Analysis of the cost-effectiveness of proton beam therapy for unresectable pancreatic cancer in Japan.

BACKGROUND: Proton beam therapy (PBT) has recently been included in Japan's social health insurance benefits package. This study aimed to determine the cost-effectiveness of PBT for unresectable, locally advanced pancreatic cancer (LAPC) as a replacement for conventional photon radiotherapy (RT). METHODS: We estimated the incremental cost-effectiveness ratio (ICER) of PBT as a replacement for three-dimensional conformal RT (3DCRT), a conventional photon RT, using clinical evidence in the literature and expense complemented by expert opinions. We used a decision tree and an economic and Markov model to illustrate the disease courses followed by LAPC patients. Effectiveness was estimated as quality-adjusted life years (QALY) using utility weights for the health state. Social insurance fees were calculated as the costs. The stability of the ICER against the assumptions made was appraised using sensitivity analyses. RESULTS: The effectiveness of PBT and 3DCRT was 1.67610615 and 0.97181271 QALY, respectively. The ICER was estimated to be ¥5,376,915 (US$46,756) per QALY. According to the suggested threshold for anti-cancer therapy from the Japanese authority of ¥7,500,000 (US$65,217) per QALY gain, such a replacement would be considered cost-effective. The one-way and probabilistic sensitivity analyses demonstrated stability of the base-case ICER. CONCLUSION: PBT, as a replacement for conventional photon radiotherapy, is cost-effective and justifiable as an efficient use of finite healthcare resources. Making it a standard treatment option and available to every patient in Japan is socially acceptable from the perspective of health economics.

Longitudinal health-related quality of life analysis in childhood cancer survivors after proton beam therapy.

PURPOSE: Whilst proton beam therapy (PBT) for children with cancer is expected to reduce their comorbidities, to date only a limited number of studies have been published. To analyze the long-term comorbidity and health-related quality of life (HRQoL) of childhood cancer survivors (CCSs) after PBT, we conducted a questionnaire-based study. METHODS: Questionnaires were sent to CCSs who underwent PBT at the University of Tsukuba Hospital during the period from 1984 to 2020. Scores from 41 CCSs who did not undergo PBT (noPBT-CCSs) and from the general population were used for comparison. RESULTS: In total, 110 individuals who underwent PBT participated in the study. Among them, 40 individuals were longitudinally analyzed. The range of change in the scores was significantly greater in the CCSs whose initial scores were low. Although the comorbidity levels were more severe, HRQoL tended to be better in the PBT-CCSs than in the noPBT-CCSs with central nervous system (CNS) or solid tumors, respectively. When compared with the general population, the psychosocial health summary scores and its components were not different in the noPBT-CNS-CCSs. On the other hand, the psychosocial health summary scores and/or at least one of the scores of emotional, social, and school functioning were significantly higher in the other CCSs groups. CONCLUSIONS: The HRQoL scores of CCSs with low initial scores can be greatly changed over time. Appropriate psychosocial support for this population is warranted. PBT may avoid reduction in HRQoL in terms of the psychosocial functioning of CCSs with CNS tumors.

Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study.

BACKGROUND: Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms-group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study. METHODS: We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists. RESULTS: The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B. CONCLUSIONS: The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.

Cost-effectiveness of mass screening for dipstick hematuria in Japan.

BACKGROUND: Dipstick urine tests are a simple and inexpensive method for detecting kidney and urological diseases, such as IgA nephropathy and bladder cancer. The nationwide mass screening program, Specific Health Checkup (SHC), started in Japan in 2008 and targeted all adults between 40 and 74 years of age. Dipstick urine tests for proteinuria and glucosuria are mandatory as part of the SHC, but dipstick urine tests for hematuria are not. However, the dipstick hematuria test is often administered simultaneously with these mandatory tests by some health insurers. Hematuria is common in Japanese general screening participants, particularly elderly women, and the necessity of mass screening using the dipstick hematuria test has been discussed. This study aimed to evaluate the cost-effectiveness of mass screening for dipstick hematuria tests in addition to the SHC. METHODS: Using a decision tree and Markov modeling, we conducted a cost-effectiveness analysis from a Japanese societal perspective. RESULTS: Compared with the current SHC, mass screening for dipstick hematuria tests, in addition to the SHC, costs less and gains more, which means cost-saving. Similar findings were observed in the sex-specific analysis. CONCLUSION: Our results suggest that mandating the dipstick hematuria test could be justifiable as an efficient use of finite healthcare resources. The results have implications for mass screening programs not only in Japan but worldwide.

Physical functioning in patients with chronic kidney disease stage G3b-5 in Japan: The reach-J CKD cohort study.

AIM: Chronic kidney disease (CKD) is an important public health problem. Recently, CKD has been found to be associated with poor physical functioning in community-dwelling elderly individuals. However, the physical functioning of non-dialysis (ND) patients with advanced CKD treated by nephrologists is unknown. METHODS: Patients with ND-CKD stage G3b-5 who participated in a nationwide Reach-J CKD cohort study were included in this study. Physical functioning and physical activity were assessed by the Katz Index, Lawton-Body instrumental activities of daily living (IADL) scale, and Rapid Assessment of Physical Activity questionnaire of the international CKD Outcomes and Practice Patterns Study (CKDopps) questionnaires. Dichotomies between good and poor physical functioning and physical activity scores were explored. RESULTS: Among 1628 patients, 84.3% had good physical functioning. Poor physical functioning was more common with older age (p < .001), higher CKD stage (p < .05), and comorbid conditions such as diabetes (p < .001), cardiovascular disease (p < .05), cerebrovascular disease (p < .001), and cancer (non-skin) (p < .05). Forty percent of the patients were inactive. Physical inactivity was more common with older age (p < .001) and higher CKD stage (p < .001). CONCLUSION: A minority, but sizeable proportion of patients with advanced CKD treated by nephrologists in Japan have some disability in ADLs/IADLs. Nephrologists need to routinely assess the physical functioning and physical activity of patients with advanced CKD to provide individualized guidance and comprehensive support to these patients for their daily life.

Cost-effectiveness of a New Opportunistic Screening Strategy for Walk-in Fingertip HbA1c Testing at Community Pharmacies in Japan.

OBJECTIVE: A new opportunistic community-based strategy was launched in Japan in April 2014 to detect lifestyle-related diseases, including diabetes, by creating Specimen Measurement Offices (SMOs). SMOs offer walk-in fingertip HbA1c testing. This article aimed to assess the value-for-money of HbA1c testing services at SMOs by conducting a cost-effectiveness analysis. RESEARCH DESIGN AND METHODS: We compared two scenarios: 1) status quo, defined as HbA1c testing that is available only through conventional screening, and 2) HbA1c testing available at SMOs as a complement to the status quo scenario. The model consisted of a screening module with a decision tree and a disease progression module with a Markov model. We calculated incremental cost-effectiveness ratios (i.e., cost per quality-adjusted life-years [QALYs]) over the lifetime analytic horizon as the primary end point of the cost-effectiveness analysis. In this model, we assumed the participant cohort to be people 40-74 years of age who sought walk-in fingertip HbA1c testing at SMOs on the premises of community pharmacies. Costs and outcomes were discounted at a rate of 3%. The cost-effectiveness was analyzed from a societal perspective. RESULTS: The incremental cost per individual for those 40-74 years of age was estimated to be -527 U.S. dollars (USD) (-52,722 Japanese yen [JPY]) for HbA1c testing at SMOs compared with the status quo. Incremental effectiveness was estimated to be 0.0203 QALYs for HbA1c testing at SMOs compared with the status quo. Therefore, this cost-effectiveness analysis showed that compared with the status quo, HbA1c testing at SMOs was more effective and had lower cost for the population studied. CONCLUSIONS: We consider our results to be robust because most simulations were under the threshold of USD 50,000 (JPY 5,000,000) per QALYs gained, by sensitivity analysis. These results will be useful to managers of pharmacies or other health institutions and/or policy makers in local government.

Cost-effectiveness of obstructive sleep apnea screening for patients with diabetes or chronic kidney disease.

PURPOSE: Obstructive sleep apnea (OSA) is a common disorder with a high prevalence among patients with cardiovascular disease (CVD), diabetes, and chronic kidney disease (CKD). Routine evaluation of OSA for patients with CVD including hypertension has been performed according to the clinical guidelines for both OSA and CVD. However, most patients with diabetes and CKD who could benefit from treatment remain undiagnosed because routine screening of OSA is not recognized as part of standard practice. This study aims to evaluate the cost-effectiveness of OSA screening for patients with diabetes and CKD. METHODS: Cost-effectiveness analysis by a decision tree and Markov modeling from the societal perspective in Japan was carried out to provide evidence based on the economic evaluation of current clinical practice concerning diabetes and CKD. RESULTS: Incremental cost-effectiveness ratios of OSA screening compared with do-nothing were calculated as ¥3,516,976 to 4,514,813/quality-adjusted life year (QALY) (US$35,170 to 45,148/QALY) for diabetes patients and ¥3,666,946 to 4,006,866/QALY (US$36,669 to 40,069/QALY) for CKD patients. CONCLUSIONS: Taking the threshold to judge cost-effectiveness according to a suggested value of social willingness to pay for one QALY gain in Japan as ¥5 million/QALY (US$50,000QALY), OSA screening is cost-effective. Our results suggest that active case screening and treatment of OSA for untreated middle-aged male patients with diabetes or CKD could be justifiable as an efficient use of finite health-care resources in the world with high prevalence of these diseases.

A novel beta1,3-N-acetylglucosaminyltransferase (beta3Gn-T8), which synthesizes poly-N-acetyllactosamine, is dramatically upregulated in colon cancer.

A new member of the UDP-N-acetylglucosamine: beta-galactose beta1,3-N-acetylglucosaminyltransferase (beta3Gn-T) family having the beta3-glycosyltransferase motifs was identified using an in silico method. This novel beta3Gn-T was cloned from a human colon cancer cell line and named beta3Gn-T8 based on its position in a phylogenetic tree and enzymatic activity. Beta3Gn-T8 transfers GlcNAc to the non-reducing terminus of the Galbeta1-4GlcNAc of tetraantennary N-glycan in vitro. HCT15 cells transfected with beta3Gn-T8 cDNA showed an increase in reactivity to both LEA and PHA-L4 in a flow cytometric analysis. These results indicated that beta3Gn-T8 is involved in the biosynthesis of poly-N-acetyllactosamine chains on tetraantennary (beta1,6-branched) N-glycan. In most of the colorectal cancer tissues examined, the level of beta3Gn-T8 transcript was significantly higher than in normal tissue. Beta3Gn-T8 could be an enzyme involved in the synthesis of poly-N-acetyllactosamine on beta1-6 branched N-glycans in colon cancer.

Molecular cloning and identification of 3'-phosphoadenosine 5'-phosphosulfate transporter.

Nucleotide sulfate, namely 3'-phosphoadenosine 5'-phosphosulfate (PAPS), is a universal sulfuryl donor for sulfation. Although a specific PAPS transporter is present in Golgi membrane, no study has reported the corresponding gene. We have identified a novel human gene encoding a PAPS transporter, which we have named PAPST1, and the Drosophila melanogaster ortholog, slalom (sll). The amino acid sequence of PAPST1 (432 amino acids) exhibited 48.1% identity with SLL (465 amino acids), and hydropathy analysis predicted the two to be type III transmembrane proteins. The transient expression of PAPST1 in SW480 cells showed a subcellular localization in Golgi membrane. The expression of PAPST1 and SLL in yeast Saccharomyces cerevisiae significantly increased the transport of PAPS into the Golgi membrane fraction. In human tissues, PAPST1 is highly expressed in the placenta and pancreas and present at lower levels in the colon and heart. An RNA interference fly of sll produced with a GAL4-UAS system revealed that the PAPS transporter is essential for viability. It is well known that mutations of some genes related to PAPS synthesis are responsible for human inherited disorders. Our findings provide insights into the significance of PAPS transport and post-translational sulfation.