Screening rate for hepatitis B virus infection in patients undergoing chemotherapy in Japan.

BACKGROUND: The aim of this study was to investigate the screening rate for hepatitis B virus (HBV) infection, which is recommended by some guidelines for the prevention of HBV reactivation, in patients undergoing chemotherapy for malignancy in Japan. METHODS: The study subjects were 3302 patients who had received first-line chemotherapy for malignancy from Apr 2008 through Mar 2013 utilizing the Claims Database of the Japan Medical Data Center. The proportion of patients who had been tested for HBsAg (P-HBsAg) and the proportion of HBsAg-negative patients who had undergone tests for anti-HBc and anti-HBs (P-HBc/HBsAb) before chemotherapy were investigated. RESULTS: P-HBsAg and P-HBc/HBsAb in all 3302 patients were 66.3 and 19.9 %, respectively. P-HBsAg in patients with solid tumors and those with hematological malignancies were 66.1 and 67.5 % (p = 0.61), respectively, and P-HBc/HBsAb were 12.3 and 75.8 % (p < 0.0001), respectively. P-HBsAg in patients from cancer centers and non-cancer centers were 66.9 and 65.5 % (p = 0.43), respectively, and P-HBc/HBsAb were 25.1 and 12.4 % (p < 0.0001), respectively. P-HBsAg in patients encountered before and after the announcement of the Japanese guideline were 51.3 and 67.1 % (p < 0.001), respectively, and P-HBc/HBsAb were 7.9 and 20.4 % (p = 0.01), respectively. CONCLUSIONS: The screening rate for HBV among cancer patients scheduled for chemotherapy remains unsatisfactory, especially in patients with solid tumors and those from non-cancer centers. Although the figures are improving after the announcement of the Japanese guideline, intensive measures to improve awareness about HBV reactivation during/after chemotherapy are needed.

Association of dipeptidyl peptidase-4 inhibitor use and risk of pancreatic cancer in individuals with diabetes in Japan.

AIMS/INTRODUCTION: This study was designed and carried out to investigate the association of dipeptidyl peptidase-4 inhibitor (DPP-4i) use with pancreatic cancer (PC) in individuals with diabetes in Japan. MATERIALS AND METHODS: The JMDC Claims Database, which contains the medical and prescription information of Japanese employment-based health insurance programs, was used. The primary outcome was duration to the first occurrence of PC (International Classification of Diseases 10th Revision code C25), both all and hospitalized, from prescription of DPP-4is or other oral glucose-lowering agents (GLAs). RESULTS: Individuals with diabetes who received DPP-4is (n = 61,430) or other oral GLAs (n = 83,304) were analyzed. Follow-up periods (median [interquartile range]) were 17 months (8-33) for DPP-4is and 14 months (7-28) for other oral GLAs. Kaplan-Meier curve analysis to determine the duration of first use of DPP4i or other oral GLA to diagnosis of PC disclosed no differences between the two groups in duration to all or hospitalized PC (log-rank test: all, P = 0.7140; hospitalized, P = 0.3446). Cox proportional hazards models showed that use of DPP-4is did not affect the PC risk adjusted for medications, age, sex and risk comorbidities (all, hazard ratio 1.1, 95% confidence interval 0.8-1.3, P = 0.6518; hospitalized, hazard ratio 1.1, 95% confidence interval 0.8-1.4, P = 0.6662). Similar results were obtained when individuals with ≥2 years oral GLA treatment and those with medical checkup data (e.g., smoking or drinking habit) available were analyzed. CONCLUSION: This database study shows that there is not a significant PC risk due to DPP-4i treatment in individuals with diabetes in Japan, but larger studies with longer follow up are required to confirm these findings.

Occupational difference in use of heated tobacco products: a cross-sectional analysis of retail workers in Japan.

OBJECTIVE: Although heated tobacco products (HTPs) have become popular worldwide, research on occupational differences in smoking HTPs remains scarce. We aimed to examine the prevalence of smoking HTPs among a working population in Japan. SETTING, DESIGN AND PARTICIPANTS: In 2018, we conducted a cross-sectional study comprised of 7714 retail business workers in the service industry in Japan. PRIMARY AND SECONDARY OUTCOME MEASURES: For the definition of smoking HTPs, we identified current HTP smokers who only smoked HTPs, using five mutual categories of current smoking status (never, former, HTPs only, combustible cigarettes only and dual smokers who smoked both combustible cigarettes and HTPs). Occupational classes were classified into office workers (eg, upper non-manual workers) and other workers. ORs and 95% CIs of office workers were estimated for HTP usage, adjusted for age, sex, employment type and cigarette smoking-related health knowledge. RESULTS: The overall prevalence of smoking HTPs was 3.0% (male 5.0%, female 2.2%). The prevalence of HTP smokers differed across occupational classes (5.6% in office workers vs 2.5% in others; p<0.05). Compared with other workers, the adjusted odds of office workers for smoking HTPs remained elevated (OR: 1.97, 95% CI: 1.40 to 2.77). Sensitivity analyses with workers of all smoking status showed the same pattern. When stratified by sex, the occupational difference only remained significant in male workers. CONCLUSIONS: We found a positive occupational difference in smoking HTPs, particularly among male workers in the retail sector in Japan. National tobacco control should explicitly address this occupational gap and further encourage individuals to quit smoking.

Predictive factors associated with bleeding in atrial fibrillation patients treated with anti-coagulant drugs using a large claims database.

OBJECTIVE: To identify risk factors for bleeding in atrial fibrillation (AF) patients treated with anti-coagulants such as warfarin, apixaban, edoxaban, dabigatran, rivaroxaban using a large claims database. METHODS: A claims database for 8926 AF patients from 2004 to 2016 was obtained from JMDC. Inc. We performed a retrospective cohort study in 2796 Japanese AF patients with 4-month screening and 12-month observation periods. Polypharmacy was defined as prescription of over six drugs. Logistic regression analysis was conducted after stratification based on the presence and absence of cerebrovascular diseases to detect the predictive factors for bleeding. RESULTS: Polypharmacy was observed in 815 of 2796 (29.1%) patients. A total of 371 AF patients (13.3%) experienced bleeding in the 12-month observation period. Bleeding risk assessment using multiple logistic regression analysis revealed that the odds ratio for the number of co-administered drugs in the elderly (age for ≥60, ≤74) was not significant in those without and with cerebrovascular diseases (1.05 [0.99-1.12], N.S. and 1.10 [0.96-1.27], N.S.). In contrast, in the young (age for <60), the number of co-administered drugs was a significant predictive factor in those without and with cerebrovascular diseases (1.09 [1.03-1.16], p = 0.0054 and 1.20 [1.05-1.36], p = 0.0059). Other observed predictors were"history of bleeding" in young and elderly, but "polypharmacy" and "start from warfarin" were observed in only young. CONCLUSION: We determined the bleeding risk in the clinical setting using a large claims database. Physicians and pharmacists need to monitor patients for the initial bleeding signs, particularly in those with these predictive risk factors.

Short-term impacts of sodium/glucose co-transporter 2 inhibitors in Japanese clinical practice: considerations for their appropriate use to avoid serious adverse events.

Sodium/glucose co-transporter 2 inhibitors (SGLT2i) represent a novel class of glucose-lowering agents that lower plasma glucose levels through pharmacological inhibition of glucose reuptake from the kidney, independent of insulin secretion and action. Clinical trials of SGLT2i demonstrated therapeutic benefits on glycemic control and bodyweight in individuals with type 2 diabetes, with few cases of serious adverse events (SAEs). However, a considerable number of SAEs were reported in patients receiving SGLT2i clinically in Japan during the first 3 months of their use. These included urogenital infections, hypoglycemia and dehydration. Unexpectedly, serious skin and subcutaneous disorders, mainly reported as generalized rash or skin eruption, were prominent in patients receiving SGLT2i, but with unknown mechanisms. There is also concern for potential SAEs associated with chronic SGLT2i administration, especially in the non-obese type 2 diabetes characterized by reduced insulin secretion often seen in East Asia. Chronic SAEs may include severe hypoglycemia due to depletion of hepatic glycogen storage, acceleration of diabetes-associated sarcopenia and ketosis/ketoacidosis. The current information on acute SAEs confirms the importance of caution in the appropriate use of SGLT2i. Furthermore, careful long-term observation of patients receiving SGLT2i is essential to avoid SAEs and for better clinical use of this drug class.

Targeted introduction of V642I mutation in amyloid precursor protein gene causes functional abnormality resembling early stage of Alzheimer's disease in aged mice.

While the exact aetiology of Alzheimer's disease (AD) is unknown, distinct genetic mutations have been identified for the rare cases of familial AD (FAD). V642I mutation in amyloid precursor protein (APP) co-segregates with FAD with perfect penetration, and the clinicopathological characteristics of patients with this mutation resemble that of sporadic AD. To examine the pathogenic process of this FAD-linked trait in vivo, we produced a mouse with the corresponding point mutation in the APP gene using homologous recombination and Cre-loxP site-specific recombination ('knock-in' technique). Mice with the heterozygous V642I-APP allele most precisely reflected the genotype of humans bearing this mutation. For the observation period of 2.5 years the mutants stayed apparently indistinguishable from the wild-type littermates. However, behavioural analysis revealed significantly deteriorated long-term memory in mutants when examined for the retention of spatial attention. Interestingly, acquisition of spatial memory was slightly affected but short-term working memory was not deteriorated at all. Histological examination was negative for formation of neuritic plaques or neurofibrillary tangles, whereas the relative amount of longer form of beta-amyloid species A beta 42(43) was significantly increased against that of the shorter form (A beta 40) in the mutant brain homogenates. We conclude that a V642I-APP mutant allele in aged mice confers functional components, but not organic components, of the AD-related phenotype that are observed in the early stage of AD. This V642I-APP knock-in mutant line may serve as a model to study the early pathogenic processes of AD in vivo and to develop therapeutics for this stage.