Cost-effectiveness analysis of adult living-donor liver transplantation in Japan.

AIM: Living-donor liver transplantation (LDLT) is a highly effective life-saving procedure; however, it requires substantial medical resources, and the cost-effectiveness of LDLT versus conservative management (CM) for adult patients with end-stage liver disease (ESLD) remains unclear in Japan. METHODS: We performed a cost-effectiveness analysis using the Diagnostic Procedure Combination (DPC) data from the nationwide database of the DPC research group. We selected adult patients (18 years or older) who were admitted or discharged between 2010 and 2021 with a diagnosis of ESLD with Child-Pugh class C or B. A decision tree and Markov model were constructed, and all event probabilities were computed in 3-month cycles over a 10-year period. The willingness-to-pay per quality-adjusted life-year (QALY) was set at 5 million Japanese yen (JPY) (49,801 US dollars [USD]) from the perspective of the public health-care payer. RESULTS: After propensity score matching, we identified 1297 and 111,849 patients in the LDLT and CM groups, respectively. The incremental cost-effectiveness ratio for LDLT versus CM for Child-Pugh classes C and B was 2.08 million JPY/QALY (20,708 USD/QALY) and 5.24 million JPY/QALY (52,153 USD/QALY), respectively. The cost-effectiveness acceptability curves showed the probabilities of being below the willingness-to-pay of 49,801 USD/QALY as 95.4% in class C and 48.5% in class B. Tornado diagrams revealed all variables in class C were below 49,801 USD/QALY while their ranges included or exceeded 49,801 USD/QALY in class B. CONCLUSIONS: Living-donor liver transplantation for adult patients with Child-Pugh class C was cost-effective compared with CM, whereas LDLT versus CM for class B patients was not cost-effective in Japan.

A Survey of the Awareness and Educational Needs of Nurses in Nagasaki Prefecture Regarding Hereditary Breast and Ovarian Cancer.

The aim of this study was to evaluate the knowledge and educational needs with regard to hereditary breast and ovarian cancer among nurses working in breast cancer care in the Nagasaki Prefecture. In breast cancer care, the identification of patients at risk for hereditary breast and ovarian cancer is necessary for the implementation of genetic testing and counseling. Nurses should be involved in this process, since they play a crucial role in the care of patients with breast cancer. However, the knowledge regarding hereditary breast and ovarian cancer among nurses working in oncology care in Japan has not been assessed. The design of this study is cross-sectional design. We distributed 597 surveys to nurses working in breast cancer care. The surveys assessed the nurses' demographic data, their current knowledge and practices regarding cancer genetics and hereditary breast and ovarian cancer, and their attitude and preferences regarding learning about the condition. We received 317 valid replies. Nurses had limited knowledge about hereditary breast and ovarian cancer characteristics: 41.6% reported that they do not know about the condition, whereas less than 10% knew its characteristics. However, nurses were aware of hereditary breast and ovarian cancer significance and were willing to learn about it: 91% wished to learn about the condition, and 88.6% wanted to participate in study group meetings. Further, nurses' preferences regarding educational programs were clarified. Overall, our results show that educational programs should be implemented to advance nurses' knowledge of hereditary breast and ovarian cancer characteristics.

New aspects of clinical and immunological characteristics in patients with anti-asparaginyl tRNA synthetase (anti-KS) autoantibody.

OBJECTIVES: Anti-asparaginyl tRNA synthetase (anti-KS) antibody is present in patients with interstitial lung disease (ILD) accompanied by polymyositis/dermatomyositis. We examined clinical/immunological features of these patients. METHODS: Polymyositis/dermatomyositis or ILD patients were screened for autoantibodies, and clinical/immunological data were collected retrospectively. ILD was diagnosed by computed tomography, and clinical/immunological features of anti-KS-positive patients were compared with those of anti-Jo-1-positive patients. RESULTS: Sixteen anti-KS-positive patients [female = 11; male = 5; average age 63.6 years (range, 40-81) years] were diagnosed: seven had ILD, four had clinically amyopathic DM (CADM) and ILD, three had Sjögren's syndrome (SS) and ILD one each had rheumatoid arthritis and ILD, or CADM/SS overlap and ILD. All patients had ILD with chronic onset and clinical course; 11/16 (69%) had nonspecific interstitial pneumonia, and five (31%) had usual interstitial pneumonia pattern. Regarding skin manifestations, 4 (27%) had typical DM rash and 11 (69%) had mechanic's hands. All anti-KS-positive patients had no clinical muscle weakness or serum creatine kinase elevation; 8/16 patients (50%) had sicca symptoms at a significantly high frequency compared with anti-Jo-1-positive patients (50% vs 11%, P = 0.01). CONCLUSIONS: Anti-KS-positive patients might form a distinguishable subset closely associated with sicca symptoms, CADM and chronic-type ILD with a relatively favourable prognosis.

Endogenous oxytocin levels in extracted saliva elevates during breastfeeding correlated with lower postpartum anxiety in primiparous mothers.

BACKGROUND: Breastfeeding in the early postpartum period is expected to have mental benefits for mothers; however, the underlying psychobiological mechanisms remain unclear. Previously, we hypothesized that the release of oxytocin in response to the suckling stimuli during breastfeeding would mediate a calming effect on primiparous mothers, and we examined salivary oxytocin measurements in primiparous mothers at postpartum day 4 using saliva samples without extraction, which was erroneous. Thus, further confirmation of this hypothesis with a precise methodology was needed. METHODS: We collected saliva samples at three time points (baseline, feeding, and post-feeding) to measure oxytocin in 24 primiparous mothers on postpartum day 2 (PD2) and 4 (PD4) across the breastfeeding cycle. Salivary oxytocin levels using both extracted and unextracted methods were measured and compared to determine the qualitative differences. State and trait anxiety and clinical demographics were evaluated to determine their association with oxytocin changes. RESULTS: Breastfeeding elevated salivary oxytocin levels; however, it was not detected to a significant increase in the extraction method at PD4. We found a weak but significant positive correlation between changes in extracted and unextracted oxytocin levels during breastfeeding (feeding minus baseline); there were no other significant positive correlations. Therefore, we used the extracted measurement index for subsequent analysis. We showed that the greater the increase in oxytocin during breastfeeding, the lower the state anxiety, but not trait anxiety. Mothers who exclusively breastfed at the 1-month follow-up tended to be associated with slightly higher oxytocin change at PD2 than those who did not. CONCLUSIONS: Breastfeeding in early postpartum days could be accompanied by the frequent release of oxytocin and lower state anxiety, potentially contributing to exclusive breastfeeding.

Evaluations of Funerals and Health Trajectories in the Second Year After Bereavement-The Ongoing Japan National Survey.

Our nationwide postal survey analyzing 190 responses from Japanese bereaved who had responded a year earlier found that funeral dissatisfaction rose during the second year after the funeral. Controverting previous research advocating participation in funeral planning, elderly bereaved spouses forced to decide about and/or pay for the funeral showed elevated grief as much as 2 years later. While not reaching levels diagnosed as prolonged, traumatic, or complicated grief, nevertheless one out of three of our bereaved sample showed continuing daily symptoms of grief from 14 to 24 months after their bereavement, with continued or increasing use of tranquillizers or antidepressants. The medical and pharmaceutical costs incurred by mourners more than a year after bereavement warrant further research into what factors improve or exacerbate the health of grieving bereaved, not limited to a single year after the bereavement.

Serum PreS1 and HBsAg ratio reflects liver fibrosis and predicts the development of hepatocellular carcinoma in chronic hepatitis B patients.

While the preS1 region of the large hepatitis B surface protein plays an essential role in hepatitis B virus (HBV) infection, the effect of preS1 on liver fibrosis and hepatocarcinogenesis in chronic hepatitis B (CHB) patients is not well known. In this study, we measured serum preS1 levels by chemiluminescent immunoassay technology in 690 CHB patients and evaluated the correlation between serum preS1 levels and HBV, liver function markers and liver inflammation, fibrosis assessed by histological findings. Predictive factors for hepatocellular carcinoma (HCC) development in patients who had no previous history of HCC at the time of preS1 level measurement were also analysed. Median hepatitis B surface antigen (HBsAg) and preS1 levels were 3.08 log IU/mL and 98 ng/mL, respectively. PreS1 values were significantly correlated with serum HBsAg (p <0.001), hepatitis B core-related antigen (HBcrAg) (p <0.001) and HBV DNA levels (p <0.01). PreS1 values were also significantly correlated with serum alanine aminotransferase levels (p <0.001) and were significantly higher in patients who had higher grading of liver inflammatory activity (p <0.05). HBsAg level was correlated, but preS1/HBsAg ratio reflected liver fibrosis staging more directly than HBsAg alone. Multivariate analysis identified age ≥53 years (hazard ratio [HR], 18.360 for <53 years; p = 0.021) and preS1/HBsAg ratio ≥0.12 (HR, 6.205 for <0.12; p = 0.040) as significant and independent factors for HCC development in CHB patients. The preS1/HBsAg ratio directly reflects liver fibrosis, and the ratio might be a predictive marker for HCC development in CHB patients.

Nationwide multicenter questionnaire surveys on countermeasures against antimicrobial resistance and infections in hospitals.

BACKGROUND: The goals of the National Action Plan on Antimicrobial Resistance (AMR) of Japan include "implementing appropriate infection prevention and control" and "appropriate use of antimicrobials," which are relevant to healthcare facilities. Specifically, linking efforts between existing infection control teams and antimicrobial stewardship programs was suggested to be important. Previous studies reported that human resources, such as full-time equivalents of infection control practitioners, were related to improvements in antimicrobial stewardship. METHODS: We posted questionnaires to all teaching hospitals (n = 1017) regarding hospital countermeasures against AMR and infections. To evaluate changes over time, surveys were conducted twice (1st survey: Nov 2016, 2nd survey: Feb 2018). A latent transition analysis (LTA) was performed to identify latent statuses, which refer to underlying subgroups of hospitals, and effects of the number of members in infection control teams per bed on being in the better statuses. RESULTS: The number of valid responses was 678 (response rate, 66.7%) for the 1st survey and 559 (55.0%) for the 2nd survey. More than 99% of participating hospitals had infection control teams, with differences in activity among hospitals. Roughly 70% had their own intervention criteria for antibiotics therapies, whereas only about 60 and 50% had criteria established for the use of anti-methicillin-resistant Staphylococcus aureus antibiotics and broad-spectrum antibiotics, respectively. Only 50 and 40% of hospitals conducted surveillance of catheter-associated urinary tract infections and ventilator-associated pneumonia, respectively. Less than 50% of hospitals used maximal barrier precautions for central line catheter insertion. The LTA identified five latent statuses. The membership probability of the most favorable status in the 2nd study period was slightly increased from the 1st study period (23.6 to 25.3%). However, the increase in the least favorable status was higher (26.3 to 31.8%). Results of the LTA did not support a relationship between increasing the number of infection control practitioners per bed, which is reportedly related to improvements in antimicrobial stewardship, and being in more favorable latent statuses. CONCLUSIONS: Our results suggest the need for more comprehensive antimicrobial stewardship programs and increased surveillance activities for healthcare-associated infections to improve antimicrobial stewardship and infection control in hospitals.

Unexplored Costs of Bereavement Grief in Japan: Patterns of Increased Use of Medical, Pharmaceutical, and Financial Services.

Bereaved families may experience psychological and physical problems increasing their reliance on medical, pharmaceutical, and financial/legal services. Our Japan-wide survey (n = 1078) researched bereaved who showed increased reliance on medical, pharmaceutical, and financial/legal services. Increased use was most evident in the '50's age bracket, and for unemployed widows; it corresponded less with low annual income than with high income declining significantly after bereavement. Increased users showed higher psychological and physical symptoms of grief, and reported their decline in physical health seriously influencing their work and lives, suggesting "presenteeism"-reduced productivity for those continuing to work. Increased users spent 2.7 times more for medical and pharmaceutical services than those reporting continual use, portending 4 to 10 times more Japanese government expense for this group, half of whom considered their own out-of-pocket expenses a financial burden. These findings warrant further research on cost-effectiveness of interventions to reduce declining health of the bereaved.

Urothelial hyperplasia with calculi (papillomatosis) in the urinary bladder of a male spontaneous diabetic Torii rat.

A 40-week-old male spontaneous diabetic Torii rat, an animal model of type 2 diabetes mellitus, was found to have marked urinary calculi with hematuria in the urinary bladder on necropsy. Histological findings in the urinary bladder included a papillary growth pattern with a fibrovascular stroma without atypia. Fine granular materials in the bladder lumen were positive for Von Kossa staining but negative for periodic acid-Schiff or Gram staining, indicating no apparent bacterial infection in the urinary bladder. Scanning electron microscopy revealed that the urinary calculi were magnesium ammonium phosphate crystals (struvite). On the basis of the results, the lesion was diagnosed as urothelial hyperplasia with calculi (papillomatosis). Chronic inciting stimuli by struvite crystals were considered the primary cause of the bladder findings.

The personal cost of dementia care in Japan: A comparative analysis of residence types.

OBJECTIVE: We aimed to quantify the personal economic burden of dementia care in Japan according to residence type. METHODS: A cross-sectional online survey was conducted on 3841 caregivers of people with dementia. An opportunity cost approach was used to calculate informal care costs. All costs and the observed/expected (OE) ratio of costs were adjusted using patient sex, age, and care-needs levels, and compared among the residence types. RESULTS: The mean daily informal care time was 8.2 hours, and the mean monthly informal care costs for community-dwelling people with dementia were US$1559. The OE ratio for informal care costs in community-dwelling patients was higher than in institutionalized patients. CONCLUSION: The inclusion of informal care costs reduced the differences in total personal costs among the residence types. The economic burden of informal care should be considered when quantifying dementia care costs.

Identification and characterization of thermostable glucose dehydrogenases from thermophilic filamentous fungi.

FAD-dependent glucose dehydrogenase (FAD-GDH), which contains FAD as a cofactor, catalyzes the oxidation of D-glucose to D-glucono-1,5-lactone, and plays an important role in biosensors measuring blood glucose levels. In order to obtain a novel FAD-GDH gene homolog, we performed degenerate PCR screening of genomic DNAs from 17 species of thermophilic filamentous fungi. Two FAD-GDH gene homologs were identified and cloned from Talaromyces emersonii NBRC 31232 and Thermoascus crustaceus NBRC 9129. We then prepared the recombinant enzymes produced by Escherichia coli and Pichia pastoris. Absorption spectra and enzymatic assays revealed that the resulting enzymes contained oxidized FAD as a cofactor and exhibited glucose dehydrogenase activity. The transition midpoint temperatures (T m) were 66.4 and 62.5 °C for glycosylated FAD-GDHs of T. emersonii and T. crustaceus prepared by using P. pastoris as a host, respectively. Therefore, both FAD-GDHs exhibited high thermostability. In conclusion, we propose that these thermostable FAD-GDHs could be ideal enzymes for use as thermotolerant glucose sensors with high accuracy.

Asymptomatic C-reactive protein elevation in neutropenic children.

BACKGROUND: Febrile neutropenia (FN) can be a life-threatening complication in children with malignancies. There is no standardized preventive treatment for childhood FN, and information on C-reactive protein (CRP) elevation in afebrile patients with neutropenia (CEAN) is limited. The aim of this study was therefore to identify the association between CEAN and FN onset, and evaluate the efficacy of broad-spectrum antibiotics for FN prophylaxis. METHODS: We retrospectively reviewed the medical records of 22 consecutive pediatric patients with hematologic malignancies (acute myeloid leukemia, n = 2; acute lymphoid leukemia, n = 20) admitted to the present institution between 2006 and 2011. CEAN was defined as CRP elevation ≥0.05 mg/dL between the two most recent blood tests with no fever. We identified CEAN before FN onset, and assessed the efficacy of broad-spectrum antibiotics for FN prevention in CEAN. FN incidence within 48 h after CEAN detection was compared between prophylactic and non-prophylactic episodes. RESULTS: CEAN was observed before FN onset in 20 (55.6%), of 36 FN episodes. Among the 95 analyzed CEAN episodes, broad-spectrum antibiotics had been used for 30 episodes (prophylactic episodes), whereas these antibiotics had not been used in 60 episodes (non-prophylactic episodes). Prophylactic episodes had a significantly lower FN incidence than non-prophylactic episodes (6.7% and 31%, respectively, P < 0.01) within 48 h after CEAN detection. Bacteremia was observed in three non-prophylactic episodes. CONCLUSION: Patients with CEAN are at higher risk of FN, and physicians may consider the use of broad-spectrum antibiotics to prevent FN development.

Development of a risk-adjusted in-hospital mortality prediction model for community-acquired pneumonia: a retrospective analysis using a Japanese administrative database.

BACKGROUND: Community-acquired pneumonia (CAP) is a common cause of patient hospitalization and death, and its burden on the healthcare system is increasing in aging societies. Here, we develop and internally validate risk-adjustment models and scoring systems for predicting mortality in CAP patients to enable more precise measurements of hospital performance. METHODS: Using a multicenter administrative claims database, we analyzed 35,297 patients hospitalized for CAP who had been discharged between April 1, 2012 and September 30, 2013 from 303 acute care hospitals in Japan. We developed hierarchical logistic regression models to analyze predictors of in-hospital mortality, and validated the models using the bootstrap method. Discrimination of the models was assessed using c-statistics. Additionally, we developed scoring systems based on predictors identified in the regression models. RESULTS: The 30-day in-hospital mortality rate was 5.8%. Predictors of in-hospital mortality included advanced age, high blood urea nitrogen level or dehydration, orientation disturbance, respiratory failure, low blood pressure, high C-reactive protein levels or high degree of pneumonic infiltration, cancer, and use of mechanical ventilation or vasopressors. Our models showed high levels of discrimination for mortality prediction, with a c-statistic of 0.89 (95% confidence interval: 0.89-0.90) in the bootstrap-corrected model. The scoring system based on 8 selected variables also showed good discrimination, with a c-statistic of 0.87 (95% confidence interval: 0.86-0.88). CONCLUSIONS: Our mortality prediction models using administrative data showed good discriminatory power in CAP patients. These risk-adjustment models may support improvements in quality of care through accurate hospital evaluations and inter-hospital comparisons.

Early Initiation of Plasma Exchange Therapy for Anti-MDA5+Dermatomyositis with Refractory Rapidly Progressive Interstitial Lung Disease.

Objectives Dermatomyositis (DM) is often associated with fatal anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive rapidly progressive interstitial lung disease (RP-ILD). RP-ILD often fails to respond to intensive treatment and has a poor prognosis. We examined the effectiveness of early plasma exchange therapy plus intensive treatment with high-dose corticosteroids and multiple immunosuppressants. Methods Autoantibodies were identified by an immunoprecipitation assay and enzyme-linked immunosorbent assay. All clinical and immunological data were collected retrospectively from medical charts. We divided patients into two groups based on treatment regimen: intensive immunosuppressive therapy alone as initial treatment (IS group) and early initiation of plasma exchange (PE) plus intensive immunosuppressive therapy (ePE group). Early PE therapy was designated if PE therapy was initiated within two weeks of starting treatment. Comparisons of the treatment response and prognosis between groups were performed. Patients Anti-MDA5-positive DM with RP-ILD was screened. Results Forty-four RP-ILD and DM patients had anti-MDA5 antibodies. Four patients were excluded because they died before receiving sufficient combined immunosuppressive therapy or before the evaluation of the immunosuppressive treatment effectiveness (IS, n=31; ePE, n=9). All 9 patients in the ePE group had improved respiratory symptoms and were alive, whereas 12 of 31 patients in the IS group died (100 vs. 61%, p=0.037). Of the 8 patients who had 2 values for a poor prognosis, indicating the highest risk for death using the MCK model, 3 of 3 patients in the ePE group and 2 of 5 in the IS group were alive (100 vs. 40%, p=0.20). Conclusion The early initiation of ePE therapy plus intensive immunosuppressive therapy was effective for patients with DM and refractory RP-ILD.

Derivation and validation of in-hospital mortality prediction models in ischaemic stroke patients using administrative data.

BACKGROUND: Stroke and other cerebrovascular diseases are a major cause of death and disability. Predicting in-hospital mortality in ischaemic stroke patients can help to identify high-risk patients and guide treatment approaches. Chart reviews provide important clinical information for mortality prediction, but are laborious and limiting in sample sizes. Administrative data allow for large-scale multi-institutional analyses but lack the necessary clinical information for outcome research. However, administrative claims data in Japan has seen the recent inclusion of patient consciousness and disability information, which may allow more accurate mortality prediction using administrative data alone. The aim of this study was to derive and validate models to predict in-hospital mortality in patients admitted for ischaemic stroke using administrative data. METHODS: The sample consisted of 21,445 patients from 176 Japanese hospitals, who were randomly divided into derivation and validation subgroups. Multivariable logistic regression models were developed using 7- and 30-day and overall in-hospital mortality as dependent variables. Independent variables included patient age, sex, comorbidities upon admission, Japan Coma Scale (JCS) score, Barthel Index score, modified Rankin Scale (mRS) score, and admissions after hours and on weekends/public holidays. Models were developed in the derivation subgroup, and coefficients from these models were applied to the validation subgroup. Predictive ability was analysed using C-statistics; calibration was evaluated with Hosmer-Lemeshow χ(2) tests. RESULTS: All three models showed predictive abilities similar or surpassing that of chart review-based models. The C-statistics were highest in the 7-day in-hospital mortality prediction model, at 0.906 and 0.901 in the derivation and validation subgroups, respectively. For the 30-day in-hospital mortality prediction models, the C-statistics for the derivation and validation subgroups were 0.893 and 0.872, respectively; in overall in-hospital mortality prediction these values were 0.883 and 0.876. CONCLUSIONS: In this study, we have derived and validated in-hospital mortality prediction models for three different time spans using a large population of ischaemic stroke patients in a multi-institutional analysis. The recent inclusion of JCS, Barthel Index, and mRS scores in Japanese administrative data has allowed the prediction of in-hospital mortality with accuracy comparable to that of chart review analyses. The models developed using administrative data had consistently high predictive abilities for all models in both the derivation and validation subgroups. These results have implications in the role of administrative data in future mortality prediction analyses.

Development and validation of prediction models for the discharge destination of elderly patients with aspiration pneumonia.

BACKGROUND: Discharge planning enhances the safe and timely transfer of inpatients between facilities. Predicting the discharge destination of inpatients with aspiration pneumonia is important for discharge planning. We aimed to develop and validate prediction models for the discharge destination of elderly patients with aspiration pneumonia. METHODS: Using a nationwide inpatient database, we identified aspiration pneumonia cases for patients aged ≥65 years who had been admitted to hospital from their home or from a nursing home between April 2020 and March 2021. We divided the cases into derivation and validation cohorts according to the location of the admitting hospital. We developed two prediction models by dividing the cases based on the patient's place of residence prior to admission, one model to predict the home discharge of cases admitted from home and the other to predict the home or to a nursing home discharge of cases admitted from a nursing home. The models were internally validated with bootstrapping and internal-externally validated using a validation cohort. Nomograms that could be used easily in clinical practice were also created. RESULTS: The derivation cohort included 19,746 cases admitted from home and 14,359 cases admitted from a nursing home. Of the former, 10,760 (54.5%) cases were discharged home; from the latter, 7,071 (49.2%) were discharged to either home or a nursing home. The validation cohort included 6,262 cases admitted from home and 6,352 cases admitted from a nursing home. In the internal-external validation, the C-statistics of the final model for the cases admitted from home and the cases admitted from a nursing home were 0.71 and 0.67, respectively. CONCLUSIONS: We developed and validated new prediction models for the discharge of elderly patients with aspiration pneumonia either to home or to a nursing home. Our models and nomograms could facilitate the early implementation of discharge planning.

Heterogeneous sphingosine-1-phosphate lyase gene expression and its regulatory mechanism in human lung cancer cell lines.

The role of sphingolipid metabolic pathway has been recognized in determining cellular fate. Although sphingolipid degradation has been extensively studied, gene expression of human sphingosine 1-phosphate lyase (SPL) catalyzing sphingosine 1-phosphate (S1P) remains to be determined. Among 5 human lung cancer cell lines examined, SPL protein levels paralleled the respective mRNA and enzyme activities. Between H1155 and H1299 cells used for further experiments, higher cellular S1P was observed in H1155 with higher SPL activity compared with H1299 with low SPL activity. GATA-4 has been reported to affect SPL transcription in Dictyostelium discoideum. GATA-4 was observed in H1155 but not in other cell lines. Overexpression of GATA-4 in H1299 increased SPL expression. However, promoter analysis of human SPL revealed that the most important region was located between -136bp and -88bp from the first exon, where 2 Sp1 sites exist but no GATA site. DNA pull-down assay of H1155 showed increased DNA binding of Sp1 and GATA-4 within this promoter region compared with H1299. Electrophoresis mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) assay, reporter assay using mutated binding motif, and mithramycin A, a specific Sp1 inhibitor, suggest the major role of Sp1 in SPL transcription and no direct binding of GATA-4 with this 5' promoter region. The collaborative role of GATA-4 was proved by showing coimmunoprecipitation of Sp1 and GATA-4 using GST-Sp1 and overexpressed GATA-4. Thus, high SPL transcription of H1155 cells was regulated by Sp1 and GATA-4/Sp1 complex formation, both of which bind to Sp1 sites of the 5'-SPL promoter.

Mourners' Dissatisfaction with Funerals May Influence Their Subsequent Medical/Welfare Expenses-A Nationwide Survey in Japan.

Japan's super-aged mortality rate bereaves millions of people annually, threatening the mental health of the bereaved population. Previous research suggests that participation in satisfying funeral rituals can protect or improve the health of a bereaved population-but pandemic restrictions threaten traditional funeral assemblies. To determine how bereaved mourners' mental health-and consequent dependence upon medical, pharmaceutical, or social services-are affected by funerals and the aspects of funerals most likely to cause satisfaction or dissatisfaction, we conducted an anonymous nationwide survey across Japan. In total, 1078 bereaved Japanese responded; we analyzed their responses by comparing the 106 citing funeral dissatisfaction with the 972 citing no dissatisfaction. The cohort showing greatest satisfaction with funerals tended to be older widows or parents who lost children; they showed greater grief but spent less on medical, pharmaceutical, or social services thereafter than the dissatisfied. Conversely, mourners with the greatest dissatisfaction toward their interactions with funeral directors and Buddhist priests tended to spend more on medical, pharmaceutical, or social services after bereavement. We conclude that training or education to improve priests' and funeral directors' interactions may reduce dissatisfaction with funerals, potentially reducing subsequent costs of medical, pharmaceutical, or social services for the rapidly growing population of bereaved Japanese.

Identifying bereaved grievers with greatest medical or social service needs in Japan.

OBJECTIVE: Severe grief adversely affects the health of bereaved families, potentially burdening medical and community health services. Interventions for effective community health maintenance must identify the people likely to face severe effects of bereavement. The present study identified characteristics of mourners who experience severe grief within a year of bereavement to confirm whether this grief increased their reliance on Japanese medical and social services. DESIGN: We conducted a nationwide postal survey of Japanese bereaved within the previous year, to compare those reporting daily or overwhelming 'heavy' grief to those with less heavy grief, in terms of demographic and socioeconomic details, daily work and non-work activity, frequency of medical and social service use. SETTING/PARTICIPANTS: In 2019, with the support of the Ministry of Education and the All Japan Funeral Co-Operation, we distributed approximately 5500 questionnaires to Japanese who had presided at funerals within the past year for anonymous return. By January of 2020, we received 1078 complete voluntary responses from bereaved Japanese. RESULTS: Half of the 'heavy grief' group (n=143) reported adverse effects on health and daily life, including needs for pharmacological, medical or welfare support. Losses of husbands or children were particularly connected to severe grief; 'unexpected' death from cancer caused the greatest shock. Employment (even part-time) buffered against severe grief; grief was greater for the unemployed and substantially worse for those who lost significant income at the same time as they lost loved ones. CONCLUSION: These findings suggest that prior counselling should reduce the shock of bereavement and economic loss, which increases subsequent medical dependence. Medical professionals and community health workers can use the above factors to target in advance the family members in greatest danger of heavy grief, to intervene lest grief adversely affect their physical and psychological health after bereavement.

Pharmacokinetics of tacrolimus following an overdose in a patient with extreme obesity and genotype CYP3A5*3/*3: a case report.

This case involved a 27-year-old man with extreme obesity (body mass index 45.6 kg/m2) who had a history of fulminant hepatitis and living-donor liver transplantation at 11 years of age. He had been receiving oral sustained-release tacrolimus (TAC) 1.5 mg daily, and the trough concentration in the blood was below 2.0 ng/mL. He has an intrinsic cytochrome P450 3A5 (CYP3A5)*3/*3 (G/G) genotype and graft liver with CYP3A5*3 allele donated by his biological father. Additionally, there were no data on the phenotype of P-glycoprotein. He did not take medications, grapefruit, or St. John's wort, which interact with CYP3A4 and P-glycoprotein. He intentionally took 30 mg of TAC and presented with symptoms of general malaise and poisoning. On the day of hospitalization (day 0), TAC was discontinued due to an elevated blood TAC concentration of > 60 ng/mL. Additionally, the blood TAC concentration exceeded 10 ng/mL for more than 3 days. He exhibited mild elevation of alanine aminotransferase, aspartate aminotransferase, and creatinine phosphokinase without apparent clinical symptoms. After discharge, blood TAC concentration decreased to 7.4 and 3.7 ng/mL on days 14 and 28, respectively, from the day of excessive TAC intake. Finally, the blood TAC concentration fell below 2.0 ng/mL on day 66. This case report showed that extreme obesity and the liver CYP3A5*3 allele delayed the elimination of TAC after excessive intake of the drug.