Post-transplant outcomes and financial burden of donation after circulatory death donor liver transplant after the implementation of acuity circle policy.

BACKGROUND: After implementation of the Acuity Circles (AC) allocation policy, use of DCD liver grafts has increased in the United States. METHODS: We evaluated the impact of AC on rates of DCD-liver transplants (LT), their outcomes, and medical costs in a single practice. Adult LT patients were classified into three eras: Era 1 (pre-AC, 1/01/2015-12/31/2017); Era 2 (late pre-AC era, 1/01/2018-02/03/2020); and Era 3 (AC era, 05/10/2020-09/30/2021). RESULTS: A total of 520 eligible LTs were performed; 87 were DCD, and 433 were DBD. With each successive era, the proportion of DCD increased (Era 1: 11%; Era 2: 20%; Era 3: 24%; p < .001). DCD recipients had longer ICU stays, higher re-admission/re-operation rates, and higher incidence of ischemic cholangiopathy compared to those with DBD. Direct, surgical, and ICU costs during first admission were higher with DCD than DBD (+8.0%, p < .001; +4.2%, p < .001; and +33.3%, p = .001). DCD-related costs increased after Era 1 (Direct: +4.9% [Era 2 vs. 1] and +12.4% [Era 3 vs. 1], p = .04; Surgical: +17.7% and +21.7%, p < .001). In the AC era, there was a significantly higher proportion of donors ≥50 years, and more national organ sharing. Compared to DCD from donors <50 years, DCD from donors ≥50 years was associated with significantly higher total direct, surgical, and ICU costs (+12.6%, p = .01; +9.5%, p = .01; +84.6%, p = .03). CONCLUSIONS: The proportion of DCD-LT, especially from older donors, has increased after the implementation of AC policies. These changes are likely to be associated with higher costs in the AC era.

Disparities in the Effects of Acuity Circle-based Liver Allocation on Waitlist and Transplant Practice Between Centers.

Liver allocation in the United States was updated on February 4, 2020, by introducing the acuity circle (AC)-based model. This study evaluated the early effects of the AC-based allocation on waitlist outcomes. Methods: Adult liver transplant (LT) candidates listed between January 1, 2019, and September 30, 2021, were assessed. Two periods were defined according to listing date (pre- and post-AC), and 90-d waitlist outcomes were compared. Median transplant Model for End-stage Liver Disease (MELD) score of each transplant center was calculated, with centers categorized as low- (<25 percentile), mid- (25-75 percentile), and high-MELD (>75 percentile) centers. Results: A total of 12 421 and 17 078 LT candidates in the pre- and post-AC eras were identified. Overall, the post-AC era was associated with higher cause-specific 90-d hazards of transplant (csHR, 1.32; 95% confidence interval [CI], 1.27-1.38; P < 0.001) and waitlist mortality (cause-specific hazard ratio [csHR], 1.20; 95% CI, 1.09-1.32; P < 0.001). The latter effect was primarily driven by high-MELD centers. Low-MELD centers had a higher proportion of donations after circulatory death (DCDs) used. Compared with low-MELD centers, mid-MELD and high-MELD centers had significantly lower cause-specific hazards of DCD-LT in both eras (mid-MELD: csHR, 0.47; 95% CI, 0.38-0.59 in pre-AC and csHR, 0.56; 95% CI, 0.46-0.67 in post-AC and high-MELD: csHR, 0.11; 95% CI, 0.07-0.17 in pre-AC and csHR, 0.14; 95% CI, 0.10-0.20 in post-AC; all P < 0.001). Using a structural Bayesian time-series model, the AC policy was associated with an increase in the actual monthly DCD-LTs in low-, mid-, and high-MELD centers (actual/predicted: low-MELD: 19/16; mid-MELD: 21/14; high-MELD: 4/3), whereas the increase in monthly donation after brain death-LTs were only present in mid- and high-MELD centers. Conclusions: Although AC-based allocation may improve waitlist outcomes, regional variation exists in the drivers of such outcomes between centers.

Assessment of a software for semi-automatically calculating the bone scan index on bone scintigraphy scans.

AIMS: The incidence of bone metastases exceeds 85% in patients who die from prostate cancer. Bone scintigraphy is the most widely used method for the early detection of bone metastases in prostate cancer. We developed a software program that semi-automatically calculated the bone scan index (BSI) on technetium-99m hydroxymethylene diphosphonate bone scintigraphy scans with a computer-aided diagnosis system (CAD) and examined whether the BSI calculated using this software could replace the extent of disease (EOD) score. METHODS: The subjects were 175 patients who were diagnosed with prostate cancer at our hospital and underwent bone scintigraphy. We analyzed receiver operating characteristic curves to determine the BSI cutoff value between EOD groups. The cutoff value was determined based on the maximum value of the sum of the sensitivity and specificity. RESULTS: BSI cutoff values of 0.20, 1.56, and 4.56 were used to distinguish between EOD 0 and 1-4 (sensitivity [87.2%] and specificity [100.0%]), between EOD 0- and 2-4 (sensitivity [85.2%] and specificity [92.0%]), and between EOD 0-2 and 3-4 (sensitivity [88.4%] and specificity [99.2%]), respectively. CONCLUSION: Our results suggest that this software can calculate BSI, and the software may play a role in predicting prognosis and selecting an appropriate treatment strategy. If a sufficient number of other nuclear medicine tests are performed, creating a similar CAD system is possible.

Immediate Postoperative Extubation Decreases Pulmonary Complications in Liver Transplant Patients.

BACKGROUND: Fast-track anesthesia in liver transplantation (LT) has been discussed over the past few decades; however, factors associated with immediate extubation after LT surgery are not well defined. This study aimed to identify predictive factors and examine impacts of immediate extubation on post-LT outcomes. METHODS: A total of 279 LT patients between January 2014 and May 2017 were included. Primary outcome was immediate extubation after LT. Other postoperative outcomes included reintubation, intensive care unit stay and cost, pulmonary complications within 90 days, and 90-day graft survival. Logistic regression was performed to identify factors that were predictive for immediate extubation. A matched control was used to study immediate extubation effect on the other postoperative outcomes. RESULTS: Of these 279 patients, 80 (28.7%) underwent immediate extubation. Patients with anhepatic time >75 minutes and with total intraoperative blood transfusion ≥12 units were less likely to be immediately extubated (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.89; P = 0.02; OR, 0.11; 95% CI, 0.05-0.21; P < 0.001). The multivariable analysis showed immediate extubation significantly decreased the risk of pulmonary complications (OR, 0.34; 95% CI, 0.15-0.77; P = 0.01). According to a matched case-control model (immediate group [n = 72], delayed group [n = 72]), the immediate group had a significantly lower rate of pulmonary complications (11.1% versus 27.8%; P = 0.012). Intensive care unit stay and cost were relatively lower in the immediate group (2 versus 3 d; P = 0.082; $5700 versus $7710; P = 0.11). Reintubation rates (2.8% versus 2.8%; P > 0.9) and 90-day graft survival rates (95.8% versus 98.6%; P = 0.31) were similar. CONCLUSIONS: Immediate extubation post-LT in appropriate patients is safe and may improve patient outcomes and resource allocation.

Prediction of treatment failure during infliximab induction therapy in inflammatory bowel disease patients based on pharmacokinetic and pharmacodynamic modeling.

BACKGROUND: In infliximab (IFX) treatment for Crohn's disease (CD) and ulcerative colitis (UC), it is difficult to predict treatment failure during the induction phase. In the present study for optimal IFX treatment, we attempted to estimate serum IFX concentration and clinical response in individual patients during the induction phase to predict the indication of therapeutic effect and the possibility of treatment failure in the maintenance phase. METHODS: We estimated pharmacokinetic and pharmacodynamic (PK/PD) parameters and predicted the serum IFX concentration and clinical response using a PK/PD model and Markov chain Monte Carlo Bayesian analysis method during the induction phase. Then, we determined whether the indication of therapeutic effect between predicted and observed clinical response were matched during the maintenance phase. RESULTS: Data obtained from 15 patients were analyzed. The correlation between predicted and observed values of serum IFX concentration (Pearson product-moment correlation coefficient, 0.700; P < 0.0001, n = 68) and clinical response of CD patients (0.790; P < 0.0001, n = 25) and UC patients (0.702; P = 0.0004, n = 21) were significantly high. The indication of therapeutic effect at the final time point of each patient (from day 115 to day 203) were successfully predicted in 14 of 15 patients (93.3%). CONCLUSIONS: This study presents prediction of serum IFX concentration and clinical response in individual patients during induction therapy, with presumption of the indication of therapeutic effect and the treatment failure in the maintenance phase. Our results show the possibility of optimizing IFX therapy during the induction phase.

Prevalence, disease burden, and treatment reality of patients with severe, uncontrolled asthma in Japan.

BACKGROUND: The severe asthma and severe, uncontrolled asthma (SUA) populations in Japan are not well-studied. We investigated the prevalence of continuously treated severe asthma and SUA patients, their disease burden, and the treatment reality via a Japanese health insurance claims database. METHODS: Continuously treated asthma patients (patients prescribed inhaled corticosteroids for asthma ≥4 times in the past year) aged ≥17 years at the index date (latest visit between April 2014 and March 2015 for asthma treatment) were included in this analysis (KEIFU study, UMIN000027695). Asthma severity and control status at the index date were defined using modified criteria of ERS/ATS guidelines. Asthma hospitalization, oral corticosteroid (OCS) use, and total medical expenses were calculated using data up to 12 months post-index date. RESULTS: We identified 10,579 patients as continuously treated asthma patients. Of these, 823 (7.8%) had severe asthma; 267 (2.5%) and 556 (5.3%) patients had SUA and severe, controlled asthma (SCA), respectively. Compared with SCA and mild to moderate asthma patients, a greater percentage of SUA patients required hospitalization (13.7%, 6.2%, and 3.0%, respectively) and were prescribed OCSs (67.4%, 45.9%, and 16.2%, respectively). Yearly total medical expenses were also greater for SUA patients (mean [standard deviation]: 8346 [12,280], vs 5989 [10,483] and 3422 [8800] USD, respectively). CONCLUSIONS: The percentages of severe asthma and SUA patients continuously treated in Japan were obtained through this large-scale analysis using a health insurance claims database. SUA patients had greater medical and economic burdens, suggesting more appropriate treatment is required according to the treatment guidelines.

The Role of Inverted Internal Limiting Membrane Flap in Macular Hole Closure.

Purpose: To investigate the mechanism of macular hole (MH) closure following the inverted internal limiting membrane (ILM) technique. Methods: We performed the inverted ILM flap surgical technique as an experimental MH model in monkeys, and investigated the process of MH closure immunohistochemically. We then investigated the effects of type IV collagen, fibronectin, and laminin, which are constituent proteins of the ILM, on the proliferation and migration of cultivated Müller cells (MIO-M1). We also investigated the expression of neurotrophic factors and basic fibroblast growth factor (bFGF) in human ILM and MIO-M1 cells, and the effect of MIO-M1 migration on the expression of these factors, via immunohistochemical staining and the real-time reverse transcription polymerase chain reaction. Results: Ten days after inverted ILM flap surgery, the MH had closed and proliferating glial fibrillary acidic protein (GFAP)-positive cells surrounded the ILM. Type IV collagen, fibronectin, and laminin all enhanced the proliferation of MIO-M1 cells, and type IV collagen and fibronectin enhanced the migration of MIO-M1 cells. Neurotrophic factors and bFGF were present on the surface of the human ILM, and MIO-M1 cells produced these factors. Neurotrophic factors and bFGF were expressed to a significantly greater extent by migrating MIO-M1 cells than by these cells in their static state. Conclusions: During MH closure, the ILM functioned as a scaffold for the proliferation and migration of Müller cells, and may promote Müller cell activation. Neurotrophic factors and bFGF produced by activated Müller cells and present on the surface of the ILM may contribute to MH closure.

Asian Perspectives on Diagnostic and Therapeutic Strategies in Inflammatory Bowel Disease: Report and Analysis of a Survey with Questionnaires.

BACKGROUND: Diagnostic and therapeutic strategies in inflammatory bowel disease (IBD) vary among countries in terms of availability of modalities, affordability of health care resource, health care policy and cultural background. This may be the case in different countries in Eastern Asia. The aim of this study was to determine and understand the differences in diagnostic and therapeutic strategies of IBD between Japan and the rest of Asian countries (ROA). METHODS: Questionnaires with regard to clinical practice in IBD were distributed to members of the International Gastroenterology Consensus Symposium Study Group. The responders were allowed to select multiple items for each question, as multiple modalities are frequently utilized in the diagnosis and the management of IBD. Dependency and independency of selected items for each question were evaluated by the Bayesian network analysis. RESULTS: The selected diagnostic modalities were not very different between Japan and ROA, except for those related to small bowel investigations. Balloon-assisted enteroscopy and small bowel follow through are frequently used in Japan, while CT/MR enterography is popular in ROA. Therapeutic modalities for IBD depend on availability of such modalities in clinical practice. As far as modalities commonly available in both regions are concerned, there seemed to be similarity in the selection of each therapeutic modality. However, evaluation of dependency of separate therapeutic modalities by Bayesian network analysis disclosed some difference in therapeutic strategies between Japan and ROA. CONCLUSION: Although selected modalities showed some similarity, Bayesian network analysis elicited certain differences in the clinical approaches combining multiple modalities in various aspects of IBD between Japan and ROA.

Effects of family budgeting responsibility on subjective health status: An empirical study of Japanese wives.

We examine whether the decision-making power of Japanese wives affects their health status. Looking at cross-sectional data from the Japanese Panel Survey of Consumers (JPSC) conducted with women, we create a new measure for decision-making power based on participation in family budgeting. The data sample covers 1,306 married women aged 25 to 45 years in 2004. We find that Japanese wives are more likely to report good health when they have more responsibility than their husbands for household budgeting. Additionally, having more education or being fully employed increased the probability of reporting "good health" by more than six percentage points.

Societal cost-effectiveness analysis of the 21-gene assay in estrogen-receptor-positive, lymph-node-negative early-stage breast cancer in Japan.

BACKGROUND: Breast-cancer incidence and mortality have been increasing in Japan. Japanese-specific clinical validity and utility data for the 21-gene assay (Oncotype DX® Breast Cancer Assay; Genomic Health, Inc., Redwood City, USA) are now available. The objective of this study was to evaluate the cost-effectiveness of the 21-gene assay for the guidance of adjuvant chemotherapy decisions in estrogen-receptor-positive, lymph-node-negative, early-stage breast cancer patients, from the Japanese societal perspective. METHODS: The recurrence risk group distribution by the 21-gene assay result and the assay's influence on adjuvant chemotherapy recommendations were obtained from a study of 104 patients. A state-transition cohort (Markov) model tracked time from surgery until distant recurrence and from distant recurrence to death. Adjuvant chemotherapy benefit by 21-gene assay risk group was based on published clinical validation studies. Direct and indirect medical costs were obtained from the referral centers. Utilities associated with progression and chemotherapy-related adverse events were extracted from literature. Sensitivity analyses assessed the key drivers and robustness of the primary outcomes. RESULTS: The 21-gene assay identified 48% of patients as low-risk, 36% as intermediate-risk, and 16% as high-risk. Total acute chemotherapy-related costs decreased by ¥154,066 due to less adjuvant chemotherapy usage. In the high-risk group, adjuvant chemotherapy use increased 18%, leading to survival benefits. Chemotherapy use overall decreased by 19%. Monitoring costs increased by ¥3,744 but recurrence costs declined by ¥46,113 per patient. Use of the 21-gene assay increased quality-adjusted-life-years (QALYs) by 0.241 per patient on average; the net cost per QALY gained was ¥636,752 ($6,368). CONCLUSIONS: The 21-gene assay for women with estrogen-receptor-positive, lymph-node-negative, early-stage breast cancer is projected to be cost-effective in Japan.

Assessment of noninvasive, percutaneous hemoglobin measurement in pregnant and early postpartum women.

PURPOSE: Using the Pronto-7® analyzer, we measured percutaneous hemoglobin (SpHb) noninvasively in pregnant and early postpartum women, and assessed the accuracy of the measurements by comparing them with laboratory measurements of hemoglobin. METHODS: We obtained SpHb measurements from 193 pregnant women, 269 early postpartum women, and 76 nonpregnant women. A laboratory total hemoglobin (tHb) measurement, from venous blood sampling, was obtained immediately prior to the SpHb measurement. The total number of measurements obtained from the nonpregnant, pregnant, and postpartum women was 76, 438, and 347, respectively. RESULTS: The mean biases (SpHb - tHb) among the nonpregnant, first trimester, second trimester, third trimester, and early postpartum women were -0.20, 0.19, 1.01, 1.32, and 1.10 g/dL, respectively. The Bland-Altman comparison showed neither the tendency of a fixed bias nor proportional biases among the measurements in the category of nonpregnant and first trimester women. But in the second and third trimester and postpartum category, a significant fixed bias was noted, without any tendencies of proportional bias. CONCLUSION: In this study, we found higher hemoglobin values with the Pronto-7 analyzer than were measured in the laboratory. We consider that the device has certain limitations in obstetrical utility and requires further modifications for use in the perinatal period.

Clinical assessment of delayed gastric emptying and diabetic complications using gastric emptying scintigraphy: involvement of vascular disorder.

AIM: Delayed gastric emptying, including gastroparesis, is a common complication in diabetes mellitus. The association between delayed gastric emptying and overall diabetic complications remains to be studied in detail. We analysed this association. METHODS: We performed gastric emptying scintigraphy of (99m) Tc-diethylenetriaminepentaacetic acid in 34 patients with diabetes to measure the gastric emptying half-times (T1/2) of the whole stomach (WS), proximal stomach (PS) and distal stomach (DS). We assessed T1/2, diabetic-related factors and complications. RESULTS: The prevalence of autonomic neuropathy was higher in the group with delayed T1/2 of the WS than in the normal group. Analysis of intima-media thickness (IMT) and ankle brachial pressure index (ABI), which are risk indicators for vascular disorder, showed that IMT of the carotid bulb was greater in the group with delayed T1/2 of the WS than in the normal group (2·41 mm [1·50-2·81] versus 1·40 mm [0·81-2·08], P = 0·015). T1/2 of the WS correlated positively with IMT of the carotid bulb (r = 0·391, P = 0·027) and negatively with ABI (r = -0·389, P = 0·028). These correlations were mainly attributed to PS and were the same in patients without autonomic neuropathy. In seven of nine patients who received scintigraphy again after diabetic treatment, glycosylated haemoglobin (HbA1c) levels decreased and T1/2 of the WS shortened compared with before treatment. CONCLUSION: Vascular disorder, among other cofactors such as autonomic neuropathy, could be involved in the pathophysiology of delayed gastric emptying. Medium- to long-term glycaemic control was associated with gastric emptying.

Assessment of the cardioankle vascular index in pregnant women complicated with hypertensive disorders.

It was previously reported that the brachial-ankle pulse wave velocity (baPWV) is elevated in preeclamptic women. However, baPWV is strongly affected by blood pressure. Recently, a new index of vascular stiffness, the cardioankle vascular index (CAVI), was developed. CAVI is thought to be an index independent of blood pressure. We assessed CAVI in normotensive and hypertensive pregnant women. We studied a total of 109 Japanese women consisting of 23 nonpregnant healthy women (group A), 45 normotensive pregnant women (group B), 28 pregnant women complicated with established preeclampsia (group C), and 13 pregnant women with chronic hypertension (group D). The subject remained supine while the blood pressure, baPWV, and CAVI were recorded. No significant difference in baPWV was present between groups C and D, but the difference in CAVI was significantly high in group D. We believe that we can distinguish the vessel structural change between chronic hypertension and preeclampsia through simultaneous baPWV and CAVI measurements.

Hospital safety climate, psychosocial risk factors and needlestick injuries in Japan.

To investigate the interactions between safety climate, psychosocial issues and Needlestick and Sharps Injuries (NSI), a cross-sectional study was undertaken among nurses at a university teaching hospital in Japan (89% response rate). NSI were correlated with various aspects of hospital safety climate including supporting one another at work, the protection of staff against blood-borne diseases being a high management priority, managers doing their part to protect staff from blood-borne disease, having unsafe work practices corrected by supervisors, having the opportunity to use safety equipment to protect against blood-borne disease exposures, having an uncluttered work area, and having minimal conflict within their department. In conclusion, this study has demonstrated the importance of hospital safety climate in Japanese health care practice, particularly its relationship with NSI. Although the provision of safer devices remains critical in preventing injuries, ensuring a positive safety climate will also be essential in meeting these important challenges for nurses' occupational health.

Hand-assisted laparoscopic living-donor nephrectomy as an alternative to traditional laparoscopic living-donor nephrectomy.

The benefits of laparoscopic living-donor nephrectomy (LDN) are well described, while similar data on hand-assisted laparoscopic living-donor nephrectomy (HALDN) are lacking. We compare hand-assisted laparoscopic living-donor nephrectomy with open donor nephrectomy. One hundred consecutive hand-assisted laparoscopic living-donor nephrectomy (10/98-8/01) donor/recipient pairs were compared to 50 open donor nephrectomy pairs (8/97-1/00). Mean donor weights were similar (179.6 +/- 40.8 vs. 167.4 +/- 30.3 lb; p = NS), while donor age was greater among hand-assisted laparoscopic living-donor nephrectomy (38.2 +/- 9.5 vs. 31.2 +/- 7.8 year; p < 0.01). Right nephrectomies was fewer in hand-assisted laparoscopic living-donor nephrectomy [17/100 (17%) vs. 22/50 (44%); p < 0.05]. Operative time for hand-assisted laparoscopic living-donor nephrectomy (3.9 +/- 0.7 vs. 2.9 +/- 0.5 h; p < 0.01) was longer; however, return to diet (6.9 +/- 2.8 vs. 25.6 +/- 6.1 h; p < 0.01), narcotics requirement (17.9 +/- 6.3 vs. 56.3 +/- 6.4h; p < 0.01) and length of stay (51.7 +/- 22.2 vs. 129.6 +/- 65.7 h; p < 0.01) were less than open donor nephrectomy. Costs were similar ($11072 vs. 10840). Graft function and 1-week Cr of 1.4 +/- 0.9 vs. 1.6 +/- 1.1 g/dL (p = NS) were similar. With the introduction of HALDN, our laparoscopic living-donor nephrectomy program has increased by 20%. Thus, similar to traditional laparoscopic donor nephrectomy, hand-assisted laparoscopic living-donor nephrectomy provides advantages over open donor nephrectomy without increasing costs.