliative care education to primary care providers, specialist palliative care services, and regional palliative care. CONCLUSION: Comprehensive quality indicators for palliative care programs were identified. The indicators are currently being used, and the feasibility of measuring change over time will be examined. It is expected that the indicators will be used effectively in the future. It is important to evaluate outcomes of the program, to improve weaknesses, improve outcomes, and promote the welfare of cancer patients.

How to Manage Hospital-Based Palliative Care Teams Without Full-Time Palliative Care Physicians in Designated Cancer Care Hospitals: A Qualitative Study.

OBJECTIVE: To clarify how highly active hospital palliative care teams can provide efficient and effective care regardless of the lack of full-time palliative care physicians. METHODS: Semistructured focus group interviews were conducted, and content analysis was performed. RESULTS: A total of 7 physicians and 6 nurses participated. We extracted 209 codes from the transcripts and organized them into 3 themes and 21 categories, which were classified as follows: (1) tips for managing palliative care teams efficiently and effectively (7 categories); (2) ways of acquiring specialist palliative care expertise (9 categories); and (3) ways of treating symptoms that are difficult to alleviate (5 categories). CONCLUSIONS: The findings of this study can be used as a nautical chart of hospital-based palliative care team (HPCT) without full-time PC physician. Full-time nurses who have high management and coordination abilities play a central role in resource-limited HPCTs.