Hericenone C attenuates the second phase of formalin-induced nociceptive behavior by suppressing the accumulation of CD11c-positive cells in the paw epidermis via phosphorylated P65.

Hericenone C is one of the most abundant secondary metabolites derived from Hericium erinaceus, under investigation for medicinal properties. Here, we report that Hericenone C inhibits the second phase of formalin-induced nociceptive behavior in mice. As the second phase is involved in inflammation, in a mechanistic analysis on cultured cells targeting NF-κB response element (NRE): luciferase (Luc)-expressing cells, lipopolysaccharide (LPS)-induced NRE::Luc luciferase activity was found to be significantly inhibited by Hericenone C. Phosphorylation of p65, which is involved in the inflammatory responses of the NF-κB signaling pathway, was also induced by LPS and significantly reduced by Hericenone C. Additionally, in mice, the number of CD11c-positive cells increased in the paw during the peak of the second phase of the formalin test, which decreased upon Hericenone C intake. Our findings confirm the possibility of Hericenone C as a novel therapeutic target for pain-associated inflammation.

Association between pulse pressure and progression of chronic kidney disease.

The aim of this study was to investigate the association between pulse pressure (PP) and chronic kidney disease (CKD) progression among the general population in Japan. We conducted a population-based cohort study of the residents of Iki Island, Nagasaki, Japan, from 2008 to 2018. We identified 1042 participants who had CKD (estimated glomerular filtration rate(eGFR) < 60 mL/min/1.73 m2 or the presence of proteinuria) at baseline. Cox's proportional hazard model was used to evaluate the association between PP and progression of CKD. During a 4.66-year mean follow-up, there were 241 cases of CKD progression (incident rate: 49.8 per 1000 person-years). A significant increase existed in CKD progression per 10 mmHg of PP elevation, even when adjusted for confounding factors [adjusted hazard ratio 1.17 (1.06-1.29) p < 0.001]. Similar results were obtained even after dividing PP into quartiles [Q2: 1.14 (0.74-1.76), Q3: 1.35 (0.88-2.06), Q4: 1.87 (1.23-2.83) p = 0.003 for trend]. This trend did not change significantly irrespective of baseline systolic or diastolic blood pressures. PP remained a potential predictive marker, especially for eGFR decline. In conclusion, we found a significant association between PP and CKD progression. PP might be a potential predictive marker for CKD progression.

Comparison of regional with general anesthesia on mortality and perioperative length of stay in older patients after hip fracture surgery.

OBJECTIVE: The aim of this study was to examine whether anesthetic technique is associated with 30- or 90-day mortality and perioperative length of stay (LOS). DESIGN: We used a retrospective cohort design using a healthcare insurance claims database. SETTING: The Fukuoka Prefecture's claims database of older patients who underwent hip fracture surgery under general or regional (spinal or epidural) anesthesia from April 2012 to March 2016 was used for analyses. PARTICIPANTS: The database under analyses contained 16 125 participants of hip fracture surgery under general or regional anesthesia. MAIN OUTCOME MEASURE: We measured 30- and 90-day mortalities and perioperative LOS. RESULTS: In a propensity score-matched cohort, we found no significant differences in 30- and 90-day mortalities after adjusting for confounding factors. The reconverted perioperative LOS for the general and regional anesthesia groups was, respectively, 29.7 (29.1-30.4) and 28.0 (27.4-28.6) days in the matched cohort. Therefore, the perioperative LOS in the regional anesthesia group was significantly shorter by 1.7 days than in the general anesthesia group (P < 0.001). CONCLUSIONS: This study demonstrated that the use of regional anesthesia was not associated with 30- or 90-day mortality, but it was associated with slightly shorter perioperative LOS. Since Japan has much longer LOS than other countries, our findings have implications for more efficient healthcare resource utilization and quality assurance in geriatric care.

Association between dipeptidyl peptidase-4 inhibitors and urinary tract infection in elderly patients: A retrospective cohort study.

PURPOSE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. Although they have been reported to increase the risk of infection, the findings are controversial. Given that urinary tract infections (UTIs) are common in the elderly, we conducted a retrospective cohort study by using health care insurance claims data, to elucidate the association between the DPP-4 inhibitors and the incidence of UTI in latter-stage elderly patients. METHODS: We analyzed 25,111 Japanese patients aged 75 years and older between the fiscal years 2011 and 2016. Patients using DPP-4 inhibitors and sulfonylureas (SUs) were matched at a 1:1 ratio using propensity scoring. The Incidence rate ratio (IRR) of UTI was compared between users of SUs and users of DPP-4 inhibitors by Poisson regression. Moreover, subgroup analyses stratified by sex were conducted to evaluate whether the combination of prostatic hyperplasia and DPP-4 inhibitors is associated with the incidence of UTI in male patients. RESULTS: The use of DPP-4 inhibitors was associated with an increased risk of UTI (adjusted IRR 1.23, 95% CI [1.04-1.45]). After propensity score matching, the association remained significant (adjusted IRR 1.28, 95% CI [1.05-1.56]). Moreover, elderly male patients with prostatic hyperplasia who received DPP-4 inhibitors had a higher risk of UTI than SU users without prostatic hyperplasia (Matched: crude IRR 2.90, 95% CI [1.78-4.71]; adjusted IRR 2.32, 95% CI [1.40-3.84]). CONCLUSIONS: The long-term use of DPP-4 inhibitors by elderly patients, particularly male patients with prostatic hyperplasia, may increase the risk of UTI.

Association Between Financial Incentives for Regional Care Coordination and Health Care Resource Utilization Among Older Patients after Femoral Neck Fracture Surgery: A Retrospective Cohort Study Using a Claims Database.

The incidence rates of hip fracture have been increasing in Japan. Length of stay among hip fracture patients in Japan is much longer than other developed countries, and the Japanese government introduced financial incentives for regionally coordinated femoral neck fracture care to reduce health care resource utilization. The objective of this study was to evaluate whether the financial incentives reduce health care resource utilization among patients 75 years or older with femoral neck fracture in Japan. Claims data from the Fukuoka Prefecture Regional Association for Late-Stage Healthcare for Older People were analyzed for the period from April 2010 to March 2016. The authors identified 4641 eligible subjects after femoral neck fracture surgery, and categorized them into groups based on care pathways: coordinated care, integrated care, and other. Length of stay by care phase and total charges were used as measures of health care resource utilization. The models showed that coordinated and integrated care were significantly associated with shorter length of stay during perioperative care: coordinated care, multiplicative effect, 0.90 (P < 0.001); integrated care, 0.77 (P < 0.001). However, only integrated care was associated with shorter rehabilitation and overall length of stay: 0.66 (P < 0.001) in rehabilitation; 0.70 (P < 0.001) in overall duration. Integrated care also was associated with lower total charges: 0.70 (P < 0.001). Current financial incentives for regionally coordinated femoral neck fracture care do not affect health care resource utilization. Further health care reforms should be implemented to promote effective regional care coordination in Japan.

The effect of diabetes with pharmacotherapy for breast cancer on care resource use.

INTRODUCTION: The aim of this study was to quantify the effects of diabetes with pharmacotherapy-treated breast cancer on care resource use. MATERIALS AND METHODS: The study was designed as a single institutional retrospective cohort study using hospital administrative data. The subjects were 152 patients admitted to a hospital from 2008 to 2012 diagnosed with breast cancer, and who underwent pharmacotherapy. We identified diabetes group and nondiabetes group in addition to other variables and quantified the effects of diabetes with breast cancer patients undergoing pharmacotherapy on care resource use, using a multilevel linear regression model. RESULTS: Diabetes was significantly correlated to both longer length of stay (coefficient standard error: 0.75 [0.19], P < 0.001) and higher total hospital charge (0.72 [0.18], P < 0.001), controlled for age, pharmacotherapeutic agent, steroid use, admission route, procedures, and postpharmacotherapy events. CONCLUSION: This study showed that diabetes itself is a risk factor for greater care resource use after controlling for confounding factors. Pharmacotherapy for breast cancer may influence poor glycemic control, thus leading to greater care resource use. Early detection and careful monitoring of diabetes are essential in malignancy to eliminate this burden on the health care system.

Investigation of the Existence of Supplier-Induced Demand in use of Gastrostomy Among Older Adults: A Retrospective Cohort Study.

The aim of this study is to clarify whether there is small area variation in the use of gastrostomy that is explained by hospital physician density, so as to detect the existence of supplier-induced demand (SID).The study design is a retrospective cohort using claim data of Fukuoka Late Elders' Health Insurance, submitted from 2010 to 2013. Study participants included 51,785 older adults who had been diagnosed with eating difficulties. We designated use of gastrostomy as an event. Multilevel logistic analyses were then used to investigate the existence of SID.After controlling for patient factors, we found significant regional level variance in gastrectomy use (median odds ratio [MOR]: 1.72, 1.37-2.51). Hospital physician density was significantly positively related with gastrostomy (adjusted OR of hospital physician density: 1.75, 1.25-2.45; P < 0.001). MORs were largely reduced for the input variable of hospital physician density.We found that the small area variation in use of gastrostomy among older adults could be explained by hospital physician density, which might indicate the existence of SID.

The Impact of Opportunistic Infections on Clinical Outcome and Healthcare Resource Uses for Adult T Cell Leukaemia.

We examined the impact of opportunistic infections on in-hospital mortality, hospital length of stay (LOS), and the total cost (TC) among adult T-cell leukaemia (ATL) patients. In this retrospective cohort study, we identified 3712 patients with ATL using national hospital administrative data. Analysed opportunistic infections included Aspergillus spp., Candida spp., cytomegalovirus (CMV), herpes simplex virus (HSV), pneumocystis pneumonia (PCP), tuberculosis, varicella zoster virus (VZV), Cryptococcus spp., nontuberculous mycobacteria, and Strongyloides spp. Multilevel logistic regression analysis for in-hospital mortality and a multilevel linear regression analysis for LOS and TC were employed to determine the impact of opportunistic infections on clinical outcomes and healthcare resources. We found ATL patients infected with CMV had significantly higher in-hospital mortality (adjusted odds ratio (AOR) 2.29 [1.50-3.49] p < 0.001), longer LOS (coefficient (B): 0.13 [0.06-0.20] p < 0.001) and higher TC (B: 0.25 [0.17-0.32] p < 0.001) than those without CMV. Those with CAN and PCP were associated with a lower in-hospital mortality rate (AOR 0.72 [0.53-0.98] p = 0.035 and 0.54[0.41-0.73] p < 0.001, respectively) than their infections. VZV was associated with longer LOS (B: 0.13 [0.06-0.19] p < 0.001), while aspergillosis, HSV, or VZV infections were associated with higher TC (B: 0.16 [0.07-0.24] p < 0.001, 0.12 [0.02-0.23] p = 0.025, and 0.17 [0.10-0.24] p < 0.001, respectively). Our findings reveal that CMV infection is a major determinant of poor prognosis in patients affected by ATL.

Quantification of the effect of chemotherapy and steroids on risk of Pneumocystis jiroveci among hospitalized patients with adult T-cell leukaemia.

This study aimed to quantify the risks of Pneumocystis pneumonia (PCP) among adult T-cell leukaemia (ATL) patients without prophylaxis. We used hospital administrative data collected nationwide in Japan over 4 years. The research design was a retrospective cohort study. Subjects were 4369 patients diagnosed with ATL aged 18 years or older. The subjects were categorized into four treatment groups: no agent, chemotherapy, chemotherapy + steroids and steroids. We described the risks of PCP among ATL patients without prophylaxis. Risks of PCP were 3·2% for the no agent group, 9·7% for the chemotherapy group, 10·0% for the chemotherapy + steroids group and 16·6% for the steroids group. Logistic regression analyses showed that the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risk of PCP than did the no agent group [adjusted odds ratio (AOR) 3·30 (1·55-7·02), P = 0·002 for the chemotherapy group; AOR 3·35 (2·18-5·17), P < 0·001 for the chemotherapy + steroids group; AOR 6·12 (3·99-9·38), P < 0·001 for the steroids group]. In conclusion, the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risks of PCP. Prophylaxis for PCP among ATL patients being treated with chemotherapy, chemotherapy + steroids and steroids is highly recommended.

Regional differences in performance of bone marrow transplantation, care-resource use and outcome for adult T-cell leukaemia in Japan.

BACKGROUND: Japan has a high prevalence of adult T-cell leukaemia (ATL), especially in the Kyushu/Okinawa region. Regional differences in prevalence might cause regional differences in physicians' experiences and the efficiency of care-resource use. This study investigated regional differences in the performance of bone marrow transplantation (BMT), outcome and care-resource use in patients with ATL in Japan. METHODS: This was a cross-sectional study using a Japanese hospital administrative database in 2010, with a diagnostic-procedure combination/per diem payment system. We examined the association between BMT performance, resource use, outcomes and region. RESULTS: We analysed data for 712 subjects of whom 60.5% were Kyushu/Okinawa residents. Significantly more patients with ATL underwent BMT in Kanto (p = 0.018) and Kansai (p < 0.001) regions compared with the Kyushu/Okinawa regions. The lengths of hospital stay were longer in Kanto (p = 0.002) and Kansai (p = 0.006) regions than in the Kyushu/Okinawa region. Total health-care costs were higher in Kanto (p = 0.001) and Kansai (p = 0.005) regions than the Kyushu/Okinawa region. The risks of in hospital mortality were not significantly different between regions. CONCLUSIONS: There were significant regional differences in BMT performance and resource use within Japan. ATL prevalence was not related to the performance of BMTs, resource use or outcomes. Factors related to regional socioeconomics might affect the performance of BMTs and care resource use within Japan.

Influence of psychiatric disorders on surgical outcomes and care resource use in Japan.

OBJECTIVE: The aim of this study was to quantify the effects of psychiatric disorders on major surgery outcomes and care resource use. METHODS: This study adopted a retrospective cohort study design. The samples consisted of hospital stays. Subjects were patients who had undergone major surgery. We used multilevel regression analysis to quantify the influence of psychiatric disorders on major surgery outcomes and care resource use. RESULTS: The total number of hospital stays included in the study was 5569, of which 250 were patients with psychiatric disorders. Compared with those without psychiatric disorders, those with schizophrenia had a significantly higher risk of complications, and those with neurotic disorder tended to have fewer complications. Total cost was significantly higher for those with schizophrenia and mood disorder and significantly lower in those with neurotic disorder. Lengths of stay were significantly longer for those with schizophrenia and mood disorder but not for those with neurotic disorder. Post-surgical mortality was equivalent among those with any psychiatric disorder and among those without a psychiatric disorder. CONCLUSION: The study revealed that surgical outcomes and care resource use are differentiated by psychiatric disorders.