Exclusive waterpipe smoking and the risk of nasopharynx cancer in Vietnamese men, a prospective cohort study.

Tobacco smoking is carcinogenic to humans. Besides cigarettes, the most common form of tobacco smoking, there was sparse evidence of waterpipe's carcinogenicity-induced nasopharyngeal cancer (NPC). This study investigated the association between waterpipe smoking and NPC mortality. Our study followed up with 20,144 eligible man participants from nine northern Vietnam communes between 2007 and 2019. Face-to-face interviews were conducted to gather data on exclusive waterpipe and cigarette smoking and dietary intake using structured semi-quantitative food frequency and lifestyle questionnaires. Nasopharyngeal cancer was determined by accessing the medical records at the state health facilities. We estimated the Cox proportional hazard ratio and 95% confidence intervals, HR (95% CI). The proportion of never smokers, exclusive waterpipe, exclusive cigarette, and dual waterpipe and cigarette smokers was 55.8%, 14.5%, 16.6%, and 13.1%, respectively. Exclusively waterpipe smokers increased the risk of NPC death compared to exclusively cigarette smokers, HR (95% CI): 4.51 (1.25, 16.31), p = 0.022. A dose-dependent positive relationship between NPC and exclusive waterpipe smoking was significantly seen for higher intensity HR (95% CI): 1.35 (1.07, 1.71), earlier age of smoking initiation HR (95% CI): 1.26 (1.06, 1.50), longer duration HR (95% CI): 1.31 (1.04, 1.66), and the cumulative number of a smoke lifetime HR (95% CI): 1.37 (1.08, 1.74). We observed a significant positive association between exclusive waterpipe smoking and NPC in men. The findings suggested that waterpipe smoking is likely more harmful than cigarettes in developing this cancer. A firm tobacco control against waterpipe smoking is highly recommended.

Calcium Intake Contributed by Whole Foods and Gastric Cancer in Viet Nam: A Case­Control Study.

BACKGROUND: Recent studies revealed the potential tumor-suppressive effects of calcium. We aimed to investigate the association between dietary calcium intake contributed by whole foods and gastric cancer. METHODS: 466 gastric cancer cases and 1531 controls were extracted from the completed case-control studies in hospitals in Hanoi from 2017 to 2019. A validated semi-quantitative food frequency questionnaire was used to obtain data via face-to-face interviews with the trained interviewer. Calcium intake was calculated based on the food frequency intake per year. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. RESULTS: The study participants consumed less than 50% of 700 mg/day compared to the recommended calcium intake. With increasing calcium intake, we found a reduction in gastric cancer in both genders, men and women (adjusted OR and 95%CI, 5th vs. 1st quintile: 0.50 (0.36, 0.70), p_trend 0.000; 0.62 (0.42, 0.92), p_trend 0.019; and 0.30 (0.16, 0.57), p_trend 0.000, respectively). The inverse association remained in the subgroups of never-smokers and those with positive H. pylori infection. CONCLUSION: We observed substantial benefits of calcium intake from whole foods against gastric cancer in the Vietnamese population with a low nutritious status.

Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy.

Background: New therapies for glioblastoma (GBM) are urgently needed because the disease prognosis is poor. Chimeric antigen receptor (CAR)-T cell therapy that targets GBM-specific cell surface antigens is a promising therapeutic strategy. However, extensive transcriptome analyses have uncovered few GBM-specific target antigens. Methods: We established a library of monoclonal antibodies (mAbs) against a tumor cell line derived from a patient with GBM. We identified mAbs that reacted with tumor cell lines from patients with GBM but not with nonmalignant human brain cells. We then detected the antigens they recognized using expression cloning. CAR-T cells derived from a candidate mAb were generated and tested in vitro and in vivo. Results: We detected 507 mAbs that bound to tumor cell lines from patients with GBM. Among them, E61 and A13 reacted with tumor cell lines from most patients with GBM, but not with nonmalignant human brain cells. We found that B7-H3 was the antigen recognized but E61. CAR-T cells were established using the antigen-recognition domain of E61-secreted cytokines and exerted cytotoxicity in co-culture with tumor cells from patients with GBM. Conclusions: Cancer-specific targets for CAR-T cells were identified using a mAb library raised against primary GBM tumor cells from a patient. We identified a GBM-specific mAb and its antigen. More mAbs against various GBM samples and novel target antigens are expected to be identified using this strategy.

Occupation- and industry-specific cancer mortality among Japanese women from 1980 to 2015.

BACKGROUND: The number of women in Japan who continue working after childbirth is on the rise. Over the past few years, Japan's cancer mortality rate has increased. About 50% of all cancer deaths among Japanese women aged 25-64 are caused by lung, gastric, pancreatic and colorectal cancers. This study aims to examine the difference in mortality risk for key cancers among women and explore the effect of the economic crisis in the mid-1990s separately for occupational and industrial categories. METHODS: Data from 1980 to 2015 were gathered from the Japanese Population Census and National Vital Statistics conducted in the same year. A Poisson regression analysis was used to estimate mortality risk and mortality trends for lung, gastric, pancreatic and colorectal cancer among Japanese working women aged 25-64 years. RESULTS: Across most industrial and occupational groups, the trends in age-standardised cancer mortality rate for women have declined. Workers in management, security and transportation have a higher cancer mortality risk than sales workers. The risk of death from all four cancers is higher for workers in the mining and electricity industries than for wholesale and retail workers. CONCLUSION: To improve the health and well-being of employed Japanese women, it is crucial to monitor cancer mortality trends. Using these population-level quantitative risk estimates, industry- and occupation-specific prevention programmes can be developed to target women at higher cancer risk and enable the early detection and treatment of cancer.

Systematic Literature Review of the Use of Productivity Losses/Gains in Cost-Effectiveness Analyses of Immune-Mediated Disorders.

INTRODUCTION: In light of the lack of an agreed international standard for how to conduct cost-effectiveness analyses (CEAs), including cost-utility analyses (CUAs) from a societal perspective, there is uncertainty regarding to what extent the inclusion of productivity losses/gains in economic evaluations can affect cost-effectiveness results and subsequently decisions on whether to recommend new health technologies. To investigate this, we conducted a systematic review of CEAs and CUAs of drug-based therapies for a set of chronic immune-mediated disorders to understand how cost elements and calculation methods related to productivity losses/gains are used, examine the impact on the incremental cost-effectiveness ratio (ICER) of including productivity costs, and explore factors that affect the inclusion of productivity loss. METHODS: Databases (MEDLINE® In-process, MEDLINE, Embase and Cochrane Library) were searched from January 2010 to October 2020 by two independent reviewers for all CEAs and CUAs in adults with any of the following conditions: ankylosing spondylitis, chronic idiopathic urticaria, Crohn's disease, fibromyalgia, juvenile idiopathic arthritis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis. Relevant study data were extracted and evidence was synthesized for both qualitative and quantitative analysis. Productivity cost elements including absenteeism, presenteeism, unemployment/early retirement, premature mortality and informal care were extracted, along with the method used to determine them. A multivariate analysis was performed to identify factors associated with the inclusion of productivity loss. RESULTS: Our searches identified 5016 records, culminating in 198 unique studies from 234 publications following screening. Most of the studies investigated rheumatoid arthritis (37.0%) or psoriasis (32.0%). The majority were CUAs, with some including both a CEA and a CUA (73.0%). Most studies used a payer perspective only (28.5%) or a societal perspective only (21.0%). Of the 49 studies incorporating productivity losses/gains, 42 reported the type of cost element used; all of these used patient absenteeism, either alone or in addition with other elements. Only 16 studies reported the method used to value productivity changes, of which eight used a human capital approach, four used a friction cost approach and four used both approaches. Twenty-eight of the 49 studies (57.1%) reported inclusion of productivity losses/gains as contributing to more favourable cost-effectiveness outcomes and ICERs, while 12 (24.5%) reported no substantial impact. On the basis of a multivariate analysis, rheumatoid arthritis as the target disease had a statistically significant association with the inclusion of productivity loss compared with psoriasis and inflammatory bowel disease. CONCLUSIONS: The results of our review suggest that incorporating productivity cost elements may positively affect cost-effectiveness outcomes in evaluations of therapeutics for immune-mediated disorders. Our work highlights the continued need for clarity when reporting how CEAs and CUAs in this disease area are conducted, in order to better inform healthcare decision-making.

Health state utilities of patients with hepatitis B and C and hepatitis-related conditions in Japan.

Health state utilities are global measurements of quality of life and have been used to evaluate health outcomes for the cost-utility analysis. This study aimed to estimate the health state utilities of patients with hepatitis B (HB), hepatitis C (HC), and hepatitis-related diseases in Japan. We distributed a self-administered questionnaire, including the EuroQol 5-Dimension 5-Level (EQ-5D-5L), to 9,952 outpatients with several clinical conditions caused by HB or HC virus infection (such as asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis) and estimated the condition-specific utilities of patients with HB or HC. In patients with more severe conditions (patients with acute hepatitis, fulminant hepatitis, and hepatocellular carcinoma and patients undergoing post-liver transplantation), the utilities of these severe conditions were estimated by three hepatitis experts using the EQ-5D-5L. The means of the utilities for acute hepatitis, fulminant hepatitis, asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, compensated cirrhosis, hepatocellular carcinoma stage I/II, hepatocellular carcinoma stage III/IV, and post-liver transplantation were 0.529, - 0.111, 0.904, 0.868, 0.845, 0.722, 0,675, 0,428, and 0.651 and 0.876, 0.821, 0.737, 0.671, 0.675, 0.428, and 0.651 in HB and HC, respectively. To the best of our knowledge, this is the first study that comprehensively assessed the health state utilities of patients with HB, HC and hepatitis-related conditions from a nationwide survey in Japan using the EQ-5D-5L.

Difference in Mortality Rates by Occupation in Japanese Male Workers Aged 25 to 64 Years from 1980 to 2015.

This study examines the trends in mortality among Japanese working men, across various occupational categories, from 1980 to 2015. A Poisson model of trend, occupational category, and step variable was analysed for eight occupational categories separately, by cause, to explore the trends in mortality. This study found a sharp increase in mortality in the late 1990s, especially among professionals and managers. The overall trends in cancer, ischemic heart disease (IHD), cerebrovascular disease (CVD), and suicide mortality decreased across almost all occupational categories from 1980 to 2015, although there was an increasing trend in cancer of 0.5% among managers. Clerical workers had the greatest relative decrease in mortality rates from cancer (-82.9%), IHD (-81.7%), and CVD (-89.1%). Japan continues to make gains in lowering mortality and extending life expectancy, but its workplace culture must improve to ensure that those working at the heart of the Japanese corporate world can also benefit from Japan's progress in health. Mortality rates in working-aged Japanese men have been declining. However, similar declines are not evident among managers, for whom the mortality rate is remaining stable or slightly increasing. There is a need to address the needs of managers and improve workplace environments for these workers.

A prospective cohort study on the association between waterpipe tobacco smoking and gastric cancer mortality in Northern Vietnam.

Tobacco consumption, as a worldwide problem, is a risk factor for several types of cancer. In Vietnam, tobacco consumption in the form of waterpipe tobacco smoking is common. This prospective cohort study aimed to study the association between waterpipe tobacco smoking and gastric cancer mortality in Northern Vietnam. A total of 25,619 eligible participants were followed up between 2008 and 2019. Waterpipe tobacco and cigarette smoking data were collected; semi-quantitative food frequency and lifestyle questionnaires were also utilized. Gastric cancer mortality was determined via medical records available at the state health facilities. A Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). During 314,992.8 person-years of follow-up, 55 men and 25 women deaths due to gastric cancer were identified. With never-smokers as the reference, the risk of gastric cancer mortality was significantly increased in participants who were ever-smoking (HR = 2.43, 95% CI = 1.35-4.36). The positive risk was also observed in men but was not significantly increased in women. By types of tobacco use, exclusive waterpipe smokers showed a significantly increased risk of gastric cancer mortality (HR = 3.22, 95% CI = 1.67-6.21) but that was not significantly increased in exclusive cigarette smokers (HR = 1.90, 95% CI = 0.88-4.07). There was a significant positive association between tobacco smoking and gastric cancer death for indicators of longer smoking duration, higher frequency per day, and cumulative frequency of both waterpipe and cigarette smoking. Waterpipe tobacco smoking would significantly increase the risk of gastric cancer mortality in the Vietnamese population. Further studies are required to understand the waterpipe tobacco smoking-driven gastric cancer burden and promote necessary interventions.

Improvement in prescriptions while maintaining overall health outcomes: a prospective observational study conducted in Japanese facilities for older people.

BACKGROUND: Improvements in the use of polypharmacy or potentially inappropriate medication (PIM) may reduce medication costs in Japan. We aimed to evaluate the impact of improvement in prescription on both overall health outcomes and medication costs in Japanese facilities for older people. METHODS: Residents in Japanese facilities for older people between March 2019 and March 2020 were included in this study. The following five indices were used to evaluate overall health outcomes: EuroQoL-5D-5L, Barthel Index, Mini Mental State Examination, Dementia Behaviour Disturbance Scale, and Vitality Index. The team, which consisted of one physician and several pharmacists, suggested improved prescriptions for the attending physicians of the participants. The impact of improvement in prescriptions on the health outcomes score, medication costs, and the number of medications were evaluated through two comparison groups: those whose number of medications decreased (decrement group, DG) and those whose medications did not (not decrement group, NDG); those prescribed PIMs in March 2019 and those not prescribed PIMs in March 2020 (improvement group, IG) and those prescribed PIMs both in March 2019 and March 2020 (not improvement group, NIG). In both comparison groups, propensity score matching was performed to balance demographics, and all health outcome scores, medication costs, and the number of medications in March 2020 were assessed using a t-test. Statistical significance was set at a p-value of < 0.05. RESULTS: Eight-hundred-and-ninety-one participants (75.5% women, 86.2 ± 7.9 years old) were enrolled. After matching, in the comparison between the DG (N = 232, 77.2%, 85.7 ± 8.5) and NDG (N = 232, 78.5%, 86.0 ± 3.1), changes in the health outcomes score were nonsignificant. However, the medication costs and the number of medications significantly decreased. After matching, in the comparison between IG (N = 141, 75.2%, 86.7 ± 8.1) and NIG (N = 273, 74.2%, 86.2 ± 8.3), changes in health outcome scores and medication costs were not significant. However, the number of medications significantly decreased. CONCLUSIONS: Improvements in prescriptions did not adversely affect the overall health outcomes. However, it impacted medication costs and the number of medications. Improvement in prescriptions could decrease medication costs while maintaining overall health outcomes.

Selective targeting of multiple myeloma cells with a monoclonal antibody recognizing the ubiquitous protein CD98 heavy chain.

Cancer-specific cell surface antigens are ideal therapeutic targets for monoclonal antibody (mAb)-based therapy. Here, we report that multiple myeloma (MM), an incurable hematological malignancy, can be specifically targeted by an mAb that recognizes a ubiquitously present protein, CD98 heavy chain (hc) (also known as SLC3A2). We screened more than 10,000 mAb clones raised against MM cells and identified R8H283, an mAb that bound MM cells but not normal hematopoietic or nonhematopoietic cells. R8H283 specifically recognized CD98hc. R8H283 did not react with monomers of CD98hc; instead, it bound CD98hc in heterodimers with a CD98 light chain (CD98lc), a complex that functions as an amino acid transporter. CD98 heterodimers were abundant on MM cells and took up amino acids for constitutive production of immunoglobulin. Although CD98 heterodimers were also present on normal leukocytes, R8H283 did not react with them. The glycoforms of CD98hc present on normal leukocytes were distinct from those present on MM cells, which may explain the lack of R8H283 reactivity to normal leukocytes. R8H283 exerted anti-MM effects without damaging normal hematopoietic cells. These findings suggested that R8H283 is a candidate for mAb-based therapies for MM. In addition, our findings showed that a cancer-specific conformational epitope in a ubiquitous protein, which cannot be identified by transcriptome or proteome analyses, can be found by extensive screening of primary human tumor samples.

Cost-Effectiveness of Lenvatinib in the Treatment of Patients With Unresectable Hepatocellular Carcinomas in Japan: An Analysis Using Data From Japanese Patients in the REFLECT Trial.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Japan. Prognosis is poor, and until recently sorafenib was the only treatment option available for patients with unresectable disease. Lenvatinib is the first therapy to demonstrate noninferiority to sorafenib. An analysis was conducted using clinical data from Japanese patients in the phase III REFLECT trial to assess the cost-effectiveness of lenvatinib versus sorafenib for first-line treatment of unresectable HCC in Japan. METHODS: A partitioned survival model was implemented adopting the perspective of the Japanese healthcare system, with costs and outcomes modeled over a lifetime horizon and using a discount rate of 2%, as per Japanese guidelines. Population data from the Japanese subpopulation of REFLECT were used to extrapolate outcomes, and costs and resource use were based on Japanese sources. The Japanese tariff was applied to EQ-5D data collected during the REFLECT clinical trial to obtain utility values reflecting the preferences of the Japanese population. RESULTS: Compared with sorafenib, lenvatinib is dominant because it is associated with a reduction in incremental costs of ¥156 799 and incremental quality-adjusted life-years of 0.31. These results were robust to changes in key assumptions, and probabilistic outcomes aligned with deterministic outcomes. CONCLUSION: Given the use of Japan-specific data in the cost-effectiveness model, it is expected that the use of lenvatinib as a first-line treatment in Japan will be associated with cost savings and improved clinical outcomes versus sorafenib for patients with unresectable HCC.

Investigation of Factors Considered by Health Technology Assessment Agencies in Eight Countries.

BACKGROUND: Health technology assessment (HTA) organizations play a crucial role in optimizing healthcare resources, but the factors influencing decision making vary by country. OBJECTIVE: HTAs of cancer and hepatitis C drugs were evaluated across developed countries to understand differences in decision processes and criteria. METHODS: The HTA organizations evaluated are from France, Germany, Italy, Spain, the United Kingdom (UK), Australia, Canada and Japan. Economic evaluation types and 28 factors in the following categories were evaluated: clinical uncertainties/issues; disease/population/treatment consideration factors including National Institute for Health and Care Excellence's (NICE) special circumstances factors (e.g. end-of-life and innovation); and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) additional value elements. Qualitative and correspondence analyses were conducted to assess the differences across organizations. RESULTS: Incremental cost-effectiveness ratio (ICER) using quality-adjusted life-year (QALY) was evaluated in Canada, the UK, Australia and Japan. The highest observed clinical uncertainties were clinical benefits and comparator. For cancer drugs, correspondence analysis showed France, Australia, Canada and the UK to have common attributes observed, such as unmet needs and stakeholder persuasion. In addition, the UK reported end-of-life, issues around current treatment and innovation, whereas Germany reported manageable/insignificant adverse events more frequently. Finally, fear of contagion, equity and scientific spillover value elements were only observed in Australia. CONCLUSION: Although clinical factors play a predominant role in the decision to reimburse medicine, HTA organizations consider additional aspects as well. If the methodology of HTA was clearly outlined, there would be more transparency in HTA systems leading to better understanding amongst stakeholders about decision making.

Gastric cancer mortality rates by occupation and industry among male and female workers aged 25-64 years in Japan.

Differences in risk for gastric cancer exist among occupations and industries in Japan. Using a 2015 national dataset, we estimated the mortality rates due to gastric cancer in Japanese male and female workers aged 25-64 yr. Regression models were used to estimate the mortality rate ratios separately for men and women with adjustment for age. The occupation with the highest risk ratio was "Service" in men (2.06, 95% confidence interval: 1.63-2.61) and "Construction and Mining" in women compared with "Sales". For industries, workers in "Mining", "Electricity, Gas, Heat supply and Water", "Fisheries", "Agriculture and Forestry", and "Construction" had a higher mortality risk. Our results showed that occupations and industries with higher mortality rates in men had the same trend as the results from 2010, and occupations and industries with higher mortality rates in women were almost the same as those in men. The analyses also indicated that managerial and professional workers in Japan had higher mortality as opposed to developed Western countries. In conclusion, this study suggests that occupations and industries still impact men and women's health in terms of mortality due to gastric cancer in Japan.

Systematic literature review of clinical outcomes in adults with metastatic or advanced synovial sarcoma.

Background: Synovial sarcoma (SS) is a rare, aggressive soft tissue sarcoma with a poor prognosis after metastasis. The objective of this study was to conduct a systematic review of the clinical evidence for therapeutic options for adults with metastatic or advanced SS. Materials & methods: Relevant databases were searched with predefined keywords. Results: Thirty-nine publications reported clinical data for systemic treatment and other interventions. Data on survival outcomes varied but were generally poor (progression-free survival: 1.0-7.7 months; overall survival: 6.7-29.2 months) for adults with metastatic and advanced SS. A high frequency of neutropenia with systemic treatment and low quality of life post-progression were reported. Conclusion: Reported evidence suggests poor outcomes in adults with metastatic and advanced SS and the need for the development of new treatment modalities.

Fruit and Vegetable Intake and Stomach Cancer among Male Adults: A Case-Control Study in Northern Viet Nam.

OBJECTIVE: This study investigated the association between fruit and vegetable intake and stomach cancer, with considering the impacts of Helicobacter pylori (H. pylori) infection and tobacco smoking. METHODS: A case-control study featuring 80 male incident stomach-cancer cases and 146 male controls was conducted in a general hospital in Viet Nam. A semi-quantitative food frequency and demographic lifestyle questionnaire were used; and venous blood samples were collected to determine H. pylori status by IgG ELISA. The respective associations between fruit and vegetable intake and stomach cancer were examined using unconditional logistic regression analysis with adjustments for possible cofactors. RESULTS: Fruit intake and stomach cancer showed a weak inverse association when this became non-significant after adjusting for H. pylori infection (OR = 0.50, 95%CI: 0.22-1.12, p trend = 0.094). Stratifying by H. pylori status returned a negative trend for fruit intake and stomach cancer among H. pylori-negative participants (OR = 0.21, 95%CI: 0.06-0.69, p trend = 0.010), but no significant interaction for H. pylori-positive participants (OR = 0.76, 95%CI: 0.21-2.68, p trend = 0.670). Vegetable intake and stomach cancer showed no association, regardless of H. pylori status. Compared to ever-smokers with low intake, never-smokers with high vegetable (OR = 0.25, 95% CI: 0.06-0.95) and fruit intake (OR = 0.20, 95%CI: 0.06-0.65) showed the lowest odds of stomach cancer. CONCLUSIONS: Fruit, but not vegetable, intake showed a weak inverse association with stomach cancer. H. pylori infection and tobacco-smoking status may influence the protective effects of fruit and vegetable intake on stomach cancer.
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Mortality due to HIV/AIDS in Viet Nam: time trend and related socio-economic status in some populations and periods from 2005 to 2014.

The study examined mortality due to HIV/AIDS and its time trend and ecological variables of socio-economic status during 2005-2014. Mortality data were obtained from the database of population-based mortality registration. Five variables including name, age, sex, date of death, and cause of death were collected from 10,184 of 10,769 local state health centers. Mortality rates ratio and 95% confidence interval (MRR, 95%CI) were calculated to observe the risk of death from HIV/AIDS-related to socio-economic status and time trends. The age-adjusted HIV/AIDS mortality rate increased from 5.49 per 100,000 during 2005 to 6.03 during 2006 and 6.20 during 2007. An elevated risk of death was seen in high mountain districts in Nghe An province, adjusted MRR = 5.38, 95%, CI: 4.76-6.08 relative to the urban areas of Vinh and Cua Lo cities. The highest age-adjusted mortality rate (147.1 per 100,000) was observed in a commune located in Thai Nguyen province. There was a statically significant decrease in HIV/AIDS mortality in Nghe An province from 2005-2006 to 2013-2014 (p < 0.05). The findings suggest that people living with HIV/AIDS in disadvantaged regions have a higher risk of death but there was a significant decrease in HIV/AIDS mortality in Nghe An province by 2013-2014.

Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan.

BACKGROUND: Lenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan. METHODS: A partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts. RESULTS: For lenvatinib versus sorafenib, the incremental cost was - 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer's willingness-to-pay-per-QALY of 5 million JPY. CONCLUSIONS: Lenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan.

The Effect of Preoperative Subcutaneous Fat Thickness on Surgical Site Infection Risk in Patients Undergoing Colorectal Surgery: Results of a Multisite, Prospective Cohort Study.

Surgical site infection (SSI) is one of the most frequent postoperative complications among patients undergoing elective colorectal surgery. A multisite, prospective cohort study was conducted to investigate whether the thickness of subcutaneous fat (TSF) influences the occurrence of SSI in patients undergoing colorectal surgery. Participants included patients scheduled to receive colorectal laparotomy for colorectal cancer and who were under the care of a wound ostomy continence nurse at 17 participating general hospitals in Japan. Patients were not eligible to participate if they had undergone emergency surgery, reoperation, or laparoscopic surgery. Demographic, wound, and surgical data and American Society of Anesthesiologists (ASA) scale scores were collected and assessed, along with nutritional status, TSF, body mass index, and risk factors for SSI (ie, length of surgery and wound classification). The incidence of SSI and nutritional conditions was assessed weekly for 30 days after surgery. Of the 155 participants (mean age 68.9 ± 10.8 years, 53 [34.2%] of whom were women), 90 (58.1%) underwent rectal surgery, and the remaining 65 underwent colon surgery. Seventy-two (72, 46.5%) of the 155 patients underwent colostomy surgery; 24 (15.5%) developed a SSI. The mean onset of SSI was 7.3 ± 2.9 days after surgery and commonly observed in the stoma group when the ASA score was 3 or higher (P = 0.02). Patients who developed SSI resumed oral dietary intake later than those without SSI (7.4 days versus 4.6 days, P = 0.02). Multivariate analysis indicated TSF >15 mm (P = 0.01), Alb level <3.5 g/dL at postoperative days 14 (P = 0.03) and 21 (P = 0.02), and total protein level <6.8 g/dL at postoperative day 7 (P = 0.02) were statistically significantly correlated with SSI occurrence. These results suggest preoperative TSF and preoperative and postoperative serum albumin levels are independent risk factors for SSI in patients undergoing colorectal surgery, confirming current recommendations to maximize the preoperative nutritional status of patients in order to prevent major complications. The results also confirm obesity/TSF should be assessed preoperatively to ascertain the risk of SSI in patients undergoing colorectal surgery.

The Effects of Diagnostic Definitions in Claims Data on Healthcare Cost Estimates: Evidence from a Large-Scale Panel Data Analysis of Diabetes Care in Japan.

BACKGROUND: Inaccurate estimates of diabetes-related healthcare costs can undermine the efficiency of resource allocation for diabetes care. The quantification of these costs using claims data may be affected by the method for defining diagnoses. OBJECTIVES: The aims were to use panel data analysis to estimate diabetes-related healthcare costs and to comparatively evaluate the effects of diagnostic definitions on cost estimates. RESEARCH DESIGN: Monthly panel data analysis of Japanese claims data. SUBJECTS: The study included a maximum of 141,673 patients with type 2 diabetes who received treatment between 2005 and 2013. MEASURES: Additional healthcare costs associated with diabetes and diabetes-related complications were estimated for various diagnostic definition methods using fixed-effects panel data regression models. RESULTS: The average follow-up period per patient ranged from 49.4 to 52.3 months. The number of patients identified as having type 2 diabetes varied widely among the diagnostic definition methods, ranging from 14,743 patients to 141,673 patients. The fixed-effects models showed that the additional costs per patient per month associated with diabetes ranged from US$180 [95 % confidence interval (CI) 178-181] to US$223 (95 % CI 221-224). When the diagnostic definition excluded rule-out diagnoses, the diabetes-related complications associated with higher additional healthcare costs were ischemic heart disease with surgery (US$13,595; 95 % CI 13,568-13,622), neuropathy/extremity disease with surgery (US$4594; 95 % CI 3979-5208), and diabetic nephropathy with dialysis (US$3689; 95 % CI 3667-3711). CONCLUSIONS: Diabetes-related healthcare costs are sensitive to diagnostic definition methods. Determining appropriate diagnostic definitions can further advance healthcare cost research for diabetes and its applications in healthcare policies.